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Conserved domains on  [gi|27777648|ref|NP_034742|]
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vascular endothelial growth factor receptor 2 isoform 1 precursor [Mus musculus]

Protein Classification

Graphical summary

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List of domain hits

Name Accession Description Interval E-value
PTKc_VEGFR2 cd05103
Catalytic domain of the Protein Tyrosine Kinase, Vascular Endothelial Growth Factor Receptor 2; ...
824-1165 0e+00

Catalytic domain of the Protein Tyrosine Kinase, Vascular Endothelial Growth Factor Receptor 2; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. VEGFR2 (or Flk1) binds the ligands VEGFA, VEGFC, VEGFD and VEGFE. VEGFR2 signaling is implicated in all aspects of normal and pathological vascular endothelial cell biology. It induces a variety of cellular effects including migration, survival, and proliferation. It is critical in regulating embryonic vascular development and angiogenesis. VEGFR2 is the major signal transducer in pathological angiogenesis including cancer and diabetic retinopathy, and is a target for inhibition in cancer therapy. The carboxyl terminus of VEGFR2 plays an important role in its autophosphorylation and activation. VEGFR2 is a member of the VEGFR subfamily of proteins, which are receptor PTKs (RTKs) containing an extracellular ligand-binding region with seven immunoglobulin (Ig)-like domains, a transmembrane segment, and an intracellular catalytic domain. The binding of VEGFRs to their ligands, the VEGFs, leads to receptor dimerization, activation, and intracellular signaling. The VEGFR2 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


:

Pssm-ID: 270681 [Multi-domain]  Cd Length: 343  Bit Score: 716.76  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  824 KWEFPRDRLKLGKPLGRGAFGQVIEADAFGIDKTATCKTVAVKMLKEGATHSEHRALMSELKILIHIGHHLNVVNLLGAC 903
Cdd:cd05103    1 KWEFPRDRLKLGKPLGRGAFGQVIEADAFGIDKTATCRTVAVKMLKEGATHSEHRALMSELKILIHIGHHLNVVNLLGAC 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  904 TKPGGPLMVIVEFCKFGNLSTYLRGKRNEFVPYKSKGARFRQGKDYVGELSVDLKRRLDSITSSQSSASSGFVEEKSLSD 983
Cdd:cd05103   81 TKPGGPLMVIVEFCKFGNLSAYLRSKRSEFVPYKTKGARFRQGKDYVGDISVDLKRRLDSITSSQSSASSGFVEEKSLSD 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  984 VEEEEASEE-LYKDFLTLEHLICYSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIYKDPDYVRKGD 1062
Cdd:cd05103  161 VEEEEAGQEdLYKDFLTLEDLICYSFQVAKGMEFLASRKCIHRDLAARNILLSENNVVKICDFGLARDIYKDPDYVRKGD 240
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1063 ARLPLKWMAPETIFDRVYTIQSDVWSFGVLLWEIFSLGASPYPGVKIDEEFCRRLKEGTRMRAPDYTTPEMYQTMLDCWH 1142
Cdd:cd05103  241 ARLPLKWMAPETIFDRVYTIQSDVWSFGVLLWEIFSLGASPYPGVKIDEEFCRRLKEGTRMRAPDYTTPEMYQTMLDCWH 320
                        330       340
                 ....*....|....*....|...
gi 27777648 1143 EDPNQRPSFSELVEHLGNLLQAN 1165
Cdd:cd05103  321 GEPSQRPTFSELVEHLGNLLQAN 343
Ig super family cl11960
Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found ...
331-419 9.51e-40

Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins, including T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, including butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E, and D strands in one sheet and A', G, F, C, C' and C" in the other. The structures in C1-set are smaller than those in the V-set; they have one beta sheet that is formed by strands A, B, E, and D and the other by strands G, F, C, and C'. Moreover, a C1-set Ig domain contains a short C' strand (three residues) and lacks A' and C" strand. Unlike other Ig domain sets, C2-set structures do not have a D strand. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


The actual alignment was detected with superfamily member cd05864:

Pssm-ID: 472250  Cd Length: 89  Bit Score: 141.99  E-value: 9.51e-40
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  331 FIAFGSGMKSLVEATVGSQVRIPVKYLSYPAPDIKWYRNGRPIESNYTMIVGDELTIMEVTERDAGNYTVILTNPISMEK 410
Cdd:cd05864    1 FIALGSGMESLVEAKVGERVRIPVKYLGYPPPEIKWYKNGIPIESNHTIKAGHVLTIMEVTEKDAGNYTVVLTNPISKEK 80

                 ....*....
gi 27777648  411 QSHMVSLVV 419
Cdd:cd05864   81 QRHTFSLVV 89
Ig super family cl11960
Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found ...
226-327 2.07e-39

Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins, including T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, including butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E, and D strands in one sheet and A', G, F, C, C' and C" in the other. The structures in C1-set are smaller than those in the V-set; they have one beta sheet that is formed by strands A, B, E, and D and the other by strands G, F, C, and C'. Moreover, a C1-set Ig domain contains a short C' strand (three residues) and lacks A' and C" strand. Unlike other Ig domain sets, C2-set structures do not have a D strand. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


The actual alignment was detected with superfamily member cd05862:

Pssm-ID: 472250  Cd Length: 102  Bit Score: 141.81  E-value: 2.07e-39
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  226 YDVILSPPHEIELSAGEKLVLNCTARTELNVGLDFTWHSPPSKSHHKKIVNRDVKPFPGTvAKMFLSTLTIESVTKSDQG 305
Cdd:cd05862    1 YDVQLSPPKPVELLVGEKLVLNCTARTELNVGVDFQWDYPGKKEQRRASVRRRRKQQSSE-ATEFSSTLTIDNVTLSDKG 79
                         90       100
                 ....*....|....*....|..
gi 27777648  306 EYTCVASSGRMIKRNRTFVRVH 327
Cdd:cd05862   80 LYTCAASSGPMFKKNSTSVIVH 101
I-set pfam07679
Immunoglobulin I-set domain;
665-742 1.02e-18

Immunoglobulin I-set domain;


:

Pssm-ID: 400151 [Multi-domain]  Cd Length: 90  Bit Score: 82.31  E-value: 1.02e-18
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648    665 PMITGNLENQTTTIGETIEVTCPASGNPTPHITWFKDNETLVEDSGIVLR--DGNRNLTIRRVRKEDGGLYTCQACNVLG 742
Cdd:pfam07679    1 PKFTQKPKDVEVQEGESARFTCTVTGTPDPEVSWFKDGQPLRSSDRFKVTyeGGTYTLTISNVQPDDSGKYTCVATNSAG 80
VEGFR-2_TMD pfam17988
VEGFR-2 Transmembrane domain; This is a transmembrane domain (TMD) of vascular endothelial ...
757-791 8.26e-15

VEGFR-2 Transmembrane domain; This is a transmembrane domain (TMD) of vascular endothelial growth factor receptor 2 which regulates blood vessel homeostasis. Transmembrane signalling by receptor tyrosine kinases (RTKs) requires specific orientation of the intracellular kinase domains in active receptor dimers. Two mutants in VEGFR-2 TMD showed constitutive kinase activity, suggesting that precise TMD orientation is mandatory for kinase activation. Scanning mutagenesis and structural analysis indicated that introducing two polar amino acids in distinct positions of the TMD (G770E/F777E and I771E/L778E mutations) reorients transmembrane helices and leads to stable dimer formation. Therefore, it has been suggested that the transition between the inactive and the active dimeric state of VEGFR-2 implicates alternative dimeric TMD conformations.


:

Pssm-ID: 375470  Cd Length: 35  Bit Score: 69.29  E-value: 8.26e-15
                           10        20        30
                   ....*....|....*....|....*....|....*
gi 27777648    757 EKTNLEVIILVGTAVIAMFFWLLLVIVLRTVKRAN 791
Cdd:pfam17988    1 DKTNVELIILIGTGVIAMFFWLLLVLVIRNLKRPN 35
Ig_3 pfam13927
Immunoglobulin domain; This family contains immunoglobulin-like domains.
549-642 1.50e-05

Immunoglobulin domain; This family contains immunoglobulin-like domains.


:

Pssm-ID: 464046 [Multi-domain]  Cd Length: 78  Bit Score: 44.48  E-value: 1.50e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648    549 PEITVQPAAQ-PTEQESVSLLCTADRNTFENLTWYKLGSQATSVHMGESltpvcknldalwklngtmFSNSTNDILIVaf 627
Cdd:pfam13927    2 PVITVSPSSVtVREGETVTLTCEATGSPPPTITWYKNGEPISSGSTRSR------------------SLSGSNSTLTI-- 61
                           90
                   ....*....|....*
gi 27777648    628 QNASLQDQGDYVCSA 642
Cdd:pfam13927   62 SNVTRSDAGTYTCVA 76
 
Name Accession Description Interval E-value
PTKc_VEGFR2 cd05103
Catalytic domain of the Protein Tyrosine Kinase, Vascular Endothelial Growth Factor Receptor 2; ...
824-1165 0e+00

Catalytic domain of the Protein Tyrosine Kinase, Vascular Endothelial Growth Factor Receptor 2; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. VEGFR2 (or Flk1) binds the ligands VEGFA, VEGFC, VEGFD and VEGFE. VEGFR2 signaling is implicated in all aspects of normal and pathological vascular endothelial cell biology. It induces a variety of cellular effects including migration, survival, and proliferation. It is critical in regulating embryonic vascular development and angiogenesis. VEGFR2 is the major signal transducer in pathological angiogenesis including cancer and diabetic retinopathy, and is a target for inhibition in cancer therapy. The carboxyl terminus of VEGFR2 plays an important role in its autophosphorylation and activation. VEGFR2 is a member of the VEGFR subfamily of proteins, which are receptor PTKs (RTKs) containing an extracellular ligand-binding region with seven immunoglobulin (Ig)-like domains, a transmembrane segment, and an intracellular catalytic domain. The binding of VEGFRs to their ligands, the VEGFs, leads to receptor dimerization, activation, and intracellular signaling. The VEGFR2 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270681 [Multi-domain]  Cd Length: 343  Bit Score: 716.76  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  824 KWEFPRDRLKLGKPLGRGAFGQVIEADAFGIDKTATCKTVAVKMLKEGATHSEHRALMSELKILIHIGHHLNVVNLLGAC 903
Cdd:cd05103    1 KWEFPRDRLKLGKPLGRGAFGQVIEADAFGIDKTATCRTVAVKMLKEGATHSEHRALMSELKILIHIGHHLNVVNLLGAC 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  904 TKPGGPLMVIVEFCKFGNLSTYLRGKRNEFVPYKSKGARFRQGKDYVGELSVDLKRRLDSITSSQSSASSGFVEEKSLSD 983
Cdd:cd05103   81 TKPGGPLMVIVEFCKFGNLSAYLRSKRSEFVPYKTKGARFRQGKDYVGDISVDLKRRLDSITSSQSSASSGFVEEKSLSD 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  984 VEEEEASEE-LYKDFLTLEHLICYSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIYKDPDYVRKGD 1062
Cdd:cd05103  161 VEEEEAGQEdLYKDFLTLEDLICYSFQVAKGMEFLASRKCIHRDLAARNILLSENNVVKICDFGLARDIYKDPDYVRKGD 240
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1063 ARLPLKWMAPETIFDRVYTIQSDVWSFGVLLWEIFSLGASPYPGVKIDEEFCRRLKEGTRMRAPDYTTPEMYQTMLDCWH 1142
Cdd:cd05103  241 ARLPLKWMAPETIFDRVYTIQSDVWSFGVLLWEIFSLGASPYPGVKIDEEFCRRLKEGTRMRAPDYTTPEMYQTMLDCWH 320
                        330       340
                 ....*....|....*....|...
gi 27777648 1143 EDPNQRPSFSELVEHLGNLLQAN 1165
Cdd:cd05103  321 GEPSQRPTFSELVEHLGNLLQAN 343
PK_Tyr_Ser-Thr pfam07714
Protein tyrosine and serine/threonine kinase; Protein phosphorylation, which plays a key role ...
832-1158 7.80e-123

Protein tyrosine and serine/threonine kinase; Protein phosphorylation, which plays a key role in most cellular activities, is a reversible process mediated by protein kinases and phosphoprotein phosphatases. Protein kinases catalyze the transfer of the gamma phosphate from nucleotide triphosphates (often ATP) to one or more amino acid residues in a protein substrate side chain, resulting in a conformational change affecting protein function. Phosphoprotein phosphatases catalyze the reverse process. Protein kinases fall into three broad classes, characterized with respect to substrate specificity; Serine/threonine-protein kinases, tyrosine-protein kinases, and dual specificity protein kinases (e.g. MEK - phosphorylates both Thr and Tyr on target proteins). This entry represents the catalytic domain found in a number of serine/threonine- and tyrosine-protein kinases. It does not include the catalytic domain of dual specificity kinases.


Pssm-ID: 462242 [Multi-domain]  Cd Length: 258  Bit Score: 381.46  E-value: 7.80e-123
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648    832 LKLGKPLGRGAFGQVIEADAFGiDKTATCKTVAVKMLKEGATHSEHRALMSELKILIHIgHHLNVVNLLGACTKpGGPLM 911
Cdd:pfam07714    1 LTLGEKLGEGAFGEVYKGTLKG-EGENTKIKVAVKTLKEGADEEEREDFLEEASIMKKL-DHPNIVKLLGVCTQ-GEPLY 77
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648    912 VIVEFCKFGNLSTYLRGKRNEfvpykskgarfrqgkdyvgelsvdlkrrldsitssqssassgfveekslsdveeeease 991
Cdd:pfam07714   78 IVTEYMPGGDLLDFLRKHKRK----------------------------------------------------------- 98
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648    992 elykdfLTLEHLICYSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIYKDPDYVRKGDARLPLKWMA 1071
Cdd:pfam07714   99 ------LTLKDLLSMALQIAKGMEYLESKNFVHRDLAARNCLVSENLVVKISDFGLSRDIYDDDYYRKRGGGKLPIKWMA 172
                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648   1072 PETIFDRVYTIQSDVWSFGVLLWEIFSLGASPYPGVKiDEEFCRRLKEGTRMRAPDYTTPEMYQTMLDCWHEDPNQRPSF 1151
Cdd:pfam07714  173 PESLKDGKFTSKSDVWSFGVLLWEIFTLGEQPYPGMS-NEEVLEFLEDGYRLPQPENCPDELYDLMKQCWAYDPEDRPTF 251

                   ....*..
gi 27777648   1152 SELVEHL 1158
Cdd:pfam07714  252 SELVEDL 258
STYKc smart00221
Protein kinase; unclassified specificity; Phosphotransferases. The specificity of this class ...
832-1158 7.17e-114

Protein kinase; unclassified specificity; Phosphotransferases. The specificity of this class of kinases can not be predicted. Possible dual-specificity Ser/Thr/Tyr kinase.


Pssm-ID: 214568 [Multi-domain]  Cd Length: 258  Bit Score: 357.24  E-value: 7.17e-114
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648     832 LKLGKPLGRGAFGQVIEADAFGIDKTATCKtVAVKMLKEGATHSEHRALMSELKILIHIgHHLNVVNLLGACTKPGgPLM 911
Cdd:smart00221    1 LTLGKKLGEGAFGEVYKGTLKGKGDGKEVE-VAVKTLKEDASEQQIEEFLREARIMRKL-DHPNIVKLLGVCTEEE-PLM 77
                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648     912 VIVEFCKFGNLSTYLRGKRNEFvpykskgarfrqgkdyvgelsvdlkrrldsitssqssassgfveekslsdveeeease 991
Cdd:smart00221   78 IVMEYMPGGDLLDYLRKNRPKE---------------------------------------------------------- 99
                           170       180       190       200       210       220       230       240
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648     992 elykdfLTLEHLICYSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIYKDpDYVRKGDARLPLKWMA 1071
Cdd:smart00221  100 ------LSLSDLLSFALQIARGMEYLESKNFIHRDLAARNCLVGENLVVKISDFGLSRDLYDD-DYYKVKGGKLPIRWMA 172
                           250       260       270       280       290       300       310       320
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648    1072 PETIFDRVYTIQSDVWSFGVLLWEIFSLGASPYPGVKiDEEFCRRLKEGTRMRAPDYTTPEMYQTMLDCWHEDPNQRPSF 1151
Cdd:smart00221  173 PESLKEGKFTSKSDVWSFGVLLWEIFTLGEEPYPGMS-NAEVLEYLKKGYRLPKPPNCPPELYKLMLQCWAEDPEDRPTF 251

                    ....*..
gi 27777648    1152 SELVEHL 1158
Cdd:smart00221  252 SELVEIL 258
IgI_VEGFR-2 cd05864
Immunoglobulin (Ig)-like domain of vascular endothelial growth factor receptor 2 (VEGFR-2); ...
331-419 9.51e-40

Immunoglobulin (Ig)-like domain of vascular endothelial growth factor receptor 2 (VEGFR-2); member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin (Ig)-like domain of vascular endothelial growth factor receptor 2 (VEGFR-2). The VEGFRs have an extracellular component with seven Ig-like domains, a transmembrane segment, and an intracellular tyrosine kinase domain interrupted by a kinase-insert domain. VEGFRs bind VEGFs with high affinity at the Ig-like domains. VEGFR-2 (KDR/Flk-1) is a major mediator of the mitogenic, angiogenic and microvascular permeability-enhancing effects of VEGF-A; VEGF-A is important to the growth and maintenance of vascular endothelial cells and to the development of new blood- and lymphatic-vessels in physiological and pathological states. VEGF-A also interacts with VEGFR-1, which it binds more strongly than VEGFR-2. VEGFR-1 and VEGFR-2 may mediate a chemotactic and a survival signal in hematopoietic stem cells or leukemia cells. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409450  Cd Length: 89  Bit Score: 141.99  E-value: 9.51e-40
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  331 FIAFGSGMKSLVEATVGSQVRIPVKYLSYPAPDIKWYRNGRPIESNYTMIVGDELTIMEVTERDAGNYTVILTNPISMEK 410
Cdd:cd05864    1 FIALGSGMESLVEAKVGERVRIPVKYLGYPPPEIKWYKNGIPIESNHTIKAGHVLTIMEVTEKDAGNYTVVLTNPISKEK 80

                 ....*....
gi 27777648  411 QSHMVSLVV 419
Cdd:cd05864   81 QRHTFSLVV 89
IgI_VEGFR cd05862
Immunoglobulin (Ig)-like domain of vascular endothelial growth factor (VEGF) receptor(R); ...
226-327 2.07e-39

Immunoglobulin (Ig)-like domain of vascular endothelial growth factor (VEGF) receptor(R); member of the I-set of IgSF domains; The members here are composed of the immunoglobulin (Ig)-like domain of vascular endothelial growth factor (VEGF) receptor(R). The VEGFRs have an extracellular component with seven Ig-like domains, a transmembrane segment, and an intracellular tyrosine kinase domain interrupted by a kinase-insert domain. The VEGFR family consists of three members, VEGFR-1 (also known as Flt-1), VEGFR-2 (also known as KDR or Flk-1) and VEGFR-3 (also known as Flt-4). VEGF_A interacts with both VEGFR-1 and VEGFR-2. VEGFR-1 binds strongest to VEGF, VEGF-2 binds more weakly. VEGFR-3 appears not to bind VEGF, but binds other members of the VEGF family (VEGF-C and -D). VEGFRs bind VEGFs with high affinity with the IG-like domains. VEGF-A is important to the growth and maintenance of vascular endothelial cells and to the development of new blood- and lymphatic-vessels in physiological and pathological states. VEGFR-2 is a major mediator of the mitogenic, angiogenic and microvascular permeability-enhancing effects of VEGF-A. VEGFR-1 may play an inhibitory part in these processes by binding VEGF and interfering with its interaction with VEGFR-2. VEGFR-1 has a signaling role in mediating monocyte chemotaxis. VEGFR-2 and -1 may mediate a chemotactic and a survival signal in hematopoietic stem cells or leukemia cells. VEGFR-3 has been shown to be involved in tumor angiogenesis and growth.


Pssm-ID: 409448  Cd Length: 102  Bit Score: 141.81  E-value: 2.07e-39
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  226 YDVILSPPHEIELSAGEKLVLNCTARTELNVGLDFTWHSPPSKSHHKKIVNRDVKPFPGTvAKMFLSTLTIESVTKSDQG 305
Cdd:cd05862    1 YDVQLSPPKPVELLVGEKLVLNCTARTELNVGVDFQWDYPGKKEQRRASVRRRRKQQSSE-ATEFSSTLTIDNVTLSDKG 79
                         90       100
                 ....*....|....*....|..
gi 27777648  306 EYTCVASSGRMIKRNRTFVRVH 327
Cdd:cd05862   80 LYTCAASSGPMFKKNSTSVIVH 101
SPS1 COG0515
Serine/threonine protein kinase [Signal transduction mechanisms];
829-1167 1.17e-19

Serine/threonine protein kinase [Signal transduction mechanisms];


Pssm-ID: 440281 [Multi-domain]  Cd Length: 482  Bit Score: 93.92  E-value: 1.17e-19
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  829 RDRLKLGKPLGRGAFGQVIEADAFGIDKTatcktVAVKMLKEGATHSEH--RALMSELKILIHIGHHlNVVNLLGACTKP 906
Cdd:COG0515    6 LGRYRILRLLGRGGMGVVYLARDLRLGRP-----VALKVLRPELAADPEarERFRREARALARLNHP-NIVRVYDVGEED 79
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  907 GGPLMViVEFCKFGNLSTYLRGKrnefvpykskgarfrqgkdyvGELSVDLKRRLdsitssqssassgfveekslsdvee 986
Cdd:COG0515   80 GRPYLV-MEYVEGESLADLLRRR---------------------GPLPPAEALRI------------------------- 112
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  987 eeaseelykdfltlehLIcysfQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIyKDPDYVRKGDARLP 1066
Cdd:COG0515  113 ----------------LA----QLAEALAAAHAAGIVHRDIKPANILLTPDGRVKLIDFGIARAL-GGATLTQTGTVVGT 171
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1067 LKWMAPETIFDRVYTIQSDVWSFGVLLWEIFSlGASPYPGVKIDEEFCRRL-KEGTRMRAPDYTTPEMYQTMLD-CWHED 1144
Cdd:COG0515  172 PGYMAPEQARGEPVDPRSDVYSLGVTLYELLT-GRPPFDGDSPAELLRAHLrEPPPPPSELRPDLPPALDAIVLrALAKD 250
                        330       340
                 ....*....|....*....|....
gi 27777648 1145 PNQRP-SFSELVEHLGNLLQANAQ 1167
Cdd:COG0515  251 PEERYqSAAELAAALRAVLRSLAA 274
I-set pfam07679
Immunoglobulin I-set domain;
665-742 1.02e-18

Immunoglobulin I-set domain;


Pssm-ID: 400151 [Multi-domain]  Cd Length: 90  Bit Score: 82.31  E-value: 1.02e-18
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648    665 PMITGNLENQTTTIGETIEVTCPASGNPTPHITWFKDNETLVEDSGIVLR--DGNRNLTIRRVRKEDGGLYTCQACNVLG 742
Cdd:pfam07679    1 PKFTQKPKDVEVQEGESARFTCTVTGTPDPEVSWFKDGQPLRSSDRFKVTyeGGTYTLTISNVQPDDSGKYTCVATNSAG 80
IG_like smart00410
Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.
672-748 1.02e-17

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.


Pssm-ID: 214653 [Multi-domain]  Cd Length: 85  Bit Score: 79.09  E-value: 1.02e-17
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648     672 ENQTTTIGETIEVTCPASGNPTPHITWFKDNETLVEDSGIVLRDGNRN---LTIRRVRKEDGGLYTCQACNVLGCARAET 748
Cdd:smart00410    2 PSVTVKEGESVTLSCEASGSPPPEVTWYKQGGKLLAESGRFSVSRSGStstLTISNVTPEDSGTYTCAATNSSGSASSGT 81
Ig cd00096
Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found ...
682-742 3.63e-15

Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins, including T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, including butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E, and D strands in one sheet and A', G, F, C, C' and C" in the other. The structures in C1-set are smaller than those in the V-set; they have one beta sheet that is formed by strands A, B, E, and D and the other by strands G, F, C, and C'. Moreover, a C1-set Ig domain contains a short C' strand (three residues) and lacks A' and C" strand. Unlike other Ig domain sets, C2-set structures do not have a D strand. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409353 [Multi-domain]  Cd Length: 70  Bit Score: 71.59  E-value: 3.63e-15
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 27777648  682 IEVTCPASGNPTPHITWFKDNETLVEDS--GIVLRDGNRNLTIRRVRKEDGGLYTCQACNVLG 742
Cdd:cd00096    1 VTLTCSASGNPPPTITWYKNGKPLPPSSrdSRRSELGNGTLTISNVTLEDSGTYTCVASNSAG 63
VEGFR-2_TMD pfam17988
VEGFR-2 Transmembrane domain; This is a transmembrane domain (TMD) of vascular endothelial ...
757-791 8.26e-15

VEGFR-2 Transmembrane domain; This is a transmembrane domain (TMD) of vascular endothelial growth factor receptor 2 which regulates blood vessel homeostasis. Transmembrane signalling by receptor tyrosine kinases (RTKs) requires specific orientation of the intracellular kinase domains in active receptor dimers. Two mutants in VEGFR-2 TMD showed constitutive kinase activity, suggesting that precise TMD orientation is mandatory for kinase activation. Scanning mutagenesis and structural analysis indicated that introducing two polar amino acids in distinct positions of the TMD (G770E/F777E and I771E/L778E mutations) reorients transmembrane helices and leads to stable dimer formation. Therefore, it has been suggested that the transition between the inactive and the active dimeric state of VEGFR-2 implicates alternative dimeric TMD conformations.


Pssm-ID: 375470  Cd Length: 35  Bit Score: 69.29  E-value: 8.26e-15
                           10        20        30
                   ....*....|....*....|....*....|....*
gi 27777648    757 EKTNLEVIILVGTAVIAMFFWLLLVIVLRTVKRAN 791
Cdd:pfam17988    1 DKTNVELIILIGTGVIAMFFWLLLVLVIRNLKRPN 35
PTZ00283 PTZ00283
serine/threonine protein kinase; Provisional
1009-1155 2.31e-13

serine/threonine protein kinase; Provisional


Pssm-ID: 240344 [Multi-domain]  Cd Length: 496  Bit Score: 74.14  E-value: 2.31e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  1009 QVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARdIYKD--PDYVRKGDARLPLkWMAPETIFDRVYTIQSDV 1086
Cdd:PTZ00283  151 QVLLAVHHVHSKHMIHRDIKSANILLCSNGLVKLGDFGFSK-MYAAtvSDDVGRTFCGTPY-YVAPEIWRRKPYSKKADM 228
                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 27777648  1087 WSFGVLLWEIFSLgASPYPGVKIDEEFCRRLKeGTRMRAPDYTTPEMYQTMLDCWHEDPNQRPSFSELV 1155
Cdd:PTZ00283  229 FSLGVLLYELLTL-KRPFDGENMEEVMHKTLA-GRYDPLPPSISPEMQEIVTALLSSDPKRRPSSSKLL 295
Ig_3 pfam13927
Immunoglobulin domain; This family contains immunoglobulin-like domains.
339-404 5.56e-10

Immunoglobulin domain; This family contains immunoglobulin-like domains.


Pssm-ID: 464046 [Multi-domain]  Cd Length: 78  Bit Score: 56.80  E-value: 5.56e-10
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 27777648    339 KSLVEATVGSQVRIPVKYLSYPAPDIKWYRNGRPIESNYTMIVGDE-----LTIMEVTERDAGNYTVILTN 404
Cdd:pfam13927    8 PSSVTVREGETVTLTCEATGSPPPTITWYKNGEPISSGSTRSRSLSgsnstLTISNVTRSDAGTYTCVASN 78
IG_like smart00410
Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.
233-326 1.09e-08

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.


Pssm-ID: 214653 [Multi-domain]  Cd Length: 85  Bit Score: 53.66  E-value: 1.09e-08
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648     233 PHEIELSAGEKLVLNCTARTELNVglDFTWH----SPPSKSHHKKIVNRDvkpfpgtvakmFLSTLTIESVTKSDQGEYT 308
Cdd:smart00410    1 PPSVTVKEGESVTLSCEASGSPPP--EVTWYkqggKLLAESGRFSVSRSG-----------STSTLTISNVTPEDSGTYT 67
                            90
                    ....*....|....*...
gi 27777648     309 CVASSGRMIKRNRTFVRV 326
Cdd:smart00410   68 CAATNSSGSASSGTTLTV 85
ig pfam00047
Immunoglobulin domain; Members of the immunoglobulin superfamily are found in hundreds of ...
231-312 5.27e-08

Immunoglobulin domain; Members of the immunoglobulin superfamily are found in hundreds of proteins of different functions. Examples include antibodies, the giant muscle kinase titin and receptor tyrosine kinases. Immunoglobulin-like domains may be involved in protein-protein and protein-ligand interactions.


Pssm-ID: 395002  Cd Length: 86  Bit Score: 51.43  E-value: 5.27e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648    231 SPPHEIELSAGEKLVLNCTARTeLNVGLDFTWH----SPPSKSHHKKIVNRdvkpfpgtvakMFLSTLTIESVTKSDQGE 306
Cdd:pfam00047    1 SAPPTVTVLEGDSATLTCSAST-GSPGPDVTWSkeggTLIESLKVKHDNGR-----------TTQSSLLISNVTKEDAGT 68

                   ....*.
gi 27777648    307 YTCVAS 312
Cdd:pfam00047   69 YTCVVN 74
IG_like smart00410
Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.
342-419 1.82e-07

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.


Pssm-ID: 214653 [Multi-domain]  Cd Length: 85  Bit Score: 50.20  E-value: 1.82e-07
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648     342 VEATVGSQVRIPVKYLSYPAPDIKWYRNGR--PIESNYTMIVGD----ELTIMEVTERDAGNYTVILTNPISMEKQShmV 415
Cdd:smart00410    4 VTVKEGESVTLSCEASGSPPPEVTWYKQGGklLAESGRFSVSRSgstsTLTISNVTPEDSGTYTCAATNSSGSASSG--T 81

                    ....
gi 27777648     416 SLVV 419
Cdd:smart00410   82 TLTV 85
Ig_3 pfam13927
Immunoglobulin domain; This family contains immunoglobulin-like domains.
549-642 1.50e-05

Immunoglobulin domain; This family contains immunoglobulin-like domains.


Pssm-ID: 464046 [Multi-domain]  Cd Length: 78  Bit Score: 44.48  E-value: 1.50e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648    549 PEITVQPAAQ-PTEQESVSLLCTADRNTFENLTWYKLGSQATSVHMGESltpvcknldalwklngtmFSNSTNDILIVaf 627
Cdd:pfam13927    2 PVITVSPSSVtVREGETVTLTCEATGSPPPTITWYKNGEPISSGSTRSR------------------SLSGSNSTLTI-- 61
                           90
                   ....*....|....*
gi 27777648    628 QNASLQDQGDYVCSA 642
Cdd:pfam13927   62 SNVTRSDAGTYTCVA 76
IG_like smart00410
Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.
563-649 2.22e-03

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.


Pssm-ID: 214653 [Multi-domain]  Cd Length: 85  Bit Score: 38.64  E-value: 2.22e-03
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648     563 ESVSLLCTADRNTFENLTWYKLGsqatsvhmgesLTPVCKNLDALWKLNGTMFSnstndiLIvaFQNASLQDQGDYVCSA 642
Cdd:smart00410   10 ESVTLSCEASGSPPPEVTWYKQG-----------GKLLAESGRFSVSRSGSTST------LT--ISNVTPEDSGTYTCAA 70

                    ....*..
gi 27777648     643 QDKKTKK 649
Cdd:smart00410   71 TNSSGSA 77
 
Name Accession Description Interval E-value
PTKc_VEGFR2 cd05103
Catalytic domain of the Protein Tyrosine Kinase, Vascular Endothelial Growth Factor Receptor 2; ...
824-1165 0e+00

Catalytic domain of the Protein Tyrosine Kinase, Vascular Endothelial Growth Factor Receptor 2; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. VEGFR2 (or Flk1) binds the ligands VEGFA, VEGFC, VEGFD and VEGFE. VEGFR2 signaling is implicated in all aspects of normal and pathological vascular endothelial cell biology. It induces a variety of cellular effects including migration, survival, and proliferation. It is critical in regulating embryonic vascular development and angiogenesis. VEGFR2 is the major signal transducer in pathological angiogenesis including cancer and diabetic retinopathy, and is a target for inhibition in cancer therapy. The carboxyl terminus of VEGFR2 plays an important role in its autophosphorylation and activation. VEGFR2 is a member of the VEGFR subfamily of proteins, which are receptor PTKs (RTKs) containing an extracellular ligand-binding region with seven immunoglobulin (Ig)-like domains, a transmembrane segment, and an intracellular catalytic domain. The binding of VEGFRs to their ligands, the VEGFs, leads to receptor dimerization, activation, and intracellular signaling. The VEGFR2 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270681 [Multi-domain]  Cd Length: 343  Bit Score: 716.76  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  824 KWEFPRDRLKLGKPLGRGAFGQVIEADAFGIDKTATCKTVAVKMLKEGATHSEHRALMSELKILIHIGHHLNVVNLLGAC 903
Cdd:cd05103    1 KWEFPRDRLKLGKPLGRGAFGQVIEADAFGIDKTATCRTVAVKMLKEGATHSEHRALMSELKILIHIGHHLNVVNLLGAC 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  904 TKPGGPLMVIVEFCKFGNLSTYLRGKRNEFVPYKSKGARFRQGKDYVGELSVDLKRRLDSITSSQSSASSGFVEEKSLSD 983
Cdd:cd05103   81 TKPGGPLMVIVEFCKFGNLSAYLRSKRSEFVPYKTKGARFRQGKDYVGDISVDLKRRLDSITSSQSSASSGFVEEKSLSD 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  984 VEEEEASEE-LYKDFLTLEHLICYSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIYKDPDYVRKGD 1062
Cdd:cd05103  161 VEEEEAGQEdLYKDFLTLEDLICYSFQVAKGMEFLASRKCIHRDLAARNILLSENNVVKICDFGLARDIYKDPDYVRKGD 240
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1063 ARLPLKWMAPETIFDRVYTIQSDVWSFGVLLWEIFSLGASPYPGVKIDEEFCRRLKEGTRMRAPDYTTPEMYQTMLDCWH 1142
Cdd:cd05103  241 ARLPLKWMAPETIFDRVYTIQSDVWSFGVLLWEIFSLGASPYPGVKIDEEFCRRLKEGTRMRAPDYTTPEMYQTMLDCWH 320
                        330       340
                 ....*....|....*....|...
gi 27777648 1143 EDPNQRPSFSELVEHLGNLLQAN 1165
Cdd:cd05103  321 GEPSQRPTFSELVEHLGNLLQAN 343
PTKc_VEGFR cd05054
Catalytic domain of the Protein Tyrosine Kinases, Vascular Endothelial Growth Factor Receptors; ...
824-1161 0e+00

Catalytic domain of the Protein Tyrosine Kinases, Vascular Endothelial Growth Factor Receptors; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. The VEGFR subfamily consists of VEGFR1 (Flt1), VEGFR2 (Flk1), VEGFR3 (Flt4), and similar proteins. VEGFR subfamily members are receptor PTKss (RTKs) containing an extracellular ligand-binding region with seven immunoglobulin (Ig)-like domains, a transmembrane segment, and an intracellular catalytic domain. In VEGFR3, the fifth Ig-like domain is replaced by a disulfide bridge. The binding of VEGFRs to their ligands, the VEGFs, leads to receptor dimerization, activation, and intracellular signaling. There are five VEGF ligands in mammals, which bind, in an overlapping pattern to the three VEGFRs, which can form homo or heterodimers. VEGFRs regulate the cardiovascular system. They are critical for vascular development during embryogenesis and blood vessel formation in adults. They induce cellular functions common to other growth factor receptors such as cell migration, survival, and proliferation. The VEGFR subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270647 [Multi-domain]  Cd Length: 298  Bit Score: 620.66  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  824 KWEFPRDRLKLGKPLGRGAFGQVIEADAFGIDKTATCKTVAVKMLKEGATHSEHRALMSELKILIHIGHHLNVVNLLGAC 903
Cdd:cd05054    1 KWEFPRDRLKLGKPLGRGAFGKVIQASAFGIDKSATCRTVAVKMLKEGATASEHKALMTELKILIHIGHHLNVVNLLGAC 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  904 TKPGGPLMVIVEFCKFGNLSTYLRGKRNEFVPYKSKGARFRQGKDYVGELsvdlkrrldsitssqssassgfveekslsd 983
Cdd:cd05054   81 TKPGGPLMVIVEFCKFGNLSNYLRSKREEFVPYRDKGARDVEEEEDDDEL------------------------------ 130
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  984 veeeeaseelYKDFLTLEHLICYSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIYKDPDYVRKGDA 1063
Cdd:cd05054  131 ----------YKEPLTLEDLICYSFQVARGMEFLASRKCIHRDLAARNILLSENNVVKICDFGLARDIYKDPDYVRKGDA 200
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1064 RLPLKWMAPETIFDRVYTIQSDVWSFGVLLWEIFSLGASPYPGVKIDEEFCRRLKEGTRMRAPDYTTPEMYQTMLDCWHE 1143
Cdd:cd05054  201 RLPLKWMAPESIFDKVYTTQSDVWSFGVLLWEIFSLGASPYPGVQMDEEFCRRLKEGTRMRAPEYTTPEIYQIMLDCWHG 280
                        330
                 ....*....|....*...
gi 27777648 1144 DPNQRPSFSELVEHLGNL 1161
Cdd:cd05054  281 EPKERPTFSELVEKLGDL 298
PTKc_VEGFR1 cd14207
Catalytic domain of the Protein Tyrosine Kinases, Vascular Endothelial Growth Factor Receptors; ...
824-1161 0e+00

Catalytic domain of the Protein Tyrosine Kinases, Vascular Endothelial Growth Factor Receptors; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. VEGFR1 (or Flt1) binds VEGFA, VEGFB, and placenta growth factor (PLGF). It regulates monocyte and macrophage migration, vascular permeability, haematopoiesis, and the recruitment of haematopietic progenitor cells from the bone marrow. VEGFR1 is a member of the VEGFR subfamily of proteins, which are receptor PTKs (RTKs) containing an extracellular ligand-binding region with seven immunoglobulin (Ig)-like domains, a transmembrane segment, and an intracellular catalytic domain. The binding of VEGFRs to their ligands, the VEGFs, leads to receptor dimerization, activation, and intracellular signaling. The VEGFR1 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271109 [Multi-domain]  Cd Length: 340  Bit Score: 572.33  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  824 KWEFPRDRLKLGKPLGRGAFGQVIEADAFGIDKTATCKTVAVKMLKEGATHSEHRALMSELKILIHIGHHLNVVNLLGAC 903
Cdd:cd14207    1 KWEFARERLKLGKSLGRGAFGKVVQASAFGIKKSPTCRVVAVKMLKEGATASEYKALMTELKILIHIGHHLNVVNLLGAC 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  904 TKPGGPLMVIVEFCKFGNLSTYLRGKRNEFVPYKSKGARFRQGKDYVG-ELSVDLKRRLDSITSSQSSASSGFVEEKSLS 982
Cdd:cd14207   81 TKSGGPLMVIVEYCKYGNLSNYLKSKRDFFVTNKDTSLQEELIKEKKEaEPTGGKKKRLESVTSSESFASSGFQEDKSLS 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  983 DVEEEEASEE-LYKDFLTLEHLICYSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIYKDPDYVRKG 1061
Cdd:cd14207  161 DVEEEEEDSGdFYKRPLTMEDLISYSFQVARGMEFLSSRKCIHRDLAARNILLSENNVVKICDFGLARDIYKNPDYVRKG 240
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1062 DARLPLKWMAPETIFDRVYTIQSDVWSFGVLLWEIFSLGASPYPGVKIDEEFCRRLKEGTRMRAPDYTTPEMYQTMLDCW 1141
Cdd:cd14207  241 DARLPLKWMAPESIFDKIYSTKSDVWSYGVLLWEIFSLGASPYPGVQIDEDFCSKLKEGIRMRAPEFATSEIYQIMLDCW 320
                        330       340
                 ....*....|....*....|
gi 27777648 1142 HEDPNQRPSFSELVEHLGNL 1161
Cdd:cd14207  321 QGDPNERPRFSELVERLGDL 340
PTKc_VEGFR3 cd05102
Catalytic domain of the Protein Tyrosine Kinase, Vascular Endothelial Growth Factor Receptor 3; ...
824-1165 0e+00

Catalytic domain of the Protein Tyrosine Kinase, Vascular Endothelial Growth Factor Receptor 3; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. VEGFR3 (or Flt4) preferentially binds the ligands VEGFC and VEGFD. VEGFR3 is essential for lymphatic endothelial cell (EC) development and function. It has been shown to regulate adaptive immunity during corneal transplantation. VEGFR3 is upregulated on blood vascular ECs in pathological conditions such as vascular tumors and the periphery of solid tumors. It plays a role in cancer progression and lymph node metastasis. Missense mutations in the VEGFR3 gene are associated with primary human lymphedema. VEGFR3 is a member of the VEGFR subfamily of proteins, which are receptor PTKs (RTKs) containing an extracellular ligand-binding region with seven immunoglobulin (Ig)-like domains, a transmembrane segment, and an intracellular catalytic domain. In VEGFR3, the fifth Ig-like domain is replaced by a disulfide bridge. The binding of VEGFRs to their ligands, the VEGFs, leads to receptor dimerization, activation, and intracellular signaling. The VEGFR3 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270680 [Multi-domain]  Cd Length: 336  Bit Score: 570.77  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  824 KWEFPRDRLKLGKPLGRGAFGQVIEADAFGIDKTATCKTVAVKMLKEGATHSEHRALMSELKILIHIGHHLNVVNLLGAC 903
Cdd:cd05102    1 QWEFPRDRLRLGKVLGHGAFGKVVEASAFGIDKSSSCETVAVKMLKEGATASEHKALMSELKILIHIGNHLNVVNLLGAC 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  904 TKPGGPLMVIVEFCKFGNLSTYLRGKRNEFVPYKSKGARFRQGKDYVGELSvdlkrRLDSITSSQSSASSGFVEEKSlSD 983
Cdd:cd05102   81 TKPNGPLMVIVEFCKYGNLSNFLRAKREGFSPYRERSPRTRSQVRSMVEAV-----RADRRSRQGSDRVASFTESTS-ST 154
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  984 VEEEEASEELYKDFLTLEHLICYSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIYKDPDYVRKGDA 1063
Cdd:cd05102  155 NQPRQEVDDLWQSPLTMEDLICYSFQVARGMEFLASRKCIHRDLAARNILLSENNVVKICDFGLARDIYKDPDYVRKGSA 234
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1064 RLPLKWMAPETIFDRVYTIQSDVWSFGVLLWEIFSLGASPYPGVKIDEEFCRRLKEGTRMRAPDYTTPEMYQTMLDCWHE 1143
Cdd:cd05102  235 RLPLKWMAPESIFDKVYTTQSDVWSFGVLLWEIFSLGASPYPGVQINEEFCQRLKDGTRMRAPEYATPEIYRIMLSCWHG 314
                        330       340
                 ....*....|....*....|..
gi 27777648 1144 DPNQRPSFSELVEHLGNLLQAN 1165
Cdd:cd05102  315 DPKERPTFSDLVEILGDLLQEN 336
PTKc_PDGFR cd05055
Catalytic domain of the Protein Tyrosine Kinases, Platelet Derived Growth Factor Receptors; ...
817-1162 6.84e-129

Catalytic domain of the Protein Tyrosine Kinases, Platelet Derived Growth Factor Receptors; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. The PDGFR subfamily consists of PDGFR alpha, PDGFR beta, KIT, CSF-1R, the mammalian FLT3, and similar proteins. They are receptor PTKs (RTKs) containing an extracellular ligand-binding region with five immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. PDGFR kinase domains are autoinhibited by their juxtamembrane regions containing tyr residues. The binding to their ligands leads to receptor dimerization, trans phosphorylation and activation, and intracellular signaling. PDGFR subfamily receptors are important in the development of a variety of cells. PDGFRs are expressed in a many cells including fibroblasts, neurons, endometrial cells, mammary epithelial cells, and vascular smooth muscle cells. PDGFR signaling is critical in normal embryonic development, angiogenesis, and wound healing. Kit is important in the development of melanocytes, germ cells, mast cells, hematopoietic stem cells, the interstitial cells of Cajal, and the pacemaker cells of the GI tract. CSF-1R signaling is critical in the regulation of macrophages and osteoclasts. Mammalian FLT3 plays an important role in the survival, proliferation, and differentiation of stem cells. The PDGFR subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase .


Pssm-ID: 133186 [Multi-domain]  Cd Length: 302  Bit Score: 399.55  E-value: 6.84e-129
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  817 RLPYDaSKWEFPRDRLKLGKPLGRGAFGQVIEADAFGIDKTATCKTVAVKMLKEGATHSEHRALMSELKILIHIGHHLNV 896
Cdd:cd05055   23 QLPYD-LKWEFPRNNLSFGKTLGAGAFGKVVEATAYGLSKSDAVMKVAVKMLKPTAHSSEREALMSELKIMSHLGNHENI 101
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  897 VNLLGACTKpGGPLMVIVEFCKFGNLSTYLRGKRNEFvpykskgarfrqgkdyvgelsvdlkrrldsitssqssassgfv 976
Cdd:cd05055  102 VNLLGACTI-GGPILVITEYCCYGDLLNFLRRKRESF------------------------------------------- 137
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  977 eekslsdveeeeaseelykdfLTLEHLICYSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIYKDPD 1056
Cdd:cd05055  138 ---------------------LTLEDLLSFSYQVAKGMAFLASKNCIHRDLAARNVLLTHGKIVKICDFGLARDIMNDSN 196
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1057 YVRKGDARLPLKWMAPETIFDRVYTIQSDVWSFGVLLWEIFSLGASPYPGVKIDEEFCRRLKEGTRMRAPDYTTPEMYQT 1136
Cdd:cd05055  197 YVVKGNARLPVKWMAPESIFNCVYTFESDVWSYGILLWEIFSLGSNPYPGMPVDSKFYKLIKEGYRMAQPEHAPAEIYDI 276
                        330       340
                 ....*....|....*....|....*.
gi 27777648 1137 MLDCWHEDPNQRPSFSELVEHLGNLL 1162
Cdd:cd05055  277 MKTCWDADPLKRPTFKQIVQLIGKQL 302
PTKc_FGFR cd05053
Catalytic domain of the Protein Tyrosine Kinases, Fibroblast Growth Factor Receptors; PTKs ...
809-1162 4.01e-127

Catalytic domain of the Protein Tyrosine Kinases, Fibroblast Growth Factor Receptors; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. The FGFR subfamily consists of FGFR1, FGFR2, FGFR3, FGFR4, and similar proteins. They are receptor PTKs (RTKs) containing an extracellular ligand-binding region with three immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. The binding of FGFRs to their ligands, the FGFs, and to heparin/heparan sulfate (HS) results in the formation of a ternary complex, which leads to receptor dimerization and activation, and intracellular signaling. There are at least 23 FGFs and four types of FGFRs. The binding of FGFs to FGFRs is promiscuous, in that a receptor may be activated by several ligands and a ligand may bind to more that one type of receptor. FGF/FGFR signaling is important in the regulation of embryonic development, homeostasis, and regenerative processes. Depending on the cell type and stage, FGFR signaling produces diverse cellular responses including proliferation, growth arrest, differentiation, and apoptosis. Aberrant signaling leads to many human diseases such as skeletal, olfactory, and metabolic disorders, as well as cancer. The FGFR subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase .


Pssm-ID: 270646 [Multi-domain]  Cd Length: 294  Bit Score: 394.48  E-value: 4.01e-127
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  809 LPLDErcerlpydasKWEFPRDRLKLGKPLGRGAFGQVIEADAFGIDKTATCK-TVAVKMLKEGATHSEHRALMSELKIL 887
Cdd:cd05053    1 LPLDP----------EWELPRDRLTLGKPLGEGAFGQVVKAEAVGLDNKPNEVvTVAVKMLKDDATEKDLSDLVSEMEMM 70
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  888 IHIGHHLNVVNLLGACTKpGGPLMVIVEFCKFGNLSTYLRGKRnefvPykskgarfrQGKDYvgelSVDLKRRLdsitss 967
Cdd:cd05053   71 KMIGKHKNIINLLGACTQ-DGPLYVVVEYASKGNLREFLRARR----P---------PGEEA----SPDDPRVP------ 126
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  968 qssassgfvEEKslsdveeeeaseelykdfLTLEHLICYSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGL 1047
Cdd:cd05053  127 ---------EEQ------------------LTQKDLVSFAYQVARGMEYLASKKCIHRDLAARNVLVTEDNVMKIADFGL 179
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1048 ARDIYkDPDYVRK-GDARLPLKWMAPETIFDRVYTIQSDVWSFGVLLWEIFSLGASPYPGVKIDEEFcRRLKEGTRMRAP 1126
Cdd:cd05053  180 ARDIH-HIDYYRKtTNGRLPVKWMAPEALFDRVYTHQSDVWSFGVLLWEIFTLGGSPYPGIPVEELF-KLLKEGHRMEKP 257
                        330       340       350
                 ....*....|....*....|....*....|....*.
gi 27777648 1127 DYTTPEMYQTMLDCWHEDPNQRPSFSELVEHLGNLL 1162
Cdd:cd05053  258 QNCTQELYMLMRDCWHEVPSQRPTFKQLVEDLDRIL 293
PTKc_Kit cd05104
Catalytic domain of the Protein Tyrosine Kinase, Kit; PTKs catalyze the transfer of the ...
817-1156 4.53e-126

Catalytic domain of the Protein Tyrosine Kinase, Kit; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Kit is important in the development of melanocytes, germ cells, mast cells, hematopoietic stem cells, the interstitial cells of Cajal, and the pacemaker cells of the GI tract. Kit signaling is involved in major cellular functions including cell survival, proliferation, differentiation, adhesion, and chemotaxis. Mutations in Kit, which result in constitutive ligand-independent activation, are found in human cancers such as gastrointestinal stromal tumor (GIST) and testicular germ cell tumor (TGCT). The aberrant expression of Kit and/or SCF is associated with other tumor types such as systemic mastocytosis and cancers of the breast, neurons, lung, prostate, colon, and rectum. Although the structure of the human Kit catalytic domain is known, it is excluded from this specific alignment model because it contains a deletion in its sequence. Kit is a member of the Platelet Derived Growth Factor Receptor (PDGFR) subfamily of proteins, which are receptor PTKs (RTKs) containing an extracellular ligand-binding region with five immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. The binding of Kit to its ligand, the stem-cell factor (SCF), leads to receptor dimerization, trans phosphorylation and activation, and intracellular signaling. The Kit subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270682 [Multi-domain]  Cd Length: 375  Bit Score: 395.04  E-value: 4.53e-126
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  817 RLPYDaSKWEFPRDRLKLGKPLGRGAFGQVIEADAFGIDKTATCKTVAVKMLKEGATHSEHRALMSELKILIHIGHHLNV 896
Cdd:cd05104   23 QLPYD-HKWEFPRDRLRFGKTLGAGAFGKVVEATAYGLAKADSAMTVAVKMLKPSAHSTEREALMSELKVLSYLGNHINI 101
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  897 VNLLGACTKpGGPLMVIVEFCKFGNLSTYLRGKRNEFVPYK----SKGARFRQ--------------------GKDYVGE 952
Cdd:cd05104  102 VNLLGACTV-GGPTLVITEYCCYGDLLNFLRRKRDSFICPKfedlAEAALYRNllhqremacdslneymdmkpSVSYVVP 180
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  953 LSVDLKRRLDSITSSQSSASSGFVEEKSLSdveeeeaseelykdfLTLEHLICYSFQVAKGMEFLASRKCIHRDLAARNI 1032
Cdd:cd05104  181 TKADKRRGVRSGSYVDQDVTSEILEEDELA---------------LDTEDLLSFSYQVAKGMEFLASKNCIHRDLAARNI 245
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1033 LLSEKNVVKICDFGLARDIYKDPDYVRKGDARLPLKWMAPETIFDRVYTIQSDVWSFGVLLWEIFSLGASPYPGVKIDEE 1112
Cdd:cd05104  246 LLTHGRITKICDFGLARDIRNDSNYVVKGNARLPVKWMAPESIFECVYTFESDVWSYGILLWEIFSLGSSPYPGMPVDSK 325
                        330       340       350       360
                 ....*....|....*....|....*....|....*....|....
gi 27777648 1113 FCRRLKEGTRMRAPDYTTPEMYQTMLDCWHEDPNQRPSFSELVE 1156
Cdd:cd05104  326 FYKMIKEGYRMDSPEFAPSEMYDIMRSCWDADPLKRPTFKQIVQ 369
PTKc_CSF-1R cd05106
Catalytic domain of the Protein Tyrosine Kinase, Colony-Stimulating Factor-1 Receptor; PTKs ...
804-1162 2.83e-124

Catalytic domain of the Protein Tyrosine Kinase, Colony-Stimulating Factor-1 Receptor; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. CSF-1R, also called c-Fms, is a member of the Platelet Derived Growth Factor Receptor (PDGFR) subfamily of proteins, which are receptor PTKs (RTKs) containing an extracellular ligand-binding region with five immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. The binding of CSF-1R to its ligand, CSF-1, leads to receptor dimerization, trans phosphorylation and activation, and intracellular signaling. CSF-1R signaling is critical in the regulation of macrophages and osteoclasts. It leads to increases in gene transcription and protein translation, and induces cytoskeletal remodeling. CSF-1R signaling leads to a variety of cellular responses including survival, proliferation, and differentiation of target cells. It plays an important role in innate immunity, tissue development and function, and the pathogenesis of some diseases including atherosclerosis and cancer. CSF-1R signaling is also implicated in mammary gland development during pregnancy and lactation. Aberrant CSF-1/CSF-1R expression correlates with tumor cell invasiveness, poor clinical prognosis, and bone metastasis in breast cancer. Although the structure of the human CSF-1R catalytic domain is known, it is excluded from this specific alignment model because it contains a deletion in its sequence. The CSF-1R subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 133237 [Multi-domain]  Cd Length: 374  Bit Score: 389.97  E-value: 2.83e-124
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  804 MDPDELPLDErcerlpydasKWEFPRDRLKLGKPLGRGAFGQVIEADAFGIDKTATCKTVAVKMLKEGATHSEHRALMSE 883
Cdd:cd05106   22 IDPTQLPYNE----------KWEFPRDNLQFGKTLGAGAFGKVVEATAFGLGKEDNVLRVAVKMLKASAHTDEREALMSE 91
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  884 LKILIHIGHHLNVVNLLGACTKpGGPLMVIVEFCKFGNLSTYLRGKRNEFV-PYKSKGARFRQGKDYVgelSVDLKRR-L 961
Cdd:cd05106   92 LKILSHLGQHKNIVNLLGACTH-GGPVLVITEYCCYGDLLNFLRKKAETFLnFVMALPEISETSSDYK---NITLEKKyI 167
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  962 DSITSSQSSASSGFVEEKSLSDVEEEEASEELYKDF-----LTLEHLICYSFQVAKGMEFLASRKCIHRDLAARNILLSE 1036
Cdd:cd05106  168 RSDSGFSSQGSDTYVEMRPVSSSSSQSSDSKDEEDTedswpLDLDDLLRFSSQVAQGMDFLASKNCIHRDVAARNVLLTD 247
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1037 KNVVKICDFGLARDIYKDPDYVRKGDARLPLKWMAPETIFDRVYTIQSDVWSFGVLLWEIFSLGASPYPGVKIDEEFCRR 1116
Cdd:cd05106  248 GRVAKICDFGLARDIMNDSNYVVKGNARLPVKWMAPESIFDCVYTVQSDVWSYGILLWEIFSLGKSPYPGILVNSKFYKM 327
                        330       340       350       360
                 ....*....|....*....|....*....|....*....|....*.
gi 27777648 1117 LKEGTRMRAPDYTTPEMYQTMLDCWHEDPNQRPSFSELVEHLGNLL 1162
Cdd:cd05106  328 VKRGYQMSRPDFAPPEIYSIMKMCWNLEPTERPTFSQISQLIQRQL 373
PTKc cd00192
Catalytic domain of Protein Tyrosine Kinases; PTKs catalyze the transfer of the ...
836-1158 5.75e-124

Catalytic domain of Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. They can be classified into receptor and non-receptor tyr kinases. PTKs play important roles in many cellular processes including, lymphocyte activation, epithelium growth and maintenance, metabolism control, organogenesis regulation, survival, proliferation, differentiation, migration, adhesion, motility, and morphogenesis. Receptor tyr kinases (RTKs) are integral membrane proteins which contain an extracellular ligand-binding region, a transmembrane segment, and an intracellular tyr kinase domain. RTKs are usually activated through ligand binding, which causes dimerization and autophosphorylation of the intracellular tyr kinase catalytic domain, leading to intracellular signaling. Some RTKs are orphan receptors with no known ligands. Non-receptor (or cytoplasmic) tyr kinases are distributed in different intracellular compartments and are usually multi-domain proteins containing a catalytic tyr kinase domain as well as various regulatory domains such as SH3 and SH2. PTKs are usually autoinhibited and require a mechanism for activation. In many PTKs, the phosphorylation of tyr residues in the activation loop is essential for optimal activity. Aberrant expression of PTKs is associated with many development abnormalities and cancers.The PTK family is part of a larger superfamily that includes the catalytic domains of serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270623 [Multi-domain]  Cd Length: 262  Bit Score: 384.58  E-value: 5.75e-124
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  836 KPLGRGAFGQVIEADAFGIDKTATckTVAVKMLKEGATHSEHRALMSELKILIHIGHHlNVVNLLGACTKPGgPLMVIVE 915
Cdd:cd00192    1 KKLGEGAFGEVYKGKLKGGDGKTV--DVAVKTLKEDASESERKDFLKEARVMKKLGHP-NVVRLLGVCTEEE-PLYLVME 76
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  916 FCKFGNLSTYLRGKRNEFvpykskgarfrqgkdyvgelsvdlkrrldsitssqssassgfveekslsdveeeeasEELYK 995
Cdd:cd00192   77 YMEGGDLLDFLRKSRPVF---------------------------------------------------------PSPEP 99
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  996 DFLTLEHLICYSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIYKDPDYVRKGDARLPLKWMAPETI 1075
Cdd:cd00192  100 STLSLKDLLSFAIQIAKGMEYLASKKFVHRDLAARNCLVGEDLVVKISDFGLSRDIYDDDYYRKKTGGKLPIRWMAPESL 179
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1076 FDRVYTIQSDVWSFGVLLWEIFSLGASPYPGVKiDEEFCRRLKEGTRMRAPDYTTPEMYQTMLDCWHEDPNQRPSFSELV 1155
Cdd:cd00192  180 KDGIFTSKSDVWSFGVLLWEIFTLGATPYPGLS-NEEVLEYLRKGYRLPKPENCPDELYELMLSCWQLDPEDRPTFSELV 258

                 ...
gi 27777648 1156 EHL 1158
Cdd:cd00192  259 ERL 261
PK_Tyr_Ser-Thr pfam07714
Protein tyrosine and serine/threonine kinase; Protein phosphorylation, which plays a key role ...
832-1158 7.80e-123

Protein tyrosine and serine/threonine kinase; Protein phosphorylation, which plays a key role in most cellular activities, is a reversible process mediated by protein kinases and phosphoprotein phosphatases. Protein kinases catalyze the transfer of the gamma phosphate from nucleotide triphosphates (often ATP) to one or more amino acid residues in a protein substrate side chain, resulting in a conformational change affecting protein function. Phosphoprotein phosphatases catalyze the reverse process. Protein kinases fall into three broad classes, characterized with respect to substrate specificity; Serine/threonine-protein kinases, tyrosine-protein kinases, and dual specificity protein kinases (e.g. MEK - phosphorylates both Thr and Tyr on target proteins). This entry represents the catalytic domain found in a number of serine/threonine- and tyrosine-protein kinases. It does not include the catalytic domain of dual specificity kinases.


Pssm-ID: 462242 [Multi-domain]  Cd Length: 258  Bit Score: 381.46  E-value: 7.80e-123
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648    832 LKLGKPLGRGAFGQVIEADAFGiDKTATCKTVAVKMLKEGATHSEHRALMSELKILIHIgHHLNVVNLLGACTKpGGPLM 911
Cdd:pfam07714    1 LTLGEKLGEGAFGEVYKGTLKG-EGENTKIKVAVKTLKEGADEEEREDFLEEASIMKKL-DHPNIVKLLGVCTQ-GEPLY 77
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648    912 VIVEFCKFGNLSTYLRGKRNEfvpykskgarfrqgkdyvgelsvdlkrrldsitssqssassgfveekslsdveeeease 991
Cdd:pfam07714   78 IVTEYMPGGDLLDFLRKHKRK----------------------------------------------------------- 98
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648    992 elykdfLTLEHLICYSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIYKDPDYVRKGDARLPLKWMA 1071
Cdd:pfam07714   99 ------LTLKDLLSMALQIAKGMEYLESKNFVHRDLAARNCLVSENLVVKISDFGLSRDIYDDDYYRKRGGGKLPIKWMA 172
                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648   1072 PETIFDRVYTIQSDVWSFGVLLWEIFSLGASPYPGVKiDEEFCRRLKEGTRMRAPDYTTPEMYQTMLDCWHEDPNQRPSF 1151
Cdd:pfam07714  173 PESLKDGKFTSKSDVWSFGVLLWEIFTLGEQPYPGMS-NEEVLEFLEDGYRLPQPENCPDELYDLMKQCWAYDPEDRPTF 251

                   ....*..
gi 27777648   1152 SELVEHL 1158
Cdd:pfam07714  252 SELVEDL 258
PTKc_PDGFR_beta cd05107
Catalytic domain of the Protein Tyrosine Kinase, Platelet Derived Growth Factor Receptor beta; ...
798-1162 2.87e-116

Catalytic domain of the Protein Tyrosine Kinase, Platelet Derived Growth Factor Receptor beta; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. PDGFR beta is a receptor PTK (RTK) containing an extracellular ligand-binding region with five immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. The binding to its ligands, the PDGFs, leads to receptor dimerization, trans phosphorylation and activation, and intracellular signaling. PDGFR beta forms homodimers or heterodimers with PDGFR alpha, depending on the nature of the PDGF ligand. PDGF-BB and PDGF-DD induce PDGFR beta homodimerization. PDGFR signaling plays many roles in normal embryonic development and adult physiology. PDGFR beta signaling leads to a variety of cellular effects including the stimulation of cell growth and chemotaxis, as well as the inhibition of apoptosis and GAP junctional communication. It is critical in normal angiogenesis as it is involved in the recruitment of pericytes and smooth muscle cells essential for vessel stability. Aberrant PDGFR beta expression is associated with some human cancers. The continuously-active fusion proteins of PDGFR beta with COL1A1 and TEL are associated with dermatofibrosarcoma protuberans (DFSP) and a subset of chronic myelomonocytic leukemia (CMML), respectively. The PDGFR beta subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 133238 [Multi-domain]  Cd Length: 401  Bit Score: 369.72  E-value: 2.87e-116
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  798 GYLSIVMDPDELPLDercerlpydaSKWEFPRDRLKLGKPLGRGAFGQVIEADAFGIDKTATCKTVAVKMLKEGATHSEH 877
Cdd:cd05107   15 GHEYIYVDPMQLPYD----------SAWEMPRDNLVLGRTLGSGAFGRVVEATAHGLSHSQSTMKVAVKMLKSTARSSEK 84
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  878 RALMSELKILIHIGHHLNVVNLLGACTKpGGPLMVIVEFCKFGNLSTYLRGKRNEFVPYKSKGARfRQGKDYVGELSVDL 957
Cdd:cd05107   85 QALMSELKIMSHLGPHLNIVNLLGACTK-GGPIYIITEYCRYGDLVDYLHRNKHTFLQYYLDKNR-DDGSLISGGSTPLS 162
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  958 KRRldSITSSQSSASSGFVE---EKSLSDVEEEEASEEL-YKDF-------------------------------LTLEH 1002
Cdd:cd05107  163 QRK--SHVSLGSESDGGYMDmskDESADYVPMQDMKGTVkYADIessnyespydqylpsapertrrdtlinespaLSYMD 240
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1003 LICYSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIYKDPDYVRKGDARLPLKWMAPETIFDRVYTI 1082
Cdd:cd05107  241 LVGFSYQVANGMEFLASKNCVHRDLAARNVLICEGKLVKICDFGLARDIMRDSNYISKGSTFLPLKWMAPESIFNNLYTT 320
                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1083 QSDVWSFGVLLWEIFSLGASPYPGVKIDEEFCRRLKEGTRMRAPDYTTPEMYQTMLDCWHEDPNQRPSFSELVEHLGNLL 1162
Cdd:cd05107  321 LSDVWSFGILLWEIFTLGGTPYPELPMNEQFYNAIKRGYRMAKPAHASDEIYEIMQKCWEEKFEIRPDFSQLVHLVGDLL 400
PTKc_PDGFR_alpha cd05105
Catalytic domain of the Protein Tyrosine Kinase, Platelet Derived Growth Factor Receptor alpha; ...
798-1162 3.08e-116

Catalytic domain of the Protein Tyrosine Kinase, Platelet Derived Growth Factor Receptor alpha; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. PDGFR alpha is a receptor PTK (RTK) containing an extracellular ligand-binding region with five immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. The binding to its ligands, the PDGFs, leads to receptor dimerization, trans phosphorylation and activation, and intracellular signaling. PDGFR alpha forms homodimers or heterodimers with PDGFR beta, depending on the nature of the PDGF ligand. PDGF-AA, PDGF-AB, and PDGF-CC induce PDGFR alpha homodimerization. PDGFR signaling plays many roles in normal embryonic development and adult physiology. PDGFR alpha signaling is important in the formation of lung alveoli, intestinal villi, mesenchymal dermis, and hair follicles, as well as in the development of oligodendrocytes, retinal astrocytes, neural crest cells, and testicular cells. Aberrant PDGFR alpha expression is associated with some human cancers. Mutations in PDGFR alpha have been found within a subset of gastrointestinal stromal tumors (GISTs). An active fusion protein FIP1L1-PDGFR alpha, derived from interstitial deletion, is associated with idiopathic hypereosinophilic syndrome and chronic eosinophilic leukemia. The PDGFR alpha subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173653 [Multi-domain]  Cd Length: 400  Bit Score: 369.35  E-value: 3.08e-116
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  798 GYLSIVMDPDELPLDercerlpydaSKWEFPRDRLKLGKPLGRGAFGQVIEADAFGIDKTATCKTVAVKMLKEGATHSEH 877
Cdd:cd05105   15 GHEYIYVDPMQLPYD----------SRWEFPRDGLVLGRILGSGAFGKVVEGTAYGLSRSQPVMKVAVKMLKPTARSSEK 84
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  878 RALMSELKILIHIGHHLNVVNLLGACTKpGGPLMVIVEFCKFGNLSTYLRGKRNEFV---PYKSKGA------------- 941
Cdd:cd05105   85 QALMSELKIMTHLGPHLNIVNLLGACTK-SGPIYIITEYCFYGDLVNYLHKNRDNFLsrhPEKPKKDldifginpadest 163
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  942 ------RFRQGKDYVGELSVDLKR---RLDSITSSQSSASSGFV-----EEKSLSDVEEEEASEELYKDFLTLEHLICYS 1007
Cdd:cd05105  164 rsyvilSFENKGDYMDMKQADTTQyvpMLEIKEASKYSDIQRSNydrpaSYKGSNDSEVKNLLSDDGSEGLTTLDLLSFT 243
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1008 FQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIYKDPDYVRKGDARLPLKWMAPETIFDRVYTIQSDVW 1087
Cdd:cd05105  244 YQVARGMEFLASKNCVHRDLAARNVLLAQGKIVKICDFGLARDIMHDSNYVSKGSTFLPVKWMAPESIFDNLYTTLSDVW 323
                        330       340       350       360       370       380       390
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 27777648 1088 SFGVLLWEIFSLGASPYPGVKIDEEFCRRLKEGTRMRAPDYTTPEMYQTMLDCWHEDPNQRPSFSELVEHLGNLL 1162
Cdd:cd05105  324 SYGILLWEIFSLGGTPYPGMIVDSTFYNKIKSGYRMAKPDHATQEVYDIMVKCWNSEPEKRPSFLHLSDIVESLL 398
STYKc smart00221
Protein kinase; unclassified specificity; Phosphotransferases. The specificity of this class ...
832-1158 7.17e-114

Protein kinase; unclassified specificity; Phosphotransferases. The specificity of this class of kinases can not be predicted. Possible dual-specificity Ser/Thr/Tyr kinase.


Pssm-ID: 214568 [Multi-domain]  Cd Length: 258  Bit Score: 357.24  E-value: 7.17e-114
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648     832 LKLGKPLGRGAFGQVIEADAFGIDKTATCKtVAVKMLKEGATHSEHRALMSELKILIHIgHHLNVVNLLGACTKPGgPLM 911
Cdd:smart00221    1 LTLGKKLGEGAFGEVYKGTLKGKGDGKEVE-VAVKTLKEDASEQQIEEFLREARIMRKL-DHPNIVKLLGVCTEEE-PLM 77
                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648     912 VIVEFCKFGNLSTYLRGKRNEFvpykskgarfrqgkdyvgelsvdlkrrldsitssqssassgfveekslsdveeeease 991
Cdd:smart00221   78 IVMEYMPGGDLLDYLRKNRPKE---------------------------------------------------------- 99
                           170       180       190       200       210       220       230       240
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648     992 elykdfLTLEHLICYSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIYKDpDYVRKGDARLPLKWMA 1071
Cdd:smart00221  100 ------LSLSDLLSFALQIARGMEYLESKNFIHRDLAARNCLVGENLVVKISDFGLSRDLYDD-DYYKVKGGKLPIRWMA 172
                           250       260       270       280       290       300       310       320
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648    1072 PETIFDRVYTIQSDVWSFGVLLWEIFSLGASPYPGVKiDEEFCRRLKEGTRMRAPDYTTPEMYQTMLDCWHEDPNQRPSF 1151
Cdd:smart00221  173 PESLKEGKFTSKSDVWSFGVLLWEIFTLGEEPYPGMS-NAEVLEYLKKGYRLPKPPNCPPELYKLMLQCWAEDPEDRPTF 251

                    ....*..
gi 27777648    1152 SELVEHL 1158
Cdd:smart00221  252 SELVEIL 258
TyrKc smart00219
Tyrosine kinase, catalytic domain; Phosphotransferases. Tyrosine-specific kinase subfamily.
832-1158 1.23e-113

Tyrosine kinase, catalytic domain; Phosphotransferases. Tyrosine-specific kinase subfamily.


Pssm-ID: 197581 [Multi-domain]  Cd Length: 257  Bit Score: 356.46  E-value: 1.23e-113
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648     832 LKLGKPLGRGAFGQVIEADAFGIDKTaTCKTVAVKMLKEGATHSEHRALMSELKILIHIgHHLNVVNLLGACTKPGgPLM 911
Cdd:smart00219    1 LTLGKKLGEGAFGEVYKGKLKGKGGK-KKVEVAVKTLKEDASEQQIEEFLREARIMRKL-DHPNVVKLLGVCTEEE-PLY 77
                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648     912 VIVEFCKFGNLSTYLRGKRNEfvpykskgarfrqgkdyvgelsvdlkrrldsitssqssassgfveekslsdveeeease 991
Cdd:smart00219   78 IVMEYMEGGDLLSYLRKNRPK----------------------------------------------------------- 98
                           170       180       190       200       210       220       230       240
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648     992 elykdfLTLEHLICYSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIYKDpDYVRKGDARLPLKWMA 1071
Cdd:smart00219   99 ------LSLSDLLSFALQIARGMEYLESKNFIHRDLAARNCLVGENLVVKISDFGLSRDLYDD-DYYRKRGGKLPIRWMA 171
                           250       260       270       280       290       300       310       320
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648    1072 PETIFDRVYTIQSDVWSFGVLLWEIFSLGASPYPGVKiDEEFCRRLKEGTRMRAPDYTTPEMYQTMLDCWHEDPNQRPSF 1151
Cdd:smart00219  172 PESLKEGKFTSKSDVWSFGVLLWEIFTLGEQPYPGMS-NEEVLEYLKNGYRLPQPPNCPPELYDLMLQCWAEDPEDRPTF 250

                    ....*..
gi 27777648    1152 SELVEHL 1158
Cdd:smart00219  251 SELVEIL 257
PTKc_FGFR4 cd05099
Catalytic domain of the Protein Tyrosine Kinase, Fibroblast Growth Factor Receptor 4; PTKs ...
818-1168 5.61e-111

Catalytic domain of the Protein Tyrosine Kinase, Fibroblast Growth Factor Receptor 4; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Unlike other FGFRs, there is only one splice form of FGFR4. It binds FGF1, FGF2, FGF6, FGF19, and FGF23. FGF19 is a selective ligand for FGFR4. Although disruption of FGFR4 in mice causes no obvious phenotype, in vivo inhibition of FGFR4 in cultured skeletal muscle cells resulted in an arrest of muscle progenitor differentiation. FGF6 and FGFR4 are uniquely expressed in myofibers and satellite cells. FGF6/FGFR4 signaling appears to play a key role in the regulation of muscle regeneration. A polymorphism in FGFR4 is found in head and neck squamous cell carcinoma. FGFR4 is part of the FGFR subfamily, which are receptor PTKs (RTKs) containing an extracellular ligand-binding region with three immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. The binding of FGFRs to their ligands, the FGFs, results in receptor dimerization and activation, and intracellular signaling. The binding of FGFs to FGFRs is promiscuous, in that a receptor may be activated by several ligands and a ligand may bind to more that one type of receptor. The FGFR4 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 133230 [Multi-domain]  Cd Length: 314  Bit Score: 351.96  E-value: 5.61e-111
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  818 LPYDAsKWEFPRDRLKLGKPLGRGAFGQVIEADAFGIDKTATCK--TVAVKMLKEGATHSEHRALMSELKILIHIGHHLN 895
Cdd:cd05099    1 LPLDP-KWEFPRDRLVLGKPLGEGCFGQVVRAEAYGIDKSRPDQtvTVAVKMLKDNATDKDLADLISEMELMKLIGKHKN 79
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  896 VVNLLGACTKPGgPLMVIVEFCKFGNLSTYLRGKRNEfvpykskgarfrqGKDYvgelSVDLKRrldsitssqssassgf 975
Cdd:cd05099   80 IINLLGVCTQEG-PLYVIVEYAAKGNLREFLRARRPP-------------GPDY----TFDITK---------------- 125
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  976 VEEKSLSdveeeeaseelYKDfltlehLICYSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIYkDP 1055
Cdd:cd05099  126 VPEEQLS-----------FKD------LVSCAYQVARGMEYLESRRCIHRDLAARNVLVTEDNVMKIADFGLARGVH-DI 187
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1056 DYVRK-GDARLPLKWMAPETIFDRVYTIQSDVWSFGVLLWEIFSLGASPYPGVKIDEEFcRRLKEGTRMRAPDYTTPEMY 1134
Cdd:cd05099  188 DYYKKtSNGRLPVKWMAPEALFDRVYTHQSDVWSFGILMWEIFTLGGSPYPGIPVEELF-KLLREGHRMDKPSNCTHELY 266
                        330       340       350
                 ....*....|....*....|....*....|....
gi 27777648 1135 QTMLDCWHEDPNQRPSFSELVEHLGNLLQANAQQ 1168
Cdd:cd05099  267 MLMRECWHAVPTQRPTFKQLVEALDKVLAAVSEE 300
PTKc_FGFR2 cd05101
Catalytic domain of the Protein Tyrosine Kinase, Fibroblast Growth Factor Receptor 2; PTKs ...
807-1169 4.21e-107

Catalytic domain of the Protein Tyrosine Kinase, Fibroblast Growth Factor Receptor 2; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. There are many splice variants of FGFR2 which show differential expression and binding to FGF ligands. Disruption of either FGFR2 or FGFR2b is lethal in mice, due to defects in the placenta or severe impairment of tissue development including lung, limb, and thyroid, respectively. Disruption of FGFR2c in mice results in defective bone and skull development. Genetic alterations of FGFR2 are associated with many human skeletal disorders including Apert syndrome, Crouzon syndrome, Jackson-Weiss syndrome, and Pfeiffer syndrome. FGFR2 is part of the FGFR subfamily, which are receptor PTKs (RTKs) containing an extracellular ligand-binding region with three immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. The binding of FGFRs to their ligands, the FGFs, results in receptor dimerization and activation, and intracellular signaling. The binding of FGFs to FGFRs is promiscuous, in that a receptor may be activated by several ligands and a ligand may bind to more that one type of receptor. The FGFR2 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270679 [Multi-domain]  Cd Length: 313  Bit Score: 341.22  E-value: 4.21e-107
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  807 DELPLDERCE-RLPYDAsKWEFPRDRLKLGKPLGRGAFGQVIEADAFGIDKTATCK--TVAVKMLKEGATHSEHRALMSE 883
Cdd:cd05101    1 DAPMLAGVSEyELPEDP-KWEFPRDKLTLGKPLGEGCFGQVVMAEAVGIDKDKPKEavTVAVKMLKDDATEKDLSDLVSE 79
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  884 LKILIHIGHHLNVVNLLGACTKpGGPLMVIVEFCKFGNLSTYLRGKRNEFVPYkskgarfrqgkdyvgelSVDLKRRLDS 963
Cdd:cd05101   80 MEMMKMIGKHKNIINLLGACTQ-DGPLYVIVEYASKGNLREYLRARRPPGMEY-----------------SYDINRVPEE 141
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  964 ItssqssassgfveekslsdveeeeaseelykdfLTLEHLICYSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKIC 1043
Cdd:cd05101  142 Q---------------------------------MTFKDLVSCTYQLARGMEYLASQKCIHRDLAARNVLVTENNVMKIA 188
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1044 DFGLARDIYKDPDYVRKGDARLPLKWMAPETIFDRVYTIQSDVWSFGVLLWEIFSLGASPYPGVKIDEEFcRRLKEGTRM 1123
Cdd:cd05101  189 DFGLARDINNIDYYKKTTNGRLPVKWMAPEALFDRVYTHQSDVWSFGVLMWEIFTLGGSPYPGIPVEELF-KLLKEGHRM 267
                        330       340       350       360
                 ....*....|....*....|....*....|....*....|....*.
gi 27777648 1124 RAPDYTTPEMYQTMLDCWHEDPNQRPSFSELVEHLGNLLQANAQQD 1169
Cdd:cd05101  268 DKPANCTNELYMMMRDCWHAVPSQRPTFKQLVEDLDRILTLTTNEE 313
PTKc_FGFR1 cd05098
Catalytic domain of the Protein Tyrosine Kinase, Fibroblast Growth Factor Receptor 1; PTKs ...
818-1169 6.28e-105

Catalytic domain of the Protein Tyrosine Kinase, Fibroblast Growth Factor Receptor 1; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Alternative splicing of FGFR1 transcripts produces a variety of isoforms, which are differentially expressed in cells. FGFR1 binds the ligands, FGF1 and FGF2, with high affinity and has also been reported to bind FGF4, FGF6, and FGF9. FGFR1 signaling is critical in the control of cell migration during embryo development. It promotes cell proliferation in fibroblasts. Nuclear FGFR1 plays a role in the regulation of transcription. Mutations, insertions or deletions of FGFR1 have been identified in patients with Kallman's syndrome (KS), an inherited disorder characterized by hypogonadotropic hypogonadism and loss of olfaction. Aberrant FGFR1 expression has been found in some human cancers including 8P11 myeloproliferative syndrome (EMS), breast cancer, and pancreatic adenocarcinoma. FGFR1 is part of the FGFR subfamily, which are receptor PTKs (RTKs) containing an extracellular ligand-binding region with three immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. The binding of FGFRs to their ligands, the FGFs, results in receptor dimerization and activation, and intracellular signaling. The binding of FGFs to FGFRs is promiscuous, in that a receptor may be activated by several ligands and a ligand may bind to more that one type of receptor. The FGFR1 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270678 [Multi-domain]  Cd Length: 302  Bit Score: 335.06  E-value: 6.28e-105
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  818 LPYDaSKWEFPRDRLKLGKPLGRGAFGQVIEADAFGIDKTATCKT--VAVKMLKEGATHSEHRALMSELKILIHIGHHLN 895
Cdd:cd05098    2 LPED-PRWELPRDRLVLGKPLGEGCFGQVVLAEAIGLDKDKPNRVtkVAVKMLKSDATEKDLSDLISEMEMMKMIGKHKN 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  896 VVNLLGACTKpGGPLMVIVEFCKFGNLSTYLRGKRnefvpykSKGARFRQGKDYVGElsvdlkrrldsitssqssassgf 975
Cdd:cd05098   81 IINLLGACTQ-DGPLYVIVEYASKGNLREYLQARR-------PPGMEYCYNPSHNPE----------------------- 129
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  976 veekslsdveeeeaseelykDFLTLEHLICYSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIYKDP 1055
Cdd:cd05098  130 --------------------EQLSSKDLVSCAYQVARGMEYLASKKCIHRDLAARNVLVTEDNVMKIADFGLARDIHHID 189
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1056 DYVRKGDARLPLKWMAPETIFDRVYTIQSDVWSFGVLLWEIFSLGASPYPGVKIDEEFcRRLKEGTRMRAPDYTTPEMYQ 1135
Cdd:cd05098  190 YYKKTTNGRLPVKWMAPEALFDRIYTHQSDVWSFGVLLWEIFTLGGSPYPGVPVEELF-KLLKEGHRMDKPSNCTNELYM 268
                        330       340       350
                 ....*....|....*....|....*....|....
gi 27777648 1136 TMLDCWHEDPNQRPSFSELVEHLGNLLQANAQQD 1169
Cdd:cd05098  269 MMRDCWHAVPSQRPTFKQLVEDLDRIVALTSNQE 302
PTKc_FGFR3 cd05100
Catalytic domain of the Protein Tyrosine Kinase, Fibroblast Growth Factor Receptor 3; PTKs ...
818-1199 3.13e-103

Catalytic domain of the Protein Tyrosine Kinase, Fibroblast Growth Factor Receptor 3; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Many FGFR3 splice variants have been reported with the IIIb and IIIc isoforms being the predominant forms. FGFR3 IIIc is the isoform expressed in chondrocytes, the cells affected in dwarfism, while IIIb is expressed in epithelial cells. FGFR3 ligands include FGF1, FGF2, FGF4, FGF8, FGF9, and FGF23. It is a negative regulator of long bone growth. In the cochlear duct and in the lens, FGFR3 is involved in differentiation while it appears to have a role in cell proliferation in epithelial cells. Germline mutations in FGFR3 are associated with skeletal disorders including several forms of dwarfism. Some missense mutations are associated with multiple myeloma and carcinomas of the bladder and cervix. Overexpression of FGFR3 is found in thyroid carcinoma. FGFR3 is part of the FGFR subfamily, which are receptor PTKs (RTKs) containing an extracellular ligand-binding region with three immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. The binding of FGFRs to their ligands, the FGFs, results in receptor dimerization and activation, and intracellular signaling. The binding of FGFs to FGFRs is promiscuous, in that a receptor may be activated by several ligands and a ligand may bind to more that one type of receptor. The FGFR3 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173652 [Multi-domain]  Cd Length: 334  Bit Score: 331.60  E-value: 3.13e-103
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  818 LPYDAsKWEFPRDRLKLGKPLGRGAFGQVIEADAFGIDKTATCK--TVAVKMLKEGATHSEHRALMSELKILIHIGHHLN 895
Cdd:cd05100    1 LPADP-KWELSRTRLTLGKPLGEGCFGQVVMAEAIGIDKDKPNKpvTVAVKMLKDDATDKDLSDLVSEMEMMKMIGKHKN 79
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  896 VVNLLGACTKpGGPLMVIVEFCKFGNLSTYLRGKRNEfvpykskgarfrqGKDYvgelSVDLKRrldsitssqssassgf 975
Cdd:cd05100   80 IINLLGACTQ-DGPLYVLVEYASKGNLREYLRARRPP-------------GMDY----SFDTCK---------------- 125
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  976 veekslsdveeeeaseeLYKDFLTLEHLICYSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIYKDP 1055
Cdd:cd05100  126 -----------------LPEEQLTFKDLVSCAYQVARGMEYLASQKCIHRDLAARNVLVTEDNVMKIADFGLARDVHNID 188
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1056 DYVRKGDARLPLKWMAPETIFDRVYTIQSDVWSFGVLLWEIFSLGASPYPGVKIDEEFcRRLKEGTRMRAPDYTTPEMYQ 1135
Cdd:cd05100  189 YYKKTTNGRLPVKWMAPEALFDRVYTHQSDVWSFGVLLWEIFTLGGSPYPGIPVEELF-KLLKEGHRMDKPANCTHELYM 267
                        330       340       350       360       370       380
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 27777648 1136 TMLDCWHEDPNQRPSFSELVEHLGNLLQANAQQDGKDYIVlPMsetlsmeEDSGLSLPTSPVSC 1199
Cdd:cd05100  268 IMRECWHAVPSQRPTFKQLVEDLDRVLTVTSTDEYLDLSV-PF-------EQYSPGCPDSPSSC 323
PTKc_RET cd05045
Catalytic domain of the Protein Tyrosine Kinase, REarranged during Transfection protein; PTKs ...
831-1165 3.39e-89

Catalytic domain of the Protein Tyrosine Kinase, REarranged during Transfection protein; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. RET is a receptor PTK (RTK) containing an extracellular region with four cadherin-like repeats, a calcium-binding site, and a cysteine-rich domain, a transmembrane segment, and an intracellular catalytic domain. It is part of a multisubunit complex that binds glial-derived neurotropic factor (GDNF) family ligands (GFLs) including GDNF, neurturin, artemin, and persephin. GFLs bind RET along with four GPI-anchored coreceptors, bringing two RET molecules together, leading to autophosphorylation, activation, and intracellular signaling. RET is essential for the development of the sympathetic, parasympathetic and enteric nervous systems, and the kidney. RET disruption by germline mutations causes diseases in humans including congenital aganglionosis of the gastrointestinal tract (Hirschsprung's disease) and three related inherited cancers: multiple endocrine neoplasia type 2A (MEN2A), MEN2B, and familial medullary thyroid carcinoma. The RET subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173631 [Multi-domain]  Cd Length: 290  Bit Score: 291.10  E-value: 3.39e-89
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  831 RLKLGKPLGRGAFGQVIEADAFGIDKTATCKTVAVKMLKEGATHSEHRALMSELKILIHIGHHlNVVNLLGACTKpGGPL 910
Cdd:cd05045    1 NLVLGKTLGEGEFGKVVKATAFRLKGRAGYTTVAVKMLKENASSSELRDLLSEFNLLKQVNHP-HVIKLYGACSQ-DGPL 78
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  911 MVIVEFCKFGNLSTYLRGKRnefvpykskgarfRQGKDYVGELSVDLKRRLDSITSSQssassgfveekslsdveeeeas 990
Cdd:cd05045   79 LLIVEYAKYGSLRSFLRESR-------------KVGPSYLGSDGNRNSSYLDNPDERA---------------------- 123
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  991 eelykdfLTLEHLICYSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIYKDPDYVRKGDARLPLKWM 1070
Cdd:cd05045  124 -------LTMGDLISFAWQISRGMQYLAEMKLVHRDLAARNVLVAEGRKMKISDFGLSRDVYEEDSYVKRSKGRIPVKWM 196
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1071 APETIFDRVYTIQSDVWSFGVLLWEIFSLGASPYPGVKiDEEFCRRLKEGTRMRAPDYTTPEMYQTMLDCWHEDPNQRPS 1150
Cdd:cd05045  197 AIESLFDHIYTTQSDVWSFGVLLWEIVTLGGNPYPGIA-PERLFNLLKTGYRMERPENCSEEMYNLMLTCWKQEPDKRPT 275
                        330
                 ....*....|....*
gi 27777648 1151 FSELVEHLGNLLQAN 1165
Cdd:cd05045  276 FADISKELEKMMVKS 290
PTKc_InsR_like cd05032
Catalytic domain of Insulin Receptor-like Protein Tyrosine Kinases; PTKs catalyze the transfer ...
825-1158 4.67e-76

Catalytic domain of Insulin Receptor-like Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. The InsR subfamily is composed of InsR, Insulin-like Growth Factor-1 Receptor (IGF-1R), and similar proteins. InsR and IGF-1R are receptor PTKs (RTKs) composed of two alphabeta heterodimers. Binding of the ligand (insulin, IGF-1, or IGF-2) to the extracellular alpha subunit activates the intracellular tyr kinase domain of the transmembrane beta subunit. Receptor activation leads to autophosphorylation, stimulating downstream kinase activities, which initiate signaling cascades and biological function. InsR and IGF-1R, which share 84% sequence identity in their kinase domains, display physiologically distinct yet overlapping functions in cell growth, differentiation, and metabolism. InsR activation leads primarily to metabolic effects while IGF-1R activation stimulates mitogenic pathways. In cells expressing both receptors, InsR/IGF-1R hybrids are found together with classical receptors. Both receptors can interact with common adaptor molecules such as IRS-1 and IRS-2. The InsR-like subfamily is part of a larger superfamily that includes the catalytic domains of serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173625 [Multi-domain]  Cd Length: 277  Bit Score: 253.42  E-value: 4.67e-76
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  825 WEFPRDRLKLGKPLGRGAFGQVIEADAFGIDKTATCKTVAVKMLKEGATHSEHRALMSELKILIHIGHHlNVVNLLGACT 904
Cdd:cd05032    1 WELPREKITLIRELGQGSFGMVYEGLAKGVVKGEPETRVAIKTVNENASMRERIEFLNEASVMKEFNCH-HVVRLLGVVS 79
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  905 KpGGPLMVIVEFCKFGNLSTYLRGKRNEfvpykskgARFRQGKDyvgelsvdlkrrldsitssqssassgfveekslsdv 984
Cdd:cd05032   80 T-GQPTLVVMELMAKGDLKSYLRSRRPE--------AENNPGLG------------------------------------ 114
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  985 eeeeaseelykdFLTLEHLICYSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIYKDpDYVRK-GDA 1063
Cdd:cd05032  115 ------------PPTLQKFIQMAAEIADGMAYLAAKKFVHRDLAARNCMVAEDLTVKIGDFGMTRDIYET-DYYRKgGKG 181
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1064 RLPLKWMAPETIFDRVYTIQSDVWSFGVLLWEIFSLGASPYPGvKIDEEFCRRLKEGTRMRAPDYTTPEMYQTMLDCWHE 1143
Cdd:cd05032  182 LLPVRWMAPESLKDGVFTTKSDVWSFGVVLWEMATLAEQPYQG-LSNEEVLKFVIDGGHLDLPENCPDKLLELMRMCWQY 260
                        330
                 ....*....|....*
gi 27777648 1144 DPNQRPSFSELVEHL 1158
Cdd:cd05032  261 NPKMRPTFLEIVSSL 275
PTKc_ALK_LTK cd05036
Catalytic domain of the Protein Tyrosine Kinases, Anaplastic Lymphoma Kinase and Leukocyte ...
826-1159 4.83e-69

Catalytic domain of the Protein Tyrosine Kinases, Anaplastic Lymphoma Kinase and Leukocyte Tyrosine Kinase; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyr residues in protein substrates. ALK and LTK are orphan receptor PTKs (RTKs) whose ligands are not yet well-defined. ALK appears to play an important role in mammalian neural development as well as visceral muscle differentiation in Drosophila. ALK is aberrantly expressed as fusion proteins, due to chromosomal translocations, in about 60% of anaplastic large cell lymphomas (ALCLs). ALK fusion proteins are also found in rare cases of diffuse large B cell lymphomas (DLBCLs). LTK is mainly expressed in B lymphocytes and neuronal tissues. It is important in cell proliferation and survival. Transgenic mice expressing TLK display retarded growth and high mortality rate. In addition, a polymorphism in mouse and human LTK is implicated in the pathogenesis of systemic lupus erythematosus. RTKs contain an extracellular ligand-binding domain, a transmembrane region, and an intracellular tyr kinase domain. They are usually activated through ligand binding, which causes dimerization and autophosphorylation of the intracellular tyr kinase catalytic domain. The ALK/LTK subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270632 [Multi-domain]  Cd Length: 277  Bit Score: 233.43  E-value: 4.83e-69
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  826 EFPRDRLKLGKPLGRGAFGQVIEADAFGIDKTATCKTVAVKMLKEGAT-HSEHRALMSELkiLIHIGHHLNVVNLLGACT 904
Cdd:cd05036    2 EVPRKNLTLIRALGQGAFGEVYEGTVSGMPGDPSPLQVAVKTLPELCSeQDEMDFLMEAL--IMSKFNHPNIVRCIGVCF 79
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  905 KPGgPLMVIVEFCKFGNLSTYLRGKRNEfvpykskgarfrqgkdyvgelsvdlkrrldsitssqssassgfvEEKSLSdv 984
Cdd:cd05036   80 QRL-PRFILLELMAGGDLKSFLRENRPR--------------------------------------------PEQPSS-- 112
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  985 eeeeaseelykdfLTLEHLICYSFQVAKGMEFLASRKCIHRDLAARNILLSEK---NVVKICDFGLARDIYKdPDYVRKG 1061
Cdd:cd05036  113 -------------LTMLDLLQLAQDVAKGCRYLEENHFIHRDIAARNCLLTCKgpgRVAKIGDFGMARDIYR-ADYYRKG 178
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1062 D-ARLPLKWMAPETIFDRVYTIQSDVWSFGVLLWEIFSLGASPYPGvKIDEEFCRRLKEGTRMRAPDYTTPEMYQTMLDC 1140
Cdd:cd05036  179 GkAMLPVKWMPPEAFLDGIFTSKTDVWSFGVLLWEIFSLGYMPYPG-KSNQEVMEFVTSGGRMDPPKNCPGPVYRIMTQC 257
                        330
                 ....*....|....*....
gi 27777648 1141 WHEDPNQRPSFSELVEHLG 1159
Cdd:cd05036  258 WQHIPEDRPNFSTILERLN 276
PTKc_Csk_like cd05039
Catalytic domain of C-terminal Src kinase-like Protein Tyrosine Kinases; PTKs catalyze the ...
825-1161 4.84e-67

Catalytic domain of C-terminal Src kinase-like Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. This subfamily is composed of Csk, Chk, and similar proteins. They are cytoplasmic (or nonreceptor) PTKs containing the Src homology domains, SH3 and SH2, N-terminal to the catalytic tyr kinase domain. They negatively regulate the activity of Src kinases that are anchored to the plasma membrane. To inhibit Src kinases, Csk and Chk are translocated to the membrane via binding to specific transmembrane proteins, G-proteins, or adaptor proteins near the membrane. Csk catalyzes the tyr phosphorylation of the regulatory C-terminal tail of Src kinases, resulting in their inactivation. Chk inhibit Src kinases using a noncatalytic mechanism by simply binding to them. As negative regulators of Src kinases, Csk and Chk play important roles in cell proliferation, survival, and differentiation, and consequently, in cancer development and progression. The Csk-like subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270635 [Multi-domain]  Cd Length: 256  Bit Score: 226.85  E-value: 4.84e-67
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  825 WEFPRDRLKLGKPLGRGAFGQVIEADAFGidktatcKTVAVKMLKEGATHSEhrALMSELKILIHIgHHLNVVNLLGACT 904
Cdd:cd05039    1 WAINKKDLKLGELIGKGEFGDVMLGDYRG-------QKVAVKCLKDDSTAAQ--AFLAEASVMTTL-RHPNLVQLLGVVL 70
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  905 KpGGPLMVIVEFCKFGNLSTYLRgkrnefvpykSKGarfrqgkdyvgelsvdlkrrldsitssqssassgfveekslsdv 984
Cdd:cd05039   71 E-GNGLYIVTEYMAKGSLVDYLR----------SRG-------------------------------------------- 95
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  985 eeeeaseelyKDFLTLEHLICYSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIYKDPDyvrkgDAR 1064
Cdd:cd05039   96 ----------RAVITRKDQLGFALDVCEGMEYLESKKFVHRDLAARNVLVSEDNVAKVSDFGLAKEASSNQD-----GGK 160
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1065 LPLKWMAPETIFDRVYTIQSDVWSFGVLLWEIFSLGASPYPGVKIDeEFCRRLKEGTRMRAPDYTTPEMYQTMLDCWHED 1144
Cdd:cd05039  161 LPIKWTAPEALREKKFSTKSDVWSFGILLWEIYSFGRVPYPRIPLK-DVVPHVEKGYRMEAPEGCPPEVYKVMKNCWELD 239
                        330
                 ....*....|....*..
gi 27777648 1145 PNQRPSFSELVEHLGNL 1161
Cdd:cd05039  240 PAKRPTFKQLREKLEHI 256
PTKc_c-ros cd05044
Catalytic domain of the Protein Tyrosine Kinase, C-ros; PTKs catalyze the transfer of the ...
838-1160 1.12e-65

Catalytic domain of the Protein Tyrosine Kinase, C-ros; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. This subfamily contains c-ros, Sevenless, and similar proteins. The proto-oncogene c-ros encodes an orphan receptor PTK (RTK) with an unknown ligand. RTKs contain an extracellular ligand-binding domain, a transmembrane region, and an intracellular tyr kinase domain. RTKs are usually activated through ligand binding, which causes dimerization and autophosphorylation of the intracellular tyr kinase catalytic domain. C-ros is expressed in embryonic cells of the kidney, intestine and lung, but disappears soon after birth. It persists only in the adult epididymis. Male mice bearing inactive mutations of c-ros lack the initial segment of the epididymis and are infertile. The Drosophila protein, Sevenless, is required for the specification of the R7 photoreceptor cell during eye development. The c-ros subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270640 [Multi-domain]  Cd Length: 268  Bit Score: 223.45  E-value: 1.12e-65
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  838 LGRGAFGQVIEADAFGIDKTATCKT-VAVKMLKEGATHSEHR------ALMSELKilihighHLNVVNLLGACTKpGGPL 910
Cdd:cd05044    3 LGSGAFGEVFEGTAKDILGDGSGETkVAVKTLRKGATDQEKAeflkeaHLMSNFK-------HPNILKLLGVCLD-NDPQ 74
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  911 MVIVEFCKFGNLSTYLRGKRNEfVPYKSKgarfrqgkdyvgelsvdlkrrldsitssqssassgfveekslsdveeeeas 990
Cdd:cd05044   75 YIILELMEGGDLLSYLRAARPT-AFTPPL--------------------------------------------------- 102
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  991 eelykdfLTLEHLICYSFQVAKGMEFLASRKCIHRDLAARNILLSEKN----VVKICDFGLARDIYKDpDYVRK-GDARL 1065
Cdd:cd05044  103 -------LTLKDLLSICVDVAKGCVYLEDMHFVHRDLAARNCLVSSKDyrerVVKIGDFGLARDIYKN-DYYRKeGEGLL 174
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1066 PLKWMAPETIFDRVYTIQSDVWSFGVLLWEIFSLGASPYPGvKIDEEFCRRLKEGTRMRAPDYTTPEMYQTMLDCWHEDP 1145
Cdd:cd05044  175 PVRWMAPESLVDGVFTTQSDVWAFGVLMWEILTLGQQPYPA-RNNLEVLHFVRAGGRLDQPDNCPDDLYELMLRCWSTDP 253
                        330
                 ....*....|....*
gi 27777648 1146 NQRPSFSELVEHLGN 1160
Cdd:cd05044  254 EERPSFARILEQLQN 268
PTKc_Musk cd05050
Catalytic domain of the Protein Tyrosine Kinase, Muscle-specific kinase; PTKs catalyze the ...
826-1154 3.11e-65

Catalytic domain of the Protein Tyrosine Kinase, Muscle-specific kinase; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Musk is a receptor PTK (RTK) containing an extracellular region with four immunoglobulin-like domains and a cysteine-rich cluster, a transmembrane segment, and an intracellular catalytic domain. Musk is expressed and concentrated in the postsynaptic membrane in skeletal muscle. It is essential for the establishment of the neuromuscular junction (NMJ), a peripheral synapse that conveys signals from motor neurons to muscle cells. Agrin, a large proteoglycan released from motor neurons, stimulates Musk autophosphorylation and activation, leading to the clustering of acetylcholine receptors (AChRs). To date, there is no evidence to suggest that agrin binds directly to Musk. Mutations in AChR, Musk and other partners are responsible for diseases of the NMJ, such as the autoimmune syndrome myasthenia gravis. The Musk subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 133181 [Multi-domain]  Cd Length: 288  Bit Score: 223.17  E-value: 3.11e-65
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  826 EFPRDRLKLGKPLGRGAFGQVIEADAFGIDKTATCKTVAVKMLKEGATHSEHR------ALMSELKilihighHLNVVNL 899
Cdd:cd05050    1 EYPRNNIEYVRDIGQGAFGRVFQARAPGLLPYEPFTMVAVKMLKEEASADMQAdfqreaALMAEFD-------HPNIVKL 73
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  900 LGACTKpGGPLMVIVEFCKFGNLSTYLRGKRNEFVPykskgarfrqgkdyvgelsvdlkrrldsitssqssassgfveek 979
Cdd:cd05050   74 LGVCAV-GKPMCLLFEYMAYGDLNEFLRHRSPRAQC-------------------------------------------- 108
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  980 SLSDVEEEEASEELYKDFLTLEHLICYSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIYKDPDYVR 1059
Cdd:cd05050  109 SLSHSTSSARKCGLNPLPLSCTEQLCIAKQVAAGMAYLSERKFVHRDLATRNCLVGENMVVKIADFGLSRNIYSADYYKA 188
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1060 KGDARLPLKWMAPETIFDRVYTIQSDVWSFGVLLWEIFSLGASPYPGVKiDEEFCRRLKEGTRMRAPDYTTPEMYQTMLD 1139
Cdd:cd05050  189 SENDAIPIRWMPPESIFYNRYTTESDVWAYGVVLWEIFSYGMQPYYGMA-HEEVIYYVRDGNVLSCPDNCPLELYNLMRL 267
                        330
                 ....*....|....*
gi 27777648 1140 CWHEDPNQRPSFSEL 1154
Cdd:cd05050  268 CWSKLPSDRPSFASI 282
PTKc_Ror cd05048
Catalytic Domain of the Protein Tyrosine Kinases, Receptor tyrosine kinase-like Orphan ...
826-1161 9.59e-65

Catalytic Domain of the Protein Tyrosine Kinases, Receptor tyrosine kinase-like Orphan Receptors; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. The Ror subfamily consists of Ror1, Ror2, and similar proteins. Ror proteins are orphan receptor PTKs (RTKs) containing an extracellular region with immunoglobulin-like, cysteine-rich, and kringle domains, a transmembrane segment, and an intracellular catalytic domain. Ror RTKs are unrelated to the nuclear receptor subfamily called retinoid-related orphan receptors (RORs). RTKs are usually activated through ligand binding, which causes dimerization and autophosphorylation of the intracellular tyr kinase catalytic domain. Ror kinases are expressed in many tissues during development. They play important roles in bone and heart formation. Mutations in human Ror2 result in two different bone development genetic disorders, recessive Robinow syndrome and brachydactyly type B. Drosophila Ror is expressed only in the developing nervous system during neurite outgrowth and neuronal differentiation, suggesting a role for Drosophila Ror in neural development. More recently, mouse Ror1 and Ror2 have also been found to play an important role in regulating neurite growth in central neurons. Ror1 and Ror2 are believed to have some overlapping and redundant functions. The Ror subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270642 [Multi-domain]  Cd Length: 283  Bit Score: 221.48  E-value: 9.59e-65
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  826 EFPRDRLKLGKPLGRGAFGQVIEADAFGIDKTATCKTVAVKMLKEGA---THSEHR---ALMSELkilihigHHLNVVNL 899
Cdd:cd05048    1 EIPLSAVRFLEELGEGAFGKVYKGELLGPSSEESAISVAIKTLKENAspkTQQDFRreaELMSDL-------QHPNIVCL 73
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  900 LGACTKpGGPLMVIVEFCKFGNLSTYLrgkrNEFVPYKSKGArfrqgkdyvgelsvdlkrrldsitssqssaSSGFVEEK 979
Cdd:cd05048   74 LGVCTK-EQPQCMLFEYMAHGDLHEFL----VRHSPHSDVGV------------------------------SSDDDGTA 118
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  980 SLSDveeeeaseelYKDFLtlehliCYSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIYKDpDYVR 1059
Cdd:cd05048  119 SSLD----------QSDFL------HIAIQIAAGMEYLSSHHYVHRDLAARNCLVGDGLTVKISDFGLSRDIYSS-DYYR 181
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1060 -KGDARLPLKWMAPETIFDRVYTIQSDVWSFGVLLWEIFSLGASPYPGVKiDEEFCRRLKEGTRMRAPDYTTPEMYQTML 1138
Cdd:cd05048  182 vQSKSLLPVRWMPPEAILYGKFTTESDVWSFGVVLWEIFSYGLQPYYGYS-NQEVIEMIRSRQLLPCPEDCPARVYSLMV 260
                        330       340
                 ....*....|....*....|...
gi 27777648 1139 DCWHEDPNQRPSFSELVEHLGNL 1161
Cdd:cd05048  261 ECWHEIPSRRPRFKEIHTRLRTW 283
PTKc_Src_like cd05034
Catalytic domain of Src kinase-like Protein Tyrosine Kinases; PTKs catalyze the transfer of ...
836-1158 9.75e-64

Catalytic domain of Src kinase-like Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Src subfamily members include Src, Lck, Hck, Blk, Lyn, Fgr, Fyn, Yrk, and Yes. Src (or c-Src) proteins are cytoplasmic (or non-receptor) PTKs which are anchored to the plasma membrane. They contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). Src proteins are involved in signaling pathways that regulate cytokine and growth factor responses, cytoskeleton dynamics, cell proliferation, survival, and differentiation. They were identified as the first proto-oncogene products, and they regulate cell adhesion, invasion, and motility in cancer cells and tumor vasculature, contributing to cancer progression and metastasis. Src kinases are overexpressed in a variety of human cancers, making them attractive targets for therapy. They are also implicated in acute inflammatory responses and osteoclast function. Src, Fyn, Yes, and Yrk are widely expressed, while Blk, Lck, Hck, Fgr, and Lyn show a limited expression pattern. The Src-like subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270630 [Multi-domain]  Cd Length: 248  Bit Score: 217.15  E-value: 9.75e-64
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  836 KPLGRGAFGQVIEADAFGIDKtatcktVAVKMLKEGATHSEhrALMSELKILiHIGHHLNVVNLLGACTKpGGPLMVIVE 915
Cdd:cd05034    1 KKLGAGQFGEVWMGVWNGTTK------VAVKTLKPGTMSPE--AFLQEAQIM-KKLRHDKLVQLYAVCSD-EEPIYIVTE 70
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  916 FCKFGNLSTYLRGKRnefvpykskgarfrqGKDyvgelsvdlkrrldsitssqssassgfveekslsdveeeeaseelyk 995
Cdd:cd05034   71 LMSKGSLLDYLRTGE---------------GRA----------------------------------------------- 88
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  996 dfLTLEHLICYSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIyKDPDYVRKGDARLPLKWMAPETI 1075
Cdd:cd05034   89 --LRLPQLIDMAAQIASGMAYLESRNYIHRDLAARNILVGENNVCKVADFGLARLI-EDDEYTAREGAKFPIKWTAPEAA 165
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1076 FDRVYTIQSDVWSFGVLLWEIFSLGASPYPGVKiDEEFCRRLKEGTRMRAPDYTTPEMYQTMLDCWHEDPNQRPSFSELV 1155
Cdd:cd05034  166 LYGRFTIKSDVWSFGILLYEIVTYGRVPYPGMT-NREVLEQVERGYRMPKPPGCPDELYDIMLQCWKKEPEERPTFEYLQ 244

                 ...
gi 27777648 1156 EHL 1158
Cdd:cd05034  245 SFL 247
PTKc_Tie cd05047
Catalytic domain of Tie Protein Tyrosine Kinases; PTKs catalyze the transfer of the ...
838-1163 4.74e-62

Catalytic domain of Tie Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Tie proteins, consisting of Tie1 and Tie2, are receptor PTKs (RTKs) containing an extracellular region, a transmembrane segment, and an intracellular catalytic domain. The extracellular region contains an immunoglobulin (Ig)-like domain, three epidermal growth factor (EGF)-like domains, a second Ig-like domain, and three fibronectin type III repeats. Tie receptors are specifically expressed in endothelial cells and hematopoietic stem cells. The angiopoietins (Ang-1 to Ang-4) serve as ligands for Tie2, while no specific ligand has been identified for Tie1. The binding of Ang-1 to Tie2 leads to receptor autophosphorylation and activation, promoting cell migration and survival. In contrast, Ang-2 binding to Tie2 does not result in the same response, suggesting that Ang-2 may function as an antagonist. In vivo studies of Tie1 show that it is critical in vascular development. The Tie subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270641 [Multi-domain]  Cd Length: 270  Bit Score: 213.36  E-value: 4.74e-62
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  838 LGRGAFGQVIEADafgIDKTATCKTVAVKMLKEGATHSEHRALMSELKILIHIGHHLNVVNLLGACTKPGgPLMVIVEFC 917
Cdd:cd05047    3 IGEGNFGQVLKAR---IKKDGLRMDAAIKRMKEYASKDDHRDFAGELEVLCKLGHHPNIINLLGACEHRG-YLYLAIEYA 78
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  918 KFGNLSTYLRGKRnefvpykskgarfrqgkdyvgELSVDlkrrldsitssqssasSGFVEEKSLSDVeeeeaseelykdf 997
Cdd:cd05047   79 PHGNLLDFLRKSR---------------------VLETD----------------PAFAIANSTAST------------- 108
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  998 LTLEHLICYSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDiykDPDYVRKGDARLPLKWMAPETIFD 1077
Cdd:cd05047  109 LSSQQLLHFAADVARGMDYLSQKQFIHRDLAARNILVGENYVAKIADFGLSRG---QEVYVKKTMGRLPVRWMAIESLNY 185
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1078 RVYTIQSDVWSFGVLLWEIFSLGASPYPGVKIDEEFcRRLKEGTRMRAPDYTTPEMYQTMLDCWHEDPNQRPSFSELVEH 1157
Cdd:cd05047  186 SVYTTNSDVWSYGVLLWEIVSLGGTPYCGMTCAELY-EKLPQGYRLEKPLNCDDEVYDLMRQCWREKPYERPSFAQILVS 264

                 ....*.
gi 27777648 1158 LGNLLQ 1163
Cdd:cd05047  265 LNRMLE 270
PTKc_Trk cd05049
Catalytic domain of the Protein Tyrosine Kinases, Tropomyosin Related Kinases; PTKs catalyze ...
826-1158 5.33e-62

Catalytic domain of the Protein Tyrosine Kinases, Tropomyosin Related Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. The Trk subfamily consists of TrkA, TrkB, TrkC, and similar proteins. They are receptor PTKs (RTKs) containing an extracellular region with arrays of leucine-rich motifs flanked by two cysteine-rich clusters followed by two immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. Binding to their ligands, the nerve growth factor (NGF) family of neutrotrophins, leads to Trk receptor oligomerization and activation of the catalytic domain. Trk receptors are mainly expressed in the peripheral and central nervous systems. They play important roles in cell fate determination, neuronal survival and differentiation, as well as in the regulation of synaptic plasticity. Altered expression of Trk receptors is associated with many human diseases. The Trk subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270643 [Multi-domain]  Cd Length: 280  Bit Score: 213.48  E-value: 5.33e-62
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  826 EFPRDRLKLGKPLGRGAFGQVIEADAFGIDKTATCKTVAVKMLKEGATHSEHRALMSELKILIHIGHHlNVVNLLGACTK 905
Cdd:cd05049    1 HIKRDTIVLKRELGEGAFGKVFLGECYNLEPEQDKMLVAVKTLKDASSPDARKDFEREAELLTNLQHE-NIVKFYGVCTE 79
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  906 pGGPLMVIVEFCKFGNLSTYLRgkrnefvpykskgarfRQGKDYVGELSVDLKrrldsitssqssassgfveekslsdve 985
Cdd:cd05049   80 -GDPLLMVFEYMEHGDLNKFLR----------------SHGPDAAFLASEDSA--------------------------- 115
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  986 eeeaseelyKDFLTLEHLICYSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIYKDpDYVR-KGDAR 1064
Cdd:cd05049  116 ---------PGELTLSQLLHIAVQIASGMVYLASQHFVHRDLATRNCLVGTNLVVKIGDFGMSRDIYST-DYYRvGGHTM 185
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1065 LPLKWMAPETIFDRVYTIQSDVWSFGVLLWEIFSLGASPYPGVKiDEEFCRRLKEGTRMRAPDYTTPEMYQTMLDCWHED 1144
Cdd:cd05049  186 LPIRWMPPESILYRKFTTESDVWSFGVVLWEIFTYGKQPWFQLS-NTEVIECITQGRLLQRPRTCPSEVYAVMLGCWKRE 264
                        330
                 ....*....|....
gi 27777648 1145 PNQRPSFSELVEHL 1158
Cdd:cd05049  265 PQQRLNIKDIHKRL 278
PTKc_Tie1 cd05089
Catalytic domain of the Protein Tyrosine Kinase, Tie1; Protein Tyrosine Kinase (PTK) family; ...
825-1183 1.62e-61

Catalytic domain of the Protein Tyrosine Kinase, Tie1; Protein Tyrosine Kinase (PTK) family; Tie1; catalytic (c) domain. The PTKc family is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, and phosphoinositide 3-kinase (PI3K). PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Tie1 is a receptor tyr kinase (RTK) containing an extracellular region, a transmembrane segment, and an intracellular catalytic domain. The extracellular region contains an immunoglobulin (Ig)-like domain, three epidermal growth factor (EGF)-like domains, a second Ig-like domain, and three fibronectin type III repeats. Tie receptors are specifically expressed in endothelial cells and hematopoietic stem cells. No specific ligand has been identified for Tie1, although the angiopoietin, Ang-1, binds to Tie1 through integrins at high concentrations. In vivo studies of Tie1 show that it is critical in vascular development.


Pssm-ID: 270671 [Multi-domain]  Cd Length: 297  Bit Score: 212.55  E-value: 1.62e-61
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  825 WEfprdRLKLGKPLGRGAFGQVIEAdafGIDKTATCKTVAVKMLKEGATHSEHRALMSELKILIHIGHHLNVVNLLGACT 904
Cdd:cd05089    1 WE----DIKFEDVIGEGNFGQVIKA---MIKKDGLKMNAAIKMLKEFASENDHRDFAGELEVLCKLGHHPNIINLLGACE 73
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  905 KPGgPLMVIVEFCKFGNLSTYLRGKRnefvpykskgarfrqgkdyvgELSVDlkrrldsitssqssasSGFVEEKSLSDV 984
Cdd:cd05089   74 NRG-YLYIAIEYAPYGNLLDFLRKSR---------------------VLETD----------------PAFAKEHGTAST 115
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  985 eeeeaseelykdfLTLEHLICYSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDiykDPDYVRKGDAR 1064
Cdd:cd05089  116 -------------LTSQQLLQFASDVAKGMQYLSEKQFIHRDLAARNVLVGENLVSKIADFGLSRG---EEVYVKKTMGR 179
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1065 LPLKWMAPETIFDRVYTIQSDVWSFGVLLWEIFSLGASPYPGVKIDEEFcRRLKEGTRMRAPDYTTPEMYQTMLDCWHED 1144
Cdd:cd05089  180 LPVRWMAIESLNYSVYTTKSDVWSFGVLLWEIVSLGGTPYCGMTCAELY-EKLPQGYRMEKPRNCDDEVYELMRQCWRDR 258
                        330       340       350
                 ....*....|....*....|....*....|....*....
gi 27777648 1145 PNQRPSFSELVEHLGNLLQANaqqdgKDYIVLPMSETLS 1183
Cdd:cd05089  259 PYERPPFSQISVQLSRMLEAR-----KAYVNMALFENFT 292
PTKc_Fes_like cd05041
Catalytic domain of Fes-like Protein Tyrosine Kinases; Protein Tyrosine Kinase (PTK) family; ...
838-1158 2.34e-61

Catalytic domain of Fes-like Protein Tyrosine Kinases; Protein Tyrosine Kinase (PTK) family; Fes subfamily; catalytic (c) domain. Fes subfamily members include Fes (or Fps), Fer, and similar proteins. The PTKc family is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, and phosphoinositide 3-kinase (PI3K). PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Fes subfamily proteins are cytoplasmic (or nonreceptor) tyr kinases containing an N-terminal region with FCH (Fes/Fer/CIP4 homology) and coiled-coil domains, followed by a SH2 domain, and a C-terminal catalytic domain. The genes for Fes (feline sarcoma) and Fps (Fujinami poultry sarcoma) were first isolated from tumor-causing retroviruses. The viral oncogenes encode chimeric Fes proteins consisting of Gag sequences at the N-termini, resulting in unregulated tyr kinase activity. Fes and Fer kinases play roles in haematopoiesis, inflammation and immunity, growth factor signaling, cytoskeletal regulation, cell migration and adhesion, and the regulation of cell-cell interactions. Fes and Fer show redundancy in their biological functions.


Pssm-ID: 270637 [Multi-domain]  Cd Length: 251  Bit Score: 210.38  E-value: 2.34e-61
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  838 LGRGAFGQVIEadafGIDKTATCKtVAVKMLKEGATHSEHRALMSELKILIHIGHHlNVVNLLGACTKPGgPLMVIVEFC 917
Cdd:cd05041    3 IGRGNFGDVYR----GVLKPDNTE-VAVKTCRETLPPDLKRKFLQEARILKQYDHP-NIVKLIGVCVQKQ-PIMIVMELV 75
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  918 KFGNLSTYLRGKRNEfvpykskgarfrqgkdyvgelsvdlkrrldsitssqssassgfveekslsdveeeeaseelykdf 997
Cdd:cd05041   76 PGGSLLTFLRKKGAR----------------------------------------------------------------- 90
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  998 LTLEHLICYSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIYKDPDYVRKGDARLPLKWMAPETIFD 1077
Cdd:cd05041   91 LTVKQLLQMCLDAAAGMEYLESKNCIHRDLAARNCLVGENNVLKISDFGMSREEEDGEYTVSDGLKQIPIKWTAPEALNY 170
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1078 RVYTIQSDVWSFGVLLWEIFSLGASPYPGVKiDEEFCRRLKEGTRMRAPDYTTPEMYQTMLDCWHEDPNQRPSFSELVEH 1157
Cdd:cd05041  171 GRYTSESDVWSFGILLWEIFSLGATPYPGMS-NQQTREQIESGYRMPAPELCPEAVYRLMLQCWAYDPENRPSFSEIYNE 249

                 .
gi 27777648 1158 L 1158
Cdd:cd05041  250 L 250
PTKc_Jak_rpt2 cd05038
Catalytic (repeat 2) domain of the Protein Tyrosine Kinases, Janus kinases; The Jak subfamily ...
827-1158 3.29e-61

Catalytic (repeat 2) domain of the Protein Tyrosine Kinases, Janus kinases; The Jak subfamily is composed of Jak1, Jak2, Jak3, TYK2, and similar proteins. They are PTKs, catalyzing the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Jaks are cytoplasmic (or nonreceptor) PTKs containing an N-terminal FERM domain, followed by a Src homology 2 (SH2) domain, a pseudokinase domain, and a C-terminal tyr kinase catalytic domain. Most Jaks are expressed in a wide variety of tissues, except for Jak3, which is expressed only in hematopoietic cells. Jaks are crucial for cytokine receptor signaling. They are activated by autophosphorylation upon cytokine-induced receptor aggregation, and subsequently trigger downstream signaling events such as the phosphorylation of signal transducers and activators of transcription (STATs). Jaks are also involved in regulating the surface expression of some cytokine receptors. The Jak-STAT pathway is involved in many biological processes including hematopoiesis, immunoregulation, host defense, fertility, lactation, growth, and embryogenesis. The Jak subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270634 [Multi-domain]  Cd Length: 284  Bit Score: 211.09  E-value: 3.29e-61
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  827 FPRDRLKLGKPLGRGAFGQViEADAFGIDKTATCKTVAVKMLKEGATHSEHRALMSELKILiHIGHHLNVVNLLGACTKP 906
Cdd:cd05038    1 FEERHLKFIKQLGEGHFGSV-ELCRYDPLGDNTGEQVAVKSLQPSGEEQHMSDFKREIEIL-RTLDHEYIVKYKGVCESP 78
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  907 GGP-LMVIVEFCKFGNLSTYLRGKRNEfvpykskgarfrqgkdyvgelsVDLKRrldsitssqssassgfveekslsdve 985
Cdd:cd05038   79 GRRsLRLIMEYLPSGSLRDYLQRHRDQ----------------------IDLKR-------------------------- 110
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  986 eeeaseelykdfltlehLICYSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIYKDPDYVR-KGDAR 1064
Cdd:cd05038  111 -----------------LLLFASQICKGMEYLGSQRYIHRDLAARNILVESEDLVKISDFGLAKVLPEDKEYYYvKEPGE 173
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1065 LPLKWMAPETIFDRVYTIQSDVWSFGVLLWEIFSLGAS-------------PYPGVKIDEEFCRRLKEGTRMRAPDYTTP 1131
Cdd:cd05038  174 SPIFWYAPECLRESRFSSASDVWSFGVTLYELFTYGDPsqsppalflrmigIAQGQMIVTRLLELLKSGERLPRPPSCPD 253
                        330       340
                 ....*....|....*....|....*..
gi 27777648 1132 EMYQTMLDCWHEDPNQRPSFSELVEHL 1158
Cdd:cd05038  254 EVYDLMKECWEYEPQDRPSFSDLILII 280
PTKc_Frk_like cd05068
Catalytic domain of Fyn-related kinase-like Protein Tyrosine Kinases; PTKs catalyze the ...
824-1154 5.38e-61

Catalytic domain of Fyn-related kinase-like Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Frk and Srk are members of the Src subfamily of proteins, which are cytoplasmic (or non-receptor) PTKs. Frk, also known as Rak, is specifically expressed in liver, lung, kidney, intestine, mammary glands, and the islets of Langerhans. Rodent homologs were previously referred to as GTK (gastrointestinal tyr kinase), BSK (beta-cell Src-like kinase), or IYK (intestinal tyr kinase). Studies in mice reveal that Frk is not essential for viability. It plays a role in the signaling that leads to cytokine-induced beta-cell death in Type I diabetes. It also regulates beta-cell number during embryogenesis and early in life. Src kinases contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). The Frk-like subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270653 [Multi-domain]  Cd Length: 267  Bit Score: 209.96  E-value: 5.38e-61
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  824 KWEFPRDRLKLGKPLGRGAFGQVIEadafGIDKTATckTVAVKMLKEGATHSEhrALMSELKILIHIgHHLNVVNLLGAC 903
Cdd:cd05068    2 QWEIDRKSLKLLRKLGSGQFGEVWE----GLWNNTT--PVAVKTLKPGTMDPE--DFLREAQIMKKL-RHPKLIQLYAVC 72
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  904 TKpGGPLMVIVEFCKFGNLSTYLRGKrnefvpykskgarfrqgkdyvgelsvdlkrrldsitssqssassgfveekslsd 983
Cdd:cd05068   73 TL-EEPIYIITELMKHGSLLEYLQGK------------------------------------------------------ 97
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  984 veeeeaseelyKDFLTLEHLICYSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIYKDPDYVRKGDA 1063
Cdd:cd05068   98 -----------GRSLQLPQLIDMAAQVASGMAYLESQNYIHRDLAARNVLVGENNICKVADFGLARVIKVEDEYEAREGA 166
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1064 RLPLKWMAPETIFDRVYTIQSDVWSFGVLLWEIFSLGASPYPGVKiDEEFCRRLKEGTRMRAPDYTTPEMYQTMLDCWHE 1143
Cdd:cd05068  167 KFPIKWTAPEAANYNRFSIKSDVWSFGILLTEIVTYGRIPYPGMT-NAEVLQQVERGYRMPCPPNCPPQLYDIMLECWKA 245
                        330
                 ....*....|.
gi 27777648 1144 DPNQRPSFSEL 1154
Cdd:cd05068  246 DPMERPTFETL 256
PTKc_EGFR_like cd05057
Catalytic domain of Epidermal Growth Factor Receptor-like Protein Tyrosine Kinases; PTKs ...
826-1177 1.29e-60

Catalytic domain of Epidermal Growth Factor Receptor-like Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. EGFR (HER, ErbB) subfamily members include EGFR (HER1, ErbB1), HER2 (ErbB2), HER3 (ErbB3), HER4 (ErbB4), and similar proteins. They are receptor PTKs (RTKs) containing an extracellular EGF-related ligand-binding region, a transmembrane helix, and a cytoplasmic region with a tyr kinase domain and a regulatory C-terminal tail. Unlike other PTKs, phosphorylation of the activation loop of EGFR proteins is not critical to their activation. Instead, they are activated by ligand-induced dimerization, resulting in the phosphorylation of tyr residues in the C-terminal tail, which serve as binding sites for downstream signaling molecules. Collectively, they can recognize a variety of ligands including EGF, TGFalpha, and neuregulins, among others. All four subfamily members can form homo- or heterodimers. HER3 contains an impaired kinase domain and depends on its heterodimerization partner for activation. EGFR subfamily members are involved in signaling pathways leading to a broad range of cellular responses including cell proliferation, differentiation, migration, growth inhibition, and apoptosis. Gain of function alterations, through their overexpression, deletions, or point mutations in their kinase domains, have been implicated in various cancers. These receptors are targets of many small molecule inhibitors and monoclonal antibodies used in cancer therapy. The EGFR subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270648 [Multi-domain]  Cd Length: 279  Bit Score: 209.19  E-value: 1.29e-60
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  826 EFPRDRLKLGKPLGRGAFGQVIEadafGI---DKTATCKTVAVKMLKEGATHSEHRALMSELKILIHIGHhLNVVNLLGA 902
Cdd:cd05057    3 IVKETELEKGKVLGSGAFGTVYK----GVwipEGEKVKIPVAIKVLREETGPKANEEILDEAYVMASVDH-PHLVRLLGI 77
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  903 CtkPGGPLMVIVEFCKFGNLSTYLRGKRNEFVPYkskgarfrqgkdyvgelsvdlkrrldsitssqssassgfveeksls 982
Cdd:cd05057   78 C--LSSQVQLITQLMPLGCLLDYVRNHRDNIGSQ---------------------------------------------- 109
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  983 dveeeeaseelykdfltleHLICYSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIYKDPDYVRKGD 1062
Cdd:cd05057  110 -------------------LLLNWCVQIAKGMSYLEEKRLVHRDLAARNVLVKTPNHVKITDFGLAKLLDVDEKEYHAEG 170
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1063 ARLPLKWMAPETIFDRVYTIQSDVWSFGVLLWEIFSLGASPYPGVKIdEEFCRRLKEGTRMRAPDYTTPEMYQTMLDCWH 1142
Cdd:cd05057  171 GKVPIKWMALESIQYRIYTHKSDVWSYGVTVWELMTFGAKPYEGIPA-VEIPDLLEKGERLPQPPICTIDVYMVLVKCWM 249
                        330       340       350
                 ....*....|....*....|....*....|....*
gi 27777648 1143 EDPNQRPSFSELVEHLGNLLqanaqQDGKDYIVLP 1177
Cdd:cd05057  250 IDAESRPTFKELANEFSKMA-----RDPQRYLVIQ 279
PTKc_TAM cd05035
Catalytic Domain of TAM (Tyro3, Axl, Mer) Protein Tyrosine Kinases; PTKs catalyze the transfer ...
832-1162 1.09e-59

Catalytic Domain of TAM (Tyro3, Axl, Mer) Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. The TAM subfamily consists of Tyro3 (or Sky), Axl, Mer (or Mertk), and similar proteins. TAM subfamily members are receptor tyr kinases (RTKs) containing an extracellular ligand-binding region with two immunoglobulin-like domains followed by two fibronectin type III repeats, a transmembrane segment, and an intracellular catalytic domain. Binding to their ligands, Gas6 and protein S, leads to receptor dimerization, autophosphorylation, activation, and intracellular signaling. TAM proteins are implicated in a variety of cellular effects including survival, proliferation, migration, and phagocytosis. They are also associated with several types of cancer as well as inflammatory, autoimmune, vascular, and kidney diseases. The TAM subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270631 [Multi-domain]  Cd Length: 273  Bit Score: 206.62  E-value: 1.09e-59
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  832 LKLGKPLGRGAFGQVIEADaFGIDKTATCKtVAVKMLK-EGATHSEHRALMSELKILIHIGHHlNVVNLLGAC------T 904
Cdd:cd05035    1 LKLGKILGEGEFGSVMEAQ-LKQDDGSQLK-VAVKTMKvDIHTYSEIEEFLSEAACMKDFDHP-NVMRLIGVCftasdlN 77
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  905 KPGGPlMVIVEFCKFGNLSTYLRGKRNEFVPYKskgarfrqgkdyvgelsvdlkrrldsitssqssassgfveekslsdv 984
Cdd:cd05035   78 KPPSP-MVILPFMKHGDLHSYLLYSRLGGLPEK----------------------------------------------- 109
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  985 eeeeaseelykdfLTLEHLICYSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIYKDpDYVRKGD-A 1063
Cdd:cd05035  110 -------------LPLQTLLKFMVDIAKGMEYLSNRNFIHRDLAARNCMLDENMTVCVADFGLSRKIYSG-DYYRQGRiS 175
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1064 RLPLKWMAPETIFDRVYTIQSDVWSFGVLLWEIFSLGASPYPGVKiDEEFCRRLKEGTRMRAPDYTTPEMYQTMLDCWHE 1143
Cdd:cd05035  176 KMPVKWIALESLADNVYTSKSDVWSFGVTMWEIATRGQTPYPGVE-NHEIYDYLRNGNRLKQPEDCLDEVYFLMYFCWTV 254
                        330
                 ....*....|....*....
gi 27777648 1144 DPNQRPSFSELVEHLGNLL 1162
Cdd:cd05035  255 DPKDRPTFTKLREVLENIL 273
PTKc_Srm_Brk cd05148
Catalytic domain of the Protein Tyrosine Kinases, Src-related kinase lacking C-terminal ...
825-1160 1.65e-58

Catalytic domain of the Protein Tyrosine Kinases, Src-related kinase lacking C-terminal regulatory tyrosine and N-terminal myristylation sites (Srm) and Breast tumor kinase (Brk); PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Srm and Brk (also called protein tyrosine kinase 6) are members of the Src subfamily of proteins, which are cytoplasmic (or non-receptor) PTKs. Brk has been found to be overexpressed in a majority of breast tumors. Src kinases in general contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr; they are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). Srm and Brk however, lack the N-terminal myristylation sites. Src proteins are involved in signaling pathways that regulate cytokine and growth factor responses, cytoskeleton dynamics, cell proliferation, survival, and differentiation. The Srm/Brk subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 133248 [Multi-domain]  Cd Length: 261  Bit Score: 202.66  E-value: 1.65e-58
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  825 WEFPRDRLKLGKPLGRGAFGQVIEAdafgidKTATCKTVAVKMLKEGAThSEHRALMSELKILIHIgHHLNVVNLLGACT 904
Cdd:cd05148    1 WERPREEFTLERKLGSGYFGEVWEG------LWKNRVRVAIKILKSDDL-LKQQDFQKEVQALKRL-RHKHLISLFAVCS 72
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  905 KpGGPLMVIVEFCKFGNLSTYLRGKrnefvpykskgarfrqgkdyvgelsvdlkrrldsitssqssassgfvEEKSLsdv 984
Cdd:cd05148   73 V-GEPVYIITELMEKGSLLAFLRSP-----------------------------------------------EGQVL--- 101
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  985 eeeeaseelykdflTLEHLICYSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARdIYKDPDYVRKgDAR 1064
Cdd:cd05148  102 --------------PVASLIDMACQVAEGMAYLEEQNSIHRDLAARNILVGEDLVCKVADFGLAR-LIKEDVYLSS-DKK 165
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1065 LPLKWMAPETIFDRVYTIQSDVWSFGVLLWEIFSLGASPYPGVKIDEEFcRRLKEGTRMRAPDYTTPEMYQTMLDCWHED 1144
Cdd:cd05148  166 IPYKWTAPEAASHGTFSTKSDVWSFGILLYEMFTYGQVPYPGMNNHEVY-DQITAGYRMPCPAKCPQEIYKIMLECWAAE 244
                        330
                 ....*....|....*.
gi 27777648 1145 PNQRPSFSELVEHLGN 1160
Cdd:cd05148  245 PEDRPSFKALREELDN 260
PTKc_Mer cd14204
Catalytic Domain of the Protein Tyrosine Kinase, Mer; PTKs catalyze the transfer of the ...
829-1164 8.17e-58

Catalytic Domain of the Protein Tyrosine Kinase, Mer; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Mer (or Mertk) is named after its original reported expression pattern (monocytes, epithelial, and reproductive tissues). It is required for the ingestion of apoptotic cells by phagocytes such as macrophages, retinal pigment epithelial cells, and dendritic cells. Mer is also important in maintaining immune homeostasis. Mer is a member of the TAM subfamily, composed of receptor PTKs (RTKs) containing an extracellular ligand-binding region with two immunoglobulin-like domains followed by two fibronectin type III repeats, a transmembrane segment, and an intracellular catalytic domain. Binding to their ligands, Gas6 and protein S, leads to receptor dimerization, autophosphorylation, activation, and intracellular signaling. The Mer subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271106 [Multi-domain]  Cd Length: 284  Bit Score: 201.70  E-value: 8.17e-58
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  829 RDRLKLGKPLGRGAFGQVIEADAFGIDktATCKTVAVKMLK-EGATHSEHRALMSELKILIHIgHHLNVVNLLGACTKPG 907
Cdd:cd14204    6 RNLLSLGKVLGEGEFGSVMEGELQQPD--GTNHKVAVKTMKlDNFSQREIEEFLSEAACMKDF-NHPNVIRLLGVCLEVG 82
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  908 G-----PlMVIVEFCKFGNLSTYLRGKRNEFVPykskgarfrqgkdyvgelsvdlkrrldsitssqssassgfveeksls 982
Cdd:cd14204   83 SqripkP-MVILPFMKYGDLHSFLLRSRLGSGP----------------------------------------------- 114
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  983 dveeeeaseelykDFLTLEHLICYSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIYKDpDYVRKGD 1062
Cdd:cd14204  115 -------------QHVPLQTLLKFMIDIALGMEYLSSRNFLHRDLAARNCMLRDDMTVCVADFGLSKKIYSG-DYYRQGR 180
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1063 -ARLPLKWMAPETIFDRVYTIQSDVWSFGVLLWEIFSLGASPYPGVKiDEEFCRRLKEGTRMRAPDYTTPEMYQTMLDCW 1141
Cdd:cd14204  181 iAKMPVKWIAVESLADRVYTVKSDVWAFGVTMWEIATRGMTPYPGVQ-NHEIYDYLLHGHRLKQPEDCLDELYDIMYSCW 259
                        330       340
                 ....*....|....*....|...
gi 27777648 1142 HEDPNQRPSFSELVEHLGNLLQA 1164
Cdd:cd14204  260 RSDPTDRPTFTQLRENLEKLLES 282
PTK_CCK4 cd05046
Pseudokinase domain of the Protein Tyrosine Kinase, Colon Carcinoma Kinase 4; CCK4, also ...
827-1160 1.40e-57

Pseudokinase domain of the Protein Tyrosine Kinase, Colon Carcinoma Kinase 4; CCK4, also called protein tyrosine kinase 7 (PTK7), is an orphan receptor PTK (RTK) containing an extracellular region with seven immunoglobulin domains, a transmembrane segment, and an intracellular inactive pseudokinase domain, which shows similarity to tyr kinases but lacks crucial residues for catalytic activity and ATP binding. Studies in mice reveal that CCK4 is essential for neural development. Mouse embryos containing a truncated CCK4 die perinatally and display craniorachischisis, a severe form of neural tube defect. The mechanism of action of the CCK4 pseudokinase is still unknown. Other pseudokinases such as HER3 rely on the activity of partner RTKs. The CCK4 subfamily is part of a larger superfamily that includes other pseudokinases and the catalytic domains of active kinases including PTKs, protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 133178 [Multi-domain]  Cd Length: 275  Bit Score: 200.38  E-value: 1.40e-57
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  827 FPRDRLKLGKPLGRGAFGQVIEADAFGIDKTATCKTVAVKMLKEGATHSEHRALMSELKILIHIGHHlNVVNLLGACtKP 906
Cdd:cd05046    2 FPRSNLQEITTLGRGEFGEVFLAKAKGIEEEGGETLVLVKALQKTKDENLQSEFRRELDMFRKLSHK-NVVRLLGLC-RE 79
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  907 GGPLMVIVEFCKFGNLSTYLRGKRNEFVPYKSKGarfrqgkdyvgelsvdlkrrldsitssqssassgfveekslsdvee 986
Cdd:cd05046   80 AEPHYMILEYTDLGDLKQFLRATKSKDEKLKPPP---------------------------------------------- 113
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  987 eeaseelykdfLTLEHLICYSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIYKDpDYVRKGDARLP 1066
Cdd:cd05046  114 -----------LSTKQKVALCTQIALGMDHLSNARFVHRDLAARNCLVSSQREVKVSLLSLSKDVYNS-EYYKLRNALIP 181
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1067 LKWMAPETIFDRVYTIQSDVWSFGVLLWEIFSLGASPYPGVKiDEEFCRRLKEG-TRMRAPDYTTPEMYQTMLDCWHEDP 1145
Cdd:cd05046  182 LRWLAPEAVQEDDFSTKSDVWSFGVLMWEVFTQGELPFYGLS-DEEVLNRLQAGkLELPVPEGCPSRLYKLMTRCWAVNP 260
                        330
                 ....*....|....*
gi 27777648 1146 NQRPSFSELVEHLGN 1160
Cdd:cd05046  261 KDRPSFSELVSALGE 275
PTKc_InsR cd05061
Catalytic domain of the Protein Tyrosine Kinase, Insulin Receptor; PTKs catalyze the transfer ...
825-1168 1.53e-57

Catalytic domain of the Protein Tyrosine Kinase, Insulin Receptor; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. InsR is a receptor PTK (RTK) that is composed of two alphabeta heterodimers. Binding of the insulin ligand to the extracellular alpha subunit activates the intracellular tyr kinase domain of the transmembrane beta subunit. Receptor activation leads to autophosphorylation, stimulating downstream kinase activities, which initiate signaling cascades and biological function. InsR signaling plays an important role in many cellular processes including glucose homeostasis, glycogen synthesis, lipid and protein metabolism, ion and amino acid transport, cell cycle and proliferation, cell differentiation, gene transcription, and nitric oxide synthesis. Insulin resistance, caused by abnormalities in InsR signaling, has been described in diabetes, hypertension, cardiovascular disease, metabolic syndrome, heart failure, and female infertility. The InsR subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 133192 [Multi-domain]  Cd Length: 288  Bit Score: 200.97  E-value: 1.53e-57
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  825 WEFPRDRLKLGKPLGRGAFGQVIEADAFGIDKTATCKTVAVKMLKEGATHSEHRALMSELKILIHIGHHlNVVNLLGACT 904
Cdd:cd05061    1 WEVSREKITLLRELGQGSFGMVYEGNARDIIKGEAETRVAVKTVNESASLRERIEFLNEASVMKGFTCH-HVVRLLGVVS 79
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  905 KpGGPLMVIVEFCKFGNLSTYLRGKRNEfvpykskgARFRQGKDYVgelsvdlkrrldsitssqssassgfveekslsdv 984
Cdd:cd05061   80 K-GQPTLVVMELMAHGDLKSYLRSLRPE--------AENNPGRPPP---------------------------------- 116
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  985 eeeeaseelykdflTLEHLICYSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIYkDPDYVRKG-DA 1063
Cdd:cd05061  117 --------------TLQEMIQMAAEIADGMAYLNAKKFVHRDLAARNCMVAHDFTVKIGDFGMTRDIY-ETDYYRKGgKG 181
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1064 RLPLKWMAPETIFDRVYTIQSDVWSFGVLLWEIFSLGASPYPGVKiDEEFCRRLKEGTRMRAPDYTTPEMYQTMLDCWHE 1143
Cdd:cd05061  182 LLPVRWMAPESLKDGVFTTSSDMWSFGVVLWEITSLAEQPYQGLS-NEQVLKFVMDGGYLDQPDNCPERVTDLMRMCWQF 260
                        330       340
                 ....*....|....*....|....*
gi 27777648 1144 DPNQRPSFSELVEHLGNLLQANAQQ 1168
Cdd:cd05061  261 NPKMRPTFLEIVNLLKDDLHPSFPE 285
STKc_MAP3K-like cd13999
Catalytic domain of Mitogen-Activated Protein Kinase (MAPK) Kinase Kinase-like Serine ...
838-1158 1.79e-57

Catalytic domain of Mitogen-Activated Protein Kinase (MAPK) Kinase Kinase-like Serine/Threonine kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed mainly of MAP3Ks and similar proteins, including TGF-beta Activated Kinase-1 (TAK1, also called MAP3K7), MAP3K12, MAP3K13, Mixed lineage kinase (MLK), MLK-Like mitogen-activated protein Triple Kinase (MLTK), and Raf (Rapidly Accelerated Fibrosarcoma) kinases. MAP3Ks (MKKKs or MAPKKKs) phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. Also included in this subfamily is the pseudokinase Kinase Suppressor of Ras (KSR), which is a scaffold protein that functions downstream of Ras and upstream of Raf in the Extracellular signal-Regulated Kinase (ERK) pathway.


Pssm-ID: 270901 [Multi-domain]  Cd Length: 245  Bit Score: 198.92  E-value: 1.79e-57
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  838 LGRGAFGQVIEADAFGIDktatcktVAVKMLKEGATHSEH-RALMSELKILIHIgHHLNVVNLLGACTKPGgPLMVIVEF 916
Cdd:cd13999    1 IGSGSFGEVYKGKWRGTD-------VAIKKLKVEDDNDELlKEFRREVSILSKL-RHPNIVQFIGACLSPP-PLCIVTEY 71
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  917 CKFGNLSTYLRGKRNEFvpykskgarfrqgkdyvgelsvDLKRRLDsitssqssassgfveekslsdveeeeaseelykd 996
Cdd:cd13999   72 MPGGSLYDLLHKKKIPL----------------------SWSLRLK---------------------------------- 95
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  997 fltlehlicYSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARdiYKDPDYVRKGDARLPLKWMAPETIF 1076
Cdd:cd13999   96 ---------IALDIARGMNYLHSPPIIHRDLKSLNILLDENFTVKIADFGLSR--IKNSTTEKMTGVVGTPRWMAPEVLR 164
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1077 DRVYTIQSDVWSFGVLLWEIFSlGASPYPGVKIDEEFCRRLKEGTRMRAPDYTTPEMYQTMLDCWHEDPNQRPSFSELVE 1156
Cdd:cd13999  165 GEPYTEKADVYSFGIVLWELLT-GEVPFKELSPIQIAAAVVQKGLRPPIPPDCPPELSKLIKRCWNEDPEKRPSFSEIVK 243

                 ..
gi 27777648 1157 HL 1158
Cdd:cd13999  244 RL 245
PTKc_Met_Ron cd05058
Catalytic domain of the Protein Tyrosine Kinases, Met and Ron; PTKs catalyze the transfer of ...
838-1155 3.08e-57

Catalytic domain of the Protein Tyrosine Kinases, Met and Ron; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Met and Ron are receptor PTKs (RTKs) composed of an alpha-beta heterodimer. The extracellular alpha chain is disulfide linked to the beta chain, which contains an extracellular ligand-binding region with a sema domain, a PSI domain and four IPT repeats, a transmembrane segment, and an intracellular catalytic domain. Binding to their ligands leads to receptor dimerization, autophosphorylation, activation, and intracellular signaling. Met binds to the ligand, hepatocyte growth factor/scatter factor (HGF/SF), and is also called the HGF receptor. HGF/Met signaling plays a role in growth, transformation, cell motility, invasion, metastasis, angiogenesis, wound healing, and tissue regeneration. Aberrant expression of Met through mutations or gene amplification is associated with many human cancers including hereditary papillary renal and gastric carcinomas. The ligand for Ron is macrophage stimulating protein (MSP). Ron signaling is important in regulating cell motility, adhesion, proliferation, and apoptosis. Aberrant Ron expression is implicated in tumorigenesis and metastasis. The Met/Ron subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270649 [Multi-domain]  Cd Length: 262  Bit Score: 198.85  E-value: 3.08e-57
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  838 LGRGAFGQVIEADAfgIDKTATCKTVAVKMLKEGATHSEHRALMSElKILIHIGHHLNVVNLLGACTKPGGPLMVIVEFC 917
Cdd:cd05058    3 IGKGHFGCVYHGTL--IDSDGQKIHCAVKSLNRITDIEEVEQFLKE-GIIMKDFSHPNVLSLLGICLPSEGSPLVVLPYM 79
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  918 KFGNLSTYLRG-KRNEFVpykskgarfrqgKDYVGelsvdlkrrldsitssqssassgfveekslsdveeeeaseelykd 996
Cdd:cd05058   80 KHGDLRNFIRSeTHNPTV------------KDLIG--------------------------------------------- 102
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  997 fltlehlicYSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIYkDPDYV---RKGDARLPLKWMAPE 1073
Cdd:cd05058  103 ---------FGLQVAKGMEYLASKKFVHRDLAARNCMLDESFTVKVADFGLARDIY-DKEYYsvhNHTGAKLPVKWMALE 172
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1074 TIFDRVYTIQSDVWSFGVLLWEIFSLGASPYPGVKiDEEFCRRLKEGTRMRAPDYTTPEMYQTMLDCWHEDPNQRPSFSE 1153
Cdd:cd05058  173 SLQTQKFTTKSDVWSFGVLLWELMTRGAPPYPDVD-SFDITVYLLQGRRLLQPEYCPDPLYEVMLSCWHPKPEMRPTFSE 251

                 ..
gi 27777648 1154 LV 1155
Cdd:cd05058  252 LV 253
PTKc_Tec_like cd05059
Catalytic domain of Tec-like Protein Tyrosine Kinases; PTKs catalyze the transfer of the ...
832-1159 1.21e-56

Catalytic domain of Tec-like Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. The Tec-like subfamily is composed of Tec, Btk, Bmx (Etk), Itk (Tsk, Emt), Rlk (Txk), and similar proteins. They are cytoplasmic (or nonreceptor) PTKs with similarity to Src kinases in that they contain Src homology protein interaction domains (SH3, SH2) N-terminal to the catalytic tyr kinase domain. Unlike Src kinases, most Tec subfamily members except Rlk also contain an N-terminal pleckstrin homology (PH) domain, which binds the products of PI3K and allows membrane recruitment and activation. In addition, some members contain the Tec homology (TH) domain, which contains proline-rich and zinc-binding regions. Tec kinases form the second largest subfamily of nonreceptor PTKs and are expressed mainly by haematopoietic cells, although Tec and Bmx are also found in endothelial cells. B-cells express Btk and Tec, while T-cells express Itk, Txk, and Tec. Collectively, Tec kinases are expressed in a variety of myeloid cells such as mast cells, platelets, macrophages, and dendritic cells. Each Tec kinase shows a distinct cell-type pattern of expression. Tec kinases play important roles in the development, differentiation, maturation, regulation, survival, and function of B-cells and T-cells. Mutations in Btk cause the severe B-cell immunodeficiency, X-linked agammaglobulinaemia (XLA). The Tec-like subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173637 [Multi-domain]  Cd Length: 256  Bit Score: 196.90  E-value: 1.21e-56
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  832 LKLGKPLGRGAFGQVIEADAFGIDKtatcktVAVKMLKEGATHSEHraLMSELKILIHIGHHlNVVNLLGACTKpGGPLM 911
Cdd:cd05059    6 LTFLKELGSGQFGVVHLGKWRGKID------VAIKMIKEGSMSEDD--FIEEAKVMMKLSHP-KLVQLYGVCTK-QRPIF 75
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  912 VIVEFCKFGNLSTYLRGKRNEFvpykskgarfrqgkdyvgelsvdlkrrldsitssqssassgfveekslsdveeeease 991
Cdd:cd05059   76 IVTEYMANGCLLNYLRERRGKF---------------------------------------------------------- 97
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  992 elykdflTLEHLICYSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIYKDpDYVRKGDARLPLKWMA 1071
Cdd:cd05059   98 -------QTEQLLEMCKDVCEAMEYLESNGFIHRDLAARNCLVGEQNVVKVSDFGLARYVLDD-EYTSSVGTKFPVKWSP 169
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1072 PETIFDRVYTIQSDVWSFGVLLWEIFSLGASPYPGVKiDEEFCRRLKEGTRMRAPDYTTPEMYQTMLDCWHEDPNQRPSF 1151
Cdd:cd05059  170 PEVFMYSKFSSKSDVWSFGVLMWEVFSEGKMPYERFS-NSEVVEHISQGYRLYRPHLAPTEVYTIMYSCWHEKPEERPTF 248

                 ....*...
gi 27777648 1152 SELVEHLG 1159
Cdd:cd05059  249 KILLSQLT 256
PTKc_Abl cd05052
Catalytic domain of the Protein Tyrosine Kinase, Abelson kinase; PTKs catalyze the transfer of ...
825-1161 1.32e-56

Catalytic domain of the Protein Tyrosine Kinase, Abelson kinase; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Abl (or c-Abl) is a ubiquitously-expressed cytoplasmic (or nonreceptor) PTK that contains SH3, SH2, and tyr kinase domains in its N-terminal region, as well as nuclear localization motifs, a putative DNA-binding domain, and F- and G-actin binding domains in its C-terminal tail. It also contains a short autoinhibitory cap region in its N-terminus. Abl function depends on its subcellular localization. In the cytoplasm, Abl plays a role in cell proliferation and survival. In response to DNA damage or oxidative stress, Abl is transported to the nucleus where it induces apoptosis. In chronic myelogenous leukemia (CML) patients, an aberrant translocation results in the replacement of the first exon of Abl with the BCR (breakpoint cluster region) gene. The resulting BCR-Abl fusion protein is constitutively active and associates into tetramers, resulting in a hyperactive kinase sending a continuous signal. This leads to uncontrolled proliferation, morphological transformation and anti-apoptotic effects. BCR-Abl is the target of selective inhibitors, such as imatinib (Gleevec), used in the treatment of CML. Abl2, also known as ARG (Abelson-related gene), is thought to play a cooperative role with Abl in the proper development of the nervous system. The Tel-ARG fusion protein, resulting from reciprocal translocation between chromosomes 1 and 12, is associated with acute myeloid leukemia (AML). The TEL gene is a frequent fusion partner of other tyr kinase oncogenes, including Tel/Abl, Tel/PDGFRbeta, and Tel/Jak2, found in patients with leukemia and myeloproliferative disorders. The Abl subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270645 [Multi-domain]  Cd Length: 263  Bit Score: 197.26  E-value: 1.32e-56
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  825 WEFPRDRLKLGKPLGRGAFGQVIEAdafgIDKTATcKTVAVKMLKEGATHSE----HRALMSELKilihighHLNVVNLL 900
Cdd:cd05052    1 WEIERTDITMKHKLGGGQYGEVYEG----VWKKYN-LTVAVKTLKEDTMEVEeflkEAAVMKEIK-------HPNLVQLL 68
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  901 GACTKPGgPLMVIVEFCKFGNLSTYLRGKRNEFVPYkskgarfrqgkdyvgelsvdlkrrldsitssqssassgfveeks 980
Cdd:cd05052   69 GVCTREP-PFYIITEFMPYGNLLDYLRECNREELNA-------------------------------------------- 103
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  981 lsdveeeeaseelykdfLTLEHLicySFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARdIYKDPDYVRK 1060
Cdd:cd05052  104 -----------------VVLLYM---ATQIASAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSR-LMTGDTYTAH 162
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1061 GDARLPLKWMAPETIFDRVYTIQSDVWSFGVLLWEIFSLGASPYPGVKIDEEFcRRLKEGTRMRAPDYTTPEMYQTMLDC 1140
Cdd:cd05052  163 AGAKFPIKWTAPESLAYNKFSIKSDVWAFGVLLWEIATYGMSPYPGIDLSQVY-ELLEKGYRMERPEGCPPKVYELMRAC 241
                        330       340
                 ....*....|....*....|.
gi 27777648 1141 WHEDPNQRPSFSELVEHLGNL 1161
Cdd:cd05052  242 WQWNPSDRPSFAEIHQALETM 262
PTKc_FAK cd05056
Catalytic domain of the Protein Tyrosine Kinase, Focal Adhesion Kinase; PTKs catalyze the ...
825-1163 1.70e-56

Catalytic domain of the Protein Tyrosine Kinase, Focal Adhesion Kinase; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. FAK is a cytoplasmic (or nonreceptor) PTK that contains an autophosphorylation site and a FERM domain at the N-terminus, a central tyr kinase domain, proline-rich regions, and a C-terminal FAT (focal adhesion targeting) domain. FAK activity is dependent on integrin-mediated cell adhesion, which facilitates N-terminal autophosphorylation. Full activation is achieved by the phosphorylation of its two adjacent A-loop tyrosines. FAK is important in mediating signaling initiated at sites of cell adhesions and at growth factor receptors. Through diverse molecular interactions, FAK functions as a biosensor or integrator to control cell motility. It is a key regulator of cell survival, proliferation, migration and invasion, and thus plays an important role in the development and progression of cancer. Src binds to autophosphorylated FAK forming the FAK-Src dual kinase complex, which is activated in a wide variety of tumor cells and generates signals promoting growth and metastasis. FAK is being developed as a target for cancer therapy. The FAK subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 133187 [Multi-domain]  Cd Length: 270  Bit Score: 197.26  E-value: 1.70e-56
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  825 WEFPRDRLKLGKPLGRGAFGQVIEAdaFGIDKTATCKTVAVKMLKEGATHSEHRALMSELKILIHIGHHlNVVNLLGACT 904
Cdd:cd05056    1 YEIQREDITLGRCIGEGQFGDVYQG--VYMSPENEKIAVAVKTCKNCTSPSVREKFLQEAYIMRQFDHP-HIVKLIGVIT 77
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  905 KPggPLMVIVEFCKFGNLSTYLRgkrnefvpykskgarfrqgkdyvgelsvdlkrrldsitssqssassgfveekslsdv 984
Cdd:cd05056   78 EN--PVWIVMELAPLGELRSYLQ--------------------------------------------------------- 98
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  985 eeeeaseeLYKDFLTLEHLICYSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIyKDPDYVRKGDAR 1064
Cdd:cd05056   99 --------VNKYSLDLASLILYAYQLSTALAYLESKRFVHRDIAARNVLVSSPDCVKLGDFGLSRYM-EDESYYKASKGK 169
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1065 LPLKWMAPETIFDRVYTIQSDVWSFGVLLWEIFSLGASPYPGVKiDEEFCRRLKEGTRMRAPDYTTPEMYQTMLDCWHED 1144
Cdd:cd05056  170 LPIKWMAPESINFRRFTSASDVWMFGVCMWEILMLGVKPFQGVK-NNDVIGRIENGERLPMPPNCPPTLYSLMTKCWAYD 248
                        330
                 ....*....|....*....
gi 27777648 1145 PNQRPSFSELVEHLGNLLQ 1163
Cdd:cd05056  249 PSKRPRFTELKAQLSDILQ 267
PTKc_Syk_like cd05060
Catalytic domain of Spleen Tyrosine Kinase-like Protein Tyrosine Kinases; PTKs catalyze the ...
836-1163 2.83e-56

Catalytic domain of Spleen Tyrosine Kinase-like Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. The Syk-like subfamily is composed of Syk, ZAP-70, Shark, and similar proteins. They are cytoplasmic (or nonreceptor) PTKs containing two Src homology 2 (SH2) domains N-terminal to the catalytic tyr kinase domain. They are involved in the signaling downstream of activated receptors (including B-cell, T-cell, and Fc receptors) that contain ITAMs (immunoreceptor tyr activation motifs), leading to processes such as cell proliferation, differentiation, survival, adhesion, migration, and phagocytosis. Syk is important in B-cell receptor signaling, while Zap-70 is primarily expressed in T-cells and NK cells, and is a crucial component in T-cell receptor signaling. Syk also plays a central role in Fc receptor-mediated phagocytosis in the adaptive immune system. Shark is exclusively expressed in ectodermally derived epithelia, and is localized preferentially to the apical surface of the epithelial cells, it may play a role in a signaling pathway for epithelial cell polarity. The Syk-like subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270650 [Multi-domain]  Cd Length: 257  Bit Score: 196.03  E-value: 2.83e-56
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  836 KPLGRGAFGQVIEadafGIDKTATCK--TVAVKMLKEGATHSEHRALMSELKILIHIGHHlNVVNLLGACTKPggPLMVI 913
Cdd:cd05060    1 KELGHGNFGSVRK----GVYLMKSGKevEVAVKTLKQEHEKAGKKEFLREASVMAQLDHP-CIVRLIGVCKGE--PLMLV 73
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  914 VEFCKFGNLSTYLRGKRNEFVpykskgarfrqgkdyvgelsvdlkrrldsitssqssassgfveekslsdveeeeaseel 993
Cdd:cd05060   74 MELAPLGPLLKYLKKRREIPV----------------------------------------------------------- 94
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  994 yKDFLTLEHlicysfQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIYKDPDYVRKGDA-RLPLKWMAP 1072
Cdd:cd05060   95 -SDLKELAH------QVAMGMAYLESKHFVHRDLAARNVLLVNRHQAKISDFGMSRALGAGSDYYRATTAgRWPLKWYAP 167
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1073 ETIFDRVYTIQSDVWSFGVLLWEIFSLGASPYPGVKiDEEFCRRLKEGTRMRAPDYTTPEMYQTMLDCWHEDPNQRPSFS 1152
Cdd:cd05060  168 ECINYGKFSSKSDVWSYGVTLWEAFSYGAKPYGEMK-GPEVIAMLESGERLPRPEECPQEIYSIMLSCWKYRPEDRPTFS 246
                        330
                 ....*....|.
gi 27777648 1153 ELVEHLGNLLQ 1163
Cdd:cd05060  247 ELESTFRRDPE 257
PTKc_DDR cd05051
Catalytic domain of the Protein Tyrosine Kinases, Discoidin Domain Receptors; PTKs catalyze ...
826-1154 4.14e-56

Catalytic domain of the Protein Tyrosine Kinases, Discoidin Domain Receptors; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. The DDR subfamily consists of homologs of mammalian DDR1, DDR2, and similar proteins. They are receptor PTKs (RTKs) containing an extracellular discoidin homology domain, a transmembrane segment, an extended juxtamembrane region, and an intracellular catalytic domain. The binding of the ligand, collagen, to DDRs results in a slow but sustained receptor activation. DDRs regulate cell adhesion, proliferation, and extracellular matrix remodeling. They have been linked to a variety of human cancers including breast, colon, ovarian, brain, and lung. There is no evidence showing that DDRs act as transforming oncogenes. They are more likely to play a role in the regulation of tumor growth and metastasis. The DDR subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270644 [Multi-domain]  Cd Length: 297  Bit Score: 197.17  E-value: 4.14e-56
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  826 EFPRDRLKLGKPLGRGAFGQV-----------IEADAFGIDKTATCKTVAVKMLKEGATHSEHRALMSELKILIHIgHHL 894
Cdd:cd05051    1 EFPREKLEFVEKLGEGQFGEVhlceanglsdlTSDDFIGNDNKDEPVLVAVKMLRPDASKNAREDFLKEVKIMSQL-KDP 79
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  895 NVVNLLGACTKPGgPLMVIVEFCKFGNLSTYLRgkrnefvpykskgarfrqgkDYVGELSVDLKrrldsitssqssassg 974
Cdd:cd05051   80 NIVRLLGVCTRDE-PLCMIVEYMENGDLNQFLQ--------------------KHEAETQGASA---------------- 122
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  975 fveekslsdveeeeaseeLYKDFLTLEHLICYSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIYKD 1054
Cdd:cd05051  123 ------------------TNSKTLSYGTLLYMATQIASGMKYLESLNFVHRDLATRNCLVGPNYTIKIADFGMSRNLYSG 184
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1055 pDYVR-KGDARLPLKWMAPETIFDRVYTIQSDVWSFGVLLWEIFSLG-ASPYpGVKIDE-------EFCRRLKEGTRMRA 1125
Cdd:cd05051  185 -DYYRiEGRAVLPIRWMAWESILLGKFTTKSDVWAFGVTLWEILTLCkEQPY-EHLTDEqvienagEFFRDDGMEVYLSR 262
                        330       340
                 ....*....|....*....|....*....
gi 27777648 1126 PDYTTPEMYQTMLDCWHEDPNQRPSFSEL 1154
Cdd:cd05051  263 PPNCPKEIYELMLECWRRDEEDRPTFREI 291
PTKc_Csk cd05082
Catalytic domain of the Protein Tyrosine Kinase, C-terminal Src kinase; PTKs catalyze the ...
825-1158 1.26e-55

Catalytic domain of the Protein Tyrosine Kinase, C-terminal Src kinase; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Csk catalyzes the tyr phosphorylation of the regulatory C-terminal tail of Src kinases, resulting in their inactivation. Csk is expressed in a wide variety of tissues. As a negative regulator of Src, Csk plays a role in cell proliferation, survival, and differentiation, and consequently, in cancer development and progression. Csk is a cytoplasmic (or nonreceptor) PTK containing the Src homology domains, SH3 and SH2, N-terminal to the catalytic tyr kinase domain. To inhibit Src kinases, Csk is translocated to the membrane via binding to specific transmembrane proteins, G-proteins, or adaptor proteins near the membrane. In addition, Csk also shows Src-independent functions. It is a critical component in G-protein signaling, and plays a role in cytoskeletal reorganization and cell migration. The Csk subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 133213 [Multi-domain]  Cd Length: 256  Bit Score: 194.04  E-value: 1.26e-55
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  825 WEFPRDRLKLGKPLGRGAFGQVIEADAFGidktatcKTVAVKMLKEGATHsehRALMSELKILIHIGHHlNVVNLLGACT 904
Cdd:cd05082    1 WALNMKELKLLQTIGKGEFGDVMLGDYRG-------NKVAVKCIKNDATA---QAFLAEASVMTQLRHS-NLVQLLGVIV 69
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  905 KPGGPLMVIVEFCKFGNLSTYLRGKrnefvpykskgarfrqGKDYVGElsvdlkrrldsitssqssassgfveekslsdv 984
Cdd:cd05082   70 EEKGGLYIVTEYMAKGSLVDYLRSR----------------GRSVLGG-------------------------------- 101
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  985 eeeeaseelykdfltlEHLICYSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIYKDPDyvrkgDAR 1064
Cdd:cd05082  102 ----------------DCLLKFSLDVCEAMEYLEGNNFVHRDLAARNVLVSEDNVAKVSDFGLTKEASSTQD-----TGK 160
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1065 LPLKWMAPETIFDRVYTIQSDVWSFGVLLWEIFSLGASPYPGVKIdEEFCRRLKEGTRMRAPDYTTPEMYQTMLDCWHED 1144
Cdd:cd05082  161 LPVKWTAPEALREKKFSTKSDVWSFGILLWEIYSFGRVPYPRIPL-KDVVPRVEKGYKMDAPDGCPPAVYDVMKNCWHLD 239
                        330
                 ....*....|....
gi 27777648 1145 PNQRPSFSELVEHL 1158
Cdd:cd05082  240 AAMRPSFLQLREQL 253
PTKc_Chk cd05083
Catalytic domain of the Protein Tyrosine Kinase, Csk homologous kinase; PTKs catalyze the ...
825-1158 3.19e-55

Catalytic domain of the Protein Tyrosine Kinase, Csk homologous kinase; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Chk is also referred to as megakaryocyte-associated tyrosine kinase (Matk). Chk inhibits Src kinases using a noncatalytic mechanism by simply binding to them. As a negative regulator of Src kinases, Chk may play important roles in cell proliferation, survival, and differentiation, and consequently, in cancer development and progression. Chk is expressed in brain and hematopoietic cells. Like Csk, it is a cytoplasmic (or nonreceptor) tyr kinase containing the Src homology domains, SH3 and SH2, N-terminal to the catalytic tyr kinase domain. To inhibit Src kinases that are anchored to the plasma membrane, Chk is translocated to the membrane via binding to specific transmembrane proteins, G-proteins, or adaptor proteins near the membrane. Studies in mice reveal that Chk is not functionally redundant with Csk and that it plays an important role as a regulator of immune responses. Chk also plays a role in neural differentiation in a manner independent of Src by enhancing Mapk activation via Ras-mediated signaling. The Chk subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270666 [Multi-domain]  Cd Length: 254  Bit Score: 192.78  E-value: 3.19e-55
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  825 WEFPRDRLKLGKPLGRGAFGQVIEADAFGidktatcKTVAVKMLKEGATHsehRALMSELKILIHIgHHLNVVNLLGACT 904
Cdd:cd05083    1 WLLNLQKLTLGEIIGEGEFGAVLQGEYMG-------QKVAVKNIKCDVTA---QAFLEETAVMTKL-QHKNLVRLLGVIL 69
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  905 KPGgpLMVIVEFCKFGNLSTYLRGKRNEFVPykskgarfrqgkdyvgelsvdlkrrldsitssqssassgfveekslsdv 984
Cdd:cd05083   70 HNG--LYIVMELMSKGNLVNFLRSRGRALVP------------------------------------------------- 98
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  985 eeeeaseelykdfltLEHLICYSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIYKDPDyvrkgDAR 1064
Cdd:cd05083   99 ---------------VIQLLQFSLDVAEGMEYLESKKLVHRDLAARNILVSEDGVAKISDFGLAKVGSMGVD-----NSR 158
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1065 LPLKWMAPETIFDRVYTIQSDVWSFGVLLWEIFSLGASPYPGVKIdEEFCRRLKEGTRMRAPDYTTPEMYQTMLDCWHED 1144
Cdd:cd05083  159 LPVKWTAPEALKNKKFSSKSDVWSYGVLLWEVFSYGRAPYPKMSV-KEVKEAVEKGYRMEPPEGCPPDVYSIMTSCWEAE 237
                        330
                 ....*....|....
gi 27777648 1145 PNQRPSFSELVEHL 1158
Cdd:cd05083  238 PGKRPSFKKLREKL 251
PTKc_Tyro3 cd05074
Catalytic domain of the Protein Tyrosine Kinase, Tyro3; PTKs catalyze the transfer of the ...
828-1162 5.16e-54

Catalytic domain of the Protein Tyrosine Kinase, Tyro3; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Tyro3 (or Sky) is predominantly expressed in the central nervous system and the brain, and functions as a neurotrophic factor. It is also expressed in osteoclasts and has a role in bone resorption. Tyro3 is a member of the TAM subfamily, composed of receptor PTKs (RTKs) containing an extracellular ligand-binding region with two immunoglobulin-like domains followed by two fibronectin type III repeats, a transmembrane segment, and an intracellular catalytic domain. Binding to their ligands, Gas6 and protein S, leads to receptor dimerization, autophosphorylation, activation, and intracellular signaling. The Tyro3 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270659 [Multi-domain]  Cd Length: 284  Bit Score: 190.51  E-value: 5.16e-54
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  828 PRDRLKLGKPLGRGAFGQVIEAdaFGIDKTATCKTVAVKMLKEGATHS-------EHRALMSELkilihigHHLNVVNLL 900
Cdd:cd05074    7 QEQQFTLGRMLGKGEFGSVREA--QLKSEDGSFQKVAVKMLKADIFSSsdieeflREAACMKEF-------DHPNVIKLI 77
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  901 GAC--TKPGGPL---MVIVEFCKFGNLSTYLRGKRnefvpykskgarfrqgkdyVGELSVDLkrrldsitssqssassgf 975
Cdd:cd05074   78 GVSlrSRAKGRLpipMVILPFMKHGDLHTFLLMSR-------------------IGEEPFTL------------------ 120
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  976 veekslsdveeeeaseelykdflTLEHLICYSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIYKDp 1055
Cdd:cd05074  121 -----------------------PLQTLVRFMIDIASGMEYLSSKNFIHRDLAARNCMLNENMTVCVADFGLSKKIYSG- 176
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1056 DYVRKGDA-RLPLKWMAPETIFDRVYTIQSDVWSFGVLLWEIFSLGASPYPGVKiDEEFCRRLKEGTRMRAPDYTTPEMY 1134
Cdd:cd05074  177 DYYRQGCAsKLPVKWLALESLADNVYTTHSDVWAFGVTMWEIMTRGQTPYAGVE-NSEIYNYLIKGNRLKQPPDCLEDVY 255
                        330       340
                 ....*....|....*....|....*...
gi 27777648 1135 QTMLDCWHEDPNQRPSFSELVEHLGNLL 1162
Cdd:cd05074  256 ELMCQCWSPEPKCRPSFQHLRDQLELIW 283
PTKc_Tie2 cd05088
Catalytic domain of the Protein Tyrosine Kinase, Tie2; PTKs catalyze the transfer of the ...
832-1163 1.71e-53

Catalytic domain of the Protein Tyrosine Kinase, Tie2; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Tie2 is a receptor PTK (RTK) containing an extracellular region, a transmembrane segment, and an intracellular catalytic domain. The extracellular region contains an immunoglobulin (Ig)-like domain, three epidermal growth factor (EGF)-like domains, a second Ig-like domain, and three fibronectin type III repeats. Tie2 is expressed mainly in endothelial cells and hematopoietic stem cells. It is also found in a subset of tumor-associated monocytes and eosinophils. The angiopoietins (Ang-1 to Ang-4) serve as ligands for Tie2. The binding of Ang-1 to Tie2 leads to receptor autophosphorylation and activation, promoting cell migration and survival. In contrast, Ang-2 binding to Tie2 does not result in the same response, suggesting that Ang-2 may function as an antagonist. Tie2 signaling plays key regulatory roles in vascular integrity and quiescence, and in inflammation. The Tie2 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 133219 [Multi-domain]  Cd Length: 303  Bit Score: 189.82  E-value: 1.71e-53
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  832 LKLGKPLGRGAFGQVIEADafgIDKTATCKTVAVKMLKEGATHSEHRALMSELKILIHIGHHLNVVNLLGACTKPGgPLM 911
Cdd:cd05088    9 IKFQDVIGEGNFGQVLKAR---IKKDGLRMDAAIKRMKEYASKDDHRDFAGELEVLCKLGHHPNIINLLGACEHRG-YLY 84
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  912 VIVEFCKFGNLSTYLRGKRnefvpykskgarfrqgkdyvgELSVDlkrrldsitssqssasSGFVEEKSLSDVeeeease 991
Cdd:cd05088   85 LAIEYAPHGNLLDFLRKSR---------------------VLETD----------------PAFAIANSTAST------- 120
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  992 elykdfLTLEHLICYSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDiykDPDYVRKGDARLPLKWMA 1071
Cdd:cd05088  121 ------LSSQQLLHFAADVARGMDYLSQKQFIHRDLAARNILVGENYVAKIADFGLSRG---QEVYVKKTMGRLPVRWMA 191
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1072 PETIFDRVYTIQSDVWSFGVLLWEIFSLGASPYPGVKIDEEFcRRLKEGTRMRAPDYTTPEMYQTMLDCWHEDPNQRPSF 1151
Cdd:cd05088  192 IESLNYSVYTTNSDVWSYGVLLWEIVSLGGTPYCGMTCAELY-EKLPQGYRLEKPLNCDDEVYDLMRQCWREKPYERPSF 270
                        330
                 ....*....|..
gi 27777648 1152 SELVEHLGNLLQ 1163
Cdd:cd05088  271 AQILVSLNRMLE 282
PTKc_Axl cd05075
Catalytic domain of the Protein Tyrosine Kinase, Axl; PTKs catalyze the transfer of the ...
831-1164 4.73e-53

Catalytic domain of the Protein Tyrosine Kinase, Axl; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Axl is widely expressed in a variety of organs and cells including epithelial, mesenchymal, hematopoietic, as well as non-transformed cells. It is important in many cellular functions such as survival, anti-apoptosis, proliferation, migration, and adhesion. Axl was originally isolated from patients with chronic myelogenous leukemia and a chronic myeloproliferative disorder. It is overexpressed in many human cancers including colon, squamous cell, thyroid, breast, and lung carcinomas. Axl is a member of the TAM subfamily, composed of receptor PTKs (RTKs) containing an extracellular ligand-binding region with two immunoglobulin-like domains followed by two fibronectin type III repeats, a transmembrane segment, and an intracellular catalytic domain. Binding to its ligands, Gas6 and protein S, leads to receptor dimerization, autophosphorylation, activation, and intracellular signaling. The Axl subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270660 [Multi-domain]  Cd Length: 277  Bit Score: 187.52  E-value: 4.73e-53
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  831 RLKLGKPLGRGAFGQVIEADafgIDKTATCKTVAVKMLKEG-ATHSEHRALMSELKILIHIGHHlNVVNLLGACTK---- 905
Cdd:cd05075    1 KLALGKTLGEGEFGSVMEGQ---LNQDDSVLKVAVKTMKIAiCTRSEMEDFLSEAVCMKEFDHP-NVMRLIGVCLQntes 76
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  906 PGGPL-MVIVEFCKFGNLSTYLRGKRnefvpykskgarfrqgkdyVGELSVdlkrrldsitssqssassgfveekslsdv 984
Cdd:cd05075   77 EGYPSpVVILPFMKHGDLHSFLLYSR-------------------LGDCPV----------------------------- 108
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  985 eeeeaseelykdFLTLEHLICYSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIYkDPDYVRKGD-A 1063
Cdd:cd05075  109 ------------YLPTQMLVKFMTDIASGMEYLSSKNFIHRDLAARNCMLNENMNVCVADFGLSKKIY-NGDYYRQGRiS 175
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1064 RLPLKWMAPETIFDRVYTIQSDVWSFGVLLWEIFSLGASPYPGVKiDEEFCRRLKEGTRMRAPDYTTPEMYQTMLDCWHE 1143
Cdd:cd05075  176 KMPVKWIAIESLADRVYTTKSDVWSFGVTMWEIATRGQTPYPGVE-NSEIYDYLRQGNRLKQPPDCLDGLYELMSSCWLL 254
                        330       340
                 ....*....|....*....|.
gi 27777648 1144 DPNQRPSFSELVEHLGNLLQA 1164
Cdd:cd05075  255 NPKDRPSFETLRCELEKILKD 275
PTKc_Fer cd05085
Catalytic domain of the Protein Tyrosine Kinase, Fer; Protein Tyrosine Kinase (PTK) family; ...
835-1158 6.04e-53

Catalytic domain of the Protein Tyrosine Kinase, Fer; Protein Tyrosine Kinase (PTK) family; Fer kinase; catalytic (c) domain. The PTKc family is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, and phosphoinositide 3-kinase (PI3K). PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Fer kinase is a member of the Fes subfamily of proteins which are cytoplasmic (or nonreceptor) tyr kinases containing an N-terminal region with FCH (Fes/Fer/CIP4 homology) and coiled-coil domains, followed by a SH2 domain, and a C-terminal catalytic domain. Fer kinase is expressed in a wide variety of tissues, and is found to reside in both the cytoplasm and the nucleus. It plays important roles in neuronal polarization and neurite development, cytoskeletal reorganization, cell migration, growth factor signaling, and the regulation of cell-cell interactions mediated by adherens junctions and focal adhesions. Fer kinase also regulates cell cycle progression in malignant cells.


Pssm-ID: 270668 [Multi-domain]  Cd Length: 251  Bit Score: 186.36  E-value: 6.04e-53
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  835 GKPLGRGAFGQVIEADAfgIDKTAtcktVAVKMLKEGATHSEHRALMSELKILIHIGHHlNVVNLLGACTKPGgPLMVIV 914
Cdd:cd05085    1 GELLGKGNFGEVYKGTL--KDKTP----VAVKTCKEDLPQELKIKFLSEARILKQYDHP-NIVKLIGVCTQRQ-PIYIVM 72
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  915 EFCKFGNLSTYLRGKRNEfvpykskgarfrqgkdyvgelsvdlkrrldsitssqssassgfveekslsdveeeeaseely 994
Cdd:cd05085   73 ELVPGGDFLSFLRKKKDE-------------------------------------------------------------- 90
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  995 kdfLTLEHLICYSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDiYKDPDYVRKGDARLPLKWMAPET 1074
Cdd:cd05085   91 ---LKTKQLVKFSLDAAAGMAYLESKNCIHRDLAARNCLVGENNALKISDFGMSRQ-EDDGVYSSSGLKQIPIKWTAPEA 166
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1075 IFDRVYTIQSDVWSFGVLLWEIFSLGASPYPGVKiDEEFCRRLKEGTRMRAPDYTTPEMYQTMLDCWHEDPNQRPSFSEL 1154
Cdd:cd05085  167 LNYGRYSSESDVWSFGILLWETFSLGVCPYPGMT-NQQAREQVEKGYRMSAPQRCPEDIYKIMQRCWDYNPENRPKFSEL 245

                 ....
gi 27777648 1155 VEHL 1158
Cdd:cd05085  246 QKEL 249
PTK_Ryk cd05043
Pseudokinase domain of Ryk (Receptor related to tyrosine kinase); Ryk is a receptor tyr kinase ...
829-1158 8.08e-52

Pseudokinase domain of Ryk (Receptor related to tyrosine kinase); Ryk is a receptor tyr kinase (RTK) containing an extracellular region with two leucine-rich motifs, a transmembrane segment, and an intracellular inactive pseudokinase domain, which shows similarity to tyr kinases but lacks crucial residues for catalytic activity and ATP binding. The extracellular region of Ryk shows homology to the N-terminal domain of Wnt inhibitory factor-1 (WIF) and serves as the ligand (Wnt) binding domain of Ryk. Ryk is expressed in many different tissues both during development and in adults, suggesting a widespread function. It acts as a chemorepulsive axon guidance receptor of Wnt glycoproteins and is responsible for the establishment of axon tracts during the development of the central nervous system. In addition, studies in mice reveal that Ryk is essential in skeletal, craniofacial, and cardiac development. Thus, it appears Ryk is involved in signal transduction despite its lack of kinase activity. Ryk may function as an accessory protein that modulates the signals coming from catalytically active partner RTKs such as the Eph receptors. The Ryk subfamily is part of a larger superfamily that includes other pseudokinases and the catalytic domains of active kinases including PTKs, protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270639 [Multi-domain]  Cd Length: 279  Bit Score: 184.19  E-value: 8.08e-52
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  829 RDRLKLGKPLGRGAFGQVIEADAfgIDKTATCKTVAVKMLKEGATHSEHRALMSELKILIHIgHHLNVVNLLGACTKPGG 908
Cdd:cd05043    5 RERVTLSDLLQEGTFGRIFHGIL--RDEKGKEEEVLVKTVKDHASEIQVTMLLQESSLLYGL-SHQNLLPILHVCIEDGE 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  909 PLMVIVEFCKFGNLSTYLRGKRnefvpykskgarfrqgkdyvgelsvdlkrrldsitssqssassgfveeksLSDVEEEE 988
Cdd:cd05043   82 KPMVLYPYMNWGNLKLFLQQCR--------------------------------------------------LSEANNPQ 111
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  989 AseelykdfLTLEHLICYSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIYKDpDYVRKGDAR-LPL 1067
Cdd:cd05043  112 A--------LSTQQLVHMALQIACGMSYLHRRGVIHKDIAARNCVIDDELQVKITDNALSRDLFPM-DYHCLGDNEnRPI 182
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1068 KWMAPETIFDRVYTIQSDVWSFGVLLWEIFSLGASPYpgVKID-EEFCRRLKEGTRMRAPDYTTPEMYQTMLDCWHEDPN 1146
Cdd:cd05043  183 KWMSLESLVNKEYSSASDVWSFGVLLWELMTLGQTPY--VEIDpFEMAAYLKDGYRLAQPINCPDELFAVMACCWALDPE 260
                        330
                 ....*....|..
gi 27777648 1147 QRPSFSELVEHL 1158
Cdd:cd05043  261 ERPSFQQLVQCL 272
PTKc_Fes cd05084
Catalytic domain of the Protein Tyrosine Kinase, Fes; PTKs catalyze the transfer of the ...
835-1159 1.50e-51

Catalytic domain of the Protein Tyrosine Kinase, Fes; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Fes (or Fps) is a cytoplasmic (or nonreceptor) PTK containing an N-terminal region with FCH (Fes/Fer/CIP4 homology) and coiled-coil domains, followed by a SH2 domain, and a C-terminal catalytic domain. The genes for Fes (feline sarcoma) and Fps (Fujinami poultry sarcoma) were first isolated from tumor-causing retroviruses. The viral oncogenes encode chimeric Fes proteins consisting of Gag sequences at the N-termini, resulting in unregulated PTK activity. Fes kinase is expressed in myeloid, vascular endothelial, epithelial, and neuronal cells. It plays important roles in cell growth and differentiation, angiogenesis, inflammation and immunity, and cytoskeletal regulation. A recent study implicates Fes kinase as a tumor suppressor in colorectal cancer. The Fes subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270667 [Multi-domain]  Cd Length: 252  Bit Score: 182.44  E-value: 1.50e-51
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  835 GKPLGRGAFGQVieadaFGIDKTATCKTVAVKMLKEGATHSEHRALMSELKILIHIGHHlNVVNLLGACTKPGgPLMVIV 914
Cdd:cd05084    1 GERIGRGNFGEV-----FSGRLRADNTPVAVKSCRETLPPDLKAKFLQEARILKQYSHP-NIVRLIGVCTQKQ-PIYIVM 73
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  915 EFCKFGNLSTYLRgkrnefvpykSKGARFRqgkdyvgelsvdlkrrldsitssqssassgfveekslsdveeeeaseely 994
Cdd:cd05084   74 ELVQGGDFLTFLR----------TEGPRLK-------------------------------------------------- 93
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  995 kdfltLEHLICYSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDiYKDPDYVRKGDAR-LPLKWMAPE 1073
Cdd:cd05084   94 -----VKELIRMVENAAAGMEYLESKHCIHRDLAARNCLVTEKNVLKISDFGMSRE-EEDGVYAATGGMKqIPVKWTAPE 167
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1074 TIFDRVYTIQSDVWSFGVLLWEIFSLGASPYPGVKiDEEFCRRLKEGTRMRAPDYTTPEMYQTMLDCWHEDPNQRPSFSE 1153
Cdd:cd05084  168 ALNYGRYSSESDVWSFGILLWETFSLGAVPYANLS-NQQTREAVEQGVRLPCPENCPDEVYRLMEQCWEYDPRKRPSFST 246

                 ....*.
gi 27777648 1154 LVEHLG 1159
Cdd:cd05084  247 VHQDLQ 252
PTKc_Lck_Blk cd05067
Catalytic domain of the Protein Tyrosine Kinases, Lymphocyte-specific kinase and Blk; PTKs ...
824-1163 5.87e-51

Catalytic domain of the Protein Tyrosine Kinases, Lymphocyte-specific kinase and Blk; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Lck and Blk are members of the Src subfamily of proteins, which are cytoplasmic (or non-receptor) PTKs. Lck is expressed in T-cells and natural killer cells. It plays a critical role in T-cell maturation, activation, and T-cell receptor (TCR) signaling. Lck phosphorylates ITAM (immunoreceptor tyr activation motif) sequences on several subunits of TCRs, leading to the activation of different second messenger cascades. Phosphorylated ITAMs serve as binding sites for other signaling factor such as Syk and ZAP-70, leading to their activation and propagation of downstream events. In addition, Lck regulates drug-induced apoptosis by interfering with the mitochondrial death pathway. The apototic role of Lck is independent of its primary function in T-cell signaling. Blk is expressed specifically in B-cells. It is involved in pre-BCR (B-cell receptor) signaling. Src kinases contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). The Lck/Blk subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270652 [Multi-domain]  Cd Length: 264  Bit Score: 180.85  E-value: 5.87e-51
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  824 KWEFPRDRLKLGKPLGRGAFGQVieadAFGIDKTATckTVAVKMLKEGATHSEhrALMSELKILIHIgHHLNVVNLLGAC 903
Cdd:cd05067    1 EWEVPRETLKLVERLGAGQFGEV----WMGYYNGHT--KVAIKSLKQGSMSPD--AFLAEANLMKQL-QHQRLVRLYAVV 71
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  904 TKPggPLMVIVEFCKFGNLSTYLRgkrnefvpyKSKGARfrqgkdyvgelsvdlkrrldsitssqssassgfveekslsd 983
Cdd:cd05067   72 TQE--PIYIITEYMENGSLVDFLK---------TPSGIK----------------------------------------- 99
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  984 veeeeaseelykdfLTLEHLICYSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARdIYKDPDYVRKGDA 1063
Cdd:cd05067  100 --------------LTINKLLDMAAQIAEGMAFIEERNYIHRDLRAANILVSDTLSCKIADFGLAR-LIEDNEYTAREGA 164
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1064 RLPLKWMAPETIFDRVYTIQSDVWSFGVLLWEIFSLGASPYPGVKiDEEFCRRLKEGTRMRAPDYTTPEMYQTMLDCWHE 1143
Cdd:cd05067  165 KFPIKWTAPEAINYGTFTIKSDVWSFGILLTEIVTHGRIPYPGMT-NPEVIQNLERGYRMPRPDNCPEELYQLMRLCWKE 243
                        330       340
                 ....*....|....*....|
gi 27777648 1144 DPNQRPSFselvEHLGNLLQ 1163
Cdd:cd05067  244 RPEDRPTF----EYLRSVLE 259
PTKc_Ack_like cd05040
Catalytic domain of the Protein Tyrosine Kinase, Activated Cdc42-associated kinase; PTKs ...
1002-1158 3.09e-50

Catalytic domain of the Protein Tyrosine Kinase, Activated Cdc42-associated kinase; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. This subfamily includes Ack1, thirty-eight-negative kinase 1 (Tnk1), and similar proteins. They are cytoplasmic (or nonreceptor) PTKs containing an N-terminal catalytic domain, an SH3 domain, a Cdc42-binding CRIB domain, and a proline-rich region. They are mainly expressed in brain and skeletal tissues and are involved in the regulation of cell adhesion and growth, receptor degradation, and axonal guidance. Ack1 is also associated with androgen-independent prostate cancer progression. Tnk1 regulates TNFalpha signaling and may play an important role in cell death. The Ack-like subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270636 [Multi-domain]  Cd Length: 258  Bit Score: 178.69  E-value: 3.09e-50
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1002 HLIC-YSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIYKDPD-YVRKGDARLPLKWMAPETIFDRV 1079
Cdd:cd05040   98 STLCdYAVQIANGMAYLESKRFIHRDLAARNILLASKDKVKIGDFGLMRALPQNEDhYVMQEHRKVPFAWCAPESLKTRK 177
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1080 YTIQSDVWSFGVLLWEIFSLGASPYPGV-------KIDeefcrrlKEGTRMRAPDYTTPEMYQTMLDCWHEDPNQRPSFS 1152
Cdd:cd05040  178 FSHASDVWMFGVTLWEMFTYGEEPWLGLngsqileKID-------KEGERLERPDDCPQDIYNVMLQCWAHKPADRPTFV 250

                 ....*.
gi 27777648 1153 ELVEHL 1158
Cdd:cd05040  251 ALRDFL 256
PTKc_EphR cd05033
Catalytic domain of Ephrin Receptor Protein Tyrosine Kinases; PTKs catalyze the transfer of ...
832-1162 4.30e-50

Catalytic domain of Ephrin Receptor Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. EphRs comprise the largest subfamily of receptor PTKs (RTKs). They can be classified into two classes (EphA and EphB), according to their extracellular sequences, which largely correspond to binding preferences for either GPI-anchored ephrin-A ligands or transmembrane ephrin-B ligands. Vertebrates have ten EphA and six EphB receptors, which display promiscuous ligand interactions within each class. EphRs contain an ephrin binding domain and two fibronectin repeats extracellularly, a transmembrane segment, and a cytoplasmic tyr kinase domain. Binding of the ephrin ligand to EphR requires cell-cell contact since both are anchored to the plasma membrane. This allows ephrin/EphR dimers to form, leading to the activation of the intracellular tyr kinase domain. The resulting downstream signals occur bidirectionally in both EphR-expressing cells (forward signaling) and ephrin-expressing cells (reverse signaling). The main effect of ephrin/EphR interaction is cell-cell repulsion or adhesion. Ephrin/EphR signaling is important in neural development and plasticity, cell morphogenesis and proliferation, cell-fate determination, embryonic development, tissue patterning, and angiogenesis.The EphR subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270629 [Multi-domain]  Cd Length: 266  Bit Score: 178.72  E-value: 4.30e-50
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  832 LKLGKPLGRGAFGQVIEadafGIDKTATCK--TVAVKMLKEGATHSEHRALMSELKILIHIGHHlNVVNLLGACTKpGGP 909
Cdd:cd05033    6 VTIEKVIGGGEFGEVCS----GSLKLPGKKeiDVAIKTLKSGYSDKQRLDFLTEASIMGQFDHP-NVIRLEGVVTK-SRP 79
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  910 LMVIVEFCKFGNLSTYLRGKRNEFVPykskgarfrqgkdyvgelsvdlkrrldsitssqssassgfveekslsdveeeea 989
Cdd:cd05033   80 VMIVTEYMENGSLDKFLRENDGKFTV------------------------------------------------------ 105
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  990 seelykdfltlEHLICYSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDI-YKDPDYVRKGdARLPLK 1068
Cdd:cd05033  106 -----------TQLVGMLRGIASGMKYLSEMNYVHRDLAARNILVNSDLVCKVSDFGLSRRLeDSEATYTTKG-GKIPIR 173
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1069 WMAPETIFDRVYTIQSDVWSFGVLLWEIFSLGASPYPGVKiDEEFCRRLKEGTRMRAPDYTTPEMYQTMLDCWHEDPNQR 1148
Cdd:cd05033  174 WTAPEAIAYRKFTSASDVWSFGIVMWEVMSYGERPYWDMS-NQDVIKAVEDGYRLPPPMDCPSALYQLMLDCWQKDRNER 252
                        330
                 ....*....|....
gi 27777648 1149 PSFSELVEHLGNLL 1162
Cdd:cd05033  253 PTFSQIVSTLDKMI 266
S_TKc smart00220
Serine/Threonine protein kinases, catalytic domain; Phosphotransferases. Serine or ...
833-1157 7.00e-50

Serine/Threonine protein kinases, catalytic domain; Phosphotransferases. Serine or threonine-specific kinase subfamily.


Pssm-ID: 214567 [Multi-domain]  Cd Length: 254  Bit Score: 177.34  E-value: 7.00e-50
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648     833 KLGKPLGRGAFGQVIEAdafgIDKTaTCKTVAVKMLKEGATHSEHRALMSELKILIHIgHHLNVVNLLGACTKPGgPLMV 912
Cdd:smart00220    2 EILEKLGEGSFGKVYLA----RDKK-TGKLVAIKVIKKKKIKKDRERILREIKILKKL-KHPNIVRLYDVFEDED-KLYL 74
                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648     913 IVEFCKFGNLSTYLRGKRnefvpykskgarfrqgkdyvgelsvdlkrrldsitssqssassgfveekslsdveeeeasee 992
Cdd:smart00220   75 VMEYCEGGDLFDLLKKRG-------------------------------------------------------------- 92
                           170       180       190       200       210       220       230       240
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648     993 lykdFLTLEHLICYSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARdIYKDPDYVRKGDArlPLKWMAP 1072
Cdd:smart00220   93 ----RLSEDEARFYLRQILSALEYLHSKGIVHRDLKPENILLDEDGHVKLADFGLAR-QLDPGEKLTTFVG--TPEYMAP 165
                           250       260       270       280       290       300       310       320
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648    1073 ETIFDRVYTIQSDVWSFGVLLWEIFSlGASPYPGVKIDEEFCRRLKEGTR--MRAPDYTTPEMYQTMLDCWHEDPNQRPS 1150
Cdd:smart00220  166 EVLLGKGYGKAVDIWSLGVILYELLT-GKPPFPGDDQLLELFKKIGKPKPpfPPPEWDISPEAKDLIRKLLVKDPEKRLT 244

                    ....*..
gi 27777648    1151 FSELVEH 1157
Cdd:smart00220  245 AEEALQH 251
PTKc_IGF-1R cd05062
Catalytic domain of the Protein Tyrosine Kinase, Insulin-like Growth Factor-1 Receptor; PTKs ...
825-1158 9.11e-50

Catalytic domain of the Protein Tyrosine Kinase, Insulin-like Growth Factor-1 Receptor; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. IGF-1R is a receptor PTK (RTK) that is composed of two alphabeta heterodimers. Binding of the ligand (IGF-1 or IGF-2) to the extracellular alpha subunit activates the intracellular tyr kinase domain of the transmembrane beta subunit. Receptor activation leads to autophosphorylation, which stimulates downstream kinase activities and biological function. IGF-1R signaling is important in the differentiation, growth, and survival of normal cells. In cancer cells, where it is frequently overexpressed, IGF-1R is implicated in proliferation, the suppression of apoptosis, invasion, and metastasis. IGF-1R is being developed as a therapeutic target in cancer treatment. The IGF-1R subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 133193 [Multi-domain]  Cd Length: 277  Bit Score: 177.92  E-value: 9.11e-50
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  825 WEFPRDRLKLGKPLGRGAFGQVIEADAFGIDKTATCKTVAVKMLKEGATHSEHRALMSELKILIHIGHHlNVVNLLGACT 904
Cdd:cd05062    1 WEVAREKITMSRELGQGSFGMVYEGIAKGVVKDEPETRVAIKTVNEAASMRERIEFLNEASVMKEFNCH-HVVRLLGVVS 79
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  905 KpGGPLMVIVEFCKFGNLSTYLRGKRNEfvpykskgarfrqgkdyvgelsvdlkrrldsitssqssassgfvEEKSLSDV 984
Cdd:cd05062   80 Q-GQPTLVIMELMTRGDLKSYLRSLRPE--------------------------------------------MENNPVQA 114
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  985 EEeeaseelykdflTLEHLICYSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIYKDPDYVRKGDAR 1064
Cdd:cd05062  115 PP------------SLKKMIQMAGEIADGMAYLNANKFVHRDLAARNCMVAEDFTVKIGDFGMTRDIYETDYYRKGGKGL 182
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1065 LPLKWMAPETIFDRVYTIQSDVWSFGVLLWEIFSLGASPYPGVKiDEEFCRRLKEGTRMRAPDYTTPEMYQTMLDCWHED 1144
Cdd:cd05062  183 LPVRWMSPESLKDGVFTTYSDVWSFGVVLWEIATLAEQPYQGMS-NEQVLRFVMEGGLLDKPDNCPDMLFELMRMCWQYN 261
                        330
                 ....*....|....
gi 27777648 1145 PNQRPSFSELVEHL 1158
Cdd:cd05062  262 PKMRPSFLEIISSI 275
PTKc_Hck cd05073
Catalytic domain of the Protein Tyrosine Kinase, Hematopoietic cell kinase; PTKs catalyze the ...
820-1163 2.12e-48

Catalytic domain of the Protein Tyrosine Kinase, Hematopoietic cell kinase; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Hck is a member of the Src subfamily of proteins, which are cytoplasmic (or non-receptor) PTKs. Hck is present in myeloid and lymphoid cells that play a role in the development of cancer. It may be important in the oncogenic signaling of the protein Tel-Abl, which induces a chronic myelogenous leukemia (CML)-like disease. Hck also acts as a negative regulator of G-CSF-induced proliferation of granulocytic precursors, suggesting a possible role in the development of acute myeloid leukemia (AML). In addition, Hck is essential in regulating the degranulation of polymorphonuclear leukocytes. Genetic polymorphisms affect the expression level of Hck, which affects PMN mediator release and influences the development of chronic obstructive pulmonary disease (COPD). Src kinases contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). The Hck subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270658 [Multi-domain]  Cd Length: 265  Bit Score: 173.67  E-value: 2.12e-48
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  820 YDASKWEFPRDRLKLGKPLGRGAFGQVIEADAFGIDKtatcktVAVKMLKEGATHSEhrALMSELKILIHIGHHlNVVNL 899
Cdd:cd05073    1 WEKDAWEIPRESLKLEKKLGAGQFGEVWMATYNKHTK------VAVKTMKPGSMSVE--AFLAEANVMKTLQHD-KLVKL 71
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  900 LGACTKPggPLMVIVEFCKFGNLSTYLRGKRNEFVPykskgarfrqgkdyvgelsvdlkrrldsitssqssassgfveek 979
Cdd:cd05073   72 HAVVTKE--PIYIITEFMAKGSLLDFLKSDEGSKQP-------------------------------------------- 105
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  980 slsdveeeeaseelykdfltLEHLICYSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARdIYKDPDYVR 1059
Cdd:cd05073  106 --------------------LPKLIDFSAQIAEGMAFIEQRNYIHRDLRAANILVSASLVCKIADFGLAR-VIEDNEYTA 164
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1060 KGDARLPLKWMAPETIFDRVYTIQSDVWSFGVLLWEIFSLGASPYPGVKiDEEFCRRLKEGTRMRAPDYTTPEMYQTMLD 1139
Cdd:cd05073  165 REGAKFPIKWTAPEAINFGSFTIKSDVWSFGILLMEIVTYGRIPYPGMS-NPEVIRALERGYRMPRPENCPEELYNIMMR 243
                        330       340
                 ....*....|....*....|....
gi 27777648 1140 CWHEDPNQRPSFselvEHLGNLLQ 1163
Cdd:cd05073  244 CWKNRPEERPTF----EYIQSVLD 263
PTKc_TrkA cd05092
Catalytic domain of the Protein Tyrosine Kinase, Tropomyosin Related Kinase A; PTKs catalyze ...
824-1154 3.68e-48

Catalytic domain of the Protein Tyrosine Kinase, Tropomyosin Related Kinase A; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. TrkA is a receptor PTK (RTK) containing an extracellular region with arrays of leucine-rich motifs flanked by two cysteine-rich clusters followed by two immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. Binding of TrkA to its ligand, nerve growth factor (NGF), results in receptor oligomerization and activation of the catalytic domain. TrkA is expressed mainly in neural-crest-derived sensory and sympathetic neurons of the peripheral nervous system, and in basal forebrain cholinergic neurons of the central nervous system. It is critical for neuronal growth, differentiation and survival. Alternative TrkA splicing has been implicated as a pivotal regulator of neuroblastoma (NB) behavior. Normal TrkA expression is associated with better NB prognosis, while the hypoxia-regulated TrkAIII splice variant promotes NB pathogenesis and progression. Aberrant TrkA expression has also been demonstrated in non-neural tumors including prostate, breast, lung, and pancreatic cancers. The TrkA subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270674 [Multi-domain]  Cd Length: 280  Bit Score: 173.61  E-value: 3.68e-48
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  824 KWEfprdrlklgkpLGRGAFGQVIEADAFGIDKTATCKTVAVKMLKEgATHSEHRALMSELKILIHIGHHlNVVNLLGAC 903
Cdd:cd05092   10 KWE-----------LGEGAFGKVFLAECHNLLPEQDKMLVAVKALKE-ATESARQDFQREAELLTVLQHQ-HIVRFYGVC 76
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  904 TKpGGPLMVIVEFCKFGNLSTYLRGK-RNEFVPYKSKGARFRQgkdyvgelsvdlkrrldsitssqssassgfveeksls 982
Cdd:cd05092   77 TE-GEPLIMVFEYMRHGDLNRFLRSHgPDAKILDGGEGQAPGQ------------------------------------- 118
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  983 dveeeeaseelykdfLTLEHLICYSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIYKDPDYVRKGD 1062
Cdd:cd05092  119 ---------------LTLGQMLQIASQIASGMVYLASLHFVHRDLATRNCLVGQGLVVKIGDFGMSRDIYSTDYYRVGGR 183
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1063 ARLPLKWMAPETIFDRVYTIQSDVWSFGVLLWEIFSLGASPYPGVKiDEEFCRRLKEGTRMRAPDYTTPEMYQTMLDCWH 1142
Cdd:cd05092  184 TMLPIRWMPPESILYRKFTTESDIWSFGVVLWEIFTYGKQPWYQLS-NTEAIECITQGRELERPRTCPPEVYAIMQGCWQ 262
                        330
                 ....*....|..
gi 27777648 1143 EDPNQRPSFSEL 1154
Cdd:cd05092  263 REPQQRHSIKDI 274
PTKc_Lyn cd05072
Catalytic domain of the Protein Tyrosine Kinase, Lyn; PTKs catalyze the transfer of the ...
825-1168 2.03e-47

Catalytic domain of the Protein Tyrosine Kinase, Lyn; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Lyn is a member of the Src subfamily of proteins, which are cytoplasmic (or non-receptor) PTKs. Lyn is expressed in B lymphocytes and myeloid cells. It exhibits both positive and negative regulatory roles in B cell receptor (BCR) signaling. Lyn, as well as Fyn and Blk, promotes B cell activation by phosphorylating ITAMs (immunoreceptor tyr activation motifs) in CD19 and in Ig components of BCR. It negatively regulates signaling by its unique ability to phosphorylate ITIMs (immunoreceptor tyr inhibition motifs) in cell surface receptors like CD22 and CD5. Lyn also plays an important role in G-CSF receptor signaling by phosphorylating a variety of adaptor molecules. Src kinases contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). The Lyn subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270657 [Multi-domain]  Cd Length: 272  Bit Score: 170.99  E-value: 2.03e-47
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  825 WEFPRDRLKLGKPLGRGAFGQVieadAFGIDKTATckTVAVKMLKEGATHSEhrALMSELKILIHIGHHlNVVNLLGACT 904
Cdd:cd05072    2 WEIPRESIKLVKKLGAGQFGEV----WMGYYNNST--KVAVKTLKPGTMSVQ--AFLEEANLMKTLQHD-KLVRLYAVVT 72
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  905 KPGgPLMVIVEFCKFGNLSTYLRGKrnefvpyksKGARfrqgkdyvgelsvdlkrrldsitssqssassgfveekslsdv 984
Cdd:cd05072   73 KEE-PIYIITEYMAKGSLLDFLKSD---------EGGK------------------------------------------ 100
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  985 eeeeaseelykdfLTLEHLICYSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIyKDPDYVRKGDAR 1064
Cdd:cd05072  101 -------------VLLPKLIDFSAQIAEGMAYIERKNYIHRDLRAANVLVSESLMCKIADFGLARVI-EDNEYTAREGAK 166
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1065 LPLKWMAPETIFDRVYTIQSDVWSFGVLLWEIFSLGASPYPGVKiDEEFCRRLKEGTRMRAPDYTTPEMYQTMLDCWHED 1144
Cdd:cd05072  167 FPIKWTAPEAINFGSFTIKSDVWSFGILLYEIVTYGKIPYPGMS-NSDVMSALQRGYRMPRMENCPDELYDIMKTCWKEK 245
                        330       340
                 ....*....|....*....|....
gi 27777648 1145 PNQRPSFSELVEHLGNLLQANAQQ 1168
Cdd:cd05072  246 AEERPTFDYLQSVLDDFYTATEGQ 269
PTKc_EphR_A2 cd05063
Catalytic domain of the Protein Tyrosine Kinase, Ephrin Receptor A2; PTKs catalyze the ...
836-1162 2.14e-46

Catalytic domain of the Protein Tyrosine Kinase, Ephrin Receptor A2; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. The EphA2 receptor is overexpressed in tumor cells and tumor blood vessels in a variety of cancers including breast, prostate, lung, and colon. As a result, it is an attractive target for drug design since its inhibition could affect several aspects of tumor progression. EphRs comprise the largest subfamily of receptor PTKs (RTKs). Class EphA receptors bind GPI-anchored ephrin-A ligands. There are ten vertebrate EphA receptors (EphA1-10), which display promiscuous interactions with six ephrin-A ligands. EphRs contain an ephrin binding domain and two fibronectin repeats extracellularly, a transmembrane segment, and a cytoplasmic tyr kinase domain. Binding of the ephrin ligand to EphR requires cell-cell contact since both are anchored to the plasma membrane. The resulting downstream signals occur bidirectionally in both EphR-expressing cells (forward signaling) and ephrin-expressing cells (reverse signaling). Ephrin/EphR interaction mainly results in cell-cell repulsion or adhesion, making it important in neural development and plasticity, cell morphogenesis, cell-fate determination, embryonic development, tissue patterning, and angiogenesis. The EphA2 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, and phosphoinositide 3-kinase (PI3K).


Pssm-ID: 133194 [Multi-domain]  Cd Length: 268  Bit Score: 168.23  E-value: 2.14e-46
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  836 KPLGRGAFGQVIEadafGIDKTATCK--TVAVKMLKEGATHSEHRALMSELKILIHIGHHlNVVNLLGACTKpGGPLMVI 913
Cdd:cd05063   11 KVIGAGEFGEVFR----GILKMPGRKevAVAIKTLKPGYTEKQRQDFLSEASIMGQFSHH-NIIRLEGVVTK-FKPAMII 84
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  914 VEFCKFGNLSTYLRGKRNEFVPYKskgarfrqgkdYVGELSvdlkrrldsitssqssassgfveekslsdveeeeaseel 993
Cdd:cd05063   85 TEYMENGALDKYLRDHDGEFSSYQ-----------LVGMLR--------------------------------------- 114
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  994 ykdfltlehlicysfQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIYKDPD--YVRKGdARLPLKWMA 1071
Cdd:cd05063  115 ---------------GIAAGMKYLSDMNYVHRDLAARNILVNSNLECKVSDFGLSRVLEDDPEgtYTTSG-GKIPIRWTA 178
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1072 PETIFDRVYTIQSDVWSFGVLLWEIFSLGASPYPGVKiDEEFCRRLKEGTRMRAPDYTTPEMYQTMLDCWHEDPNQRPSF 1151
Cdd:cd05063  179 PEAIAYRKFTSASDVWSFGIVMWEVMSFGERPYWDMS-NHEVMKAINDGFRLPAPMDCPSAVYQLMLQCWQQDRARRPRF 257
                        330
                 ....*....|.
gi 27777648 1152 SELVEHLGNLL 1162
Cdd:cd05063  258 VDIVNLLDKLL 268
PTKc_EphR_A cd05066
Catalytic domain of the Protein Tyrosine Kinases, Class EphA Ephrin Receptors; PTKs catalyze ...
831-1162 9.31e-46

Catalytic domain of the Protein Tyrosine Kinases, Class EphA Ephrin Receptors; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. This subfamily is composed of most class EphA receptors including EphA3, EphA4, EphA5, and EphA7, but excluding EphA1, EphA2 and EphA10. Class EphA receptors bind GPI-anchored ephrin-A ligands. There are ten vertebrate EphA receptors (EphA1-10), which display promiscuous interactions with six ephrin-A ligands. One exception is EphA4, which also binds ephrins-B2/B3. EphA receptors and ephrin-A ligands are expressed in multiple areas of the developing brain, especially in the retina and tectum. They are part of a system controlling retinotectal mapping. EphRs comprise the largest subfamily of receptor PTKs (RTKs). EphRs contain an ephrin-binding domain and two fibronectin repeats extracellularly, a transmembrane segment, and a cytoplasmic tyr kinase domain. Binding of the ephrin ligand to EphR requires cell-cell contact since both are anchored to the plasma membrane. The resulting downstream signals occur bidirectionally in both EphR-expressing cells (forward signaling) and ephrin-expressing cells (reverse signaling). Ephrin/EphR interaction mainly results in cell-cell repulsion or adhesion, making it important in neural development and plasticity, cell morphogenesis, cell-fate determination, embryonic development, tissue patterning, and angiogenesis. The EphA subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270651 [Multi-domain]  Cd Length: 267  Bit Score: 166.20  E-value: 9.31e-46
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  831 RLKLGKPLGRGAFGQVIEADAFGIDKTATCktVAVKMLKEGATHSEHRALMSELKILIHIGHHlNVVNLLGACTKpGGPL 910
Cdd:cd05066    5 CIKIEKVIGAGEFGEVCSGRLKLPGKREIP--VAIKTLKAGYTEKQRRDFLSEASIMGQFDHP-NIIHLEGVVTR-SKPV 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  911 MVIVEFCKFGNLSTYLRGKRNEFvpykskgarfrqgkdyvgelsvdlkrrldsitssqssassgfveekslsdveeeeas 990
Cdd:cd05066   81 MIVTEYMENGSLDAFLRKHDGQF--------------------------------------------------------- 103
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  991 eelykdflTLEHLICYSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIYKDPD--YVRKGdARLPLK 1068
Cdd:cd05066  104 --------TVIQLVGMLRGIASGMKYLSDMGYVHRDLAARNILVNSNLVCKVSDFGLSRVLEDDPEaaYTTRG-GKIPIR 174
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1069 WMAPETIFDRVYTIQSDVWSFGVLLWEIFSLGASPYPGVKiDEEFCRRLKEGTRMRAPDYTTPEMYQTMLDCWHEDPNQR 1148
Cdd:cd05066  175 WTAPEAIAYRKFTSASDVWSYGIVMWEVMSYGERPYWEMS-NQDVIKAIEEGYRLPAPMDCPAALHQLMLDCWQKDRNER 253
                        330
                 ....*....|....
gi 27777648 1149 PSFSELVEHLGNLL 1162
Cdd:cd05066  254 PKFEQIVSILDKLI 267
PTKc_Ror2 cd05091
Catalytic domain of the Protein Tyrosine Kinase, Receptor tyrosine kinase-like Orphan Receptor ...
838-1154 2.81e-45

Catalytic domain of the Protein Tyrosine Kinase, Receptor tyrosine kinase-like Orphan Receptor 2; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Ror2 plays important roles in skeletal and heart formation. Ror2-deficient mice show widespread bone abnormalities, ventricular defects in the heart, and respiratory dysfunction. Mutations in human Ror2 result in two different bone development genetic disorders, recessive Robinow syndrome and brachydactyly type B. Ror2 is also implicated in neural development. Ror proteins are orphan receptor PTKs (RTKs) containing an extracellular region with immunoglobulin-like, cysteine-rich, and kringle domains, a transmembrane segment, and an intracellular catalytic domain. Ror RTKs are unrelated to the nuclear receptor subfamily called retinoid-related orphan receptors (RORs). RTKs are usually activated through ligand binding, which causes dimerization and autophosphorylation of the intracellular tyr kinase catalytic domain. The Ror2 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270673 [Multi-domain]  Cd Length: 284  Bit Score: 165.58  E-value: 2.81e-45
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  838 LGRGAFGQVIEADAFGIDKTATCKTVAVKMLK---EGATHSE--HRALM-SELKilihighHLNVVNLLGACTKPGgPLM 911
Cdd:cd05091   14 LGEDRFGKVYKGHLFGTAPGEQTQAVAIKTLKdkaEGPLREEfrHEAMLrSRLQ-------HPNIVCLLGVVTKEQ-PMS 85
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  912 VIVEFCKFGNLSTYLRGKRnefvPYKSKGarfrqgkdyvgelSVDlkrrldsitssqssassgfvEEKSLSDVEEEEase 991
Cdd:cd05091   86 MIFSYCSHGDLHEFLVMRS----PHSDVG-------------STD--------------------DDKTVKSTLEPA--- 125
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  992 elykDFLtleHLICysfQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIYKDPDYVRKGDARLPLKWMA 1071
Cdd:cd05091  126 ----DFL---HIVT---QIAAGMEYLSSHHVVHKDLATRNVLVFDKLNVKISDLGLFREVYAADYYKLMGNSLLPIRWMS 195
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1072 PETIFDRVYTIQSDVWSFGVLLWEIFSLGASPYPGVKiDEEFCRRLKEGTRMRAPDYTTPEMYQTMLDCWHEDPNQRPSF 1151
Cdd:cd05091  196 PEAIMYGKFSIDSDIWSYGVVLWEVFSYGLQPYCGYS-NQDVIEMIRNRQVLPCPDDCPAWVYTLMLECWNEFPSRRPRF 274

                 ...
gi 27777648 1152 SEL 1154
Cdd:cd05091  275 KDI 277
PTKc_Btk_Bmx cd05113
Catalytic domain of the Protein Tyrosine Kinases, Bruton's tyrosine kinase and Bone marrow ...
828-1155 6.90e-45

Catalytic domain of the Protein Tyrosine Kinases, Bruton's tyrosine kinase and Bone marrow kinase on the X chromosome; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Btk and Bmx (also named Etk) are members of the Tec-like subfamily of proteins, which are cytoplasmic (or nonreceptor) PTKs with similarity to Src kinases in that they contain Src homology protein interaction domains (SH3, SH2) N-terminal to the catalytic tyr kinase domain. Unlike Src kinases, most Tec subfamily members except Rlk also contain an N-terminal pleckstrin homology (PH) domain, which binds the products of PI3K and allows membrane recruitment and activation. In addition, Btk contains the Tec homology (TH) domain with proline-rich and zinc-binding regions. Btk is expressed in B-cells, and a variety of myeloid cells including mast cells, platelets, neutrophils, and dendrictic cells. It interacts with a variety of partners, from cytosolic proteins to nuclear transcription factors, suggesting a diversity of functions. Stimulation of a diverse array of cell surface receptors, including antigen engagement of the B-cell receptor, leads to PH-mediated membrane translocation of Btk and subsequent phosphorylation by Src kinase and activation. Btk plays an important role in the life cycle of B-cells including their development, differentiation, proliferation, survival, and apoptosis. Mutations in Btk cause the primary immunodeficiency disease, X-linked agammaglobulinaemia (XLA) in humans. Bmx is primarily expressed in bone marrow and the arterial endothelium, and plays an important role in ischemia-induced angiogenesis. It facilitates arterial growth, capillary formation, vessel maturation, and bone marrow-derived endothelial progenitor cell mobilization. The Btk/Bmx subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173657 [Multi-domain]  Cd Length: 256  Bit Score: 163.13  E-value: 6.90e-45
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  828 PRDrLKLGKPLGRGAFGQVieadAFGidKTATCKTVAVKMLKEGATHSEHraLMSELKILIHIgHHLNVVNLLGACTKPG 907
Cdd:cd05113    3 PKD-LTFLKELGTGQFGVV----KYG--KWRGQYDVAIKMIKEGSMSEDE--FIEEAKVMMNL-SHEKLVQLYGVCTKQR 72
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  908 gPLMVIVEFCKFGNLSTYLRGKRNEFVPYKskgarfrqgkdyvgelsvdlkrrldsitssqssassgfveekslsdveee 987
Cdd:cd05113   73 -PIFIITEYMANGCLLNYLREMRKRFQTQQ-------------------------------------------------- 101
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  988 easeelykdflTLEhlICYSfqVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIYKDpDYVRKGDARLPL 1067
Cdd:cd05113  102 -----------LLE--MCKD--VCEAMEYLESKQFLHRDLAARNCLVNDQGVVKVSDFGLSRYVLDD-EYTSSVGSKFPV 165
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1068 KWMAPETIFDRVYTIQSDVWSFGVLLWEIFSLGASPYPGVKiDEEFCRRLKEGTRMRAPDYTTPEMYQTMLDCWHEDPNQ 1147
Cdd:cd05113  166 RWSPPEVLMYSKFSSKSDVWAFGVLMWEVYSLGKMPYERFT-NSETVEHVSQGLRLYRPHLASEKVYTIMYSCWHEKADE 244

                 ....*...
gi 27777648 1148 RPSFSELV 1155
Cdd:cd05113  245 RPTFKILL 252
PTKc_Ror1 cd05090
Catalytic domain of the Protein Tyrosine Kinase, Receptor tyrosine kinase-like Orphan Receptor ...
826-1154 1.13e-44

Catalytic domain of the Protein Tyrosine Kinase, Receptor tyrosine kinase-like Orphan Receptor 1; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Ror kinases are expressed in many tissues during development. Avian Ror1 was found to be involved in late limb development. Studies in mice reveal that Ror1 is important in the regulation of neurite growth in central neurons, as well as in respiratory development. Loss of Ror1 also enhances the heart and skeletal abnormalities found in Ror2-deficient mice. Ror proteins are orphan receptor PTKs (RTKs) containing an extracellular region with immunoglobulin-like, cysteine-rich, and kringle domains, a transmembrane segment, and an intracellular catalytic domain. Ror RTKs are unrelated to the nuclear receptor subfamily called retinoid-related orphan receptors (RORs). RTKs are usually activated through ligand binding, which causes dimerization and autophosphorylation of the intracellular tyr kinase catalytic domain. The Ror1 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270672 [Multi-domain]  Cd Length: 283  Bit Score: 163.64  E-value: 1.13e-44
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  826 EFPRDRLKLGKPLGRGAFGQVIEADAF--GIDKTatcKTVAVKMLKEGATHSEHRALMSELKILIHIgHHLNVVNLLGAC 903
Cdd:cd05090    1 ELPLSAVRFMEELGECAFGKIYKGHLYlpGMDHA---QLVAIKTLKDYNNPQQWNEFQQEASLMTEL-HHPNIVCLLGVV 76
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  904 TKPGgPLMVIVEFCKFGNLstylrgkrNEFVPYKSKGARFRQGKDYVGELsvdlKRRLDsitssqssassgfveekslsd 983
Cdd:cd05090   77 TQEQ-PVCMLFEFMNQGDL--------HEFLIMRSPHSDVGCSSDEDGTV----KSSLD--------------------- 122
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  984 veeeeaseelYKDFLTLehlicySFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIYKDPDYVRKGDA 1063
Cdd:cd05090  123 ----------HGDFLHI------AIQIAAGMEYLSSHFFVHKDLAARNILVGEQLHVKISDLGLSREIYSSDYYRVQNKS 186
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1064 RLPLKWMAPETIFDRVYTIQSDVWSFGVLLWEIFSLGASPYPGVKiDEEFCRRLKEGTRMRAPDYTTPEMYQTMLDCWHE 1143
Cdd:cd05090  187 LLPIRWMPPEAIMYGKFSSDSDIWSFGVVLWEIFSFGLQPYYGFS-NQEVIEMVRKRQLLPCSEDCPPRMYSLMTECWQE 265
                        330
                 ....*....|.
gi 27777648 1144 DPNQRPSFSEL 1154
Cdd:cd05090  266 IPSRRPRFKDI 276
PTKc_Itk cd05112
Catalytic domain of the Protein Tyrosine Kinase, Interleukin-2-inducible T-cell Kinase; PTKs ...
830-1158 1.22e-44

Catalytic domain of the Protein Tyrosine Kinase, Interleukin-2-inducible T-cell Kinase; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Itk, also known as Tsk or Emt, is a member of the Tec-like subfamily of proteins, which are cytoplasmic (or nonreceptor) PTKs with similarity to Src kinases in that they contain Src homology protein interaction domains (SH3, SH2) N-terminal to the catalytic tyr kinase domain. Unlike Src kinases, most Tec subfamily members except Rlk also contain an N-terminal pleckstrin homology (PH) domain, which binds the products of PI3K and allows membrane recruitment and activation. In addition, Itk contains the Tec homology (TH) domain containing one proline-rich region and a zinc-binding region. Itk is expressed in T-cells and mast cells, and is important in their development and differentiation. Of the three Tec kinases expressed in T-cells, Itk plays the predominant role in T-cell receptor (TCR) signaling. It is activated by phosphorylation upon TCR crosslinking and is involved in the pathway resulting in phospholipase C-gamma1 activation and actin polymerization. It also plays a role in the downstream signaling of the T-cell costimulatory receptor CD28, the T-cell surface receptor CD2, and the chemokine receptor CXCR4. In addition, Itk is crucial for the development of T-helper(Th)2 effector responses. The Itk subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 133243 [Multi-domain]  Cd Length: 256  Bit Score: 162.43  E-value: 1.22e-44
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  830 DRLKLGKPLGRGAFGQVIEADAFGIDKtatcktVAVKMLKEGATHSEHraLMSELKILIHIGHHlNVVNLLGACTKpGGP 909
Cdd:cd05112    4 SELTFVQEIGSGQFGLVHLGYWLNKDK------VAIKTIREGAMSEED--FIEEAEVMMKLSHP-KLVQLYGVCLE-QAP 73
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  910 LMVIVEFCKFGNLSTYLRGKRNEFvpykskgarfrqgkdyvgelsvdlkrrldsitssqssassgfveekslsdveeeea 989
Cdd:cd05112   74 ICLVFEFMEHGCLSDYLRTQRGLF-------------------------------------------------------- 97
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  990 seelykdflTLEHLICYSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARdIYKDPDYVRKGDARLPLKW 1069
Cdd:cd05112   98 ---------SAETLLGMCLDVCEGMAYLEEASVIHRDLAARNCLVGENQVVKVSDFGMTR-FVLDDQYTSSTGTKFPVKW 167
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1070 MAPETIFDRVYTIQSDVWSFGVLLWEIFSLGASPYPGvKIDEEFCRRLKEGTRMRAPDYTTPEMYQTMLDCWHEDPNQRP 1149
Cdd:cd05112  168 SSPEVFSFSRYSSKSDVWSFGVLMWEVFSEGKIPYEN-RSNSEVVEDINAGFRLYKPRLASTHVYEIMNHCWKERPEDRP 246

                 ....*....
gi 27777648 1150 SFSELVEHL 1158
Cdd:cd05112  247 SFSLLLRQL 255
PTKc_EGFR cd05108
Catalytic domain of the Protein Tyrosine Kinase, Epidermal Growth Factor Receptor; PTKs ...
826-1155 1.50e-44

Catalytic domain of the Protein Tyrosine Kinase, Epidermal Growth Factor Receptor; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. EGFR (HER1, ErbB1) is a receptor PTK (RTK) containing an extracellular EGF-related ligand-binding region, a transmembrane helix, and a cytoplasmic region with a tyr kinase domain and a regulatory C-terminal tail. Unlike other PTKs, phosphorylation of the activation loop of EGFR proteins is not critical to their activation. Instead, they are activated by ligand-induced dimerization, leading to the phosphorylation of tyr residues in the C-terminal tail, which serve as binding sites for downstream signaling molecules. Ligands for EGFR include EGF, heparin binding EGF-like growth factor (HBEGF), epiregulin, amphiregulin, TGFalpha, and betacellulin. Upon ligand binding, EGFR can form homo- or heterodimers with other EGFR subfamily members. The EGFR signaling pathway is one of the most important pathways regulating cell proliferation, differentiation, survival, and growth. Overexpression and mutation in the kinase domain of EGFR have been implicated in the development and progression of a variety of cancers. A number of monoclonal antibodies and small molecule inhibitors have been developed that target EGFR, including the antibodies Cetuximab and Panitumumab, which are used in combination with other therapies for the treatment of colorectal cancer and non-small cell lung carcinoma (NSCLC). The small molecule inhibitors Gefitinib (Iressa) and Erlotinib (Tarceva), already used for NSCLC, are undergoing clinical trials for other types of cancer including gastrointestinal, breast, head and neck, and bladder. The EGFR subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270683 [Multi-domain]  Cd Length: 313  Bit Score: 164.43  E-value: 1.50e-44
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  826 EFPRDRLklgkpLGRGAFGQVIEAdaFGIDKTATCKT-VAVKMLKEGATHSEHRALMSELKILIHIgHHLNVVNLLGACT 904
Cdd:cd05108    8 EFKKIKV-----LGSGAFGTVYKG--LWIPEGEKVKIpVAIKELREATSPKANKEILDEAYVMASV-DNPHVCRLLGICL 79
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  905 KpgGPLMVIVEFCKFGNLSTYLRgkrnefvpykskgarfrQGKDYVGElsvdlkrrldsitssqssassgfveekslsdv 984
Cdd:cd05108   80 T--STVQLITQLMPFGCLLDYVR-----------------EHKDNIGS-------------------------------- 108
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  985 eeeeaseelykdfltlEHLICYSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIYKDPDYVRKGDAR 1064
Cdd:cd05108  109 ----------------QYLLNWCVQIAKGMNYLEDRRLVHRDLAARNVLVKTPQHVKITDFGLAKLLGAEEKEYHAEGGK 172
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1065 LPLKWMAPETIFDRVYTIQSDVWSFGVLLWEIFSLGASPYPGVKIdEEFCRRLKEGTRMRAPDYTTPEMYQTMLDCWHED 1144
Cdd:cd05108  173 VPIKWMALESILHRIYTHQSDVWSYGVTVWELMTFGSKPYDGIPA-SEISSILEKGERLPQPPICTIDVYMIMVKCWMID 251
                        330
                 ....*....|.
gi 27777648 1145 PNQRPSFSELV 1155
Cdd:cd05108  252 ADSRPKFRELI 262
PKc cd00180
Catalytic domain of Protein Kinases; PKs catalyze the transfer of the gamma-phosphoryl group ...
838-1158 3.05e-44

Catalytic domain of Protein Kinases; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine or tyrosine residues on protein substrates. PKs make up a large family of serine/threonine kinases (STKs), protein tyrosine kinases (PTKs), and dual-specificity PKs that phosphorylate both serine/threonine and tyrosine residues of target proteins. Majority of protein phosphorylation occurs on serine residues while only 1% occurs on tyrosine residues. Protein phosphorylation is a mechanism by which a wide variety of cellular proteins, such as enzymes and membrane channels, are reversibly regulated in response to certain stimuli. PKs often function as components of signal transduction pathways in which one kinase activates a second kinase, which in turn, may act on other kinases; this sequential action transmits a signal from the cell surface to target proteins, which results in cellular responses. The PK family is one of the largest known protein families with more than 100 homologous yeast enzymes and more than 500 human proteins. A fraction of PK family members are pseudokinases that lack crucial residues for catalytic activity. The mutiplicity of kinases allows for specific regulation according to substrate, tissue distribution, and cellular localization. PKs regulate many cellular processes including proliferation, division, differentiation, motility, survival, metabolism, cell-cycle progression, cytoskeletal rearrangement, immunity, and neuronal functions. Many kinases are implicated in the development of various human diseases including different types of cancer. The PK family is part of a larger superfamily that includes the catalytic domains of RIO kinases, aminoglycoside phosphotransferase, choline kinase, phosphoinositide 3-kinase (PI3K), and actin-fragmin kinase.


Pssm-ID: 270622 [Multi-domain]  Cd Length: 215  Bit Score: 159.74  E-value: 3.05e-44
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  838 LGRGAFGQVIEADafgidKTATCKTVAVKMLKEGATHSEHRALMSELKILIHIgHHLNVVNLLGACTKPGGPLMViVEFC 917
Cdd:cd00180    1 LGKGSFGKVYKAR-----DKETGKKVAVKVIPKEKLKKLLEELLREIEILKKL-NHPNIVKLYDVFETENFLYLV-MEYC 73
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  918 KFGNLSTYLRGKRNefvpykskgarfrqgkdyvgelsvdlkrrldsitssqssassgfveekslsdveeeeaseelykdF 997
Cdd:cd00180   74 EGGSLKDLLKENKG-----------------------------------------------------------------P 88
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  998 LTLEHLICYSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIYKDPDYVRKGDARLPLKWMAPETIFD 1077
Cdd:cd00180   89 LSEEEALSILRQLLSALEYLHSNGIIHRDLKPENILLDSDGTVKLADFGLAKDLDSDDSLLKTTGGTTPPYYAPPELLGG 168
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1078 RVYTIQSDVWSFGVLLWEIfslgaspypgvkideefcrrlkegtrmrapdyttPEMYQTMLDCWHEDPNQRPSFSELVEH 1157
Cdd:cd00180  169 RYYGPKVDIWSLGVILYEL----------------------------------EELKDLIRRMLQYDPKKRPSAKELLEH 214

                 .
gi 27777648 1158 L 1158
Cdd:cd00180  215 L 215
PTKc_Tec_Rlk cd05114
Catalytic domain of the Protein Tyrosine Kinases, Tyrosine kinase expressed in hepatocellular ...
832-1163 1.95e-43

Catalytic domain of the Protein Tyrosine Kinases, Tyrosine kinase expressed in hepatocellular carcinoma and Resting lymphocyte kinase; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Tec and Rlk (also named Txk) are members of the Tec-like subfamily of proteins, which are cytoplasmic (or nonreceptor) PTKs with similarity to Src kinases in that they contain Src homology protein interaction domains (SH3, SH2) N-terminal to the catalytic tyr kinase domain. Unlike Src kinases, most Tec subfamily members except Rlk also contain an N-terminal pleckstrin homology (PH) domain, which binds the products of PI3K and allows membrane recruitment and activation. Instead of PH, Rlk contains an N-terminal cysteine-rich region. In addition to PH, Tec also contains the Tec homology (TH) domain with proline-rich and zinc-binding regions. Tec kinases are expressed mainly by haematopoietic cells. Tec is more widely-expressed than other Tec-like subfamily kinases. It is found in endothelial cells, both B- and T-cells, and a variety of myeloid cells including mast cells, erythroid cells, platelets, macrophages and neutrophils. Rlk is expressed in T-cells and mast cell lines. Tec and Rlk are both key components of T-cell receptor (TCR) signaling. They are important in TCR-stimulated proliferation, IL-2 production and phopholipase C-gamma1 activation. The Tec/Rlk subfamily is part of a larger superfamily, that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270685 [Multi-domain]  Cd Length: 260  Bit Score: 159.26  E-value: 1.95e-43
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  832 LKLGKPLGRGAFGQVieadafGIDKTATCKTVAVKMLKEGATHSEHraLMSELKILIHIGHHlNVVNLLGACTKPGgPLM 911
Cdd:cd05114    6 LTFMKELGSGLFGVV------RLGKWRAQYKVAIKAIREGAMSEED--FIEEAKVMMKLTHP-KLVQLYGVCTQQK-PIY 75
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  912 VIVEFCKFGNLSTYLRGKRnefvpykskgarfrqgkdyvGELSVDLkrrldsitssqssassgfveekslsdveeeease 991
Cdd:cd05114   76 IVTEFMENGCLLNYLRQRR--------------------GKLSRDM---------------------------------- 101
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  992 elykdfltlehLICYSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIYKDpDYVRKGDARLPLKWMA 1071
Cdd:cd05114  102 -----------LLSMCQDVCEGMEYLERNNFIHRDLAARNCLVNDTGVVKVSDFGMTRYVLDD-QYTSSSGAKFPVKWSP 169
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1072 PETIFDRVYTIQSDVWSFGVLLWEIFSLGASPYPGvKIDEEFCRRLKEGTRMRAPDYTTPEMYQTMLDCWHEDPNQRPSF 1151
Cdd:cd05114  170 PEVFNYSKFSSKSDVWSFGVLMWEVFTEGKMPFES-KSNYEVVEMVSRGHRLYRPKLASKSVYEVMYSCWHEKPEGRPTF 248
                        330
                 ....*....|..
gi 27777648 1152 SELVEHLGNLLQ 1163
Cdd:cd05114  249 ADLLRTITEIAE 260
PTKc_Jak3_rpt2 cd05081
Catalytic (repeat 2) domain of the Protein Tyrosine Kinase, Janus kinase 3; PTKs catalyze the ...
827-1154 2.56e-43

Catalytic (repeat 2) domain of the Protein Tyrosine Kinase, Janus kinase 3; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Jak3 is expressed only in hematopoietic cells. It binds the shared receptor subunit common gamma chain and thus, is essential in the signaling of cytokines that use it such as IL-2, IL-4, IL-7, IL-9, IL-15, and IL-21. Jak3 is important in lymphoid development and myeloid cell differentiation. Inactivating mutations in Jak3 have been reported in humans with severe combined immunodeficiency (SCID). Jak3 is a member of the Janus kinase (Jak) subfamily of proteins, which are cytoplasmic (or nonreceptor) PTKs containing an N-terminal FERM domain, followed by a Src homology 2 (SH2) domain, a pseudokinase domain, and a C-terminal catalytic tyr kinase domain. Jaks are crucial for cytokine receptor signaling. They are activated by autophosphorylation upon cytokine-induced receptor aggregation, and subsequently trigger downstream signaling events such as the phosphorylation of signal transducers and activators of transcription (STATs). The PTKc family is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270665 [Multi-domain]  Cd Length: 283  Bit Score: 159.67  E-value: 2.56e-43
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  827 FPRDRLKLGKPLGRGAFGQV--IEADAFGiDKTAtcKTVAVKMLKEgATHSEHRALMSELKILiHIGHHLNVVNLLGACT 904
Cdd:cd05081    1 FEERHLKYISQLGKGNFGSVelCRYDPLG-DNTG--ALVAVKQLQH-SGPDQQRDFQREIQIL-KALHSDFIVKYRGVSY 75
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  905 KPGGP-LMVIVEFCKFGNLSTYLRGKRNefvpykskgarfrqgkdyvgelsvdlkrRLDSItssqssassgfveekslsd 983
Cdd:cd05081   76 GPGRRsLRLVMEYLPSGCLRDFLQRHRA----------------------------RLDAS------------------- 108
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  984 veeeeaseelykdfltleHLICYSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIYKDPD-YVRKGD 1062
Cdd:cd05081  109 ------------------RLLLYSSQICKGMEYLGSRRCVHRDLAARNILVESEAHVKIADFGLAKLLPLDKDyYVVREP 170
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1063 ARLPLKWMAPETIFDRVYTIQSDVWSFGVLLWEIFSL---GASPypgvkiDEEFCRR----------------LKEGTRM 1123
Cdd:cd05081  171 GQSPIFWYAPESLSDNIFSRQSDVWSFGVVLYELFTYcdkSCSP------SAEFLRMmgcerdvpalcrllelLEEGQRL 244
                        330       340       350
                 ....*....|....*....|....*....|.
gi 27777648 1124 RAPDYTTPEMYQTMLDCWHEDPNQRPSFSEL 1154
Cdd:cd05081  245 PAPPACPAEVHELMKLCWAPSPQDRPSFSAL 275
PTKc_DDR_like cd05097
Catalytic domain of Discoidin Domain Receptor-like Protein Tyrosine Kinases; PTKs catalyze the ...
826-1154 5.73e-43

Catalytic domain of Discoidin Domain Receptor-like Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. DDR-like proteins are members of the DDR subfamily, which are receptor PTKs (RTKs) containing an extracellular discoidin homology domain, a transmembrane segment, an extended juxtamembrane region, and an intracellular catalytic domain. The binding of the ligand, collagen, to DDRs results in a slow but sustained receptor activation. DDRs regulate cell adhesion, proliferation, and extracellular matrix remodeling. They have been linked to a variety of human cancers including breast, colon, ovarian, brain, and lung. There is no evidence showing that DDRs act as transforming oncogenes. They are more likely to play a role in the regulation of tumor growth and metastasis. The DDR-like subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 133228 [Multi-domain]  Cd Length: 295  Bit Score: 158.99  E-value: 5.73e-43
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  826 EFPRDRLKLGKPLGRGAFGQVIEADAFGI---------DKTATCKTVAVKMLKEGATHSEHRALMSELKILIHIgHHLNV 896
Cdd:cd05097    1 EFPRQQLRLKEKLGEGQFGEVHLCEAEGLaeflgegapEFDGQPVLVAVKMLRADVTKTARNDFLKEIKIMSRL-KNPNI 79
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  897 VNLLGACTKpGGPLMVIVEFCKFGNLstylrgkrNEFVPYKSKGARFRQGKDyvgelsvdlkrrldsitssqssassgfV 976
Cdd:cd05097   80 IRLLGVCVS-DDPLCMITEYMENGDL--------NQFLSQREIESTFTHANN---------------------------I 123
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  977 EEKSLSDveeeeaseelykdfltlehLICYSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIYKDPD 1056
Cdd:cd05097  124 PSVSIAN-------------------LLYMAVQIASGMKYLASLNFVHRDLATRNCLVGNHYTIKIADFGMSRNLYSGDY 184
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1057 YVRKGDARLPLKWMAPETIFDRVYTIQSDVWSFGVLLWEIFSL-GASPYpGVKIDE-------EFCRRLKEGTRMRAPDY 1128
Cdd:cd05097  185 YRIQGRAVLPIRWMAWESILLGKFTTASDVWAFGVTLWEMFTLcKEQPY-SLLSDEqvientgEFFRNQGRQIYLSQTPL 263
                        330       340
                 ....*....|....*....|....*.
gi 27777648 1129 TTPEMYQTMLDCWHEDPNQRPSFSEL 1154
Cdd:cd05097  264 CPSPVFKLMMRCWSRDIKDRPTFNKI 289
PTKc_TrkB cd05093
Catalytic domain of the Protein Tyrosine Kinase, Tropomyosin Related Kinase B; PTKs catalyze ...
829-1165 8.14e-43

Catalytic domain of the Protein Tyrosine Kinase, Tropomyosin Related Kinase B; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. TrkB is a receptor PTK (RTK) containing an extracellular region with arrays of leucine-rich motifs flanked by two cysteine-rich clusters followed by two immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. Binding of TrkB to its ligands, brain-derived neurotrophic factor (BDNF) or neurotrophin 4 (NT4), results in receptor oligomerization and activation of the catalytic domain. TrkB is broadly expressed in the nervous system and in some non-neural tissues. It plays important roles in cell proliferation, differentiation, and survival. BDNF/Trk signaling plays a key role in regulating activity-dependent synaptic plasticity. TrkB also contributes to protection against gp120-induced neuronal cell death. TrkB overexpression is associated with poor prognosis in neuroblastoma (NB) and other human cancers. It acts as a suppressor of anoikis (detachment-induced apoptosis) and contributes to tumor metastasis. The TrkB subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270675 [Multi-domain]  Cd Length: 288  Bit Score: 158.28  E-value: 8.14e-43
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  829 RDRLKLGKPLGRGAFGQVIEADAFGIDKTATCKTVAVKMLKEgATHSEHRALMSELKILIHIGHHlNVVNLLGACTKpGG 908
Cdd:cd05093    4 RHNIVLKRELGEGAFGKVFLAECYNLCPEQDKILVAVKTLKD-ASDNARKDFHREAELLTNLQHE-HIVKFYGVCVE-GD 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  909 PLMVIVEFCKFGNLSTYLRGkrnefvpykskgarfrQGKDYVgeLSVDLKRRLDsitssqssassgfveekslsdveeee 988
Cdd:cd05093   81 PLIMVFEYMKHGDLNKFLRA----------------HGPDAV--LMAEGNRPAE-------------------------- 116
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  989 aseelykdfLTLEHLICYSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIYKDPDYVRKGDARLPLK 1068
Cdd:cd05093  117 ---------LTQSQMLHIAQQIAAGMVYLASQHFVHRDLATRNCLVGENLLVKIGDFGMSRDVYSTDYYRVGGHTMLPIR 187
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1069 WMAPETIFDRVYTIQSDVWSFGVLLWEIFSLGASPYPGVKiDEEFCRRLKEGTRMRAPDYTTPEMYQTMLDCWHEDPNQR 1148
Cdd:cd05093  188 WMPPESIMYRKFTTESDVWSLGVVLWEIFTYGKQPWYQLS-NNEVIECITQGRVLQRPRTCPKEVYDLMLGCWQREPHMR 266
                        330
                 ....*....|....*..
gi 27777648 1149 PSFSELVEHLGNLLQAN 1165
Cdd:cd05093  267 LNIKEIHSLLQNLAKAS 283
PTKc_Syk cd05116
Catalytic domain of the Protein Tyrosine Kinase, Spleen tyrosine kinase; PTKs catalyze the ...
836-1152 1.31e-42

Catalytic domain of the Protein Tyrosine Kinase, Spleen tyrosine kinase; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Syk is a cytoplasmic (or nonreceptor) PTK containing two Src homology 2 (SH2) domains N-terminal to the catalytic tyr kinase domain. Syk was first cloned from the spleen, and its function in hematopoietic cells is well-established. It is involved in the signaling downstream of activated receptors (including B-cell and Fc receptors) that contain ITAMs (immunoreceptor tyr activation motifs), leading to processes such as cell proliferation, differentiation, survival, adhesion, migration, and phagocytosis. More recently, Syk expression has been detected in other cell types (including epithelial cells, vascular endothelial cells, neurons, hepatocytes, and melanocytes), suggesting a variety of biological functions in non-immune cells. Syk plays a critical role in maintaining vascular integrity and in wound healing during embryogenesis. It also regulates Vav3, which is important in osteoclast function including bone development. In breast epithelial cells, where Syk acts as a negative regulator for EGFR signaling, loss of Syk expression is associated with abnormal proliferation during cancer development suggesting a potential role as a tumor suppressor. In mice, Syk has been shown to inhibit malignant transformation of mammary epithelial cells induced with murine mammary tumor virus (MMTV). The Syk subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 133247 [Multi-domain]  Cd Length: 257  Bit Score: 156.66  E-value: 1.31e-42
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  836 KPLGRGAFGQVIEAdAFGIDKTAtcKTVAVKMLKegaTHSEHRALMSELKILIHIGHHLN---VVNLLGACTkpGGPLMV 912
Cdd:cd05116    1 GELGSGNFGTVKKG-YYQMKKVV--KTVAVKILK---NEANDPALKDELLREANVMQQLDnpyIVRMIGICE--AESWML 72
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  913 IVEFCKFGNLSTYLRGKRNefvpykskgarfrqgkdyvgelsvdlkrrldsitssqssassgfVEEKSLSDveeeeasee 992
Cdd:cd05116   73 VMEMAELGPLNKFLQKNRH--------------------------------------------VTEKNITE--------- 99
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  993 lykdfltLEHlicysfQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIYKDPDYVR-KGDARLPLKWMA 1071
Cdd:cd05116  100 -------LVH------QVSMGMKYLEESNFVHRDLAARNVLLVTQHYAKISDFGLSKALRADENYYKaQTHGKWPVKWYA 166
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1072 PETIFDRVYTIQSDVWSFGVLLWEIFSLGASPYPGVKiDEEFCRRLKEGTRMRAPDYTTPEMYQTMLDCWHEDPNQRPSF 1151
Cdd:cd05116  167 PECMNYYKFSSKSDVWSFGVLMWEAFSYGQKPYKGMK-GNEVTQMIEKGERMECPAGCPPEMYDLMKLCWTYDVDERPGF 245

                 .
gi 27777648 1152 S 1152
Cdd:cd05116  246 A 246
PTKc_TrkC cd05094
Catalytic domain of the Protein Tyrosine Kinase, Tropomyosin Related Kinase C; PTKs catalyze ...
829-1164 2.71e-42

Catalytic domain of the Protein Tyrosine Kinase, Tropomyosin Related Kinase C; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. TrkC is a receptor PTK (RTK) containing an extracellular region with arrays of leucine-rich motifs flanked by two cysteine-rich clusters followed by two immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. Binding of TrkC to its ligand, neurotrophin 3 (NT3), results in receptor oligomerization and activation of the catalytic domain. TrkC is broadly expressed in the nervous system and in some non-neural tissues including the developing heart. NT3/TrkC signaling plays an important role in the innervation of the cardiac conducting system and the development of smooth muscle cells. Mice deficient with NT3 and TrkC have multiple heart defects. NT3/TrkC signaling is also critical for the development and maintenance of enteric neurons that are important for the control of gut peristalsis. The TrkC subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270676 [Multi-domain]  Cd Length: 287  Bit Score: 156.71  E-value: 2.71e-42
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  829 RDRLKLGKPLGRGAFGQVIEADAFGIDKTATCKTVAVKMLKEgATHSEHRALMSELKILIHIGHHlNVVNLLGACTKpGG 908
Cdd:cd05094    4 RRDIVLKRELGEGAFGKVFLAECYNLSPTKDKMLVAVKTLKD-PTLAARKDFQREAELLTNLQHD-HIVKFYGVCGD-GD 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  909 PLMVIVEFCKFGNLSTYLRGkrnefvpykskgarfrQGKDYVgeLSVDLKRRLDsitssqssassgfveekslsdveeee 988
Cdd:cd05094   81 PLIMVFEYMKHGDLNKFLRA----------------HGPDAM--ILVDGQPRQA-------------------------- 116
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  989 aseelyKDFLTLEHLICYSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIYKDPDYVRKGDARLPLK 1068
Cdd:cd05094  117 ------KGELGLSQMLHIATQIASGMVYLASQHFVHRDLATRNCLVGANLLVKIGDFGMSRDVYSTDYYRVGGHTMLPIR 190
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1069 WMAPETIFDRVYTIQSDVWSFGVLLWEIFSLGASPYPGVKiDEEFCRRLKEGTRMRAPDYTTPEMYQTMLDCWHEDPNQR 1148
Cdd:cd05094  191 WMPPESIMYRKFTTESDVWSFGVILWEIFTYGKQPWFQLS-NTEVIECITQGRVLERPRVCPKEVYDIMLGCWQREPQQR 269
                        330
                 ....*....|....*.
gi 27777648 1149 PSFSELVEHLGNLLQA 1164
Cdd:cd05094  270 LNIKEIYKILHALGKA 285
PTKc_EphR_B cd05065
Catalytic domain of the Protein Tyrosine Kinases, Class EphB Ephrin Receptors; PTKs catalyze ...
832-1162 4.45e-42

Catalytic domain of the Protein Tyrosine Kinases, Class EphB Ephrin Receptors; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Class EphB receptors bind to transmembrane ephrin-B ligands. There are six vertebrate EphB receptors (EphB1-6), which display promiscuous interactions with three ephrin-B ligands. One exception is EphB2, which also interacts with ephrin A5. EphB receptors play important roles in synapse formation and plasticity, spine morphogenesis, axon guidance, and angiogenesis. In the intestinal epithelium, EphBs are Wnt signaling target genes that control cell compartmentalization. They function as suppressors of colon cancer progression. EphRs comprise the largest subfamily of receptor PTKs (RTKs). They contain an ephrin-binding domain and two fibronectin repeats extracellularly, a transmembrane segment, and a cytoplasmic tyr kinase domain. Binding of the ephrin ligand to EphR requires cell-cell contact since both are anchored to the plasma membrane. The resulting downstream signals occur bidirectionally in both EphR-expressing cells (forward signaling) and ephrin-expressing cells (reverse signaling). Ephrin/EphR interaction mainly results in cell-cell repulsion or adhesion. The EphB subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173638 [Multi-domain]  Cd Length: 269  Bit Score: 155.80  E-value: 4.45e-42
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  832 LKLGKPLGRGAFGQVIEADAFGIDKTATCktVAVKMLKEGATHSEHRALMSELKILIHIgHHLNVVNLLGACTKpGGPLM 911
Cdd:cd05065    6 VKIEEVIGAGEFGEVCRGRLKLPGKREIF--VAIKTLKSGYTEKQRRDFLSEASIMGQF-DHPNIIHLEGVVTK-SRPVM 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  912 VIVEFCKFGNLSTYLRGKRNEFVPYKskgarfrqgkdYVGELSvdlkrrldsitssqssassgfveekslsdveeeease 991
Cdd:cd05065   82 IITEFMENGALDSFLRQNDGQFTVIQ-----------LVGMLR------------------------------------- 113
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  992 elykdfltlehlicysfQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLAR---DIYKDPDYVRKGDARLPLK 1068
Cdd:cd05065  114 -----------------GIAAGMKYLSEMNYVHRDLAARNILVNSNLVCKVSDFGLSRfleDDTSDPTYTSSLGGKIPIR 176
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1069 WMAPETIFDRVYTIQSDVWSFGVLLWEIFSLGASPYPGVKiDEEFCRRLKEGTRMRAPDYTTPEMYQTMLDCWHEDPNQR 1148
Cdd:cd05065  177 WTAPEAIAYRKFTSASDVWSYGIVMWEVMSYGERPYWDMS-NQDVINAIEQDYRLPPPMDCPTALHQLMLDCWQKDRNLR 255
                        330
                 ....*....|....
gi 27777648 1149 PSFSELVEHLGNLL 1162
Cdd:cd05065  256 PKFGQIVNTLDKMI 269
PTK_HER3 cd05111
Pseudokinase domain of the Protein Tyrosine Kinase, HER3; HER3 (ErbB3) is a member of the EGFR ...
827-1154 8.18e-42

Pseudokinase domain of the Protein Tyrosine Kinase, HER3; HER3 (ErbB3) is a member of the EGFR (HER, ErbB) subfamily of proteins, which are receptor PTKs (RTKs) containing an extracellular EGF-related ligand-binding region, a transmembrane helix, and a cytoplasmic region with a tyr kinase domain and a regulatory C-terminal tail. Unlike other PTKs, phosphorylation of the activation loop of EGFR proteins is not critical to their activation. Instead, they are activated by ligand-induced dimerization, leading to the phosphorylation of tyr residues in the C-terminal tail, which serve as binding sites for downstream signaling molecules. HER3 contains an impaired tyr kinase domain, which lacks crucial residues for catalytic activity against exogenous substrates but is still able to bind ATP and autophosphorylate. HER3 binds the neuregulin ligands, NRG1 and NRG2, and it relies on its heterodimerization partners for activity following ligand binding. The HER2-HER3 heterodimer constitutes a high affinity co-receptor capable of potent mitogenic signaling. HER3 participates in a signaling pathway involved in the proliferation, survival, adhesion, and motility of tumor cells. The HER3 subfamily is part of a larger superfamily that includes other pseudokinases and the the catalytic domains of active kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173656 [Multi-domain]  Cd Length: 279  Bit Score: 155.11  E-value: 8.18e-42
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  827 FPRDRLKLGKPLGRGAFGQVieADAFGIDKTATCKT-VAVKMLKEGATHSEHRALMSELkilIHIGH--HLNVVNLLGAC 903
Cdd:cd05111    4 FKETELRKLKVLGSGVFGTV--HKGIWIPEGDSIKIpVAIKVIQDRSGRQSFQAVTDHM---LAIGSldHAYIVRLLGIC 78
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  904 tkPGGPLMVIVEFCKFGNLSTYLRGKRNEFVPykskgarfrqgkdyvgelsvdlkrrldsitssqssassgfveekslsd 983
Cdd:cd05111   79 --PGASLQLVTQLLPLGSLLDHVRQHRGSLGP------------------------------------------------ 108
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  984 veeeeaseelykdfltlEHLICYSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIYKDPDYVRKGDA 1063
Cdd:cd05111  109 -----------------QLLLNWCVQIAKGMYYLEEHRMVHRNLAARNVLLKSPSQVQVADFGVADLLYPDDKKYFYSEA 171
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1064 RLPLKWMAPETIFDRVYTIQSDVWSFGVLLWEIFSLGASPYPGVKIdEEFCRRLKEGTRMRAPDYTTPEMYQTMLDCWHE 1143
Cdd:cd05111  172 KTPIKWMALESIHFGKYTHQSDVWSYGVTVWEMMTFGAEPYAGMRL-AEVPDLLEKGERLAQPQICTIDVYMVMVKCWMI 250
                        330
                 ....*....|.
gi 27777648 1144 DPNQRPSFSEL 1154
Cdd:cd05111  251 DENIRPTFKEL 261
PTKc_HER2 cd05109
Catalytic domain of the Protein Tyrosine Kinase, HER2; PTKs catalyze the transfer of the ...
995-1176 1.14e-41

Catalytic domain of the Protein Tyrosine Kinase, HER2; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. HER2 (ErbB2, HER2/neu) is a member of the EGFR (HER, ErbB) subfamily of proteins, which are receptor PTKs (RTKs) containing an extracellular EGF-related ligand-binding region, a transmembrane helix, and a cytoplasmic region with a tyr kinase domain and a regulatory C-terminal tail. Unlike other PTKs, phosphorylation of the activation loop of EGFR proteins is not critical to their activation. Instead, they are activated by ligand-induced dimerization, leading to the phosphorylation of tyr residues in the C-terminal tail, which serve as binding sites for downstream signaling molecules. HER2 does not bind to any known EGFR subfamily ligands, but contributes to the kinase activity of all possible heterodimers. It acts as the preferred partner of other ligand-bound EGFR proteins and functions as a signal amplifier, with the HER2-HER3 heterodimer being the most potent pair in mitogenic signaling. HER2 plays an important role in cell development, proliferation, survival and motility. Overexpression of HER2 results in its activation and downstream signaling, even in the absence of ligand. HER2 overexpression, mainly due to gene amplification, has been shown in a variety of human cancers. Its role in breast cancer is especially well-documented. HER2 is up-regulated in about 25% of breast tumors and is associated with increases in tumor aggressiveness, recurrence and mortality. HER2 is a target for monoclonal antibodies and small molecule inhibitors, which are being developed as treatments for cancer. The first humanized antibody approved for clinical use is Trastuzumab (Herceptin), which is being used in combination with other therapies to improve the survival rates of patients with HER2-overexpressing breast cancer. The HER2 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270684 [Multi-domain]  Cd Length: 279  Bit Score: 154.80  E-value: 1.14e-41
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  995 KDFLTLEHLICYSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIYKDPDYVRKGDARLPLKWMAPET 1074
Cdd:cd05109  103 KDRIGSQDLLNWCVQIAKGMSYLEEVRLVHRDLAARNVLVKSPNHVKITDFGLARLLDIDETEYHADGGKVPIKWMALES 182
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1075 IFDRVYTIQSDVWSFGVLLWEIFSLGASPYPGVKIdEEFCRRLKEGTRMRAPDYTTPEMYQTMLDCWHEDPNQRPSFSEL 1154
Cdd:cd05109  183 ILHRRFTHQSDVWSYGVTVWELMTFGAKPYDGIPA-REIPDLLEKGERLPQPPICTIDVYMIMVKCWMIDSECRPRFREL 261
                        170       180
                 ....*....|....*....|..
gi 27777648 1155 VEHLGNLlqanaQQDGKDYIVL 1176
Cdd:cd05109  262 VDEFSRM-----ARDPSRFVVI 278
PTKc_DDR1 cd05096
Catalytic domain of the Protein Tyrosine Kinase, Discoidin Domain Receptor 1; PTKs catalyze ...
826-1154 1.98e-41

Catalytic domain of the Protein Tyrosine Kinase, Discoidin Domain Receptor 1; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. DDR1 is a receptor PTK (RTK) containing an extracellular discoidin homology domain, a transmembrane segment, an extended juxtamembrane region, and an intracellular catalytic domain. The binding of the ligand, collagen, to DDR1 results in a slow but sustained receptor activation. DDR1 binds to all collagens tested to date (types I-IV). It is widely expressed in many tissues. It is abundant in the brain and is also found in keratinocytes, colonic mucosa epithelium, lung epithelium, thyroid follicles, and the islets of Langerhans. During embryonic development, it is found in the developing neuroectoderm. DDR1 is a key regulator of cell morphogenesis, differentiation and proliferation. It is important in the development of the mammary gland, the vasculator and the kidney. DDR1 is also found in human leukocytes, where it facilitates cell adhesion, migration, maturation, and cytokine production. The DDR1 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 133227 [Multi-domain]  Cd Length: 304  Bit Score: 155.09  E-value: 1.98e-41
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  826 EFPRDRLKLGKPLGRGAFGQV--IEADA----------FGIDKTATCkTVAVKMLKEGATHSEHRALMSELKILIHIGHH 893
Cdd:cd05096    1 KFPRGHLLFKEKLGEGQFGEVhlCEVVNpqdlptlqfpFNVRKGRPL-LVAVKILRPDANKNARNDFLKEVKILSRLKDP 79
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  894 lNVVNLLGACTKPGgPLMVIVEFCKFGNLSTYLRGKRNEfvpykSKGARFRQGKDYVGELSVdlkrrldsitssqssass 973
Cdd:cd05096   80 -NIIRLLGVCVDED-PLCMITEYMENGDLNQFLSSHHLD-----DKEENGNDAVPPAHCLPA------------------ 134
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  974 gfveekslsdveeeeaseelykdfLTLEHLICYSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIYK 1053
Cdd:cd05096  135 ------------------------ISYSSLLHVALQIASGMKYLSSLNFVHRDLATRNCLVGENLTIKIADFGMSRNLYA 190
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1054 DPDYVRKGDARLPLKWMAPETIFDRVYTIQSDVWSFGVLLWEIFSL-GASPYpGVKIDE-------EFCRRLKEGTRMRA 1125
Cdd:cd05096  191 GDYYRIQGRAVLPIRWMAWECILMGKFTTASDVWAFGVTLWEILMLcKEQPY-GELTDEqvienagEFFRDQGRQVYLFR 269
                        330       340
                 ....*....|....*....|....*....
gi 27777648 1126 PDYTTPEMYQTMLDCWHEDPNQRPSFSEL 1154
Cdd:cd05096  270 PPPCPQGLYELMLQCWSRDCRERPSFSDI 298
PTKc_Yes cd05069
Catalytic domain of the Protein Tyrosine Kinase, Yes; PTKs catalyze the transfer of the ...
825-1168 2.83e-40

Catalytic domain of the Protein Tyrosine Kinase, Yes; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Yes (or c-Yes) is a member of the Src subfamily of proteins, which are cytoplasmic (or non-receptor) PTKs. c-Yes kinase is the cellular homolog of the oncogenic protein (v-Yes) encoded by the Yamaguchi 73 and Esh sarcoma viruses. It displays functional overlap with other Src subfamily members, particularly Src. It also shows some unique functions such as binding to occludins, transmembrane proteins that regulate extracellular interactions in tight junctions. Yes also associates with a number of proteins in different cell types that Src does not interact with, like JAK2 and gp130 in pre-adipocytes, and Pyk2 in treated pulmonary vein endothelial cells. Although the biological function of Yes remains unclear, it appears to have a role in regulating cell-cell interactions and vesicle trafficking in polarized cells. Src kinases contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). The Yes subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase (PI3K).


Pssm-ID: 270654 [Multi-domain]  Cd Length: 279  Bit Score: 150.61  E-value: 2.83e-40
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  825 WEFPRDRLKLGKPLGRGAFGQVIEADAFGIDKtatcktVAVKMLKEGATHSEhrALMSELKILIHIGHHlNVVNLLGACT 904
Cdd:cd05069    7 WEIPRESLRLDVKLGQGCFGEVWMGTWNGTTK------VAIKTLKPGTMMPE--AFLQEAQIMKKLRHD-KLVPLYAVVS 77
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  905 KPggPLMVIVEFCKFGNLSTYLRGKrnefvpykskgarfrQGKdyvgelsvdlkrrldsitssqssassgfveekslsdv 984
Cdd:cd05069   78 EE--PIYIVTEFMGKGSLLDFLKEG---------------DGK------------------------------------- 103
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  985 eeeeaseelykdFLTLEHLICYSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIyKDPDYVRKGDAR 1064
Cdd:cd05069  104 ------------YLKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGDNLVCKIADFGLARLI-EDNEYTARQGAK 170
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1065 LPLKWMAPETIFDRVYTIQSDVWSFGVLLWEIFSLGASPYPGVkIDEEFCRRLKEGTRMRAPDYTTPEMYQTMLDCWHED 1144
Cdd:cd05069  171 FPIKWTAPEAALYGRFTIKSDVWSFGILLTELVTKGRVPYPGM-VNREVLEQVERGYRMPCPQGCPESLHELMKLCWKKD 249
                        330       340
                 ....*....|....*....|....
gi 27777648 1145 PNQRPSFSELVEHLGNLLQANAQQ 1168
Cdd:cd05069  250 PDERPTFEYIQSFLEDYFTATEPQ 273
PTKc_Src_Fyn_like cd14203
Catalytic domain of a subset of Src kinase-like Protein Tyrosine Kinases; PTKs catalyze the ...
836-1163 3.26e-40

Catalytic domain of a subset of Src kinase-like Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. This subfamily includes a subset of Src-like PTKs including Src, Fyn, Yrk, and Yes, which are all widely expressed. Yrk has been detected only in chickens. It is primarily found in neuronal and epithelial cells and in macrophages. It may play a role in inflammation and in response to injury. Src (or c-Src) proteins are cytoplasmic (or non-receptor) PTKs which are anchored to the plasma membrane. They contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). Src proteins are involved in signaling pathways that regulate cytokine and growth factor responses, cytoskeleton dynamics, cell proliferation, survival, and differentiation. They were identified as the first proto-oncogene products, and they regulate cell adhesion, invasion, and motility in cancer cells and tumor vasculature, contributing to cancer progression and metastasis. They are also implicated in acute inflammatory responses and osteoclast function. The Src/Fyn-like subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271105 [Multi-domain]  Cd Length: 248  Bit Score: 149.68  E-value: 3.26e-40
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  836 KPLGRGAFGQVIEADAFGIDKtatcktVAVKMLKEGATHSEhrALMSELKILIHIGHHlNVVNLLGACTKPggPLMVIVE 915
Cdd:cd14203    1 VKLGQGCFGEVWMGTWNGTTK------VAIKTLKPGTMSPE--AFLEEAQIMKKLRHD-KLVQLYAVVSEE--PIYIVTE 69
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  916 FCKFGNLSTYLRGKrnefvpykskgarfrQGKdyvgelsvdlkrrldsitssqssassgfveekslsdveeeeaseelyk 995
Cdd:cd14203   70 FMSKGSLLDFLKDG---------------EGK------------------------------------------------ 86
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  996 dFLTLEHLICYSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIyKDPDYVRKGDARLPLKWMAPETI 1075
Cdd:cd14203   87 -YLKLPQLVDMAAQIASGMAYIERMNYIHRDLRAANILVGDNLVCKIADFGLARLI-EDNEYTARQGAKFPIKWTAPEAA 164
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1076 FDRVYTIQSDVWSFGVLLWEIFSLGASPYPGVkIDEEFCRRLKEGTRMRAPDYTTPEMYQTMLDCWHEDPNQRPSFselv 1155
Cdd:cd14203  165 LYGRFTIKSDVWSFGILLTELVTKGRVPYPGM-NNREVLEQVERGYRMPCPPGCPESLHELMCQCWRKDPEERPTF---- 239

                 ....*...
gi 27777648 1156 EHLGNLLQ 1163
Cdd:cd14203  240 EYLQSFLE 247
PTKc_Jak1_rpt2 cd05079
Catalytic (repeat 2) domain of the Protein Tyrosine Kinase, Janus kinase 1; PTKs catalyze the ...
827-1162 3.97e-40

Catalytic (repeat 2) domain of the Protein Tyrosine Kinase, Janus kinase 1; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Jak1 is widely expressed in many tissues. Many cytokines are dependent on Jak1 for signaling, including those that use the shared receptor subunits common gamma chain (IL-2, IL-4, IL-7, IL-9, IL-15, IL-21) and gp130 (IL-6, IL-11, oncostatin M, G-CSF, and IFNs, among others). The many varied interactions of Jak1 and its ubiquitous expression suggest many biological roles. Jak1 is important in neurological development, as well as in lymphoid development and function. It also plays a role in the pathophysiology of cardiac hypertrophy and heart failure. A mutation in the ATP-binding site of Jak1 was identified in a human uterine leiomyosarcoma cell line, resulting in defective cytokine induction and antigen presentation, thus allowing the tumor to evade the immune system. Jak1 is a member of the Janus kinase (Jak) subfamily of proteins, which are cytoplasmic (or nonreceptor) PTKs containing an N-terminal FERM domain, followed by a Src homology 2 (SH2) domain, a pseudokinase domain, and a C-terminal tyr kinase domain. Jaks are crucial for cytokine receptor signaling. They are activated by autophosphorylation upon cytokine-induced receptor aggregation, and subsequently trigger downstream signaling events such as the phosphorylation of signal transducers and activators of transcription (STATs). The Jak1 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173644 [Multi-domain]  Cd Length: 284  Bit Score: 150.46  E-value: 3.97e-40
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  827 FPRDRLKLGKPLGRGAFGQViEADAFGIDKTATCKTVAVKMLKEGATHSEHRALMSELKILIHIgHHLNVVNLLGACTKP 906
Cdd:cd05079    1 FEKRFLKRIRDLGEGHFGKV-ELCRYDPEGDNTGEQVAVKSLKPESGGNHIADLKKEIEILRNL-YHENIVKYKGICTED 78
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  907 GGP-LMVIVEFCKFGNLSTYLrgKRNefvpykskgarfrqgkdyvgelsvdlkrrldsitssqssassgfveekslsdve 985
Cdd:cd05079   79 GGNgIKLIMEFLPSGSLKEYL--PRN------------------------------------------------------ 102
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  986 eeeaseelyKDFLTLEHLICYSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIYKDPDYVR-KGDAR 1064
Cdd:cd05079  103 ---------KNKINLKQQLKYAVQICKGMDYLGSRQYVHRDLAARNVLVESEHQVKIGDFGLTKAIETDKEYYTvKDDLD 173
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1065 LPLKWMAPETIFDRVYTIQSDVWSFGVLLWEIFSLGAS-------------PYPGVKIDEEFCRRLKEGTRMRAPDYTTP 1131
Cdd:cd05079  174 SPVFWYAPECLIQSKFYIASDVWSFGVTLYELLTYCDSesspmtlflkmigPTHGQMTVTRLVRVLEEGKRLPRPPNCPE 253
                        330       340       350
                 ....*....|....*....|....*....|.
gi 27777648 1132 EMYQTMLDCWHEDPNQRPSFSELVEHLGNLL 1162
Cdd:cd05079  254 EVYQLMRKCWEFQPSKRTTFQNLIEGFEAIL 284
PTKc_DDR2 cd05095
Catalytic domain of the Protein Tyrosine Kinase, Discoidin Domain Receptor 2; PTKs catalyze ...
826-1154 4.55e-40

Catalytic domain of the Protein Tyrosine Kinase, Discoidin Domain Receptor 2; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. DDR2 is a receptor PTK (RTK) containing an extracellular discoidin homology domain, a transmembrane segment, an extended juxtamembrane region, and an intracellular catalytic domain. The binding of the ligand, collagen, to DDR2 results in a slow but sustained receptor activation. DDR2 binds mostly to fibrillar collagens as well as collagen X. DDR2 is widely expressed in many tissues with the highest levels found in skeletal muscle, skin, kidney and lung. It is important in cell proliferation and development. Mice, with a deletion of DDR2, suffer from dwarfism and delayed healing of epidermal wounds. DDR2 also contributes to collagen (type I) regulation by inhibiting fibrillogenesis and altering the morphology of collagen fibers. It is also expressed in immature dendritic cells (DCs), where it plays a role in DC activation and function. The DDR2 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase (PI3K).


Pssm-ID: 270677 [Multi-domain]  Cd Length: 297  Bit Score: 150.91  E-value: 4.55e-40
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  826 EFPRDRLKLGKPLGRGAFGQVIEADAFGI----DKTATCKT-------VAVKMLKEGATHSEHRALMSELKILIHIgHHL 894
Cdd:cd05095    1 EFPRKLLTFKEKLGEGQFGEVHLCEAEGMekfmDKDFALEVsenqpvlVAVKMLRADANKNARNDFLKEIKIMSRL-KDP 79
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  895 NVVNLLGACTKpGGPLMVIVEFCKFGNLSTYLRGKRNEFVPYKSKGARfrqgkdyvgelsvdlkrrldsitssqssassg 974
Cdd:cd05095   80 NIIRLLAVCIT-DDPLCMITEYMENGDLNQFLSRQQPEGQLALPSNAL-------------------------------- 126
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  975 fveEKSLSDveeeeaseelykdfltLEHLicySFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIYKD 1054
Cdd:cd05095  127 ---TVSYSD----------------LRFM---AAQIASGMKYLSSLNFVHRDLATRNCLVGKNYTIKIADFGMSRNLYSG 184
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1055 PDYVRKGDARLPLKWMAPETIFDRVYTIQSDVWSFGVLLWEIFSL-GASPYPGVKiDE-------EFCRRLKEGTRMRAP 1126
Cdd:cd05095  185 DYYRIQGRAVLPIRWMSWESILLGKFTTASDVWAFGVTLWETLTFcREQPYSQLS-DEqvientgEFFRDQGRQTYLPQP 263
                        330       340
                 ....*....|....*....|....*...
gi 27777648 1127 DYTTPEMYQTMLDCWHEDPNQRPSFSEL 1154
Cdd:cd05095  264 ALCPDSVYKLMLSCWRRDTKDRPSFQEI 291
PTKc_Src cd05071
Catalytic domain of the Protein Tyrosine Kinase, Src; PTKs catalyze the transfer of the ...
825-1168 4.86e-40

Catalytic domain of the Protein Tyrosine Kinase, Src; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Src (or c-Src) is a cytoplasmic (or non-receptor) PTK, containing an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region with a conserved tyr. It is activated by autophosphorylation at the tyr kinase domain, and is negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). c-Src is the vertebrate homolog of the oncogenic protein (v-Src) from Rous sarcoma virus. Together with other Src subfamily proteins, it is involved in signaling pathways that regulate cytokine and growth factor responses, cytoskeleton dynamics, cell proliferation, survival, and differentiation. Src also play a role in regulating cell adhesion, invasion, and motility in cancer cells and tumor vasculature, contributing to cancer progression and metastasis. Elevated levels of Src kinase activity have been reported in a variety of human cancers. Several inhibitors of Src have been developed as anti-cancer drugs. Src is also implicated in acute inflammatory responses and osteoclast function. The Src subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270656 [Multi-domain]  Cd Length: 277  Bit Score: 149.84  E-value: 4.86e-40
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  825 WEFPRDRLKLGKPLGRGAFGQVIEADAFGIDKtatcktVAVKMLKEGATHSEhrALMSELKILIHIGHHlNVVNLLGACT 904
Cdd:cd05071    4 WEIPRESLRLEVKLGQGCFGEVWMGTWNGTTR------VAIKTLKPGTMSPE--AFLQEAQVMKKLRHE-KLVQLYAVVS 74
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  905 KPggPLMVIVEFCKFGNLSTYLRGKrnefvpykskgarfrqgkdyvgelsvdlkrrldsitssqssassgfveekslsdv 984
Cdd:cd05071   75 EE--PIYIVTEYMSKGSLLDFLKGE------------------------------------------------------- 97
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  985 eeeeaseelYKDFLTLEHLICYSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIyKDPDYVRKGDAR 1064
Cdd:cd05071   98 ---------MGKYLRLPQLVDMAAQIASGMAYVERMNYVHRDLRAANILVGENLVCKVADFGLARLI-EDNEYTARQGAK 167
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1065 LPLKWMAPETIFDRVYTIQSDVWSFGVLLWEIFSLGASPYPGVkIDEEFCRRLKEGTRMRAPDYTTPEMYQTMLDCWHED 1144
Cdd:cd05071  168 FPIKWTAPEAALYGRFTIKSDVWSFGILLTELTTKGRVPYPGM-VNREVLDQVERGYRMPCPPECPESLHDLMCQCWRKE 246
                        330       340
                 ....*....|....*....|....
gi 27777648 1145 PNQRPSFSELVEHLGNLLQANAQQ 1168
Cdd:cd05071  247 PEERPTFEYLQAFLEDYFTSTEPQ 270
PTKc_Zap-70 cd05115
Catalytic domain of the Protein Tyrosine Kinase, Zeta-chain-associated protein of 70kDa; PTKs ...
829-1151 8.78e-40

Catalytic domain of the Protein Tyrosine Kinase, Zeta-chain-associated protein of 70kDa; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Zap-70 is a cytoplasmic (or nonreceptor) PTK containing two Src homology 2 (SH2) domains N-terminal to the catalytic tyr kinase domain. Zap-70 is primarily expressed in T-cells and NK cells, and is a crucial component in T-cell receptor (TCR) signaling. Zap-70 binds the phosphorylated ITAM (immunoreceptor tyr activation motif) sequences of the activated TCR zeta-chain through its SH2 domains, leading to its phosphorylation and activation. It then phosphorylates target proteins, which propagate the signals to downstream pathways. Zap-70 is hardly detected in normal peripheral B-cells, but is present in some B-cell malignancies. It is used as a diagnostic marker for chronic lymphocytic leukemia (CLL) as it is associated with the more aggressive subtype of the disease. The Zap-70 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270686 [Multi-domain]  Cd Length: 269  Bit Score: 148.94  E-value: 8.78e-40
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  829 RDRLKLGK-PLGRGAFGQVIEAdAFGIDKTATckTVAVKMLKEGATHSEHRALMSELKILihigHHLN---VVNLLGACT 904
Cdd:cd05115    2 RDNLLIDEvELGSGNFGCVKKG-VYKMRKKQI--DVAIKVLKQGNEKAVRDEMMREAQIM----HQLDnpyIVRMIGVCE 74
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  905 KPGgpLMVIVEFCKFGNLSTYLRGKRNEfvpykskgarfrqgkdyvgelsvdlkrrldsitssqssassgfveekslsdv 984
Cdd:cd05115   75 AEA--LMLVMEMASGGPLNKFLSGKKDE---------------------------------------------------- 100
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  985 eeeeaseelykdfLTLEHLICYSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIYKDPDYVR-KGDA 1063
Cdd:cd05115  101 -------------ITVSNVVELMHQVSMGMKYLEEKNFVHRDLAARNVLLVNQHYAKISDFGLSKALGADDSYYKaRSAG 167
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1064 RLPLKWMAPETIFDRVYTIQSDVWSFGVLLWEIFSLGASPYPGVKiDEEFCRRLKEGTRMRAPDYTTPEMYQTMLDCWHE 1143
Cdd:cd05115  168 KWPLKWYAPECINFRKFSSRSDVWSYGVTMWEAFSYGQKPYKKMK-GPEVMSFIEQGKRMDCPAECPPEMYALMSDCWIY 246

                 ....*...
gi 27777648 1144 DPNQRPSF 1151
Cdd:cd05115  247 KWEDRPNF 254
IgI_VEGFR-2 cd05864
Immunoglobulin (Ig)-like domain of vascular endothelial growth factor receptor 2 (VEGFR-2); ...
331-419 9.51e-40

Immunoglobulin (Ig)-like domain of vascular endothelial growth factor receptor 2 (VEGFR-2); member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin (Ig)-like domain of vascular endothelial growth factor receptor 2 (VEGFR-2). The VEGFRs have an extracellular component with seven Ig-like domains, a transmembrane segment, and an intracellular tyrosine kinase domain interrupted by a kinase-insert domain. VEGFRs bind VEGFs with high affinity at the Ig-like domains. VEGFR-2 (KDR/Flk-1) is a major mediator of the mitogenic, angiogenic and microvascular permeability-enhancing effects of VEGF-A; VEGF-A is important to the growth and maintenance of vascular endothelial cells and to the development of new blood- and lymphatic-vessels in physiological and pathological states. VEGF-A also interacts with VEGFR-1, which it binds more strongly than VEGFR-2. VEGFR-1 and VEGFR-2 may mediate a chemotactic and a survival signal in hematopoietic stem cells or leukemia cells. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409450  Cd Length: 89  Bit Score: 141.99  E-value: 9.51e-40
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  331 FIAFGSGMKSLVEATVGSQVRIPVKYLSYPAPDIKWYRNGRPIESNYTMIVGDELTIMEVTERDAGNYTVILTNPISMEK 410
Cdd:cd05864    1 FIALGSGMESLVEAKVGERVRIPVKYLGYPPPEIKWYKNGIPIESNHTIKAGHVLTIMEVTEKDAGNYTVVLTNPISKEK 80

                 ....*....
gi 27777648  411 QSHMVSLVV 419
Cdd:cd05864   81 QRHTFSLVV 89
IgI_VEGFR cd05862
Immunoglobulin (Ig)-like domain of vascular endothelial growth factor (VEGF) receptor(R); ...
226-327 2.07e-39

Immunoglobulin (Ig)-like domain of vascular endothelial growth factor (VEGF) receptor(R); member of the I-set of IgSF domains; The members here are composed of the immunoglobulin (Ig)-like domain of vascular endothelial growth factor (VEGF) receptor(R). The VEGFRs have an extracellular component with seven Ig-like domains, a transmembrane segment, and an intracellular tyrosine kinase domain interrupted by a kinase-insert domain. The VEGFR family consists of three members, VEGFR-1 (also known as Flt-1), VEGFR-2 (also known as KDR or Flk-1) and VEGFR-3 (also known as Flt-4). VEGF_A interacts with both VEGFR-1 and VEGFR-2. VEGFR-1 binds strongest to VEGF, VEGF-2 binds more weakly. VEGFR-3 appears not to bind VEGF, but binds other members of the VEGF family (VEGF-C and -D). VEGFRs bind VEGFs with high affinity with the IG-like domains. VEGF-A is important to the growth and maintenance of vascular endothelial cells and to the development of new blood- and lymphatic-vessels in physiological and pathological states. VEGFR-2 is a major mediator of the mitogenic, angiogenic and microvascular permeability-enhancing effects of VEGF-A. VEGFR-1 may play an inhibitory part in these processes by binding VEGF and interfering with its interaction with VEGFR-2. VEGFR-1 has a signaling role in mediating monocyte chemotaxis. VEGFR-2 and -1 may mediate a chemotactic and a survival signal in hematopoietic stem cells or leukemia cells. VEGFR-3 has been shown to be involved in tumor angiogenesis and growth.


Pssm-ID: 409448  Cd Length: 102  Bit Score: 141.81  E-value: 2.07e-39
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  226 YDVILSPPHEIELSAGEKLVLNCTARTELNVGLDFTWHSPPSKSHHKKIVNRDVKPFPGTvAKMFLSTLTIESVTKSDQG 305
Cdd:cd05862    1 YDVQLSPPKPVELLVGEKLVLNCTARTELNVGVDFQWDYPGKKEQRRASVRRRRKQQSSE-ATEFSSTLTIDNVTLSDKG 79
                         90       100
                 ....*....|....*....|..
gi 27777648  306 EYTCVASSGRMIKRNRTFVRVH 327
Cdd:cd05862   80 LYTCAASSGPMFKKNSTSVIVH 101
PTKc_Jak2_rpt2 cd14205
Catalytic (repeat 2) domain of the Protein Tyrosine Kinase, Janus kinase 2; PTKs catalyze the ...
827-1154 4.10e-39

Catalytic (repeat 2) domain of the Protein Tyrosine Kinase, Janus kinase 2; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Jak2 is widely expressed in many tissues and is essential for the signaling of hormone-like cytokines such as growth hormone, erythropoietin, thrombopoietin, and prolactin, as well as some IFNs and cytokines that signal through the IL-3 and gp130 receptors. Disruption of Jak2 in mice results in an embryonic lethal phenotype with multiple defects including erythropoietic and cardiac abnormalities. It is the only Jak gene that results in a lethal phenotype when disrupted in mice. A mutation in the pseudokinase domain of Jak2, V617F, is present in many myeloproliferative diseases, including almost all patients with polycythemia vera, and 50% of patients with essential thrombocytosis and myelofibrosis. Jak2 is a member of the Janus kinase (Jak) subfamily of proteins, which are cytoplasmic (or nonreceptor) PTKs containing an N-terminal FERM domain, followed by a Src homology 2 (SH2) domain, a pseudokinase domain, and a C-terminal catalytic tyr kinase domain. Jaks are crucial for cytokine receptor signaling. They are activated by autophosphorylation upon cytokine-induced receptor aggregation, and subsequently trigger downstream signaling events such as the phosphorylation of signal transducers and activators of transcription (STATs). The PTKc family is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271107 [Multi-domain]  Cd Length: 284  Bit Score: 147.47  E-value: 4.10e-39
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  827 FPRDRLKLGKPLGRGAFGQViEADAFGIDKTATCKTVAVKMLKEgaTHSEH-RALMSELKILIHIGHHlNVVNLLGACTK 905
Cdd:cd14205    1 FEERHLKFLQQLGKGNFGSV-EMCRYDPLQDNTGEVVAVKKLQH--STEEHlRDFEREIEILKSLQHD-NIVKYKGVCYS 76
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  906 PG-GPLMVIVEFCKFGNLSTYLRGKRNEFvpykskgarfrqgkdyvgelsvDLKRrldsitssqssassgfveekslsdv 984
Cdd:cd14205   77 AGrRNLRLIMEYLPYGSLRDYLQKHKERI----------------------DHIK------------------------- 109
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  985 eeeeaseelykdfltlehLICYSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIYKDPDYVR-KGDA 1063
Cdd:cd14205  110 ------------------LLQYTSQICKGMEYLGTKRYIHRDLATRNILVENENRVKIGDFGLTKVLPQDKEYYKvKEPG 171
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1064 RLPLKWMAPETIFDRVYTIQSDVWSFGVLLWEIFSL---GASP-----------YPGVKIDEEFCRRLKEGTRMRAPDYT 1129
Cdd:cd14205  172 ESPIFWYAPESLTESKFSVASDVWSFGVVLYELFTYiekSKSPpaefmrmigndKQGQMIVFHLIELLKNNGRLPRPDGC 251
                        330       340
                 ....*....|....*....|....*
gi 27777648 1130 TPEMYQTMLDCWHEDPNQRPSFSEL 1154
Cdd:cd14205  252 PDEIYMIMTECWNNNVNQRPSFRDL 276
PTKc_Fyn cd05070
Catalytic domain of the Protein Tyrosine Kinase, Fyn; PTKs catalyze the transfer of the ...
825-1168 2.94e-38

Catalytic domain of the Protein Tyrosine Kinase, Fyn; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Fyn and Yrk are members of the Src subfamily of proteins, which are cytoplasmic (or non-receptor) PTKs. Fyn, together with Lck, plays a critical role in T-cell signal transduction by phosphorylating ITAM (immunoreceptor tyr activation motif) sequences on T-cell receptors, ultimately leading to the proliferation and differentiation of T-cells. In addition, Fyn is involved in the myelination of neurons, and is implicated in Alzheimer's and Parkinson's diseases. Src kinases contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). The Fyn/Yrk subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, and phosphoinositide 3-kinase.


Pssm-ID: 270655 [Multi-domain]  Cd Length: 274  Bit Score: 144.83  E-value: 2.94e-38
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  825 WEFPRDRLKLGKPLGRGAFGQVIEADAFGIDKtatcktVAVKMLKEGATHSEhrALMSELKILIHIGHHlNVVNLLGACT 904
Cdd:cd05070    4 WEIPRESLQLIKRLGNGQFGEVWMGTWNGNTK------VAIKTLKPGTMSPE--SFLEEAQIMKKLKHD-KLVQLYAVVS 74
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  905 KPggPLMVIVEFCKFGNLSTYLrgkrnefvpykskgarfrqgKDYVGELsvdlkrrldsitssqssassgfveekslsdv 984
Cdd:cd05070   75 EE--PIYIVTEYMSKGSLLDFL--------------------KDGEGRA------------------------------- 101
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  985 eeeeaseelykdfLTLEHLICYSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIyKDPDYVRKGDAR 1064
Cdd:cd05070  102 -------------LKLPNLVDMAAQVAAGMAYIERMNYIHRDLRSANILVGNGLICKIADFGLARLI-EDNEYTARQGAK 167
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1065 LPLKWMAPETIFDRVYTIQSDVWSFGVLLWEIFSLGASPYPGVKiDEEFCRRLKEGTRMRAPDYTTPEMYQTMLDCWHED 1144
Cdd:cd05070  168 FPIKWTAPEAALYGRFTIKSDVWSFGILLTELVTKGRVPYPGMN-NREVLEQVERGYRMPCPQDCPISLHELMIHCWKKD 246
                        330       340
                 ....*....|....*....|....
gi 27777648 1145 PNQRPSFSELVEHLGNLLQANAQQ 1168
Cdd:cd05070  247 PEERPTFEYLQGFLEDYFTATEPQ 270
PTKc_HER4 cd05110
Catalytic domain of the Protein Tyrosine Kinase, HER4; PTKs catalyze the transfer of the ...
832-1176 5.83e-38

Catalytic domain of the Protein Tyrosine Kinase, HER4; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. HER4 (ErbB4) is a member of the EGFR (HER, ErbB) subfamily of proteins, which are receptor PTKs (RTKs) containing an extracellular EGF-related ligand-binding region, a transmembrane helix, and a cytoplasmic region with a tyr kinase domain and a regulatory C-terminal tail. Unlike other PTKs, phosphorylation of the activation loop of EGFR proteins is not critical to their activation. Instead, they are activated by ligand-induced dimerization, leading to the phosphorylation of tyr residues in the C-terminal tail, which serve as binding sites for downstream signaling molecules. Ligands that bind HER4 fall into two groups, the neuregulins (or heregulins) and some EGFR (HER1) ligands including betacellulin, HBEGF, and epiregulin. All four neuregulins (NRG1-4) interact with HER4. Upon ligand binding, HER4 forms homo- or heterodimers with other HER proteins. HER4 is essential in embryonic development. It is implicated in mammary gland, cardiac, and neural development. As a postsynaptic receptor of NRG1, HER4 plays an important role in synaptic plasticity and maturation. The impairment of NRG1/HER4 signaling may contribute to schizophrenia. The HER4 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173655 [Multi-domain]  Cd Length: 303  Bit Score: 144.82  E-value: 5.83e-38
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  832 LKLGKPLGRGAFGQVIEAdaFGIDKTATCKT-VAVKMLKEGATHSEHRALMSELKILIHIGH-HLnvVNLLGACTKPggP 909
Cdd:cd05110    9 LKRVKVLGSGAFGTVYKG--IWVPEGETVKIpVAIKILNETTGPKANVEFMDEALIMASMDHpHL--VRLLGVCLSP--T 82
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  910 LMVIVEFCKFGNLSTYLRgkrnefvpykskgarfrQGKDYVGElsvdlkrrldsitssqssassgfveekslsdveeeea 989
Cdd:cd05110   83 IQLVTQLMPHGCLLDYVH-----------------EHKDNIGS------------------------------------- 108
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  990 seelykdfltlEHLICYSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIYKDPDYVRKGDARLPLKW 1069
Cdd:cd05110  109 -----------QLLLNWCVQIAKGMMYLEERRLVHRDLAARNVLVKSPNHVKITDFGLARLLEGDEKEYNADGGKMPIKW 177
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1070 MAPETIFDRVYTIQSDVWSFGVLLWEIFSLGASPYPGVKIdEEFCRRLKEGTRMRAPDYTTPEMYQTMLDCWHEDPNQRP 1149
Cdd:cd05110  178 MALECIHYRKFTHQSDVWSYGVTIWELMTFGGKPYDGIPT-REIPDLLEKGERLPQPPICTIDVYMVMVKCWMIDADSRP 256
                        330       340
                 ....*....|....*....|....*..
gi 27777648 1150 SFSELVEHLGNLlqanaQQDGKDYIVL 1176
Cdd:cd05110  257 KFKELAAEFSRM-----ARDPQRYLVI 278
PTKc_Tyk2_rpt2 cd05080
Catalytic (repeat 2) domain of the Protein Tyrosine Kinase, Tyrosine kinase 2; PTKs catalyze ...
827-1158 3.14e-36

Catalytic (repeat 2) domain of the Protein Tyrosine Kinase, Tyrosine kinase 2; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Tyk2 is widely expressed in many tissues. It is involved in signaling via the cytokine receptors IFN-alphabeta, IL-6, IL-10, IL-12, IL-13, and IL-23. It mediates cell surface urokinase receptor (uPAR) signaling and plays a role in modulating vascular smooth muscle cell (VSMC) functional behavior in response to injury. Tyk2 is also important in dendritic cell function and T helper (Th)1 cell differentiation. A homozygous mutation of Tyk2 was found in a patient with hyper-IgE syndrome (HIES), a primary immunodeficiency characterized by recurrent skin abscesses, pneumonia, and elevated serum IgE. This suggests that Tyk2 may play important roles in multiple cytokine signaling involved in innate and adaptive immunity. Tyk2 is a member of the Janus kinase (Jak) subfamily of proteins, which are cytoplasmic (or nonreceptor) PTKs containing an N-terminal FERM domain, followed by a Src homology 2 (SH2) domain, a pseudokinase domain, and a C-terminal tyr kinase catalytic domain. Jaks are crucial for cytokine receptor signaling. They are activated by autophosphorylation upon cytokine-induced receptor aggregation, and subsequently trigger downstream signaling events such as the phosphorylation of signal transducers and activators of transcription (STATs). The Tyk2 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270664 [Multi-domain]  Cd Length: 283  Bit Score: 139.26  E-value: 3.14e-36
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  827 FPRDRLKLGKPLGRGAFGQVIeadAFGIDKT--ATCKTVAVKMLKEGATHSEHRALMSELKILIHIgHHLNVVNLLGACT 904
Cdd:cd05080    1 FHKRYLKKIRDLGEGHFGKVS---LYCYDPTndGTGEMVAVKALKADCGPQHRSGWKQEIDILKTL-YHENIVKYKGCCS 76
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  905 KPGGP-LMVIVEFCKFGNLSTYLRgkrnefvpykskgarfrqgkdyvgelsvdlkrrldsitssqssassgfveekslsd 983
Cdd:cd05080   77 EQGGKsLQLIMEYVPLGSLRDYLP-------------------------------------------------------- 100
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  984 veeeeaseelyKDFLTLEHLICYSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIYKDPDYVR-KGD 1062
Cdd:cd05080  101 -----------KHSIGLAQLLLFAQQICEGMAYLHSQHYIHRDLAARNVLLDNDRLVKIGDFGLAKAVPEGHEYYRvRED 169
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1063 ARLPLKWMAPETIFDRVYTIQSDVWSFGVLLWEIFS-LGASPYPGVKIDE------------EFCRRLKEGTRMRAPDYT 1129
Cdd:cd05080  170 GDSPVFWYAPECLKEYKFYYASDVWSFGVTLYELLThCDSSQSPPTKFLEmigiaqgqmtvvRLIELLERGERLPCPDKC 249
                        330       340
                 ....*....|....*....|....*....
gi 27777648 1130 TPEMYQTMLDCWHEDPNQRPSFSELVEHL 1158
Cdd:cd05080  250 PQEVYHLMKNCWETEASFRPTFENLIPIL 278
STKc_TAK1 cd14058
Catalytic domain of the Serine/Threonine Kinase, Transforming Growth Factor beta Activated ...
838-1165 2.67e-35

Catalytic domain of the Serine/Threonine Kinase, Transforming Growth Factor beta Activated Kinase-1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TAK1 is also known as mitogen-activated protein kinase kinase kinase 7 (MAPKKK7 or MAP3K7), TAK, or MEKK7. As a MAPKKK, it is an important mediator of cellular responses to extracellular signals. It regulates both the c-Jun N-terminal kinase and p38 MAPK cascades by activating the MAPK kinases, MKK4 and MKK3/6. In addition, TAK1 plays diverse roles in immunity and development, in different biological contexts, through many signaling pathways including TGFbeta/BMP, Wnt/Fz, and NF-kB. It is also implicated in the activation of the tumor suppressor kinase, LKB1. The TAK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270960 [Multi-domain]  Cd Length: 253  Bit Score: 135.64  E-value: 2.67e-35
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  838 LGRGAFGQVIEAdafgidkTATCKTVAVKMLKegaTHSEHRALMSELKILIHIGHHlNVVNLLGACTKpGGPLMVIVEFC 917
Cdd:cd14058    1 VGRGSFGVVCKA-------RWRNQIVAVKIIE---SESEKKAFEVEVRQLSRVDHP-NIIKLYGACSN-QKPVCLVMEYA 68
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  918 KFGNLSTYLRGKRNefvpykskgarfrqgkdyvgelsvdlkrrldsitssqssassgfveekslsdveeeeaseelyKDF 997
Cdd:cd14058   69 EGGSLYNVLHGKEP---------------------------------------------------------------KPI 85
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  998 LTLEHLICYSFQVAKGMEFLAS---RKCIHRDLAARNILLSEK-NVVKICDFGLARDIyKDPDYVRKGDARlplkWMAPE 1073
Cdd:cd14058   86 YTAAHAMSWALQCAKGVAYLHSmkpKALIHRDLKPPNLLLTNGgTVLKICDFGTACDI-STHMTNNKGSAA----WMAPE 160
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1074 TIFDRVYTIQSDVWSFGVLLWEIFSLgASPYPGvkIDEEFCRRLK---EGTRmraPDYTT--PE-MYQTMLDCWHEDPNQ 1147
Cdd:cd14058  161 VFEGSKYSEKCDVFSWGIILWEVITR-RKPFDH--IGGPAFRIMWavhNGER---PPLIKncPKpIESLMTRCWSKDPEK 234
                        330
                 ....*....|....*...
gi 27777648 1148 RPSFSELVEHLGNLLQAN 1165
Cdd:cd14058  235 RPSMKEIVKIMSHLMQFF 252
PTKc_Aatyk3 cd14206
Catalytic domain of the Protein Tyrosine Kinases, Apoptosis-associated tyrosine kinase 3; PTKs ...
838-1154 5.62e-35

Catalytic domain of the Protein Tyrosine Kinases, Apoptosis-associated tyrosine kinase 3; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Aatyk3, also called lemur tyrosine kinase 3 (Lmtk3) is a receptor kinase containing a transmembrane segment and a long C-terminal cytoplasmic tail with a catalytic domain. The function of Aatyk3 is still unknown. The Aatyk3 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, and phosphoinositide 3-kinase (PI3K).


Pssm-ID: 271108 [Multi-domain]  Cd Length: 276  Bit Score: 135.46  E-value: 5.62e-35
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  838 LGRGAFGQVIEADAFGidkTATCKTVAVKMLKEGATHSEHRALMSELKILIHIgHHLNVVNLLGACTKPGgPLMVIVEFC 917
Cdd:cd14206    5 IGNGWFGKVILGEIFS---DYTPAQVVVKELRVSAGPLEQRKFISEAQPYRSL-QHPNILQCLGLCTETI-PFLLIMEFC 79
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  918 KFGNLSTYLRGKRnefvpyKSKGarfrqgkdyvgeLSVDLKRRldsitssqssassgfveekslsdveeeeaseelykDF 997
Cdd:cd14206   80 QLGDLKRYLRAQR------KADG------------MTPDLPTR-----------------------------------DL 106
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  998 LTLEHLicySFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIYKDPDYVRKGDARLPLKWMAPEtIFD 1077
Cdd:cd14206  107 RTLQRM---AYEITLGLLHLHKNNYIHSDLALRNCLLTSDLTVRIGDYGLSHNNYKEDYYLTPDRLWIPLRWVAPE-LLD 182
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1078 RVY--------TIQSDVWSFGVLLWEIFSLGASPYPGVKiDEE---FCRRLKEGT----RMRAP--DYttpeMYQTMLDC 1140
Cdd:cd14206  183 ELHgnlivvdqSKESNVWSLGVTIWELFEFGAQPYRHLS-DEEvltFVVREQQMKlakpRLKLPyaDY----WYEIMQSC 257
                        330
                 ....*....|....
gi 27777648 1141 WHEdPNQRPSFSEL 1154
Cdd:cd14206  258 WLP-PSQRPSVEEL 270
IgI_VEGFR cd04976
Immunoglobulin (Ig)-like domain of vascular endothelial growth factor receptor (VEGFR); member ...
331-419 2.74e-34

Immunoglobulin (Ig)-like domain of vascular endothelial growth factor receptor (VEGFR); member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin (Ig)-like domain of vascular endothelial growth factor receptor (VEGFR). The VEGFRs have an extracellular component with seven Ig-like domains, a transmembrane segment, and an intracellular tyrosine kinase domain interrupted by a kinase-insert domain. The VEGFR family consists of three members, VEGFR-1 (Flt-1), VEGFR-2 (KDR/Flk-1), and VEGFR-3 (Flt-4). VEGFRs bind VEGFs with high affinity at the Ig-like domains. VEGF-A is important to the growth and maintenance of vascular endothelial cells and to the development of new blood- and lymphatic-vessels in physiological and pathological states. VEGFR-2 is a major mediator of the mitogenic, angiogenic, and microvascular permeability-enhancing effects of VEGF-A. VEGFR-1 may play an inhibitory part in these processes by binding VEGF and interfering with its interaction with VEGFR-2. VEGFR-1 has a signaling role in mediating monocyte chemotaxis. VEGFR-1 and VEGFR-2 may mediate a chemotactic and a survival signal in hematopoietic stem cells or leukemia cells. VEGFR-3 has been shown to be involved in tumor angiogenesis and growth. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409365  Cd Length: 90  Bit Score: 126.56  E-value: 2.74e-34
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  331 FIAFGSGMKSLVEATVGSQ-VRIPVKYLSYPAPDIKWYRNGRPIESNYTMIVGDELTIMEVTERDAGNYTVILTNPISME 409
Cdd:cd04976    1 FITVKHRKQQVLEATAGKRsVRLPMKVKAYPPPEVVWYKDGLPLTEKARYLTRHSLIIKEVTEEDTGNYTILLSNKQSNV 80
                         90
                 ....*....|
gi 27777648  410 KQSHMVSLVV 419
Cdd:cd04976   81 FKNLTATLVV 90
STKc_MLK cd14061
Catalytic domain of the Serine/Threonine Kinases, Mixed Lineage Kinases; STKs catalyze the ...
838-1161 2.16e-33

Catalytic domain of the Serine/Threonine Kinases, Mixed Lineage Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MLKs act as mitogen-activated protein kinase kinase kinases (MAP3Ks, MKKKs, MAPKKKs), which phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. Mammals have four MLKs (MLK1-4), mostly conserved in vertebrates, which contain an SH3 domain, a catalytic kinase domain, a leucine zipper, a proline-rich region, and a CRIB domain that mediates binding to GTP-bound Cdc42 and Rac. MLKs play roles in immunity and inflammation, as well as in cell death, proliferation, and cell cycle regulation. The MLK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270963 [Multi-domain]  Cd Length: 258  Bit Score: 130.21  E-value: 2.16e-33
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  838 LGRGAFGQVIEADAFGidktatcKTVAVKMLK----EGATHSEHRaLMSELKiLIHIGHHLNVVNLLGACTKPggP-LMV 912
Cdd:cd14061    2 IGVGGFGKVYRGIWRG-------EEVAVKAARqdpdEDISVTLEN-VRQEAR-LFWMLRHPNIIALRGVCLQP--PnLCL 70
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  913 IVEFCKFGNLSTYLRGKRnefVPykskgarfrqgkdyvgelsvdlkrrldsitssqssassgfveekslsdveeeeasee 992
Cdd:cd14061   71 VMEYARGGALNRVLAGRK---IP--------------------------------------------------------- 90
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  993 lykdfltLEHLICYSFQVAKGMEFLASRK---CIHRDLAARNILLSEK--------NVVKICDFGLARDIYKdpdyVRKG 1061
Cdd:cd14061   91 -------PHVLVDWAIQIARGMNYLHNEApvpIIHRDLKSSNILILEAienedlenKTLKITDFGLAREWHK----TTRM 159
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1062 DARLPLKWMAPETIFDRVYTIQSDVWSFGVLLWEIFSlGASPYPGvkIDeefCRRLKEGTRMRA-----PDyTTPEMY-Q 1135
Cdd:cd14061  160 SAAGTYAWMAPEVIKSSTFSKASDVWSYGVLLWELLT-GEVPYKG--ID---GLAVAYGVAVNKltlpiPS-TCPEPFaQ 232
                        330       340
                 ....*....|....*....|....*.
gi 27777648 1136 TMLDCWHEDPNQRPSFSELVEHLGNL 1161
Cdd:cd14061  233 LMKDCWQPDPHDRPSFADILKQLENI 258
STKc_MAPKKK cd06606
Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein Kinase Kinase ...
831-1157 3.47e-33

Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein Kinase Kinase Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAPKKKs (MKKKs or MAP3Ks) are also called MAP/ERK kinase kinases (MEKKs) in some cases. They phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. This subfamily is composed of the Apoptosis Signal-regulating Kinases ASK1 (or MAPKKK5) and ASK2 (or MAPKKK6), MEKK1, MEKK2, MEKK3, MEKK4, as well as plant and fungal MAPKKKs. Also included in this subfamily are the cell division control proteins Schizosaccharomyces pombe Cdc7 and Saccharomyces cerevisiae Cdc15. The MAPKKK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270783 [Multi-domain]  Cd Length: 258  Bit Score: 129.56  E-value: 3.47e-33
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  831 RLKLGKPLGRGAFGQVIEAdafgIDKTaTCKTVAVKMLK-EGATHSEHRALMSELKILIHIGHHlNVVNLLGACTKPGGp 909
Cdd:cd06606    1 RWKKGELLGKGSFGSVYLA----LNLD-TGELMAVKEVElSGDSEEELEALEREIRILSSLKHP-NIVRYLGTERTENT- 73
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  910 LMVIVEFCKFGNLSTYLRgkrnefvpyksKGARFRqgkdyvgelsvdlkrrldsitssqssassgfveekslsdveeeea 989
Cdd:cd06606   74 LNIFLEYVPGGSLASLLK-----------KFGKLP--------------------------------------------- 97
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  990 seelykdfltlEHLIC-YSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDI----YKDPDYVRKGDAR 1064
Cdd:cd06606   98 -----------EPVVRkYTRQILEGLEYLHSNGIVHRDIKGANILVDSDGVVKLADFGCAKRLaeiaTGEGTKSLRGTPY 166
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1065 lplkWMAPETIFDRVYTIQSDVWSFGVLLWEIFSlGASPYPGV--------KIDEEfcrrlKEGTRMraPDYTTPEMYQT 1136
Cdd:cd06606  167 ----WMAPEVIRGEGYGRAADIWSLGCTVIEMAT-GKPPWSELgnpvaalfKIGSS-----GEPPPI--PEHLSEEAKDF 234
                        330       340
                 ....*....|....*....|.
gi 27777648 1137 MLDCWHEDPNQRPSFSELVEH 1157
Cdd:cd06606  235 LRKCLQRDPKKRPTADELLQH 255
PTKc_EphR_A10 cd05064
Catalytic domain of the Protein Tyrosine Kinase, Ephrin Receptor A10; PTKs catalyze the ...
826-1162 6.97e-32

Catalytic domain of the Protein Tyrosine Kinase, Ephrin Receptor A10; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. EphA10, which contains an inactive tyr kinase domain, may function to attenuate signals of co-clustered active receptors. EphA10 is mainly expressed in the testis. Ephrin/EphR interaction results in cell-cell repulsion or adhesion, making it important in neural development and plasticity, cell morphogenesis, cell-fate determination, embryonic development, tissue patterning, and angiogenesis. EphRs comprise the largest subfamily of receptor tyr kinases (RTKs). In general, class EphA receptors bind GPI-anchored ephrin-A ligands. There are ten vertebrate EphA receptors (EphA1-10), which display promiscuous interactions with six ephrin-A ligands. EphRs contain an ephrin binding domain and two fibronectin repeats extracellularly, a transmembrane segment, and a cytoplasmic tyr kinase domain. Binding of the ephrin ligand to EphR requires cell-cell contact since both are anchored to the plasma membrane. The resulting downstream signals occur bidirectionally in both EphR-expressing cells (forward signaling) and ephrin-expressing cells (reverse signaling). The EphA10 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 133195 [Multi-domain]  Cd Length: 266  Bit Score: 126.19  E-value: 6.97e-32
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  826 EFPRDRLKLGKPLGRGAFGQVIEadafGIDKTATCKT--VAVKMLKEGATHSEHRALMSELKILIHIGHHlNVVNLLGAC 903
Cdd:cd05064    1 ELDNKSIKIERILGTGRFGELCR----GCLKLPSKRElpVAIHTLRAGCSDKQRRGFLAEALTLGQFDHS-NIVRLEGVI 75
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  904 TKpGGPLMVIVEFCKFGNLSTYLRgkRNEfvpykskgarfrqGKDYVGELsvdlkrrldsitssqssassgfveekslsd 983
Cdd:cd05064   76 TR-GNTMMIVTEYMSNGALDSFLR--KHE-------------GQLVAGQL------------------------------ 109
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  984 veeeeaseelyKDFLTlehlicysfQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIYKDPDYVRKGdA 1063
Cdd:cd05064  110 -----------MGMLP---------GLASGMKYLSEMGYVHKGLAAHKVLVNSDLVCKISGFRRLQEDKSEAIYTTMS-G 168
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1064 RLPLKWMAPETIFDRVYTIQSDVWSFGVLLWEIFSLGASPYPGVKiDEEFCRRLKEGTRMRAPDYTTPEMYQTMLDCWHE 1143
Cdd:cd05064  169 KSPVLWAAPEAIQYHHFSSASDVWSFGIVMWEVMSYGERPYWDMS-GQDVIKAVEDGFRLPAPRNCPNLLHQLMLDCWQK 247
                        330
                 ....*....|....*....
gi 27777648 1144 DPNQRPSFSELVEHLGNLL 1162
Cdd:cd05064  248 ERGERPRFSQIHSILSKMV 266
STKc_IRAK cd14066
Catalytic domain of the Serine/Threonine kinases, Interleukin-1 Receptor Associated Kinases ...
861-1161 1.29e-31

Catalytic domain of the Serine/Threonine kinases, Interleukin-1 Receptor Associated Kinases and related STKs; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. IRAKs are involved in Toll-like receptor (TLR) and interleukin-1 (IL-1) signalling pathways, and are thus critical in regulating innate immune responses and inflammation. Some IRAKs may also play roles in T- and B-cell signaling, and adaptive immunity. Vertebrates contain four IRAKs (IRAK-1, -2, -3 (or -M), and -4) that display distinct functions and patterns of expression and subcellular distribution, and can differentially mediate TLR signaling. IRAK-1, -2, and -4 are ubiquitously expressed and are active kinases, while IRAK-M is only induced in monocytes and macrophages and is an inactive kinase. Variations in IRAK genes are linked to diverse diseases including infection, sepsis, cancer, and autoimmune diseases. IRAKs contain an N-terminal Death domain (DD), a proST region (rich in serines, prolines, and threonines), a central kinase domain (a pseudokinase domain in the case of IRAK3), and a C-terminal domain; IRAK-4 lacks the C-terminal domain. This subfamily includes plant receptor-like kinases (RLKs) including Arabidopsis thaliana BAK1 and CLAVATA1 (CLV1). BAK1 functions in BR (brassinosteroid)-regulated plant development and in pathways involved in plant resistance to pathogen infection and herbivore attack. CLV1, directly binds small signaling peptides, CLAVATA3 (CLV3) and CLAVATA3/EMBRYO SURROUNDING REGI0N (CLE), to restrict stem cell proliferation: the CLV3-CLV1-WUS (WUSCHEL) module influences stem cell maintenance in the shoot apical meristem, and the CLE40 (CLAVATA3/EMBRYO SURROUNDING REGION40) -ACR4 (CRINKLY4) -CLV1- WOX5 (WUSCHEL-RELATED HOMEOBOX5) module at the root apical meristem. The IRAK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270968 [Multi-domain]  Cd Length: 272  Bit Score: 125.46  E-value: 1.29e-31
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  861 KTVAVKMLKEGATHSEHRALMSELKILIHIgHHLNVVNLLGACTKPGGPLMVIvEFCKFGNLSTYLRGKRNEFVpykskg 940
Cdd:cd14066   18 TVVAVKRLNEMNCAASKKEFLTELEMLGRL-RHPNLVRLLGYCLESDEKLLVY-EYMPNGSLEDRLHCHKGSPP------ 89
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  941 arfrqgkdyvgelsVDLKRRLDsitssqssassgfveekslsdveeeeaseelykdfltlehlICysFQVAKGMEFL--- 1017
Cdd:cd14066   90 --------------LPWPQRLK-----------------------------------------IA--KGIARGLEYLhee 112
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1018 ASRKCIHRDLAARNILLSEKNVVKICDFGLARDIYKDPDYVRKGDARLPLKWMAPETIFDRVYTIQSDVWSFGVLLWEIF 1097
Cdd:cd14066  113 CPPPIIHGDIKSSNILLDEDFEPKLTDFGLARLIPPSESVSKTSAVKGTIGYLAPEYIRTGRVSTKSDVYSFGVVLLELL 192
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1098 SlGASP-YPGVKIDE-----EFCRRLKEGTRMR------APDYTTPE-----MYQTMLDCWHEDPNQRPSFSELVEHLGN 1160
Cdd:cd14066  193 T-GKPAvDENRENASrkdlvEWVESKGKEELEDildkrlVDDDGVEEeeveaLLRLALLCTRSDPSLRPSMKEVVQMLEK 271

                 .
gi 27777648 1161 L 1161
Cdd:cd14066  272 L 272
PTKc_Aatyk cd05042
Catalytic domain of the Protein Tyrosine Kinases, Apoptosis-associated tyrosine kinases; PTKs ...
836-1154 9.65e-31

Catalytic domain of the Protein Tyrosine Kinases, Apoptosis-associated tyrosine kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. The Aatyk subfamily is also referred to as the lemur tyrosine kinase (Lmtk) subfamily. It consists of Aatyk1 (Lmtk1), Aatyk2 (Lmtk2, Brek), Aatyk3 (Lmtk3), and similar proteins. Aatyk proteins are mostly receptor PTKs (RTKs) containing a transmembrane segment and a long C-terminal cytoplasmic tail with a catalytic domain. Aatyk1 does not contain a transmembrane segment and is a cytoplasmic (or nonreceptor) kinase. Aatyk proteins are classified as PTKs based on overall sequence similarity and the phylogenetic tree. However, analysis of catalytic residues suggests that Aatyk proteins may be multispecific kinases, functioning also as serine/threonine kinases. They are involved in neural differentiation, nerve growth factor (NGF) signaling, apoptosis, and spermatogenesis. The Aatyk subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270638 [Multi-domain]  Cd Length: 269  Bit Score: 122.70  E-value: 9.65e-31
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  836 KPLGRGAFGQVIEADafgIDKTATCKTVAVKMLKEGATHSEHRALMSELKILiHIGHHLNVVNLLGACTKpGGPLMVIVE 915
Cdd:cd05042    1 QEIGNGWFGKVLLGE---IYSGTSVAQVVVKELKASANPKEQDTFLKEGQPY-RILQHPNILQCLGQCVE-AIPYLLVME 75
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  916 FCKFGNLSTYLRGKRNEFVPYKskgarfrqgkdyvgelsvdlkrrldsitssqssassgfveekslsdveeeeaseelyk 995
Cdd:cd05042   76 FCDLGDLKAYLRSEREHERGDS---------------------------------------------------------- 97
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  996 DFLTLEHLICysfQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIYKDpDYVRKGDAR-LPLKWMAPE- 1073
Cdd:cd05042   98 DTRTLQRMAC---EVAAGLAHLHKLNFVHSDLALRNCLLTSDLTVKIGDYGLAHSRYKE-DYIETDDKLwFPLRWTAPEl 173
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1074 --TIFDRVYTI----QSDVWSFGVLLWEIFSLGASPYPGVKiDEEFcrrLKEGTRMRAPDYTTPEMYQTMLDCWHE---- 1143
Cdd:cd05042  174 vtEFHDRLLVVdqtkYSNIWSLGVTLWELFENGAQPYSNLS-DLDV---LAQVVREQDTKLPKPQLELPYSDRWYEvlqf 249
                        330
                 ....*....|....
gi 27777648 1144 ---DPNQRPSFSEL 1154
Cdd:cd05042  250 cwlSPEQRPAAEDV 263
PTKc_Aatyk1 cd05087
Catalytic domain of the Protein Tyrosine Kinases, Apoptosis-associated tyrosine kinase 1; PTKs ...
836-1158 1.64e-30

Catalytic domain of the Protein Tyrosine Kinases, Apoptosis-associated tyrosine kinase 1; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Aatyk1 (or simply Aatyk) is also called lemur tyrosine kinase 1 (Lmtk1). It is a cytoplasmic (or nonreceptor) kinase containing a long C-terminal region. The expression of Aatyk1 is upregulated during growth arrest and apoptosis in myeloid cells. Aatyk1 has been implicated in neural differentiation, and is a regulator of the Na-K-2Cl cotransporter, a membrane protein involved in cell proliferation and survival, epithelial transport, and blood pressure control. The Aatyk1 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270670 [Multi-domain]  Cd Length: 271  Bit Score: 122.40  E-value: 1.64e-30
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  836 KPLGRGAFGQVI--EADAfGIDKTatckTVAVKMLKEGATHSEHRALMSELKILIHIGHHlNVVNLLGACTKPGgPLMVI 913
Cdd:cd05087    3 KEIGHGWFGKVFlgEVNS-GLSST----QVVVKELKASASVQDQMQFLEEAQPYRALQHT-NLLQCLAQCAEVT-PYLLV 75
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  914 VEFCKFGNLSTYLRGKRnefvpykskgarfrqgkdyvgelsvdlkrrldsitssqssassgfveekslsdveeeeASEEL 993
Cdd:cd05087   76 MEFCPLGDLKGYLRSCR----------------------------------------------------------AAESM 97
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  994 YKDFLTLEHLICysfQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIYKDPDYVRKGDARLPLKWMAPE 1073
Cdd:cd05087   98 APDPLTLQRMAC---EVACGLLHLHRNNFVHSDLALRNCLLTADLTVKIGDYGLSHCKYKEDYFVTADQLWVPLRWIAPE 174
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1074 TIfDRVY--------TIQSDVWSFGVLLWEIFSLGASPYPGVKIDEEFCRRLKEgTRMRAPDYTTP-----EMYQTMLDC 1140
Cdd:cd05087  175 LV-DEVHgnllvvdqTKQSNVWSLGVTIWELFELGNQPYRHYSDRQVLTYTVRE-QQLKLPKPQLKlslaeRWYEVMQFC 252
                        330
                 ....*....|....*...
gi 27777648 1141 WHEdPNQRPSFSELveHL 1158
Cdd:cd05087  253 WLQ-PEQRPTAEEV--HL 267
IgI_VEGFR_like cd05742
Immunoglobulin (Ig)-like domain of vascular endothelial growth factor (VEGF) receptor (R) and ...
226-327 2.97e-29

Immunoglobulin (Ig)-like domain of vascular endothelial growth factor (VEGF) receptor (R) and similar proteins; member of the I-set of IgSF domains; The members here are composed of the immunoglobulin (Ig)-like domain of vascular endothelial growth factor (VEGF) receptor (R) and related proteins. The VEGFRs have an extracellular component with seven Ig-like domains, a transmembrane segment, and an intracellular tyrosine kinase domain interrupted by a kinase-insert domain. The VEGFR family consists of three members: VEGFR-1 (Flt-1), VEGFR-2 (KDR/Flk-1) and VEGFR-3 (Flt-4). VEGF-A interacts with both VEGFR-1 and VEGFR-2. VEGFR-1 binds strongest to VEGF; VEGF-2 binds more weakly. VEGFR-3 appears not to bind VEGF, but binds other members of the VEGF family (VEGF-C and -D). VEGFRs bind VEGFs with high affinity with the IG-like domains. VEGF-A is important to the growth and maintenance of vascular endothelial cells and to the development of new blood- and lymphatic-vessels in physiological and pathological states. VEGFR-2 is a major mediator of the mitogenic, angiogenic, and microvascular permeability-enhancing effects of VEGF-A. VEGFR-1 may play an inhibitory part in these processes by binding VEGF and interfering with its interaction with VEGFR-2. VEGFR-1 has a signaling role in mediating monocyte chemotaxis. VEGFR-1 and VEGFR-2 may mediate a chemotactic and a survival signal in hematopoietic stem cells or leukemia cells. VEGFR-3 has been shown to be involved in tumor angiogenesis and growth. This group also contains alpha-type platelet-derived growth factor receptor precursor (PDGFR)-alpha (CD140a), and PDGFR-beta (CD140b). PDGFRs alpha and beta have an extracellular component with five Ig-like domains, a transmembrane segment, and a cytoplasmic portion that has protein tyrosine kinase activity.


Pssm-ID: 409404  Cd Length: 102  Bit Score: 112.63  E-value: 2.97e-29
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  226 YDVILSPP-HEIELSAGEKLVLNCTARTELNVGLDFTWHSPPSKSHHKKIVNRDVKpFPGTVAKMFLSTLTIESVTKSDQ 304
Cdd:cd05742    1 SDLELSPNaEPTVLPQGETLVLNCTANVNLNEVVDFQWTYPSEKEGKLALLKPDIK-VDWSEPGEFVSTLTIPEATLKDS 79
                         90       100
                 ....*....|....*....|...
gi 27777648  305 GEYTCVASSGRMIKRNRTFVRVH 327
Cdd:cd05742   80 GTYTCAARSGVMKKEKQTSVSVH 102
STKc_Cdc7_like cd06627
Catalytic domain of Cell division control protein 7-like Serine/Threonine Kinases; STKs ...
834-1157 3.75e-27

Catalytic domain of Cell division control protein 7-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Members of this subfamily include Schizosaccharomyces pombe Cdc7, Saccharomyces cerevisiae Cdc15, Arabidopsis thaliana mitogen-activated protein kinase kinase kinase (MAPKKK) epsilon, and related proteins. MAPKKKs phosphorylate and activate MAPK kinases, which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. Fission yeast Cdc7 is essential for cell division by playing a key role in the initiation of septum formation and cytokinesis. Budding yeast Cdc15 functions to coordinate mitotic exit with cytokinesis. Arabidopsis MAPKKK epsilon is required for pollen development in the plasma membrane. The Cdc7-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270797 [Multi-domain]  Cd Length: 254  Bit Score: 111.93  E-value: 3.75e-27
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  834 LGKPLGRGAFGQVIEadafGIDKTaTCKTVAVKMLK-EGATHSEHRALMSELKILIHIgHHLNVVNLLGaCTKPGGPLMV 912
Cdd:cd06627    4 LGDLIGRGAFGSVYK----GLNLN-TGEFVAIKQISlEKIPKSDLKSVMGEIDLLKKL-NHPNIVKYIG-SVKTKDSLYI 76
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  913 IVEFCKFGNLSTylrgkrnefvpykskgarfrqgkdyvgelsvdlkrrldsitssqssassgfveekslsdveeeeasee 992
Cdd:cd06627   77 ILEYVENGSLAS-------------------------------------------------------------------- 88
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  993 LYKDFLTL-EHLI-CYSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLArdiykdpdyvrkgdARLPLK-- 1068
Cdd:cd06627   89 IIKKFGKFpESLVaVYIYQVLEGLAYLHEQGVIHRDIKGANILTTKDGLVKLADFGVA--------------TKLNEVek 154
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1069 ----------WMAPETIFDRVYTIQSDVWSFGVLLWEIFSlGASPYpgvkideeFCR-------RLKEGTRMRAPDYTTP 1131
Cdd:cd06627  155 densvvgtpyWMAPEVIEMSGVTTASDIWSVGCTVIELLT-GNPPY--------YDLqpmaalfRIVQDDHPPLPENISP 225
                        330       340
                 ....*....|....*....|....*.
gi 27777648 1132 EMYQTMLDCWHEDPNQRPSFSELVEH 1157
Cdd:cd06627  226 ELRDFLLQCFQKDPTLRPSAKELLKH 251
STKc_MLK3 cd14147
Catalytic domain of the Serine/Threonine Kinase, Mixed Lineage Kinase 3; STKs catalyze the ...
1003-1161 5.93e-27

Catalytic domain of the Serine/Threonine Kinase, Mixed Lineage Kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MLK3 is a mitogen-activated protein kinase kinase kinases (MAP3K, MKKK, MAPKKK), which phosphorylates and activates MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. MLK3 activates multiple MAPK pathways and plays a role in apoptosis, proliferation, migration, and differentiation, depending on the cellular context. It is highly expressed in breast cancer cells and its signaling through c-Jun N-terminal kinase has been implicated in the migration, invasion, and malignancy of cancer cells. MLK3 also functions as a negative regulator of Inhibitor of Nuclear Factor-KappaB Kinase (IKK) and consequently, it also impacts inflammation and immunity. Mammals have four MLKs, mostly conserved in vertebrates, which contain an SH3 domain, a catalytic kinase domain, a leucine zipper, a proline-rich region, and a CRIB domain that mediates binding to GTP-bound Cdc42 and Rac. MLKs play roles in immunity and inflammation, as well as in cell death, proliferation, and cell cycle regulation.The MLK3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271049 [Multi-domain]  Cd Length: 267  Bit Score: 111.66  E-value: 5.93e-27
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1003 LICYSFQVAKGMEFLASRK---CIHRDLAARNILLS--------EKNVVKICDFGLARDIYKDPDYVRKGDarlpLKWMA 1071
Cdd:cd14147  103 LVNWAVQIARGMHYLHCEAlvpVIHRDLKSNNILLLqpienddmEHKTLKITDFGLAREWHKTTQMSAAGT----YAWMA 178
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1072 PETIFDRVYTIQSDVWSFGVLLWEIFSlGASPYPGVKideefCRRLKEG---TRMRAP-DYTTPEMY-QTMLDCWHEDPN 1146
Cdd:cd14147  179 PEVIKASTFSKGSDVWSFGVLLWELLT-GEVPYRGID-----CLAVAYGvavNKLTLPiPSTCPEPFaQLMADCWAQDPH 252
                        170
                 ....*....|....*
gi 27777648 1147 QRPSFSELVEHLGNL 1161
Cdd:cd14147  253 RRPDFASILQQLEAL 267
STKc_MLK4 cd14146
Catalytic domain of the Serine/Threonine Kinase, Mixed Lineage Kinase 4; STKs catalyze the ...
1003-1158 1.23e-26

Catalytic domain of the Serine/Threonine Kinase, Mixed Lineage Kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MLK4 is a mitogen-activated protein kinase kinase kinase (MAP3K, MKKK, MAPKKK), which phosphorylates and activates MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. The specific function of MLK4 is yet to be determined. Mutations in the kinase domain of MLK4 have been detected in colorectal cancers. Mammals have four MLKs, mostly conserved in vertebrates, which contain an SH3 domain, a catalytic kinase domain, a leucine zipper, a proline-rich region, and a CRIB domain that mediates binding to GTP-bound Cdc42 and Rac. MLKs play roles in immunity and inflammation, as well as in cell death, proliferation, and cell cycle regulation.The MLK4 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271048 [Multi-domain]  Cd Length: 268  Bit Score: 110.90  E-value: 1.23e-26
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1003 LICYSFQVAKGMEFL---ASRKCIHRDLAARNILLSEK--------NVVKICDFGLARDIYKdpdyVRKGDARLPLKWMA 1071
Cdd:cd14146  104 LVNWAVQIARGMLYLheeAVVPILHRDLKSSNILLLEKiehddicnKTLKITDFGLAREWHR----TTKMSAAGTYAWMA 179
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1072 PETIFDRVYTIQSDVWSFGVLLWEIFSlGASPYPGvkIDEEFCRRLKEGTRMRAP-DYTTPEMY-QTMLDCWHEDPNQRP 1149
Cdd:cd14146  180 PEVIKSSLFSKGSDIWSYGVLLWELLT-GEVPYRG--IDGLAVAYGVAVNKLTLPiPSTCPEPFaKLMKECWEQDPHIRP 256

                 ....*....
gi 27777648 1150 SFSELVEHL 1158
Cdd:cd14146  257 SFALILEQL 265
PKc_STE cd05122
Catalytic domain of STE family Protein Kinases; PKs catalyze the transfer of the ...
833-1157 6.67e-26

Catalytic domain of STE family Protein Kinases; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. This family is composed of STKs, and some dual-specificity PKs that phosphorylate both threonine and tyrosine residues of target proteins. Most members are kinases involved in mitogen-activated protein kinase (MAPK) signaling cascades, acting as MAPK kinases (MAPKKs), MAPKK kinases (MAPKKKs), or MAPKKK kinases (MAP4Ks). The MAPK signaling pathways are important mediators of cellular responses to extracellular signals. The pathways involve a triple kinase core cascade comprising of the MAPK, which is phosphorylated and activated by a MAPKK, which itself is phosphorylated and activated by a MAPKKK. Each MAPK cascade is activated either by a small GTP-binding protein or by an adaptor protein, which transmits the signal either directly to a MAPKKK to start the triple kinase core cascade or indirectly through a mediator kinase, a MAP4K. Other STE family members include p21-activated kinases (PAKs) and class III myosins, among others. PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. Class III myosins are motor proteins containing an N-terminal kinase catalytic domain and a C-terminal actin-binding domain, which can phosphorylate several cytoskeletal proteins, conventional myosin regulatory light chains, as well as autophosphorylate the C-terminal motor domain. They play an important role in maintaining the structural integrity of photoreceptor cell microvilli. The STE family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270692 [Multi-domain]  Cd Length: 254  Bit Score: 108.44  E-value: 6.67e-26
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  833 KLGKPLGRGAFGQVIEAdafgIDKtATCKTVAVKMLK-EGATHSEHraLMSELKILIHIgHHLNVVNLLGACTKPGgPLM 911
Cdd:cd05122    3 EILEKIGKGGFGVVYKA----RHK-KTGQIVAIKKINlESKEKKES--ILNEIAILKKC-KHPNIVKYYGSYLKKD-ELW 73
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  912 VIVEFCKFGNLSTYLRGKrnefvpykskgarfrqgkdyvgelsvdlKRRLDsitssqssassgfveEKSLSdveeeease 991
Cdd:cd05122   74 IVMEFCSGGSLKDLLKNT----------------------------NKTLT---------------EQQIA--------- 101
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  992 elykdfltlehliCYSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIYKDPDyvRKGDARLPLkWMA 1071
Cdd:cd05122  102 -------------YVCKEVLKGLEYLHSHGIIHRDIKAANILLTSDGEVKLIDFGLSAQLSDGKT--RNTFVGTPY-WMA 165
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1072 PETIFDRVYTIQSDVWSFGVLLWEIFsLGASPYPG-------VKIDEEFCRRLKEGTRMrapdytTPEMYQTMLDCWHED 1144
Cdd:cd05122  166 PEVIQGKPYGFKADIWSLGITAIEMA-EGKPPYSElppmkalFLIATNGPPGLRNPKKW------SKEFKDFLKKCLQKD 238
                        330
                 ....*....|...
gi 27777648 1145 PNQRPSFSELVEH 1157
Cdd:cd05122  239 PEKRPTAEQLLKH 251
STKc_MAP3K12_13 cd14059
Catalytic domain of the Serine/Threonine Kinases, Mitogen-Activated Protein Kinase Kinase ...
998-1158 7.86e-26

Catalytic domain of the Serine/Threonine Kinases, Mitogen-Activated Protein Kinase Kinase Kinases 12 and 13; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAP3K12 is also called MAPK upstream kinase (MUK), dual leucine zipper-bearing kinase (DLK) or leucine-zipper protein kinase (ZPK). It is involved in the c-Jun N-terminal kinase (JNK) pathway that directly regulates axonal regulation through the phosphorylation of microtubule-associated protein 1B (MAP1B). It also regulates the differentiation of many cell types including adipocytes and may play a role in adipogenesis. MAP3K13, also called leucine zipper-bearing kinase (LZK), directly phosphorylates and activates MKK7, which in turn activates the JNK pathway. It also activates NF-kB through IKK activation and this activity is enhanced by antioxidant protein-1 (AOP-1). MAP3Ks (MKKKs or MAPKKKs) phosphorylate and activate MAP2Ks (MAPKKs or MKKs), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. The MAP3K12/13 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270961 [Multi-domain]  Cd Length: 237  Bit Score: 107.58  E-value: 7.86e-26
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  998 LTLEHLICYSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIykdPDYVRKGDARLPLKWMAPETIFD 1077
Cdd:cd14059   78 ITPSLLVDWSKQIASGMNYLHLHKIIHRDLKSPNVLVTYNDVLKISDFGTSKEL---SEKSTKMSFAGTVAWMAPEVIRN 154
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1078 RVYTIQSDVWSFGVLLWEIFSlGASPYPGVKIDEEFCRRLKEGTRMRAPDyTTPEMYQTMLD-CWHEDPNQRPSFSELVE 1156
Cdd:cd14059  155 EPCSEKVDIWSFGVVLWELLT-GEIPYKDVDSSAIIWGVGSNSLQLPVPS-TCPDGFKLLMKqCWNSKPRNRPSFRQILM 232

                 ..
gi 27777648 1157 HL 1158
Cdd:cd14059  233 HL 234
STKc_MLK2 cd14148
Catalytic domain of the Serine/Threonine Kinase, Mixed Lineage Kinase 2; STKs catalyze the ...
1003-1158 8.57e-26

Catalytic domain of the Serine/Threonine Kinase, Mixed Lineage Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MLK2 is a mitogen-activated protein kinase kinase kinase (MAP3K, MKKK, MAPKKK) and is also called MAP3K10. MAP3Ks phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. MLK2 is abundant in brain, skeletal muscle, and testis. It functions upstream of the MAPK, c-Jun N-terminal kinase. It binds hippocalcin, a calcium-sensor protein that protects neurons against calcium-induced cell death. Both MLK2 and hippocalcin may be associated with the pathogenesis of Parkinson's disease. MLK2 also binds to normal huntingtin (Htt), which is important in neuronal transcription, development, and survival. MLK2 does not bind to the polyglutamine-expanded Htt, which is implicated in the pathogeneis of Huntington's disease, leading to neuronal toxicity. Mammals have four MLKs, mostly conserved in vertebrates, which contain an SH3 domain, a catalytic kinase domain, a leucine zipper, a proline-rich region, and a CRIB domain that mediates binding to GTP-bound Cdc42 and Rac. MLKs play roles in immunity and inflammation, as well as in cell death, proliferation, and cell cycle regulation. The MLK2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase (PI3K).


Pssm-ID: 271050 [Multi-domain]  Cd Length: 258  Bit Score: 108.15  E-value: 8.57e-26
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1003 LICYSFQVAKGMEFL---ASRKCIHRDLAARNILLSEK--------NVVKICDFGLARDIYKdpdyVRKGDARLPLKWMA 1071
Cdd:cd14148   94 LVNWAVQIARGMNYLhneAIVPIIHRDLKSSNILILEPienddlsgKTLKITDFGLAREWHK----TTKMSAAGTYAWMA 169
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1072 PETIFDRVYTIQSDVWSFGVLLWEIFSlGASPYPgvKIDEEFCRRLKEGTRMRAP-DYTTPEMYQTMLD-CWHEDPNQRP 1149
Cdd:cd14148  170 PEVIRLSLFSKSSDVWSFGVLLWELLT-GEVPYR--EIDALAVAYGVAMNKLTLPiPSTCPEPFARLLEeCWDPDPHGRP 246

                 ....*....
gi 27777648 1150 SFSELVEHL 1158
Cdd:cd14148  247 DFGSILKRL 255
STKc_LRRK cd14000
Catalytic domain of the Serine/Threonine kinase, Leucine-Rich Repeat Kinase; STKs catalyze the ...
838-1158 9.44e-26

Catalytic domain of the Serine/Threonine kinase, Leucine-Rich Repeat Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. LRRKs are also classified as ROCO proteins because they contain a ROC (Ras of complex proteins)/GTPase domain followed by a COR (C-terminal of ROC) domain of unknown function. In addition, LRRKs contain a catalytic kinase domain and protein-protein interaction motifs including a WD40 domain, LRRs and ankyrin (ANK) repeats. LRRKs possess both GTPase and kinase activities, with the ROC domain acting as a molecular switch for the kinase domain, cycling between a GTP-bound state which drives kinase activity and a GDP-bound state which decreases the activity. Vertebrates contain two members, LRRK1 and LRRK2, which show complementary expression in the brain. Mutations in LRRK2 are linked to both familial and sporadic forms of Parkinson's disease. The normal roles of LRRKs are not clearly defined. They may be involved in mitogen-activated protein kinase (MAPK) pathways, protein translation control, programmed cell death pathways, and cytoskeletal dynamics. The LRRK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270902 [Multi-domain]  Cd Length: 275  Bit Score: 108.47  E-value: 9.44e-26
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  838 LGRGAFGQVIEADAFGidktatcKTVAVKML------------------KEGATHS--EHRALMSELKILIHIgHHLNVV 897
Cdd:cd14000    2 LGDGGFGSVYRASYKG-------EPVAVKIFnkhtssnfanvpadtmlrHLRATDAmkNFRLLRQELTVLSHL-HHPSIV 73
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  898 NLLGACTKPggpLMVIVEFCKFGNLSTYLRGKRNEFVPykskgarfrqgkdyvgelsvdLKRrldsitssqssassgfve 977
Cdd:cd14000   74 YLLGIGIHP---LMLVLELAPLGSLDHLLQQDSRSFAS---------------------LGR------------------ 111
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  978 ekslsdveeeeaseelykdflTLEHLICYsfQVAKGMEFLASRKCIHRDLAARNILLSEKNV-----VKICDFGLARDIY 1052
Cdd:cd14000  112 ---------------------TLQQRIAL--QVADGLRYLHSAMIIYRDLKSHNVLVWTLYPnsaiiIKIADYGISRQCC 168
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1053 KDPdyvRKGDARLPlKWMAPETI-FDRVYTIQSDVWSFGVLLWEIFSLGASPYPGVKIDEEFcrRLKEGTRMRAPDYTT- 1130
Cdd:cd14000  169 RMG---AKGSEGTP-GFRAPEIArGNVIYNEKVDVFSFGMLLYEILSGGAPMVGHLKFPNEF--DIHGGLRPPLKQYECa 242
                        330       340       350
                 ....*....|....*....|....*....|
gi 27777648 1131 --PEMYQTMLDCWHEDPNQRPSFSELVEHL 1158
Cdd:cd14000  243 pwPEVEVLMKKCWKENPQQRPTAVTVVSIL 272
STKc_Aurora cd14007
Catalytic domain of the Serine/Threonine kinase, Aurora kinase; STKs catalyze the transfer of ...
833-1157 1.17e-25

Catalytic domain of the Serine/Threonine kinase, Aurora kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Aurora kinases are key regulators of mitosis and are essential for the accurate and equal division of genomic material from parent to daughter cells. Yeast contains only one Aurora kinase while most higher eukaryotes have two. Vertebrates contain at least 2 Aurora kinases (A and B); mammals contains a third Aurora kinase gene (C). Aurora-A regulates cell cycle events from the late S-phase through the M-phase including centrosome maturation, mitotic entry, centrosome separation, spindle assembly, chromosome alignment, cytokinesis, and mitotic exit. Aurora-A activation depends on its autophosphorylation and binding to the microtubule-associated protein TPX2. Aurora-B is most active at the transition during metaphase to the end of mitosis. It is critical for accurate chromosomal segregation, cytokinesis, protein localization to the centrosome and kinetochore, correct microtubule-kinetochore attachments, and regulation of the mitotic checkpoint. Aurora-C is mainly expressed in meiotically dividing cells; it was originally discovered in mice as a testis-specific STK called Aie1. Both Aurora-B and -C are chromosomal passenger proteins that can form complexes with INCENP and survivin, and they may have redundant cellular functions. The Aurora subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270909 [Multi-domain]  Cd Length: 253  Bit Score: 107.56  E-value: 1.17e-25
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  833 KLGKPLGRGAFGQVIEAdafgIDKTaTCKTVAVKML--KEGATHSEHRALMSELKILIHIgHHLNVVNLLGACTKPGGpL 910
Cdd:cd14007    3 EIGKPLGKGKFGNVYLA----REKK-SGFIVALKVIskSQLQKSGLEHQLRREIEIQSHL-RHPNILRLYGYFEDKKR-I 75
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  911 MVIVEFCKFGNLSTYLRgkrnefvpykskgarfRQGKdyvgelsvdlkrrldsitssqssassgFVEEKSLSdveeeeas 990
Cdd:cd14007   76 YLILEYAPNGELYKELK----------------KQKR---------------------------FDEKEAAK-------- 104
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  991 eelykdfltlehlicYSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIykdPDYVRK---GDarlpL 1067
Cdd:cd14007  105 ---------------YIYQLALALDYLHSKNIIHRDIKPENILLGSNGELKLADFGWSVHA---PSNRRKtfcGT----L 162
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1068 KWMAPETIFDRVYTIQSDVWSFGVLLWEIFSlGASPYPGvKIDEEFCRRLKEGtRMRAPDYTTPEMYQTMLDCWHEDPNQ 1147
Cdd:cd14007  163 DYLPPEMVEGKEYDYKVDIWSLGVLCYELLV-GKPPFES-KSHQETYKRIQNV-DIKFPSSVSPEAKDLISKLLQKDPSK 239
                        330
                 ....*....|
gi 27777648 1148 RPSFSELVEH 1157
Cdd:cd14007  240 RLSLEQVLNH 249
STKc_MLK1 cd14145
Catalytic domain of the Serine/Threonine Kinase, Mixed Lineage Kinase 1; STKs catalyze the ...
1003-1158 2.57e-24

Catalytic domain of the Serine/Threonine Kinase, Mixed Lineage Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MLK1 is a mitogen-activated protein kinase kinase kinase (MAP3K, MKKK, MAPKKK) and is also called MAP3K9. MAP3Ks phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. Little is known about the specific function of MLK1. It is capable of activating the c-Jun N-terminal kinase pathway. Mice lacking both MLK1 and MLK2 are viable, fertile, and have normal life spans. There could be redundancy in the function of MLKs. Mammals have four MLKs, mostly conserved in vertebrates, which contain an SH3 domain, a catalytic kinase domain, a leucine zipper, a proline-rich region, and a CRIB domain that mediates binding to GTP-bound Cdc42 and Rac. MLKs play roles in immunity and inflammation, as well as in cell death, proliferation, and cell cycle regulation. The MLK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271047 [Multi-domain]  Cd Length: 270  Bit Score: 104.35  E-value: 2.57e-24
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1003 LICYSFQVAKGMEFL---ASRKCIHRDLAARNILLSEK--------NVVKICDFGLARDIYKdpdyVRKGDARLPLKWMA 1071
Cdd:cd14145  106 LVNWAVQIARGMNYLhceAIVPVIHRDLKSSNILILEKvengdlsnKILKITDFGLAREWHR----TTKMSAAGTYAWMA 181
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1072 PETIFDRVYTIQSDVWSFGVLLWEIFSlGASPYPGvkIDEEFCRRLKEGTRMRAP-DYTTPEMY-QTMLDCWHEDPNQRP 1149
Cdd:cd14145  182 PEVIRSSMFSKGSDVWSYGVLLWELLT-GEVPFRG--IDGLAVAYGVAMNKLSLPiPSTCPEPFaRLMEDCWNPDPHSRP 258

                 ....*....
gi 27777648 1150 SFSELVEHL 1158
Cdd:cd14145  259 PFTNILDQL 267
STKc_Raf cd14062
Catalytic domain of the Serine/Threonine Kinases, Raf (Rapidly Accelerated Fibrosarcoma) ...
838-1158 4.13e-24

Catalytic domain of the Serine/Threonine Kinases, Raf (Rapidly Accelerated Fibrosarcoma) kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Raf kinases act as mitogen-activated protein kinase kinase kinases (MAP3Ks, MKKKs, MAPKKKs), which phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. They function in the linear Ras-Raf-MEK-ERK pathway that regulates many cellular processes including cycle regulation, proliferation, differentiation, survival, and apoptosis. Aberrant expression or activation of components in this pathway are associated with tumor initiation, progression, and metastasis. Raf proteins contain a Ras binding domain, a zinc finger cysteine-rich domain, and a catalytic kinase domain. Vertebrates have three Raf isoforms (A-, B-, and C-Raf) with different expression profiles, modes of regulation, and abilities to function in the ERK cascade, depending on cellular context and stimuli. They have essential and non-overlapping roles during embryo- and organogenesis. Knockout of each isoform results in a lethal phenotype or abnormality in most mouse strains. The Raf subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270964 [Multi-domain]  Cd Length: 253  Bit Score: 103.24  E-value: 4.13e-24
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  838 LGRGAFGQVIEADAFGidktatckTVAVKMLK-EGATHSEHRALMSELKILiHIGHHLNVVNLLGACTKPGgpLMVIVEF 916
Cdd:cd14062    1 IGSGSFGTVYKGRWHG--------DVAVKKLNvTDPTPSQLQAFKNEVAVL-RKTRHVNILLFMGYMTKPQ--LAIVTQW 69
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  917 CKFGNLSTYLrgkrnefvpykskgarfrqgkdYVGELSVDLKRRLDsitssqssassgfveekslsdveeeeaseelykd 996
Cdd:cd14062   70 CEGSSLYKHL----------------------HVLETKFEMLQLID---------------------------------- 93
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  997 fltlehlICYsfQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIYKdpdYVRKGDARLP---LKWMAPE 1073
Cdd:cd14062   94 -------IAR--QTAQGMDYLHAKNIIHRDLKSNNIFLHEDLTVKIGDFGLATVKTR---WSGSQQFEQPtgsILWMAPE 161
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1074 TIF---DRVYTIQSDVWSFGVLLWEIFSlGASPYPGVKIDEEFCRRLKEGtrMRAPDYT-----TP-EMYQTMLDCWHED 1144
Cdd:cd14062  162 VIRmqdENPYSFQSDVYAFGIVLYELLT-GQLPYSHINNRDQILFMVGRG--YLRPDLSkvrsdTPkALRRLMEDCIKFQ 238
                        330
                 ....*....|....
gi 27777648 1145 PNQRPSFSELVEHL 1158
Cdd:cd14062  239 RDERPLFPQILASL 252
STKc_PknB_like cd14014
Catalytic domain of bacterial Serine/Threonine kinases, PknB and similar proteins; STKs ...
833-1158 4.20e-24

Catalytic domain of bacterial Serine/Threonine kinases, PknB and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily includes many bacterial eukaryotic-type STKs including Staphylococcus aureus PknB (also called PrkC or Stk1), Bacillus subtilis PrkC, and Mycobacterium tuberculosis Pkn proteins (PknB, PknD, PknE, PknF, PknL, and PknH), among others. S. aureus PknB is the only eukaryotic-type STK present in this species, although many microorganisms encode for several such proteins. It is important for the survival and pathogenesis of S. aureus as it is involved in the regulation of purine and pyrimidine biosynthesis, cell wall metabolism, autolysis, virulence, and antibiotic resistance. M. tuberculosis PknB is essential for growth and it acts on diverse substrates including proteins involved in peptidoglycan synthesis, cell division, transcription, stress responses, and metabolic regulation. B. subtilis PrkC is located at the inner membrane of endospores and functions to trigger spore germination. Bacterial STKs in this subfamily show varied domain architectures. The well-characterized members such as S. aureus and M. tuberculosis PknB, and B. subtilis PrkC, contain an N-terminal cytosolic kinase domain, a transmembrane (TM) segment, and mutliple C-terminal extracellular PASTA domains. The PknB subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270916 [Multi-domain]  Cd Length: 260  Bit Score: 103.05  E-value: 4.20e-24
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  833 KLGKPLGRGAFGQVIEAdafgIDkTATCKTVAVKMLKEGATHSE--HRALMSELKILIHIGHHlNVVNLLGACTKPGGPL 910
Cdd:cd14014    3 RLVRLLGRGGMGEVYRA----RD-TLLGRPVAIKVLRPELAEDEefRERFLREARALARLSHP-NIVRVYDVGEDDGRPY 76
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  911 MVIvEFCKFGNLSTYLRgkrnefvpykskgarfRQGKdyvgelsvdlkrrldsitssqssassgfveekslsdveeeeas 990
Cdd:cd14014   77 IVM-EYVEGGSLADLLR----------------ERGP------------------------------------------- 96
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  991 eelykdfLTLEHLICYSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIyKDPDYVRKGDARLPLKWM 1070
Cdd:cd14014   97 -------LPPREALRILAQIADALAAAHRAGIVHRDIKPANILLTEDGRVKLTDFGIARAL-GDSGLTQTGSVLGTPAYM 168
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1071 APETIFDRVYTIQSDVWSFGVLLWEIFSlGASPYPGvKIDEEFCRRLKEGTRMRAPDY---TTPEMYQTMLDCWHEDPNQ 1147
Cdd:cd14014  169 APEQARGGPVDPRSDIYSLGVVLYELLT-GRPPFDG-DSPAAVLAKHLQEAPPPPSPLnpdVPPALDAIILRALAKDPEE 246
                        330
                 ....*....|..
gi 27777648 1148 RP-SFSELVEHL 1158
Cdd:cd14014  247 RPqSAAELLAAL 258
PKc_MAPKK_plant_like cd06623
Catalytic domain of Plant dual-specificity Mitogen-Activated Protein Kinase Kinases and ...
832-1157 2.11e-23

Catalytic domain of Plant dual-specificity Mitogen-Activated Protein Kinase Kinases and similar proteins; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. Members of this group include MAPKKs from plants, kinetoplastids, alveolates, and mycetozoa. The MAPKK, LmxPK4, from Leishmania mexicana, is important in differentiation and virulence. Dictyostelium discoideum MEK1 is required for proper chemotaxis; MEK1 null mutants display severe defects in cell polarization and directional movement. Plants contain multiple MAPKKs like other eukaryotes. The Arabidopsis genome encodes for 10 MAPKKs while poplar and rice contain 13 MAPKKs each. The functions of these proteins have not been fully elucidated. There is evidence to suggest that MAPK cascades are involved in plant stress responses. In Arabidopsis, MKK3 plays a role in pathogen signaling; MKK2 is involved in cold and salt stress signaling; MKK4/MKK5 participates in innate immunity; and MKK7 regulates basal and systemic acquired resistance. The MAPKK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 132954 [Multi-domain]  Cd Length: 264  Bit Score: 101.13  E-value: 2.11e-23
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  832 LKLGKPLGRGAFGQVIEAdafgIDKtATCKTVAVKMLKEGATHSEHRALMSELKILIHIGHHlNVVNLLGACTKPGgPLM 911
Cdd:cd06623    3 LERVKVLGQGSSGVVYKV----RHK-PTGKIYALKKIHVDGDEEFRKQLLRELKTLRSCESP-YVVKCYGAFYKEG-EIS 75
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  912 VIVEFCKFGNLSTYLrgKRNEFVPykskgarfrqgkdyvgelsvdlkrrldsitssqssassgfveEKSLSdveeeease 991
Cdd:cd06623   76 IVLEYMDGGSLADLL--KKVGKIP------------------------------------------EPVLA--------- 102
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  992 elykdfltlehLICYsfQVAKGMEFL-ASRKCIHRDLAARNILLSEKNVVKICDFGLARDI----YKDPDYVrkGDArlp 1066
Cdd:cd06623  103 -----------YIAR--QILKGLDYLhTKRHIIHRDIKPSNLLINSKGEVKIADFGISKVLentlDQCNTFV--GTV--- 164
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1067 lKWMAPETIFDRVYTIQSDVWSFGVLLWEiFSLGASPYPGVKIDE--EFCRRLKEGTRMRAPD-YTTPEMYQTMLDCWHE 1143
Cdd:cd06623  165 -TYMSPERIQGESYSYAADIWSLGLTLLE-CALGKFPFLPPGQPSffELMQAICDGPPPSLPAeEFSPEFRDFISACLQK 242
                        330
                 ....*....|....
gi 27777648 1144 DPNQRPSFSELVEH 1157
Cdd:cd06623  243 DPKKRPSAAELLQH 256
STKc_CMGC cd05118
Catalytic domain of CMGC family Serine/Threonine Kinases; STKs catalyze the transfer of the ...
836-1157 2.43e-23

Catalytic domain of CMGC family Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The CMGC family consists of Cyclin-Dependent protein Kinases (CDKs), Mitogen-activated protein kinases (MAPKs) such as Extracellular signal-regulated kinase (ERKs), c-Jun N-terminal kinases (JNKs), and p38, and other kinases. CDKs belong to a large subfamily of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. MAPKs serve as important mediators of cellular responses to extracellular signals. They control critical cellular functions including differentiation, proliferation, migration, and apoptosis. They are also implicated in the pathogenesis of many diseases including multiple types of cancer, stroke, diabetes, and chronic inflammation. Other members of the CMGC family include casein kinase 2 (CK2), Dual-specificity tYrosine-phosphorylated and -Regulated Kinase (DYRK), Glycogen Synthase Kinase 3 (GSK3), among many others. The CMGC family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270688 [Multi-domain]  Cd Length: 249  Bit Score: 100.77  E-value: 2.43e-23
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  836 KPLGRGAFGQVIEAdafgIDKtATCKTVAVKMLKEGATHSEhRALmSELKILIHIGH---HLNVVNLLGACTKPGGPLMV 912
Cdd:cd05118    5 RKIGEGAFGTVWLA----RDK-VTGEKVAIKKIKNDFRHPK-AAL-REIKLLKHLNDvegHPNIVKLLDVFEHRGGNHLC 77
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  913 IVefCKFGNLSTYlrgkrnEFVpykskgarfrqgKDYVGELSVDLKRRldsitssqssassgfveekslsdveeeeasee 992
Cdd:cd05118   78 LV--FELMGMNLY------ELI------------KDYPRGLPLDLIKS-------------------------------- 105
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  993 lykdfltlehlicYSFQVAKGMEFLASRKCIHRDLAARNILLSEKN-VVKICDFGLARdIYKDPDYVRKGdarLPLKWMA 1071
Cdd:cd05118  106 -------------YLYQLLQALDFLHSNGIIHRDLKPENILINLELgQLKLADFGLAR-SFTSPPYTPYV---ATRWYRA 168
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1072 PETIF-DRVYTIQSDVWSFGVLLWEIFSlgASP-YPGVK-IDEEFCRRLKEGtrmrapdytTPEMYQTMLDCWHEDPNQR 1148
Cdd:cd05118  169 PEVLLgAKPYGSSIDIWSLGCILAELLT--GRPlFPGDSeVDQLAKIVRLLG---------TPEALDLLSKMLKYDPAKR 237

                 ....*....
gi 27777648 1149 PSFSELVEH 1157
Cdd:cd05118  238 ITASQALAH 246
STKc_B-Raf cd14151
Catalytic domain of the Serine/Threonine Kinase, B-Raf (Rapidly Accelerated Fibrosarcoma) ...
825-1161 5.80e-23

Catalytic domain of the Serine/Threonine Kinase, B-Raf (Rapidly Accelerated Fibrosarcoma) kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. B-Raf activates ERK with the strongest magnitude, compared with other Raf kinases. Mice embryos deficient in B-Raf die around midgestation due to vascular hemorrhage caused by apoptotic endothelial cells. Mutations in B-Raf have been implicated in initiating tumorigenesis and tumor progression, and are found in malignant cutaneous melanoma, papillary thyroid cancer, as well as in ovarian and colorectal carcinomas. Most oncogenic B-Raf mutations are located at the activation loop of the kinase and surrounding regions; the V600E mutation accounts for around 90% of oncogenic mutations. The V600E mutant constitutively activates MEK, resulting in sustained activation of ERK. B-Raf is a mitogen-activated protein kinase kinase kinase (MAP3K, MKKK, MAPKKK), which phosphorylates and activates MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. They function in the linear Ras-Raf-MEK-ERK pathway that regulates many cellular processes including cycle regulation, proliferation, differentiation, survival, and apoptosis. The B-Raf subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271053 [Multi-domain]  Cd Length: 274  Bit Score: 100.52  E-value: 5.80e-23
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  825 WEFPRDRLKLGKPLGRGAFGQVIEADAFGidktatckTVAVKMLKEGA-THSEHRALMSELKILIHIgHHLNVVNLLGAC 903
Cdd:cd14151    3 WEIPDGQITVGQRIGSGSFGTVYKGKWHG--------DVAVKMLNVTApTPQQLQAFKNEVGVLRKT-RHVNILLFMGYS 73
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  904 TKPggPLMVIVEFCKFGNLSTYLRGKRNEFvpykskgarfrqgkdyvgelsvdlkrrldsitssqssassgfvEEKSLSD 983
Cdd:cd14151   74 TKP--QLAIVTQWCEGSSLYHHLHIIETKF-------------------------------------------EMIKLID 108
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  984 VEEeeaseelykdfltlehlicysfQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIYKDPDYVRKGDA 1063
Cdd:cd14151  109 IAR----------------------QTAQGMDYLHAKSIIHRDLKSNNIFLHEDLTVKIGDFGLATVKSRWSGSHQFEQL 166
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1064 RLPLKWMAPETIF---DRVYTIQSDVWSFGVLLWEIFSlGASPYPGVKIDEEFCRRLKEGTrmRAPDYTT------PEMY 1134
Cdd:cd14151  167 SGSILWMAPEVIRmqdKNPYSFQSDVYAFGIVLYELMT-GQLPYSNINNRDQIIFMVGRGY--LSPDLSKvrsncpKAMK 243
                        330       340
                 ....*....|....*....|....*..
gi 27777648 1135 QTMLDCWHEDPNQRPSFSELVEHLGNL 1161
Cdd:cd14151  244 RLMAECLKKKRDERPLFPQILASIELL 270
Pkinase pfam00069
Protein kinase domain;
834-1157 1.01e-22

Protein kinase domain;


Pssm-ID: 459660 [Multi-domain]  Cd Length: 217  Bit Score: 98.08  E-value: 1.01e-22
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648    834 LGKPLGRGAFGQVIEAdafgIDKtATCKTVAVKML-KEGATHSEHRALMSELKILIHIgHHLNVVNLLGACTKPGGPLMV 912
Cdd:pfam00069    3 VLRKLGSGSFGTVYKA----KHR-DTGKIVAIKKIkKEKIKKKKDKNILREIKILKKL-NHPNIVRLYDAFEDKDNLYLV 76
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648    913 IvEFCKFGNLSTYLRGKRNefvpykskgarfrqgkdyvgelsvdlkrrldsitssqssassgfveekslsdveeeeasee 992
Cdd:pfam00069   77 L-EYVEGGSLFDLLSEKGA------------------------------------------------------------- 94
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648    993 lykdfLTLEHLICYSFQVAKGMEflasrkcihrdlaarnillseknvvkicdfglardiyKDPDY-VRKGDARlplkWMA 1071
Cdd:pfam00069   95 -----FSEREAKFIMKQILEGLE-------------------------------------SGSSLtTFVGTPW----YMA 128
                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648   1072 PETIFDRVYTIQSDVWSFGVLLWEIFSlGASPYPGVKIDEEFCRRLKEGTRM-RAPDYTTPEMYQTMLDCWHEDPNQRPS 1150
Cdd:pfam00069  129 PEVLGGNPYGPKVDVWSLGCILYELLT-GKPPFPGINGNEIYELIIDQPYAFpELPSNLSEEAKDLLKKLLKKDPSKRLT 207

                   ....*..
gi 27777648   1151 FSELVEH 1157
Cdd:pfam00069  208 ATQALQH 214
PKc_LIMK_like cd14065
Catalytic domain of the LIM domain kinase-like protein kinases; PKs catalyze the transfer of ...
838-1158 1.02e-22

Catalytic domain of the LIM domain kinase-like protein kinases; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine or tyrosine residues on protein substrates. Members of this subfamily include LIMK, Testicular or testis-specific protein kinase (TESK), and similar proteins. LIMKs are characterized as serine/threonine kinases (STKs) while TESKs are dual-specificity protein kinases. Both LIMK and TESK phosphorylate and inactivate cofilin, an actin depolymerizing factor, to induce the reorganization of the actin cytoskeleton. They are implicated in many cellular functions including cell spreading, motility, morphogenesis, meiosis, mitosis, and spermatogenesis. The LIMK-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270967 [Multi-domain]  Cd Length: 252  Bit Score: 99.10  E-value: 1.02e-22
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  838 LGRGAFGQVIEADafgidKTATCKTVAVKMLKEgatHSEHRALMSELKILIHIGHHlNVVNLLGACTKPGgPLMVIVEFC 917
Cdd:cd14065    1 LGKGFFGEVYKVT-----HRETGKVMVMKELKR---FDEQRSFLKEVKLMRRLSHP-NILRFIGVCVKDN-KLNFITEYV 70
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  918 KFGNLSTYLRgkrNEFVPYkSKGARFRQGKDyvgelsvdlkrrldsitssqssassgfveekslsdveeeeaseelykdf 997
Cdd:cd14065   71 NGGTLEELLK---SMDEQL-PWSQRVSLAKD------------------------------------------------- 97
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  998 ltlehlicysfqVAKGMEFLASRKCIHRDLAARNILL----SEKNVVkICDFGLARDIykdPDY-VRKGDARLPLK---- 1068
Cdd:cd14065   98 ------------IASGMAYLHSKNIIHRDLNSKNCLVreanRGRNAV-VADFGLAREM---PDEkTKKPDRKKRLTvvgs 161
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1069 --WMAPETIFDRVYTIQSDVWSFGVLLWEIFSLgaspypgVKIDEEFCRRLK------EGTRMRAPDYTTPEMYQTMLDC 1140
Cdd:cd14065  162 pyWMAPEMLRGESYDEKVDVFSFGIVLCEIIGR-------VPADPDYLPRTMdfgldvRAFRTLYVPDCPPSFLPLAIRC 234
                        330
                 ....*....|....*...
gi 27777648 1141 WHEDPNQRPSFSELVEHL 1158
Cdd:cd14065  235 CQLDPEKRPSFVELEHHL 252
STKc_RIP cd13978
Catalytic domain of the Serine/Threonine kinase, Receptor Interacting Protein; STKs catalyze ...
838-1153 2.06e-22

Catalytic domain of the Serine/Threonine kinase, Receptor Interacting Protein; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. RIP kinases serve as essential sensors of cellular stress. They are involved in regulating NF-kappaB and MAPK signaling, and are implicated in mediating cellular processes such as apoptosis, necroptosis, differentiation, and survival. RIP kinases contain a homologous N-terminal kinase domain and varying C-terminal domains. Higher vertebrates contain multiple RIP kinases, with mammals harboring at least five members. RIP1 and RIP2 harbor C-terminal domains from the Death domain (DD) superfamily while RIP4 contains ankyrin (ANK) repeats. RIP3 contain a RIP homotypic interaction motif (RHIM) that facilitates binding to RIP1. RIP1 and RIP3 are important in apoptosis and necroptosis, while RIP2 and RIP4 play roles in keratinocyte differentiation and inflammatory immune responses. The RIP subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270880 [Multi-domain]  Cd Length: 263  Bit Score: 98.29  E-value: 2.06e-22
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  838 LGRGAFGQVIEAdafgidKTATCKT-VAVKMLKEGATHSEHR-ALMSELKILiHIGHHLNVVNLLGACTKPGgPLMVIVE 915
Cdd:cd13978    1 LGSGGFGTVSKA------RHVSWFGmVAIKCLHSSPNCIEERkALLKEAEKM-ERARHSYVLPLLGVCVERR-SLGLVME 72
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  916 FCKFGNLSTYLRGKrnefvpykskgarfrqgkdyVGELSVDLKRRLdsitssqssassgfveekslsdveeeeaseelyk 995
Cdd:cd13978   73 YMENGSLKSLLERE--------------------IQDVPWSLRFRI---------------------------------- 98
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  996 dfltlehlicySFQVAKGMEFL--ASRKCIHRDLAARNILLSEKNVVKICDFGLARDIYKDPDYVRKGDARL---PLKWM 1070
Cdd:cd13978   99 -----------IHEIALGMNFLhnMDPPLLHHDLKPENILLDNHFHVKISDFGLSKLGMKSISANRRRGTENlggTPIYM 167
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1071 APETI--FDRVYTIQSDVWSFGVLLWEIFSlGASPYPGVKIDEEFCRRLKEGTRMRAPDYT-------TPEMYQTMLDCW 1141
Cdd:cd13978  168 APEAFddFNKKPTSKSDVYSFAIVIWAVLT-RKEPFENAINPLLIMQIVSKGDRPSLDDIGrlkqienVQELISLMIRCW 246
                        330
                 ....*....|..
gi 27777648 1142 HEDPNQRPSFSE 1153
Cdd:cd13978  247 DGNPDARPTFLE 258
STKc_Mos cd13979
Catalytic domain of the Serine/Threonine kinase, Oocyte maturation factor Mos; STKs catalyze ...
830-1153 2.57e-22

Catalytic domain of the Serine/Threonine kinase, Oocyte maturation factor Mos; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Mos (or c-Mos) is a germ-cell specific kinase that plays roles in both the release of primary arrest and the induction of secondary arrest in oocytes. It is expressed towards the end of meiosis I and is quickly degraded upon fertilization. It is a component of the cytostatic factor (CSF), which is responsible for metaphase II arrest. In addition, Mos activates a phoshorylation cascade that leads to the activation of the p34 subunit of MPF (mitosis-promoting factor or maturation promoting factor), a cyclin-dependent kinase that is responsible for the release of primary arrest in meiosis I. The Mos subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270881 [Multi-domain]  Cd Length: 265  Bit Score: 98.22  E-value: 2.57e-22
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  830 DRLKLGKPLGRGAFGQVIEADAFGidktatcKTVAVKMLKegaTHSEHRALMSELKILIHIGH--HLNVVNLLGA--CTK 905
Cdd:cd13979    3 EPLRLQEPLGSGGFGSVYKATYKG-------ETVAVKIVR---RRRKNRASRQSFWAELNAARlrHENIVRVLAAetGTD 72
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  906 PGGPLMVIVEFCkfgnlstylrGKRNefvpykskgarfrqgkdyvgelsvdLKRRLDSITSSqssassgfveekslsdve 985
Cdd:cd13979   73 FASLGLIIMEYC----------GNGT-------------------------LQQLIYEGSEP------------------ 99
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  986 eeeaseelykdfLTLEHLICYSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIYK-----DPDYVRK 1060
Cdd:cd13979  100 ------------LPLAHRILISLDIARALRFCHSHGIVHLDVKPANILISEQGVCKLCDFGCSVKLGEgnevgTPRSHIG 167
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1061 GDARlplkWMAPETIFDRVYTIQSDVWSFGVLLWEIFSlGASPYPGvkiDEEFCRRLKEGTRMRAPDY-----TTPEMYQ 1135
Cdd:cd13979  168 GTYT----YRAPELLKGERVTPKADIYSFGITLWQMLT-RELPYAG---LRQHVLYAVVAKDLRPDLSgledsEFGQRLR 239
                        330
                 ....*....|....*....
gi 27777648 1136 TMLD-CWHEDPNQRPSFSE 1153
Cdd:cd13979  240 SLISrCWSAQPAERPNADE 258
STKc_MLTK cd14060
Catalytic domain of the Serine/Threonine Kinase, Mixed lineage kinase-Like mitogen-activated ...
839-1161 2.80e-22

Catalytic domain of the Serine/Threonine Kinase, Mixed lineage kinase-Like mitogen-activated protein Triple Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MLTK, also called zipper sterile-alpha-motif kinase (ZAK), contains a catalytic kinase domain and a leucine zipper. There are two alternatively-spliced variants, MLTK-alpha and MLTK-beta. MLTK-alpha contains a sterile-alpha-motif (SAM) at the C-terminus. MLTK regulates the c-Jun N-terminal kinase, extracellular signal-regulated kinase, p38 MAPK, and NF-kB pathways. ZAK is the MAP3K involved in the signaling cascade that leads to the ribotoxic stress response initiated by cellular damage due to Shiga toxins and ricin. It may also play a role in cell transformation and cancer development. MAP3Ks (MKKKs or MAPKKKs) phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals.The MLTK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270962 [Multi-domain]  Cd Length: 242  Bit Score: 97.34  E-value: 2.80e-22
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  839 GRGAFGQVIEADAFGIDKTatcktVAVKMLKEGATHSEHRALMSelkilihighHLNVVNLLGACTKPggPLMVIV-EFC 917
Cdd:cd14060    2 GGGSFGSVYRAIWVSQDKE-----VAVKKLLKIEKEAEILSVLS----------HRNIIQFYGAILEA--PNYGIVtEYA 64
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  918 KFGNLSTYLRGKRNEfvpykskgarfrqgkdyvgELSVDlkrrldsitssqssassgfveekslsdveeeeaseelykdf 997
Cdd:cd14060   65 SYGSLFDYLNSNESE-------------------EMDMD----------------------------------------- 84
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  998 ltleHLICYSFQVAKGMEFL---ASRKCIHRDLAARNILLSEKNVVKICDFGLARDIYKDPDYVRKGDarlpLKWMAPET 1074
Cdd:cd14060   85 ----QIMTWATDIAKGMHYLhmeAPVKVIHRDLKSRNVVIAADGVLKICDFGASRFHSHTTHMSLVGT----FPWMAPEV 156
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1075 IFDRVYTIQSDVWSFGVLLWEIFSLGAsPYPGVKIDEEFCRRLKEGTRMRAPDYTTPEMYQTMLDCWHEDPNQRPSFSEL 1154
Cdd:cd14060  157 IQSLPVSETCDTYSYGVVLWEMLTREV-PFKGLEGLQVAWLVVEKNERPTIPSSCPRSFAELMRRCWEADVKERPSFKQI 235

                 ....*..
gi 27777648 1155 VEHLGNL 1161
Cdd:cd14060  236 IGILESM 242
PTKc_Aatyk2 cd05086
Catalytic domain of the Protein Tyrosine Kinase, Apoptosis-associated tyrosine kinase 2; PTKs ...
838-1154 7.39e-22

Catalytic domain of the Protein Tyrosine Kinase, Apoptosis-associated tyrosine kinase 2; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Aatyk2 is a member of the Aatyk subfamily of proteins, which are receptor kinases containing a transmembrane segment and a long C-terminal cytoplasmic tail with a catalytic domain. Aatyk2 is also called lemur tyrosine kinase 2 (Lmtk2) or brain-enriched kinase (Brek). It is expressed at high levels in early postnatal brain, and has been shown to play a role in nerve growth factor (NGF) signaling. Studies with knockout mice reveal that Aatyk2 is essential for late stage spermatogenesis. Although it is classified as a PTK based on sequence similarity and the phylogenetic tree, Aatyk2 has been functionally characterized as a serine/threonine kinase. The Aatyk2 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270669 [Multi-domain]  Cd Length: 271  Bit Score: 96.86  E-value: 7.39e-22
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  838 LGRGAFGQVIEADAFgiDKTATCKTVaVKMLKEGATHSEHRALMSELKILiHIGHHLNVVNLLGACTKpGGPLMVIVEFC 917
Cdd:cd05086    5 IGNGWFGKVLLGEIY--TGTSVARVV-VKELKASANPKEQDDFLQQGEPY-YILQHPNILQCVGQCVE-AIPYLLVFEFC 79
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  918 KFGNLSTYLRGKRnefvpykskgarfrqgkdyvgelsvdlkrrldsitssqssassgfveEKSLSDveeeeaseelyKDF 997
Cdd:cd05086   80 DLGDLKTYLANQQ-----------------------------------------------EKLRGD-----------SQI 101
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  998 LTLEHLICysfQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIYKDpDYVRKGDARL-PLKWMAPETIF 1076
Cdd:cd05086  102 MLLQRMAC---EIAAGLAHMHKHNFLHSDLALRNCYLTSDLTVKVGDYGIGFSRYKE-DYIETDDKKYaPLRWTAPELVT 177
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1077 ---DRVYTIQ----SDVWSFGVLLWEIFSLGASPYPGVKIDEEFCRRLKE-GTRMRAPDYTTP---EMYQTMLDCWHEdP 1145
Cdd:cd05086  178 sfqDGLLAAEqtkySNIWSLGVTLWELFENAAQPYSDLSDREVLNHVIKErQVKLFKPHLEQPysdRWYEVLQFCWLS-P 256

                 ....*....
gi 27777648 1146 NQRPSFSEL 1154
Cdd:cd05086  257 EKRPTAEEV 265
STKc_MEKK1_plant cd06632
Catalytic domain of the Serine/Threonine Kinase, Plant Mitogen-Activated Protein (MAP) ...
831-1157 1.07e-21

Catalytic domain of the Serine/Threonine Kinase, Plant Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of plant MAPK kinase kinases (MAPKKKs) including Arabidopsis thaliana MEKK1 and MAPKKK3. Arabidopsis thaliana MEKK1 activates MPK4, a MAPK that regulates systemic acquired resistance. MEKK1 also participates in the regulation of temperature-sensitive and tissue-specific cell death. MAPKKKs phosphorylate and activate MAPK kinases, which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. The plant MEKK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270802 [Multi-domain]  Cd Length: 259  Bit Score: 96.32  E-value: 1.07e-21
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  831 RLKLGKPLGRGAFGQVIEAdaFGIDKTATCKTVAVKMLKEGATHSEH-RALMSELKILIHIgHHLNVVNLLGAcTKPGGP 909
Cdd:cd06632    1 RWQKGQLLGSGSFGSVYEG--FNGDTGDFFAVKEVSLVDDDKKSRESvKQLEQEIALLSKL-RHPNIVQYYGT-EREEDN 76
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  910 LMVIVEFCKFGNLSTylrgkrnefvpykskgarfrqgkdyvgelsvdlkrrldsitssqssassgfveekslsdveeeea 989
Cdd:cd06632   77 LYIFLEYVPGGSIHK----------------------------------------------------------------- 91
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  990 seeLYKDFLTL-EHLI-CYSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIyKDPDYVR--KGDARl 1065
Cdd:cd06632   92 ---LLQRYGAFeEPVIrLYTRQILSGLAYLHSRNTVHRDIKGANILVDTNGVVKLADFGMAKHV-EAFSFAKsfKGSPY- 166
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1066 plkWMAPETI--FDRVYTIQSDVWSFGVLLWEIfSLGASP---YPGVKIdeeFCRRLKEGTRMRAPDYTTPEMYQTMLDC 1140
Cdd:cd06632  167 ---WMAPEVImqKNSGYGLAVDIWSLGCTVLEM-ATGKPPwsqYEGVAA---IFKIGNSGELPPIPDHLSPDAKDFIRLC 239
                        330
                 ....*....|....*..
gi 27777648 1141 WHEDPNQRPSFSELVEH 1157
Cdd:cd06632  240 LQRDPEDRPTASQLLEH 256
STKc_AMPK-like cd14003
Catalytic domain of AMP-activated protein kinase-like Serine/Threonine Kinases; STKs catalyze ...
833-1157 2.24e-21

Catalytic domain of AMP-activated protein kinase-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The AMPK-like subfamily is composed of AMPK, MARK, BRSK, NUAK, MELK, SNRK, TSSK, and SIK, among others. LKB1 serves as a master upstream kinase that activates AMPK and most AMPK-like kinases. AMPK, also called SNF1 (sucrose non-fermenting1) in yeasts and SnRK1 (SNF1-related kinase1) in plants, is a heterotrimeric enzyme composed of a catalytic alpha subunit and two regulatory subunits, beta and gamma. It is a stress-activated kinase that serves as master regulator of glucose and lipid metabolism by monitoring carbon and energy supplies, via sensing the cell's AMP:ATP ratio. MARKs phosphorylate tau and related microtubule-associated proteins (MAPs), and regulates microtubule-based intracellular transport. They are involved in embryogenesis, epithelial cell polarization, cell signaling, and neuronal differentiation. BRSKs play important roles in establishing neuronal polarity. TSSK proteins are almost exclusively expressed postmeiotically in the testis and play important roles in spermatogenesis and/or spermiogenesis. The AMPK-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270905 [Multi-domain]  Cd Length: 252  Bit Score: 94.89  E-value: 2.24e-21
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  833 KLGKPLGRGAFGQVIEAdafgIDKtATCKTVAVKML-KEGATHSEHRALMSELKILIHIgHHLNVVNLLGACTKPGGPLM 911
Cdd:cd14003    3 ELGKTLGEGSFGKVKLA----RHK-LTGEKVAIKIIdKSKLKEEIEEKIKREIEIMKLL-NHPNIIKLYEVIETENKIYL 76
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  912 ViVEFCKFGNLSTYLRGKrnefvpykskgarfrqgkdyvGELSVDLKRRLdsitssqssassgfveekslsdveeeease 991
Cdd:cd14003   77 V-MEYASGGELFDYIVNN---------------------GRLSEDEARRF------------------------------ 104
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  992 elykdFltlehlicysFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIYKD---------PDYvrkgd 1062
Cdd:cd14003  105 -----F----------QQLISAVDYCHSNGIVHRDLKLENILLDKNGNLKIIDFGLSNEFRGGsllktfcgtPAY----- 164
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1063 arlplkwMAPETIFDRVY-TIQSDVWSFGVLLweiFSL--GASPYPGVKIDEEFcRRLKEGTrMRAPDYTTPE---MYQT 1136
Cdd:cd14003  165 -------AAPEVLLGRKYdGPKADVWSLGVIL---YAMltGYLPFDDDNDSKLF-RKILKGK-YPIPSHLSPDardLIRR 232
                        330       340
                 ....*....|....*....|.
gi 27777648 1137 MLDcwhEDPNQRPSFSELVEH 1157
Cdd:cd14003  233 MLV---VDPSKRITIEEILNH 250
STKc_CNK2-like cd08530
Catalytic domain of the Serine/Threonine Kinases, Chlamydomonas reinhardtii CNK2 and similar ...
831-1157 9.50e-21

Catalytic domain of the Serine/Threonine Kinases, Chlamydomonas reinhardtii CNK2 and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Chlamydomonas reinhardtii CNK2 has both cilliary and cell cycle functions. It influences flagellar length through promoting flagellar disassembly, and it regulates cell size, through influencing the size threshold at which cells commit to mitosis. This subfamily belongs to the (NIMA)-related kinase (Nek) family, which includes seven different Chlamydomonas Neks (CNKs 1-6 and Fa2). This subfamily includes CNK1, and -2. The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270869 [Multi-domain]  Cd Length: 256  Bit Score: 93.22  E-value: 9.50e-21
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  831 RLKLGKPLGRGAFGQVieadaFGIDKTATCKTVAVKMLKEGA-THSEHRALMSELKILIHIGHHlNVVNLLGACTKpGGP 909
Cdd:cd08530    1 DFKVLKKLGKGSYGSV-----YKVKRLSDNQVYALKEVNLGSlSQKEREDSVNEIRLLASVNHP-NIIRYKEAFLD-GNR 73
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  910 LMVIVEFCKFGNLSTYLRGKRNefvpykskgarfrqgkdyvgelsvdlKRRLdsitssqssassgFVEEkslsdveeeea 989
Cdd:cd08530   74 LCIVMEYAPFGDLSKLISKRKK--------------------------KRRL-------------FPED----------- 103
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  990 seELYKDFLtlehlicysfQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIYKDPDYVRKGDarlPLkW 1069
Cdd:cd08530  104 --DIWRIFI----------QMLRGLKALHDQKILHRDLKSANILLSAGDLVKIGDLGISKVLKKNLAKTQIGT---PL-Y 167
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1070 MAPETIFDRVYTIQSDVWSFGVLLWEIFSLgASPYPGvKIDEEFCRRLKEGTRMRAPDYTTPEMYQTMLDCWHEDPNQRP 1149
Cdd:cd08530  168 AAPEVWKGRPYDYKSDIWSLGCLLYEMATF-RPPFEA-RTMQELRYKVCRGKFPPIPPVYSQDLQQIIRSLLQVNPKKRP 245

                 ....*...
gi 27777648 1150 SFSELVEH 1157
Cdd:cd08530  246 SCDKLLQS 253
STKc_CDK_like cd07829
Catalytic domain of Cyclin-Dependent protein Kinase-like Serine/Threonine Kinases; STKs ...
833-1157 1.02e-20

Catalytic domain of Cyclin-Dependent protein Kinase-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. CDKs are partly regulated by their subcellular localization, which defines substrate phosphorylation and the resulting specific function. CDK1, CDK2, CDK4, and CDK6 have well-defined functions in the cell cycle, such as the regulation of the early G1 phase by CDK4 or CDK6, the G1/S phase transition by CDK2, or the entry of mitosis by CDK1. They also exhibit overlapping cyclin specificity and functions in certain conditions. Knockout mice with a single CDK deleted remain viable with specific phenotypes, showing that some CDKs can compensate for each other. For example, CDK4 can compensate for the loss of CDK6, however, double knockout mice with both CDK4 and CDK6 deleted die in utero. CDK8 and CDK9 are mainly involved in transcription while CDK5 is implicated in neuronal function. CDK7 plays essential roles in both the cell cycle as a CDK-Activating Kinase (CAK) and in transcription as a component of the general transcription factor TFIIH. The CDK-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270823 [Multi-domain]  Cd Length: 282  Bit Score: 93.70  E-value: 1.02e-20
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  833 KLGKpLGRGAFGQVIEAdafgIDKtATCKTVAVKMLK-----EGATHSEHR--ALMSELKilihighHLNVVNLLGACTK 905
Cdd:cd07829    3 KLEK-LGEGTYGVVYKA----KDK-KTGEIVALKKIRldneeEGIPSTALReiSLLKELK-------HPNIVKLLDVIHT 69
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  906 PGGpLMVIVEFCkfgnlstylrgkrnefvpykskgarfrqgkDYvgelsvDLKRRLDSITSSqssassgfveekslsdve 985
Cdd:cd07829   70 ENK-LYLVFEYC------------------------------DQ------DLKKYLDKRPGP------------------ 94
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  986 eeeaseelykdfLTLEHLICYSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIykdpdyvrkgdaRL 1065
Cdd:cd07829   95 ------------LPPNLIKSIMYQLLRGLAYCHSHRILHRDLKPQNLLINRDGVLKLADFGLARAF------------GI 150
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1066 PLK---------WM-APETIF-DRVYTIQSDVWSFG----------VL---------LWEIFSLGASP----YPGVK--- 1108
Cdd:cd07829  151 PLRtythevvtlWYrAPEILLgSKHYSTAVDIWSVGcifaelitgkPLfpgdseidqLFKIFQILGTPteesWPGVTklp 230
                        330       340       350       360       370
                 ....*....|....*....|....*....|....*....|....*....|...
gi 27777648 1109 -IDEEFCRRLKEGTRMRAPDYtTPEMY---QTMLDCwheDPNQRPSFSELVEH 1157
Cdd:cd07829  231 dYKPTFPKWPKNDLEKVLPRL-DPEGIdllSKMLQY---NPAKRISAKEALKH 279
STKc_Byr2_like cd06628
Catalytic domain of the Serine/Threonine Kinases, fungal Byr2-like Mitogen-Activated Protein ...
1009-1157 1.47e-20

Catalytic domain of the Serine/Threonine Kinases, fungal Byr2-like Mitogen-Activated Protein Kinase Kinase Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Members of this group include the MAPKKKs Schizosaccharomyces pombe Byr2, Saccharomyces cerevisiae and Cryptococcus neoformans Ste11, and related proteins. They contain an N-terminal SAM (sterile alpha-motif) domain, which mediates protein-protein interaction, and a C-terminal catalytic domain. MAPKKKs phosphorylate and activate MAPK kinases, which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. Fission yeast Byr2 is regulated by Ras1. It responds to pheromone signaling and controls mating through the MAPK pathway. Budding yeast Ste11 functions in MAPK cascades that regulate mating, high osmolarity glycerol, and filamentous growth responses. The Byr2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270798 [Multi-domain]  Cd Length: 267  Bit Score: 92.98  E-value: 1.47e-20
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1009 QVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIYKDPDYVRKGDARLPLK----WMAPETIFDRVYTIQS 1084
Cdd:cd06628  114 QILKGLNYLHNRGIIHRDIKGANILVDNKGGIKISDFGISKKLEANSLSTKNNGARPSLQgsvfWMAPEVVKQTSYTRKA 193
                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 27777648 1085 DVWSFGVLLWEIFSlGASPYPGV-KIDEEFcrRLKEGTRMRAPDYTTPEMYQTMLDCWHEDPNQRPSFSELVEH 1157
Cdd:cd06628  194 DIWSLGCLVVEMLT-GTHPFPDCtQMQAIF--KIGENASPTIPSNISSEARDFLEKTFEIDHNKRPTADELLKH 264
STKc_PAK cd06614
Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase; STKs catalyze the ...
980-1157 2.38e-20

Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. PAKs are implicated in the regulation of many cellular processes including growth factor receptor-mediated proliferation, cell polarity, cell motility, cell death and survival, and actin cytoskeleton organization. PAK deregulation is associated with tumor development. PAKs from higher eukaryotes are classified into two groups (I and II), according to their biochemical and structural features. Group I PAKs contain a PBD (p21-binding domain) overlapping with an AID (autoinhibitory domain), a C-terminal catalytic domain, SH3 binding sites and a non-classical SH3 binding site for PIX (PAK-interacting exchange factor). Group II PAKs contain a PBD and a catalytic domain, but lack other motifs found in group I PAKs. Since group II PAKs do not contain an obvious AID, they may be regulated differently from group I PAKs. Group I PAKs interact with the SH3 containing proteins Nck, Grb2 and PIX; no such binding has been demonstrated for group II PAKs. The PAK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270789 [Multi-domain]  Cd Length: 255  Bit Score: 92.27  E-value: 2.38e-20
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  980 SLSDVeeeeaseeLYKDFLTL-EHLICY-SFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIYKDPDY 1057
Cdd:cd06614   82 SLTDI--------ITQNPVRMnESQIAYvCREVLQGLEYLHSQNVIHRDIKSDNILLSKDGSVKLADFGFAAQLTKEKSK 153
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1058 vRKGDARLPLkWMAPETIFDRVYTIQSDVWSFGVLLWEIFSlGASPYpgvkIDEEFCRRLK----EGT-RMRAPDYTTPE 1132
Cdd:cd06614  154 -RNSVVGTPY-WMAPEVIKRKDYGPKVDIWSLGIMCIEMAE-GEPPY----LEEPPLRALFlittKGIpPLKNPEKWSPE 226
                        170       180
                 ....*....|....*....|....*
gi 27777648 1133 MYQTMLDCWHEDPNQRPSFSELVEH 1157
Cdd:cd06614  227 FKDFLNKCLVKDPEKRPSAEELLQH 251
STKc_CAMK cd05117
The catalytic domain of CAMK family Serine/Threonine Kinases; STKs catalyze the transfer of ...
833-1157 8.59e-20

The catalytic domain of CAMK family Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CaMKs are multifunctional calcium and calmodulin (CaM) stimulated STKs involved in cell cycle regulation. There are several types of CaMKs including CaMKI, CaMKII, and CaMKIV. CaMKI proteins are monomeric and they play pivotal roles in the nervous system, including long-term potentiation, dendritic arborization, neurite outgrowth, and the formation of spines, synapses, and axons. CaMKII is a signaling molecule that translates upstream calcium and reactive oxygen species (ROS) signals into downstream responses that play important roles in synaptic function and cardiovascular physiology. CAMKIV is implicated in regulating several transcription factors like CREB, MEF2, and retinoid orphan receptors, as well as in T-cell development and signaling. The CAMK family also consists of other related kinases including the Phosphorylase kinase Gamma subunit (PhKG), the C-terminal kinase domains of Ribosomal S6 kinase (RSK) and Mitogen and stress-activated kinase (MSK), Doublecortin-like kinase (DCKL), and the MAPK-activated protein kinases MK2, MK3, and MK5, among others. The CAMK family is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270687 [Multi-domain]  Cd Length: 258  Bit Score: 90.61  E-value: 8.59e-20
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  833 KLGKPLGRGAFGQVIEAdafgIDKtATCKTVAVKML-KEGATHSEHRALMSELKILIHIGHHlNVVNLLGA-CTKpgGPL 910
Cdd:cd05117    3 ELGKVLGRGSFGVVRLA----VHK-KTGEEYAVKIIdKKKLKSEDEEMLRREIEILKRLDHP-NIVKLYEVfEDD--KNL 74
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  911 MVIVEFCKFGNLSTYL--RGKRNEfvpykskgarfRQGKDYVgelsvdlkrrldsitssqssassgfveekslsdveeee 988
Cdd:cd05117   75 YLVMELCTGGELFDRIvkKGSFSE-----------REAAKIM-------------------------------------- 105
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  989 aseelykdfltlehlicysFQVAKGMEFLASRKCIHRDLAARNILLSEKN---VVKICDFGLARDIykDPDYVRKGDARL 1065
Cdd:cd05117  106 -------------------KQILSAVAYLHSQGIVHRDLKPENILLASKDpdsPIKIIDFGLAKIF--EEGEKLKTVCGT 164
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1066 PLkWMAPETIFDRVYTIQSDVWSFGVLLWEIFSlGASPYPGvKIDEEFCRRLKEGtrmrapDYTTPEmyqtmlDCWHE-- 1143
Cdd:cd05117  165 PY-YVAPEVLKGKGYGKKCDIWSLGVILYILLC-GYPPFYG-ETEQELFEKILKG------KYSFDS------PEWKNvs 229
                        330       340
                 ....*....|....*....|....*..
gi 27777648 1144 -------------DPNQRPSFSELVEH 1157
Cdd:cd05117  230 eeakdlikrllvvDPKKRLTAAEALNH 256
STKc_AGC cd05123
Catalytic domain of AGC family Serine/Threonine Kinases; STKs catalyze the transfer of the ...
838-1157 1.02e-19

Catalytic domain of AGC family Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. AGC kinases regulate many cellular processes including division, growth, survival, metabolism, motility, and differentiation. Many are implicated in the development of various human diseases. Members of this family include cAMP-dependent Protein Kinase (PKA), cGMP-dependent Protein Kinase (PKG), Protein Kinase C (PKC), Protein Kinase B (PKB), G protein-coupled Receptor Kinase (GRK), Serum- and Glucocorticoid-induced Kinase (SGK), and 70 kDa ribosomal Protein S6 Kinase (p70S6K or S6K), among others. AGC kinases share an activation mechanism based on the phosphorylation of up to three sites: the activation loop (A-loop), the hydrophobic motif (HM) and the turn motif. Phosphorylation at the A-loop is required of most AGC kinases, which results in a disorder-to-order transition of the A-loop. The ordered conformation results in the access of substrates and ATP to the active site. A subset of AGC kinases with C-terminal extensions containing the HM also requires phosphorylation at this site. Phosphorylation at the HM allows the C-terminal extension to form an ordered structure that packs into the hydrophobic pocket of the catalytic domain, which then reconfigures the kinase into an active bi-lobed state. In addition, growth factor-activated AGC kinases such as PKB, p70S6K, RSK, MSK, PKC, and SGK, require phosphorylation at the turn motif (also called tail or zipper site), located N-terminal to the HM at the C-terminal extension. The AGC family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and Phosphoinositide 3-Kinase.


Pssm-ID: 270693 [Multi-domain]  Cd Length: 250  Bit Score: 90.27  E-value: 1.02e-19
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  838 LGRGAFGQVieadaFGIDKTATCKTVAVKMLKEGA--THSEHRALMSELKILIHIgHHLNVVNLLGACTKPGGpLMVIVE 915
Cdd:cd05123    1 LGKGSFGKV-----LLVRKKDTGKLYAMKVLRKKEiiKRKEVEHTLNERNILERV-NHPFIVKLHYAFQTEEK-LYLVLD 73
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  916 FCKFGNLSTYLR--GKRNEfvpyksKGARFrqgkdYVGELSvdlkrrldsitssqssassgfveekslsdveeeeaseel 993
Cdd:cd05123   74 YVPGGELFSHLSkeGRFPE------ERARF-----YAAEIV--------------------------------------- 103
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  994 ykdfLTLEHLicysfqvakgmeflASRKCIHRDLAARNILLSEKNVVKICDFGLARDIYKD----------PDYvrkgda 1063
Cdd:cd05123  104 ----LALEYL--------------HSLGIIYRDLKPENILLDSDGHIKLTDFGLAKELSSDgdrtytfcgtPEY------ 159
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1064 rlplkwMAPETIFDRVYTIQSDVWSFGVLLWEIFSlGASPYPGVKIDEEFCRRLKEGTRMraPDYTTPEMYQTMLDCWHE 1143
Cdd:cd05123  160 ------LAPEVLLGKGYGKAVDWWSLGVLLYEMLT-GKPPFYAENRKEIYEKILKSPLKF--PEYVSPEAKSLISGLLQK 230
                        330
                 ....*....|....*..
gi 27777648 1144 DPNQR---PSFSELVEH 1157
Cdd:cd05123  231 DPTKRlgsGGAEEIKAH 247
SPS1 COG0515
Serine/threonine protein kinase [Signal transduction mechanisms];
829-1167 1.17e-19

Serine/threonine protein kinase [Signal transduction mechanisms];


Pssm-ID: 440281 [Multi-domain]  Cd Length: 482  Bit Score: 93.92  E-value: 1.17e-19
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  829 RDRLKLGKPLGRGAFGQVIEADAFGIDKTatcktVAVKMLKEGATHSEH--RALMSELKILIHIGHHlNVVNLLGACTKP 906
Cdd:COG0515    6 LGRYRILRLLGRGGMGVVYLARDLRLGRP-----VALKVLRPELAADPEarERFRREARALARLNHP-NIVRVYDVGEED 79
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  907 GGPLMViVEFCKFGNLSTYLRGKrnefvpykskgarfrqgkdyvGELSVDLKRRLdsitssqssassgfveekslsdvee 986
Cdd:COG0515   80 GRPYLV-MEYVEGESLADLLRRR---------------------GPLPPAEALRI------------------------- 112
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  987 eeaseelykdfltlehLIcysfQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIyKDPDYVRKGDARLP 1066
Cdd:COG0515  113 ----------------LA----QLAEALAAAHAAGIVHRDIKPANILLTPDGRVKLIDFGIARAL-GGATLTQTGTVVGT 171
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1067 LKWMAPETIFDRVYTIQSDVWSFGVLLWEIFSlGASPYPGVKIDEEFCRRL-KEGTRMRAPDYTTPEMYQTMLD-CWHED 1144
Cdd:COG0515  172 PGYMAPEQARGEPVDPRSDVYSLGVTLYELLT-GRPPFDGDSPAELLRAHLrEPPPPPSELRPDLPPALDAIVLrALAKD 250
                        330       340
                 ....*....|....*....|....
gi 27777648 1145 PNQRP-SFSELVEHLGNLLQANAQ 1167
Cdd:COG0515  251 PEERYqSAAELAAALRAVLRSLAA 274
STKc_myosinIII_N_like cd06608
N-terminal Catalytic domain of Class III myosin-like Serine/Threonine Kinases; STKs catalyze ...
828-1157 4.90e-19

N-terminal Catalytic domain of Class III myosin-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Class III myosins are motor proteins with an N-terminal kinase catalytic domain and a C-terminal actin-binding motor domain. Class III myosins are present in the photoreceptors of invertebrates and vertebrates and in the auditory hair cells of mammals. The kinase domain of myosin III can phosphorylate several cytoskeletal proteins, conventional myosin regulatory light chains, and can autophosphorylate the C-terminal motor domain. Myosin III may play an important role in maintaining the structural integrity of photoreceptor cell microvilli. It may also function as a cargo carrier during light-dependent translocation, in photoreceptor cells, of proteins such as transducin and arrestin. The Drosophila class III myosin, called NinaC (Neither inactivation nor afterpotential protein C), is critical in normal adaptation and termination of photoresponse. Vertebrates contain two isoforms of class III myosin, IIIA and IIIB. This subfamily also includes mammalian NIK-like embryo-specific kinase (NESK), Traf2- and Nck-interacting kinase (TNIK), and mitogen-activated protein kinase (MAPK) kinase kinase kinase 4/6. MAP4Ks are involved in some MAPK signaling pathways by activating a MAPK kinase kinase. MAPK signaling cascades are important in mediating cellular responses to extracellular signals. The class III myosin-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270785 [Multi-domain]  Cd Length: 275  Bit Score: 88.90  E-value: 4.90e-19
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  828 PRDRLKLGKPLGRGAFGQVIEADafgidKTATCKTVAVKMLKegATHSEHRALMSELKILIHIGHHLNVVNLLGACTKPG 907
Cdd:cd06608    4 PAGIFELVEVIGEGTYGKVYKAR-----HKKTGQLAAIKIMD--IIEDEEEEIKLEINILRKFSNHPNIATFYGAFIKKD 76
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  908 GP-----LMVIVEFCKFGNLSTYLRGKRnefvpykskgarfrqgkdyvgelsvDLKRRLDsitssqssassgfveeksls 982
Cdd:cd06608   77 PPggddqLWLVMEYCGGGSVTDLVKGLR-------------------------KKGKRLK-------------------- 111
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  983 dveeeeaseelykdfltlEHLICY-SFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIykDPDYVRKG 1061
Cdd:cd06608  112 ------------------EEWIAYiLRETLRGLAYLHENKVIHRDIKGQNILLTEEAEVKLVDFGVSAQL--DSTLGRRN 171
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1062 DARLPLKWMAPETI-----FDRVYTIQSDVWSFGVLLWEIfSLGASPYpgvkIDEEFCRRLKEGTRMRAPDYTTPEMYQT 1136
Cdd:cd06608  172 TFIGTPYWMAPEVIacdqqPDASYDARCDVWSLGITAIEL-ADGKPPL----CDMHPMRALFKIPRNPPPTLKSPEKWSK 246
                        330       340
                 ....*....|....*....|....*.
gi 27777648 1137 MLD-----CWHEDPNQRPSFSELVEH 1157
Cdd:cd06608  247 EFNdfiseCLIKNYEQRPFTEELLEH 272
STKc_A-Raf cd14150
Catalytic domain of the Serine/Threonine Kinase, A-Raf (Rapidly Accelerated Fibrosarcoma) ...
836-1155 5.93e-19

Catalytic domain of the Serine/Threonine Kinase, A-Raf (Rapidly Accelerated Fibrosarcoma) kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. A-Raf cooperates with C-Raf in regulating ERK transient phosphorylation that is associated with cyclin D expression and cell cycle progression. Mice deficient in A-Raf are born alive but show neurological and intestinal defects. A-Raf demonstrates low kinase activity to MEK, compared with B- and C-Raf, and may also have alternative functions other than in the ERK signaling cascade. It regulates the M2 type pyruvate kinase, a key glycolytic enzyme. It also plays a role in endocytic membrane trafficking. A-Raf is a mitogen-activated protein kinase kinase kinase (MAP3K, MKKK, MAPKKK), which phosphorylates and activates MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. It functions in the linear Ras-Raf-MEK-ERK pathway that regulates many cellular processes including cycle regulation, proliferation, differentiation, survival, and apoptosis. The A-Raf subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271052 [Multi-domain]  Cd Length: 265  Bit Score: 88.54  E-value: 5.93e-19
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  836 KPLGRGAFGQVIEADAFGidktatckTVAVKMLKEGATHSEH-RALMSELKILIHIgHHLNVVNLLGACTKPGgpLMVIV 914
Cdd:cd14150    6 KRIGTGSFGTVFRGKWHG--------DVAVKILKVTEPTPEQlQAFKNEMQVLRKT-RHVNILLFMGFMTRPN--FAIIT 74
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  915 EFCKFGNLSTYLrgkrnefvpykskgarfrqgkdYVGELSVDLKRRLDSITssqssassgfveekslsdveeeeaseely 994
Cdd:cd14150   75 QWCEGSSLYRHL----------------------HVTETRFDTMQLIDVAR----------------------------- 103
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  995 kdfltlehlicysfQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLA--RDIYKDPDYVRKGDARlpLKWMAP 1072
Cdd:cd14150  104 --------------QTAQGMDYLHAKNIIHRDLKSNNIFLHEGLTVKIGDFGLAtvKTRWSGSQQVEQPSGS--ILWMAP 167
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1073 ETIF---DRVYTIQSDVWSFGVLLWEIFSlGASPYPGVKIDEEFCRRLKEGtrmrapdYTTPE-----------MYQTML 1138
Cdd:cd14150  168 EVIRmqdTNPYSFQSDVYAYGVVLYELMS-GTLPYSNINNRDQIIFMVGRG-------YLSPDlsklssncpkaMKRLLI 239
                        330
                 ....*....|....*..
gi 27777648 1139 DCWHEDPNQRPSFSELV 1155
Cdd:cd14150  240 DCLKFKREERPLFPQIL 256
PKc_MAPKK cd06605
Catalytic domain of the dual-specificity Protein Kinase, Mitogen-Activated Protein Kinase ...
1007-1157 7.14e-19

Catalytic domain of the dual-specificity Protein Kinase, Mitogen-Activated Protein Kinase Kinase; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. MAPKKs are dual-specificity PKs that phosphorylate their downstream targets, MAPKs, at specific threonine and tyrosine residues. The MAPK signaling pathways are important mediators of cellular responses to extracellular signals. The pathways involve a triple kinase core cascade comprising the MAPK, which is phosphorylated and activated by a MAPK kinase (MAPKK or MKK or MAP2K), which itself is phosphorylated and activated by a MAPKK kinase (MAPKKK or MKKK or MAP3K). There are three MAPK subfamilies: extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38. In mammalian cells, there are seven MAPKKs (named MKK1-7) and 20 MAPKKKs. Each MAPK subfamily can be activated by at least two cognate MAPKKs and by multiple MAPKKKs. The MAPKK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270782 [Multi-domain]  Cd Length: 265  Bit Score: 88.17  E-value: 7.14e-19
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1007 SFQVAKGMEFLAS-RKCIHRDLAARNILLSEKNVVKICDFG----LARDIYKdpDYVrkGDArlplKWMAPETIFDRVYT 1081
Cdd:cd06605  105 AVAVVKGLIYLHEkHKIIHRDVKPSNILVNSRGQVKLCDFGvsgqLVDSLAK--TFV--GTR----SYMAPERISGGKYT 176
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1082 IQSDVWSFGVLLWEIfSLGASPYPGVKIDE-----EFCRRLKEGTRMRAPDYTTPEMYQTMLD-CWHEDPNQRPSFSELV 1155
Cdd:cd06605  177 VKSDIWSLGLSLVEL-ATGRFPYPPPNAKPsmmifELLSYIVDEPPPLLPSGKFSPDFQDFVSqCLQKDPTERPSYKELM 255

                 ..
gi 27777648 1156 EH 1157
Cdd:cd06605  256 EH 257
I-set pfam07679
Immunoglobulin I-set domain;
665-742 1.02e-18

Immunoglobulin I-set domain;


Pssm-ID: 400151 [Multi-domain]  Cd Length: 90  Bit Score: 82.31  E-value: 1.02e-18
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648    665 PMITGNLENQTTTIGETIEVTCPASGNPTPHITWFKDNETLVEDSGIVLR--DGNRNLTIRRVRKEDGGLYTCQACNVLG 742
Cdd:pfam07679    1 PKFTQKPKDVEVQEGESARFTCTVTGTPDPEVSWFKDGQPLRSSDRFKVTyeGGTYTLTISNVQPDDSGKYTCVATNSAG 80
STKc_RIP1 cd14027
Catalytic domain of the Serine/Threonine kinase, Receptor Interacting Protein 1; STKs catalyze ...
1009-1156 1.76e-18

Catalytic domain of the Serine/Threonine kinase, Receptor Interacting Protein 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. RIP1 harbors a C-terminal Death domain (DD), which binds death receptors (DRs) including TNF receptor 1, Fas, TNF-related apoptosis-inducing ligand receptor 1 (TRAILR1), and TRAILR2. It also interacts with other DD-containing adaptor proteins such as TRADD and FADD. RIP1 can also recruit other kinases including MEKK1, MEKK3, and RIP3 through an intermediate domain (ID) that bears a RIP homotypic interaction motif (RHIM). RIP1 plays a crucial role in determining a cell's fate, between survival or death, following exposure to stress signals. It is important in the signaling of NF-kappaB and MAPKs, and it links DR-associated signaling to reactive oxygen species (ROS) production. Abnormal RIP1 function may result in ROS accummulation affecting inflammatory responses, innate immunity, stress responses, and cell survival. RIP kinases serve as essential sensors of cellular stress. The RIP1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270929 [Multi-domain]  Cd Length: 267  Bit Score: 87.17  E-value: 1.76e-18
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1009 QVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARdiYKDPDYVRKGDARL-------------PLKWMAPETI 1075
Cdd:cd14027   98 EIIEGMAYLHGKGVIHKDLKPENILVDNDFHIKIADLGLAS--FKMWSKLTKEEHNEqrevdgtakknagTLYYMAPEHL 175
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1076 FD--RVYTIQSDVWSFGVLLWEIFSlGASPYPGVKIDEEFCRRLKEGTR---MRAPDYTTPEMYQTMLDCWHEDPNQRPS 1150
Cdd:cd14027  176 NDvnAKPTEKSDVYSFAIVLWAIFA-NKEPYENAINEDQIIMCIKSGNRpdvDDITEYCPREIIDLMKLCWEANPEARPT 254

                 ....*.
gi 27777648 1151 FSELVE 1156
Cdd:cd14027  255 FPGIEE 260
STKc_Nek2 cd08217
Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase ...
1018-1157 2.09e-18

Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The Nek2 subfamily includes Aspergillus nidulans NIMA kinase, the founding member of the Nek family, which was identified in a screen for cell cycle mutants prevented from entering mitosis. NIMA is essential for mitotic entry and progression through mitosis, and its degradation is essential for mitotic exit. NIMA is involved in nuclear membrane fission. Vertebrate Nek2 is a cell cycle-regulated STK, localized in centrosomes and kinetochores, that regulates centrosome splitting at the G2/M phase. It also interacts with other mitotic kinases such as Polo-like kinase 1 and may play a role in spindle checkpoint. An increase in the expression of the human NEK2 gene is strongly associated with the progression of non-Hodgkin lymphoma. Nek2 is one in a family of 11 different Neks (Nek1-11) that are involved in cell cycle control. It The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270857 [Multi-domain]  Cd Length: 265  Bit Score: 86.83  E-value: 2.09e-18
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1018 ASRKCIHRDLAARNILLSEKNVVKICDFGLARDIYKD----------PDYvrkgdarlplkwMAPETIFDRVYTIQSDVW 1087
Cdd:cd08217  127 GGGKILHRDLKPANIFLDSDNNVKLGDFGLARVLSHDssfaktyvgtPYY------------MSPELLNEQSYDEKSDIW 194
                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1088 SFGVLLWEIFSLgASPYPGvKIDEEFCRRLKEGTRMRAPDYTTPEMYQTMLDCWHEDPNQRPSFSELVEH 1157
Cdd:cd08217  195 SLGCLIYELCAL-HPPFQA-ANQLELAKKIKEGKFPRIPSRYSSELNEVIKSMLNVDPDKRPSVEELLQL 262
PTK_Jak_rpt1 cd05037
Pseudokinase (repeat 1) domain of the Protein Tyrosine Kinases, Janus kinases; The Jak ...
1009-1159 2.46e-18

Pseudokinase (repeat 1) domain of the Protein Tyrosine Kinases, Janus kinases; The Jak subfamily is composed of Jak1, Jak2, Jak3, TYK2, and similar proteins. They are cytoplasmic (or nonreceptor) PTKs containing an N-terminal FERM domain, followed by a Src homology 2 (SH2) domain, a pseudokinase domain, and a C-terminal catalytic tyr kinase domain. The pseudokinase domain shows similarity to tyr kinases but lacks crucial residues for catalytic activity and ATP binding. It modulates the kinase activity of the C-terminal catalytic domain. In the case of Jak2, the presumed pseudokinase (repeat 1) domain exhibits dual-specificity kinase activity, phosphorylating two negative regulatory sites in Jak2: Ser523 and Tyr570. Most Jaks are expressed in a wide variety of tissues, except for Jak3, which is expressed only in hematopoietic cells. Jaks are crucial for cytokine receptor signaling. They are activated by autophosphorylation upon cytokine-induced receptor aggregation, and subsequently trigger downstream signaling events such as the phosphorylation of signal transducers and activators of transcription (STATs). Jaks are also involved in regulating the surface expression of some cytokine receptors. The Jak-STAT pathway is involved in many biological processes including hematopoiesis, immunoregulation, host defense, fertility, lactation, growth, and embryogenesis. The Jak subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270633 [Multi-domain]  Cd Length: 259  Bit Score: 86.38  E-value: 2.46e-18
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1009 QVAKGMEFLASRKCIHRDLAARNILLSEKNV------VKICDFGLARDIykdpdyVRKGDARLPLKWMAPETIFD--RVY 1080
Cdd:cd05037  110 QLASALHYLEDKKLIHGNVRGRNILLAREGLdgyppfIKLSDPGVPITV------LSREERVDRIPWIAPECLRNlqANL 183
                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 27777648 1081 TIQSDVWSFGVLLWEIFSLGASPYPGVKIDEEFcRRLKEGTRMRAPDYttPEMYQTMLDCWHEDPNQRPSFSELVEHLG 1159
Cdd:cd05037  184 TIAADKWSFGTTLWEICSGGEEPLSALSSQEKL-QFYEDQHQLPAPDC--AELAELIMQCWTYEPTKRPSFRAILRDLN 259
PK_GC cd13992
Pseudokinase domain of membrane Guanylate Cyclase receptors; The pseudokinase domain shows ...
1010-1151 2.96e-18

Pseudokinase domain of membrane Guanylate Cyclase receptors; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. Membrane (or particulate) GCs consist of an extracellular ligand-binding domain, a single transmembrane region, and an intracellular tail that contains a PK-like domain, an amphiphatic region and a catalytic GC domain that catalyzes the conversion of GTP into cGMP and pyrophosphate. Membrane GCs act as receptors that transduce an extracellular signal to the intracellular production of cGMP, which has been implicated in many processes including cell proliferation, phototransduction, and muscle contractility, through its downstream effectors such as PKG. The PK-like domain of GCs lack a critical aspartate involved in ATP binding and does not exhibit kinase activity. It functions as a negative regulator of the catalytic GC domain and may also act as a docking site for interacting proteins such as GC-activating proteins. The GC subfamily is part of a larger superfamily that includes the catalytic domains of protein serine/threonine kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270894 [Multi-domain]  Cd Length: 268  Bit Score: 86.29  E-value: 2.96e-18
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1010 VAKGMEFL-ASRKCIHRDLAARNILLSEKNVVKICDFGLARDIYKDPDYVRKGDARLP-LKWMAPETIFDRVY----TIQ 1083
Cdd:cd13992  106 IVKGMNYLhSSSIGYHGRLKSSNCLVDSRWVVKLTDFGLRNLLEEQTNHQLDEDAQHKkLLWTAPELLRGSLLevrgTQK 185
                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 27777648 1084 SDVWSFGVLLWEIFsLGASPYPGVKIDEEFCRRLKEGTRMRAPDY------TTPEMYQTMLDCWHEDPNQRPSF 1151
Cdd:cd13992  186 GDVYSFAIILYEIL-FRSDPFALEREVAIVEKVISGGNKPFRPELavlldeFPPRLVLLVKQCWAENPEKRPSF 258
STKc_Nek cd08215
Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase; ...
838-1154 4.00e-18

Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The Nek family is composed of 11 different mammalian members (Nek1-11) with similarity to the catalytic domain of Aspergillus nidulans NIMA kinase, the founding member of the Nek family, which was identified in a screen for cell cycle mutants that were prevented from entering mitosis. Neks contain a conserved N-terminal catalytic domain and a more divergent C-terminal regulatory region of various sizes and structures. They are involved in the regulation of downstream processes following the activation of Cdc2, and many of their functions are cell cycle-related. They play critical roles in microtubule dynamics during ciliogenesis and mitosis. The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270855 [Multi-domain]  Cd Length: 258  Bit Score: 85.59  E-value: 4.00e-18
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  838 LGRGAFGQVIEADAFGIDKTATCKTVAVKMLKEgathSEHRALMSELKILIHIgHHLNVVNLLGACTKpGGPLMVIVEFC 917
Cdd:cd08215    8 IGKGSFGSAYLVRRKSDGKLYVLKEIDLSNMSE----KEREEALNEVKLLSKL-KHPNIVKYYESFEE-NGKLCIVMEYA 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  918 KFGNLSTYLRGKRNEFVPYKskgarfrqgkdyvgelsvdlkrrldsitssqssassgfveekslsdveeeeaseelykdf 997
Cdd:cd08215   82 DGGDLAQKIKKQKKKGQPFP------------------------------------------------------------ 101
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  998 ltlEHLICYSF-QVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARdIYKD-----------PDYvrkgdarl 1065
Cdd:cd08215  102 ---EEQILDWFvQICLALKYLHSRKILHRDLKTQNIFLTKDGVVKLGDFGISK-VLESttdlaktvvgtPYY-------- 169
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1066 plkwMAPETIFDRVYTIQSDVWSFGVLLWEIFSL----GASPYPGVkideefCRRLKEGTRMRAPDYTTPEMYQTMLDCW 1141
Cdd:cd08215  170 ----LSPELCENKPYNYKSDIWALGCVLYELCTLkhpfEANNLPAL------VYKIVKGQYPPIPSQYSSELRDLVNSML 239
                        330
                 ....*....|...
gi 27777648 1142 HEDPNQRPSFSEL 1154
Cdd:cd08215  240 QKDPEKRPSANEI 252
STKc_CDKL2_3 cd07846
Catalytic domain of the Serine/Threonine Kinases, Cyclin-Dependent protein Kinase Like 2 and 3; ...
1006-1157 4.63e-18

Catalytic domain of the Serine/Threonine Kinases, Cyclin-Dependent protein Kinase Like 2 and 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDKL2, also called p56 KKIAMRE, is expressed in testis, kidney, lung, and brain. It functions mainly in mature neurons and plays an important role in learning and memory. Inactivation of CDKL3, also called NKIAMRE (NKIATRE in rat), by translocation is associated with mild mental retardation. It has been reported that CDKL3 is lost in leukemic cells having a chromosome arm 5q deletion, and may contribute to the transformed phenotype. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDKL2/3 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270836 [Multi-domain]  Cd Length: 286  Bit Score: 86.32  E-value: 4.63e-18
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1006 YSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLAR------DIYKdpDYVrkgdarlPLKWM-APETIF-D 1077
Cdd:cd07846  105 YLFQILRGIDFCHSHNIIHRDIKPENILVSQSGVVKLCDFGFARtlaapgEVYT--DYV-------ATRWYrAPELLVgD 175
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1078 RVYTIQSDVWSFGVLLWEIFSlGASPYPG----------VKIDEEFCRRLKE-------GTRMRAPDYTTPE-------- 1132
Cdd:cd07846  176 TKYGKAVDVWAVGCLVTEMLT-GEPLFPGdsdidqlyhiIKCLGNLIPRHQElfqknplFAGVRLPEVKEVEplerrypk 254
                        170       180
                 ....*....|....*....|....*....
gi 27777648 1133 ----MYQTMLDCWHEDPNQRPSFSELVEH 1157
Cdd:cd07846  255 lsgvVIDLAKKCLHIDPDKRPSCSELLHH 283
Ig_3 pfam13927
Immunoglobulin domain; This family contains immunoglobulin-like domains.
665-737 9.93e-18

Immunoglobulin domain; This family contains immunoglobulin-like domains.


Pssm-ID: 464046 [Multi-domain]  Cd Length: 78  Bit Score: 79.15  E-value: 9.93e-18
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 27777648    665 PMITGNLENQTTTIGETIEVTCPASGNPTPHITWFKDNETLVE--DSGIVLRDGNRNLTIRRVRKEDGGLYTCQA 737
Cdd:pfam13927    2 PVITVSPSSVTVREGETVTLTCEATGSPPPTITWYKNGEPISSgsTRSRSLSGSNSTLTISNVTRSDAGTYTCVA 76
IG_like smart00410
Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.
672-748 1.02e-17

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.


Pssm-ID: 214653 [Multi-domain]  Cd Length: 85  Bit Score: 79.09  E-value: 1.02e-17
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648     672 ENQTTTIGETIEVTCPASGNPTPHITWFKDNETLVEDSGIVLRDGNRN---LTIRRVRKEDGGLYTCQACNVLGCARAET 748
Cdd:smart00410    2 PSVTVKEGESVTLSCEASGSPPPEVTWYKQGGKLLAESGRFSVSRSGStstLTISNVTPEDSGTYTCAATNSSGSASSGT 81
STKc_STK36 cd14002
Catalytic domain of Serine/Threonine Kinase 36; STKs catalyze the transfer of the ...
830-1157 1.15e-17

Catalytic domain of Serine/Threonine Kinase 36; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. STK36, also called Fused (or Fu) kinase, is involved in the Hedgehog signaling pathway. It is activated by the Smoothened (SMO) signal transducer, resulting in the stabilization of GLI transcription factors and the phosphorylation of SUFU to facilitate the nuclear accumulation of GLI. In Drosophila, Fused kinase is maternally required for proper segmentation during embryonic development and for the development of legs and wings during the larval stage. In mice, STK36 is not necessary for embryonic development, although mice deficient in STK36 display growth retardation postnatally. The STK36 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270904 [Multi-domain]  Cd Length: 253  Bit Score: 84.23  E-value: 1.15e-17
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  830 DRLKLGKPLGRGAFGQVIEADafgidKTATCKTVAVKML-KEGATHSEHRALMSELKILIHIgHHLNVVNLLGACTKPGg 908
Cdd:cd14002    1 ENYHVLELIGEGSFGKVYKGR-----RKYTGQVVALKFIpKRGKSEKELRNLRQEIEILRKL-NHPNIIEMLDSFETKK- 73
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  909 PLMVIVEFCKfGNLSTYLrgkrnefvpykskgarfrqgkDYVGELSVDLKRRldsitssqssassgfveekslsdveeee 988
Cdd:cd14002   74 EFVVVTEYAQ-GELFQIL---------------------EDDGTLPEEEVRS---------------------------- 103
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  989 aseelykdfltlehlICYsfQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIYKDPDYVR--KGDarlP 1066
Cdd:cd14002  104 ---------------IAK--QLVSALHYLHSNRIIHRDMKPQNILIGKGGVVKLCDFGFARAMSCNTLVLTsiKGT---P 163
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1067 LkWMAPETIFDRVYTIQSDVWSFGVLLWEIFsLGASPYPGVKIDEEFCRRLKEGTRMraPDYTTPE---MYQTMLDcwhE 1143
Cdd:cd14002  164 L-YMAPELVQEQPYDHTADLWSLGCILYELF-VGQPPFYTNSIYQLVQMIVKDPVKW--PSNMSPEfksFLQGLLN---K 236
                        330
                 ....*....|....
gi 27777648 1144 DPNQRPSFSELVEH 1157
Cdd:cd14002  237 DPSKRLSWPDLLEH 250
STKc_OSR1_SPAK cd06610
Catalytic domain of the Serine/Threonine Kinases, Oxidative stress response kinase and ...
1009-1157 1.19e-17

Catalytic domain of the Serine/Threonine Kinases, Oxidative stress response kinase and Ste20-related proline alanine-rich kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SPAK is also referred to as STK39 or PASK (proline-alanine-rich STE20-related kinase). OSR1 and SPAK regulate the activity of cation-chloride cotransporters through direct interaction and phosphorylation. They are also implicated in cytoskeletal rearrangement, cell differentiation, transformation and proliferation. OSR1 and SPAK contain a conserved C-terminal (CCT) domain, which recognizes a unique motif ([RK]FX[VI]) present in their activating kinases (WNK1/WNK4) and their substrates. The OSR1 and SPAK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270787 [Multi-domain]  Cd Length: 267  Bit Score: 84.72  E-value: 1.19e-17
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1009 QVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIYKDPD---YVRKGDARLPLkWMAPETIF-DRVYTIQS 1084
Cdd:cd06610  110 EVLKGLEYLHSNGQIHRDVKAGNILLGEDGSVKIADFGVSASLATGGDrtrKVRKTFVGTPC-WMAPEVMEqVRGYDFKA 188
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1085 DVWSFGVLLWEIfSLGASPY---PGVKIdeeFCRRLKEGtrmrAPDYTTPE-------MYQTMLD-CWHEDPNQRPSFSE 1153
Cdd:cd06610  189 DIWSFGITAIEL-ATGAAPYskyPPMKV---LMLTLQND----PPSLETGAdykkyskSFRKMISlCLQKDPSKRPTAEE 260

                 ....
gi 27777648 1154 LVEH 1157
Cdd:cd06610  261 LLKH 264
STKc_Bck1_like cd06629
Catalytic domain of the Serine/Threonine Kinases, fungal Bck1-like Mitogen-Activated Protein ...
1009-1157 1.71e-17

Catalytic domain of the Serine/Threonine Kinases, fungal Bck1-like Mitogen-Activated Protein Kinase Kinase Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Members of this group include the MAPKKKs Saccharomyces cerevisiae Bck1 and Schizosaccharomyces pombe Mkh1, and related proteins. Budding yeast Bck1 is part of the cell integrity MAPK pathway, which is activated by stresses and aggressions to the cell wall. The MAPKKK Bck1, MAPKKs Mkk1 and Mkk2, and the MAPK Slt2 make up the cascade that is important in the maintenance of cell wall homeostasis. Fission yeast Mkh1 is involved in MAPK cascades regulating cell morphology, cell wall integrity, salt resistance, and filamentous growth in response to stress. MAPKKKs phosphorylate and activate MAPK kinases, which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. The Bck1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270799 [Multi-domain]  Cd Length: 270  Bit Score: 83.97  E-value: 1.71e-17
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1009 QVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLAR---DIY-KDPDYVRKGDarlpLKWMAPETI--FDRVYTI 1082
Cdd:cd06629  116 QILDGLAYLHSKGILHRDLKADNILVDLEGICKISDFGISKksdDIYgNNGATSMQGS----VFWMAPEVIhsQGQGYSA 191
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1083 QSDVWSFGVLLWEIFSlGASPYPGvkiDEEFCRRLKEGTRMRAPD-----YTTPEMYQTMLDCWHEDPNQRPSFSELVEH 1157
Cdd:cd06629  192 KVDIWSLGCVVLEMLA-GRRPWSD---DEAIAAMFKLGNKRSAPPvpedvNLSPEALDFLNACFAIDPRDRPTAAELLSH 267
STKc_MAPK cd07834
Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein Kinase; STKs ...
831-1097 1.86e-17

Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAPKs serve as important mediators of cellular responses to extracellular signals. They control critical cellular functions including differentiation, proliferation, migration, and apoptosis. They are also implicated in the pathogenesis of many diseases including multiple types of cancer, stroke, diabetes, and chronic inflammation. Typical MAPK pathways involve a triple kinase core cascade comprising of the MAPK, which is phosphorylated and activated by a MAPK kinase (MAP2K or MKK), which itself is phosphorylated and activated by a MAPK kinase kinase (MAP3K or MKKK). Each cascade is activated either by a small GTP-binding protein or by an adaptor protein, which transmits the signal either directly to a MAP3K to start the triple kinase core cascade or indirectly through a mediator kinase, a MAP4K. There are three typical MAPK subfamilies: Extracellular signal-Regulated Kinase (ERK), c-Jun N-terminal Kinase (JNK), and p38. Some MAPKs are atypical in that they are not regulated by MAP2Ks. These include MAPK4, MAPK6, NLK, and ERK7. The MAPK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270828 [Multi-domain]  Cd Length: 329  Bit Score: 85.27  E-value: 1.86e-17
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  831 RLKLGKPLGRGAFGQVIEAdafgIDKTaTCKTVAVKMLKEGATHSEH--RALmSELKILIHIGHHlNVVNLLGactkpgg 908
Cdd:cd07834    1 RYELLKPIGSGAYGVVCSA----YDKR-TGRKVAIKKISNVFDDLIDakRIL-REIKILRHLKHE-NIIGLLD------- 66
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  909 pLMVIVEFCKFGNLstYLrgkrnefvpykskgarfrqgkdyVGEL-SVDLKRRLdsitssqssassgfveeKSlsdveee 987
Cdd:cd07834   67 -ILRPPSPEEFNDV--YI-----------------------VTELmETDLHKVI-----------------KS------- 96
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  988 easeelyKDFLTLEHlICY-SFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIYKDP------DYV-- 1058
Cdd:cd07834   97 -------PQPLTDDH-IQYfLYQILRGLKYLHSAGVIHRDLKPSNILVNSNCDLKICDFGLARGVDPDEdkgfltEYVvt 168
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|..
gi 27777648 1059 RkgdarlplkWM-APETI--FDRvYTIQSDVWSFGVLLWEIF 1097
Cdd:cd07834  169 R---------WYrAPELLlsSKK-YTKAIDIWSVGCIFAELL 200
PKc_PBS2_like cd06622
Catalytic domain of fungal PBS2-like dual-specificity Mitogen-Activated Protein Kinase Kinases; ...
1007-1157 2.50e-17

Catalytic domain of fungal PBS2-like dual-specificity Mitogen-Activated Protein Kinase Kinases; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. Members of this group include the MAPKKs Polymyxin B resistance protein 2 (PBS2) from Saccharomyces cerevisiae, Wis1 from Schizosaccharomyces pombe, and related proteins. PBS2 and Wis1 are components of stress-activated MAPK cascades in budding and fission yeast, respectively. PBS2 is the specific activator of the MAPK Hog1, which plays a central role in the response of budding yeast to stress including exposure to arsenite and hyperosmotic environments. Wis1 phosphorylates and activates the MAPK Sty1 (also called Spc1 or Phh1), which stimulates a transcriptional response to a wide range of cellular insults through the bZip transcription factors Atf1, Pcr1, and Pap1. The PBS2 subfamily is part of a larger superfamily that includes the catalytic domains of STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 132953 [Multi-domain]  Cd Length: 286  Bit Score: 84.13  E-value: 2.50e-17
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1007 SFQVAKGMEFLASR-KCIHRDLAARNILLSEKNVVKICDFGLARDIYKDPDYVRKGDArlplKWMAPETI-----FDR-V 1079
Cdd:cd06622  108 TYAVVKGLKFLKEEhNIIHRDVKPTNVLVNGNGQVKLCDFGVSGNLVASLAKTNIGCQ----SYMAPERIksggpNQNpT 183
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1080 YTIQSDVWSFGVLLWEIfSLGASPYPGVKIDEEFCR--RLKEGTRMRAPDYTTPEMYQTMLDCWHEDPNQRPSFSELVEH 1157
Cdd:cd06622  184 YTVQSDVWSLGLSILEM-ALGRYPYPPETYANIFAQlsAIVDGDPPTLPSGYSDDAQDFVAKCLNKIPNRRPTYAQLLEH 262
PKc_Wee1_like cd13997
Catalytic domain of the Wee1-like Protein Kinases; PKs catalyze the transfer of the ...
838-1157 3.09e-17

Catalytic domain of the Wee1-like Protein Kinases; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine or tyrosine residues on protein substrates. This subfamily is composed of the dual-specificity kinase Myt1, the protein tyrosine kinase Wee1, and similar proteins. These proteins are cell cycle checkpoint kinases that are involved in the regulation of cyclin-dependent kinase CDK1, the master engine for mitosis. CDK1 is kept inactivated through phosphorylation of N-terminal thr (T14 by Myt1) and tyr (Y15 by Myt1 and Wee1) residues. Mitosis progression is ensured through activation of CDK1 by dephoshorylation and inactivation of Myt1/Wee1. The Wee1-like subfamily is part of a larger superfamily that includes the catalytic domains of other protein serine/threonine PKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270899 [Multi-domain]  Cd Length: 252  Bit Score: 82.82  E-value: 3.09e-17
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  838 LGRGAFGQVIEAdafgIDKTATCKTVAVKMLKEGATHSEHRALMSELKILIHIGHHLNVVNLLGACTKpGGPLMVIVEFC 917
Cdd:cd13997    8 IGSGSFSEVFKV----RSKVDGCLYAVKKSKKPFRGPKERARALREVEAHAALGQHPNIVRYYSSWEE-GGHLYIQMELC 82
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  918 KFGNLSTYLrgkrNEFVPykskgarfrqgKDYVGELSVdlkrrldsitssqssassgfveekslsdveeeeaseelyKDF 997
Cdd:cd13997   83 ENGSLQDAL----EELSP-----------ISKLSEAEV---------------------------------------WDL 108
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  998 LTlehlicysfQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIYKDPDyVRKGDARlplkWMAPETIFD 1077
Cdd:cd13997  109 LL---------QVALGLAFIHSKGIVHLDIKPDNIFISNKGTCKIGDFGLATRLETSGD-VEEGDSR----YLAPELLNE 174
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1078 -RVYTIQSDVWSFGVLLWEIfsLGASPYPGvkiDEEFCRRLKEGtrmRAPDYTTP----EMYQTMLDCWHEDPNQRPSFS 1152
Cdd:cd13997  175 nYTHLPKADIFSLGVTVYEA--ATGEPLPR---NGQQWQQLRQG---KLPLPPGLvlsqELTRLLKVMLDPDPTRRPTAD 246

                 ....*
gi 27777648 1153 ELVEH 1157
Cdd:cd13997  247 QLLAH 251
STKc_CDKL cd07833
Catalytic domain of Cyclin-Dependent protein Kinase Like Serine/Threonine Kinases; STKs ...
838-1157 4.15e-17

Catalytic domain of Cyclin-Dependent protein Kinase Like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of CDKL1-5 and similar proteins. Some CDKLs, like CDKL1 and CDKL3, may be implicated in transformation and others, like CDKL3 and CDKL5, are associated with mental retardation when impaired. CDKL2 plays a role in learning and memory. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDKL subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270827 [Multi-domain]  Cd Length: 288  Bit Score: 83.52  E-value: 4.15e-17
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  838 LGRGAFGQVIEADafgiDKtATCKTVAVKMLKEGATHSE-HRALMSELKILIHIgHHLNVVNLLGACtKPGGPLMVIVEF 916
Cdd:cd07833    9 VGEGAYGVVLKCR----NK-ATGEIVAIKKFKESEDDEDvKKTALREVKVLRQL-RHENIVNLKEAF-RRKGRLYLVFEY 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  917 CKfGNLSTYLrgkrnefvpykskgarfrqgKDYVGELSVDLKRRldsitssqssassgfveekslsdveeeeaseelykd 996
Cdd:cd07833   82 VE-RTLLELL--------------------EASPGGLPPDAVRS------------------------------------ 104
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  997 fltlehlicYSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIYKDP-----DYVRKgdarlplKWM- 1070
Cdd:cd07833  105 ---------YIWQLLQAIAYCHSHNIIHRDIKPENILVSESGVLKLCDFGFARALTARPaspltDYVAT-------RWYr 168
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1071 APETIF-DRVYTIQSDVWSFGVLLWEIFSlGASPYPG-VKIDEEFCRRLKEG----------------TRMRAPDYTTPE 1132
Cdd:cd07833  169 APELLVgDTNYGKPVDVWAIGCIMAELLD-GEPLFPGdSDIDQLYLIQKCLGplppshqelfssnprfAGVAFPEPSQPE 247
                        330       340       350
                 ....*....|....*....|....*....|....*...
gi 27777648 1133 ----MYQTMLD---------CWHEDPNQRPSFSELVEH 1157
Cdd:cd07833  248 slerRYPGKVSspaldflkaCLRMDPKERLTCDELLQH 285
PKc_MKK3_6 cd06617
Catalytic domain of the dual-specificity Protein Kinases, Mitogen-activated protein Kinase ...
1007-1157 5.16e-17

Catalytic domain of the dual-specificity Protein Kinases, Mitogen-activated protein Kinase Kinases 3 and 6; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. MKK3 and MKK6 are dual-specificity PKs that phosphorylate and activate their downstream target, p38 MAPK, on specific threonine and tyrosine residues. MKK3/6 play roles in the regulation of cell cycle progression, cytokine- and stress-induced apoptosis, oncogenic transformation, and adult tissue regeneration. In addition, MKK6 plays a critical role in osteoclast survival in inflammatory disease while MKK3 is associated with tumor invasion, progression, and poor patient survival in glioma. The MKK3/6 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173729 [Multi-domain]  Cd Length: 283  Bit Score: 82.86  E-value: 5.16e-17
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1007 SFQVAKGMEFLASR-KCIHRDLAARNILLSEKNVVKICDFG----LARDIYKDPDYVRKgdarlplKWMAPETI----FD 1077
Cdd:cd06617  109 AVSIVKALEYLHSKlSVIHRDVKPSNVLINRNGQVKLCDFGisgyLVDSVAKTIDAGCK-------PYMAPERInpelNQ 181
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1078 RVYTIQSDVWSFGVLLWEIfSLGASPYPGVKIDEEFCRRLKEGTRMRAPDYTTPEMYQTMLDCW-HEDPNQRPSFSELVE 1156
Cdd:cd06617  182 KGYDVKSDVWSLGITMIEL-ATGRFPYDSWKTPFQQLKQVVEEPSPQLPAEKFSPEFQDFVNKClKKNYKERPNYPELLQ 260

                 .
gi 27777648 1157 H 1157
Cdd:cd06617  261 H 261
PKc_TNNI3K cd14064
Catalytic domain of the Dual-specificity protein kinase, TNNI3-interacting kinase; ...
1007-1158 5.30e-17

Catalytic domain of the Dual-specificity protein kinase, TNNI3-interacting kinase; Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine as well as tyrosine residues on protein substrates. TNNI3K, also called cardiac ankyrin repeat kinase (CARK), is a cardiac-specific troponin I-interacting kinase that promotes cardiac myogenesis, improves cardiac performance, and protects the myocardium from ischemic injury. It contains N-terminal ankyrin repeats, a catalytic kinase domain, and a C-terminal serine-rich domain. TNNI3K exerts a disease-accelerating effect on cardiac dysfunction and reduced survival in mouse models of cardiomyopathy. The TNNI3K subfamily is part of a larger superfamily that includes the catalytic domains of other protein serine/threonine PKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270966 [Multi-domain]  Cd Length: 254  Bit Score: 82.19  E-value: 5.30e-17
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1007 SFQVAKGMEFL--ASRKCIHRDLAARNILLSEKNVVKICDFGLARDIYK-DPDYVRKGDARlpLKWMAPEtIFDRV--YT 1081
Cdd:cd14064   99 AVDVAKGMEYLhnLTQPIIHRDLNSHNILLYEDGHAVVADFGESRFLQSlDEDNMTKQPGN--LRWMAPE-VFTQCtrYS 175
                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 27777648 1082 IQSDVWSFGVLLWEIFSlGASPYPGVKIDEEFCRRLKEGTRMRAPdYTTPEMYQTML-DCWHEDPNQRPSFSELVEHL 1158
Cdd:cd14064  176 IKADVFSYALCLWELLT-GEIPFAHLKPAAAAADMAYHHIRPPIG-YSIPKPISSLLmRGWNAEPESRPSFVEIVALL 251
STKc_MST1_2 cd06612
Catalytic domain of the Serine/Threonine Kinases, Mammalian STe20-like protein kinase 1 and 2; ...
1003-1157 6.66e-17

Catalytic domain of the Serine/Threonine Kinases, Mammalian STe20-like protein kinase 1 and 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of MST1, MST2, and related proteins including Drosophila Hippo and Dictyostelium discoideum Krs1 (kinase responsive to stress 1). MST1/2 and Hippo are involved in a conserved pathway that governs cell contact inhibition, organ size control, and tumor development. MST1 activates the mitogen-activated protein kinases (MAPKs) p38 and c-Jun N-terminal kinase (JNK) through MKK7 and MEKK1 by acting as a MAPK kinase kinase kinase. Activation of JNK by MST1 leads to caspase activation and apoptosis. MST1 has also been implicated in cell proliferation and differentiation. Krs1 may regulate cell growth arrest and apoptosis in response to cellular stress. The MST1/2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 132943 [Multi-domain]  Cd Length: 256  Bit Score: 81.93  E-value: 6.66e-17
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1003 LICYsfQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLA---RDIYKDPDYVrkgdARLPLkWMAPETIFDRV 1079
Cdd:cd06612  103 AILY--QTLKGLEYLHSNKKIHRDIKAGNILLNEEGQAKLADFGVSgqlTDTMAKRNTV----IGTPF-WMAPEVIQEIG 175
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1080 YTIQSDVWSFGVLLWEIFSlGASPYPGVKIdeefCRRLKEGTRMRAPDYTTPEMYQTMLD-----CWHEDPNQRPSFSEL 1154
Cdd:cd06612  176 YNNKADIWSLGITAIEMAE-GKPPYSDIHP----MRAIFMIPNKPPPTLSDPEKWSPEFNdfvkkCLVKDPEERPSAIQL 250

                 ...
gi 27777648 1155 VEH 1157
Cdd:cd06612  251 LQH 253
STKc_CDK7 cd07841
Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 7; STKs ...
831-1095 7.81e-17

Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 7; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK7 plays essential roles in the cell cycle and in transcription. It associates with cyclin H and MAT1 and acts as a CDK-Activating Kinase (CAK) by phosphorylating and activating cell cycle CDKs (CDK1/2/4/6). In the brain, it activates CDK5. CDK7 is also a component of the general transcription factor TFIIH, which phosphorylates the C-terminal domain (CTD) of RNA polymerase II when it is bound with unphosphorylated DNA, as present in the pre-initiation complex. Following phosphorylation, the CTD dissociates from the DNA which allows transcription initiation. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK7 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270833 [Multi-domain]  Cd Length: 298  Bit Score: 82.62  E-value: 7.81e-17
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  831 RLKLGKPLGRGAFGQVIEAdafgIDKtATCKTVAVKMLKEG----ATHSEHRALMSELKILIHIgHHLNVVNLLGActkp 906
Cdd:cd07841    1 RYEKGKKLGEGTYAVVYKA----RDK-ETGRIVAIKKIKLGerkeAKDGINFTALREIKLLQEL-KHPNIIGLLDV---- 70
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  907 ggplmviveFCKFGNLSTYLrgkrnEFVPYkskgarfrqgkdyvgelsvDLKrrldsitssqssassGFVEEKSLsdvee 986
Cdd:cd07841   71 ---------FGHKSNINLVF-----EFMET-------------------DLE---------------KVIKDKSI----- 97
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  987 eeaseelykdFLTLEHLICYSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARdIYKDPDyvRKGDARLP 1066
Cdd:cd07841   98 ----------VLTPADIKSYMLMTLRGLEYLHSNWILHRDLKPNNLLIASDGVLKLADFGLAR-SFGSPN--RKMTHQVV 164
                        250       260       270
                 ....*....|....*....|....*....|.
gi 27777648 1067 LKWM-APETIFD-RVYTIQSDVWSFGVLLWE 1095
Cdd:cd07841  165 TRWYrAPELLFGaRHYGVGVDMWSVGCIFAE 195
STKc_CDK9_like cd07840
Catalytic domain of Cyclin-Dependent protein Kinase 9-like Serine/Threonine Kinases; STKs ...
838-1106 8.72e-17

Catalytic domain of Cyclin-Dependent protein Kinase 9-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of CDK9 and CDK12 from higher eukaryotes, yeast BUR1, C-type plant CDKs (CdkC), and similar proteins. CDK9, BUR1, and CdkC are functionally equivalent. They act as a kinase for the C-terminal domain of RNA polymerase II and participate in regulating mutliple steps of gene expression including transcription elongation and RNA processing. CDK9 and CdkC associate with T-type cyclins while BUR1 associates with the cyclin BUR2. CDK12 is a unique CDK that contains an arginine/serine-rich (RS) domain, which is predominantly found in splicing factors. CDK12 interacts with cyclins L1 and L2, and participates in regulating transcription and alternative splicing. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK9-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270832 [Multi-domain]  Cd Length: 291  Bit Score: 82.61  E-value: 8.72e-17
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  838 LGRGAFGQVIEAdafgIDKTaTCKTVAVKMLKegaTHSEH----RALMSELKILIHIgHHLNVVNLLGACTKPGgplmvi 913
Cdd:cd07840    7 IGEGTYGQVYKA----RNKK-TGELVALKKIR---MENEKegfpITAIREIKLLQKL-DHPNVVRLKEIVTSKG------ 71
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  914 veFCKFGNlSTYLrgkrnefVpykskgarFrqgkDYvgeLSVDLKrrldsitssqssassGFVEEKSLSdveeeeaseel 993
Cdd:cd07840   72 --SAKYKG-SIYM-------V--------F----EY---MDHDLT---------------GLLDNPEVK----------- 100
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  994 ykdfLTLEHLICYSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIYKD--PDYVRKgdaRLPLKWMA 1071
Cdd:cd07840  101 ----FTESQIKCYMKQLLEGLQYLHSNGILHRDIKGSNILINNDGVLKLADFGLARPYTKEnnADYTNR---VITLWYRP 173
                        250       260       270
                 ....*....|....*....|....*....|....*.
gi 27777648 1072 PETIF-DRVYTIQSDVWSFGVLLWEIFsLGASPYPG 1106
Cdd:cd07840  174 PELLLgATRYGPEVDMWSVGCILAELF-TGKPIFQG 208
STKc_LRRK2 cd14068
Catalytic domain of the Serine/Threonine Kinase, Leucine-Rich Repeat Kinase 2; STKs catalyze ...
838-1158 9.12e-17

Catalytic domain of the Serine/Threonine Kinase, Leucine-Rich Repeat Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. LRRK2 is one of two vertebrate LRRKs which show complementary expression in the brain. Mutations in LRRK2, found in the kinase, ROC-COR, and WD40 domains, are linked to both familial and sporadic forms of Parkinson's disease. The most prevalent mutation, G2019S located in the activation loop of the kinase domain, increases kinase activity. The R1441C/G mutations in the GTPase domain have also been reported to influence kinase activity. LRRKs are also classified as ROCO proteins because they contain a ROC (Ras of complex proteins)/GTPase domain followed by a COR (C-terminal of ROC) domain of unknown function. In addition, LRRKs contain a catalytic kinase domain and protein-protein interaction motifs including a WD40 domain, LRRs and ankyrin (ANK) repeats. LRRKs possess both GTPase and kinase activities, with the ROC domain acting as a molecular switch for the kinase domain, cycling between a GTP-bound state which drives kinase activity and a GDP-bound state which decreases the activity. The LRRK2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270970 [Multi-domain]  Cd Length: 252  Bit Score: 81.54  E-value: 9.12e-17
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  838 LGRGAFGQVIEADAFGIDktatcktVAVKMLKEgatHSEHRALMSELKILIHIgHHLNVVNLLGACTKPGGPLMvivefc 917
Cdd:cd14068    2 LGDGGFGSVYRAVYRGED-------VAVKIFNK---HTSFRLLRQELVVLSHL-HHPSLVALLAAGTAPRMLVM------ 64
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  918 kfgnlstylrgkrnEFVPYKSKGARFRQgkdyvgelsvdlkrrldsitssqssassgfvEEKSLSDveeeeaseelykdf 997
Cdd:cd14068   65 --------------ELAPKGSLDALLQQ-------------------------------DNASLTR-------------- 85
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  998 lTLEHLIcySFQVAKGMEFLASRKCIHRDLAARNILL-----SEKNVVKICDFGLARdiYKDPDYVRKGDARLPLKwmAP 1072
Cdd:cd14068   86 -TLQHRI--ALHVADGLRYLHSAMIIYRDLKPHNVLLftlypNCAIIAKIADYGIAQ--YCCRMGIKTSEGTPGFR--AP 158
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1073 ETIFDRV-YTIQSDVWSFGVLLWEIFSLGASPYPGVKIDEEFCRRLKEGtrmRAPDYTT-------PEMYQTMLDCWHED 1144
Cdd:cd14068  159 EVARGNViYNQQADVYSFGLLLYDILTCGERIVEGLKFPNEFDELAIQG---KLPDPVKeygcapwPGVEALIKDCLKEN 235
                        330
                 ....*....|....
gi 27777648 1145 PNQRPSFSELVEHL 1158
Cdd:cd14068  236 PQCRPTSAQVFDIL 249
STKc_ATG1_ULK_like cd14009
Catalytic domain of the Serine/Threonine kinases, Autophagy-related protein 1 and Unc-51-like ...
838-1157 1.13e-16

Catalytic domain of the Serine/Threonine kinases, Autophagy-related protein 1 and Unc-51-like kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily includes yeast ATG1 and metazoan homologs including vertebrate ULK1-3. The ATG1/ULK complex is conserved from yeast to humans and it plays a critical role in the initiation of autophagy, the intracellular system that leads to the lysosomal degradation of cellular components and their recycling into basic metabolic units. It is involved in nutrient sensing and signaling, the assembly of autophagy factors and the execution of autophagy. In metazoans, ATG1 homologs display additional functions. Unc-51 and ULKs have been implicated in neuronal and axonal development. The ATG1/ULK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270911 [Multi-domain]  Cd Length: 251  Bit Score: 81.11  E-value: 1.13e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  838 LGRGAFGQVIEADAfgidkTATCKTVAVK-MLKEGATHSEHRALMSELKILIHIgHHLNVVNLLGaCTKPGGPLMVIVEF 916
Cdd:cd14009    1 IGRGSFATVWKGRH-----KQTGEVVAIKeISRKKLNKKLQENLESEIAILKSI-KHPNIVRLYD-VQKTEDFIYLVLEY 73
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  917 CKFGNLSTYLRgKRnefvpykskgarfrqgkdyvGELSVDLKRRldsitssqssassgfveekslsdveeeeaseelykd 996
Cdd:cd14009   74 CAGGDLSQYIR-KR--------------------GRLPEAVARH------------------------------------ 96
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  997 FLTlehlicysfQVAKGMEFLASRKCIHRDLAARNILLS---EKNVVKICDFGLARdiYKDPDYVRKGDARLPLkWMAPE 1073
Cdd:cd14009   97 FMQ---------QLASGLKFLRSKNIIHRDLKPQNLLLStsgDDPVLKIADFGFAR--SLQPASMAETLCGSPL-YMAPE 164
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1074 TIFDRVYTIQSDVWSFGVLLWEIFsLGASPYPG---VKIDEEFCRRLKEGTRMRAPDyTTPEMYQTMLDCWHEDPNQRPS 1150
Cdd:cd14009  165 ILQFQKYDAKADLWSVGAILFEML-VGKPPFRGsnhVQLLRNIERSDAVIPFPIAAQ-LSPDCKDLLRRLLRRDPAERIS 242

                 ....*..
gi 27777648 1151 FSELVEH 1157
Cdd:cd14009  243 FEEFFAH 249
STKc_LIMK1 cd14221
Catalytic domain of the Serine/Threonine Kinase, LIM domain kinase 1; STKs catalyze the ...
1004-1162 1.23e-16

Catalytic domain of the Serine/Threonine Kinase, LIM domain kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. LIMK1 activation is induced by bone morphogenic protein, vascular endothelial growth factor, and thrombin. It plays roles in microtubule disassembly and cell cycle progression, and is critical in the regulation of neurite outgrowth. LIMK1 knockout mice show abnormalities in dendritic spine morphology and synaptic function. LIMK1 is one of the genes deleted in patients with Williams Syndrome, which is characterized by distinct craniofacial features, cardiovascular problems, as well as behavioral and neurological abnormalities. LIMKs phosphorylate and inactivate cofilin, an actin depolymerizing factor, to induce the reorganization of the actin cytoskeleton. They act downstream of Rho GTPases and are expressed ubiquitously. As regulators of actin dynamics, they contribute to diverse cellular functions such as cell motility, morphogenesis, differentiation, apoptosis, meiosis, mitosis, and neurite extension. LIMKs contain the LIM (two repeats), PDZ, and catalytic kinase domains. The LIMK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271123 [Multi-domain]  Cd Length: 267  Bit Score: 81.54  E-value: 1.23e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1004 ICYSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIYKDPDY------VRKGDARLPLK------WMA 1071
Cdd:cd14221   94 VSFAKDIASGMAYLHSMNIIHRDLNSHNCLVRENKSVVVADFGLARLMVDEKTQpeglrsLKKPDRKKRYTvvgnpyWMA 173
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1072 PETIFDRVYTIQSDVWSFGVLLWEIFSLgaspypgVKIDEEFC-RRLKEGTRMRA------PDYTTPEMYQTMLDCWHED 1144
Cdd:cd14221  174 PEMINGRSYDEKVDVFSFGIVLCEIIGR-------VNADPDYLpRTMDFGLNVRGfldrycPPNCPPSFFPIAVLCCDLD 246
                        170
                 ....*....|....*...
gi 27777648 1145 PNQRPSFSELVEHLGNLL 1162
Cdd:cd14221  247 PEKRPSFSKLEHWLETLR 264
STKc_LKB1_CaMKK cd14008
Catalytic domain of the Serine/Threonine kinases, Liver Kinase B1, Calmodulin Dependent ...
998-1157 1.29e-16

Catalytic domain of the Serine/Threonine kinases, Liver Kinase B1, Calmodulin Dependent Protein Kinase Kinase, and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Both LKB1 and CaMKKs can phosphorylate and activate AMP-activated protein kinase (AMPK). LKB1, also called STK11, serves as a master upstream kinase that activates AMPK and most AMPK-like kinases. LKB1 and AMPK are part of an energy-sensing pathway that links cell energy to metabolism and cell growth. They play critical roles in the establishment and maintenance of cell polarity, cell proliferation, cytoskeletal organization, as well as T-cell metabolism, including T-cell development, homeostasis, and effector function. CaMKKs are upstream kinases of the CaM kinase cascade that phosphorylate and activate CaMKI and CamKIV. They may also phosphorylate other substrates including PKB and AMPK. Vertebrates contain two CaMKKs, CaMKK1 (or alpha) and CaMKK2 (or beta). CaMKK1 is involved in the regulation of glucose uptake in skeletal muscles. CaMKK2 is involved in regulating energy balance, glucose metabolism, adiposity, hematopoiesis, inflammation, and cancer. The LKB1/CaMKK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270910 [Multi-domain]  Cd Length: 267  Bit Score: 81.45  E-value: 1.29e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  998 LTLEHLICYSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIYKDPDYVRK--GDarlPLkWMAPEtI 1075
Cdd:cd14008  105 LPEETARKYFRDLVLGLEYLHENGIVHRDIKPENLLLTADGTVKISDFGVSEMFEDGNDTLQKtaGT---PA-FLAPE-L 179
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1076 FDRVYTIQS----DVWSFGVLLWeIFSLGASPYPGVKIDEEFCRRLKEGTRMRAPDYTTPE---MYQTMLDcwhEDPNQR 1148
Cdd:cd14008  180 CDGDSKTYSgkaaDIWALGVTLY-CLVFGRLPFNGDNILELYEAIQNQNDEFPIPPELSPElkdLLRRMLE---KDPEKR 255

                 ....*....
gi 27777648 1149 PSFSELVEH 1157
Cdd:cd14008  256 ITLKEIKEH 264
PKc_TESK cd14155
Catalytic domain of the Dual-specificity protein kinase, Testicular protein kinase; ...
995-1163 1.93e-16

Catalytic domain of the Dual-specificity protein kinase, Testicular protein kinase; Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine as well as tyrosine residues on protein substrates. TESK proteins phosphorylate cofilin and induce actin cytoskeletal reorganization. In the Drosphila eye, TESK is required for epithelial cell organization. Mammals contain two TESK proteins, TESK1 and TESK2, which are highly expressed in testis and play roles in spermatogenesis. TESK1 is found in testicular germ cells while TESK2 is expressed mainly in nongerminal Sertoli cells. TESK1 is stimulated by integrin-mediated signaling pathways. It regulates cell spreading and focal adhesion formation. The TESK subfamily is part of a larger superfamily that includes the catalytic domains of other protein serine/threonine PKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271057 [Multi-domain]  Cd Length: 253  Bit Score: 80.60  E-value: 1.93e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  995 KDFLTLEHLICYSFQVAKGMEFLASRKCIHRDLAARNILLSEKN---VVKICDFGLARDIykdPDYvRKGDARLPL---- 1067
Cdd:cd14155   82 NEPLSWTVRVKLALDIARGLSYLHSKGIFHRDLTSKNCLIKRDEngyTAVVGDFGLAEKI---PDY-SDGKEKLAVvgsp 157
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1068 KWMAPETIFDRVYTIQSDVWSFGVLLWEIFSLgaspypgVKIDEEFCRRLKE------GTRMRAPDyTTPEMYQTMLDCW 1141
Cdd:cd14155  158 YWMAPEVLRGEPYNEKADVFSYGIILCEIIAR-------IQADPDYLPRTEDfgldydAFQHMVGD-CPPDFLQLAFNCC 229
                        170       180
                 ....*....|....*....|..
gi 27777648 1142 HEDPNQRPSFSELVEHLGNLLQ 1163
Cdd:cd14155  230 NMDPKSRPSFHDIVKTLEEILE 251
PKc_Pek1_like cd06621
Catalytic domain of fungal Pek1-like dual-specificity Mitogen-Activated Protein Kinase Kinases; ...
1007-1105 1.93e-16

Catalytic domain of fungal Pek1-like dual-specificity Mitogen-Activated Protein Kinase Kinases; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. Members of this group include the MAPKKs Pek1/Skh1 from Schizosaccharomyces pombe and MKK2 from Saccharomyces cerevisiae, and related proteins. Both fission yeast Pek1 and baker's yeast MKK2 are components of the cell integrity MAPK pathway. In fission yeast, Pek1 phosphorylates and activates Pmk1/Spm1 and is regulated by the MAPKK kinase Mkh1. In baker's yeast, the pathway involves the MAPK Slt2, the MAPKKs MKK1 and MKK2, and the MAPKK kinase Bck1. The cell integrity MAPK cascade is activated by multiple stress conditions, and is essential in cell wall construction, morphogenesis, cytokinesis, and ion homeostasis. MAPK signaling pathways are important mediators of cellular responses to extracellular signals. The MAPKK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270793 [Multi-domain]  Cd Length: 287  Bit Score: 81.31  E-value: 1.93e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1007 SFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIYKDPDYVRKGDARlplkWMAPETIFDRVYTIQSDV 1086
Cdd:cd06621  111 AESVLKGLSYLHSRKIIHRDIKPSNILLTRKGQVKLCDFGVSGELVNSLAGTFTGTSY----YMAPERIQGGPYSITSDV 186
                         90
                 ....*....|....*....
gi 27777648 1087 WSFGVLLWEIfSLGASPYP 1105
Cdd:cd06621  187 WSLGLTLLEV-AQNRFPFP 204
STKc_PAK_II cd06648
Catalytic domain of the Serine/Threonine Kinase, Group II p21-activated kinase; STKs catalyze ...
975-1157 1.98e-16

Catalytic domain of the Serine/Threonine Kinase, Group II p21-activated kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Group II PAKs, also called non-conventional PAKs, include PAK4, PAK5, and PAK6. Group II PAKs contain PBD (p21-binding domain) and catalytic domains, but lack other motifs found in group I PAKs, such as an AID (autoinhibitory domain) and SH3 binding sites. Since group II PAKs do not contain an obvious AID, they may be regulated differently from group I PAKs. While group I PAKs interact with the SH3 containing proteins Nck, Grb2 and PIX, no such binding has been demonstrated for group II PAKs. Some known substrates of group II PAKs are also substrates of group I PAKs such as Raf, BAD, LIMK and GEFH1. Unique group II substrates include MARK/Par-1 and PDZ-RhoGEF. Group II PAKs play important roles in filopodia formation, neuron extension, cytoskeletal organization, and cell survival. PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. The PAK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270815 [Multi-domain]  Cd Length: 261  Bit Score: 80.95  E-value: 1.98e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  975 FVEEKSLSDVEEEEAseelykdfLTLEHLICYSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIYKD 1054
Cdd:cd06648   85 FLEGGALTDIVTHTR--------MNEEQIATVCRAVLKALSFLHSQGVIHRDIKSDSILLTSDGRVKLSDFGFCAQVSKE 156
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1055 -PDyvRKGDARLPLkWMAPETIFDRVYTIQSDVWSFGVLLWEIFSlGASPYPGVKIDEEFCR-RLKEGTRMRAPDYTTPE 1132
Cdd:cd06648  157 vPR--RKSLVGTPY-WMAPEVISRLPYGTEVDIWSLGIMVIEMVD-GEPPYFNEPPLQAMKRiRDNEPPKLKNLHKVSPR 232
                        170       180
                 ....*....|....*....|....*
gi 27777648 1133 MYQTMLDCWHEDPNQRPSFSELVEH 1157
Cdd:cd06648  233 LRSFLDRMLVRDPAQRATAAELLNH 257
STKc_YSK4 cd06631
Catalytic domain of the Serine/Threonine Kinase, Yeast Sps1/Ste20-related Kinase 4; STKs ...
833-1157 3.19e-16

Catalytic domain of the Serine/Threonine Kinase, Yeast Sps1/Ste20-related Kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. YSK4 is a putative MAPKKK, whose mammalian gene has been isolated. MAPKKKs phosphorylate and activate MAPK kinases, which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. The YSK4 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270801 [Multi-domain]  Cd Length: 266  Bit Score: 80.17  E-value: 3.19e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  833 KLGKPLGRGAFGQVieadAFGIdkTATCKTVAVKMLKEGATHS-----EHRALMSELKILIHIGHHlNVVNLLGACTKpG 907
Cdd:cd06631    4 KKGNVLGKGAYGTV----YCGL--TSTGQLIAVKQVELDTSDKekaekEYEKLQEEVDLLKTLKHV-NIVGYLGTCLE-D 75
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  908 GPLMVIVEFCKFGNLSTYLrgkrnefvpykskgARFrqgkdyvgelsvdlkrrldsitssqssassGFVEEKSLSDveee 987
Cdd:cd06631   76 NVVSIFMEFVPGGSIASIL--------------ARF------------------------------GALEEPVFCR---- 107
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  988 easeelykdfltlehlicYSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIYKDPDYVRKGDArlpL 1067
Cdd:cd06631  108 ------------------YTKQILEGVAYLHNNNVIHRDIKGNNIMLMPNGVIKLIDFGCAKRLCINLSSGSQSQL---L 166
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1068 K-------WMAPETIFDRVYTIQSDVWSFGVLLWEIFSlGASPYPGV-KIDEEFCRRLKEGTRMRAPDYTTPEMYQTMLD 1139
Cdd:cd06631  167 KsmrgtpyWMAPEVINETGHGRKSDIWSIGCTVFEMAT-GKPPWADMnPMAAIFAIGSGRKPVPRLPDKFSPEARDFVHA 245
                        330
                 ....*....|....*...
gi 27777648 1140 CWHEDPNQRPSFSELVEH 1157
Cdd:cd06631  246 CLTRDQDERPSAEQLLKH 263
STKc_MAK_like cd07830
Catalytic domain of Male germ cell-Associated Kinase-like Serine/Threonine Kinases; STKs ...
833-1157 3.42e-16

Catalytic domain of Male germ cell-Associated Kinase-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of human MAK and MAK-related kinase (MRK), Saccharomyces cerevisiae Ime2p, Schizosaccharomyces pombe Mei4-dependent protein 3 (Mde3) and Pit1, Caenorhabditis elegans dyf-5, Arabidopsis thaliana MHK, and similar proteins. These proteins play important roles during meiosis. MAK is highly expressed in testicular cells specifically in the meiotic phase, but is not essential for spermatogenesis and fertility. It functions as a coactivator of the androgen receptor in prostate cells. MRK, also called Intestinal Cell Kinase (ICK), is expressed ubiquitously, with highest expression in the ovary and uterus. A missense mutation in MRK causes endocrine-cerebro-osteodysplasia, suggesting that this protein plays an important role in the development of many organs. MAK and MRK may be involved in regulating cell cycle and cell fate. Ime2p is a meiosis-specific kinase that is important during meiotic initiation and during the later stages of meiosis. Mde3 functions downstream of the transcription factor Mei-4 which is essential for meiotic prophase I. The MAK-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270824 [Multi-domain]  Cd Length: 283  Bit Score: 80.66  E-value: 3.42e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  833 KLGKPLGRGAFGQVIEADafgidKTATCKTVAVKMLKEGATHSEHRALMSELKILIHIGHHLNVVNLLGAcTKPGGPLMV 912
Cdd:cd07830    2 KVIKQLGDGTFGSVYLAR-----NKETGELVAIKKMKKKFYSWEECMNLREVKSLRKLNEHPNIVKLKEV-FRENDELYF 75
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  913 IVEFCKfGNLstylrgkrnefvpYKskgarfrqgkdyvgeLSVDLKRRLdsitssqssassgFVEEKSLSdveeeeasee 992
Cdd:cd07830   76 VFEYME-GNL-------------YQ---------------LMKDRKGKP-------------FSESVIRS---------- 103
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  993 lykdfltlehlICYsfQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIY-KDP--DYV--Rkgdarlpl 1067
Cdd:cd07830  104 -----------IIY--QILQGLAHIHKHGFFHRDLKPENLLVSGPEVVKIADFGLAREIRsRPPytDYVstR-------- 162
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1068 kWM-APETIF-DRVYTIQSDVWSFGVLLWEIFSL-----GASpypgvKIDEEFC----------RRLKEGTRM------R 1124
Cdd:cd07830  163 -WYrAPEILLrSTSYSSPVDIWALGCIMAELYTLrplfpGSS-----EIDQLYKicsvlgtptkQDWPEGYKLasklgfR 236
                        330       340       350       360
                 ....*....|....*....|....*....|....*....|....
gi 27777648 1125 APDYT-----------TPEMYQTMLDCWHEDPNQRPSFSELVEH 1157
Cdd:cd07830  237 FPQFAptslhqlipnaSPEAIDLIKDMLRWDPKKRPTASQALQH 280
STKc_PLK cd14099
Catalytic domain of the Serine/Threonine Kinases, Polo-like kinases; STKs catalyze the ...
998-1157 3.70e-16

Catalytic domain of the Serine/Threonine Kinases, Polo-like kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PLKs play important roles in cell cycle progression and in DNA damage responses. They regulate mitotic entry, mitotic exit, and cytokinesis. In general PLKs contain an N-terminal catalytic kinase domain and a C-terminal regulatory polo box domain (PBD), which is comprised by two bipartite polo-box motifs (or polo boxes) and is involved in protein interactions. PLKs derive their names from homology to polo, a kinase first identified in Drosophila. There are five mammalian PLKs (PLK1-5) from distinct genes. There is good evidence that PLK1 may function as an oncogene while PLK2-5 have tumor suppressive properties. PLK1 functions as a positive regulator of mitosis, meiosis, and cytokinesis. PLK2 functions in G1 progression, S-phase arrest, and centriole duplication. PLK3 regulates angiogenesis and responses to DNA damage. PLK4 is required for late mitotic progression, cell survival, and embryonic development. PLK5 was first identified as a pseudogene containing a stop codon within the kinase domain, however, both murine and human genes encode expressed proteins. PLK5 functions in cell cycle arrest.


Pssm-ID: 271001 [Multi-domain]  Cd Length: 258  Bit Score: 79.91  E-value: 3.70e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  998 LTLEHLICYSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIYKD----------PDYvrkgdarlpl 1067
Cdd:cd14099   98 LTEPEVRYFMRQILSGVKYLHSNRIIHRDLKLGNLFLDENMNVKIGDFGLAARLEYDgerkktlcgtPNY---------- 167
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1068 kwMAPETIFDRV-YTIQSDVWSFGVLLWEIFsLGASPYPGVKIDEEFcRRLKEGtrmrapDYTTPE----------MYQT 1136
Cdd:cd14099  168 --IAPEVLEKKKgHSFEVDIWSLGVILYTLL-VGKPPFETSDVKETY-KRIKKN------EYSFPShlsisdeakdLIRS 237
                        170       180
                 ....*....|....*....|.
gi 27777648 1137 MLdcwHEDPNQRPSFSELVEH 1157
Cdd:cd14099  238 ML---QPDPTKRPSLDEILSH 255
STKc_LIMK cd14154
Catalytic domain of the Serine/Threonine Kinase, LIM domain kinase; STKs catalyze the transfer ...
838-1161 5.47e-16

Catalytic domain of the Serine/Threonine Kinase, LIM domain kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. LIMKs phosphorylate and inactivate cofilin, an actin depolymerizing factor, to induce the reorganization of the actin cytoskeleton. They act downstream of Rho GTPases and are expressed ubiquitously. As regulators of actin dynamics, they contribute to diverse cellular functions such as cell motility, morphogenesis, differentiation, apoptosis, meiosis, mitosis, and neurite extension. LIMKs contain the LIM (two repeats), PDZ, and catalytic kinase domains. Vertebrate have two members, LIMK1 and LIMK2. The LIMK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271056 [Multi-domain]  Cd Length: 272  Bit Score: 79.86  E-value: 5.47e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  838 LGRGAFGQVIeadafgidKTATCKTVAVKMLKEGATHSE--HRALMSELKILIHIgHHLNVVNLLGACTKpGGPLMVIVE 915
Cdd:cd14154    1 LGKGFFGQAI--------KVTHRETGEVMVMKELIRFDEeaQRNFLKEVKVMRSL-DHPNVLKFIGVLYK-DKKLNLITE 70
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  916 FCKFGNLSTYLRGKRNEFvPYKSkgaRFRQGKDyvgelsvdlkrrldsitssqssassgfveekslsdveeeeaseelyk 995
Cdd:cd14154   71 YIPGGTLKDVLKDMARPL-PWAQ---RVRFAKD----------------------------------------------- 99
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  996 dfltlehlicysfqVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIYKDPDYVRKGDARLPLK------- 1068
Cdd:cd14154  100 --------------IASGMAYLHSMNIIHRDLNSHNCLVREDKTVVVADFGLARLIVEERLPSGNMSPSETLRhlkspdr 165
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1069 -----------WMAPETIFDRVYTIQSDVWSFGVLLWEIFSLgaspypgVKIDEEFCRRLK------EGTRMRAPDYTTP 1131
Cdd:cd14154  166 kkrytvvgnpyWMAPEMLNGRSYDEKVDIFSFGIVLCEIIGR-------VEADPDYLPRTKdfglnvDSFREKFCAGCPP 238
                        330       340       350
                 ....*....|....*....|....*....|
gi 27777648 1132 EMYQTMLDCWHEDPNQRPSFSELVEHLGNL 1161
Cdd:cd14154  239 PFFKLAFLCCDLDPEKRPPFETLEEWLEAL 268
PKc_TOPK cd14001
Catalytic domain of the Dual-specificity protein kinase, Lymphokine-activated killer ...
1007-1158 6.85e-16

Catalytic domain of the Dual-specificity protein kinase, Lymphokine-activated killer T-cell-originated protein kinase; Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine as well as tyrosine residues on protein substrates. TOPK, also called PDZ-binding kinase (PBK), is activated at the early stage of mitosis and plays a critical role in cytokinesis. It partly functions as a mitogen-activated protein kinase (MAPK) kinase and is capable of phosphorylating p38, JNK1, and ERK2. TOPK also plays a role in DNA damage sensing and repair through its phosphorylation of histone H2AX. It contributes to cancer development and progression by downregulating the function of tumor suppressor p53 and reducing cell-cycle regulatory proteins. TOPK is found highly expressed in breast and skin cancer cells. The TOPK subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270903 [Multi-domain]  Cd Length: 292  Bit Score: 79.75  E-value: 6.85e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1007 SFQVAKGMEFLASRKCI-HRDLAARNILL-SEKNVVKICDFGLARDIYKDPDYVRKGDARL----PlkWMAPETIF-DRV 1079
Cdd:cd14001  116 ALSIARALEYLHNEKKIlHGDIKSGNVLIkGDFESVKLCDFGVSLPLTENLEVDSDPKAQYvgteP--WKAKEALEeGGV 193
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1080 YTIQSDVWSFGVLLWEIFSLGA-----SPYPGVKIDEEFCRRLKE--------GTRMRAPDYTTPEMYQTMLD----CWH 1142
Cdd:cd14001  194 ITDKADIFAYGLVLWEMMTLSVphlnlLDIEDDDEDESFDEDEEDeeayygtlGTRPALNLGELDDSYQKVIElfyaCTQ 273
                        170
                 ....*....|....*.
gi 27777648 1143 EDPNQRPSFSELVEHL 1158
Cdd:cd14001  274 EDPKDRPSAAHIVEAL 289
STKc_ULK3 cd14121
Catalytic domain of the Serine/Threonine kinase, Unc-51-like kinase 3; STKs catalyze the ...
838-1157 7.00e-16

Catalytic domain of the Serine/Threonine kinase, Unc-51-like kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The ATG1/ULK complex is conserved from yeast to humans and it plays a critical role in the initiation of autophagy, the intracellular system that leads to the lysosomal degradation of cellular components and their recycling into basic metabolic units. ULK3 mRNA is up-regulated in fibroblasts after Ras-induced senescence, and its overexpression induces both autophagy and senescence in a fibroblast cell line. ULK3, through its kinase activity, positively regulates Gli proteins, mediators of the Sonic hedgehog (Shh) signaling pathway that is implicated in tissue homeostasis maintenance and neurogenesis. It is inhibited by binding to Suppressor of Fused (Sufu). The ULK3 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271023 [Multi-domain]  Cd Length: 252  Bit Score: 78.87  E-value: 7.00e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  838 LGRGAFGQVIEAdafgIDKTATCKTVAVK-MLKEGATHSEHRALMSELKILIHIgHHLNVVNLLGAcTKPGGPLMVIVEF 916
Cdd:cd14121    3 LGSGTYATVYKA----YRKSGAREVVAVKcVSKSSLNKASTENLLTEIELLKKL-KHPHIVELKDF-QWDEEHIYLIMEY 76
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  917 CKFGNLSTYLRGKRnefvpykskgarfrqgkdyvgelsvdlkrrldsitssqssassgfveekslsdveeeeaseelykd 996
Cdd:cd14121   77 CSGGDLSRFIRSRR------------------------------------------------------------------ 90
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  997 flTLEHLICYSF--QVAKGMEFLASRKCIHRDLAARNILLS--EKNVVKICDFGLARdiykdpdYVRKGDARLPLK---- 1068
Cdd:cd14121   91 --TLPESTVRRFlqQLASALQFLREHNISHMDLKPQNLLLSsrYNPVLKLADFGFAQ-------HLKPNDEAHSLRgspl 161
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1069 WMAPETIFDRVYTIQSDVWSFGVLLWEIFsLGASPYPGVKIDEefcrrLKEGTRMRAPdYTTPEMYQTMLDC-------W 1141
Cdd:cd14121  162 YMAPEMILKKKYDARVDLWSVGVILYECL-FGRAPFASRSFEE-----LEEKIRSSKP-IEIPTRPELSADCrdlllrlL 234
                        330
                 ....*....|....*.
gi 27777648 1142 HEDPNQRPSFSELVEH 1157
Cdd:cd14121  235 QRDPDRRISFEEFFAH 250
PKc_LIMK_like_unk cd14156
Catalytic domain of an unknown subfamily of LIM domain kinase-like protein kinases; PKs ...
1010-1158 1.06e-15

Catalytic domain of an unknown subfamily of LIM domain kinase-like protein kinases; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine or tyrosine residues on protein substrates. This group is composed of uncharacterized proteins with similarity to LIMK and Testicular or testis-specific protein kinase (TESK). LIMKs are characterized as serine/threonine kinases (STKs) while TESKs are dual-specificity protein kinases. Both LIMK and TESK phosphorylate and inactivate cofilin, an actin depolymerizing factor, to induce the reorganization of the actin cytoskeleton. They are implicated in many cellular functions including cell spreading, motility, morphogenesis, meiosis, mitosis, and spermatogenesis. The LIMK-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271058 [Multi-domain]  Cd Length: 256  Bit Score: 78.71  E-value: 1.06e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1010 VAKGMEFLASRKCIHRDLAARNILLSEKNVVK---ICDFGLARDIYKDPdyVRKGDARLPLK----WMAPETIFDRVYTI 1082
Cdd:cd14156   98 ISRGMVYLHSKNIYHRDLNSKNCLIRVTPRGReavVTDFGLAREVGEMP--ANDPERKLSLVgsafWMAPEMLRGEPYDR 175
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1083 QSDVWSFGVLLWEIFS-LGASPypgvkidEEFCRRLKEGTRMRAPDYTTPEMYQTMLD----CWHEDPNQRPSFSELVEH 1157
Cdd:cd14156  176 KVDVFSFGIVLCEILArIPADP-------EVLPRTGDFGLDVQAFKEMVPGCPEPFLDlaasCCRMDAFKRPSFAELLDE 248

                 .
gi 27777648 1158 L 1158
Cdd:cd14156  249 L 249
PK_SCY1_like cd14011
Pseudokinase domain of Scy1-like proteins; The pseudokinase domain shows similarity to protein ...
1004-1157 1.25e-15

Pseudokinase domain of Scy1-like proteins; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. This subfamily is composed of the catalytically inactive kinases with similarity to yeast Scy1. It includes four mammalian proteins called SCY1-like protein 1 (SCYL1), SCYL2, SCYL3, as well as Testis-EXpressed protein 14 (TEX14). SCYL1 binds to and co-localizes with the membrane trafficking coatomer I (COPI) complex, and regulates COPI-mediated vesicle trafficking. Null mutations in the SCYL1 gene are responsible for the pathology in mdf (muscle-deficient) mice which display progressive motor neuropathy. SCYL2, also called coated vesicle-associated kinase of 104 kDa (CVAK104), is involved in the trafficking of clathrin-coated vesicles. It also binds the HIV-1 accessory protein Vpu and acts as a regulatory factor that promotes the dephosphorylation of Vpu, facilitating the restriction of HIV-1 release. SCYL3, also called ezrin-binding protein PACE-1, may be involved in regulating cell adhesion and migration. TEX14 is required for spermatogenesis and male fertility. It localizes to kinetochores (KT) during mitosis and is a target of the mitotic kinase PLK1. It regulates the maturation of the outer KT and the KT-microtubule attachment. The SCY1-like subfamily is part of a larger superfamily that includes the catalytic domains of other protein serine/threonine kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270913 [Multi-domain]  Cd Length: 287  Bit Score: 78.90  E-value: 1.25e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1004 ICYS-FQVAKGMEFLASR-KCIHRDLAARNILLSEKNVVKICDFGLA---------RDIYKDPDYVRKGDARLPLKWMAP 1072
Cdd:cd14011  116 IKYGlLQISEALSFLHNDvKLVHGNICPESVVINSNGEWKLAGFDFCisseqatdqFPYFREYDPNLPPLAQPNLNYLAP 195
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1073 ETIFDRVYTIQSDVWSFGVLLWEIFSLGASPYPGVKIDEEFCRRLKEGTRMRAPDYT-TPEMYQTMLD-CWHEDPNQRPS 1150
Cdd:cd14011  196 EYILSKTCDPASDMFSLGVLIYAIYNKGKPLFDCVNNLLSYKKNSNQLRQLSLSLLEkVPEELRDHVKtLLNVTPEVRPD 275

                 ....*..
gi 27777648 1151 FSELVEH 1157
Cdd:cd14011  276 AEQLSKI 282
STKc_SLK_like cd06611
Catalytic domain of Ste20-Like Kinase-like Serine/Threonine Kinases; STKs catalyze the ...
828-1157 1.26e-15

Catalytic domain of Ste20-Like Kinase-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Members of the subfamily include SLK, STK10 (also called LOK for Lymphocyte-Oriented Kinase), SmSLK (Schistosoma mansoni SLK), and related proteins. SLK promotes apoptosis through apoptosis signal-regulating kinase 1 (ASK1) and the mitogen-activated protein kinase (MAPK) p38. It also plays a role in mediating actin reorganization. STK10 is responsible in regulating the CD28 responsive element in T cells, as well as leukocyte function associated antigen (LFA-1)-mediated lymphocyte adhesion. SmSLK is capable of activating the MAPK Jun N-terminal kinase (JNK) pathway in human embryonic kidney cells as well as in Xenopus oocytes. It may participate in regulating MAPK cascades during host-parasite interactions. The SLK-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 132942 [Multi-domain]  Cd Length: 280  Bit Score: 79.02  E-value: 1.26e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  828 PRDRLKLGKPLGRGAFGQVIEADAFGIDKTATCKTVAVKmlkEGATHSEHralMSELKILIHIGHHlNVVNLLGACTKPG 907
Cdd:cd06611    3 PNDIWEIIGELGDGAFGKVYKAQHKETGLFAAAKIIQIE---SEEELEDF---MVEIDILSECKHP-NIVGLYEAYFYEN 75
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  908 gPLMVIVEFCkfgnlstylrgkrnefvpykSKGArfrqgkdyVGELSVDLKRRLDsitssqssassgfveekslsdveee 987
Cdd:cd06611   76 -KLWILIEFC--------------------DGGA--------LDSIMLELERGLT------------------------- 101
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  988 easeelykdfltlEHLICY-SFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARdiyKDPDYVRKGDARL- 1065
Cdd:cd06611  102 -------------EPQIRYvCRQMLEALNFLHSHKVIHRDLKAGNILLTLDGDVKLADFGVSA---KNKSTLQKRDTFIg 165
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1066 -PLkWMAP-----ETIFDRVYTIQSDVWSFGVLLWEIfSLGASPYPGVKIDEEFCRRLK-EGTRMRAPDYTTPEMYQTML 1138
Cdd:cd06611  166 tPY-WMAPevvacETFKDNPYDYKADIWSLGITLIEL-AQMEPPHHELNPMRVLLKILKsEPPTLDQPSKWSSSFNDFLK 243
                        330
                 ....*....|....*....
gi 27777648 1139 DCWHEDPNQRPSFSELVEH 1157
Cdd:cd06611  244 SCLVKDPDDRPTAAELLKH 262
STKc_STK25 cd06642
Catalytic domain of Serine/Threonine Kinase 25 (also called Yeast Sps1/Ste20-related kinase 1); ...
1009-1157 1.34e-15

Catalytic domain of Serine/Threonine Kinase 25 (also called Yeast Sps1/Ste20-related kinase 1); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. STK25 is also called Ste20/oxidant stress response kinase 1 (SOK1) or yeast Sps1/Ste20-related kinase 1 (YSK1). It is localized in the Golgi apparatus through its interaction with the Golgi matrix protein GM130. It may be involved in the regulation of cell migration and polarization. STK25 binds and phosphorylates CCM3 (cerebral cavernous malformation 3), also called PCD10 (programmed cell death 10), and may play a role in apoptosis. Human STK25 is a candidate gene responsible for pseudopseudohypoparathyroidism (PPHP), a disease that shares features with the Albright hereditary osteodystrophy (AHO) phenotype. The STK25 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270810 [Multi-domain]  Cd Length: 277  Bit Score: 78.56  E-value: 1.34e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1009 QVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIyKDPDYVRKGDARLPLkWMAPETIFDRVYTIQSDVWS 1088
Cdd:cd06642  109 EILKGLDYLHSERKIHRDIKAANVLLSEQGDVKLADFGVAGQL-TDTQIKRNTFVGTPF-WMAPEVIKQSAYDFKADIWS 186
                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1089 FGVLLWEIfSLGASPYPGVKIDEEFCRRLKEGTRMRAPDYTTPemYQTMLD-CWHEDPNQRPSFSELVEH 1157
Cdd:cd06642  187 LGITAIEL-AKGEPPNSDLHPMRVLFLIPKNSPPTLEGQHSKP--FKEFVEaCLNKDPRFRPTAKELLKH 253
PK_KSR cd14063
Pseudokinase domain of Kinase Suppressor of Ras; The pseudokinase domain shows similarity to ...
832-1154 1.38e-15

Pseudokinase domain of Kinase Suppressor of Ras; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. KSR is a scaffold protein that functions downstream of Ras and upstream of Raf in the Extracellular signal-Regulated Kinase (ERK) pathway that regulates many cellular processes including cycle regulation, proliferation, differentiation, survival, and apoptosis. KSR proteins regulate the assembly and activation of the Raf/MEK/ERK module upon Ras activation at the membrane by direct association of its components. They are widely regarded as pseudokinases, but there is some debate in this designation as a few groups have reported detecting kinase catalytic activity for KSRs, specifically KSR1. Vertebrates contain two KSR proteins, KSR1 and KSR2. The KSR subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270965 [Multi-domain]  Cd Length: 271  Bit Score: 78.55  E-value: 1.38e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  832 LKLGKPLGRGAFGQVIEADAFGidktatckTVAVKMLKEGATHSEH-RALMSELKILIHIGHHlNVVNLLGACTKPggP- 909
Cdd:cd14063    2 LEIKEVIGKGRFGRVHRGRWHG--------DVAIKLLNIDYLNEEQlEAFKEEVAAYKNTRHD-NLVLFMGACMDP--Ph 70
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  910 LMVIVEFCKFGNLSTYLRGKRNEFVpyKSKGARFRQgkdyvgelsvdlkrrldsitssqssassgfveekslsdveeeea 989
Cdd:cd14063   71 LAIVTSLCKGRTLYSLIHERKEKFD--FNKTVQIAQ-------------------------------------------- 104
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  990 seelykdfltlehlicysfQVAKGMEFLASRKCIHRDLAARNILLsEKNVVKICDFGLARDIYKDPDYVRKGDARLPLKW 1069
Cdd:cd14063  105 -------------------QICQGMGYLHAKGIIHKDLKSKNIFL-ENGRVVITDFGLFSLSGLLQPGRREDTLVIPNGW 164
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1070 ---MAPETI----FDRV------YTIQSDVWSFGVLLWEIFSlGASPY----PGVKIdeefcrrLKEGTRMRAP--DYTT 1130
Cdd:cd14063  165 lcyLAPEIIralsPDLDfeeslpFTKASDVYAFGTVWYELLA-GRWPFkeqpAESII-------WQVGCGKKQSlsQLDI 236
                        330       340
                 ....*....|....*....|....*
gi 27777648 1131 P-EMYQTMLDCWHEDPNQRPSFSEL 1154
Cdd:cd14063  237 GrEVKDILMQCWAYDPEKRPTFSDL 261
STKc_MST3_like cd06609
Catalytic domain of Mammalian Ste20-like protein kinase 3-like Serine/Threonine Kinases; STKs ...
1009-1157 1.67e-15

Catalytic domain of Mammalian Ste20-like protein kinase 3-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of MST3, MST4, STK25, Schizosaccharomyces pombe Nak1 and Sid1, Saccharomyces cerevisiae sporulation-specific protein 1 (SPS1), and related proteins. Nak1 is required by fission yeast for polarizing the tips of actin cytoskeleton and is involved in cell growth, cell separation, cell morphology and cell-cycle progression. Sid1 is a component in the septation initiation network (SIN) signaling pathway, and plays a role in cytokinesis. SPS1 plays a role in regulating proteins required for spore wall formation. MST4 plays a role in mitogen-activated protein kinase (MAPK) signaling during cytoskeletal rearrangement, morphogenesis, and apoptosis. MST3 phosphorylates the STK NDR and may play a role in cell cycle progression and cell morphology. STK25 may play a role in the regulation of cell migration and polarization. The MST3-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270786 [Multi-domain]  Cd Length: 274  Bit Score: 78.44  E-value: 1.67e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1009 QVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFG----LARDIYKDPDYVrkGDarlPLkWMAPETIFDRVYTIQS 1084
Cdd:cd06609  106 EVLLGLEYLHSEGKIHRDIKAANILLSEEGDVKLADFGvsgqLTSTMSKRNTFV--GT---PF-WMAPEVIKQSGYDEKA 179
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1085 DVWSFGVLLWEIFSlGASPYPGV-------KIDEEFCRRLKegtrmraPDYTTPEMYQTMLDCWHEDPNQRPSFSELVEH 1157
Cdd:cd06609  180 DIWSLGITAIELAK-GEPPLSDLhpmrvlfLIPKNNPPSLE-------GNKFSKPFKDFVELCLNKDPKERPSAKELLKH 251
STKc_ULK1_2-like cd14120
Catalytic domain of the Serine/Threonine kinases, Unc-51-like kinases 1 and 2, and similar ...
838-1157 1.93e-15

Catalytic domain of the Serine/Threonine kinases, Unc-51-like kinases 1 and 2, and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The ATG1/ULK complex is conserved from yeast to humans and it plays a critical role in the initiation of autophagy, the intracellular system that leads to the lysosomal degradation of cellular components and their recycling into basic metabolic units. ULK1 is required for efficient amino acid starvation-induced autophagy and mitochondrial clearance. ULK2 is ubiquitously expressed and is essential in autophagy induction. ULK1 and ULK2 have unique and cell-type specific roles, but also display partially redundant roles in starvation-induced autophagy. They both display neuron-specific functions: ULK1 is involved in non-clathrin-coated endocytosis in growth cones, filopodia extension, and axon branching; ULK2 plays a role in axon development. The ULK1/2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271022 [Multi-domain]  Cd Length: 256  Bit Score: 77.79  E-value: 1.93e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  838 LGRGAFGQVIEadafGIDKTATCKTVAVK-MLKEGATHSEHrALMSELKILIHIgHHLNVVNLLGaCTKPGGPLMVIVEF 916
Cdd:cd14120    1 IGHGAFAVVFK----GRHRKKPDLPVAIKcITKKNLSKSQN-LLGKEIKILKEL-SHENVVALLD-CQETSSSVYLVMEY 73
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  917 CKFGNLSTYLRGKrnefvpykskgarfrqgkdyvGELSVDLKRRldsitssqssassgfveekslsdveeeeaseelykd 996
Cdd:cd14120   74 CNGGDLADYLQAK---------------------GTLSEDTIRV------------------------------------ 96
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  997 FLTlehlicysfQVAKGMEFLASRKCIHRDLAARNILLSEKN---------VVKICDFGLARdiykdpdYVRKGD--ARL 1065
Cdd:cd14120   97 FLQ---------QIAAAMKALHSKGIVHRDLKPQNILLSHNSgrkpspndiRLKIADFGFAR-------FLQDGMmaATL 160
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1066 ---PLkWMAPETIFDRVYTIQSDVWSFGVLLWEIFSlGASPY-----PGVKIDEEFCRRLKEgtrmRAPDYTTPEMYQTM 1137
Cdd:cd14120  161 cgsPM-YMAPEVIMSLQYDAKADLWSIGTIVYQCLT-GKAPFqaqtpQELKAFYEKNANLRP----NIPSGTSPALKDLL 234
                        330       340
                 ....*....|....*....|
gi 27777648 1138 LDCWHEDPNQRPSFSELVEH 1157
Cdd:cd14120  235 LGLLKRNPKDRIDFEDFFSH 254
STKc_PKC cd05570
Catalytic domain of the Serine/Threonine Kinase, Protein Kinase C; STKs catalyze the transfer ...
1006-1113 1.99e-15

Catalytic domain of the Serine/Threonine Kinase, Protein Kinase C; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. PKCs undergo three phosphorylations in order to take mature forms. In addition, classical PKCs depend on calcium, DAG (1,2-diacylglycerol), and in most cases, phosphatidylserine (PS) for activation. Novel PKCs are calcium-independent, but require DAG and PS for activity, while atypical PKCs only require PS. PKCs phosphorylate and modify the activities of a wide variety of cellular proteins including receptors, enzymes, cytoskeletal proteins, transcription factors, and other kinases. They play a central role in signal transduction pathways that regulate cell migration and polarity, proliferation, differentiation, and apoptosis. Also included in this subfamily are the PKC-like proteins, called PKNs. The PKC subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270722 [Multi-domain]  Cd Length: 318  Bit Score: 78.80  E-value: 1.99e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1006 YSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLAR-DIYKD---------PDYvrkgdarlplkwMAPETI 1075
Cdd:cd05570  101 YAAEICLALQFLHERGIIYRDLKLDNVLLDAEGHIKIADFGMCKeGIWGGnttstfcgtPDY------------IAPEIL 168
                         90       100       110
                 ....*....|....*....|....*....|....*...
gi 27777648 1076 FDRVYTIQSDVWSFGVLLWEIFsLGASPYPGVKIDEEF 1113
Cdd:cd05570  169 REQDYGFSVDWWALGVLLYEML-AGQSPFEGDDEDELF 205
STKc_nPKC_delta cd05620
Catalytic domain of the Serine/Threonine Kinase, Novel Protein Kinase C delta; STKs catalyze ...
1006-1148 2.97e-15

Catalytic domain of the Serine/Threonine Kinase, Novel Protein Kinase C delta; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKC-delta plays a role in cell cycle regulation and programmed cell death in many cell types. It slows down cell proliferation, inducing cell cycle arrest and enhancing cell differentiation. PKC-delta is also involved in the regulation of transcription as well as immune and inflammatory responses. It plays a central role in the genotoxic stress response that leads to DNA damaged-induced apoptosis. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. nPKCs are calcium-independent, but require DAG (1,2-diacylglycerol) and phosphatidylserine (PS) for activity. The nPKC-delta subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173710 [Multi-domain]  Cd Length: 316  Bit Score: 78.45  E-value: 2.97e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1006 YSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARD-IYKD---------PDYVrkgdarlplkwmAPETI 1075
Cdd:cd05620  101 YAAEIVCGLQFLHSKGIIYRDLKLDNVMLDRDGHIKIADFGMCKEnVFGDnrastfcgtPDYI------------APEIL 168
                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 27777648 1076 FDRVYTIQSDVWSFGVLLWEIFsLGASPYPGVKIDEEFcrrlkEGTRMRAPDY---TTPEMYQTMLDCWHEDPNQR 1148
Cdd:cd05620  169 QGLKYTFSVDWWSFGVLLYEML-IGQSPFHGDDEDELF-----ESIRVDTPHYprwITKESKDILEKLFERDPTRR 238
STKc_MST4 cd06640
Catalytic domain of the Serine/Threonine Kinase, Mammalian Ste20-like protein kinase 4; STKs ...
1009-1157 3.03e-15

Catalytic domain of the Serine/Threonine Kinase, Mammalian Ste20-like protein kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MST4 is sometimes referred to as MASK (MST3 and SOK1-related kinase). It plays a role in mitogen-activated protein kinase (MAPK) signaling during cytoskeletal rearrangement, morphogenesis, and apoptosis. It influences cell growth and transformation by modulating the extracellular signal-regulated kinase (ERK) pathway. MST4 may also play a role in tumor formation and progression. It localizes in the Golgi apparatus by interacting with the Golgi matrix protein GM130 and may play a role in cell migration. The MST4 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 132971 [Multi-domain]  Cd Length: 277  Bit Score: 77.79  E-value: 3.03e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1009 QVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIyKDPDYVRKGDARLPLkWMAPETIFDRVYTIQSDVWS 1088
Cdd:cd06640  109 EILKGLDYLHSEKKIHRDIKAANVLLSEQGDVKLADFGVAGQL-TDTQIKRNTFVGTPF-WMAPEVIQQSAYDSKADIWS 186
                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 27777648 1089 FGVLLWEIfSLGASPypgvKIDEEFCRRLKEGTRMRAPDYT---TPEMYQTMLDCWHEDPNQRPSFSELVEH 1157
Cdd:cd06640  187 LGITAIEL-AKGEPP----NSDMHPMRVLFLIPKNNPPTLVgdfSKPFKEFIDACLNKDPSFRPTAKELLKH 253
STKc_IRAK4 cd14158
Catalytic domain of the Serine/Threonine kinase, Interleukin-1 Receptor Associated Kinase 4; ...
1011-1161 3.30e-15

Catalytic domain of the Serine/Threonine kinase, Interleukin-1 Receptor Associated Kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. IRAKs are involved in Toll-like receptor (TLR) and interleukin-1 (IL-1) signalling pathways, and are thus critical in regulating innate immune responses and inflammation. IRAKs contain an N-terminal Death domain (DD), a proST region (rich in serines, prolines, and threonines), a central kinase domain, and a C-terminal domain; IRAK-4 lacks the C-terminal domain. Vertebrates contain four IRAKs (IRAK-1, -2, -3 (or -M), and -4) that display distinct functions and patterns of expression and subcellular distribution, and can differentially mediate TLR signaling. IRAK4 plays a critical role in NFkB activation by its interaction with MyD88, which acts as a scaffold that enables IRAK4 to phosphorylate and activate IRAK1 and/or IRAK2. It also plays an important role in type I IFN production induced by TLR7/8/9. The IRAK4 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271060 [Multi-domain]  Cd Length: 288  Bit Score: 77.92  E-value: 3.30e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1011 AKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIYKDPDYVRKGDARLPLKWMAPETIFDRVyTIQSDVWSFG 1090
Cdd:cd14158  127 ANGINYLHENNHIHRDIKSANILLDETFVPKISDFGLARASEKFSQTIMTERIVGTTAYMAPEALRGEI-TPKSDIFSFG 205
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1091 VLLWEIFS-LGA-----SPYPGVKIDEEFCRR---LKEGTRMRAPDYTTPE---MYQTMLDCWHEDPNQRPSFSELVEHL 1158
Cdd:cd14158  206 VVLLEIITgLPPvdenrDPQLLLDIKEEIEDEektIEDYVDKKMGDWDSTSieaMYSVASQCLNDKKNRRPDIAKVQQLL 285

                 ...
gi 27777648 1159 GNL 1161
Cdd:cd14158  286 QEL 288
Ig cd00096
Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found ...
682-742 3.63e-15

Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins, including T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, including butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E, and D strands in one sheet and A', G, F, C, C' and C" in the other. The structures in C1-set are smaller than those in the V-set; they have one beta sheet that is formed by strands A, B, E, and D and the other by strands G, F, C, and C'. Moreover, a C1-set Ig domain contains a short C' strand (three residues) and lacks A' and C" strand. Unlike other Ig domain sets, C2-set structures do not have a D strand. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409353 [Multi-domain]  Cd Length: 70  Bit Score: 71.59  E-value: 3.63e-15
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 27777648  682 IEVTCPASGNPTPHITWFKDNETLVEDS--GIVLRDGNRNLTIRRVRKEDGGLYTCQACNVLG 742
Cdd:cd00096    1 VTLTCSASGNPPPTITWYKNGKPLPPSSrdSRRSELGNGTLTISNVTLEDSGTYTCVASNSAG 63
STKc_MST3 cd06641
Catalytic domain of the Serine/Threonine Kinase, Mammalian Ste20-like protein kinase 3; STKs ...
1009-1157 3.95e-15

Catalytic domain of the Serine/Threonine Kinase, Mammalian Ste20-like protein kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MST3 phosphorylates the STK NDR and may play a role in cell cycle progression and cell morphology. It may also regulate paxillin and consequently, cell migration. MST3 is present in human placenta, where it plays an essential role in the oxidative stress-induced apoptosis of trophoblasts in normal spontaneous delivery. Dysregulation of trophoblast apoptosis may result in pregnancy complications such as preeclampsia and intrauterine growth retardation. The MST3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270809 [Multi-domain]  Cd Length: 277  Bit Score: 77.42  E-value: 3.95e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1009 QVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIyKDPDYVRKGDARLPLkWMAPETIFDRVYTIQSDVWS 1088
Cdd:cd06641  109 EILKGLDYLHSEKKIHRDIKAANVLLSEHGEVKLADFGVAGQL-TDTQIKRN*FVGTPF-WMAPEVIKQSAYDSKADIWS 186
                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 27777648 1089 FGVLLWEIfSLGASPYPGVKIDEEFCRRLKEGTRMRAPDYTTpEMYQTMLDCWHEDPNQRPSFSELVEH 1157
Cdd:cd06641  187 LGITAIEL-ARGEPPHSELHPMKVLFLIPKNNPPTLEGNYSK-PLKEFVEACLNKEPSFRPTAKELLKH 253
STKc_ULK4 cd14010
Catalytic domain of the Serine/Threonine kinase, Unc-51-like kinase 4; STKs catalyze the ...
1010-1157 4.19e-15

Catalytic domain of the Serine/Threonine kinase, Unc-51-like kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. ULK4 is a functionally uncharacterized kinase that shows similarity to ATG1/ULKs. The ATG1/ULK complex is conserved from yeast to humans and it plays a critical role in the initiation of autophagy, the intracellular system that leads to the lysosomal degradation of cellular components and their recycling into basic metabolic units. The ULK4 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270912 [Multi-domain]  Cd Length: 269  Bit Score: 76.95  E-value: 4.19e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1010 VAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLAR---DIYKDP-------DYVRKGDARLPLK----WMAPETI 1075
Cdd:cd14010  103 LVRGLHYIHSKGIIYCDLKPSNILLDGNGTLKLSDFGLARregEILKELfgqfsdeGNVNKVSKKQAKRgtpyYMAPELF 182
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1076 FDRVYTIQSDVWSFGVLLWEIFSlGASPYPGVKIDEefcrrLKEGTRMRAPDYTTPEM-------YQTMLDCWHE-DPNQ 1147
Cdd:cd14010  183 QGGVHSFASDLWALGCVLYEMFT-GKPPFVAESFTE-----LVEKILNEDPPPPPPKVsskpspdFKSLLKGLLEkDPAK 256
                        170
                 ....*....|
gi 27777648 1148 RPSFSELVEH 1157
Cdd:cd14010  257 RLSWDELVKH 266
STKc_CCRK cd07832
Catalytic domain of the Serine/Threonine Kinase, Cell Cycle-Related Kinase; STKs catalyze the ...
834-1133 4.66e-15

Catalytic domain of the Serine/Threonine Kinase, Cell Cycle-Related Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CCRK was previously called p42. It is a Cyclin-Dependent Kinase (CDK)-Activating Kinase (CAK) which is essential for the activation of CDK2. It is indispensable for cell growth and has been implicated in the progression of glioblastoma multiforme. In the heart, a splice variant of CCRK with a different C-terminal half is expressed; this variant promotes cardiac cell growth and survival and is significantly down-regulated during the development of heart failure. The CCRK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270826 [Multi-domain]  Cd Length: 287  Bit Score: 77.37  E-value: 4.66e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  834 LGKpLGRGAFGQVIEADAFGIDKTATCKTVAVKMLKEGATHSehraLMSELKILIHIGHHLNVVNLLGACTKPGGPLMVI 913
Cdd:cd07832    5 LGR-IGEGAHGIVFKAKDRETGETVALKKVALRKLEGGIPNQ----ALREIKALQACQGHPYVVKLRDVFPHGTGFVLVF 79
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  914 vefckfgnlstylrgkrnEFVPykskgarfrqgkdyvgelsvdlkrrldsitssqssassgfveeKSLSDVEEEeaseel 993
Cdd:cd07832   80 ------------------EYML-------------------------------------------SSLSEVLRD------ 92
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  994 YKDFLTLEHLICYSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIYKDPDyvRKGDARLPLKW-MAP 1072
Cdd:cd07832   93 EERPLTEAQVKRYMRMLLKGVAYMHANRIMHRDLKPANLLISSTGVLKIADFGLARLFSEEDP--RLYSHQVATRWyRAP 170
                        250       260       270       280       290       300
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 27777648 1073 ETIF-DRVYTIQSDVWSFGVLLWEIfsLGASP-YPGVKIDEEFCRRLKE-GTrmraPDYTT-PEM 1133
Cdd:cd07832  171 ELLYgSRKYDEGVDLWAVGCIFAEL--LNGSPlFPGENDIEQLAIVLRTlGT----PNEKTwPEL 229
STKc_CDKL1_4 cd07847
Catalytic domain of the Serine/Threonine Kinases, Cyclin-Dependent protein Kinase Like 1 and 4; ...
1008-1157 4.85e-15

Catalytic domain of the Serine/Threonine Kinases, Cyclin-Dependent protein Kinase Like 1 and 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDKL1, also called p42 KKIALRE, is a glial protein that is upregulated in gliosis. It is present in neuroblastoma and A431 human carcinoma cells, and may be implicated in neoplastic transformation. The function of CDKL4 is unknown. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDKL1/4 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270837 [Multi-domain]  Cd Length: 286  Bit Score: 77.03  E-value: 4.85e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1008 FQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLAR------DIYKdpDYVrkgdarlPLKWM-APETIF-DRV 1079
Cdd:cd07847  107 WQTLQAVNFCHKHNCIHRDVKPENILITKQGQIKLCDFGFARiltgpgDDYT--DYV-------ATRWYrAPELLVgDTQ 177
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1080 YTIQSDVWSFGVLLWEIFSlGASPYPG-VKIDE---------EFCRRLK--------------------EGTRMRAPDYT 1129
Cdd:cd07847  178 YGPPVDVWAIGCVFAELLT-GQPLWPGkSDVDQlylirktlgDLIPRHQqifstnqffkglsipepetrEPLESKFPNIS 256
                        170       180
                 ....*....|....*....|....*...
gi 27777648 1130 TPEMyQTMLDCWHEDPNQRPSFSELVEH 1157
Cdd:cd07847  257 SPAL-SFLKGCLQMDPTERLSCEELLEH 283
STKc_C-Raf cd14149
Catalytic domain of the Serine/Threonine Kinase, C-Raf (Rapidly Accelerated Fibrosarcoma) ...
974-1163 5.89e-15

Catalytic domain of the Serine/Threonine Kinase, C-Raf (Rapidly Accelerated Fibrosarcoma) kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. C-Raf, also known as Raf-1 or c-Raf-1, is ubiquitously expressed and was the first Raf identified. It was characterized as the acquired oncogene from an acutely transforming murine sarcoma virus (3611-MSV) and the transforming agent from the avian retrovirus MH2. C-Raf-deficient mice embryos die around midgestation with increased apoptosis of embryonic tissues, especially in the fetal liver. One of the main functions of C-Raf is restricting caspase activation to promote survival in response to specific stimuli such as Fas stimulation, macrophage apoptosis, and erythroid differentiation. C-Raf is a mitogen-activated protein kinase kinase kinase (MAP3K, MKKK, MAPKKK), which phosphorylates and activates MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. It functions in the linear Ras-Raf-MEK-ERK pathway that regulates many cellular processes including cycle regulation, proliferation, differentiation, survival, and apoptosis. The C-Raf subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271051 [Multi-domain]  Cd Length: 283  Bit Score: 76.99  E-value: 5.89e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  974 GFVEEKSLSDVEEEEASEELYKDFLTLE------HLICYSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGL 1047
Cdd:cd14149   75 GYMTKDNLAIVTQWCEGSSLYKHLHVQEtkfqmfQLIDIARQTAQGMDYLHAKNIIHRDMKSNNIFLHEGLTVKIGDFGL 154
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1048 A--RDIYKDPDYVRKGDARlpLKWMAPETIF---DRVYTIQSDVWSFGVLLWEIFSlGASPYPGVKIDEEFCRRLKEGtr 1122
Cdd:cd14149  155 AtvKSRWSGSQQVEQPTGS--ILWMAPEVIRmqdNNPFSFQSDVYSYGIVLYELMT-GELPYSHINNRDQIIFMVGRG-- 229
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*..
gi 27777648 1123 MRAPDYTT------PEMYQTMLDCWHEDPNQRPSFSELVEHLgNLLQ 1163
Cdd:cd14149  230 YASPDLSKlykncpKAMKRLVADCIKKVKEERPLFPQILSSI-ELLQ 275
PKc_Dusty cd13975
Catalytic domain of the Dual-specificity Protein Kinase, Dusty; Dual-specificity PKs catalyze ...
998-1163 6.46e-15

Catalytic domain of the Dual-specificity Protein Kinase, Dusty; Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine as well as tyrosine residues on protein substrates. Dusty protein kinase is also called Receptor-interacting protein kinase 5 (RIPK5 or RIP5) or RIP-homologous kinase. It is widely distributed in the central nervous system, and may be involved in inducing both caspase-dependent and caspase-independent cell death. The Dusty subfamily is part of a larger superfamily that includes the catalytic domains of other protein serine/threonine PKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270877 [Multi-domain]  Cd Length: 262  Bit Score: 76.38  E-value: 6.46e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  998 LTLEHLICYSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARdiykdPDYVRKGD-ARLPLKwMAPEtIF 1076
Cdd:cd13975   99 LSLEERLQIALDVVEGIRFLHSQGLVHRDIKLKNVLLDKKNRAKITDLGFCK-----PEAMMSGSiVGTPIH-MAPE-LF 171
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1077 DRVYTIQSDVWSFGVLLWEIFSlgaspyPGVKIDEEF--CRR-------LKEGTRMRAPDYTTPEMYQTMLDCWHEDPNQ 1147
Cdd:cd13975  172 SGKYDNSVDVYAFGILFWYLCA------GHVKLPEAFeqCASkdhlwnnVRKGVRPERLPVFDEECWNLMEACWSGDPSQ 245
                        170
                 ....*....|....*.
gi 27777648 1148 RPSFSELVEHLGNLLQ 1163
Cdd:cd13975  246 RPLLGIVQPKLQGIMD 261
VEGFR-2_TMD pfam17988
VEGFR-2 Transmembrane domain; This is a transmembrane domain (TMD) of vascular endothelial ...
757-791 8.26e-15

VEGFR-2 Transmembrane domain; This is a transmembrane domain (TMD) of vascular endothelial growth factor receptor 2 which regulates blood vessel homeostasis. Transmembrane signalling by receptor tyrosine kinases (RTKs) requires specific orientation of the intracellular kinase domains in active receptor dimers. Two mutants in VEGFR-2 TMD showed constitutive kinase activity, suggesting that precise TMD orientation is mandatory for kinase activation. Scanning mutagenesis and structural analysis indicated that introducing two polar amino acids in distinct positions of the TMD (G770E/F777E and I771E/L778E mutations) reorients transmembrane helices and leads to stable dimer formation. Therefore, it has been suggested that the transition between the inactive and the active dimeric state of VEGFR-2 implicates alternative dimeric TMD conformations.


Pssm-ID: 375470  Cd Length: 35  Bit Score: 69.29  E-value: 8.26e-15
                           10        20        30
                   ....*....|....*....|....*....|....*
gi 27777648    757 EKTNLEVIILVGTAVIAMFFWLLLVIVLRTVKRAN 791
Cdd:pfam17988    1 DKTNVELIILIGTGVIAMFFWLLLVLVIRNLKRPN 35
PK_GC-A_B cd14042
Pseudokinase domain of the membrane Guanylate Cyclase receptors, GC-A and GC-B; The ...
980-1154 9.11e-15

Pseudokinase domain of the membrane Guanylate Cyclase receptors, GC-A and GC-B; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity and/or ATP binding. GC-A binds and is activated by the atrial and B-type natriuretic peptides, ANP and BNP, which are important in blood pressure regulation and cardiac pathophysiology. GC-B binds the C-type natriuretic peptide, CNP, which is a potent vasorelaxant and functions in vascular remodeling and bone growth regulation. Membrane (or particulate) GCs consist of an extracellular ligand-binding domain, a single transmembrane region, and an intracellular tail that contains a PK-like domain, an amphiphatic region and a catalytic GC domain that catalyzes the conversion of GTP into cGMP and pyrophosphate. Membrane GCs act as receptors that transduce an extracellular signal to the intracellular production of cGMP, which has been implicated in many processes including cell proliferation, phototransduction, and muscle contractility, through its downstream effectors such as PKG. The PK-like domain of GCs functions as a negative regulator of the catalytic GC domain and may also act as a docking site for interacting proteins such as GC-activating proteins. The GC-A/B subfamily is part of a larger superfamily that includes the catalytic domains of protein serine/threonine kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270944 [Multi-domain]  Cd Length: 279  Bit Score: 76.09  E-value: 9.11e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  980 SLSDVeeeeaseeLYKDFLTLEHLICYSF--QVAKGMEFL-ASRKCIHRDLAARNILLSEKNVVKICDFGLA--RDIYKD 1054
Cdd:cd14042   88 SLQDI--------LENEDIKLDWMFRYSLihDIVKGMHYLhDSEIKSHGNLKSSNCVVDSRFVLKITDFGLHsfRSGQEP 159
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1055 PDYVRKGDARLpLkWMAPETIFDRVY----TIQSDVWSFGVLLWEI------FSLGASPYPGVKIDEEfCRRLKEGTRMR 1124
Cdd:cd14042  160 PDDSHAYYAKL-L-WTAPELLRDPNPpppgTQKGDVYSFGIILQEIatrqgpFYEEGPDLSPKEIIKK-KVRNGEKPPFR 236
                        170       180       190
                 ....*....|....*....|....*....|...
gi 27777648 1125 A---PDYTTPEMYQTMLDCWHEDPNQRPSFSEL 1154
Cdd:cd14042  237 PsldELECPDEVLSLMQRCWAEDPEERPDFSTL 269
STKc_NAK1_like cd06917
Catalytic domain of Fungal Nak1-like Serine/Threonine Kinases; STKs catalyze the transfer of ...
1014-1154 1.07e-14

Catalytic domain of Fungal Nak1-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of Schizosaccharomyces pombe Nak1, Saccharomyces cerevisiae Kic1p (kinase that interacts with Cdc31p) and related proteins. Nak1 (also called N-rich kinase 1), is required by fission yeast for polarizing the tips of actin cytoskeleton and is involved in cell growth, cell separation, cell morphology and cell-cycle progression. Kic1p is required by budding yeast for cell integrity and morphogenesis. Kic1p interacts with Cdc31p, the yeast homologue of centrin, and phosphorylates substrates in a Cdc31p-dependent manner. The Nak1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270822 [Multi-domain]  Cd Length: 277  Bit Score: 75.97  E-value: 1.07e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1014 MEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIYKDPDYvRKGDARLPLkWMAPETIFD-RVYTIQSDVWSFGVL 1092
Cdd:cd06917  114 LKFIHKDGIIHRDIKAANILVTNTGNVKLCDFGVAASLNQNSSK-RSTFVGTPY-WMAPEVITEgKYYDTKADIWSLGIT 191
                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 27777648 1093 LWEIfSLGASPYPgvkiDEEFCRRLKEGTRMRAP----DYTTPEMYQTMLDCWHEDPNQRPSFSEL 1154
Cdd:cd06917  192 TYEM-ATGNPPYS----DVDALRAVMLIPKSKPPrlegNGYSPLLKEFVAACLDEEPKDRLSADEL 252
STKc_ULK1 cd14202
Catalytic domain of the Serine/Threonine kinase, Unc-51-like kinase 1; STKs catalyze the ...
824-1157 1.12e-14

Catalytic domain of the Serine/Threonine kinase, Unc-51-like kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The ATG1/ULK complex is conserved from yeast to humans and it plays a critical role in the initiation of autophagy, the intracellular system that leads to the lysosomal degradation of cellular components and their recycling into basic metabolic units. ULK1 is required for efficient amino acid starvation-induced autophagy and mitochondrial clearance. It associates with three autophagy-related proteins (Atg13, FIP200 amd Atg101) to form the ULK1 complex. All fours proteins are essential for autophagosome formation. ULK1 is regulated by both mammalian target-of rapamycin complex 1 (mTORC1) and AMP-activated protein kinase (AMPK). mTORC1 negatively regulates the ULK1 complex in a nutrient-dependent manner while AMPK stimulates autophagy by inhibiting mTORC1. ULK1 also plays neuron-specific roles and is involved in non-clathrin-coated endocytosis in growth cones, filopodia extension, neurite extension, and axon branching. The ULK1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271104 [Multi-domain]  Cd Length: 267  Bit Score: 75.82  E-value: 1.12e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  824 KWEFPRDRLklgkpLGRGAFGQVIEadafGIDKTATCKTVAVKMLKEGATHSEHRALMSELKILIHIGHHlNVVNLLGAc 903
Cdd:cd14202    1 KFEFSRKDL-----IGHGAFAVVFK----GRHKEKHDLEVAVKCINKKNLAKSQTLLGKEIKILKELKHE-NIVALYDF- 69
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  904 TKPGGPLMVIVEFCKFGNLSTYLRGKRNefvpykskgarfrqgkdyvgeLSVDLKRrldsitssqssassgfveekslsd 983
Cdd:cd14202   70 QEIANSVYLVMEYCNGGDLADYLHTMRT---------------------LSEDTIR------------------------ 104
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  984 veeeeaseelykdfLTLEhlicysfQVAKGMEFLASRKCIHRDLAARNILLS--------EKNV-VKICDFGLARdiYKD 1054
Cdd:cd14202  105 --------------LFLQ-------QIAGAMKMLHSKGIIHRDLKPQNILLSysggrksnPNNIrIKIADFGFAR--YLQ 161
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1055 PDYVRKGDARLPLkWMAPETIFDRVYTIQSDVWSFGVLLWEIFSlGASPYPGVKIDEefCRRLKEGTRMRAPDY---TTP 1131
Cdd:cd14202  162 NNMMAATLCGSPM-YMAPEVIMSQHYDAKADLWSIGTIIYQCLT-GKAPFQASSPQD--LRLFYEKNKSLSPNIpreTSS 237
                        330       340
                 ....*....|....*....|....*.
gi 27777648 1132 EMYQTMLDCWHEDPNQRPSFSELVEH 1157
Cdd:cd14202  238 HLRQLLLGLLQRNQKDRMDFDEFFHH 263
STKc_STK10 cd06644
Catalytic domain of the Serine/Threonine Kinase, STK10 (also called Lymphocyte-Oriented Kinase ...
828-1157 1.21e-14

Catalytic domain of the Serine/Threonine Kinase, STK10 (also called Lymphocyte-Oriented Kinase or LOK); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. STK10/LOK is also called polo-like kinase kinase 1 in Xenopus (xPlkk1). It is highly expressed in lymphocytes and is responsible in regulating leukocyte function associated antigen (LFA-1)-mediated lymphocyte adhesion. It plays a role in regulating the CD28 responsive element in T cells, and may also function as a regulator of polo-like kinase 1 (Plk1), a protein which is overexpressed in multiple tumor types. The STK10 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 132975 [Multi-domain]  Cd Length: 292  Bit Score: 76.22  E-value: 1.21e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  828 PRDRLKLGKPLGRGAFGQVIEADAFGIDKTATCKTVAVKmlkegaTHSEHRALMSELKILIHIGHHLnVVNLLGACTKPG 907
Cdd:cd06644   10 PNEVWEIIGELGDGAFGKVYKAKNKETGALAAAKVIETK------SEEELEDYMVEIEILATCNHPY-IVKLLGAFYWDG 82
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  908 gPLMVIVEFCKFGNlstylrgkrnefvpykskgarfrqgkdyVGELSVDLKRrldsitssqssassGFVEEKSlsdveee 987
Cdd:cd06644   83 -KLWIMIEFCPGGA----------------------------VDAIMLELDR--------------GLTEPQI------- 112
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  988 easeelykdfltleHLICYsfQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARdiyKDPDYVRKGDARLPL 1067
Cdd:cd06644  113 --------------QVICR--QMLEALQYLHSMKIIHRDLKAGNVLLTLDGDIKLADFGVSA---KNVKTLQRRDSFIGT 173
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1068 K-WMAP-----ETIFDRVYTIQSDVWSFGVLLWEIFSLgaSPyPGVKIDEefCRRLKEGTRMRAPDYTTPEMY------- 1134
Cdd:cd06644  174 PyWMAPevvmcETMKDTPYDYKADIWSLGITLIEMAQI--EP-PHHELNP--MRVLLKIAKSEPPTLSQPSKWsmefrdf 248
                        330       340
                 ....*....|....*....|....
gi 27777648 1135 -QTMLDcwhEDPNQRPSFSELVEH 1157
Cdd:cd06644  249 lKTALD---KHPETRPSAAQLLEH 269
STKc_LIMK2 cd14222
Catalytic domain of the Serine/Threonine Kinase, LIM domain kinase 2; STKs catalyze the ...
996-1154 1.42e-14

Catalytic domain of the Serine/Threonine Kinase, LIM domain kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. LIMK2 activation is induced by transforming growth factor-beta l (TGFb-l) and shares the same subcellular location as the cofilin family member twinfilin, which may be its biological substrate. LIMK2 plays a role in spermatogenesis, and may contribute to tumor progression and metastasis formation in some cancer cells. LIMKs phosphorylate and inactivate cofilin, an actin depolymerizing factor, to induce the reorganization of the actin cytoskeleton. They act downstream of Rho GTPases and are expressed ubiquitously. As regulators of actin dynamics, they contribute to diverse cellular functions such as cell motility, morphogenesis, differentiation, apoptosis, meiosis, mitosis, and neurite extension. LIMKs contain the LIM (two repeats), PDZ, and catalytic kinase domains. The LIMK2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271124 [Multi-domain]  Cd Length: 272  Bit Score: 75.75  E-value: 1.42e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  996 DFLTLEHLICYSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIYKD-----PD-------YVRKGDA 1063
Cdd:cd14222   85 DPFPWQQKVSFAKGIASGMAYLHSMSIIHRDLNSHNCLIKLDKTVVVADFGLSRLIVEEkkkppPDkpttkkrTLRKNDR 164
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1064 RLPLK------WMAPETIFDRVYTIQSDVWSFGVLLWEIF-SLGASPypgvkidEEFCRRLKEGTRMR------APDYTT 1130
Cdd:cd14222  165 KKRYTvvgnpyWMAPEMLNGKSYDEKVDIFSFGIVLCEIIgQVYADP-------DCLPRTLDFGLNVRlfwekfVPKDCP 237
                        170       180
                 ....*....|....*....|....
gi 27777648 1131 PEMYQTMLDCWHEDPNQRPSFSEL 1154
Cdd:cd14222  238 PAFFPLAAICCRLEPDSRPAFSKL 261
PKc_MKK5 cd06619
Catalytic domain of the dual-specificity Protein Kinase, Mitogen-activated protein Kinase ...
1010-1157 1.48e-14

Catalytic domain of the dual-specificity Protein Kinase, Mitogen-activated protein Kinase Kinase 5; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. MKK5 (also called MEK5) is a dual-specificity PK that phosphorylates its downstream target, extracellular signal-regulated kinase 5 (ERK5), on specific threonine and tyrosine residues. MKK5 is activated by MEKK2 and MEKK3 in response to mitogenic and stress stimuli. The ERK5 cascade promotes cell proliferation, differentiation, neuronal survival, and neuroprotection. This cascade plays an essential role in heart development. Mice deficient in either ERK5 or MKK5 die around embryonic day 10 due to cardiovascular defects including underdevelopment of the myocardium. In addition, MKK5 is associated with metastasis and unfavorable prognosis in prostate cancer. The MKK5 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 132950 [Multi-domain]  Cd Length: 279  Bit Score: 75.69  E-value: 1.48e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1010 VAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIYKD--PDYVRKGdarlplKWMAPETIFDRVYTIQSDVW 1087
Cdd:cd06619  104 VVKGLTYLWSLKILHRDVKPSNMLVNTRGQVKLCDFGVSTQLVNSiaKTYVGTN------AYMAPERISGEQYGIHSDVW 177
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1088 SFGVLLWEIfSLGASPYPGVK--------------IDEEFCRRLKEGTrmrapdyTTPEMYQTMLDCWHEDPNQRPSFSE 1153
Cdd:cd06619  178 SLGISFMEL-ALGRFPYPQIQknqgslmplqllqcIVDEDPPVLPVGQ-------FSEKFVHFITQCMRKQPKERPAPEN 249

                 ....
gi 27777648 1154 LVEH 1157
Cdd:cd06619  250 LMDH 253
STKc_Nek6 cd08228
Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase ...
1006-1152 1.50e-14

Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase 6; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Nek6 is required for the transition from metaphase to anaphase. It also plays important roles in mitotic spindle formation and cytokinesis. Activated by Nek9 during mitosis, Nek6 phosphorylates Eg5, a kinesin that is important for spindle bipolarity. Nek6 localizes to spindle microtubules during metaphase and anaphase, and to the midbody during cytokinesis. It is one in a family of 11 different Neks (Nek1-11) that are involved in cell cycle control. The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270865 [Multi-domain]  Cd Length: 268  Bit Score: 75.45  E-value: 1.50e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1006 YSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARdIYKDPDYVRKGDARLPLkWMAPETIFDRVYTIQSD 1085
Cdd:cd08228  111 YFVQLCSAVEHMHSRRVMHRDIKPANVFITATGVVKLGDLGLGR-FFSSKTTAAHSLVGTPY-YMSPERIHENGYNFKSD 188
                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 27777648 1086 VWSFGVLLWEIFSLgASPYPGVKIDE-EFCRRLKEGTRMRAPDYTTPEMYQTMLD-CWHEDPNQRPSFS 1152
Cdd:cd08228  189 IWSLGCLLYEMAAL-QSPFYGDKMNLfSLCQKIEQCDYPPLPTEHYSEKLRELVSmCIYPDPDQRPDIG 256
STKc_PLK1 cd14187
Catalytic domain of the Serine/Threonine Kinase, Polo-like kinase 1; STKs catalyze the ...
1006-1155 1.53e-14

Catalytic domain of the Serine/Threonine Kinase, Polo-like kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PLKs play important roles in cell cycle progression and in DNA damage responses. They regulate mitotic entry, mitotic exit, and cytokinesis. In general PLKs contain an N-terminal catalytic kinase domain and a C-terminal regulatory polo box domain (PBD), which is comprised by two bipartite polo-box motifs (or polo boxes) and is involved in protein interactions. There are five mammalian PLKs (PLK1-5) from distinct genes. PLK1 functions as a positive regulator of mitosis, meiosis, and cytokinesis. Its localization changes during mitotic progression; associating first with centrosomes in prophase, with kinetochores in prometaphase and metaphase, at the central spindle in anaphase, and in the midbody during telophase. It carries multiple functions throughout the cell cycle through interactions with differrent substrates at these specific subcellular locations. PLK1 is overexpressed in many human cancers and is associated with poor prognosis. The PLK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271089 [Multi-domain]  Cd Length: 265  Bit Score: 75.35  E-value: 1.53e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1006 YSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIYKDPDyvRKGDARLPLKWMAPETIFDRVYTIQSD 1085
Cdd:cd14187  112 YLRQIILGCQYLHRNRVIHRDLKLGNLFLNDDMEVKIGDFGLATKVEYDGE--RKKTLCGTPNYIAPEVLSKKGHSFEVD 189
                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 27777648 1086 VWSFGVLLWEIFsLGASPYpgvkidEEFCrrLKEG-TRMRAPDYTTPE--------MYQTMLdcwHEDPNQRPSFSELV 1155
Cdd:cd14187  190 IWSIGCIMYTLL-VGKPPF------ETSC--LKETyLRIKKNEYSIPKhinpvaasLIQKML---QTDPTARPTINELL 256
STKc_myosinIIIA_N cd06638
N-terminal Catalytic domain of the Serine/Threonine Kinase, Class IIIA myosin; STKs catalyze ...
828-1157 1.69e-14

N-terminal Catalytic domain of the Serine/Threonine Kinase, Class IIIA myosin; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Class IIIA myosin is highly expressed in retina and in inner ear hair cells. It is localized to the distal ends of actin-bundled structures. Mutations in human myosin IIIA are responsible for progressive nonsyndromic hearing loss. Human myosin IIIA possesses ATPase and kinase activities, and the ability to move actin filaments in a motility assay. It may function as a cellular transporter capable of moving along actin bundles in sensory cells. Class III myosins are motor proteins containing an N-terminal kinase catalytic domain and a C-terminal actin-binding domain. Class III myosins may play an important role in maintaining the structural integrity of photoreceptor cell microvilli. In photoreceptor cells, they may also function as cargo carriers during light-dependent translocation of proteins such as transducin and arrestin. The class III myosin subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 132969 [Multi-domain]  Cd Length: 286  Bit Score: 75.43  E-value: 1.69e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  828 PRDRLKLGKPLGRGAFGQVieadaFGIDKTATCKTVAVKMLKegATHSEHRALMSELKILIHIGHHLNVVNLLGACTKP- 906
Cdd:cd06638   16 PSDTWEIIETIGKGTYGKV-----FKVLNKKNGSKAAVKILD--PIHDIDEEIEAEYNILKALSDHPNVVKFYGMYYKKd 88
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  907 ---GGPLMVIVEFCKFGNLSTYLRGkrnefvpYKSKGARFRqgkdyvgelsvdlkrrldsitssqssassgfveekslsd 983
Cdd:cd06638   89 vknGDQLWLVLELCNGGSVTDLVKG-------FLKRGERME--------------------------------------- 122
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  984 veeeeaseelykdfltlEHLICYSFQVA-KGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIyKDPDYVRKGD 1062
Cdd:cd06638  123 -----------------EPIIAYILHEAlMGLQHLHVNKTIHRDVKGNNILLTTEGGVKLVDFGVSAQL-TSTRLRRNTS 184
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1063 ARLPLkWMAPETI-----FDRVYTIQSDVWSFGVLLWEifsLGASPYPGVKIDEefCRRLKEGTRMRAPDYTTPEMYQTM 1137
Cdd:cd06638  185 VGTPF-WMAPEVIaceqqLDSTYDARCDVWSLGITAIE---LGDGDPPLADLHP--MRALFKIPRNPPPTLHQPELWSNE 258
                        330       340
                 ....*....|....*....|....*
gi 27777648 1138 LD-----CWHEDPNQRPSFSELVEH 1157
Cdd:cd06638  259 FNdfirkCLTKDYEKRPTVSDLLQH 283
STKc_PAK_I cd06647
Catalytic domain of the Serine/Threonine Kinase, Group I p21-activated kinase; STKs catalyze ...
1009-1157 3.05e-14

Catalytic domain of the Serine/Threonine Kinase, Group I p21-activated kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Group I PAKs, also called conventional PAKs, include PAK1, PAK2, and PAK3. Group I PAKs contain a PBD (p21-binding domain) overlapping with an AID (autoinhibitory domain), a C-terminal catalytic domain, SH3 binding sites and a non-classical SH3 binding site for PIX (PAK-interacting exchange factor). They interact with the SH3 domain containing proteins Nck, Grb2 and PIX. Binding of group I PAKs to activated GTPases leads to conformational changes that destabilize the AID, allowing autophosphorylation and full activation of the kinase domain. Known group I PAK substrates include MLCK, Bad, Raf, MEK1, LIMK, Merlin, Vimentin, Myc, Stat5a, and Aurora A, among others. PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. PAKs are implicated in the regulation of many cellular processes including growth factor receptor-mediated proliferation, cell polarity, cell motility, cell death and survival, and actin cytoskeleton organization. The PAK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270814 [Multi-domain]  Cd Length: 261  Bit Score: 74.19  E-value: 3.05e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1009 QVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIykDPDYVRKGDARLPLKWMAPETIFDRVYTIQSDVWS 1088
Cdd:cd06647  111 ECLQALEFLHSNQVIHRDIKSDNILLGMDGSVKLTDFGFCAQI--TPEQSKRSTMVGTPYWMAPEVVTRKAYGPKVDIWS 188
                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 27777648 1089 FGVLLWEIFSlGASPYpgvkIDEEFCRRLKEGTRMRAPDYTTPE----MYQTMLD-CWHEDPNQRPSFSELVEH 1157
Cdd:cd06647  189 LGIMAIEMVE-GEPPY----LNENPLRALYLIATNGTPELQNPEklsaIFRDFLNrCLEMDVEKRGSAKELLQH 257
STKc_MLCK-like cd14006
Catalytic kinase domain of Myosin Light Chain Kinase-like Serine/Threonine Kinases; STKs ...
838-1157 3.08e-14

Catalytic kinase domain of Myosin Light Chain Kinase-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This family is composed of MLCKs and related MLCK-like kinase domains from giant STKs such as titin, obscurin, SPEG, Unc-89, Trio, kalirin, and Twitchin. Also included in this family are Death-Associated Protein Kinases (DAPKs) and Death-associated protein kinase-Related Apoptosis-inducing protein Kinase (DRAKs). MLCK phosphorylates myosin regulatory light chain and controls the contraction of all muscle types. Titin, obscurin, Twitchin, and SPEG are muscle proteins involved in the contractile apparatus. The giant STKs are multidomain proteins containing immunoglobulin (Ig), fibronectin type III (FN3), SH3, RhoGEF, PH and kinase domains. Titin, obscurin, Twitchin, and SPEG contain many Ig domain repeats at the N-terminus, while Trio and Kalirin contain spectrin-like repeats. The MLCK-like family is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270908 [Multi-domain]  Cd Length: 247  Bit Score: 73.84  E-value: 3.08e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  838 LGRGAFGQVieadaFGIDKTATCKTVAVKMLKEGAThsEHRALMSELKILIHIgHHLNVVNLLGACTKPGGpLMVIVEFC 917
Cdd:cd14006    1 LGRGRFGVV-----KRCIEKATGREFAAKFIPKRDK--KKEAVLREISILNQL-QHPRIIQLHEAYESPTE-LVLILELC 71
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  918 KFGNLSTYLRGKrnefvpykskgarfrqgkdyvGELSvdlkrrldsitssqssassgfvEEKSlsdveeeeaseelyKDF 997
Cdd:cd14006   72 SGGELLDRLAER---------------------GSLS----------------------EEEV--------------RTY 94
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  998 LTlehlicysfQVAKGMEFLASRKCIHRDLAARNILLSEKNV--VKICDFGLARDIYK-DPDYVRKGDarlpLKWMAPET 1074
Cdd:cd14006   95 MR---------QLLEGLQYLHNHHILHLDLKPENILLADRPSpqIKIIDFGLARKLNPgEELKEIFGT----PEFVAPEI 161
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1075 IFDRVYTIQSDVWSFGVLLWEIFSlGASPYPGvKIDEEFCRRLKEGtRMR----APDYTTPEMYQTMLDCWHEDPNQRPS 1150
Cdd:cd14006  162 VNGEPVSLATDMWSIGVLTYVLLS-GLSPFLG-EDDQETLANISAC-RVDfseeYFSSVSQEAKDFIRKLLVKEPRKRPT 238

                 ....*..
gi 27777648 1151 FSELVEH 1157
Cdd:cd14006  239 AQEALQH 245
IgI_VEGFR-3 cd05863
Immunoglobulin (Ig)-like domain of vascular endothelial growth factor receptor 3 (VEGFR-3); ...
330-411 3.25e-14

Immunoglobulin (Ig)-like domain of vascular endothelial growth factor receptor 3 (VEGFR-3); member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin (Ig)-like domain of vascular endothelial growth factor receptor 3 (VEGFR-3). The VEGFRs have an extracellular component with seven Ig-like domains, a transmembrane segment, and an intracellular tyrosine kinase domain interrupted by a kinase-insert domain. VEGFRs bind VEGFs with high affinity at the Ig-like domains. VEGFR-3 (Flt-4) binds two members of the VEGF family (VEGF-C and VEGF-D) and is involved in tumor angiogenesis and growth. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409449  Cd Length: 88  Bit Score: 69.20  E-value: 3.25e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  330 PFIAFGSGMKSLVEATVGSQ-VRIPVKYLSYPAPDIKWYRNGRPIESNYTmivGDELTIMEVTERDAGNYTVILTN-PIS 407
Cdd:cd05863    1 PFISVEWRKGPVIEATAGDElVKLPVKVAAYPPPEFQWYKDGKLISGKHS---PHSLQIKDVTEASAGTYTLVLWNsAAG 77

                 ....
gi 27777648  408 MEKQ 411
Cdd:cd05863   78 LEKR 81
STKc_nPKC_theta_like cd05592
Catalytic domain of the Serine/Threonine Kinases, Novel Protein Kinase C theta, delta, and ...
1006-1113 3.44e-14

Catalytic domain of the Serine/Threonine Kinases, Novel Protein Kinase C theta, delta, and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKC-theta is selectively expressed in T-cells and plays an important and non-redundant role in several aspects of T-cell biology. PKC-delta plays a role in cell cycle regulation and programmed cell death in many cell types. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. nPKCs are calcium-independent, but require DAG (1,2-diacylglycerol) and phosphatidylserine (PS) for activity. There are four nPKC isoforms, delta, epsilon, eta, and theta. The nPKC-theta-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270744 [Multi-domain]  Cd Length: 320  Bit Score: 75.11  E-value: 3.44e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1006 YSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLAR-DIYKD---------PDYvrkgdarlplkwMAPETI 1075
Cdd:cd05592  101 YGAEIICGLQFLHSRGIIYRDLKLDNVLLDREGHIKIADFGMCKeNIYGEnkastfcgtPDY------------IAPEIL 168
                         90       100       110
                 ....*....|....*....|....*....|....*...
gi 27777648 1076 FDRVYTIQSDVWSFGVLLWEIFsLGASPYPGVKIDEEF 1113
Cdd:cd05592  169 KGQKYNQSVDWWSFGVLLYEML-IGQSPFHGEDEDELF 205
STKc_MEKK3_like cd06625
Catalytic domain of Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) ...
833-1157 3.70e-14

Catalytic domain of Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase Kinase 3-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of MEKK3, MEKK2, and related proteins; all contain an N-terminal PB1 domain, which mediates oligomerization, and a C-terminal catalytic domain. MEKK2 and MEKK3 are MAPK kinase kinases (MAPKKKs or MKKK) that activate MEK5 (also called MKK5), which activates ERK5. The ERK5 cascade plays roles in promoting cell proliferation, differentiation, neuronal survival, and neuroprotection. MEKK3 plays an essential role in embryonic angiogenesis and early heart development. MEKK2 and MEKK3 can also activate the MAPKs, c-Jun N-terminal kinase (JNK) and p38, through their respective MAPKKs. The MEKK3-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270795 [Multi-domain]  Cd Length: 260  Bit Score: 73.93  E-value: 3.70e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  833 KLGKPLGRGAFGQV---IEADafgidktaTCKTVAVKML----KEGATHSEHRALMSELKILIHIgHHLNVVNLLGaCTK 905
Cdd:cd06625    3 KQGKLLGQGAFGQVylcYDAD--------TGRELAVKQVeidpINTEASKEVKALECEIQLLKNL-QHERIVQYYG-CLQ 72
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  906 PGGPLMVIVEFCKFGNLSTYLrgkrnefvpykskgarfrqgKDYvGELSVDLKRrldsitssqssassgfveekslsdve 985
Cdd:cd06625   73 DEKSLSIFMEYMPGGSVKDEI--------------------KAY-GALTENVTR-------------------------- 105
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  986 eeeaseelykdfltlehliCYSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIykdpDYVRKGDARL 1065
Cdd:cd06625  106 -------------------KYTRQILEGLAYLHSNMIVHRDIKGANILRDSNGNVKLGDFGASKRL----QTICSSTGMK 162
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1066 PLK----WMAPETIFDRVYTIQSDVWSFGVLL---------WEIFSLGASPYpgvKIdeefcrrLKEGTRMRAPDYTTPE 1132
Cdd:cd06625  163 SVTgtpyWMSPEVINGEGYGRKADIWSVGCTVvemlttkppWAEFEPMAAIF---KI-------ATQPTNPQLPPHVSED 232
                        330       340
                 ....*....|....*....|....*
gi 27777648 1133 MYQTMLDCWHEDPNQRPSFSELVEH 1157
Cdd:cd06625  233 ARDFLSLIFVRNKKQRPSAEELLSH 257
PK_GC-2D cd14043
Pseudokinase domain of the membrane Guanylate Cyclase receptor, GC-2D; The pseudokinase domain ...
1012-1154 3.92e-14

Pseudokinase domain of the membrane Guanylate Cyclase receptor, GC-2D; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity and/or ATP binding. GC-2D is allso called Retinal Guanylyl Cyclase 1 (RETGC-1) or Rod Outer Segment membrane Guanylate Cyclase (ROS-GC). It is found in the photoreceptors of the retina where it anchors the reciprocal feedback loop between calcium and cGMP, which regulates the dark, light, and recovery phases in phototransduction. It is also found in other sensory neurons and may be a universal transduction component that plays a role in the perception of all senses. Membrane (or particulate) GCs consist of an extracellular ligand-binding domain, a single transmembrane region, and an intracellular tail that contains a PK-like domain, an amphiphatic region and a catalytic GC domain that catalyzes the conversion of GTP into cGMP and pyrophosphate. Membrane GCs act as receptors that transduce an extracellular signal to the intracellular production of cGMP, which has been implicated in many processes including cell proliferation, phototransduction, and muscle contractility, through its downstream effectors such as PKG. The PK-like domain of GCs functions as a negative regulator of the catalytic GC domain and may also act as a docking site for interacting proteins such as GC-activating proteins. The GC-2D subfamily is part of a larger superfamily that includes the catalytic domains of protein serine/threonine kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270945 [Multi-domain]  Cd Length: 267  Bit Score: 73.98  E-value: 3.92e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1012 KGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLArDIYKDPDYVRKGDARLPLKWMAPETIFDRVY----TIQSDVW 1087
Cdd:cd14043  108 KGMRYLHHRGIVHGRLKSRNCVVDGRFVLKITDYGYN-EILEAQNLPLPEPAPEELLWTAPELLRDPRLerrgTFPGDVF 186
                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 27777648 1088 SFGVLLWEIFSLGAsPYPGVKID-EEFCRRLKEGTRMRAP----DYTTPEMYQTMLDCWHEDPNQRPSFSEL 1154
Cdd:cd14043  187 SFAIIMQEVIVRGA-PYCMLGLSpEEIIEKVRSPPPLCRPsvsmDQAPLECIQLMKQCWSEAPERRPTFDQI 257
PKc_Byr1_like cd06620
Catalytic domain of fungal Byr1-like dual-specificity Mitogen-activated protein Kinase Kinases; ...
828-1157 4.07e-14

Catalytic domain of fungal Byr1-like dual-specificity Mitogen-activated protein Kinase Kinases; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. Members of this group include the MAPKKs Byr1 from Schizosaccharomyces pombe, FUZ7 from Ustilago maydis, and related proteins. Byr1 phosphorylates its downstream target, the MAPK Spk1, and is regulated by the MAPKK kinase Byr2. The Spk1 cascade is pheromone-responsive and is essential for sporulation and sexual differentiation in fission yeast. FUZ7 phosphorylates and activates its target, the MAPK Crk1, which is required in mating and virulence in U. maydis. MAPK signaling pathways are important mediators of cellular responses to extracellular signals. The Byr-1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270792 [Multi-domain]  Cd Length: 286  Bit Score: 74.40  E-value: 4.07e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  828 PRDRLKLGKpLGRGAFGQVIEadafgIDKTATCKTVAVKMLKEGATHSEHRALMSELKILiHIGHHLNVVNLLGACTKPG 907
Cdd:cd06620    4 NQDLETLKD-LGAGNGGSVSK-----VLHIPTGTIMAKKVIHIDAKSSVRKQILRELQIL-HECHSPYIVSFYGAFLNEN 76
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  908 GPLMVIVEFCKFGNLSTYLRGKrnefvpykskgarfrqgkdyvGELSVDlkrrldsitssqssassgfveekslsdveee 987
Cdd:cd06620   77 NNIIICMEYMDCGSLDKILKKK---------------------GPFPEE------------------------------- 104
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  988 easeelykdflTLEHLicySFQVAKGMEFLASR-KCIHRDLAARNILLSEKNVVKICDFGLARDIYKDPDYVRKGDArlp 1066
Cdd:cd06620  105 -----------VLGKI---AVAVLEGLTYLYNVhRIIHRDIKPSNILVNSKGQIKLCDFGVSGELINSIADTFVGTS--- 167
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1067 lKWMAPETIFDRVYTIQSDVWSFGVLLWEIfSLGASPYPGVKIDE----------EFCRRL--KEGTRMRAPDYTTPEMY 1134
Cdd:cd06620  168 -TYMSPERIQGGKYSVKSDVWSLGLSIIEL-ALGEFPFAGSNDDDdgyngpmgilDLLQRIvnEPPPRLPKDRIFPKDLR 245
                        330       340
                 ....*....|....*....|...
gi 27777648 1135 QTMLDCWHEDPNQRPSFSELVEH 1157
Cdd:cd06620  246 DFVDRCLLKDPRERPSPQLLLDH 268
STKc_RIP4_like cd14025
Catalytic domain of the Serine/Threonine kinases, Receptor Interacting Protein 4 and similar ...
1009-1163 4.21e-14

Catalytic domain of the Serine/Threonine kinases, Receptor Interacting Protein 4 and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of RIP4, ankyrin (ANK) repeat and kinase domain containing 1 (ANKK1), and similar proteins, all of which harbor C-terminal ANK repeats. RIP4, also called Protein Kinase C-associated kinase (PKK), regulates keratinocyte differentiation and cutaneous inflammation. It activates NF-kappaB and is important in the survival of diffuse large B-cell lymphoma cells. The ANKK1 protein, also called PKK2, has not been studied extensively. The ANKK1 gene, located less than 10kb downstream of the D2 dopamine receptor (DRD2) locus, is altered in the Taq1 A1 polymorphism, which is related to a reduced DRD2 binding affinity and consequently, to mental disorders. The RIP4-like subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270927 [Multi-domain]  Cd Length: 267  Bit Score: 74.07  E-value: 4.21e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1009 QVAKGMEFLASRK--CIHRDLAARNILLSEKNVVKICDFGLAR--DIYKDPDYVRKGdARLPLKWMAPETIF--DRVYTI 1082
Cdd:cd14025  100 ETAVGMNFLHCMKppLLHLDLKPANILLDAHYHVKISDFGLAKwnGLSHSHDLSRDG-LRGTIAYLPPERFKekNRCPDT 178
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1083 QSDVWSFGVLLWEIFSlGASPYPGVKIDEEFCRRLKEGTR------MRAPDYTTPEMYQTMLDCWHEDPNQRPSFSELVE 1156
Cdd:cd14025  179 KHDVYSFAIVIWGILT-QKKPFAGENNILHIMVKVVKGHRpslspiPRQRPSECQQMICLMKRCWDQDPRKRPTFQDITS 257

                 ....*..
gi 27777648 1157 HLGNLLQ 1163
Cdd:cd14025  258 ETENLLS 264
STKc_Nek7 cd08229
Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase ...
1006-1152 5.02e-14

Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase 7; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Nek7 is required for mitotic spindle formation and cytokinesis. It is enriched in the centrosome and is critical for microtubule nucleation. Nek7 is activated by Nek9 during mitosis, and may regulate the p70 ribosomal S6 kinase. It is one in a family of 11 different Neks (Nek1-11) that are involved in cell cycle control. The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270866 [Multi-domain]  Cd Length: 292  Bit Score: 74.30  E-value: 5.02e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1006 YSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARdIYKDPDYVRKGDARLPLkWMAPETIFDRVYTIQSD 1085
Cdd:cd08229  133 YFVQLCSALEHMHSRRVMHRDIKPANVFITATGVVKLGDLGLGR-FFSSKTTAAHSLVGTPY-YMSPERIHENGYNFKSD 210
                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 27777648 1086 VWSFGVLLWEIFSLgASPYPGVKID-EEFCRRLKEGTRMRAP-DYTTPEMYQTMLDCWHEDPNQRPSFS 1152
Cdd:cd08229  211 IWSLGCLLYEMAAL-QSPFYGDKMNlYSLCKKIEQCDYPPLPsDHYSEELRQLVNMCINPDPEKRPDIT 278
STKc_EIF2AK2_PKR cd14047
Catalytic domain of the Serine/Threonine kinase, eukaryotic translation Initiation Factor ...
1009-1158 6.01e-14

Catalytic domain of the Serine/Threonine kinase, eukaryotic translation Initiation Factor 2-Alpha Kinase 2 or Protein Kinase regulated by RNA; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKR (or EIF2AK2) contains an N-terminal double-stranded RNA (dsRNA) binding domain and a C-terminal catalytic kinase domain. It is activated by dsRNA, which is produced as a replication intermediate in virally infected cells. It plays a key role in mediating innate immune responses to viral infection. PKR is also directly activated by PACT (protein activator of PKR) and heparin, and is inhibited by viral proteins and RNAs. PKR also regulates transcription and signal transduction in diseased cells, playing roles in tumorigenesis and neurodegenerative diseases. EIF2AKs phosphorylate the alpha subunit of eIF-2, resulting in the downregulation of protein synthesis. The PKR subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270949 [Multi-domain]  Cd Length: 267  Bit Score: 73.68  E-value: 6.01e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1009 QVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIykdPDYVRKGDARLPLKWMAPETIFDRVYTIQSDVWS 1088
Cdd:cd14047  125 QITKGVEYIHSKKLIHRDLKPSNIFLVDTGKVKIGDFGLVTSL---KNDGKRTKSKGTLSYMSPEQISSQDYGKEVDIYA 201
                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 27777648 1089 FGVLLWEIFSLGASPYP---------GVKIDEEFCRRLKegtrmrapdyTTPEMYQTMLDcwhEDPNQRPSFSELVEHL 1158
Cdd:cd14047  202 LGLILFELLHVCDSAFEkskfwtdlrNGILPDIFDKRYK----------IEKTIIKKMLS---KKPEDRPNASEILRTL 267
PKc_MKK7 cd06618
Catalytic domain of the dual-specificity Protein Kinase, Mitogen-activated protein Kinase ...
1023-1157 6.01e-14

Catalytic domain of the dual-specificity Protein Kinase, Mitogen-activated protein Kinase Kinase 7; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. MKK7 is a dual-specificity PK that phosphorylates and activates its downstream target, c-Jun N-terminal kinase (JNK), on specific threonine and tyrosine residues. Although MKK7 is capable of dual phosphorylation, it prefers to phosphorylate the threonine residue of JNK. Thus, optimal activation of JNK requires both MKK4 and MKK7. MKK7 is primarily activated by cytokines. MKK7 is essential for liver formation during embryogenesis. It plays roles in G2/M cell cycle arrest and cell growth. In addition, it is involved in the control of programmed cell death, which is crucial in oncogenesis, cancer chemoresistance, and antagonism to TNFalpha-induced killing, through its inhibition by Gadd45beta and the subsequent suppression of the JNK cascade. The MKK7 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270791 [Multi-domain]  Cd Length: 295  Bit Score: 73.95  E-value: 6.01e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1023 IHRDLAARNILLSEKNVVKICDFGLARDIYKDPDYVRKgdARLPLkWMAPETI----FDRvYTIQSDVWSFGVLLWEIfS 1098
Cdd:cd06618  137 IHRDVKPSNILLDESGNVKLCDFGISGRLVDSKAKTRS--AGCAA-YMAPERIdppdNPK-YDIRADVWSLGISLVEL-A 211
                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 27777648 1099 LGASPYPGVKID-EEFCRRLKEGTRMRAPDYTTPEMYQTMLD-CWHEDPNQRPSFSELVEH 1157
Cdd:cd06618  212 TGQFPYRNCKTEfEVLTKILNEEPPSLPPNEGFSPDFCSFVDlCLTKDHRYRPKYRELLQH 272
STKc_Nek8 cd08220
Catalytic domain of the Protein Serine/Threonine Kinase, Never In Mitosis gene A (NIMA) ...
975-1157 6.93e-14

Catalytic domain of the Protein Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase 8; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Nek8 contains an N-terminal kinase catalytic domain and a C-terminal RCC1 (regulator of chromosome condensation) domain. A double point mutation in Nek8 causes cystic kidney disease in mice that genetically resembles human autosomal recessive polycystic kidney disease (ARPKD). Nek8 is also associated with a rare form of juvenile renal cystic disease, nephronophthisis type 9. It has been suggested that a defect in the ciliary localization of Nek8 contributes to the development of cysts manifested by these diseases. Nek8 is one in a family of 11 different Neks (Nek1-11) that are involved in cell cycle control. The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270859 [Multi-domain]  Cd Length: 256  Bit Score: 73.23  E-value: 6.93e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  975 FVEEKSLSDVEEEEASEELYK-------DFLTLEHLICYSFQVAKGMEFLASRKCIHRDLAARNILLSEK-NVVKICDFG 1046
Cdd:cd08220   68 FLEDKALMIVMEYAPGGTLFEyiqqrkgSLLSEEEILHFFVQILLALHHVHSKQILHRDLKTQNILLNKKrTVVKIGDFG 147
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1047 LARDI-YKDPDYVRKGDArlplKWMAPETIFDRVYTIQSDVWSFGVLLWEIFSLG----ASPYPGVKIdeefcrRLKEGT 1121
Cdd:cd08220  148 ISKILsSKSKAYTVVGTP----CYISPELCEGKPYNQKSDIWALGCVLYELASLKrafeAANLPALVL------KIMRGT 217
                        170       180       190
                 ....*....|....*....|....*....|....*.
gi 27777648 1122 RMRAPDYTTPEMYQTMLDCWHEDPNQRPSFSELVEH 1157
Cdd:cd08220  218 FAPISDRYSEELRHLILSMLHLDPNKRPTLSEIMAQ 253
STKc_PDK1 cd05581
Catalytic domain of the Serine/Threonine Kinase, Phosphoinositide-dependent kinase 1; STKs ...
832-1107 6.99e-14

Catalytic domain of the Serine/Threonine Kinase, Phosphoinositide-dependent kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PDK1 carries an N-terminal catalytic domain and a C-terminal pleckstrin homology (PH) domain that binds phosphoinositides. It phosphorylates the activation loop of AGC kinases that are regulated by PI3K such as PKB, SGK, and PKC, among others, and is crucial for their activation. Thus, it contributes in regulating many processes including metabolism, growth, proliferation, and survival. PDK1 also has the ability to autophosphorylate and is constitutively active in mammalian cells. It is essential for normal embryo development and is important in regulating cell volume. The PDK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270733 [Multi-domain]  Cd Length: 278  Bit Score: 73.40  E-value: 6.99e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  832 LKLGKPLGRGAFGQVIEAdafgIDKTaTCKTVAVKML------KEGATHSehraLMSElKILIHIGHHLNVVNLLGACTK 905
Cdd:cd05581    3 FKFGKPLGEGSYSTVVLA----KEKE-TGKEYAIKVLdkrhiiKEKKVKY----VTIE-KEVLSRLAHPGIVKLYYTFQD 72
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  906 PGGpLMVIVEFCKFGNLSTYLRgkrnefvpykskgarfrqgkdYVGELSVDLKRrldsitssqssassgfveekslsdve 985
Cdd:cd05581   73 ESK-LYFVLEYAPNGDLLEYIR---------------------KYGSLDEKCTR-------------------------- 104
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  986 eeeaseelykdFltlehlicYSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIykDPDYV---RKGD 1062
Cdd:cd05581  105 -----------F--------YTAEIVLALEYLHSKGIIHRDLKPENILLDEDMHIKITDFGTAKVL--GPDSSpesTKGD 163
                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 27777648 1063 ARLPLKWM--------------APETIFDRVYTIQSDVWSFGVLLWEIFSlGASPYPGV 1107
Cdd:cd05581  164 ADSQIAYNqaraasfvgtaeyvSPELLNEKPAGKSSDLWALGCIIYQMLT-GKPPFRGS 221
STKc_CDK10 cd07845
Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 10; STKs ...
1005-1097 7.50e-14

Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 10; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK10, also called PISSLRE, is essential for cell growth and proliferation, and acts through the G2/M phase of the cell cycle. CDK10 has also been identified as an important factor in endocrine therapy resistance in breast cancer. CDK10 silencing increases the transcription of c-RAF and the activation of the p42/p44 MAPK pathway, which leads to antiestrogen resistance. Patients who express low levels of CDK10 relapse early on tamoxifen. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK10 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173742 [Multi-domain]  Cd Length: 309  Bit Score: 73.94  E-value: 7.50e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1005 CYSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARdIYKDPDyvrkgDARLP----LKWMAPETIF-DRV 1079
Cdd:cd07845  112 CLMLQLLRGLQYLHENFIIHRDLKVSNLLLTDKGCLKIADFGLAR-TYGLPA-----KPMTPkvvtLWYRAPELLLgCTT 185
                         90
                 ....*....|....*...
gi 27777648 1080 YTIQSDVWSFGVLLWEIF 1097
Cdd:cd07845  186 YTTAIDMWAVGCILAELL 203
PKc_MKK4 cd06616
Catalytic domain of the dual-specificity Protein Kinase, Mitogen-activated protein Kinase ...
1021-1157 7.85e-14

Catalytic domain of the dual-specificity Protein Kinase, Mitogen-activated protein Kinase Kinase 4; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. MKK4 is a dual-specificity PK that phosphorylates and activates the downstream targets, c-Jun N-terminal kinase (JNK) and p38 MAPK, on specific threonine and tyrosine residues. JNK and p38 are collectively known as stress-activated MAPKs, as they are activated in response to a variety of environmental stresses and pro-inflammatory cytokines. Their activation is associated with the induction of cell death. Mice deficient in MKK4 die during embryogenesis and display anemia, severe liver hemorrhage, and abnormal hepatogenesis. MKK4 may also play roles in the immune system and in cardiac hypertrophy. It plays a major role in cancer as a tumor and metastasis suppressor. Under certain conditions, MKK4 is pro-oncogenic. The MKK4 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270790 [Multi-domain]  Cd Length: 291  Bit Score: 73.55  E-value: 7.85e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1021 KCIHRDLAARNILLSEKNVVKICDFGLARDIYKDPDYVRKGDARlplKWMAPETI----FDRVYTIQSDVWSFGVLLWEI 1096
Cdd:cd06616  130 KIIHRDVKPSNILLDRNGNIKLCDFGISGQLVDSIAKTRDAGCR---PYMAPERIdpsaSRDGYDVRSDVWSLGITLYEV 206
                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 27777648 1097 fSLGASPYPGVK-IDEEFCRRLK-EGTRMRaPDYT---TPEMYQTMLDCWHEDPNQRPSFSELVEH 1157
Cdd:cd06616  207 -ATGKFPYPKWNsVFDQLTQVVKgDPPILS-NSEErefSPSFVNFVNLCLIKDESKRPKYKELLKH 270
PTK_Jak1_rpt1 cd05077
Pseudokinase (repeat 1) domain of the Protein Tyrosine Kinase, Janus kinase 1; Jak1 is widely ...
1006-1155 1.06e-13

Pseudokinase (repeat 1) domain of the Protein Tyrosine Kinase, Janus kinase 1; Jak1 is widely expressed in many tissues. Many cytokines are dependent on Jak1 for signaling, including those that use the shared receptor subunits, common gamma chain (IL-2, IL-4, IL-7, IL-9, IL-15, IL-21) and gp130 (IL-6, IL-11, oncostatin M, G-CSF, and IFNs, among others). The many varied interactions of Jak1 and its ubiquitous expression suggest many biological roles. Jak1 is important in neurological development, as well as in lymphoid development and function. It also plays a role in the pathophysiology of cardiac hypertrophy and heart failure. A mutation in the ATP-binding site of Jak1 was identified in a human uterine leiomyosarcoma cell line, resulting in defective cytokine induction and antigen presentation, thus allowing the tumor to evade the immune system. Jak1 is a cytoplasmic (or nonreceptor) PTK containing an N-terminal FERM domain, followed by a Src homology 2 (SH2) domain, a pseudokinase domain, and a C-terminal tyr kinase domain. The pseudokinase domain shows similarity to tyr kinases but lacks crucial residues for catalytic activity and ATP binding. It modulates the kinase activity of the C-terminal catalytic domain. The Jak1 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270662 [Multi-domain]  Cd Length: 266  Bit Score: 72.66  E-value: 1.06e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1006 YSFQVAK----GMEFLASRKCIHRDLAARNILLSEKNV-------VKICDFGLARDIYKDPDYVRkgdaRLPlkWMAPET 1074
Cdd:cd05077  110 WKFKVAKqlasALSYLEDKDLVHGNVCTKNILLAREGIdgecgpfIKLSDPGIPITVLSRQECVE----RIP--WIAPEC 183
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1075 IFD-RVYTIQSDVWSFGVLLWEIFSLGASPYPGVKIDEEfcRRLKEGT-RMRAPDytTPEMYQTMLDCWHEDPNQRPSFS 1152
Cdd:cd05077  184 VEDsKNLSIAADKWSFGTTLWEICYNGEIPLKDKTLAEK--ERFYEGQcMLVTPS--CKELADLMTHCMNYDPNQRPFFR 259

                 ...
gi 27777648 1153 ELV 1155
Cdd:cd05077  260 AIM 262
STKc_nPKC_theta cd05619
Catalytic domain of the Serine/Threonine Kinase, Novel Protein Kinase C theta; STKs catalyze ...
1006-1128 1.32e-13

Catalytic domain of the Serine/Threonine Kinase, Novel Protein Kinase C theta; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKC-theta is selectively expressed in T-cells and plays an important and non-redundant role in several aspects of T-cell biology. Although T-cells also express other PKC isoforms, PKC-theta is unique in that upon antigen stimulation, it is translocated to the plasma membrane at the immunological synapse, where it mediates signals essential for T-cell activation. It is essential for TCR-induced proliferation, cytokine production, T-cell survival, and the differentiation and effector function of T-helper (Th) cells, particularly Th2 and Th17. PKC-theta is being developed as a therapeutic target for Th2-mediated allergic inflammation and Th17-mediated autoimmune diseases. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. nPKCs are calcium-independent, but require DAG (1,2-diacylglycerol) and phosphatidylserine (PS) for activity. The nPKC subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270770 [Multi-domain]  Cd Length: 331  Bit Score: 73.80  E-value: 1.32e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1006 YSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARD-IYKD---------PDYVrkgdarlplkwmAPETI 1075
Cdd:cd05619  111 YAAEIICGLQFLHSKGIVYRDLKLDNILLDKDGHIKIADFGMCKEnMLGDaktstfcgtPDYI------------APEIL 178
                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|...
gi 27777648 1076 FDRVYTIQSDVWSFGVLLWEIFsLGASPYPGvkIDEEfcrRLKEGTRMRAPDY 1128
Cdd:cd05619  179 LGQKYNTSVDWWSFGVLLYEML-IGQSPFHG--QDEE---ELFQSIRMDNPFY 225
STKc_PAK1 cd06654
Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 1; STKs catalyze the ...
1012-1157 1.35e-13

Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PAK1 is important in the regulation of many cellular processes including cytoskeletal dynamics, cell motility, growth, and proliferation. Although PAK1 has been regarded mainly as a cytosolic protein, recent reports indicate that PAK1 also exists in significant amounts in the nucleus, where it is involved in transcription modulation and in cell cycle regulatory events. PAK1 is also involved in transformation and tumorigenesis. Its overexpression, hyperactivation and increased nuclear accumulation is correlated to breast cancer invasiveness and progression. Nuclear accumulation is also linked to tamoxifen resistance in breast cancer cells. PAK1 belongs to the group I PAKs, which contain a PBD (p21-binding domain) overlapping with an AID (autoinhibitory domain), a C-terminal catalytic domain, SH3 binding sites and a non-classical SH3 binding site for PIX (PAK-interacting exchange factor). PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. The PAK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270820 [Multi-domain]  Cd Length: 296  Bit Score: 73.22  E-value: 1.35e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1012 KGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIykDPDYVRKGDARLPLKWMAPETIFDRVYTIQSDVWSFGV 1091
Cdd:cd06654  127 QALEFLHSNQVIHRDIKSDNILLGMDGSVKLTDFGFCAQI--TPEQSKRSTMVGTPYWMAPEVVTRKAYGPKVDIWSLGI 204
                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 27777648 1092 LLWEIFSlGASPYpgvkIDEEFCRRLKEGTRMRAPDYTTPE----MYQTMLD-CWHEDPNQRPSFSELVEH 1157
Cdd:cd06654  205 MAIEMIE-GEPPY----LNENPLRALYLIATNGTPELQNPEklsaIFRDFLNrCLEMDVEKRGSAKELLQH 270
STKc_Nek11 cd08222
Catalytic domain of the Protein Serine/Threonine Kinase, Never In Mitosis gene A (NIMA) ...
1009-1157 1.40e-13

Catalytic domain of the Protein Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase 11; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Nek11 is involved, through direct phosphorylation, in regulating the degradation of Cdc25A (Cell Division Cycle 25 homolog A), which plays a role in cell cycle progression and in activating cyclin dependent kinases. Nek11 is activated by CHK1 (CHeckpoint Kinase 1) and may be involved in the G2/M checkpoint. Nek11 may also play a role in the S-phase checkpoint as well as in DNA replication and genotoxic stress responses. It is one in a family of 11 different Neks (Nek1-11) that are involved in cell cycle control. The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270861 [Multi-domain]  Cd Length: 260  Bit Score: 72.46  E-value: 1.40e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1009 QVAKGMEFLASRKCIHRDLAARNILLsEKNVVKICDFGLARDIYKDPDYVRKGdARLPLkWMAPETIFDRVYTIQSDVWS 1088
Cdd:cd08222  114 QLLLAVQYMHERRILHRDLKAKNIFL-KNNVIKVGDFGISRILMGTSDLATTF-TGTPY-YMSPEVLKHEGYNSKSDIWS 190
                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 27777648 1089 FGVLLWEIFSL-----GASPYPGVkideefcRRLKEGTRMRAPDYTTPEMYQTMLDCWHEDPNQRPSFSELVEH 1157
Cdd:cd08222  191 LGCILYEMCCLkhafdGQNLLSVM-------YKIVEGETPSLPDKYSKELNAIYSRMLNKDPALRPSAAEILKI 257
STKc_EIF2AK3_PERK cd14048
Catalytic domain of the Serine/Threonine kinase, eukaryotic translation Initiation Factor ...
995-1157 1.66e-13

Catalytic domain of the Serine/Threonine kinase, eukaryotic translation Initiation Factor 2-Alpha Kinase 3 or PKR-like Endoplasmic Reticulum Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PERK (or EIF2AK3) is a type-I ER transmembrane protein containing a luminal domain bound with the chaperone BiP under unstressed conditions and a cytoplasmic catalytic kinase domain. In response to the accumulation of misfolded or unfolded proteins in the ER, PERK is activated through the release of BiP, allowing it to dimerize and autophosphorylate. It functions as the central regulator of translational control during the Unfolded Protein Response (UPR) pathway. In addition to the eIF-2 alpha subunit, PERK also phosphorylates Nrf2, a leucine zipper transcription factor which regulates cellular redox status and promotes cell survival during the UPR. EIF2AKs phosphorylate the alpha subunit of eIF-2, resulting in the downregulation of protein synthesis. The PERK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270950 [Multi-domain]  Cd Length: 281  Bit Score: 72.60  E-value: 1.66e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  995 KDFLTLEHLIcysFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLA---------RDIYKDPDYVRKGDARL 1065
Cdd:cd14048  115 RELFVCLNIF---KQIASAVEYLHSKGLIHRDLKPSNVFFSLDDVVKVGDFGLVtamdqgepeQTVLTPMPAYAKHTGQV 191
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1066 PLK-WMAPETIFDRVYTIQSDVWSFGVLLWE-IFSLGASpypgvkidEEFCRRLKEGTRMRAP---DYTTPEMYQTMLDC 1140
Cdd:cd14048  192 GTRlYMSPEQIHGNQYSEKVDIFALGLILFElIYSFSTQ--------MERIRTLTDVRKLKFPalfTNKYPEERDMVQQM 263
                        170
                 ....*....|....*..
gi 27777648 1141 WHEDPNQRPSFSELVEH 1157
Cdd:cd14048  264 LSPSPSERPEAHEVIEH 280
STKc_DRAK cd14106
Catalytic domain of the Serine/Threonine Kinase, Death-associated protein kinase-Related ...
1009-1157 1.87e-13

Catalytic domain of the Serine/Threonine Kinase, Death-associated protein kinase-Related Apoptosis-inducing protein Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. DRAKs, also called STK17, were named based on their similarity (around 50% identity) to the kinase domain of DAPKs. They contain an N-terminal kinase domain and a C-terminal regulatory domain. Vertebrates contain two subfamily members, DRAK1 and DRAK2. Both DRAKs are localized to the nucleus, autophosphorylate themselves, and phosphorylate myosin light chain as a substrate. They may play a role in apoptotic signaling. The DRAK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271008 [Multi-domain]  Cd Length: 268  Bit Score: 72.00  E-value: 1.87e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1009 QVAKGMEFLASRKCIHRDLAARNILLSEKNV---VKICDFGLA---------RDIYKDPDYVrkgdarlplkwmAPETIF 1076
Cdd:cd14106  116 QILEGVQYLHERNIVHLDLKPQNILLTSEFPlgdIKLCDFGISrvigegeeiREILGTPDYV------------APEILS 183
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1077 DRVYTIQSDVWSFGVLLWEIFSlGASPYPGVKIDEEFC----------RRLKEGTRMRAPDYTTPEMYQtmldcwheDPN 1146
Cdd:cd14106  184 YEPISLATDMWSIGVLTYVLLT-GHSPFGGDDKQETFLnisqcnldfpEELFKDVSPLAIDFIKRLLVK--------DPE 254
                        170
                 ....*....|.
gi 27777648 1147 QRPSFSELVEH 1157
Cdd:cd14106  255 KRLTAKECLEH 265
IgI_1_MuSK cd20970
agrin-responsive first immunoglobulin-like domains (Ig1) of the MuSK ectodomain; a member of ...
670-739 1.99e-13

agrin-responsive first immunoglobulin-like domains (Ig1) of the MuSK ectodomain; a member of the I-set of IgSF domains; The members here are composed of the first immunoglobulin-like domains (Ig1) of the Muscle-specific kinase (MuSK). MuSK is a receptor tyrosine kinase specifically expressed in skeletal muscle, where it plays a central role in the formation and maintenance of the neuromuscular junction (NMJ). MuSK is activated by agrin, a neuron-derived heparan sulfate proteoglycan. The activation of MUSK in myotubes regulates the formation of NMJs through the regulation of different processes including the specific expression of genes in subsynaptic nuclei, the reorganization of the actin cytoskeleton and the clustering of the acetylcholine receptors (AChR) in the postsynaptic membrane. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the MuSK lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409562 [Multi-domain]  Cd Length: 92  Bit Score: 67.15  E-value: 1.99e-13
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 27777648  670 NLENQTTTIGETIEVTCPASGNPTPHITWFKDNETLVE-DSGIVLRDGNRNLTIRRVRKEDGGLYTCQACN 739
Cdd:cd20970    8 PSFTVTAREGENATFMCRAEGSPEPEISWTRNGNLIIEfNTRYIVRENGTTLTIRNIRRSDMGIYLCIASN 78
PTZ00283 PTZ00283
serine/threonine protein kinase; Provisional
1009-1155 2.31e-13

serine/threonine protein kinase; Provisional


Pssm-ID: 240344 [Multi-domain]  Cd Length: 496  Bit Score: 74.14  E-value: 2.31e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  1009 QVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARdIYKD--PDYVRKGDARLPLkWMAPETIFDRVYTIQSDV 1086
Cdd:PTZ00283  151 QVLLAVHHVHSKHMIHRDIKSANILLCSNGLVKLGDFGFSK-MYAAtvSDDVGRTFCGTPY-YVAPEIWRRKPYSKKADM 228
                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 27777648  1087 WSFGVLLWEIFSLgASPYPGVKIDEEFCRRLKeGTRMRAPDYTTPEMYQTMLDCWHEDPNQRPSFSELV 1155
Cdd:PTZ00283  229 FSLGVLLYELLTL-KRPFDGENMEEVMHKTLA-GRYDPLPPSISPEMQEIVTALLSSDPKRRPSSSKLL 295
STKc_MAP4K3_like cd06613
Catalytic domain of Mitogen-activated protein kinase kinase kinase kinase (MAP4K) 3-like ...
1001-1157 2.84e-13

Catalytic domain of Mitogen-activated protein kinase kinase kinase kinase (MAP4K) 3-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily includes MAP4K3, MAP4K1, MAP4K2, MAP4K5, and related proteins. Vertebrate members contain an N-terminal catalytic domain and a C-terminal citron homology (CNH) regulatory domain. MAP4K1, also called haematopoietic progenitor kinase 1 (HPK1), is a hematopoietic-specific STK involved in many cellular signaling cascades including MAPK, antigen receptor, apoptosis, growth factor, and cytokine signaling. It participates in the regulation of T cell receptor signaling and T cell-mediated immune responses. MAP4K2 was referred to as germinal center (GC) kinase because of its preferred location in GC B cells. MAP4K3 plays a role in the nutrient-responsive pathway of mTOR (mammalian target of rapamycin) signaling. It is required in the activation of S6 kinase by amino acids and for the phosphorylation of the mTOR-regulated inhibitor of eukaryotic initiation factor 4E. MAP4K5, also called germinal center kinase-related enzyme (GCKR), has been shown to activate the MAPK c-Jun N-terminal kinase (JNK). The MAP4K3-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270788 [Multi-domain]  Cd Length: 259  Bit Score: 71.57  E-value: 2.84e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1001 EHLICY-SFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLA----RDIYKdpdyvRKGDARLPLkWMAPETI 1075
Cdd:cd06613   96 ELQIAYvCRETLKGLAYLHSTGKIHRDIKGANILLTEDGDVKLADFGVSaqltATIAK-----RKSFIGTPY-WMAPEVA 169
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1076 FDR---VYTIQSDVWSFGVLLWE----------------IFSLGASPYPGVKideefcrrLKEGTRMrapdytTPEMYQT 1136
Cdd:cd06613  170 AVErkgGYDGKCDIWALGITAIElaelqppmfdlhpmraLFLIPKSNFDPPK--------LKDKEKW------SPDFHDF 235
                        170       180
                 ....*....|....*....|.
gi 27777648 1137 MLDCWHEDPNQRPSFSELVEH 1157
Cdd:cd06613  236 IKKCLTKNPKKRPTATKLLQH 256
STKc_PAK2 cd06655
Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 2; STKs catalyze the ...
1012-1157 2.89e-13

Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PAK2 plays a role in pro-apoptotic signaling. It is cleaved and activated by caspases leading to morphological changes during apoptosis. PAK2 is also activated in response to a variety of stresses including DNA damage, hyperosmolarity, serum starvation, and contact inhibition, and may play a role in coordinating the stress response. PAK2 also contributes to cancer cell invasion through a mechanism distinct from that of PAK1. It belongs to the group I PAKs, which contain a PBD (p21-binding domain) overlapping with an AID (autoinhibitory domain), a C-terminal catalytic domain, SH3 binding sites and a non-classical SH3 binding site for PIX (PAK-interacting exchange factor). PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. The PAK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 132986 [Multi-domain]  Cd Length: 296  Bit Score: 72.06  E-value: 2.89e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1012 KGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIykDPDYVRKGDARLPLKWMAPETIFDRVYTIQSDVWSFGV 1091
Cdd:cd06655  126 QALEFLHANQVIHRDIKSDNVLLGMDGSVKLTDFGFCAQI--TPEQSKRSTMVGTPYWMAPEVVTRKAYGPKVDIWSLGI 203
                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 27777648 1092 LLWEIFSlGASPYpgvkIDEEFCRRL----KEGT-RMRAPDYTTPEMYQTMLDCWHEDPNQRPSFSELVEH 1157
Cdd:cd06655  204 MAIEMVE-GEPPY----LNENPLRALyliaTNGTpELQNPEKLSPIFRDFLNRCLEMDVEKRGSAKELLQH 269
STKc_SPEG_rpt2 cd14111
Catalytic kinase domain, second repeat, of Giant Serine/Threonine Kinase Striated muscle ...
1006-1104 3.18e-13

Catalytic kinase domain, second repeat, of Giant Serine/Threonine Kinase Striated muscle preferentially expressed protein kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The Striated muscle preferentially expressed gene (SPEG) generates 4 different isoforms through alternative promoter use and splicing in a tissue-specific manner: SPEGalpha and SPEGbeta are expressed in cardiac and skeletal striated muscle; Aortic Preferentially Expressed Protein-1 (APEG-1) is expressed in vascular smooth muscle; and Brain preferentially expressed gene (BPEG) is found in the brain and aorta. SPEG proteins have mutliple immunoglobulin (Ig), 2 fibronectin type III (FN3), and two kinase domains. They are necessary for cardiac development and survival. The SPEG subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271013 [Multi-domain]  Cd Length: 257  Bit Score: 71.39  E-value: 3.18e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1006 YSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIykDPDYVRKGDARL-PLKWMAPETIFDRVYTIQS 1084
Cdd:cd14111  104 YLVQILQGLEYLHGRRVLHLDIKPDNIMVTNLNAIKIVDFGSAQSF--NPLSLRQLGRRTgTLEYMAPEMVKGEPVGPPA 181
                         90       100
                 ....*....|....*....|
gi 27777648 1085 DVWSFGVLLWEIFSlGASPY 1104
Cdd:cd14111  182 DIWSIGVLTYIMLS-GRSPF 200
PK_GC-C cd14044
Pseudokinase domain of the membrane Guanylate Cyclase receptor, GC-C; The pseudokinase domain ...
975-1154 3.24e-13

Pseudokinase domain of the membrane Guanylate Cyclase receptor, GC-C; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity and/or ATP binding. GC-C binds and is activated by the intestinal hormones, guanylin (GN) and uroguanylin (UGN), which are secreted after salty meals to inhibit sodium absorption and induce the secretion of chloride, bicarbonate, and water. GN and UGN are also present in the kidney, where they induce increased salt and water secretion. This prevents the development of hypernatremia and hypervolemia after ingestion of high amounts of salt. Membrane (or particulate) GCs consist of an extracellular ligand-binding domain, a single transmembrane region, and an intracellular tail that contains a PK-like domain, an amphiphatic region and a catalytic GC domain that catalyzes the conversion of GTP into cGMP and pyrophosphate. Membrane GCs act as receptors that transduce an extracellular signal to the intracellular production of cGMP, which has been implicated in many processes including cell proliferation, phototransduction, and muscle contractility, through its downstream effectors such as PKG. The PK-like domain of GCs functions as a negative regulator of the catalytic GC domain and may also act as a docking site for interacting proteins such as GC-activating proteins. The GC-C subfamily is part of a larger superfamily that includes the catalytic domains of protein serine/threonine kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270946 [Multi-domain]  Cd Length: 271  Bit Score: 71.46  E-value: 3.24e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  975 FVEEKSLSDVEEEEASeelYKD--FLTLEHLICYSFQVAKGMEFLASRKC-IHRDLAARNILLSEKNVVKICDFGlardi 1051
Cdd:cd14044   84 YCERGSLRDVLNDKIS---YPDgtFMDWEFKISVMYDIAKGMSYLHSSKTeVHGRLKSTNCVVDSRMVVKITDFG----- 155
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1052 ykdpdyvrkGDARLPLK---WMAPETIFDRVYTIQSDVWSFGVLLWEIFSLGASPYpgvkidEEFCRRLKEGT-RMRAPD 1127
Cdd:cd14044  156 ---------CNSILPPSkdlWTAPEHLRQAGTSQKGDVYSYGIIAQEIILRKETFY------TAACSDRKEKIyRVQNPK 220
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|..
gi 27777648 1128 YTTP---------------EMYQTMLDCWHEDPNQRPSFSEL 1154
Cdd:cd14044  221 GMKPfrpdlnlesagererEVYGLVKNCWEEDPEKRPDFKKI 262
STKc_myosinIIIB_N cd06639
N-terminal Catalytic domain of the Serine/Threonine Kinase, Class IIIB myosin; STKs catalyze ...
828-1157 3.29e-13

N-terminal Catalytic domain of the Serine/Threonine Kinase, Class IIIB myosin; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Class IIIB myosin is expressed highly in retina. It is also present in the brain and testis. The human class IIIB myosin gene maps to a region that overlaps the locus for Bardet-Biedl syndrome, which is characterized by dysmorphic extremities, retinal dystrophy, obesity, male hypogenitalism, and renal abnormalities. Class III myosins are motor proteins containing an N-terminal kinase catalytic domain and a C-terminal actin-binding domain. They may play an important role in maintaining the structural integrity of photoreceptor cell microvilli. They may also function as cargo carriers during light-dependent translocation, in photoreceptor cells, of proteins such as transducin and arrestin. The class III myosin subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270808 [Multi-domain]  Cd Length: 291  Bit Score: 71.95  E-value: 3.29e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  828 PRDRLKLGKPLGRGAFGQVieadaFGIDKTATCKTVAVKMLKEGATHSEHraLMSELKILIHIGHHLNVVNLLGACTKP- 906
Cdd:cd06639   20 PSDTWDIIETIGKGTYGKV-----YKVTNKKDGSLAAVKILDPISDVDEE--IEAEYNILRSLPNHPNVVKFYGMFYKAd 92
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  907 ---GGPLMVIVEFCKFGNLSTYLRGkrnefvpykskgaRFRQGKdyvgelsvdlkrRLDsitssqssassgfveEKSLSD 983
Cdd:cd06639   93 qyvGGQLWLVLELCNGGSVTELVKG-------------LLKCGQ------------RLD---------------EAMISY 132
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  984 VeeeeaseeLYKDFLTLEHLicysfqvakgmeflASRKCIHRDLAARNILLSEKNVVKICDFGLARDIyKDPDYVRKGDA 1063
Cdd:cd06639  133 I--------LYGALLGLQHL--------------HNNRIIHRDVKGNNILLTTEGGVKLVDFGVSAQL-TSARLRRNTSV 189
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1064 RLPLkWMAPETI-----FDRVYTIQSDVWSFGVLLWE----------------IFSLGASPYPGVKIDEEFCRrlkegtr 1122
Cdd:cd06639  190 GTPF-WMAPEVIaceqqYDYSYDARCDVWSLGITAIEladgdpplfdmhpvkaLFKIPRNPPPTLLNPEKWCR------- 261
                        330       340       350
                 ....*....|....*....|....*....|....*
gi 27777648 1123 mrapdyttpEMYQTMLDCWHEDPNQRPSFSELVEH 1157
Cdd:cd06639  262 ---------GFSHFISQCLIKDFEKRPSVTHLLEH 287
STKc_KSR1 cd14152
Catalytic domain of the Serine/Threonine Kinase, Kinase Suppressor of Ras 1; STKs catalyze the ...
831-1165 3.56e-13

Catalytic domain of the Serine/Threonine Kinase, Kinase Suppressor of Ras 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. KSR1 functions as a transducer of TNFalpha-stimulated C-Raf activation of ERK1/2 and NF-kB. Detected activity of KSR1 is cell type specific and context dependent. It is inactive in normal colon epithelial cells and becomes activated at the onset of inflammatory bowel disease (IBD). Similarly, KSR1 activity is undetectable prior to stimulation by EGF or ceramide in COS-7 or YAMC cells, respectively. KSR proteins are widely regarded as pseudokinases, however, this matter is up for debate as catalytic activity has been detected for KSR1 in some systems. The KSR1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271054 [Multi-domain]  Cd Length: 279  Bit Score: 71.54  E-value: 3.56e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  831 RLKLGKPLGRGAFGQVIEADAFGidktatckTVAVKMLKEGATHSEHRALMSELKILIHIGHHLNVVNLLGACTKPggP- 909
Cdd:cd14152    1 QIELGELIGQGRWGKVHRGRWHG--------EVAIRLLEIDGNNQDHLKLFKKEVMNYRQTRHENVVLFMGACMHP--Ph 70
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  910 LMVIVEFCKFGNLSTYLRgkrnefvpykskgarfrqgkDYVGELSVDLKRRLdsitssqssassgfveekslsdveeeea 989
Cdd:cd14152   71 LAIITSFCKGRTLYSFVR--------------------DPKTSLDINKTRQI---------------------------- 102
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  990 seelykdfltlehlicySFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVkICDFGLARDIYKDPDYVRKGDARLPLKW 1069
Cdd:cd14152  103 -----------------AQEIIKGMGYLHAKGIVHKDLKSKNVFYDNGKVV-ITDFGLFGISGVVQEGRRENELKLPHDW 164
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1070 ---MAPETIFDRV---------YTIQSDVWSFGVLLWEifsLGASPYPGV-KIDEEFCRRLKEGTRMRAPDYTTP---EM 1133
Cdd:cd14152  165 lcyLAPEIVREMTpgkdedclpFSKAADVYAFGTIWYE---LQARDWPLKnQPAEALIWQIGSGEGMKQVLTTISlgkEV 241
                        330       340       350
                 ....*....|....*....|....*....|..
gi 27777648 1134 YQTMLDCWHEDPNQRPSFSELVEHLGNLLQAN 1165
Cdd:cd14152  242 TEILSACWAFDLEERPSFTLLMDMLEKLPKLN 273
STKc_PAK3 cd06656
Catalytic domain of the Protein Serine/Threonine Kinase, p21-activated kinase 3; Serine ...
1012-1157 3.66e-13

Catalytic domain of the Protein Serine/Threonine Kinase, p21-activated kinase 3; Serine/threonine kinases (STKs), p21-activated kinase (PAK) 3, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The PAK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. PAKs from higher eukaryotes are classified into two groups (I and II), according to their biochemical and structural features. PAK3 belongs to group I. Group I PAKs contain a PBD (p21-binding domain) overlapping with an AID (autoinhibitory domain), a C-terminal catalytic domain, SH3 binding sites and a non-classical SH3 binding site for PIX (PAK-interacting exchange factor). PAK3 is highly expressed in the brain. It is implicated in neuronal plasticity, synapse formation, dendritic spine morphogenesis, cell cycle progression, neuronal migration, and apoptosis. Inactivating mutations in the PAK3 gene cause X-linked non-syndromic mental retardation, the severity of which depends on the site of the mutation.


Pssm-ID: 132987 [Multi-domain]  Cd Length: 297  Bit Score: 71.68  E-value: 3.66e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1012 KGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIykDPDYVRKGDARLPLKWMAPETIFDRVYTIQSDVWSFGV 1091
Cdd:cd06656  126 QALDFLHSNQVIHRDIKSDNILLGMDGSVKLTDFGFCAQI--TPEQSKRSTMVGTPYWMAPEVVTRKAYGPKVDIWSLGI 203
                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 27777648 1092 LLWEIFSlGASPYpgvkIDEEFCRRLKEGTRMRAPDYTTPE----MYQTMLD-CWHEDPNQRPSFSELVEH 1157
Cdd:cd06656  204 MAIEMVE-GEPPY----LNENPLRALYLIATNGTPELQNPErlsaVFRDFLNrCLEMDVDRRGSAKELLQH 269
STKc_Aurora-A cd14116
Catalytic domain of the Serine/Threonine kinase, Aurora-A kinase; STKs catalyze the transfer ...
1006-1157 3.83e-13

Catalytic domain of the Serine/Threonine kinase, Aurora-A kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Aurora kinases are key regulators of mitosis and are essential for the accurate and equal division of genomic material from parent to daughter cells. Vertebrates contain at least 2 Aurora kinases (A and B); mammals contains a third Aurora kinase gene (C). Aurora-A regulates cell cycle events from the late S-phase through the M-phase including centrosome maturation, mitotic entry, centrosome separation, spindle assembly, chromosome alignment, cytokinesis, and mitotic exit. Aurora-A activation depends on its autophosphorylation and binding to the microtubule-associated protein TPX2, which also localizes the kinase to spindle microtubules. Aurora-A is overexpressed in many cancer types such as prostate, ovarian, breast, bladder, gastric, and pancreatic. The Aurora subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271018 [Multi-domain]  Cd Length: 258  Bit Score: 71.14  E-value: 3.83e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1006 YSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLArdiYKDPDyVRKGDARLPLKWMAPETIFDRVYTIQSD 1085
Cdd:cd14116  110 YITELANALSYCHSKRVIHRDIKPENLLLGSAGELKIADFGWS---VHAPS-SRRTTLCGTLDYLPPEMIEGRMHDEKVD 185
                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 27777648 1086 VWSFGVLLWEiFSLGASPYPgVKIDEEFCRRLKEgTRMRAPDYTTPEMYQTMLDCWHEDPNQRPSFSELVEH 1157
Cdd:cd14116  186 LWSLGVLCYE-FLVGKPPFE-ANTYQETYKRISR-VEFTFPDFVTEGARDLISRLLKHNPSQRPMLREVLEH 254
STKc_MAP4K4_6_N cd06636
N-terminal Catalytic domain of the Serine/Threonine Kinases, Mitogen-Activated Protein Kinase ...
821-1157 4.63e-13

N-terminal Catalytic domain of the Serine/Threonine Kinases, Mitogen-Activated Protein Kinase Kinase Kinase Kinase 4 and 6; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Members of this subfamily contain an N-terminal catalytic domain and a C-terminal citron homology (CNH) regulatory domain. MAP4K4 is also called Nck Interacting kinase (NIK). It facilitates the activation of the MAPKs, extracellular signal-regulated kinase (ERK) 1, ERK2, and c-Jun N-terminal kinase (JNK), by phosphorylating and activating MEKK1. MAP4K4 plays a role in tumor necrosis factor (TNF) alpha-induced insulin resistance. MAP4K4 silencing in skeletal muscle cells from type II diabetic patients restores insulin-mediated glucose uptake. MAP4K4, through JNK, also plays a broad role in cell motility, which impacts inflammation, homeostasis, as well as the invasion and spread of cancer. MAP4K4 is found to be highly expressed in most tumor cell lines relative to normal tissue. MAP4K6 (also called MINK for Misshapen/NIKs-related kinase) is activated after Ras induction and mediates activation of p38 MAPK. MAP4K6 plays a role in cell cycle arrest, cytoskeleton organization, cell adhesion, and cell motility. The MAP4K4/6 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270806 [Multi-domain]  Cd Length: 282  Bit Score: 71.19  E-value: 4.63e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  821 DASKWEFPRDRLKLGKPLGRGAFGQVIEADAFGIDKTATCKTVAVkmlkegaTHSEHRALMSELKILIHIGHHLNVVNLL 900
Cdd:cd06636    7 DLSALRDPAGIFELVEVVGNGTYGQVYKGRHVKTGQLAAIKVMDV-------TEDEEEEIKLEINMLKKYSHHRNIATYY 79
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  901 GACTKPGGP-----LMVIVEFCKFGNLSTYLRgkrnefvpyKSKGARFRQgkDYVGelsvdlkrrldsitssqssassgf 975
Cdd:cd06636   80 GAFIKKSPPghddqLWLVMEFCGAGSVTDLVK---------NTKGNALKE--DWIA------------------------ 124
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  976 veekslsdveeeeaseelykdfltlehLICYsfQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIykDP 1055
Cdd:cd06636  125 ---------------------------YICR--EILRGLAHLHAHKVIHRDIKGQNVLLTENAEVKLVDFGVSAQL--DR 173
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1056 DYVRKGDARLPLKWMAPETIF-----DRVYTIQSDVWSFGVLLWEIfSLGASPYpgvkIDEEFCRRLKEGTRMRAPDYTT 1130
Cdd:cd06636  174 TVGRRNTFIGTPYWMAPEVIAcdenpDATYDYRSDIWSLGITAIEM-AEGAPPL----CDMHPMRALFLIPRNPPPKLKS 248
                        330       340       350
                 ....*....|....*....|....*....|.
gi 27777648 1131 PEMYQTMLD----CWHEDPNQRPSFSELVEH 1157
Cdd:cd06636  249 KKWSKKFIDfiegCLVKNYLSRPSTEQLLKH 279
IgI_4_Dscam cd20956
Fourth immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; ...
664-742 5.82e-13

Fourth immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. This group is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.


Pssm-ID: 409548 [Multi-domain]  Cd Length: 96  Bit Score: 66.04  E-value: 5.82e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  664 APMITGNLENQTTTIGETIEVTCPASGNPTPHITWFKDNETLVEDSGI-----VLRDG--NRNLTIRRVRKEDGGLYTCQ 736
Cdd:cd20956    1 APVLLETFSEQTLQPGPSVSLKCVASGNPLPQITWTLDGFPIPESPRFrvgdyVTSDGdvVSYVNISSVRVEDGGEYTCT 80

                 ....*.
gi 27777648  737 ACNVLG 742
Cdd:cd20956   81 ATNDVG 86
STKc_cPKC_beta cd05616
Catalytic domain of the Serine/Threonine Kinase, Classical Protein Kinase C beta; STKs ...
1002-1113 6.37e-13

Catalytic domain of the Serine/Threonine Kinase, Classical Protein Kinase C beta; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The PKC beta isoforms (I and II), generated by alternative splicing of a single gene, are preferentially activated by hyperglycemia-induced DAG (1,2-diacylglycerol) in retinal tissues. This is implicated in diabetic microangiopathy such as ischemia, neovascularization, and abnormal vasodilator function. PKC-beta also plays an important role in VEGF signaling. In addition, glucose regulates proliferation in retinal endothelial cells via PKC-betaI. PKC-beta is also being explored as a therapeutic target in cancer. It contributes to tumor formation and is involved in the tumor host mechanisms of inflammation and angiogenesis. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. PKCs undergo three phosphorylations in order to take mature forms. In addition, cPKCs depend on calcium, DAG, and in most cases, phosphatidylserine (PS) for activation. The cPKC-beta subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270767 [Multi-domain]  Cd Length: 323  Bit Score: 71.57  E-value: 6.37e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1002 HLICYSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIYKD----------PDYVrkgdarlplkwmA 1071
Cdd:cd05616  102 HAVFYAAEIAIGLFFLQSKGIIYRDLKLDNVMLDSEGHIKIADFGMCKENIWDgvttktfcgtPDYI------------A 169
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|..
gi 27777648 1072 PETIFDRVYTIQSDVWSFGVLLWEIFSlGASPYPGVKIDEEF 1113
Cdd:cd05616  170 PEIIAYQPYGKSVDWWAFGVLLYEMLA-GQAPFEGEDEDELF 210
STKc_SBK1 cd13987
Catalytic domain of the Serine/Threonine kinase, SH3 Binding Kinase 1; STKs catalyze the ...
1009-1159 6.81e-13

Catalytic domain of the Serine/Threonine kinase, SH3 Binding Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SBK1, also called BSK146, is predominantly expressed in the brain. Its expression is increased in the developing brain during the late embryonic stage, coinciding with dramatic neuronal proliferation, migration, and maturation. SBK1 may play an important role in regulating brain development. The SBK1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270889 [Multi-domain]  Cd Length: 259  Bit Score: 70.43  E-value: 6.81e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1009 QVAKGMEFLASRKCIHRDLAARNILLSEKN--VVKICDFGLARdiyKDPDYVRKGDARLPlkWMAPE---TIFDRVYTIQ 1083
Cdd:cd13987   99 QLASALDFMHSKNLVHRDIKPENVLLFDKDcrRVKLCDFGLTR---RVGSTVKRVSGTIP--YTAPEvceAKKNEGFVVD 173
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1084 --SDVWSFGVLL---------WEIFSLGASPYpgvkidEEFCRRLKeGTRMRAPDY---TTPE---MYQTMLdcwHEDPN 1146
Cdd:cd13987  174 psIDVWAFGVLLfccltgnfpWEKADSDDQFY------EEFVRWQK-RKNTAVPSQwrrFTPKalrMFKKLL---APEPE 243
                        170
                 ....*....|...
gi 27777648 1147 QRPSFSELVEHLG 1159
Cdd:cd13987  244 RRCSIKEVFKYLG 256
STKc_TNIK cd06637
Catalytic domain of the Serine/Threonine Kinase, Traf2- and Nck-Interacting Kinase; STKs ...
828-1168 7.22e-13

Catalytic domain of the Serine/Threonine Kinase, Traf2- and Nck-Interacting Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TNIK is an effector of Rap2, a small GTP-binding protein from the Ras family. TNIK specifically activates the c-Jun N-terminal kinase (JNK) pathway and plays a role in regulating the actin cytoskeleton. The TNIK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270807 [Multi-domain]  Cd Length: 296  Bit Score: 70.90  E-value: 7.22e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  828 PRDRLKLGKPLGRGAFGQVIEADAFGIDKTATCKTVAVkmlkegaTHSEHRALMSELKILIHIGHHLNVVNLLGACTKPG 907
Cdd:cd06637    4 PAGIFELVELVGNGTYGQVYKGRHVKTGQLAAIKVMDV-------TGDEEEEIKQEINMLKKYSHHRNIATYYGAFIKKN 76
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  908 GP-----LMVIVEFCKFGNLSTYLRgkrnefvpyKSKGARFRQgkDYVGelsvdlkrrldsitssqssassgfveeksls 982
Cdd:cd06637   77 PPgmddqLWLVMEFCGAGSVTDLIK---------NTKGNTLKE--EWIA------------------------------- 114
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  983 dveeeeaseelykdfltlehLICYsfQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIykDPDYVRKGD 1062
Cdd:cd06637  115 --------------------YICR--EILRGLSHLHQHKVIHRDIKGQNVLLTENAEVKLVDFGVSAQL--DRTVGRRNT 170
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1063 ARLPLKWMAPETIF-----DRVYTIQSDVWSFGVLLWEIfSLGASPYpgvkIDEEFCRRLKEGTRMRAPDYTT---PEMY 1134
Cdd:cd06637  171 FIGTPYWMAPEVIAcdenpDATYDFKSDLWSLGITAIEM-AEGAPPL----CDMHPMRALFLIPRNPAPRLKSkkwSKKF 245
                        330       340       350
                 ....*....|....*....|....*....|....*
gi 27777648 1135 QTMLD-CWHEDPNQRPSFSELVEHLGNLLQANAQQ 1168
Cdd:cd06637  246 QSFIEsCLVKNHSQRPSTEQLMKHPFIRDQPNERQ 280
STKc_p38 cd07851
Catalytic domain of the Serine/Threonine Kinase, p38 Mitogen-Activated Protein Kinase; STKs ...
817-1106 7.30e-13

Catalytic domain of the Serine/Threonine Kinase, p38 Mitogen-Activated Protein Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. p38 kinases are mitogen-activated protein kinases (MAPKs), serving as important mediators of cellular responses to extracellular signals. They function in the regulation of the cell cycle, cell development, cell differentiation, senescence, tumorigenesis, apoptosis, pain development and pain progression, and immune responses. p38 kinases are activated by the MAPK kinases MKK3 and MKK6, which in turn are activated by upstream MAPK kinase kinases including TAK1, ASK1, and MLK3, in response to cellular stresses or inflammatory cytokines. p38 substrates include other protein kinases and factors that regulate transcription, nuclear export, mRNA stability and translation. p38 kinases are drug targets for the inflammatory diseases psoriasis, rheumatoid arthritis, and chronic pulmonary disease. Vertebrates contain four isoforms of p38, named alpha, beta, gamma, and delta, which show varying substrate specificity and expression patterns. p38alpha and p38beta are ubiquitously expressed, p38gamma is predominantly found in skeletal muscle, and p38delta is found in the heart, lung, testis, pancreas, and small intestine. The p38 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 143356 [Multi-domain]  Cd Length: 343  Bit Score: 71.56  E-value: 7.30e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  817 RLPYDASKWEFPrDRLKLGKPLGRGAFGQVIEAdafgIDkTATCKTVAVKMLK---EGATHSehRALMSELKILIHIgHH 893
Cdd:cd07851    3 RQELNKTVWEVP-DRYQNLSPVGSGAYGQVCSA----FD-TKTGRKVAIKKLSrpfQSAIHA--KRTYRELRLLKHM-KH 73
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  894 LNVVNLLGACTkPGGPLMVIVEFckfgnlstYLrgkrnefvpykskgarfrqgkdyVGEL-SVDLKRrldsitssqssas 972
Cdd:cd07851   74 ENVIGLLDVFT-PASSLEDFQDV--------YL-----------------------VTHLmGADLNN------------- 108
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  973 sgFVEEKSLSDveeeeaseelykdfltlEHlICY-SFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDI 1051
Cdd:cd07851  109 --IVKCQKLSD-----------------DH-IQFlVYQILRGLKYIHSAGIIHRDLKPSNLAVNEDCELKILDFGLARHT 168
                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 27777648 1052 YKD-PDYVRKgdarlplKW-MAPETIFDRV-YTIQSDVWSFGVLLWEIFSlGASPYPG 1106
Cdd:cd07851  169 DDEmTGYVAT-------RWyRAPEIMLNWMhYNQTVDIWSVGCIMAELLT-GKTLFPG 218
STKc_Nek9 cd08221
Catalytic domain of the Protein Serine/Threonine Kinase, Never In Mitosis gene A (NIMA) ...
1001-1156 7.43e-13

Catalytic domain of the Protein Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase 9; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Nek9, also called Nercc1, is primarily a cytoplasmic protein but can also localize in the nucleus. It is involved in modulating chromosome alignment and splitting during mitosis. It interacts with the gamma-tubulin ring complex and the Ran GTPase, and is implicated in microtubule organization. Nek9 associates with FACT (FAcilitates Chromatin Transcription) and modulates interphase progression. It also interacts with Nek6, and Nek7, during mitosis, resulting in their activation. Nek9 is one in a family of 11 different Neks (Nek1-11) that are involved in cell cycle control. The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270860 [Multi-domain]  Cd Length: 256  Bit Score: 70.15  E-value: 7.43e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1001 EHLICYSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIykDPDYVRKGDARLPLKWMAPETIFDRVY 1080
Cdd:cd08221  101 EVVLWYLYQIVSAVSHIHKAGILHRDIKTLNIFLTKADLVKLGDFGISKVL--DSESSMAESIVGTPYYMSPELVQGVKY 178
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1081 TIQSDVWSFGVLLWEIFSL-----GASPYpgvkideEFCRRLKEGTR-MRAPDYTTpEMYQTMLDCWHEDPNQRPSFSEL 1154
Cdd:cd08221  179 NFKSDIWAVGCVLYELLTLkrtfdATNPL-------RLAVKIVQGEYeDIDEQYSE-EIIQLVHDCLHQDPEDRPTAEEL 250

                 ..
gi 27777648 1155 VE 1156
Cdd:cd08221  251 LE 252
STKc_BUR1 cd07866
Catalytic domain of the Serine/Threonine Kinase, Fungal Cyclin-Dependent protein Kinase (CDK), ...
998-1097 7.54e-13

Catalytic domain of the Serine/Threonine Kinase, Fungal Cyclin-Dependent protein Kinase (CDK), Bypass UAS Requirement 1, and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. BUR1, also called SGV1, is a yeast CDK that is functionally equivalent to mammalian CDK9. It associates with the cyclin BUR2. BUR genes were orginally identified in a genetic screen as factors involved in general transcription. The BUR1/BUR2 complex phosphorylates the C-terminal domain of RNA polymerase II. In addition, this complex regulates histone modification by phosporylating Rad6 and mediating the association of the Paf1 complex with chromatin. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The BUR1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270849 [Multi-domain]  Cd Length: 311  Bit Score: 71.19  E-value: 7.54e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  998 LTLEHLICYSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIYKDPDYVRKGDARLPLK--------W 1069
Cdd:cd07866  112 LTESQIKCYMLQLLEGINYLHENHILHRDIKAANILIDNQGILKIADFGLARPYDGPPPNPKGGGGGGTRKytnlvvtrW 191
                         90       100       110
                 ....*....|....*....|....*....|
gi 27777648 1070 M-APETIF-DRVYTIQSDVWSFGVLLWEIF 1097
Cdd:cd07866  192 YrPPELLLgERRYTTAVDIWGIGCVFAEMF 221
STKc_GRK cd05577
Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase; STKs ...
1004-1148 8.00e-13

Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. GRKs phosphorylate and regulate G protein-coupled receptors (GPCRs), the largest superfamily of cell surface receptors, which regulate some part of nearly all physiological functions. Phosphorylated GPCRs bind to arrestins, which prevents further G protein signaling despite the presence of activating ligand. GRKs play important roles in the cardiovascular, immune, respiratory, skeletal, and nervous systems. They contain a central catalytic domain, flanked by N- and C-terminal extensions. The N-terminus contains an RGS (regulator of G protein signaling) homology (RH) domain and several motifs. The C-terminus diverges among different groups of GRKs. There are seven types of GRKs, named GRK1 to GRK7, which are subdivided into three main groups: visual (GRK1/7); beta-adrenergic receptor kinases (GRK2/3); and GRK4-like (GRK4/5/6). Expression of GRK2/3/5/6 is widespread while GRK1/4/7 show a limited tissue distribution. The substrate spectrum of the widely expressed GRKs partially overlaps. The GRK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270729 [Multi-domain]  Cd Length: 278  Bit Score: 70.63  E-value: 8.00e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1004 ICYSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDI-YKDPDYVRKGDArlplKWMAPETIFDRV-YT 1081
Cdd:cd05577   98 IFYAAEIICGLEHLHNRFIVYRDLKPENILLDDHGHVRISDLGLAVEFkGGKKIKGRVGTH----GYMAPEVLQKEVaYD 173
                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 27777648 1082 IQSDVWSFGVLLWEIFSlGASPYP--GVKIDEEFCRRLKEGTRMRAPDYTTPEMYQTMLDCWHEDPNQR 1148
Cdd:cd05577  174 FSVDWFALGCMLYEMIA-GRSPFRqrKEKVDKEELKRRTLEMAVEYPDSFSPEARSLCEGLLQKDPERR 241
STKc_FA2-like cd08529
Catalytic domain of the Serine/Threonine Kinases, Chlamydomonas reinhardtii FA2 and similar ...
1006-1154 1.06e-12

Catalytic domain of the Serine/Threonine Kinases, Chlamydomonas reinhardtii FA2 and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Chlamydomonas reinhardtii FA2 was discovered in a genetic screen for deflagellation-defective mutants. It is essential for basal-body/centriole-associated microtubule severing, and plays a role in cell cycle progression. No cellular function has yet been ascribed to CNK4. The Chlamydomonas reinhardtii FA2-like subfamily belongs to the (NIMA)-related kinase (Nek) family, which includes seven different Chlamydomonas Neks (CNKs 1-6 and Fa2). This subfamily contains FA2 and CNK4. The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270868 [Multi-domain]  Cd Length: 256  Bit Score: 69.75  E-value: 1.06e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1006 YSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIYKDPDYVRK--GDarlPLkWMAPETIFDRVYTIQ 1083
Cdd:cd08529  106 FFIQTLLGLSHLHSKKILHRDIKSMNIFLDKGDNVKIGDLGVAKILSDTTNFAQTivGT---PY-YLSPELCEDKPYNEK 181
                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 27777648 1084 SDVWSFGVLLWEIfSLGASPYPgVKIDEEFCRRLKEGTRMRAPDYTTPEMYQTMLDCWHEDPNQRPSFSEL 1154
Cdd:cd08529  182 SDVWALGCVLYEL-CTGKHPFE-AQNQGALILKIVRGKYPPISASYSQDLSQLIDSCLTKDYRQRPDTTEL 250
STKc_DAPK cd14105
Catalytic domain of the Serine/Threonine Kinase, Death-Associated Protein Kinase; STKs ...
995-1157 1.11e-12

Catalytic domain of the Serine/Threonine Kinase, Death-Associated Protein Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. DAPKs mediate cell death and act as tumor suppressors. They are necessary to induce cell death and their overexpression leads to death-associated changes including membrane blebbing, cell rounding, and formation of autophagic vesicles. Vertebrates contain three subfamily members with different domain architecture, localization, and function. DAPK1 is the prototypical member of the subfamily and is also simply referred to as DAPK. DAPK2 is also called DAPK-related protein 1 (DRP-1), while DAPK3 has also been named DAP-like kinase (DLK) and zipper-interacting protein kinase (ZIPk). These proteins are ubiquitously expressed in adult tissues, are capable of cross talk with each other, and may act synergistically in regulating cell death. The DAPK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271007 [Multi-domain]  Cd Length: 269  Bit Score: 69.82  E-value: 1.11e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  995 KDFLTLEHLICYSFQVAKGMEFLASRKCIHRDLAARNILLSEKNV----VKICDFGLARDIykDPDYVRKGDARLPlKWM 1070
Cdd:cd14105  102 KESLSEEEATEFLKQILDGVNYLHTKNIAHFDLKPENIMLLDKNVpiprIKLIDFGLAHKI--EDGNEFKNIFGTP-EFV 178
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1071 APETIFDRVYTIQSDVWSFGVLLWEIFSlGASPYPG----------VKIDEEFCRRLKEGTRMRAPDYttpeMYQTMLdc 1140
Cdd:cd14105  179 APEIVNYEPLGLEADMWSIGVITYILLS-GASPFLGdtkqetlaniTAVNYDFDDEYFSNTSELAKDF----IRQLLV-- 251
                        170
                 ....*....|....*..
gi 27777648 1141 whEDPNQRPSFSELVEH 1157
Cdd:cd14105  252 --KDPRKRMTIQESLRH 266
STKc_BRSK1_2 cd14081
Catalytic domain of Brain-specific serine/threonine-protein kinases 1 and 2; STKs catalyze the ...
1009-1157 1.84e-12

Catalytic domain of Brain-specific serine/threonine-protein kinases 1 and 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. BRSK1, also called SAD-B or SAD1 (Synapses of Amphids Defective homolog 1), and BRSK2, also called SAD-A, are highly expressed in mammalian forebrain. They play important roles in establishing neuronal polarity. BRSK1/2 double knock-out mice die soon after birth, showing thin cerebral cortices due to disordered subplate layers and neurons that lack distinct axons and dendrites. BRSK1 regulates presynaptic neurotransmitter release. Its activity fluctuates during cell cysle progression and it acts as a regulator of centrosome duplication. BRSK2 is also abundant in pancreatic islets, where it is involved in the regulation of glucose-stimulated insulin secretion. The BRSK1/2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270983 [Multi-domain]  Cd Length: 255  Bit Score: 68.82  E-value: 1.84e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1009 QVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARdiykdpdyVRKGDARL-----PLKWMAPETIFDRVYT-I 1082
Cdd:cd14081  109 QIISALDYCHSHSICHRDLKPENLLLDEKNNIKIADFGMAS--------LQPEGSLLetscgSPHYACPEVIKGEKYDgR 180
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1083 QSDVWSFGVLLWEIFSlGASPYpgvkiDEEFCRRLKEGTRM---RAPDYTTPE---MYQTMLDCwheDPNQRPSFSELVE 1156
Cdd:cd14081  181 KADIWSCGVILYALLV-GALPF-----DDDNLRQLLEKVKRgvfHIPHFISPDaqdLLRRMLEV---NPEKRITIEEIKK 251

                 .
gi 27777648 1157 H 1157
Cdd:cd14081  252 H 252
STKc_SLK cd06643
Catalytic domain of the Serine/Threonine Kinase, Ste20-Like Kinase; STKs catalyze the transfer ...
828-1157 1.99e-12

Catalytic domain of the Serine/Threonine Kinase, Ste20-Like Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SLK promotes apoptosis through apoptosis signal-regulating kinase 1 (ASK1) and the mitogen-activated protein kinase (MAPK) p38. It acts as a MAPK kinase kinase by phosphorylating ASK1, resulting in the phosphorylation of p38. SLK also plays a role in mediating actin reorganization. It is part of a microtubule-associated complex that is targeted at adhesion sites, and is required in focal adhesion turnover and in regulating cell migration. The SLK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270811 [Multi-domain]  Cd Length: 283  Bit Score: 69.29  E-value: 1.99e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  828 PRDRLKLGKPLGRGAFGQVIEADAFGIDKTATCKTVAVKmlkegaTHSEHRALMSELKILIHIGHHlNVVNLLGACTKPG 907
Cdd:cd06643    3 PEDFWEIVGELGDGAFGKVYKAQNKETGILAAAKVIDTK------SEEELEDYMVEIDILASCDHP-NIVKLLDAFYYEN 75
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  908 GpLMVIVEFCKFGNlstylrgkrnefvpykskgarfrqgkdyVGELSVDLKRRLdsitssqssassgfvEEKSLsdveee 987
Cdd:cd06643   76 N-LWILIEFCAGGA----------------------------VDAVMLELERPL---------------TEPQI------ 105
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  988 easeelykdfltleHLICYsfQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARdiyKDPDYVRKGDARLPL 1067
Cdd:cd06643  106 --------------RVVCK--QTLEALVYLHENKIIHRDLKAGNILFTLDGDIKLADFGVSA---KNTRTLQRRDSFIGT 166
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1068 K-WMAPETIF-----DRVYTIQSDVWSFGVLLWEIFSLgASPYPGVKIDEEFCRRLK-EGTRMRAPDYTTPEMYQTMLDC 1140
Cdd:cd06643  167 PyWMAPEVVMcetskDRPYDYKADVWSLGVTLIEMAQI-EPPHHELNPMRVLLKIAKsEPPTLAQPSRWSPEFKDFLRKC 245
                        330
                 ....*....|....*..
gi 27777648 1141 WHEDPNQRPSFSELVEH 1157
Cdd:cd06643  246 LEKNVDARWTTSQLLQH 262
STKc_Chk1 cd14069
Catalytic domain of the Serine/Threonine kinase, Checkpoint kinase 1; STKs catalyze the ...
833-1157 2.60e-12

Catalytic domain of the Serine/Threonine kinase, Checkpoint kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Chk1 is implicated in many major checkpoints of the cell cycle, providing a link between upstream sensors and the cell cycle engine. It plays an important role in DNA damage response and maintaining genomic stability. Chk1 acts as an effector of the sensor kinase, ATR (ATM and Rad3-related), a member of the PI3K family, which is activated upon DNA replication stress. Chk1 delays mitotic entry in response to replication blocks by inhibiting cyclin dependent kinase (Cdk) activity. In addition, Chk1 contributes to the function of centrosome and spindle-based checkpoints, inhibits firing of origins of DNA replication (Ori), and represses transcription of cell cycle proteins including cyclin B and Cdk1. The Chk1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270971 [Multi-domain]  Cd Length: 261  Bit Score: 68.51  E-value: 2.60e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  833 KLGKPLGRGAFGQVieadaFGIDKTATCKTVAVKML-KEGATHSEHRALMSElkILIH-IGHHLNVVNLLGACTKPGGpL 910
Cdd:cd14069    4 DLVQTLGEGAFGEV-----FLAVNRNTEEAVAVKFVdMKRAPGDCPENIKKE--VCIQkMLSHKNVVRFYGHRREGEF-Q 75
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  911 MVIVEFCKFGNLstylrgkrnefvpykskgarFRQGKDYVGELSVDLKRrldsitssqssassgfveekslsdveeeeas 990
Cdd:cd14069   76 YLFLEYASGGEL--------------------FDKIEPDVGMPEDVAQF------------------------------- 104
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  991 eelykdfltlehlicYSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLArdiykdPDYVRKGDARL----- 1065
Cdd:cd14069  105 ---------------YFQQLMAGLKYLHSCGITHRDIKPENLLLDENDNLKISDFGLA------TVFRYKGKERLlnkmc 163
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1066 -PLKWMAPETIFDRVYTIQ-SDVWSFGVLLweiFSL--GASPYpgvkiDE------EFCRRLKEGTRMRAP----DYTTP 1131
Cdd:cd14069  164 gTLPYVAPELLAKKKYRAEpVDVWSCGIVL---FAMlaGELPW-----DQpsdscqEYSDWKENKKTYLTPwkkiDTAAL 235
                        330       340
                 ....*....|....*....|....*.
gi 27777648 1132 EMYQTMLdcwHEDPNQRPSFSELVEH 1157
Cdd:cd14069  236 SLLRKIL---TENPNKRITIEDIKKH 258
STKc_HAL4_like cd13994
Catalytic domain of Fungal Halotolerance protein 4-like Serine/Threonine kinases; STKs ...
838-1156 3.07e-12

Catalytic domain of Fungal Halotolerance protein 4-like Serine/Threonine kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of HAL4, Saccharomyces cerevisiae Ptk2/Stk2, and similar fungal proteins. Proteins in this subfamily are involved in regulating ion transporters. In budding and fission yeast, HAL4 promotes potassium ion uptake, which increases cellular resistance to other cations such as sodium, lithium, and calcium ions. HAL4 stabilizes the major high-affinity K+ transporter Trk1 at the plasma membrane under low K+ conditions, which prevents endocytosis and vacuolar degradation. Budding yeast Ptk2 phosphorylates and regulates the plasma membrane H+ ATPase, Pma1. The HAL4-like subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270896 [Multi-domain]  Cd Length: 265  Bit Score: 68.49  E-value: 3.07e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  838 LGRGAFGQVIEADafgiDK-TATCKTVAVKMLKEGATHS---EHRA-LMSELKILIHIgHHLNVVNLLGACTKPGGPLMV 912
Cdd:cd13994    1 IGKGATSVVRIVT----KKnPRSGVLYAVKEYRRRDDESkrkDYVKrLTSEYIISSKL-HHPNIVKVLDLCQDLHGKWCL 75
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  913 IVEFCKFGNLSTYLrgkrnefvpykskgarfrqgkdyvgelsvdlkrrldsitssqssassgfveEKSLSdveeeeasee 992
Cdd:cd13994   76 VMEYCPGGDLFTLI---------------------------------------------------EKADS---------- 94
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  993 lykdfLTLEHLICYSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLArDIYKDPdyvrkGDARLPLK---- 1068
Cdd:cd13994   95 -----LSLEEKDCFFKQILRGVAYLHSHGIAHRDLKPENILLDEDGVLKLTDFGTA-EVFGMP-----AEKESPMSaglc 163
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1069 ----WMAPETIFDRVYTIQS-DVWSFGVLLWEIFsLGASPYPGVKIDE----EFCRRLKEGTRMRAP-DYTTPEMYQT-- 1136
Cdd:cd13994  164 gsepYMAPEVFTSGSYDGRAvDVWSCGIVLFALF-TGRFPWRSAKKSDsaykAYEKSGDFTNGPYEPiENLLPSECRRli 242
                        330       340
                 ....*....|....*....|..
gi 27777648 1137 --MLdcwHEDPNQRPSFSELVE 1156
Cdd:cd13994  243 yrML---HPDPEKRITIDEALN 261
STKc_LKB1 cd14119
Catalytic domain of the Serine/Threonine kinase, Liver Kinase B1; STKs catalyze the transfer ...
1005-1157 3.74e-12

Catalytic domain of the Serine/Threonine kinase, Liver Kinase B1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. LKB1, also called STK11, was first identified as a tumor suppressor responsible for Peutz-Jeghers syndrome, a disorder that leads to an increased risk of spontaneous epithelial cancer. It serves as a master upstream kinase that activates AMP-activated protein kinase (AMPK) and most AMPK-like kinases. LKB1 and AMPK are part of an energy-sensing pathway that links cell energy to metabolism and cell growth. They play critical roles in the establishment and maintenance of cell polarity, cell proliferation, cytoskeletal organization, as well as T-cell metabolism, including T-cell development, homeostasis, and effector function. To be activated, LKB1 requires the adaptor proteins STe20-Related ADaptor (STRAD) and mouse protein 25 (MO25). The LKB1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271021 [Multi-domain]  Cd Length: 255  Bit Score: 68.05  E-value: 3.74e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1005 CYSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLAR--DIYKDPDYVRKGDARlPlKWMAPE-----TIFD 1077
Cdd:cd14119  101 GYFVQLIDGLEYLHSQGIIHKDIKPGNLLLTTDGTLKISDFGVAEalDLFAEDDTCTTSQGS-P-AFQPPEiangqDSFS 178
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1078 RVytiQSDVWSFGVLLWEIFSlGASPYPGVKIDEEFCrRLKEGTrMRAPDYTTPEMYQTMLDCWHEDPNQRPSFSELVEH 1157
Cdd:cd14119  179 GF---KVDIWSAGVTLYNMTT-GKYPFEGDNIYKLFE-NIGKGE-YTIPDDVDPDLQDLLRGMLEKDPEKRFTIEQIRQH 252
IgC2_3_Dscam cd20957
Third immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; ...
672-739 3.74e-12

Third immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the Constant 2 (C2)-set of IgSF domains; The members here are composed of the third immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. This group belongs to the C2-set of IgSF domains, having A, B, and E strands in one beta-sheet and A', G, F, C, and C' in the other. Unlike other Ig domain sets, the C2-set lacks the D strand.


Pssm-ID: 409549 [Multi-domain]  Cd Length: 88  Bit Score: 63.32  E-value: 3.74e-12
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 27777648  672 ENQTTTIGETIEVTCPASGNPTPHITWFKDNETLVEDSGIVLRDGNRnLTIRRVRKEDGGLYTCQACN 739
Cdd:cd20957    9 PVQTVDFGRTAVFNCSVTGNPIHTVLWMKDGKPLGHSSRVQILSEDV-LVIPSVKREDKGMYQCFVRN 75
STKc_MAP3K8 cd13995
Catalytic domain of the Serine/Threonine kinase, Mitogen-Activated Protein Kinase (MAPK) ...
1003-1157 3.82e-12

Catalytic domain of the Serine/Threonine kinase, Mitogen-Activated Protein Kinase (MAPK) Kinase Kinase 8; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAP3K8 is also called Tumor progression locus 2 (Tpl2) or Cancer Osaka thyroid (Cot), and was first identified as a proto-oncogene in T-cell lymphoma induced by MoMuL virus and in breast carcinoma induced by MMTV. Activated MAP3K8 induces various MAPK pathways including Extracellular Regulated Kinase (ERK) 1/2, c-Jun N-terminal kinase (JNK), and p38. It plays a pivotal role in innate immunity, linking Toll-like receptors to the production of TNF and the activation of ERK in macrophages. It is also required in interleukin-1beta production and is critical in host defense against Gram-positive bacteria. MAP3Ks (MKKKs or MAPKKKs) phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. The MAP3K8 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270897 [Multi-domain]  Cd Length: 256  Bit Score: 68.11  E-value: 3.82e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1003 LICYSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVkICDFGLARDIYKDPDYVRkgDARLPLKWMAPETIFDRVYTI 1082
Cdd:cd13995   98 IIWVTKHVLKGLDFLHSKNIIHHDIKPSNIVFMSTKAV-LVDFGLSVQMTEDVYVPK--DLRGTEIYMSPEVILCRGHNT 174
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1083 QSDVWSFGVLLWEIFSlGASP----YPGVKIDEEFCRRLKEGTRMR-APDYTTPEMYQTMLDCWHEDPNQRPSFSELVEH 1157
Cdd:cd13995  175 KADIYSLGATIIHMQT-GSPPwvrrYPRSAYPSYLYIIHKQAPPLEdIAQDCSPAMRELLEAALERNPNHRSSAAELLKH 253
PTKc_Wee1_fungi cd14052
Catalytic domain of the Protein Tyrosine Kinases, Fungal Wee1 proteins; PTKs catalyze the ...
831-1096 4.19e-12

Catalytic domain of the Protein Tyrosine Kinases, Fungal Wee1 proteins; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. This subfamily is composed of fungal Wee1 proteins, also called Swe1 in budding yeast and Mik1 in fission yeast. Yeast Wee1 is required to control cell size. Wee1 is a cell cycle checkpoint kinase that helps keep the cyclin-dependent kinase CDK1 in an inactive state through phosphorylation of an N-terminal tyr (Y15) residue. During the late G2 phase, CDK1 is activated and mitotic entry is promoted by the removal of this inhibitory phosphorylation by the phosphatase Cdc25. Although Wee1 is functionally a tyr kinase, it is more closely related to serine/threonine kinases (STKs). It contains a catalytic kinase domain sandwiched in between N- and C-terminal regulatory domains. It is regulated by phosphorylation and degradation, and its expression levels are also controlled by circadian clock proteins. The fungal Wee1 subfamily is part of a larger superfamily that includes the catalytic domains of STKs, other PTKs, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270954 [Multi-domain]  Cd Length: 278  Bit Score: 68.22  E-value: 4.19e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  831 RLKLGKPLGRGAFGQVIEADafgiDKTATCKTVAVKMLKEGATHSEHRA-LMSELKIL--IHIGHHLNVVNLLGACtKPG 907
Cdd:cd14052    1 RFANVELIGSGEFSQVYKVS----ERVPTGKVYAVKKLKPNYAGAKDRLrRLEEVSILreLTLDGHDNIVQLIDSW-EYH 75
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  908 GPLMVIVEFCKFGNLSTYLRgkrnefvpykskgarfrqgkdyvgELSvdLKRRLDSitssqssassgFVEEKSLsdveee 987
Cdd:cd14052   76 GHLYIQTELCENGSLDVFLS------------------------ELG--LLGRLDE-----------FRVWKIL------ 112
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  988 easeelykdfltlehlicysFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIYKDPDYVRKGDArlpl 1067
Cdd:cd14052  113 --------------------VELSLGLRFIHDHHFVHLDLKPANVLITFEGTLKIGDFGMATVWPLIRGIEREGDR---- 168
                        250       260
                 ....*....|....*....|....*....
gi 27777648 1068 KWMAPETIFDRVYTIQSDVWSFGVLLWEI 1096
Cdd:cd14052  169 EYIAPEILSEHMYDKPADIFSLGLILLEA 197
STKc_Nek5 cd08225
Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase ...
1001-1156 4.29e-12

Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase 5; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Neks are involved in the regulation of downstream processes following the activation of Cdc2, and many of their functions are cell cycle-related. They play critical roles in microtubule dynamics during ciliogenesis and mitosis. The specific function of Nek5 is unknown. Nek5 is one in a family of 11 different Neks (Nek1-11). The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173765 [Multi-domain]  Cd Length: 257  Bit Score: 68.06  E-value: 4.29e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1001 EHLICYSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVV-KICDFGLARDIYKDPDYVRKGdARLPLkWMAPETIFDRV 1079
Cdd:cd08225  101 DQILSWFVQISLGLKHIHDRKILHRDIKSQNIFLSKNGMVaKLGDFGIARQLNDSMELAYTC-VGTPY-YLSPEICQNRP 178
                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 27777648 1080 YTIQSDVWSFGVLLWEIFSLgASPYPGVKIDEEFCRRLKEGTRMRAPDYTTpEMYQTMLDCWHEDPNQRPSFSELVE 1156
Cdd:cd08225  179 YNNKTDIWSLGCVLYELCTL-KHPFEGNNLHQLVLKICQGYFAPISPNFSR-DLRSLISQLFKVSPRDRPSITSILK 253
PTK_Jak2_rpt1 cd05078
Pseudokinase (repeat 1) domain of the Protein Tyrosine Kinase, Janus kinase 2; Jak2 is widely ...
1009-1158 4.78e-12

Pseudokinase (repeat 1) domain of the Protein Tyrosine Kinase, Janus kinase 2; Jak2 is widely expressed in many tissues. It is essential for the signaling of hormone-like cytokines such as growth hormone, erythropoietin, thrombopoietin, and prolactin, as well as some IFNs and cytokines that signal through the IL-3 and gp130 receptors. Disruption of Jak2 in mice results in an embryonic lethal phenotype with multiple defects including erythropoietic and cardiac abnormalities. It is the only Jak gene that results in a lethal phenotype when disrupted in mice. A mutation in the pseudokinase domain of Jak2, V617F, is present in many myeloproliferative diseases, including almost all patients with polycythemia vera, and 50% of patients with essential thrombocytosis and myelofibrosis. Jak2 is a cytoplasmic (or nonreceptor) PTK containing an N-terminal FERM domain, followed by a Src homology 2 (SH2) domain, a pseudokinase domain, and a C-terminal tyr kinase domain. The pseudokinase domain shows similarity to tyr kinases but lacks crucial residues for catalytic activity and ATP binding. Despite this, the presumed pseudokinase (repeat 1) domain of Jak2 exhibits dual-specificity kinase activity, phosphorylating two negative regulatory sites in Jak2: Ser523 and Tyr570. Inactivation of the repeat 1 domain increased Jak2 basal activity, suggesting that it modulates the kinase activity of the C-terminal catalytic (repeat 2) domain. The Jak2 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270663 [Multi-domain]  Cd Length: 262  Bit Score: 67.66  E-value: 4.78e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1009 QVAKGMEFLASRKCIHRDLAARNILLSEKN--------VVKICDFG-----LARDIYKDpdyvrkgdaRLPlkWMAPETI 1075
Cdd:cd05078  112 QLAWAMHFLEEKTLVHGNVCAKNILLIREEdrktgnppFIKLSDPGisitvLPKDILLE---------RIP--WVPPECI 180
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1076 FD-RVYTIQSDVWSFGVLLWEIFSLGASPYPGVkideEFCRRL---KEGTRMRAPDYTtpEMYQTMLDCWHEDPNQRPSF 1151
Cdd:cd05078  181 ENpKNLSLATDKWSFGTTLWEICSGGDKPLSAL----DSQRKLqfyEDRHQLPAPKWT--ELANLINNCMDYEPDHRPSF 254

                 ....*..
gi 27777648 1152 SELVEHL 1158
Cdd:cd05078  255 RAIIRDL 261
STKc_Chk2 cd14084
Catalytic domain of the Serine/Threonine kinase, Cell cycle Checkpoint Kinase 2; STKs catalyze ...
829-1157 5.08e-12

Catalytic domain of the Serine/Threonine kinase, Cell cycle Checkpoint Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Checkpoint Kinase 2 (Chk2) plays an important role in cellular responses to DNA double-strand breaks and related lesions. It is phosphorylated and activated by ATM kinase, resulting in its dissociation from sites of damage to phosphorylate downstream targets such as BRCA1, p53, cell cycle transcription factor E2F1, the promyelocytic leukemia protein (PML) involved in apoptosis, and CDC25 phosphatases, among others. Mutations in Chk2 is linked to a variety of cancers including familial breast cancer, myelodysplastic syndromes, prostate cancer, lung cancer, and osteosarcomas. Chk2 contains an N-terminal SQ/TQ cluster domain (SCD), a central forkhead-associated (FHA) domain, and a C-terminal catalytic kinase domain. The Chk2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270986 [Multi-domain]  Cd Length: 275  Bit Score: 67.80  E-value: 5.08e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  829 RDRLKLGKPLGRGAFGQVieadAFGIDKTaTCKTVAVKMLKE-------GATHSEHRALMSELKILIHIGHHlNVVNLLG 901
Cdd:cd14084    5 RKKYIMSRTLGSGACGEV----KLAYDKS-TCKKVAIKIINKrkftigsRREINKPRNIETEIEILKKLSHP-CIIKIED 78
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  902 ACTKPGGPLMVIvefckfgnlsTYLRGkrnefvpykskgarfrqgkdyvGELsvdlkrrldsitssqssassgfveeksL 981
Cdd:cd14084   79 FFDAEDDYYIVL----------ELMEG----------------------GEL---------------------------F 99
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  982 SDVeeeeaseelyKDFLTLEHLIC--YSFQVAKGMEFLASRKCIHRDLAARNILLSEKN---VVKICDFGLARDIykDPD 1056
Cdd:cd14084  100 DRV----------VSNKRLKEAICklYFYQMLLAVKYLHSNGIIHRDLKPENVLLSSQEeecLIKITDFGLSKIL--GET 167
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1057 YVRKGDARLPLkWMAPETI--FDRV-YTIQSDVWSFGVLLWEIFSlGASPYPGVKIDEEFCRRLKEGTRMRAPDY----- 1128
Cdd:cd14084  168 SLMKTLCGTPT-YLAPEVLrsFGTEgYTRAVDCWSLGVILFICLS-GYPPFSEEYTQMSLKEQILSGKYTFIPKAwknvs 245
                        330       340       350
                 ....*....|....*....|....*....|
gi 27777648 1129 -TTPEMYQTMLDCwheDPNQRPSFSELVEH 1157
Cdd:cd14084  246 eEAKDLVKKMLVV---DPSRRPSIEEALEH 272
IgI_4_hemolin-like cd20978
Fourth immunoglobulin (Ig)-like domain of hemolin, and similar domains; a member of the I-set ...
665-749 5.11e-12

Fourth immunoglobulin (Ig)-like domain of hemolin, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain of hemolin and similar proteins. Hemolin, an insect immunoglobulin superfamily (IgSF) member containing four Ig-like domains, is a lipopolysaccharide-binding immune protein induced during bacterial infection. Hemolin shares significant sequence similarity with the first four Ig-like domains of the transmembrane cell adhesion molecules (CAMs) of the L1 family. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The fourth Ig-like domain of hemolin is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409570 [Multi-domain]  Cd Length: 88  Bit Score: 63.18  E-value: 5.11e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  665 PMITGNLENQTTTI-GETIEVTCPASGNPTPHITWFKDNETLVEDSGIVLRDGNRnLTIRRVRKEDGGLYTCQACNVLGC 743
Cdd:cd20978    1 PKFIQKPEKNVVVKgGQDVTLPCQVTGVPQPKITWLHNGKPLQGPMERATVEDGT-LTIINVQPEDTGYYGCVATNEIGD 79

                 ....*.
gi 27777648  744 ARAETL 749
Cdd:cd20978   80 IYTETL 85
STKc_Yank1 cd05578
Catalytic domain of the Serine/Threonine Kinase, Yank1; STKs catalyze the transfer of the ...
1010-1153 5.39e-12

Catalytic domain of the Serine/Threonine Kinase, Yank1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily contains uncharacterized STKs with similarity to the human protein designated as Yank1 or STK32A. The Yank1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270730 [Multi-domain]  Cd Length: 257  Bit Score: 67.67  E-value: 5.39e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1010 VAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIYKDpdyvRKGDARLPLK-WMAPETIFDRVYTIQSDVWS 1088
Cdd:cd05578  109 IVLALDYLHSKNIIHRDIKPDNILLDEQGHVHITDFNIATKLTDG----TLATSTSGTKpYMAPEVFMRAGYSFAVDWWS 184
                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 27777648 1089 FGVLLWEiFSLGASPYPG--VKIDEEFCRRLKEGTRMRAPDYTTPEM--YQTMLDcwhEDPNQRPSFSE 1153
Cdd:cd05578  185 LGVTAYE-MLRGKRPYEIhsRTSIEEIRAKFETASVLYPAGWSEEAIdlINKLLE---RDPQKRLGDLS 249
STKc_Sty1_Hog1 cd07856
Catalytic domain of the Serine/Threonine Kinases, Fungal Mitogen-Activated Protein Kinases ...
836-1114 5.62e-12

Catalytic domain of the Serine/Threonine Kinases, Fungal Mitogen-Activated Protein Kinases Sty1 and Hog1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of the MAPKs Sty1 from Schizosaccharomyces pombe, Hog1 from Saccharomyces cerevisiae, and similar proteins. Sty1 and Hog1 are stress-activated MAPKs that partipate in transcriptional regulation in response to stress. Sty1 is activated in response to oxidative stress, osmotic stress, and UV radiation. It is regulated by the MAP2K Wis1, which is activated by the MAP3Ks Wis4 and Win1, which receive signals of the stress condition from membrane-spanning histidine kinases Mak1-3. Activated Sty1 stabilizes the Atf1 transcription factor and induces transcription of Atf1-dependent genes of the core environmetal stress response. Hog1 is the key element in the high osmolarity glycerol (HOG) pathway and is activated upon hyperosmotic stress. Activated Hog1 accumulates in the nucleus and regulates stress-induced transcription. The HOG pathway is mediated by two transmembrane osmosensors, Sln1 and Sho1. MAPKs are important mediators of cellular responses to extracellular signals. The Sty1/Hog1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270843 [Multi-domain]  Cd Length: 328  Bit Score: 68.75  E-value: 5.62e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  836 KPLGRGAFGQVIEADafgidKTATCKTVAVK-MLKEGATHSEHRALMSELKILIHIGHHlNVVNLLGACTKPGGPLMVIV 914
Cdd:cd07856   16 QPVGMGAFGLVCSAR-----DQLTGQNVAVKkIMKPFSTPVLAKRTYRELKLLKHLRHE-NIISLSDIFISPLEDIYFVT 89
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  915 EFckfgnlstylrgkrnefvpykskgarfrqgkdyvgeLSVDLKRRLdsitssqssassgfveekslsdveeeeASEELY 994
Cdd:cd07856   90 EL------------------------------------LGTDLHRLL---------------------------TSRPLE 106
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  995 KDFLTLehlicYSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARdiYKDPDYVRKGDARLplkWMAPET 1074
Cdd:cd07856  107 KQFIQY-----FLYQILRGLKYVHSAGVIHRDLKPSNILVNENCDLKICDFGLAR--IQDPQMTGYVSTRY---YRAPEI 176
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|.
gi 27777648 1075 IFD-RVYTIQSDVWSFGVLLWEIFsLGASPYPGVKIDEEFC 1114
Cdd:cd07856  177 MLTwQKYDVEVDIWSAGCIFAEML-EGKPLFPGKDHVNQFS 216
PTZ00024 PTZ00024
cyclin-dependent protein kinase; Provisional
834-1106 5.73e-12

cyclin-dependent protein kinase; Provisional


Pssm-ID: 240233 [Multi-domain]  Cd Length: 335  Bit Score: 68.63  E-value: 5.73e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648   834 LGKPLGRGAFGQVIEAdafgIDkTATCKTVAVKMLK-----EGATHSE--------HRALMSELKILIHIgHHLNVVNLL 900
Cdd:PTZ00024   13 KGAHLGEGTYGKVEKA----YD-TLTGKIVAIKKVKiieisNDVTKDRqlvgmcgiHFTTLRELKIMNEI-KHENIMGLV 86
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648   901 GActkpggplmviveFCK--FGNLstylrgkrnefvpykskgarfrqgkdyVGEL-SVDLKRRLDSitssqssassgfve 977
Cdd:PTZ00024   87 DV-------------YVEgdFINL---------------------------VMDImASDLKKVVDR-------------- 112
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648   978 ekslsdveeeeaseelyKDFLTLEHLICYSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLAR----DIYK 1053
Cdd:PTZ00024  113 -----------------KIRLTESQVKCILLQILNGLNVLHKWYFMHRDLSPANIFINSKGICKIADFGLARrygyPPYS 175
                         250       260       270       280       290       300
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 27777648  1054 DPDYVRKGDAR--------LPLKWMAPETIF-DRVYTIQSDVWSFGVLLWEIFSlGASPYPG 1106
Cdd:PTZ00024  176 DTLSKDETMQRreemtskvVTLWYRAPELLMgAEKYHFAVDMWSVGCIFAELLT-GKPLFPG 236
STKc_ERK1_2_like cd07849
Catalytic domain of Extracellular signal-Regulated Kinase 1 and 2-like Serine/Threonine ...
998-1106 6.02e-12

Catalytic domain of Extracellular signal-Regulated Kinase 1 and 2-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of the mitogen-activated protein kinases (MAPKs) ERK1, ERK2, baker's yeast Fus3, and similar proteins. MAPK pathways are important mediators of cellular responses to extracellular signals. ERK1/2 activation is preferentially by mitogenic factors, differentiation stimuli, and cytokines, through a kinase cascade involving the MAPK kinases MEK1/2 and a MAPK kinase kinase from the Raf family. ERK1/2 have numerous substrates, many of which are nuclear and participate in transcriptional regulation of many cellular processes. They regulate cell growth, cell proliferation, and cell cycle progression from G1 to S phase. Although the distinct roles of ERK1 and ERK2 have not been fully determined, it is known that ERK2 can maintain most functions in the absence of ERK1, and that the deletion of ERK2 is embryonically lethal. The MAPK, Fus3, regulates yeast mating processes including mating-specific gene expression, G1 arrest, mating projection, and cell fusion. This ERK1/2-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270839 [Multi-domain]  Cd Length: 336  Bit Score: 68.49  E-value: 6.02e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  998 LTLEHlICY-SFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIYKDPDYVRKGDARLPLKWM-APETI 1075
Cdd:cd07849  103 LSNDH-IQYfLYQILRGLKYIHSANVLHRDLKPSNLLLNTNCDLKICDFGLARIADPEHDHTGFLTEYVATRWYrAPEIM 181
                         90       100       110
                 ....*....|....*....|....*....|...
gi 27777648 1076 FD-RVYTIQSDVWSFGVLLWEIFSlgASP-YPG 1106
Cdd:cd07849  182 LNsKGYTKAIDIWSVGCILAEMLS--NRPlFPG 212
STKc_cGK cd05572
Catalytic domain of the Serine/Threonine Kinase, cGMP-dependent protein kinase (cGK or PKG); ...
1006-1132 6.67e-12

Catalytic domain of the Serine/Threonine Kinase, cGMP-dependent protein kinase (cGK or PKG); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Mammals have two cGK isoforms from different genes, cGKI and cGKII. cGKI exists as two splice variants, cGKI-alpha and cGKI-beta. cGK consists of an N-terminal regulatory domain containing a dimerization and an autoinhibitory pseudosubstrate region, two cGMP-binding domains, and a C-terminal catalytic domain. Binding of cGMP to both binding sites releases the inhibition of the catalytic center by the pseudosubstrate region, allowing autophosphorylation and activation of the kinase. cGKI is a soluble protein expressed in all smooth muscles, platelets, cerebellum, and kidney. It is also expressed at lower concentrations in other tissues. cGKII is a membrane-bound protein that is most abundantly expressed in the intestine. It is also present in the brain nuclei, adrenal cortex, kidney, lung, and prostate. cGKI is involved in the regulation of smooth muscle tone, smooth cell proliferation, and platelet activation. cGKII plays a role in the regulation of secretion, such as renin secretion by the kidney and aldosterone secretion by the adrenal. It also regulates bone growth and the circadian rhythm. The cGK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270724 [Multi-domain]  Cd Length: 262  Bit Score: 67.25  E-value: 6.67e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1006 YSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIYK---------DPDYvrkgdarlplkwMAPETIF 1076
Cdd:cd05572   98 YTACVVLAFEYLHSRGIIYRDLKPENLLLDSNGYVKLVDFGFAKKLGSgrktwtfcgTPEY------------VAPEIIL 165
                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 27777648 1077 DRVYTIQSDVWSFGVLLWEIFSlGASPYPGVKIDE-EFCRR-LKEGTRMRAPDYTTPE 1132
Cdd:cd05572  166 NKGYDFSVDYWSLGILLYELLT-GRPPFGGDDEDPmKIYNIiLKGIDKIEFPKYIDKN 222
STKc_PAK6 cd06659
Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 6; STKs catalyze the ...
1002-1164 6.93e-12

Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 6; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PAK6 may play a role in stress responses through its activation by the mitogen-activated protein kinase (MAPK) p38 and MAPK kinase 6 (MKK6) pathway. PAK6 is highly expressed in the brain. It is not required for viability, but together with PAK5, it is required for normal levels of locomotion and activity, and for learning and memory. Increased expression of PAK6 is found in primary and metastatic prostate cancer. PAK6 may play a role in the regulation of motility. PAK6 belongs to the group II PAKs, which contain a PBD (p21-binding domain) and a C-terminal catalytic domain, but do not harbor an AID (autoinhibitory domain) or SH3 binding sites. PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. The PAK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270821 [Multi-domain]  Cd Length: 297  Bit Score: 68.09  E-value: 6.93e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1002 HLICYSfqVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIYKD-PDyvRKGDARLPLkWMAPETIFDRVY 1080
Cdd:cd06659  120 ATVCEA--VLQALAYLHSQGVIHRDIKSDSILLTLDGRVKLSDFGFCAQISKDvPK--RKSLVGTPY-WMAPEVISRCPY 194
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1081 TIQSDVWSFGVLLWEIFSlGASPYPGvKIDEEFCRRLKEG--TRMRAPDYTTPEMYQTMLDCWHEDPNQRPSFSELVEHL 1158
Cdd:cd06659  195 GTEVDIWSLGIMVIEMVD-GEPPYFS-DSPVQAMKRLRDSppPKLKNSHKASPVLRDFLERMLVRDPQERATAQELLDHP 272

                 ....*.
gi 27777648 1159 gNLLQA 1164
Cdd:cd06659  273 -FLLQT 277
STKc_ULK2 cd14201
Catalytic domain of the Serine/Threonine kinase, Unc-51-like kinase 2; STKs catalyze the ...
838-1157 7.79e-12

Catalytic domain of the Serine/Threonine kinase, Unc-51-like kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The ATG1/ULK complex is conserved from yeast to humans and it plays a critical role in the initiation of autophagy, the intracellular system that leads to the lysosomal degradation of cellular components and their recycling into basic metabolic units. ULK2 is ubiquitously expressed and is essential in autophagy induction. It displays partially redundant functions with ULK1 and is able to compensate for the loss of ULK1 in non-selective autophagy. It also displays neuron-specific functions and is important in axon development. The ULK2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271103 [Multi-domain]  Cd Length: 271  Bit Score: 67.34  E-value: 7.79e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  838 LGRGAFGQVIEadafGIDKTATCKTVAVKMLKEGATHSEHRALMSELKILIHIGHHlNVVNLLGACTKPGGPLMVIvEFC 917
Cdd:cd14201   14 VGHGAFAVVFK----GRHRKKTDWEVAIKSINKKNLSKSQILLGKEIKILKELQHE-NIVALYDVQEMPNSVFLVM-EYC 87
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  918 KFGNLSTYLRGKrnefvpykskgarfrqgkdyvGELSVDLKRrldsitssqssassgfveekslsdveeeeaseelykdf 997
Cdd:cd14201   88 NGGDLADYLQAK---------------------GTLSEDTIR-------------------------------------- 108
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  998 ltlehliCYSFQVAKGMEFLASRKCIHRDLAARNILLSEKN---------VVKICDFGLARdiYKDPDYVRKGDARLPLk 1068
Cdd:cd14201  109 -------VFLQQIAAAMRILHSKGIIHRDLKPQNILLSYASrkkssvsgiRIKIADFGFAR--YLQSNMMAATLCGSPM- 178
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1069 WMAPETIFDRVYTIQSDVWSFGVLLWEIFsLGASPYPGVKIDEefCRRLKEGTRMRAPDY---TTPEMYQTMLDCWHEDP 1145
Cdd:cd14201  179 YMAPEVIMSQHYDAKADLWSIGTVIYQCL-VGKPPFQANSPQD--LRMFYEKNKNLQPSIpreTSPYLADLLLGLLQRNQ 255
                        330
                 ....*....|..
gi 27777648 1146 NQRPSFSELVEH 1157
Cdd:cd14201  256 KDRMDFEAFFSH 267
STKc_GRK4_like cd05605
Catalytic domain of G protein-coupled Receptor Kinase 4-like Serine/Threonine Kinases; STKs ...
998-1119 8.25e-12

Catalytic domain of G protein-coupled Receptor Kinase 4-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Members of the GRK4-like group include GRK4, GRK5, GRK6, and similar GRKs. They contain an N-terminal RGS homology (RH) domain and a catalytic domain, but lack a G protein betagamma-subunit binding domain. They are localized to the plasma membrane through post-translational lipid modification or direct binding to PIP2. GRKs phosphorylate and regulate G protein-coupled receptors (GPCRs), the largest superfamily of cell surface receptors which regulate some part of nearly all physiological functions. Phosphorylated GPCRs bind to arrestins, which prevents further G protein signaling despite the presence of activating ligand. The GRK4-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270756 [Multi-domain]  Cd Length: 285  Bit Score: 67.38  E-value: 8.25e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  998 LTLEHLICYSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIyKDPDYVRkgdARL-PLKWMAPETIF 1076
Cdd:cd05605   99 FEEERAVFYAAEITCGLEHLHSERIVYRDLKPENILLDDHGHVRISDLGLAVEI-PEGETIR---GRVgTVGYMAPEVVK 174
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*.
gi 27777648 1077 DRVYTIQSDVWSFGVLLWEIFSlGASPYPGVKID---EEFCRRLKE 1119
Cdd:cd05605  175 NERYTFSPDWWGLGCLIYEMIE-GQAPFRARKEKvkrEEVDRRVKE 219
Ig_2 pfam13895
Immunoglobulin domain; This domain contains immunoglobulin-like domains.
664-739 1.00e-11

Immunoglobulin domain; This domain contains immunoglobulin-like domains.


Pssm-ID: 464026 [Multi-domain]  Cd Length: 79  Bit Score: 62.03  E-value: 1.00e-11
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 27777648    664 APMITgnLENQTTTIGETIEVTCPASGNPTPHITWFKDNETLvedsgivlrDGNRNLTIRRVRKEDGGLYTCQACN 739
Cdd:pfam13895    1 KPVLT--PSPTVVTEGEPVTLTCSAPGNPPPSYTWYKDGSAI---------SSSPNFFTLSVSAEDSGTYTCVARN 65
STKc_CDK5 cd07839
Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 5; STKs ...
999-1158 1.02e-11

Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 5; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK5 is unusual in that it is regulated by non-cyclin proteins, p35 and p39. It is highly expressed in the nervous system and is critical in normal neural development and function. It plays a role in neuronal migration and differentiation, and is also important in synaptic plasticity and learning. CDK5 also participates in protecting against cell death and promoting angiogenesis. Impaired CDK5 activity is implicated in Alzheimer's disease, amyotrophic lateral sclerosis, Parkinson's disease, Huntington's disease and acute neuronal injury. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK5 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 143344 [Multi-domain]  Cd Length: 284  Bit Score: 67.07  E-value: 1.02e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  999 TLEHLICYSF--QVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDiYKDPdyVRKGDARLPLKWM-APETI 1075
Cdd:cd07839   95 DIDPEIVKSFmfQLLKGLAFCHSHNVLHRDLKPQNLLINKNGELKLADFGLARA-FGIP--VRCYSAEVVTLWYrPPDVL 171
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1076 FD-RVYTIQSDVWSFGVLLWEIFSLGASPYPGVKIDEEFCRRLKE-GTR--------MRAPDYTTPEMYQTMLDCWHEDP 1145
Cdd:cd07839  172 FGaKLYSTSIDMWSAGCIFAELANAGRPLFPGNDVDDQLKRIFRLlGTPteeswpgvSKLPDYKPYPMYPATTSLVNVVP 251
                        170
                 ....*....|...
gi 27777648 1146 NQRPSFSELVEHL 1158
Cdd:cd07839  252 KLNSTGRDLLQNL 264
STKc_PKN cd05589
Catalytic domain of the Serine/Threonine Kinase, Protein Kinase N; STKs catalyze the transfer ...
1006-1112 1.09e-11

Catalytic domain of the Serine/Threonine Kinase, Protein Kinase N; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKN has a C-terminal catalytic domain that is highly homologous to PKCs. Its unique N-terminal regulatory region contains antiparallel coiled-coil (ACC) domains. In mammals, there are three PKN isoforms from different genes (designated PKN-alpha, beta, and gamma), which show different enzymatic properties, tissue distribution, and varied functions. PKN can be activated by the small GTPase Rho, and by fatty acids such as arachidonic and linoleic acids. It is involved in many biological processes including cytokeletal regulation, cell adhesion, vesicle transport, glucose transport, regulation of meiotic maturation and embryonic cell cycles, signaling to the nucleus, and tumorigenesis. The PKN subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270741 [Multi-domain]  Cd Length: 326  Bit Score: 67.71  E-value: 1.09e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1006 YSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARD--IYKD--------PDYvrkgdarlplkwMAPETI 1075
Cdd:cd05589  106 YAACVVLGLQFLHEHKIVYRDLKLDNLLLDTEGYVKIADFGLCKEgmGFGDrtstfcgtPEF------------LAPEVL 173
                         90       100       110
                 ....*....|....*....|....*....|....*..
gi 27777648 1076 FDRVYTIQSDVWSFGVLLWEIFsLGASPYPGvkIDEE 1112
Cdd:cd05589  174 TDTSYTRAVDWWGLGVLIYEML-VGESPFPG--DDEE 207
STKc_CDK4_6_like cd07838
Catalytic domain of Cyclin-Dependent protein Kinase 4 and 6-like Serine/Threonine Kinases; ...
1007-1099 1.22e-11

Catalytic domain of Cyclin-Dependent protein Kinase 4 and 6-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK4 and CDK6 partner with D-type cyclins to regulate the early G1 phase of the cell cycle. They are the first kinases activated by mitogenic signals to release cells from the G0 arrested state. CDK4 and CDK6 are both expressed ubiquitously, associate with all three D cyclins (D1, D2 and D3), and phosphorylate the retinoblastoma (pRb) protein. They are also regulated by the INK4 family of inhibitors which associate with either the CDK alone or the CDK/cyclin complex. CDK4 and CDK6 show differences in subcellular localization, sensitivity to some inhibitors, timing in activation, tumor selectivity, and possibly substrate profiles. Although CDK4 and CDK6 seem to show some redundancy, they also have discrete, nonoverlapping functions. CDK6 plays an important role in cell differentiation. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK4/6-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270831 [Multi-domain]  Cd Length: 287  Bit Score: 66.92  E-value: 1.22e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1007 SFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARdIYKdpDYVRKGDARLPLKWMAPETIFDRVYTIQSDV 1086
Cdd:cd07838  113 MRQLLRGLDFLHSHRIVHRDLKPQNILVTSDGQVKLADFGLAR-IYS--FEMALTSVVVTLWYRAPEVLLQSSYATPVDM 189
                         90
                 ....*....|...
gi 27777648 1087 WSFGVLLWEIFSL 1099
Cdd:cd07838  190 WSVGCIFAELFNR 202
STKc_GRK6 cd05630
Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase 6; STKs ...
1004-1158 1.22e-11

Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase 6; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. GRK6 is widely expressed in many tissues and is expressed as multiple splice variants with different domain architectures. It is post-translationally palmitoylated and localized in the membrane. GRK6 plays important roles in the regulation of dopamine, M3 muscarinic, opioid, and chemokine receptor signaling. It also plays maladaptive roles in addiction and Parkinson's disease. GRK6-deficient mice exhibit altered dopamine receptor regulation, decreased lymphocyte chemotaxis, and increased acute inflammation and neutrophil chemotaxis. GRKs phosphorylate and regulate G protein-coupled receptors (GPCRs), the largest superfamily of cell surface receptors which regulate some part of nearly all physiological functions. Phosphorylated GPCRs bind to arrestins, which prevents further G protein signaling despite the presence of activating ligand. The GRK6 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270779 [Multi-domain]  Cd Length: 285  Bit Score: 66.97  E-value: 1.22e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1004 ICYSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLArdIYKDPDYVRKGDARlPLKWMAPETIFDRVYTIQ 1083
Cdd:cd05630  105 VFYAAEICCGLEDLHRERIVYRDLKPENILLDDHGHIRISDLGLA--VHVPEGQTIKGRVG-TVGYMAPEVVKNERYTFS 181
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1084 SDVWSFGVLLWEIFSlGASPYPGVKID---EEFCRRLKEGTRMRAPDYtTPEMYQ--TMLDCwhEDPNQR-----PSFSE 1153
Cdd:cd05630  182 PDWWALGCLLYEMIA-GQSPFQQRKKKikrEEVERLVKEVPEEYSEKF-SPQARSlcSMLLC--KDPAERlgcrgGGARE 257

                 ....*
gi 27777648 1154 LVEHL 1158
Cdd:cd05630  258 VKEHP 262
STKc_RSK1_C cd14175
C-terminal catalytic domain of the Serine/Threonine Kinase, Ribosomal S6 kinase 1 (also called ...
1008-1157 1.41e-11

C-terminal catalytic domain of the Serine/Threonine Kinase, Ribosomal S6 kinase 1 (also called Ribosomal protein S6 kinase alpha-1 or 90kDa ribosomal protein S6 kinase 1); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. RSK1 is also called S6K-alpha-1, RPS6KA1, p90RSK1 or MAPK-activated protein kinase 1a (MAPKAPK-1a). It is a component of the insulin transduction pathway, regulating the function of IRS1. It also interacts with PKA and promotes its inactivation. RSK1 is one of four RSK isoforms (RSK1-4) from distinct genes present in vertebrates. RSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family. They are activated by signaling inputs from extracellular regulated kinase (ERK) and phosphoinositide dependent kinase 1 (PDK1). ERK phosphorylates and activates the CTD of RSK, serving as a docking site for PDK1, which phosphorylates and activates the NTD, which in turn phosphorylates all known RSK substrates. RSKs act as downstream effectors of mitogen-activated protein kinase (MAPK) and play key roles in mitogen-activated cell growth, differentiation, and survival. The RSK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271077 [Multi-domain]  Cd Length: 291  Bit Score: 66.97  E-value: 1.41e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1008 FQVAKGMEFLASRKCIHRDLAARNILLSEKN----VVKICDFGLARDIYKD------PDYVRkgdarlplKWMAPETIFD 1077
Cdd:cd14175  102 HTICKTVEYLHSQGVVHRDLKPSNILYVDESgnpeSLRICDFGFAKQLRAEngllmtPCYTA--------NFVAPEVLKR 173
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1078 RVYTIQSDVWSFGVLLWEIFSlGASPYPGVKID--EEFCRRLKEGT-RMRAPDYTT-----PEMYQTMLdcwHEDPNQRP 1149
Cdd:cd14175  174 QGYDEGCDIWSLGILLYTMLA-GYTPFANGPSDtpEEILTRIGSGKfTLSGGNWNTvsdaaKDLVSKML---HVDPHQRL 249

                 ....*...
gi 27777648 1150 SFSELVEH 1157
Cdd:cd14175  250 TAKQVLQH 257
STKc_TDY_MAPK cd07859
Catalytic domain of the Serine/Threonine Kinases, Plant TDY Mitogen-Activated Protein Kinases; ...
996-1106 1.54e-11

Catalytic domain of the Serine/Threonine Kinases, Plant TDY Mitogen-Activated Protein Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Plant MAPKs are typed based on the conserved phosphorylation motif present in the activation loop, TEY and TDY. This subfamily represents the TDY subtype and is composed of Group D plant MAPKs including Arabidopsis thaliana MPK18 (AtMPK18), Oryza sativa Blast- and Wound-induced MAPK1 (OsBWMK1), OsWJUMK1 (Wound- and JA-Uninducible MAPK1), Zea mays MPK6, and the Medicago sativa TDY1 gene product. OsBWMK1 enhances resistance to pathogenic infections. It mediates stress-activated defense responses by activating a transcription factor that affects the expression of stress-related genes. AtMPK18 is involved in microtubule-related functions. In plants, MAPKs are associated with physiological, developmental, hormonal, and stress responses. Some plants show numerous gene duplications of MAPKs; Arabidopsis thaliana harbors at least 20 MAPKs, named AtMPK1-20 while Oryza sativa contains at least 17 MAPKs. Arabidopsis thaliana contains more TEY-type MAPKs than TDY-type, whereas the reverse is true for Oryza sativa. The TDY MAPK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 143364 [Multi-domain]  Cd Length: 338  Bit Score: 67.50  E-value: 1.54e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  996 DFLTLEHLICYSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIYKD-------PDYVrkgdarlPLK 1068
Cdd:cd07859   98 DDLTPEHHQFFLYQLLRALKYIHTANVFHRDLKPKNILANADCKLKICDFGLARVAFNDtptaifwTDYV-------ATR 170
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|..
gi 27777648 1069 WM-APE---TIFDRvYTIQSDVWSFGVLLWEIFsLGASPYPG 1106
Cdd:cd07859  171 WYrAPElcgSFFSK-YTPAIDIWSIGCIFAEVL-TGKPLFPG 210
STKc_PLK3 cd14189
Catalytic domain of the Serine/Threonine Kinase, Polo-like kinase 3; STKs catalyze the ...
1006-1157 1.61e-11

Catalytic domain of the Serine/Threonine Kinase, Polo-like kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PLKs play important roles in cell cycle progression and in DNA damage responses. They regulate mitotic entry, mitotic exit, and cytokinesis. In general PLKs contain an N-terminal catalytic kinase domain and a C-terminal regulatory polo box domain (PBD), which is comprised by two bipartite polo-box motifs (or polo boxes) and is involved in protein interactions. There are five mammalian PLKs (PLK1-5) from distinct genes. PLK3, also called Prk or Fnk (FGF-inducible kinase), regulates angiogenesis and responses to DNA damage. Activated PLK3 mediates Chk2 phosphorylation by ATM and the resulting checkpoint activation. PLK3 phosphorylates DNA polymerase delta and may be involved in DNA repair. It also inhibits Cdc25c, thereby regulating the onset of mitosis. The PLK3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271091 [Multi-domain]  Cd Length: 255  Bit Score: 66.10  E-value: 1.61e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1006 YSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLArdIYKDPDYVRKGDARLPLKWMAPETIFDRVYTIQSD 1085
Cdd:cd14189  106 YLKQIISGLKYLHLKGILHRDLKLGNFFINENMELKVGDFGLA--ARLEPPEQRKKTICGTPNYLAPEVLLRQGHGPESD 183
                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 27777648 1086 VWSFGVLLWEIFSlGASPYPGVKIDEEFcRRLKEgTRMRAPDYTTPEMYQTMLDCWHEDPNQRPSFSELVEH 1157
Cdd:cd14189  184 VWSLGCVMYTLLC-GNPPFETLDLKETY-RCIKQ-VKYTLPASLSLPARHLLAGILKRNPGDRLTLDQILEH 252
STKc_MPK1 cd07857
Catalytic domain of the Serine/Threonine Kinase, Fungal Mitogen-Activated Protein Kinase MPK1; ...
831-1103 2.41e-11

Catalytic domain of the Serine/Threonine Kinase, Fungal Mitogen-Activated Protein Kinase MPK1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of the MAPKs MPK1 from Saccharomyces cerevisiae, Pmk1 from Schizosaccharomyces pombe, and similar proteins. MPK1 (also called Slt2) and Pmk1 (also called Spm1) are stress-activated MAPKs that regulate the cell wall integrity pathway, and are therefore important in the maintainance of cell shape, cell wall construction, morphogenesis, and ion homeostasis. MPK1 is activated in response to cell wall stress including heat stimulation, osmotic shock, UV irradiation, and any agents that interfere with cell wall biogenesis such as chitin antagonists, caffeine, or zymolase. MPK1 is regulated by the MAP2Ks Mkk1/2, which are regulated by the MAP3K Bck1. Pmk1 is also activated by multiple stresses including elevated temperatures, hyper- or hypotonic stress, glucose deprivation, exposure to cell-wall damaging compounds, and oxidative stress. It is regulated by the MAP2K Pek1, which is regulated by the MAP3K Mkh1. MAPKs are important mediators of cellular responses to extracellular signals. The MPK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173750 [Multi-domain]  Cd Length: 332  Bit Score: 66.66  E-value: 2.41e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  831 RLKLGKPLGRGAFGQVIEADAFGidkTATCKTVAVKMLKE--GATHSEHRALmSELKILIHIGHHLNVVNLLGactkpgg 908
Cdd:cd07857    1 RYELIKELGQGAYGIVCSARNAE---TSEEETVAIKKITNvfSKKILAKRAL-RELKLLRHFRGHKNITCLYD------- 69
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  909 plMVIVEFCKFGNLstYLrgkrnefvpykskgarfrqgkdYVGELSVDLKRRLDsitssqssassgfvEEKSLSDVEeee 988
Cdd:cd07857   70 --MDIVFPGNFNEL--YL----------------------YEELMEADLHQIIR--------------SGQPLTDAH--- 106
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  989 aseelYKDFLtlehlicysFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIYKDP--------DYVRK 1060
Cdd:cd07857  107 -----FQSFI---------YQILCGLKYIHSANVLHRDLKPGNLLVNADCELKICDFGLARGFSENPgenagfmtEYVAT 172
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|....*
gi 27777648 1061 gdarlplKWM-APETIFD-RVYTIQSDVWSFGVLLWEIfsLGASP 1103
Cdd:cd07857  173 -------RWYrAPEIMLSfQSYTKAIDVWSVGCILAEL--LGRKP 208
STKc_cPKC cd05587
Catalytic domain of the Serine/Threonine Kinase, Classical (or Conventional) Protein Kinase C; ...
1002-1113 2.48e-11

Catalytic domain of the Serine/Threonine Kinase, Classical (or Conventional) Protein Kinase C; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. cPKCs are potent kinases for histones, myelin basic protein, and protamine. They depend on calcium, DAG (1,2-diacylglycerol), and in most cases, phosphatidylserine (PS) for activation. cPKCs contain a calcium-binding C2 region in their regulatory domain. There are four cPKC isoforms, named alpha, betaI, betaII, and gamma. PKC-gamma is mainly expressed in neuronal tissues. It plays a role in protection from ischemia. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. The cPKC subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270739 [Multi-domain]  Cd Length: 320  Bit Score: 66.65  E-value: 2.48e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1002 HLICYSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARD-IYKD---------PDYVrkgdarlplkwmA 1071
Cdd:cd05587   98 VAVFYAAEIAVGLFFLHSKGIIYRDLKLDNVMLDAEGHIKIADFGMCKEgIFGGkttrtfcgtPDYI------------A 165
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|..
gi 27777648 1072 PETIFDRVYTIQSDVWSFGVLLWEIFSlGASPYPGVKIDEEF 1113
Cdd:cd05587  166 PEIIAYQPYGKSVDWWAYGVLLYEMLA-GQPPFDGEDEDELF 206
STK_BAK1_like cd14664
Catalytic domain of the Serine/Threonine Kinase, BRI1 associated kinase 1 and related STKs; ...
838-1160 2.76e-11

Catalytic domain of the Serine/Threonine Kinase, BRI1 associated kinase 1 and related STKs; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily includes three leucine-rich repeat receptor-like kinases (LRR-RLKs): Arabidopsis thaliana BAK1 and CLAVATA1 (CLV1), and Physcomitrella patens CLL1B clavata1-like receptor S/T protein kinase. BAK1 functions in various signaling pathways. It plays a role in BR (brassinosteroid)-regulated plant development as a co-receptor of BRASSINOSTEROID (BR) INSENSITIVE 1 (BRI1), the receptor for BRs, and is required for full activation of BR signaling. It also modulates pathways involved in plant resistance to pathogen infection (pattern-triggered immunity, PTI) and herbivore attack (wound- or herbivore feeding-induced accumulation of jasmonic acid (JA) and JA-isoleucine. CLV1, directly binds small signaling peptides, CLAVATA3 (CLV3) and CLAVATA3/EMBRYO SURROUNDING REGI0N (CLE), to restrict stem cell proliferation: the CLV3-CLV1-WUS (WUSCHEL) module influences stem cell maintenance in the shoot apical meristem, and the CLE40 (CLAVATA3/EMBRYO SURROUNDING REGION40) -ACR4 (CRINKLY4) -CLV1- WOX5 (WUSCHEL-RELATED HOMEOBOX5) module at the root apical meristem. The STK_BAK1-like subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271134 [Multi-domain]  Cd Length: 270  Bit Score: 65.59  E-value: 2.76e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  838 LGRGAFGQVIEAdafgidKTATCKTVAVKMLKEGATHSEHRALMSELKILIHIGHHlNVVNLLGACTKPGGPLMViVEFC 917
Cdd:cd14664    1 IGRGGAGTVYKG------VMPNGTLVAVKRLKGEGTQGGDHGFQAEIQTLGMIRHR-NIVRLRGYCSNPTTNLLV-YEYM 72
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  918 KFGNLSTYLRGKRNEFVPykskgarfrqgkdyvgelsVDLKRRldsitssqssassgfveekslsdveeeeaseelykdf 997
Cdd:cd14664   73 PNGSLGELLHSRPESQPP-------------------LDWETR------------------------------------- 96
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  998 ltleHLIcySFQVAKGMEFL---ASRKCIHRDLAARNILLSEKNVVKICDFGLARDIYKDPDYVRKGDARlPLKWMAPET 1074
Cdd:cd14664   97 ----QRI--ALGSARGLAYLhhdCSPLIIHRDVKSNNILLDEEFEAHVADFGLAKLMDDKDSHVMSSVAG-SYGYIAPEY 169
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1075 IFDRVYTIQSDVWSFGVLLWEIFSlGASPY------PGVKIDEEFCRRLKEGTRMRAPD------YTTPEM---YQTMLD 1139
Cdd:cd14664  170 AYTGKVSEKSDVYSYGVVLLELIT-GKRPFdeafldDGVDIVDWVRGLLEEKKVEALVDpdlqgvYKLEEVeqvFQVALL 248
                        330       340
                 ....*....|....*....|.
gi 27777648 1140 CWHEDPNQRPSFSELVEHLGN 1160
Cdd:cd14664  249 CTQSSPMERPTMREVVRMLEG 269
STKc_Nek6_7 cd08224
Catalytic domain of the Serine/Threonine Kinases, Never In Mitosis gene A (NIMA)-related ...
833-1154 2.80e-11

Catalytic domain of the Serine/Threonine Kinases, Never In Mitosis gene A (NIMA)-related kinase 6 and 7; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Nek6 and Nek7 are the shortest Neks, consisting only of the catalytic domain and a very short N-terminal extension. They show distinct expression patterns and both appear to be downstream substrates of Nek9. They are required for mitotic spindle formation and cytokinesis. They may also be regulators of the p70 ribosomal S6 kinase. Nek6/7 is part of a family of 11 different Neks (Nek1-11) that are involved in cell cycle control. The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270863 [Multi-domain]  Cd Length: 262  Bit Score: 65.37  E-value: 2.80e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  833 KLGKPLGRGAFGQVIEADafgidKTATCKTVAVKMLK--EGATHSEHRALMSELKILIHIgHHLNVVNLLGACTKpGGPL 910
Cdd:cd08224    3 EIEKKIGKGQFSVVYRAR-----CLLDGRLVALKKVQifEMMDAKARQDCLKEIDLLQQL-NHPNIIKYLASFIE-NNEL 75
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  911 MVIVEFCKFGNLSTYLRgkrnefvpykskgaRFRQGKDYVGELSVdlkrrldsitssqssassgfveekslsdveeeeas 990
Cdd:cd08224   76 NIVLELADAGDLSRLIK--------------HFKKQKRLIPERTI----------------------------------- 106
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  991 eelYKDFLtlehlicysfQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARdIYKDPDYVRKGDARLPLkWM 1070
Cdd:cd08224  107 ---WKYFV----------QLCSALEHMHSKRIMHRDIKPANVFITANGVVKLGDLGLGR-FFSSKTTAAHSLVGTPY-YM 171
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1071 APETIFDRVYTIQSDVWSFGVLLWEIFSLgASPYPGVKID-EEFCRRLKEGTRMRAPDYTTPEMYQTMLD-CWHEDPNQR 1148
Cdd:cd08224  172 SPERIREQGYDFKSDIWSLGCLLYEMAAL-QSPFYGEKMNlYSLCKKIEKCEYPPLPADLYSQELRDLVAaCIQPDPEKR 250

                 ....*.
gi 27777648 1149 PSFSEL 1154
Cdd:cd08224  251 PDISYV 256
STKc_Nek4 cd08223
Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase ...
1009-1157 2.81e-11

Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Nek4 is highly abundant in the testis. Its specific function is unknown. Neks are involved in the regulation of downstream processes following the activation of Cdc2, and many of their functions are cell cycle-related. They play critical roles in microtubule dynamics during ciliogenesis and mitosis. Nek4 is one in a family of 11 different Neks (Nek1-11). The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270862 [Multi-domain]  Cd Length: 257  Bit Score: 65.54  E-value: 2.81e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1009 QVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIYKDPDY--VRKGDARlplkWMAPETIFDRVYTIQSDV 1086
Cdd:cd08223  110 QIAMALQYMHERNILHRDLKTQNIFLTKSNIIKVGDLGIARVLESSSDMatTLIGTPY----YMSPELFSNKPYNHKSDV 185
                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 27777648 1087 WSFGVLLWEIFSLGASpyPGVKIDEEFCRRLKEGTRMRAPDYTTPEMYQTMLDCWHEDPNQRPSFSELVEH 1157
Cdd:cd08223  186 WALGCCVYEMATLKHA--FNAKDMNSLVYKILEGKLPPMPKQYSPELGELIKAMLHQDPEKRPSVKRILRQ 254
STKc_PCTAIRE3 cd07871
Catalytic domain of the Serine/Threonine Kinase, PCTAIRE-3 kinase; STKs catalyze the transfer ...
996-1162 3.03e-11

Catalytic domain of the Serine/Threonine Kinase, PCTAIRE-3 kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PCTAIRE-3 shows a restricted pattern of expression and is present in brain, kidney, and intestine. It is elevated in Alzheimer's disease (AD) and has been shown to associate with paired helical filaments (PHFs) and stimulate Tau phosphorylation. As AD progresses, phosphorylated Tau aggregates and forms PHFs, which leads to the formation of neurofibrillary tangles. In human glioma cells, PCTAIRE-3 induces cell cycle arrest and cell death. PCTAIRE-3 shares sequence similarity with Cyclin-Dependent Kinases (CDKs), which belong to a large family of STKs that are regulated by their cognate cyclins. Together, CDKs and cyclins are involved in the control of cell-cycle progression, transcription, and neuronal function. The PCTAIRE-3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270853 [Multi-domain]  Cd Length: 288  Bit Score: 65.80  E-value: 3.03e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  996 DFLTLEHLICYSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARdiYKDPDYVRKGDARLPLKWMAPETI 1075
Cdd:cd07871   98 NLMSMHNVKIFMFQLLRGLSYCHKRKILHRDLKPQNLLINEKGELKLADFGLAR--AKSVPTKTYSNEVVTLWYRPPDVL 175
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1076 FDRV-YTIQSDVWSFGVLLWEIFSlGASPYPGVKIDEEF---CRRLKEGTRMRAPDYTTPEMYQT-MLDCWHEDP--NQR 1148
Cdd:cd07871  176 LGSTeYSTPIDMWGVGCILYEMAT-GRPMFPGSTVKEELhliFRLLGTPTEETWPGVTSNEEFRSyLFPQYRAQPliNHA 254
                        170
                 ....*....|....*
gi 27777648 1149 PSF-SELVEHLGNLL 1162
Cdd:cd07871  255 PRLdTDGIDLLSSLL 269
PLN00034 PLN00034
mitogen-activated protein kinase kinase; Provisional
1007-1177 3.09e-11

mitogen-activated protein kinase kinase; Provisional


Pssm-ID: 215036 [Multi-domain]  Cd Length: 353  Bit Score: 66.77  E-value: 3.09e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  1007 SFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIYK--DPDYVRKGDarlpLKWMAPETI----FDRVY 1080
Cdd:PLN00034  174 ARQILSGIAYLHRRHIVHRDIKPSNLLINSAKNVKIADFGVSRILAQtmDPCNSSVGT----IAYMSPERIntdlNHGAY 249
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  1081 T-IQSDVWSFGVLLWEiFSLGASPYPgvkideeFCRRLKEGTRM---------RAPDYTTPEMYQTMLDCWHEDPNQRPS 1150
Cdd:PLN00034  250 DgYAGDIWSLGVSILE-FYLGRFPFG-------VGRQGDWASLMcaicmsqppEAPATASREFRHFISCCLQREPAKRWS 321
                         170       180       190
                  ....*....|....*....|....*....|
gi 27777648  1151 FSELVEH---LGNLLQANAQQDGKDYIVLP 1177
Cdd:PLN00034  322 AMQLLQHpfiLRAQPGQGQGGPNLHQLLPP 351
STKc_AMPK_alpha cd14079
Catalytic domain of the Alpha subunit of the Serine/Threonine Kinase, AMP-activated protein ...
833-1157 3.11e-11

Catalytic domain of the Alpha subunit of the Serine/Threonine Kinase, AMP-activated protein kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. AMPK, also called SNF1 (sucrose non-fermenting1) in yeasts and SnRK1 (SNF1-related kinase1) in plants, is a heterotrimeric enzyme composed of a catalytic alpha subunit and two regulatory subunits, beta and gamma. It is a stress-activated kinase that serves as master regulator of glucose and lipid metabolism by monitoring carbon and energy supplies, via sensing the cell's AMP:ATP ratio. In response to decreased ATP levels, it enhances energy-producing processes and inhibits energy-consuming pathways. Once activated, AMPK phosphorylates a broad range of downstream targets, with effects in carbohydrate metabolism and uptake, lipid and fatty acid biosynthesis, carbon energy storage, and inflammation, among others. Defects in energy homeostasis underlie many human diseases including Type 2 diabetes, obesity, heart disease, and cancer. As a result, AMPK has emerged as a therapeutic target in the treatment of these diseases. The AMPK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270981 [Multi-domain]  Cd Length: 256  Bit Score: 65.37  E-value: 3.11e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  833 KLGKPLGRGAFGQVIEADafgidKTATCKTVAVKML-KEGATHSE-HRALMSELKILiHIGHHLNVVNLLGACTKPGGPL 910
Cdd:cd14079    5 ILGKTLGVGSFGKVKLAE-----HELTGHKVAVKILnRQKIKSLDmEEKIRREIQIL-KLFRHPHIIRLYEVIETPTDIF 78
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  911 MVIvEFCKFGNLSTYLRGKrnefvpykskgarfrqgkdyvGELSVDLKRRLdsitssqssassgfveekslsdveeeeas 990
Cdd:cd14079   79 MVM-EYVSGGELFDYIVQK---------------------GRLSEDEARRF----------------------------- 107
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  991 eelykdFLtlehlicysfQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLArDIYKDPDYVRK--GDarlPlK 1068
Cdd:cd14079  108 ------FQ----------QIISGVEYCHRHMVVHRDLKPENLLLDSNMNVKIADFGLS-NIMRDGEFLKTscGS---P-N 166
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1069 WMAPETIFDRVYT-IQSDVWSFGVLLWEIFSlGASPYpgvkiDEEFC----RRLKEGtrmrapDYTTPE--------MYQ 1135
Cdd:cd14079  167 YAAPEVISGKLYAgPEVDVWSCGVILYALLC-GSLPF-----DDEHIpnlfKKIKSG------IYTIPShlspgardLIK 234
                        330       340
                 ....*....|....*....|..
gi 27777648 1136 TMLDCwheDPNQRPSFSELVEH 1157
Cdd:cd14079  235 RMLVV---DPLKRITIPEIRQH 253
STKc_p38beta cd07878
Catalytic domain of the Serine/Threonine Kinase, p38beta Mitogen-Activated Protein Kinase ...
825-1106 3.24e-11

Catalytic domain of the Serine/Threonine Kinase, p38beta Mitogen-Activated Protein Kinase (also called MAPK11); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. p38beta/MAPK11 is widely expressed in tissues and shows more similarity with p38alpha than with the other isoforms. Both are sensitive to pyridinylimidazoles and share some common substrates such as MAPK activated protein kinase 2 (MK2) and the transcription factors ATF2, c-Fos and, ELK-1. p38beta is involved in regulating the activation of the cyclooxygenase-2 promoter and the expression of TGFbeta-induced alpha-smooth muscle cell actin. p38 kinases are mitogen-activated protein kinases (MAPKs), serving as important mediators of cellular responses to extracellular signals. They are activated by the MAPK kinases MKK3 and MKK6, which in turn are activated by upstream MAPK kinase kinases including TAK1, ASK1, and MLK3, in response to cellular stresses or inflammatory cytokines. The p38beta subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 143383 [Multi-domain]  Cd Length: 343  Bit Score: 66.61  E-value: 3.24e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  825 WEFPrDRLKLGKPLGRGAFGQVIEADafgidKTATCKTVAVKMLK---EGATHSehRALMSELKILIHIGHHlNVVNLLG 901
Cdd:cd07878   11 WEVP-ERYQNLTPVGSGAYGSVCSAY-----DTRLRQKVAVKKLSrpfQSLIHA--RRTYRELRLLKHMKHE-NVIGLLD 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  902 ACTkpggPLMVIVEFCKFgNLSTYLRGkrnefvpykskgarfrqgkdyvgelsVDLKrrldsitssqssassGFVEEKSL 981
Cdd:cd07878   82 VFT----PATSIENFNEV-YLVTNLMG--------------------------ADLN---------------NIVKCQKL 115
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  982 SDveeeeaseelykdfltlEHLICYSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIYKD-PDYVRK 1060
Cdd:cd07878  116 SD-----------------EHVQFLIYQLLRGLKYIHSAGIIHRDLKPSNVAVNEDCELRILDFGLARQADDEmTGYVAT 178
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|....*....
gi 27777648 1061 GDARLP---LKWMApetifdrvYTIQSDVWSFGVLLWEIFSlGASPYPG 1106
Cdd:cd07878  179 RWYRAPeimLNWMH--------YNQTVDIWSVGCIMAELLK-GKALFPG 218
STKc_CDC2L1 cd07843
Catalytic domain of the Serine/Threonine Kinase, Cell Division Cycle 2-like 1; STKs catalyze ...
1009-1157 3.93e-11

Catalytic domain of the Serine/Threonine Kinase, Cell Division Cycle 2-like 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDC2L1, also called PITSLRE, exists in different isoforms which are named using the alias CDK11(p). The CDC2L1 gene produces two protein products, CDK11(p110) and CDK11(p58). CDC2L1 is also represented by the caspase-processed CDK11(p46). CDK11(p110), the major isoform, associates with cyclin L and is expressed throughout the cell cycle. It is involved in RNA processing and the regulation of transcription. CDK11(p58) associates with cyclin D3 and is expressed during the G2/M phase of the cell cycle. It plays roles in spindle morphogenesis, centrosome maturation, sister chromatid cohesion, and the completion of mitosis. CDK11(p46) is formed from the larger isoforms by caspases during TNFalpha- and Fas-induced apoptosis. It functions as a downstream effector kinase in apoptotic signaling pathways and interacts with eukaryotic initiation factor 3f (eIF3f), p21-activated kinase (PAK1), and Ran-binding protein (RanBPM). CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDC2L1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173741 [Multi-domain]  Cd Length: 293  Bit Score: 65.71  E-value: 3.93e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1009 QVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDiYKDP--DYVRKgdaRLPLKWMAPETIFD-RVYTIQSD 1085
Cdd:cd07843  114 QLLSGVAHLHDNWILHRDLKTSNLLLNNRGILKICDFGLARE-YGSPlkPYTQL---VVTLWYRAPELLLGaKEYSTAID 189
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1086 VWSFGVLLWE-------------------IFSLGASP----------YPGVK----IDEEFCrRLKEGTRMRAPDYTTPE 1132
Cdd:cd07843  190 MWSVGCIFAElltkkplfpgkseidqlnkIFKLLGTPtekiwpgfseLPGAKkktfTKYPYN-QLRKKFPALSLSDNGFD 268
                        170       180
                 ....*....|....*....|....*
gi 27777648 1133 MYQTMLdcwHEDPNQRPSFSELVEH 1157
Cdd:cd07843  269 LLNRLL---TYDPAKRISAEDALKH 290
STKc_GRK4 cd05631
Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase 4; STKs ...
1001-1121 4.09e-11

Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. GRK4 has a limited tissue distribution. It is mainly found in the testis, but is also present in the cerebellum and kidney. It is expressed as multiple splice variants with different domain architectures and is post-translationally palmitoylated and localized in the membrane. GRK4 polymorphisms are associated with hypertension and salt sensitivity, as they cause hyperphosphorylation, desensitization, and internalization of the dopamine 1 (D1) receptor while increasing the expression of the angiotensin II type 1 receptor. GRK4 plays a crucial role in the D1 receptor regulation of sodium excretion and blood pressure. GRKs phosphorylate and regulate G protein-coupled receptors (GPCRs), the largest superfamily of cell surface receptors which regulate some part of nearly all physiological functions. Phosphorylated GPCRs bind to arrestins, which prevents further G protein signaling despite the presence of activating ligand. The GRK4 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173720 [Multi-domain]  Cd Length: 285  Bit Score: 65.40  E-value: 4.09e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1001 EHLICYSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIyKDPDYVRkgdARL-PLKWMAPETIFDRV 1079
Cdd:cd05631  102 QRAIFYAAELCCGLEDLQRERIVYRDLKPENILLDDRGHIRISDLGLAVQI-PEGETVR---GRVgTVGYMAPEVINNEK 177
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*
gi 27777648 1080 YTIQSDVWSFGVLLWEIFSlGASPYPGVKID---EEFCRRLKEGT 1121
Cdd:cd05631  178 YTFSPDWWGLGCLIYEMIQ-GQSPFRKRKERvkrEEVDRRVKEDQ 221
STKc_CDK4 cd07863
Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 4; STKs ...
1009-1097 4.28e-11

Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK4 partners with all three D-type cyclins (D1, D2, and D3) and is also regulated by INK4 inhibitors. It is active towards the retinoblastoma (pRb) protein and plays a role in regulating the early G1 phase of the cell cycle. It is expressed ubiquitously and is localized in the nucleus. CDK4 also shows kinase activity towards Smad3, a signal transducer of TGF-beta signaling which modulates transcription and plays a role in cell proliferation and apoptosis. CDK4 is inhibited by the p21 inhibitor and is specifically mutated in human melanoma. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK4 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 143368 [Multi-domain]  Cd Length: 288  Bit Score: 65.37  E-value: 4.28e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1009 QVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARdIYK-----DPDYVrkgdarlPLKWMAPETIFDRVYTIQ 1083
Cdd:cd07863  116 QFLRGLDFLHANCIVHRDLKPENILVTSGGQVKLADFGLAR-IYScqmalTPVVV-------TLWYRAPEVLLQSTYATP 187
                         90
                 ....*....|....
gi 27777648 1084 SDVWSFGVLLWEIF 1097
Cdd:cd07863  188 VDMWSVGCIFAEMF 201
STKc_MAST_like cd05579
Catalytic domain of Microtubule-associated serine/threonine (MAST) kinase-like proteins; STKs ...
1006-1157 4.34e-11

Catalytic domain of Microtubule-associated serine/threonine (MAST) kinase-like proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily includes MAST kinases, MAST-like (MASTL) kinases (also called greatwall kinase or Gwl), and fungal kinases with similarity to Saccharomyces cerevisiae Rim15 and Schizosaccharomyces pombe cek1. MAST kinases contain an N-terminal domain of unknown function, a central catalytic domain, and a C-terminal PDZ domain that mediates protein-protein interactions. MASTL kinases carry only a catalytic domain which contains a long insert relative to other kinases. The fungal kinases in this subfamily harbor other domains in addition to a central catalytic domain, which like in MASTL, also contains an insert relative to MAST kinases. Rim15 contains a C-terminal signal receiver (REC) domain while cek1 contains an N-terminal PAS domain. MAST kinases are cytoskeletal associated kinases of unknown function that are also expressed at neuromuscular junctions and postsynaptic densities. MASTL/Gwl is involved in the regulation of mitotic entry, mRNA stabilization, and DNA checkpoint recovery. The fungal proteins Rim15 and cek1 are involved in the regulation of meiosis and mitosis, respectively. The MAST-like kinase subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270731 [Multi-domain]  Cd Length: 272  Bit Score: 64.93  E-value: 4.34e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1006 YSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLAR-------------------DIYKD------PDYvrk 1060
Cdd:cd05579   98 YIAEIVLALEYLHSHGIIHRDLKPDNILIDANGHLKLTDFGLSKvglvrrqiklsiqkksngaPEKEDrrivgtPDY--- 174
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1061 gdarlplkwMAPETIFDRVYTIQSDVWSFGVLLWEiFSLGASPYPGVKIDEEFCRRLKEgtrmRAPDYTTPEMYQTMLD- 1139
Cdd:cd05579  175 ---------LAPEILLGQGHGKTVDWWSLGVILYE-FLVGIPPFHAETPEEIFQNILNG----KIEWPEDPEVSDEAKDl 240
                        170       180
                 ....*....|....*....|....
gi 27777648 1140 ---CWHEDPNQRP---SFSELVEH 1157
Cdd:cd05579  241 iskLLTPDPEKRLgakGIEEIKNH 264
STKc_EIF2AK cd13996
Catalytic domain of the Serine/Threonine kinase, eukaryotic translation Initiation Factor ...
1009-1154 4.36e-11

Catalytic domain of the Serine/Threonine kinase, eukaryotic translation Initiation Factor 2-Alpha Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. EIF2AKs phosphorylate the alpha subunit of eIF-2, resulting in the downregulation of protein synthesis. eIF-2 phosphorylation is induced in response to cellular stresses including virus infection, heat shock, nutrient deficiency, and the accummulation of unfolded proteins, among others. There are four distinct kinases that phosphorylate eIF-2 and control protein synthesis under different stress conditions: General Control Non-derepressible-2 (GCN2) which is activated during amino acid or serum starvation; protein kinase regulated by RNA (PKR) which is activated by double stranded RNA; heme-regulated inhibitor kinase (HRI) which is activated under heme-deficient conditions; and PKR-like endoplasmic reticulum kinase (PERK) which is activated when misfolded proteins accumulate in the ER. The EIF2AK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270898 [Multi-domain]  Cd Length: 273  Bit Score: 65.01  E-value: 4.36e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1009 QVAKGMEFLASRKCIHRDLAARNILLSEK-NVVKICDFGLARDI-------YKDPDYVRKGDARLPLK-----WMAPETI 1075
Cdd:cd13996  115 QILKGVSYIHSKGIVHRDLKPSNIFLDNDdLQVKIGDFGLATSIgnqkrelNNLNNNNNGNTSNNSVGigtplYASPEQL 194
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1076 FDRVYTIQSDVWSFGVLLWEIFslgaspYPGVKIDEEFcRRLKEGTRMRAPDYTT---PEMYQTMLDCWHEDPNQRPSFS 1152
Cdd:cd13996  195 DGENYNEKADIYSLGIILFEML------HPFKTAMERS-TILTDLRNGILPESFKakhPKEADLIQSLLSKNPEERPSAE 267

                 ..
gi 27777648 1153 EL 1154
Cdd:cd13996  268 QL 269
STKc_MEKK1 cd06630
Catalytic domain of the Protein Serine/Threonine Kinase, Mitogen-Activated Protein (MAP) ...
1003-1157 5.44e-11

Catalytic domain of the Protein Serine/Threonine Kinase, Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MEKK1 is a MAPK kinase kinase (MAPKKK or MKKK) that phosphorylates and activates activates the ERK1/2 and c-Jun N-terminal kinase (JNK) pathways by activating their respective MAPKKs, MEK1/2 and MKK4/MKK7, respectively. MEKK1 is important in regulating cell survival and apoptosis. MEKK1 also plays a role in cell migration, tissue maintenance and homeostasis, and wound healing. The MEKK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270800 [Multi-domain]  Cd Length: 268  Bit Score: 64.76  E-value: 5.44e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1003 LICYSFQVAKGMEFLASRKCIHRDLAARNILL-SEKNVVKICDFG----LARDIYKDPDYvrKGDARLPLKWMAPETIFD 1077
Cdd:cd06630  105 IINYTLQILRGLAYLHDNQIIHRDLKGANLLVdSTGQRLRIADFGaaarLASKGTGAGEF--QGQLLGTIAFMAPEVLRG 182
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1078 RVYTIQSDVWSFGVLLWEIFSlGASPYPGVKIDEEFCRRLKEGTRMRA---PDYTTPEMYQTMLDCWHEDPNQRPSFSEL 1154
Cdd:cd06630  183 EQYGRSCDVWSVGCVIIEMAT-AKPPWNAEKISNHLALIFKIASATTPppiPEHLSPGLRDVTLRCLELQPEDRPPAREL 261

                 ...
gi 27777648 1155 VEH 1157
Cdd:cd06630  262 LKH 264
STKc_PLK2 cd14188
Catalytic domain of the Serine/Threonine Kinase, Polo-like kinase 2; STKs catalyze the ...
1006-1157 5.58e-11

Catalytic domain of the Serine/Threonine Kinase, Polo-like kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PLKs play important roles in cell cycle progression and in DNA damage responses. They regulate mitotic entry, mitotic exit, and cytokinesis. In general PLKs contain an N-terminal catalytic kinase domain and a C-terminal regulatory polo box domain (PBD), which is comprised by two bipartite polo-box motifs (or polo boxes) and is involved in protein interactions. There are five mammalian PLKs (PLK1-5) from distinct genes. PLK2, also called Snk (serum-inducible kinase), functions in G1 progression, S-phase arrest, and centriole duplication. Its gene is responsive to both growth factors and cellular stress, is a transcriptional target of p53, and activates a G2-M checkpoint. The PLK2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271090 [Multi-domain]  Cd Length: 255  Bit Score: 64.65  E-value: 5.58e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1006 YSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIykDPDYVRKGDARLPLKWMAPETIFDRVYTIQSD 1085
Cdd:cd14188  106 YLRQIVSGLKYLHEQEILHRDLKLGNFFINENMELKVGDFGLAARL--EPLEHRRRTICGTPNYLSPEVLNKQGHGCESD 183
                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 27777648 1086 VWSFGVLLWEIFsLGASPYPGVKIDEEFcRRLKEGtRMRAPDYTTPEMYQTMLDCWHEDPNQRPSFSELVEH 1157
Cdd:cd14188  184 IWALGCVMYTML-LGRPPFETTNLKETY-RCIREA-RYSLPSSLLAPAKHLIASMLSKNPEDRPSLDEIIRH 252
STKc_RSK_N cd05582
N-terminal catalytic domain of the Serine/Threonine Kinase, 90 kDa ribosomal protein S6 kinase; ...
993-1138 6.61e-11

N-terminal catalytic domain of the Serine/Threonine Kinase, 90 kDa ribosomal protein S6 kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. RSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family. They are activated by signaling inputs from extracellular regulated kinase (ERK) and phosphoinositide dependent kinase 1 (PDK1). ERK phosphorylates and activates the CTD of RSK, serving as a docking site for PDK1, which phosphorylates and activates the NTD, which in turn phosphorylates all known RSK substrates. RSKs act as downstream effectors of mitogen-activated protein kinase (MAPK) and play key roles in mitogen-activated cell growth, differentiation, and survival. Mammals possess four RSK isoforms (RSK1-4) from distinct genes. RSK proteins are also referred to as MAP kinase-activated protein kinases (MAPKAPKs), p90-RSKs, or p90S6Ks. The RSK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270734 [Multi-domain]  Cd Length: 317  Bit Score: 65.11  E-value: 6.61e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  993 LYKDFL-TLEHLICYSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIYKDPD--YVRKGDarlpLKW 1069
Cdd:cd05582   88 LSKEVMfTEEDVKFYLAELALALDHLHSLGIIYRDLKPENILLDEDGHIKLTDFGLSKESIDHEKkaYSFCGT----VEY 163
                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 27777648 1070 MAPETIFDRVYTIQSDVWSFGVLLWEIFSlGASPYPGVKIDEEFCRRLKEGTRMraPDYTTPEMyQTML 1138
Cdd:cd05582  164 MAPEVVNRRGHTQSADWWSFGVLMFEMLT-GSLPFQGKDRKETMTMILKAKLGM--PQFLSPEA-QSLL 228
STKc_p38alpha cd07877
Catalytic domain of the Serine/Threonine Kinase, p38alpha Mitogen-Activated Protein Kinase ...
825-1106 6.67e-11

Catalytic domain of the Serine/Threonine Kinase, p38alpha Mitogen-Activated Protein Kinase (also called MAPK14); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. p38alpha/MAPK14 is expressed in most tissues and is the major isoform involved in the immune and inflammatory response. It is the central p38 MAPK involved in myogenesis. It plays a role in regulating cell cycle check-point transition and promoting cell differentiation. p38alpha also regulates cell proliferation and death through crosstalk with the JNK pathway. Its substrates include MAPK activated protein kinase 2 (MK2), MK5, and the transcription factors ATF2 and Mitf. p38 kinases MAPKs, serving as important mediators of cellular responses to extracellular signals. They are activated by the MAPK kinases MKK3 and MKK6, which in turn are activated by upstream MAPK kinase kinases including TAK1, ASK1, and MLK3, in response to cellular stresses or inflammatory cytokines. The p38alpha subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 143382 [Multi-domain]  Cd Length: 345  Bit Score: 65.45  E-value: 6.67e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  825 WEFPrDRLKLGKPLGRGAFGQVieADAFgidKTATCKTVAVKMLKEGATHSEH-RALMSELKILIHIGHHlNVVNLLGAC 903
Cdd:cd07877   13 WEVP-ERYQNLSPVGSGAYGSV--CAAF---DTKTGLRVAVKKLSRPFQSIIHaKRTYRELRLLKHMKHE-NVIGLLDVF 85
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  904 TkpggPLMVIVEFCKFgNLSTYLRGkrnefvpykskgarfrqgkdyvgelsVDLKrrldsitssqssassGFVEEKSLSD 983
Cdd:cd07877   86 T----PARSLEEFNDV-YLVTHLMG--------------------------ADLN---------------NIVKCQKLTD 119
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  984 veeeeaseelykdfltlEHLICYSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIYKD-PDYVRKGD 1062
Cdd:cd07877  120 -----------------DHVQFLIYQILRGLKYIHSADIIHRDLKPSNLAVNEDCELKILDFGLARHTDDEmTGYVATRW 182
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|....*..
gi 27777648 1063 ARLP---LKWMApetifdrvYTIQSDVWSFGVLLWEIFSlGASPYPG 1106
Cdd:cd07877  183 YRAPeimLNWMH--------YNQTVDIWSVGCIMAELLT-GRTLFPG 220
STKc_Rim15_like cd05611
Catalytic domain of fungal Rim15-like Protein Serine/Threonine Kinases; STKs catalyze the ...
1006-1115 7.12e-11

Catalytic domain of fungal Rim15-like Protein Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Members of this group include Saccharomyces cerevisiae Rim15, Schizosaccharomyces pombe cek1, and similar fungal proteins. They contain a central catalytic domain, which contains an insert relative to MAST kinases. In addition, Rim15 contains a C-terminal signal receiver (REC) domain while cek1 contains an N-terminal PAS domain. Rim15 (or Rim15p) functions as a regulator of meiosis. It acts as a downstream effector of PKA and regulates entry into stationary phase (G0). Thus, it plays a crucial role in regulating yeast proliferation, differentiation, and aging. Cek1 may facilitate progression of mitotic anaphase. The Rim15-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270762 [Multi-domain]  Cd Length: 263  Bit Score: 64.42  E-value: 7.12e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1006 YSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLAR---------DIYKDPDYvrkgdarlplkwMAPETIF 1076
Cdd:cd05611  102 YIAEVVLGVEDLHQRGIIHRDIKPENLLIDQTGHLKLTDFGLSRnglekrhnkKFVGTPDY------------LAPETIL 169
                         90       100       110
                 ....*....|....*....|....*....|....*....
gi 27777648 1077 DRVYTIQSDVWSFGVLLWEiFSLGASPYPGVKIDEEFCR 1115
Cdd:cd05611  170 GVGDDKMSDWWSLGCVIFE-FLFGYPPFHAETPDAVFDN 207
STKc_PKA cd14209
Catalytic subunit of the Serine/Threonine Kinase, cAMP-dependent protein kinase; STKs catalyze ...
1006-1133 7.38e-11

Catalytic subunit of the Serine/Threonine Kinase, cAMP-dependent protein kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The inactive PKA holoenzyme is a heterotetramer composed of two phosphorylated and active catalytic subunits with a dimer of regulatory (R) subunits. Activation is achieved through the binding of the important second messenger cAMP to the R subunits, which leads to the dissociation of PKA into the R dimer and two active subunits. PKA is present ubiquitously in cells and interacts with many different downstream targets. It plays a role in the regulation of diverse processes such as growth, development, memory, metabolism, gene expression, immunity, and lipolysis. The PKA subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271111 [Multi-domain]  Cd Length: 290  Bit Score: 64.73  E-value: 7.38e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1006 YSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIyKDPDYVRKGDArlplKWMAPETIFDRVYTIQSD 1085
Cdd:cd14209  106 YAAQIVLAFEYLHSLDLIYRDLKPENLLIDQQGYIKVTDFGFAKRV-KGRTWTLCGTP----EYLAPEIILSKGYNKAVD 180
                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|.
gi 27777648 1086 VWSFGVLLWEiFSLGASPYPG---VKIDEEFCrrlkEGtRMRAPDYTTPEM 1133
Cdd:cd14209  181 WWALGVLIYE-MAAGYPPFFAdqpIQIYEKIV----SG-KVRFPSHFSSDL 225
STKc_TEY_MAPK cd07858
Catalytic domain of the Serine/Threonine Kinases, Plant TEY Mitogen-Activated Protein Kinases; ...
998-1106 8.07e-11

Catalytic domain of the Serine/Threonine Kinases, Plant TEY Mitogen-Activated Protein Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Plant MAPKs are typed based on the conserved phosphorylation motif present in the activation loop, TEY and TDY. This subfamily represents the TEY subtype of plant MAPKs and is further subdivided into three groups (A, B, and C). Group A is represented by AtMPK3, AtMPK6, Nicotiana tabacum BTF4 (NtNTF4), among others. They are mostly involved in environmental and hormonal responses. AtMPK3 and AtMPK6 are also key regulators for stomatal development and patterning. Group B is represented by AtMPK4, AtMPK13, and NtNTF6, among others. They may be involved in both cell division and environmental stress response. AtMPK4 also participates in regulating innate immunity. Group C is represented by AtMPK1, AtMPK2, NtNTF3, Oryza sativa MAPK4 (OsMAPK4), among others. They may also be involved in stress responses. AtMPK1 and AtMPK2 are activated following mechanical injury and in the presence of stress chemicals such as jasmonic acid, hydrogen peroxide and abscisic acid. OsMAPK4 is also called OsMSRMK3 for Multiple Stress-Responsive MAPK3. In plants, MAPKs are associated with physiological, developmental, hormonal, and stress responses. Some plants show numerous gene duplications of MAPKs; Arabidopsis thaliana harbors at least 20 MAPKs, named AtMPK1-20. The TEY MAPK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 143363 [Multi-domain]  Cd Length: 337  Bit Score: 65.08  E-value: 8.07e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  998 LTLEHLICYSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIYKDPD----YVrkgdarLPLKWMAPE 1073
Cdd:cd07858  105 LSDDHCQYFLYQLLRGLKYIHSANVLHRDLKPSNLLLNANCDLKICDFGLARTTSEKGDfmteYV------VTRWYRAPE 178
                         90       100       110
                 ....*....|....*....|....*....|....*
gi 27777648 1074 TIFD-RVYTIQSDVWSFGVLLWEIfsLGASP-YPG 1106
Cdd:cd07858  179 LLLNcSEYTTAIDVWSVGCIFAEL--LGRKPlFPG 211
STKc_CASK cd14094
Catalytic domain of the Serine/Threonine Kinase, Calcium/calmodulin-dependent serine protein ...
997-1157 8.16e-11

Catalytic domain of the Serine/Threonine Kinase, Calcium/calmodulin-dependent serine protein kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CASK belongs to the MAGUK (membrane-associated guanylate kinase) protein family, which functions as multiple domain adaptor proteins and is characterized by the presence of a core of three domains: PDZ, SH3, and guanylate kinase (GuK). The enzymatically inactive GuK domain in MAGUK proteins mediates protein-protein interactions and associates intramolecularly with the SH3 domain. In addition, CASK contains a catalytic kinase and two L27 domains. It is highly expressed in the nervous system and plays roles in synaptic protein targeting, neural development, and regulation of gene expression. Binding partners include parkin (a Parkinson's disease molecule), neurexin (adhesion molecule), syndecans, calcium channel proteins, CINAP (nucleosome assembly protein), transcription factor Tbr-1, and the cytoplasmic adaptor proteins Mint1, Veli/mLIN-7/MALS, SAP97, caskin, and CIP98. Deletion or mutations in the CASK gene have been implicated in X-linked mental retardation. The CASK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270996 [Multi-domain]  Cd Length: 300  Bit Score: 64.87  E-value: 8.16e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  997 FLTLEHLIC-YSFQVAKGMEFLASRKCIHRDLAARNILLSEKNV---VKICDFGLARDIyKDPDYVRKGDARLPlKWMAP 1072
Cdd:cd14094  104 FVYSEAVAShYMRQILEALRYCHDNNIIHRDVKPHCVLLASKENsapVKLGGFGVAIQL-GESGLVAGGRVGTP-HFMAP 181
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1073 ETIFDRVYTIQSDVWSFGVLLWEIFSlGASPYPGVKIDeEFCRRLKEGTRMRAPDY-----TTPEMYQTMLDcwhEDPNQ 1147
Cdd:cd14094  182 EVVKREPYGKPVDVWGCGVILFILLS-GCLPFYGTKER-LFEGIIKGKYKMNPRQWshiseSAKDLVRRMLM---LDPAE 256
                        170
                 ....*....|
gi 27777648 1148 RPSFSELVEH 1157
Cdd:cd14094  257 RITVYEALNH 266
STKc_DAPK1 cd14194
Catalytic domain of the Serine/Threonine Kinase, Death-Associated Protein Kinase 1; STKs ...
995-1106 8.32e-11

Catalytic domain of the Serine/Threonine Kinase, Death-Associated Protein Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. DAPKs mediate cell death and act as tumor suppressors. They are necessary to induce cell death and their overexpression leads to death-associated changes including membrane blebbing, cell rounding, and formation of autophagic vesicles. Vertebrates contain three subfamily members with different domain architecture, localization, and function. DAPK1 is the prototypical member of the subfamily and is also simply referred to as DAPK. It is Ca2+/calmodulin (CaM)-regulated and actin-associated protein that contains an N-terminal kinase domain followed by an autoinhibitory CaM binding region and a large C-terminal extension with multiple functional domains including ankyrin (ANK) repeats, a cytoskeletal binding domain, a Death domain, and a serine-rich tail. Loss of DAPK1 expression, usually because of DNA methylation, is implicated in many tumor types. DAPK1 is highly abundant in the brain and has also been associated with neurodegeneration. The DAPK1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271096 [Multi-domain]  Cd Length: 269  Bit Score: 64.27  E-value: 8.32e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  995 KDFLTLEHLICYSFQVAKGMEFLASRKCIHRDLAARNILLSEKNV----VKICDFGLA---------RDIYKDPDYVrkg 1061
Cdd:cd14194  102 KESLTEEEATEFLKQILNGVYYLHSLQIAHFDLKPENIMLLDRNVpkprIKIIDFGLAhkidfgnefKNIFGTPEFV--- 178
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*
gi 27777648 1062 darlplkwmAPETIFDRVYTIQSDVWSFGVLLWEIFSlGASPYPG 1106
Cdd:cd14194  179 ---------APEIVNYEPLGLEADMWSIGVITYILLS-GASPFLG 213
PTZ00267 PTZ00267
NIMA-related protein kinase; Provisional
1008-1163 8.38e-11

NIMA-related protein kinase; Provisional


Pssm-ID: 140293 [Multi-domain]  Cd Length: 478  Bit Score: 66.19  E-value: 8.38e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  1008 FQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDiYKDPDYVRKGDA--RLPLkWMAPETIFDRVYTIQSD 1085
Cdd:PTZ00267  176 YQIVLALDEVHSRKMMHRDLKSANIFLMPTGIIKLGDFGFSKQ-YSDSVSLDVASSfcGTPY-YLAPELWERKRYSKKAD 253
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  1086 VWSFGVLLWEIFSLgASPYPGVKiDEEFCRRLKEGTRMRAPDYTTPEMYQTMLDCWHEDPNQRPS-----FSELVEHLGN 1160
Cdd:PTZ00267  254 MWSLGVILYELLTL-HRPFKGPS-QREIMQQVLYGKYDPFPCPVSSGMKALLDPLLSKNPALRPTtqqllHTEFLKYVAN 331

                  ...
gi 27777648  1161 LLQ 1163
Cdd:PTZ00267  332 LFQ 334
STKc_RSK2_C cd14176
C-terminal catalytic domain of the Serine/Threonine Kinase, Ribosomal S6 kinase 2 (also called ...
1008-1157 8.69e-11

C-terminal catalytic domain of the Serine/Threonine Kinase, Ribosomal S6 kinase 2 (also called 90kDa ribosomal protein S6 kinase 3 or Ribosomal protein S6 kinase alpha-3); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. RSK2 is also called p90RSK3, RPS6KA3, S6K-alpha-3, or MAPK-activated protein kinase 1b (MAPKAPK-1b). RSK2 is expressed highly in the regions of the brain with high synaptic activity. It plays a role in the maintenance and consolidation of excitatory synapses. It is a specific modulator of phospholipase D in calcium-regulated exocytosis. Mutations in the RSK2 gene, RPS6KA3, cause Coffin-Lowry syndrome (CLS), a rare syndromic form of X-linked mental retardation characterized by growth and psychomotor retardation and skeletal abnormalities. RSK2 is one of four RSK isoforms (RSK1-4) from distinct genes present in vertebrates. RSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family. They are activated by signaling inputs from extracellular regulated kinase (ERK) and phosphoinositide dependent kinase 1 (PDK1). ERK phosphorylates and activates the CTD of RSK, serving as a docking site for PDK1, which phosphorylates and activates the NTD, which in turn phosphorylates all known RSK substrates. RSKs act as downstream effectors of mitogen-activated protein kinase (MAPK) and play key roles in mitogen-activated cell growth, differentiation, and survival. The RSK2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271078 [Multi-domain]  Cd Length: 339  Bit Score: 65.04  E-value: 8.69e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1008 FQVAKGMEFLASRKCIHRDLAARNILLSEKN----VVKICDFGLARDIYKD------PDYVRKgdarlplkWMAPETIFD 1077
Cdd:cd14176  120 FTITKTVEYLHAQGVVHRDLKPSNILYVDESgnpeSIRICDFGFAKQLRAEngllmtPCYTAN--------FVAPEVLER 191
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1078 RVYTIQSDVWSFGVLLWEIFSlGASPYPGVKID--EEFCRRLKEGTRMRAPDY------TTPEMYQTMLdcwHEDPNQRP 1149
Cdd:cd14176  192 QGYDAACDIWSLGVLLYTMLT-GYTPFANGPDDtpEEILARIGSGKFSLSGGYwnsvsdTAKDLVSKML---HVDPHQRL 267

                 ....*...
gi 27777648 1150 SFSELVEH 1157
Cdd:cd14176  268 TAALVLRH 275
IgI_NCAM-1_like cd05732
Immunoglobulin (Ig)-like I-set domain of Neural Cell Adhesion Molecule 1 (NCAM-1) and similar ...
665-742 9.06e-11

Immunoglobulin (Ig)-like I-set domain of Neural Cell Adhesion Molecule 1 (NCAM-1) and similar proteins; The members here are composed of the fourth immunoglobulin (Ig)-like domain of Neural Cell Adhesion Molecule (NCAM-1). NCAM plays important roles in the development and regeneration of the central nervous system, in synaptogenesis and neural migration. NCAM mediates cell-cell and cell-substratum recognition and adhesion via homophilic (NCAM-NCAM), and heterophilic (NCAM-non-NCAM), interactions. NCAM is expressed as three major isoforms having different intracellular extensions. The extracellular portion of NCAM has five N-terminal Ig-like domains and two fibronectin type III domains. The double zipper adhesion complex model for NCAM homophilic binding involves Ig1, Ig2, and Ig3. By this model, Ig1 and Ig2 mediate dimerization of NCAM molecules situated on the same cell surface (cis interactions), and Ig3 domains mediate interactions between NCAM molecules expressed on the surface of opposing cells (trans interactions), through binding to the Ig1 and Ig2 domains. The adhesive ability of NCAM is modulated by the addition of polysialic acid chains to the fifth Ig-like domain. Also included in this group is NCAM-2 (also known as OCAM/mamFas II and RNCAM) NCAM-2 is differentially expressed in the developing and mature olfactory epithelium (OE). One of the unique features of I-set domains is the lack of a C" strand. The structures of this group show that the Ig domain lacks this strand and thus is a member of the I-set of Ig domains.


Pssm-ID: 409395 [Multi-domain]  Cd Length: 96  Bit Score: 59.85  E-value: 9.06e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  665 PMITgNLENQTTTIGETIEVTCPASGNPTPHITWFK--DNETLVE---DSGIVLRD--GNRNLTIRRVRKEDGGLYTCQA 737
Cdd:cd05732    3 PKIT-YLENQTAVELEQITLTCEAEGDPIPEITWRRatRGISFEEgdlDGRIVVRGhaRVSSLTLKDVQLTDAGRYDCEA 81

                 ....*
gi 27777648  738 CNVLG 742
Cdd:cd05732   82 SNRIG 86
STKc_MAPK15-like cd07852
Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein Kinase 15 and ...
1008-1106 9.09e-11

Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein Kinase 15 and similar MAPKs; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Human MAPK15 is also called Extracellular signal Regulated Kinase 8 (ERK8) while the rat protein is called ERK7. ERK7 and ERK8 display both similar and different biochemical properties. They autophosphorylate and activate themselves and do not require upstream activating kinases. ERK7 is constitutively active and is not affected by extracellular stimuli whereas ERK8 shows low basal activity and is activated by DNA-damaging agents. ERK7 and ERK8 also have different substrate profiles. Genome analysis shows that they are orthologs with similar gene structures. ERK7 and ERK 8 may be involved in the signaling of some nuclear receptor transcription factors. ERK7 regulates hormone-dependent degradation of estrogen receptor alpha while ERK8 down-regulates the transcriptional co-activation androgen and glucocorticoid receptors. MAPKs are important mediators of cellular responses to extracellular signals. The MAPK15 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270841 [Multi-domain]  Cd Length: 337  Bit Score: 64.89  E-value: 9.09e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1008 FQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIYKDPDYvrKGDARL----PLKWM-APETIF-DRVYT 1081
Cdd:cd07852  114 YQLLKALKYLHSGGVIHRDLKPSNILLNSDCRVKLADFGLARSLSQLEED--DENPVLtdyvATRWYrAPEILLgSTRYT 191
                         90       100
                 ....*....|....*....|....*
gi 27777648 1082 IQSDVWSFGVLLWEIFsLGASPYPG 1106
Cdd:cd07852  192 KGVDMWSVGCILGEML-LGKPLFPG 215
STKc_Nek1 cd08218
Catalytic domain of the Protein Serine/Threonine Kinase, Never In Mitosis gene A (NIMA) ...
1009-1156 9.43e-11

Catalytic domain of the Protein Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Nek1 is associated with centrosomes throughout the cell cycle. It is involved in the formation of primary cilium and in the maintenance of centrosomes. It cycles through the nucleus and may be capable of relaying signals between the cilium and the nucleus. Nek1 is implicated in the development of polycystic kidney disease, which is characterized by benign polycystic tumors formed by abnormal overgrowth of renal epithelial cells. It appears also to be involved in DNA damage response, and may be important for both correct DNA damage checkpoint activation and DNA repair. Nek1 is one in a family of 11 different Neks (Nek1-11) that are involved in cell cycle control. The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270858 [Multi-domain]  Cd Length: 256  Bit Score: 63.68  E-value: 9.43e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1009 QVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIYKDPDYVRKGDARlPLkWMAPETIFDRVYTIQSDVWS 1088
Cdd:cd08218  109 QLCLALKHVHDRKILHRDIKSQNIFLTKDGIIKLGDFGIARVLNSTVELARTCIGT-PY-YLSPEICENKPYNNKSDIWA 186
                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 27777648 1089 FGVLLWEIFSLGASPYPGVKidEEFCRRLKEGTRMRAPDYTTPEMYQTMLDCWHEDPNQRPSFSELVE 1156
Cdd:cd08218  187 LGCVLYEMCTLKHAFEAGNM--KNLVLKIIRGSYPPVPSRYSYDLRSLVSQLFKRNPRDRPSINSILE 252
STKc_CAMKK cd14118
Catalytic domain of the Serine/Threonine kinase, Calmodulin Dependent Protein Kinase Kinase; ...
1013-1157 9.77e-11

Catalytic domain of the Serine/Threonine kinase, Calmodulin Dependent Protein Kinase Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CaMKKs are upstream kinases of the CaM kinase cascade that phosphorylate and activate CaMKI and CamKIV. They may also phosphorylate other substrates including PKB and AMP-activated protein kinase (AMPK). Vertebrates contain two CaMKKs, CaMKK1 (or alpha) and CaMKK2 (or beta). CaMKK1 is involved in the regulation of glucose uptake in skeletal muscles. CaMKK2 is involved in regulating energy balance, glucose metabolism, adiposity, hematopoiesis, inflammation, and cancer. The CaMKK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271020 [Multi-domain]  Cd Length: 275  Bit Score: 64.30  E-value: 9.77e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1013 GMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLArDIYKDPDYVRKGDARLPlKWMAPETIF---DRVYTIQSDVWSF 1089
Cdd:cd14118  127 GIEYLHYQKIIHRDIKPSNLLLGDDGHVKIADFGVS-NEFEGDDALLSSTAGTP-AFMAPEALSesrKKFSGKALDIWAM 204
                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 27777648 1090 GVLLWeIFSLGASPYpgvkiDEEFCRRLKEGTR---MRAPD--YTTPEMYQTMLDCWHEDPNQRPSFSELVEH 1157
Cdd:cd14118  205 GVTLY-CFVFGRCPF-----EDDHILGLHEKIKtdpVVFPDdpVVSEQLKDLILRMLDKNPSERITLPEIKEH 271
STKc_MEKK4 cd06626
Catalytic domain of the Protein Serine/Threonine Kinase, Mitogen-Activated Protein (MAP) ...
1001-1157 1.10e-10

Catalytic domain of the Protein Serine/Threonine Kinase, Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase Kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MEKK4 is a MAPK kinase kinase that phosphorylates and activates the c-Jun N-terminal kinase (JNK) and p38 MAPK signaling pathways by directly activating their respective MAPKKs, MKK4/MKK7 and MKK3/MKK6. JNK and p38 are collectively known as stress-activated MAPKs, as they are activated in response to a variety of environmental stresses and pro-inflammatory cytokines. MEKK4 also plays roles in the re-polarization of the actin cytoskeleton in response to osmotic stress, in the proper closure of the neural tube, in cardiovascular development, and in immune responses. The MEKK4 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270796 [Multi-domain]  Cd Length: 265  Bit Score: 63.86  E-value: 1.10e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1001 EHLI-CYSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIyKDPDYVRKGDARLPLK----WMAPETI 1075
Cdd:cd06626   98 EAVIrVYTLQLLEGLAYLHENGIVHRDIKPANIFLDSNGLIKLGDFGSAVKL-KNNTTTMAPGEVNSLVgtpaYMAPEVI 176
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1076 FDRVYTIQ---SDVWSFGVLLWEIFSlGASPYPgvKIDEEFCRRLKEGTRMRAPDYTTPEMYQTMLD----CWHEDPNQR 1148
Cdd:cd06626  177 TGNKGEGHgraADIWSLGCVVLEMAT-GKRPWS--ELDNEWAIMYHVGMGHKPPIPDSLQLSPEGKDflsrCLESDPKKR 253

                 ....*....
gi 27777648 1149 PSFSELVEH 1157
Cdd:cd06626  254 PTASELLDH 262
STKc_NLK cd07853
Catalytic domain of the Serine/Threonine Kinase, Nemo-Like Kinase; STKs catalyze the transfer ...
998-1098 1.11e-10

Catalytic domain of the Serine/Threonine Kinase, Nemo-Like Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. NLK is an atypical mitogen-activated protein kinase (MAPK) that is not regulated by a MAPK kinase. It functions downstream of the MAPK kinase kinase Tak1, which also plays a role in activating the JNK and p38 MAPKs. The Tak1/NLK pathways are regulated by Wnts, a family of secreted proteins that is critical in the control of asymmetric division and cell polarity. NLK can phosphorylate transcription factors from the TCF/LEF family, inhibiting their ability to activate the transcription of target genes. In prostate cancer cells, NLK is involved in regulating androgen receptor-mediated transcription and its expression is altered during cancer progression. MAPKs are important mediators of cellular responses to extracellular signals. The NLK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173748 [Multi-domain]  Cd Length: 372  Bit Score: 65.15  E-value: 1.11e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  998 LTLEHLICYSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARdiYKDPDYVRKGDARLPLKWM-APETIF 1076
Cdd:cd07853  100 LSSDHVKVFLYQILRGLKYLHSAGILHRDIKPGNLLVNSNCVLKICDFGLAR--VEEPDESKHMTQEVVTQYYrAPEILM 177
                         90       100
                 ....*....|....*....|...
gi 27777648 1077 -DRVYTIQSDVWSFGVLLWEIFS 1098
Cdd:cd07853  178 gSRHYTSAVDIWSVGCIFAELLG 200
STKc_PAK5 cd06658
Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 5; STKs catalyze the ...
1001-1157 1.30e-10

Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 5; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PAK5 is mainly expressed in the brain. It is not required for viability, but together with PAK6, it is required for normal levels of locomotion and activity, and for learning and memory. PAK5 cooperates with Inca (induced in neural crest by AP2) in the regulation of cell adhesion and cytoskeletal organization in the embryo and in neural crest cells during craniofacial development. PAK5 may also play a role in controlling the signaling of Raf-1, an effector of Ras, at the mitochondria. PAK5 belongs to the group II PAKs, which contain a PBD (p21-binding domain) and a C-terminal catalytic domain, but do not harbor an AID (autoinhibitory domain) or SH3 binding sites. PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. The PAK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 132989 [Multi-domain]  Cd Length: 292  Bit Score: 63.90  E-value: 1.30e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1001 EHLICYSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIYKD-PDyvRKGDARLPLkWMAPETIFDRV 1079
Cdd:cd06658  118 EQIATVCLSVLRALSYLHNQGVIHRDIKSDSILLTSDGRIKLSDFGFCAQVSKEvPK--RKSLVGTPY-WMAPEVISRLP 194
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1080 YTIQSDVWSFGVLLWEIFSlGASPY---PGVKIdeefCRRLKEGTRMRAPD-YTTPEMYQTMLDCWH-EDPNQRPSFSEL 1154
Cdd:cd06658  195 YGTEVDIWSLGIMVIEMID-GEPPYfnePPLQA----MRRIRDNLPPRVKDsHKVSSVLRGFLDLMLvREPSQRATAQEL 269

                 ...
gi 27777648 1155 VEH 1157
Cdd:cd06658  270 LQH 272
IgI_5_Robo cd20952
Fifth Ig-like domain of Roundabout (Robo) homolog 1/2, and similar domains; a member of the ...
673-744 1.31e-10

Fifth Ig-like domain of Roundabout (Robo) homolog 1/2, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fifth Ig-like domain of Roundabout (Robo) homolog 1/2 and similar domains. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, -2, and -3), and three mammalian Slit homologs (Slit-1,-2, -3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, -2, and -3 are expressed by commissural neurons in the vertebrate spinal cord and Slits 1, -2, -3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of slit responsiveness, antagonizes slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be is the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. The fifth Ig-like domain of Robo 1 and 2 is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors


Pssm-ID: 409544 [Multi-domain]  Cd Length: 87  Bit Score: 59.05  E-value: 1.31e-10
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 27777648  673 NQTTTIGETIEVTCPASGNPTPHITWFKD-NETLVEDSGIVLRDgNRNLTIRRVRKEDGGLYTCQACNVLGCA 744
Cdd:cd20952    8 NQTVAVGGTVVLNCQATGEPVPTISWLKDgVPLLGKDERITTLE-NGSLQIKGAEKSDTGEYTCVALNLSGEA 79
STKc_PCTAIRE1 cd07873
Catalytic domain of the Serine/Threonine Kinase, PCTAIRE-1 kinase; STKs catalyze the transfer ...
996-1163 1.32e-10

Catalytic domain of the Serine/Threonine Kinase, PCTAIRE-1 kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PCTAIRE-1 is expressed ubiquitously and is localized in the cytoplasm. Its kinase activity is cell cycle dependent and peaks at the S and G2 phases. PCTAIRE-1 is highly expressed in the brain and may play a role in regulating neurite outgrowth. It can also associate with Trap (Tudor repeat associator with PCTAIRE-2), a physiological partner of PCTAIRE-2; with p11, a small dimeric protein with similarity to S100; and with 14-3-3 proteins, mediators of phosphorylation-dependent interactions in many different proteins. PCTAIRE-1 shares sequence similarity with Cyclin-Dependent Kinases (CDKs), which belong to a large family of STKs that are regulated by their cognate cyclins. Together, CDKs and cyclins are involved in the control of cell-cycle progression, transcription, and neuronal function. The PCTAIRE-1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270854 [Multi-domain]  Cd Length: 297  Bit Score: 64.25  E-value: 1.32e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  996 DFLTLEHLICYSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARdiyKDPDYVRKGDARLPLKWMAPETI 1075
Cdd:cd07873   95 NSINMHNVKLFLFQLLRGLAYCHRRKVLHRDLKPQNLLINERGELKLADFGLAR---AKSIPTKTYSNEVVTLWYRPPDI 171
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1076 F--DRVYTIQSDVWSFGVLLWEIfSLGASPYPGVKIDEEF---CRRLKEGTRMRAPDYTTPEMYQTM------LDCWHed 1144
Cdd:cd07873  172 LlgSTDYSTQIDMWGVGCIFYEM-STGRPLFPGSTVEEQLhfiFRILGTPTEETWPGILSNEEFKSYnypkyrADALH-- 248
                        170       180
                 ....*....|....*....|
gi 27777648 1145 pNQRPSF-SELVEHLGNLLQ 1163
Cdd:cd07873  249 -NHAPRLdSDGADLLSKLLQ 267
STKc_GRK5 cd05632
Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase 5; STKs ...
1001-1148 1.36e-10

Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase 5; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. GRK5 is widely expressed in many tissues. It associates with the membrane though an N-terminal PIP2 binding domain and also binds phospholipids via its C-terminus. GRK5 deficiency is associated with early Alzheimer's disease in humans and mouse models. GRK5 also plays a crucial role in the pathogenesis of sporadic Parkinson's disease. It participates in the regulation and desensitization of PDGFRbeta, a receptor tyrosine kinase involved in a variety of downstream cellular effects including cell growth, chemotaxis, apoptosis, and angiogenesis. GRK5 also regulates Toll-like receptor 4, which is involved in innate and adaptive immunity. GRKs phosphorylate and regulate G protein-coupled receptors (GPCRs), the largest superfamily of cell surface receptors which regulate some part of nearly all physiological functions. Phosphorylated GPCRs bind to arrestins, which prevents further G protein signaling despite the presence of activating ligand. The GRK5 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270780 [Multi-domain]  Cd Length: 313  Bit Score: 64.22  E-value: 1.36e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1001 EHLICYSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIyKDPDYVRkgdARL-PLKWMAPETIFDRV 1079
Cdd:cd05632  104 ERALFYAAEILCGLEDLHRENTVYRDLKPENILLDDYGHIRISDLGLAVKI-PEGESIR---GRVgTVGYMAPEVLNNQR 179
                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 27777648 1080 YTIQSDVWSFGVLLWEIFSlGASPYPGVK---IDEEFCRRLKEGTRMRAPDYT--TPEMYQTMLDcwhEDPNQR 1148
Cdd:cd05632  180 YTLSPDYWGLGCLIYEMIE-GQSPFRGRKekvKREEVDRRVLETEEVYSAKFSeeAKSICKMLLT---KDPKQR 249
PKc_like cd13968
Catalytic domain of the Protein Kinase superfamily; The PK superfamily contains the large ...
838-1046 1.44e-10

Catalytic domain of the Protein Kinase superfamily; The PK superfamily contains the large family of typical PKs that includes serine/threonine kinases (STKs), protein tyrosine kinases (PTKs), and dual-specificity PKs that phosphorylate both serine/threonine and tyrosine residues of target proteins, as well as pseudokinases that lack crucial residues for catalytic activity and/or ATP binding. It also includes phosphoinositide 3-kinases (PI3Ks), aminoglycoside 3'-phosphotransferases (APHs), choline kinase (ChoK), Actin-Fragmin Kinase (AFK), and the atypical RIO and Abc1p-like protein kinases. These proteins catalyze the transfer of the gamma-phosphoryl group from ATP to their target substrates; these include serine/threonine/tyrosine residues in proteins for typical or atypical PKs, the 3-hydroxyl of the inositol ring of D-myo-phosphatidylinositol (PtdIns) or its derivatives for PI3Ks, the 4-hydroxyl of PtdIns for PI4Ks, and other small molecule substrates for APH/ChoK and similar proteins such as aminoglycosides, macrolides, choline, ethanolamine, and homoserine.


Pssm-ID: 270870 [Multi-domain]  Cd Length: 136  Bit Score: 60.53  E-value: 1.44e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  838 LGRGAFGQVIEADAFGidktaTCKTVAVKMLKEGAThSEHRALMSELKILIHI-GHHLNVVNLLGACTKpGGPLMVIVEF 916
Cdd:cd13968    1 MGEGASAKVFWAEGEC-----TTIGVAVKIGDDVNN-EEGEDLESEMDILRRLkGLELNIPKVLVTEDV-DGPNILLMEL 73
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  917 CKFGNLSTYLRGkrnefvpykskgarfrqgkdyvgelsvdlkrrldsitssqssassgfvEEKSLSDVEEeeaseelykd 996
Cdd:cd13968   74 VKGGTLIAYTQE------------------------------------------------EELDEKDVES---------- 95
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|
gi 27777648  997 fltlehlICYsfQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFG 1046
Cdd:cd13968   96 -------IMY--QLAECMRLLHSFHLIHRDLNNDNILLSEDGNVKLIDFG 136
STKc_PLK4 cd14186
Catalytic domain of the Serine/Threonine Kinase, Polo-like kinase 4; STKs catalyze the ...
1009-1157 1.52e-10

Catalytic domain of the Serine/Threonine Kinase, Polo-like kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PLKs play important roles in cell cycle progression and in DNA damage responses. They regulate mitotic entry, mitotic exit, and cytokinesis. In general PLKs contain an N-terminal catalytic kinase domain and a C-terminal regulatory polo box domain (PBD), which is comprised by two bipartite polo-box motifs (or polo boxes) and is involved in protein interactions. There are five mammalian PLKs (PLK1-5) from distinct genes. PLK4, also called SAK or STK18, is structurally different from other PLKs in that it contains only one polo box that can form two adjacent polo boxes and a functional PDB by homodimerization. It is required for late mitotic progression, cell survival, and embryonic development. It localizes to centrosomes and is required for centriole duplication and chromosomal stability. Overexpression of PLK4 may be associated with colon tumors. The PLK4 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271088 [Multi-domain]  Cd Length: 256  Bit Score: 63.34  E-value: 1.52e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1009 QVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIyKDPDYVRKGDARLPlKWMAPETIFDRVYTIQSDVWS 1088
Cdd:cd14186  110 QIVTGMLYLHSHGILHRDLTLSNLLLTRNMNIKIADFGLATQL-KMPHEKHFTMCGTP-NYISPEIATRSAHGLESDVWS 187
                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 27777648 1089 FGVLLWeIFSLGASPYPGVKIDEEFCRRLKEGTRMraPDYTTPEMYQTMLDCWHEDPNQRPSFSELVEH 1157
Cdd:cd14186  188 LGCMFY-TLLVGRPPFDTDTVKNTLNKVVLADYEM--PAFLSREAQDLIHQLLRKNPADRLSLSSVLDH 253
STKc_MAPK4_6 cd07854
Catalytic domain of the Serine/Threonine Kinases, Mitogen-Activated Protein Kinases 4 (also ...
998-1106 1.63e-10

Catalytic domain of the Serine/Threonine Kinases, Mitogen-Activated Protein Kinases 4 (also called ERK4) and 6 (also called ERK3); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAPK4 (also called ERK4 or p63MAPK) and MAPK6 (also called ERK3 or p97MAPK) are atypical MAPKs that are not regulated by MAPK kinases. MAPK6 is expressed ubiquitously with highest amounts in brain and skeletal muscle. It may be involved in the control of cell differentiation by negatively regulating cell cycle progression in certain conditions. It may also play a role in glucose-induced insulin secretion. MAPK6 and MAPK4 cooperate to regulate the activity of MAPK-activated protein kinase 5 (MK5), leading to its relocation to the cytoplasm and exclusion from the nucleus. The MAPK6/MK5 and MAPK4/MK5 pathways may play critical roles in embryonic and post-natal development. MAPKs are important mediators of cellular responses to extracellular signals. The MAPK4/6 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 143359 [Multi-domain]  Cd Length: 342  Bit Score: 64.41  E-value: 1.63e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  998 LTLEHLICYSFQVAKGMEFLASRKCIHRDLAARNILLS-EKNVVKICDFGLARDIykDPDYVRKG--DARLPLKWM-APE 1073
Cdd:cd07854  111 LSEEHARLFMYQLLRGLKYIHSANVLHRDLKPANVFINtEDLVLKIGDFGLARIV--DPHYSHKGylSEGLVTKWYrSPR 188
                         90       100       110
                 ....*....|....*....|....*....|....
gi 27777648 1074 TIFD-RVYTIQSDVWSFGVLLWEIFSlGASPYPG 1106
Cdd:cd07854  189 LLLSpNNYTKAIDMWAAGCIFAEMLT-GKPLFAG 221
IgI_3_NCAM-1 cd05730
Third immunoglobulin (Ig)-like domain of Neural Cell Adhesion Molecule 1 (NCAM-1); member of ...
673-749 1.66e-10

Third immunoglobulin (Ig)-like domain of Neural Cell Adhesion Molecule 1 (NCAM-1); member of the I-set of IgSF domains; The members here are composed of the third immunoglobulin (Ig)-like domain of Neural Cell Adhesion Molecule (NCAM-1). NCAM plays important roles in the development and regeneration of the central nervous system, in synaptogenesis and neural migration. NCAM mediates cell-cell and cell-substratum recognition and adhesion via homophilic (NCAM-NCAM), and heterophilic (NCAM-non-NCAM), interactions. NCAM is expressed as three major isoforms having different intracellular extensions. The extracellular portion of NCAM has five N-terminal Ig-like domains and two fibronectin type III domains. The double zipper adhesion complex model for NCAM homophilic binding involves Ig1, Ig2, and Ig3. By this model, Ig1 and Ig2 mediate dimerization of NCAM molecules situated on the same cell surface (cis interactions), and Ig3 domains mediate interactions between NCAM molecules expressed on the surface of opposing cells (trans interactions) through binding to the Ig1 and Ig2 domains. The adhesive ability of NCAM is modulated by the addition of polysialic acid chains to the fifth Ig-like domain.


Pssm-ID: 143207 [Multi-domain]  Cd Length: 95  Bit Score: 59.18  E-value: 1.66e-10
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 27777648  673 NQTTTIGETIEVTCPASGNPTPHITWFKDNETL-VEDSGIVLRDGNRNLTIRRVRKEDGGLYTCQACNVLGCARAETL 749
Cdd:cd05730   12 NATANLGQSVTLACDADGFPEPTMTWTKDGEPIeSGEEKYSFNEDGSEMTILDVDKLDEAEYTCIAENKAGEQEAEIH 89
STKc_GRK1 cd05608
Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase 1; STKs ...
1001-1098 1.85e-10

Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. GRK1 (also called rhodopsin kinase) belongs to the visual group of GRKs and is expressed in retinal cells. It phosphorylates rhodopsin in rod cells, which leads to termination of the phototransduction cascade. Mutations in GRK1 are associated to a recessively inherited form of stationary nightblindness called Oguchi disease. GRKs phosphorylate and regulate G protein-coupled receptors (GPCRs), the largest superfamily of cell surface receptors, which regulate some part of nearly all physiological functions. Phosphorylated GPCRs bind to arrestins, which prevents further G protein signaling despite the presence of activating ligand. The GRK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270759 [Multi-domain]  Cd Length: 288  Bit Score: 63.36  E-value: 1.85e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1001 EHLIC-YSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIyKDPDYVRKGDARLPlKWMAPETIFDRV 1079
Cdd:cd05608  104 EPRACfYTAQIISGLEHLHQRRIIYRDLKPENVLLDDDGNVRISDLGLAVEL-KDGQTKTKGYAGTP-GFMAPELLLGEE 181
                         90
                 ....*....|....*....
gi 27777648 1080 YTIQSDVWSFGVLLWEIFS 1098
Cdd:cd05608  182 YDYSVDYFTLGVTLYEMIA 200
STKc_Pat1_like cd13993
Catalytic domain of Fungal Pat1-like Serine/Threonine kinases; STKs catalyze the transfer of ...
831-1155 1.87e-10

Catalytic domain of Fungal Pat1-like Serine/Threonine kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of Schizosaccharomyces pombe Pat1 (also called Ran1), Saccharomyces cerevisiae VHS1 and KSP1, and similar fungal STKs. Pat1 blocks Mei2, an RNA-binding protein which is indispensable in the initiation of meiosis. Pat1 is inactivated and Mei2 activated, which initiates meiosis, under nutrient-deprived conditions through a signaling cascade involving Ste11. Meiosis induced by Pat1 inactivation may show different characteristics than normal meiosis including aberrant positioning of centromeres. VHS1 was identified in a screen for suppressors of cell cycle arrest at the G1/S transition, while KSP1 may be involved in regulating PRP20, which is required for mRNA export and maintenance of nuclear structure. The Pat1-like subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270895 [Multi-domain]  Cd Length: 267  Bit Score: 63.14  E-value: 1.87e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  831 RLKLGKPLGRGAFGQVIEA-DAFgidktaTCKTVAVKMLKEGATHSEH------RALMSELKILIHIGHHLNVVNLL--- 900
Cdd:cd13993    1 RYQLISPIGEGAYGVVYLAvDLR------TGRKYAIKCLYKSGPNSKDgndfqkLPQLREIDLHRRVSRHPNIITLHdvf 74
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  901 --GACTkpggplMVIVEFCKFGNLSTYLRGKRNefvpykskgarfrqgkdYVGElSVDLKRRldsitssqssassgfvee 978
Cdd:cd13993   75 etEVAI------YIVLEYCPNGDLFEAITENRI-----------------YVGK-TELIKNV------------------ 112
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  979 kslsdveeeeaseelykdFLtlehlicysfQVAKGMEFLASRKCIHRDLAARNILLS-EKNVVKICDFGLARDIYKDPDY 1057
Cdd:cd13993  113 ------------------FL----------QLIDAVKHCHSLGIYHRDIKPENILLSqDEGTVKLCDFGLATTEKISMDF 164
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1058 VRKGDarlplKWMAPEtIFDRVYTIQS-------DVWSFGVLLWEIFSlGASPYPGVKI-DEEFCRRLkeGTRMRAPDYT 1129
Cdd:cd13993  165 GVGSE-----FYMAPE-CFDEVGRSLKgypcaagDIWSLGIILLNLTF-GRNPWKIASEsDPIFYDYY--LNSPNLFDVI 235
                        330       340
                 ....*....|....*....|....*....
gi 27777648 1130 TP---EMYQTMLDCWHEDPNQRPSFSELV 1155
Cdd:cd13993  236 LPmsdDFYNLLRQIFTVNPNNRILLPELQ 264
STKc_CDKL5 cd07848
Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase Like 5; STKs ...
1006-1113 1.87e-10

Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase Like 5; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Mutations in the gene encoding CDKL5, previously called STK9, are associated with early onset epilepsy and severe mental retardation [X-linked infantile spasm syndrome (ISSX) or West syndrome]. In addition, CDKL5 mutations also sometimes cause a phenotype similar to Rett syndrome (RTT), a progressive neurodevelopmental disorder. These pathogenic mutations are located in the N-terminal portion of the protein within the kinase domain. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDKL5 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270838 [Multi-domain]  Cd Length: 287  Bit Score: 63.48  E-value: 1.87e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1006 YSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIYK--DPDYVRKGDARLplkWMAPETIFDRVYTIQ 1083
Cdd:cd07848  105 YIYQLIKAIHWCHKNDIVHRDIKPENLLISHNDVLKLCDFGFARNLSEgsNANYTEYVATRW---YRSPELLLGAPYGKA 181
                         90       100       110
                 ....*....|....*....|....*....|.
gi 27777648 1084 SDVWSFGVLLWEIfSLGASPYPG-VKIDEEF 1113
Cdd:cd07848  182 VDMWSVGCILGEL-SDGQPLFPGeSEIDQLF 211
STKc_CDK6 cd07862
Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 6; STKs ...
1008-1097 1.90e-10

Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 6; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK6 is regulated by D-type cyclins and INK4 inhibitors. It is active towards the retinoblastoma (pRb) protein, implicating it to function in regulating the early G1 phase of the cell cycle. It is expressed ubiquitously and is localized in the cytoplasm. It is also present in the ruffling edge of spreading fibroblasts and may play a role in cell spreading. It binds to the p21 inhibitor without any effect on its own activity and it is overexpressed in squamous cell carcinomas and neuroblastomas. CDK6 has also been shown to inhibit cell differentiation in many cell types. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK6 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270846 [Multi-domain]  Cd Length: 290  Bit Score: 63.51  E-value: 1.90e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1008 FQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARdIYKDPdyVRKGDARLPLKWMAPETIFDRVYTIQSDVW 1087
Cdd:cd07862  117 FQLLRGLDFLHSHRVVHRDLKPQNILVTSSGQIKLADFGLAR-IYSFQ--MALTSVVVTLWYRAPEVLLQSSYATPVDLW 193
                         90
                 ....*....|
gi 27777648 1088 SFGVLLWEIF 1097
Cdd:cd07862  194 SVGCIFAEMF 203
IgI_NCAM-1 cd05869
Immunoglobulin (Ig)-like I-set domain of Neural Cell Adhesion Molecule 1 (NCAM-1); The members ...
665-742 1.94e-10

Immunoglobulin (Ig)-like I-set domain of Neural Cell Adhesion Molecule 1 (NCAM-1); The members here are composed of the fourth Ig domain of Neural Cell Adhesion Molecule 1(NCAM-1). NCAM plays important roles in the development and regeneration of the central nervous system, in synaptogenesis and neural migration. NCAM mediates cell-cell and cell-substratum recognition and adhesion via homophilic (NCAM-NCAM) and heterophilic (NCAM-non-NCAM) interactions. NCAM is expressed as three major isoforms having different intracellular extensions. The extracellular portion of NCAM has five N-terminal Ig-like domains and two fibronectin type III domains. The double zipper adhesion complex model for NCAM homophilic binding involves Ig1, Ig2, and Ig3. By this model, Ig1 and Ig2 mediate dimerization of NCAM molecules situated on the same cell surface (cis interactions), and Ig3 domains mediate interactions between NCAM molecules expressed on the surface of opposing cells (trans interactions), through binding to the Ig1 and Ig2 domains. The adhesive ability of NCAM is modulated by the addition of polysialic acid chains to the fifth Ig-like domain. One of the unique features of I-set domains is the lack of a C" strand. The structures of this group show that the Ig domain lacks this strand and thus is a member of the I-set of Ig domains.


Pssm-ID: 143277 [Multi-domain]  Cd Length: 97  Bit Score: 58.84  E-value: 1.94e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  665 PMITgNLENQTTT-IGETIEVTCPASGNPTPHITW------FKDNETLVeDSGIVLRDGNR--NLTIRRVRKEDGGLYTC 735
Cdd:cd05869    3 PKIT-YVENQTAMeLEEQITLTCEASGDPIPSITWrtstrnISSEEKTL-DGHIVVRSHARvsSLTLKYIQYTDAGEYLC 80

                 ....*..
gi 27777648  736 QACNVLG 742
Cdd:cd05869   81 TASNTIG 87
Ig5_Contactin cd04969
Fifth immunoglobulin (Ig) domain of contactin; The members here are composed of the fifth ...
677-744 1.96e-10

Fifth immunoglobulin (Ig) domain of contactin; The members here are composed of the fifth immunoglobulin (Ig) domain of contactins. Contactins are neural cell adhesion molecules and are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. The first four Ig domains form the intermolecular binding fragment, which arranges as a compact U-shaped module via contacts between Ig domains 1 and 4, and between Ig domains 2 and 3. Contactin-2 (TAG-1, axonin-1) may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. This group also includes contactin-1 and contactin-5. The different contactins show different expression patterns in the central nervous system. During development and in adulthood, contactin-2 is transiently expressed in subsets of central and peripheral neurons. Contactin-5 is expressed specifically in the rat postnatal nervous system, peaking at about 3 weeks postnatal, and a lack of contactin-5 (NB-2) results in an impairment of neuronal activity in the rat auditory system. Contactin-5 is highly expressed in the adult human brain in the occipital lobe and in the amygdala. Contactin-1 is differentially expressed in tumor tissues and may, through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma.


Pssm-ID: 409358 [Multi-domain]  Cd Length: 89  Bit Score: 58.63  E-value: 1.96e-10
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 27777648  677 TIGETIEVTCPASGNPTPHITWFKDNETLVEDSGIVLRDgNRNLTIRRVRKEDGGLYTCQACNVLGCA 744
Cdd:cd04969   15 AKGGDVIIECKPKASPKPTISWSKGTELLTNSSRICILP-DGSLKIKNVTKSDEGKYTCFAVNFFGKA 81
STKc_TAO cd06607
Catalytic domain of the Serine/Threonine Kinases, Thousand-and-One Amino acids proteins; STKs ...
1004-1091 1.98e-10

Catalytic domain of the Serine/Threonine Kinases, Thousand-and-One Amino acids proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TAO proteins possess mitogen-activated protein kinase (MAPK) kinase kinase activity. They activate the MAPKs, p38 and c-Jun N-terminal kinase (JNK), by phosphorylating and activating the respective MAP/ERK kinases (MEKs, also known as MKKs or MAPKKs), MEK3/MEK6 and MKK4/MKK7. MAPK signaling cascades are important in mediating cellular responses to extracellular signals. Vertebrates contain three TAO subfamily members, named TAO1, TAO2, and TAO3. The TAO subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270784 [Multi-domain]  Cd Length: 258  Bit Score: 62.85  E-value: 1.98e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1004 ICYsfQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIYKDPDYVRKgdarlPLkWMAPETIF---DRVY 1080
Cdd:cd06607  106 ICH--GALQGLAYLHSHNRIHRDVKAGNILLTEPGTVKLADFGSASLVCPANSFVGT-----PY-WMAPEVILamdEGQY 177
                         90
                 ....*....|.
gi 27777648 1081 TIQSDVWSFGV 1091
Cdd:cd06607  178 DGKVDVWSLGI 188
STKc_TGFbR_I cd14056
Catalytic domain of the Serine/Threonine Kinases, Transforming Growth Factor beta family Type ...
993-1150 2.26e-10

Catalytic domain of the Serine/Threonine Kinases, Transforming Growth Factor beta family Type I Receptors; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of type I receptors for the TGFbeta family of secreted signaling molecules including TGFbeta, bone morphogenetic proteins, activins, growth and differentiation factors, and anti-Mullerian hormone, among others. These receptors contain an extracellular domain that binds ligands, a single transmembrane (TM) region, and a cytoplasmic catalytic kinase domain. Type I receptors are low-affinity receptors that bind ligands only after they are recruited by the ligand/type II high-affinity receptor complex. Following activation through trans-phosphorylation by type II receptors, they start intracellular signaling to the nucleus by phosphorylating SMAD proteins. Type I receptors contain an additional domain located between the TM and kinase domains called the GS domain, which contains the activating phosphorylation site and confers preference for specific SMAD proteins. They are inhibited by the immunophilin FKBP12, which is thought to control leaky signaling caused by receptor oligomerization in the absence of ligand. The TGFbR-I subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270958 [Multi-domain]  Cd Length: 287  Bit Score: 63.06  E-value: 2.26e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  993 LYkDFLTLEHL-------ICYSfqVAKGMEFL------ASRK--CIHRDLAARNILLSEKNVVKICDFGLA------RDI 1051
Cdd:cd14056   80 LY-DYLQRNTLdteealrLAYS--AASGLAHLhteivgTQGKpaIAHRDLKSKNILVKRDGTCCIADLGLAvrydsdTNT 156
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1052 YKDPDYVRKGDARlplkWMAPETIFDRVYT------IQSDVWSFGVLLWEIFSLGAS---------PYPG-VKIDEEF-- 1113
Cdd:cd14056  157 IDIPPNPRVGTKR----YMAPEVLDDSINPksfesfKMADIYSFGLVLWEIARRCEIggiaeeyqlPYFGmVPSDPSFee 232
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....
gi 27777648 1114 CRRLKEGTRMRAP-------DYTTPEMYQTMLDCWHEDPNQRPS 1150
Cdd:cd14056  233 MRKVVCVEKLRPPipnrwksDPVLRSMVKLMQECWSENPHARLT 276
STKc_TAO3 cd06633
Catalytic domain of the Serine/Threonine Kinase, Thousand-and-One Amino acids 3; STKs catalyze ...
1012-1157 2.32e-10

Catalytic domain of the Serine/Threonine Kinase, Thousand-and-One Amino acids 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TAO3 is also known as JIK (c-Jun N-terminal kinase inhibitory kinase) or KFC (kinase from chicken). It specifically activates JNK, presumably by phosphorylating and activating MKK4/MKK7. In Saccharomyces cerevisiae, TAO3 is a component of the RAM (regulation of Ace2p activity and cellular morphogenesis) signaling pathway. TAO3 is upregulated in retinal ganglion cells after axotomy, and may play a role in apoptosis. TAO proteins possess mitogen-activated protein kinase (MAPK) kinase kinase activity. MAPK signaling cascades are important in mediating cellular responses to extracellular signals. The TAO3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270803 [Multi-domain]  Cd Length: 313  Bit Score: 63.52  E-value: 2.32e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1012 KGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIYKDPDYVRKgdarlPLkWMAPETIF---DRVYTIQSDVWS 1088
Cdd:cd06633  132 QGLAYLHSHNMIHRDIKAGNILLTEPGQVKLADFGSASIASPANSFVGT-----PY-WMAPEVILamdEGQYDGKVDIWS 205
                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1089 FGVLLWEIFSLGASPYPGVKIDEEFCRRLKEGTRMRAPDYTTPemYQTMLD-CWHEDPNQRPSFSELVEH 1157
Cdd:cd06633  206 LGITCIELAERKPPLFNMNAMSALYHIAQNDSPTLQSNEWTDS--FRGFVDyCLQKIPQERPSSAELLRH 273
PKc_Myt1 cd14050
Catalytic domain of the Dual-specificity protein kinase, Myt1; Dual-specificity PKs catalyze ...
1012-1157 2.39e-10

Catalytic domain of the Dual-specificity protein kinase, Myt1; Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine as well as tyrosine residues on protein substrates. Myt1 is a cytoplasmic cell cycle checkpoint kinase that can keep the cyclin-dependent kinase CDK1 in an inactive state through phosphorylation of N-terminal thr (T14) and tyr (Y15) residues, leading to the delay of meiosis I entry. Meiotic progression is ensured by a two-step inhibition and downregulation of Myt1 by CDK1/XRINGO and p90Rsk during oocyte maturation. In addition, Myt1 targets cyclin B1/B2 and is essential for Golgi and ER assembly during telophase. In Drosophila, Myt1 may be a downstream target of Notch during eye development. The Myt1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein serine/threonine PKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270952 [Multi-domain]  Cd Length: 249  Bit Score: 62.33  E-value: 2.39e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1012 KGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIYK-DPDYVRKGDARlplkWMAPEtIFDRVYTIQSDVWSFG 1090
Cdd:cd14050  111 KGLKHLHDHGLIHLDIKPANIFLSKDGVCKLGDFGLVVELDKeDIHDAQEGDPR----YMAPE-LLQGSFTKAADIFSLG 185
                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 27777648 1091 VLLWEIFSLGASPYPGV--------KIDEEFCRRLKEGTRmrapdyttpEMYQTMLdcwHEDPNQRPSFSELVEH 1157
Cdd:cd14050  186 ITILELACNLELPSGGDgwhqlrqgYLPEEFTAGLSPELR---------SIIKLMM---DPDPERRPTAEDLLAL 248
STKc_RSK4_C cd14177
C-terminal catalytic domain of the Serine/Threonine Kinase, Ribosomal S6 kinase 4 (also called ...
1008-1157 2.46e-10

C-terminal catalytic domain of the Serine/Threonine Kinase, Ribosomal S6 kinase 4 (also called Ribosomal protein S6 kinase alpha-6 or 90kDa ribosomal protein S6 kinase 6); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. RSK4 is also called S6K-alpha-6, RPS6KA6, p90RSK6 or pp90RSK4. RSK4 is a substrate of ERK and is a modulator of p53-dependent proliferation arrest in human cells. Deletion of the RSK4 gene, RPS6KA6, frequently occurs in patients of X-linked deafness type 3, mental retardation and choroideremia. Studies of RSK4 in cancer cells and tissues suggest that it may be oncogenic or tumor suppressive depending on many factors. RSK4 is one of four RSK isoforms (RSK1-4) from distinct genes present in vertebrates. RSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family. They are activated by signaling inputs from extracellular regulated kinase (ERK) and phosphoinositide dependent kinase 1 (PDK1). ERK phosphorylates and activates the CTD of RSK, serving as a docking site for PDK1, which phosphorylates and activates the NTD, which in turn phosphorylates all known RSK substrates. RSKs act as downstream effectors of mitogen-activated protein kinase (MAPK) and play key roles in mitogen-activated cell growth, differentiation, and survival. The RSK4 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271079 [Multi-domain]  Cd Length: 295  Bit Score: 63.11  E-value: 2.46e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1008 FQVAKGMEFLASRKCIHRDLAARNILL----SEKNVVKICDFGLARDIykdpdyvrKGDARLPL------KWMAPETIFD 1077
Cdd:cd14177  105 YTITKTVDYLHCQGVVHRDLKPSNILYmddsANADSIRICDFGFAKQL--------RGENGLLLtpcytaNFVAPEVLMR 176
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1078 RVYTIQSDVWSFGVLLWEIFSlGASPYPGVKID--EEFCRRLKEGT-RMRAPDYTT-----PEMYQTMLdcwHEDPNQRP 1149
Cdd:cd14177  177 QGYDAACDIWSLGVLLYTMLA-GYTPFANGPNDtpEEILLRIGSGKfSLSGGNWDTvsdaaKDLLSHML---HVDPHQRY 252

                 ....*...
gi 27777648 1150 SFSELVEH 1157
Cdd:cd14177  253 TAEQVLKH 260
STKc_PAK4 cd06657
Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 4; STKs catalyze the ...
1001-1157 2.48e-10

Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PAK4 regulates cell morphology and cytoskeletal organization. It is essential for embryonic viability and proper neural development. Mice lacking PAK4 die due to defects in the fetal heart. In addition, their spinal cord motor neurons showed failure to differentiate and migrate. PAK4 also plays a role in cell survival and tumorigenesis. It is overexpressed in many primary tumors including colon, esophageal, and mammary tumors. PAK4 has also been implicated in viral and bacterial infection pathways. PAK4 belongs to the group II PAKs, which contain a PBD (p21-binding domain) and a C-terminal catalytic domain, but do not harbor an AID (autoinhibitory domain) or SH3 binding sites. PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. The PAK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 132988 [Multi-domain]  Cd Length: 292  Bit Score: 63.12  E-value: 2.48e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1001 EHLICYSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIYKDPDYvRKGDARLPLkWMAPETIFDRVY 1080
Cdd:cd06657  116 EQIAAVCLAVLKALSVLHAQGVIHRDIKSDSILLTHDGRVKLSDFGFCAQVSKEVPR-RKSLVGTPY-WMAPELISRLPY 193
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1081 TIQSDVWSFGVLLWEIFSlGASPY---PGVK----IDEEFCRRLKEGTRMrapdytTPEMYQTMLDCWHEDPNQRPSFSE 1153
Cdd:cd06657  194 GPEVDIWSLGIMVIEMVD-GEPPYfnePPLKamkmIRDNLPPKLKNLHKV------SPSLKGFLDRLLVRDPAQRATAAE 266

                 ....
gi 27777648 1154 LVEH 1157
Cdd:cd06657  267 LLKH 270
STKc_DAPK2 cd14196
Catalytic domain of the Serine/Threonine Kinase, Death-Associated Protein Kinase 2; STKs ...
995-1106 2.75e-10

Catalytic domain of the Serine/Threonine Kinase, Death-Associated Protein Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. DAPKs mediate cell death and act as tumor suppressors. They are necessary to induce cell death and their overexpression leads to death-associated changes including membrane blebbing, cell rounding, and formation of autophagic vesicles. Vertebrates contain three subfamily members with different domain architecture, localization, and function. DAPK2, also called DAPK-related protein 1 (DRP-1), is a Ca2+/calmodulin (CaM)-regulated protein containing an N-terminal kinase domain, a CaM autoinhibitory site and a dimerization module. It lacks the cytoskeletal binding regions of DAPK1 and the exogenous protein has been shown to be soluble and cytoplasmic. FLAG-tagged DAPK2, however, accumulated within membrane-enclosed autophagic vesicles. It is unclear where endogenous DAPK2 is localized. DAPK2 participates in TNF-alpha and FAS-receptor induced cell death and enhances neutrophilic maturation in myeloid leukemic cells. It contributes to the induction of anoikis and its down-regulation is implicated in the beta-catenin induced resistance of malignant epithelial cells to anoikis. The DAPK2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271098 [Multi-domain]  Cd Length: 269  Bit Score: 62.67  E-value: 2.75e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  995 KDFLTLEHLICYSFQVAKGMEFLASRKCIHRDLAARNILLSEKNV----VKICDFGLA---------RDIYKDPDYVrkg 1061
Cdd:cd14196  102 KESLSEEEATSFIKQILDGVNYLHTKKIAHFDLKPENIMLLDKNIpiphIKLIDFGLAheiedgvefKNIFGTPEFV--- 178
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*
gi 27777648 1062 darlplkwmAPETIFDRVYTIQSDVWSFGVLLWEIFSlGASPYPG 1106
Cdd:cd14196  179 ---------APEIVNYEPLGLEADMWSIGVITYILLS-GASPFLG 213
STKc_PKB_beta cd05595
Catalytic domain of the Serine/Threonine Kinase, Protein Kinase B beta (also called Akt2); ...
1006-1212 2.96e-10

Catalytic domain of the Serine/Threonine Kinase, Protein Kinase B beta (also called Akt2); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKB-beta is the predominant PKB isoform expressed in insulin-responsive tissues. It plays a critical role in the regulation of glucose homeostasis. It is also implicated in muscle cell differentiation. Mice deficient in PKB-beta display normal growth weights but exhibit severe insulin resistance and diabetes, accompanied by lipoatrophy and B-cell failure. PKB contains an N-terminal pleckstrin homology (PH) domain and a C-terminal catalytic domain.The PKB-beta subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173686 [Multi-domain]  Cd Length: 323  Bit Score: 63.49  E-value: 2.96e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1006 YSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIYKDPDYVRK--GDArlplKWMAPETIFDRVYTIQ 1083
Cdd:cd05595  100 YGAEIVSALEYLHSRDVVYRDIKLENLMLDKDGHIKITDFGLCKEGITDGATMKTfcGTP----EYLAPEVLEDNDYGRA 175
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1084 SDVWSFGVLLWEIFSlGASPYPGVKIDEEFCRRLKEgtRMRAPDYTTPEMYQTMLDCWHEDPNQR----PSFSELVEHLG 1159
Cdd:cd05595  176 VDWWGLGVVMYEMMC-GRLPFYNQDHERLFELILME--EIRFPRTLSPEAKSLLAGLLKKDPKQRlgggPSDAKEVMEHR 252
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 27777648 1160 NLLQANAQQDGKDYIVLPMSETLSMEED--------SGLSLPTSP---VSCMEEEEVcDPKFHY 1212
Cdd:cd05595  253 FFLSINWQDVVQKKLLPPFKPQVTSEVDtryfddefTAQSITITPpdrYDSLDLLES-DQRTHF 315
IgI_Myotilin_C_like cd05744
Immunoglobulin (Ig)-like domain of myotilin, palladin, and myopalladin; member of the I-set of ...
665-748 3.52e-10

Immunoglobulin (Ig)-like domain of myotilin, palladin, and myopalladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin (Ig)-like domain in myotilin, palladin, and myopalladin. Myotilin, palladin, and myopalladin function as scaffolds that regulate actin organization. Myotilin and myopalladin are most abundant in skeletal and cardiac muscle; palladin is ubiquitously expressed in the organs of developing vertebrates and plays a key role in cellular morphogenesis. The three family members each interact with specific molecular partners with all three binding to alpha-actinin; In addition, palladin also binds to vasodilator-stimulated phosphoprotein (VASP) and ezrin, myotilin binds to filamin and actin, and myopalladin also binds to nebulin and cardiac ankyrin repeat protein (CARP). This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409405 [Multi-domain]  Cd Length: 91  Bit Score: 57.89  E-value: 3.52e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  665 PMITGNLENQTTTIGETIEVTCPASGNPTPHITWFKDNETLVEDSGIVL---RDGNRNLTIRRVRKEDGGLYTCQACNVL 741
Cdd:cd05744    1 PHFLQAPGDLEVQEGRLCRFDCKVSGLPTPDLFWQLNGKPVRPDSAHKMlvrENGRHSLIIEPVTKRDAGIYTCIARNRA 80

                 ....*..
gi 27777648  742 GCARAET 748
Cdd:cd05744   81 GENSFNA 87
STKc_WNK4 cd14033
Catalytic domain of the Serine/Threonine protein kinase, With No Lysine (WNK) 4; STKs catalyze ...
1006-1157 3.56e-10

Catalytic domain of the Serine/Threonine protein kinase, With No Lysine (WNK) 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. WNK4 shows a restricted expression pattern and is usually found in epithelial cells. It is expressed in nephrons and in extrarenal tissues including intestine, eye, mammary glands, and prostate. WNK4 regulates a variety of ion transport proteins including apical or basolateral ion transporters, ion channels in the transcellular pathway, and claudins in the paracellular pathway. Mutations in WNK4 cause PseudoHypoAldosteronism type II (PHAII), characterized by hypertension and hyperkalemia. WNK4 inhibits the activity of the thiazide-sensitive Na-Cl cotransporter (NCC), which is responsible for about 15% of NaCl reabsorption in the kidney. It also inhibits the renal outer medullary potassium channel (ROMK) and decreases its surface expression. Hypertension and hyperkalemia in PHAII patients with WNK4 mutations may be partly due to increased NaCl reabsorption through NCC and impaired renal potassium secretion by ROMK, respectively. The WNK4 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270935 [Multi-domain]  Cd Length: 261  Bit Score: 62.33  E-value: 3.56e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1006 YSFQVAKGMEFLASR--KCIHRDLAARNILLS-EKNVVKICDFGLArdIYKDPDYVrKGDARLPlKWMAPEtIFDRVYTI 1082
Cdd:cd14033  109 WSRQILKGLHFLHSRcpPILHRDLKCDNIFITgPTGSVKIGDLGLA--TLKRASFA-KSVIGTP-EFMAPE-MYEEKYDE 183
                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 27777648 1083 QSDVWSFGVLLWEIfSLGASPYPGVKIDEEFCRRLKEGtrmRAPD----YTTPEMYQTMLDCWHEDPNQRPSFSELVEH 1157
Cdd:cd14033  184 AVDVYAFGMCILEM-ATSEYPYSECQNAAQIYRKVTSG---IKPDsfykVKVPELKEIIEGCIRTDKDERFTIQDLLEH 258
IgI_2_Robo cd05724
Second immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of ...
678-752 3.57e-10

Second immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the second immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of the Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, and Robo3), and three mammalian Slit homologs (Slit-1,Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit-2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409389 [Multi-domain]  Cd Length: 87  Bit Score: 57.80  E-value: 3.57e-10
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 27777648  678 IGETIEVTC-PASGNPTPHITWFKDNETLVEDS-GIVLRDGNrNLTIRRVRKEDGGLYTCQACNVLGCARAETLFII 752
Cdd:cd05724   11 VGEMAVLECsPPRGHPEPTVSWRKDGQPLNLDNeRVRIVDDG-NLLIAEARKSDEGTYKCVATNMVGERESRAARLS 86
STKc_RSK3_C cd14178
C-terminal catalytic domain of the Serine/Threonine Kinase, Ribosomal S6 kinase 3 (also called ...
1010-1157 3.73e-10

C-terminal catalytic domain of the Serine/Threonine Kinase, Ribosomal S6 kinase 3 (also called Ribosomal protein S6 kinase alpha-2 or 90kDa ribosomal protein S6 kinase 2); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. RSK3 is also called S6K-alpha-2, RPS6KA2, p90RSK2 or MAPK-activated protein kinase 1c (MAPKAPK-1c). RSK3 binds muscle A-kinase anchoring protein (mAKAP)-b directly and regulates concentric cardiac myocyte growth. The RSK3 gene, RPS6KA2, is a putative tumor suppressor gene in sporadic epithelial ovarian cancer and variations to the gene may be associated with rectal cancer risk. RSK3 is one of four RSK isoforms (RSK1-4) from distinct genes present in vertebrates. RSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family. They are activated by signaling inputs from extracellular regulated kinase (ERK) and phosphoinositide dependent kinase 1 (PDK1). ERK phosphorylates and activates the CTD of RSK, serving as a docking site for PDK1, which phosphorylates and activates the NTD, which in turn phosphorylates all known RSK substrates. RSKs act as downstream effectors of mitogen-activated protein kinase (MAPK) and play key roles in mitogen-activated cell growth, differentiation, and survival. The RSK3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271080 [Multi-domain]  Cd Length: 293  Bit Score: 62.72  E-value: 3.73e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1010 VAKGMEFLASRKCIHRDLAARNILLSEKN----VVKICDFGLARDIykdpdyvRKGDARL-----PLKWMAPETIFDRVY 1080
Cdd:cd14178  106 ITKTVEYLHSQGVVHRDLKPSNILYMDESgnpeSIRICDFGFAKQL-------RAENGLLmtpcyTANFVAPEVLKRQGY 178
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1081 TIQSDVWSFGVLLWEIFSlGASPYPGVKID--EEFCRRLKEGT------RMRAPDYTTPEMYQTMLdcwHEDPNQRPSFS 1152
Cdd:cd14178  179 DAACDIWSLGILLYTMLA-GFTPFANGPDDtpEEILARIGSGKyalsggNWDSISDAAKDIVSKML---HVDPHQRLTAP 254

                 ....*
gi 27777648 1153 ELVEH 1157
Cdd:cd14178  255 QVLRH 259
STKc_GSK3 cd14137
The catalytic domain of the Serine/Threonine Kinase, Glycogen Synthase Kinase 3; STKs catalyze ...
831-1090 3.97e-10

The catalytic domain of the Serine/Threonine Kinase, Glycogen Synthase Kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. GSK3 is a mutifunctional kinase involved in many cellular processes including cell division, proliferation, differentiation, adhesion, and apoptosis. In plants, GSK3 plays a role in the response to osmotic stress. In Caenorhabditis elegans, it plays a role in regulating normal oocyte-to-embryo transition and response to oxidative stress. In Chlamydomonas reinhardtii, GSK3 regulates flagellar length and assembly. In mammals, there are two isoforms, GSK3alpha and GSK3beta, which show both distinct and redundant functions. The two isoforms differ mainly in their N-termini. They are both involved in axon formation and in Wnt signaling.They play distinct roles in cardiogenesis, with GSKalpha being essential in cardiomyocyte survival, and GSKbeta regulating heart positioning and left-right symmetry. GSK3beta was first identified as a regulator of glycogen synthesis, but has since been determined to play other roles. It regulates the degradation of beta-catenin and IkB. Beta-catenin is the main effector of Wnt, which is involved in normal haematopoiesis and stem cell function. IkB is a central inhibitor of NF-kB, which is critical in maintaining leukemic cell growth. GSK3beta is enriched in the brain and is involved in regulating neuronal signaling pathways. It is implicated in the pathogenesis of many diseases including Type II diabetes, obesity, mood disorders, Alzheimer's disease, osteoporosis, and some types of cancer, among others. The GSK3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271039 [Multi-domain]  Cd Length: 293  Bit Score: 62.52  E-value: 3.97e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  831 RLKLGKPLGRGAFGQVIEAdafgIDKTaTCKTVAVKMlkegaTHSEHRALMSELKILIHIGHHlNVVNLLGACTKPGGPL 910
Cdd:cd14137    5 SYTIEKVIGSGSFGVVYQA----KLLE-TGEVVAIKK-----VLQDKRYKNRELQIMRRLKHP-NIVKLKYFFYSSGEKK 73
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  911 MVIVEfckfgNLSTylrgkrnEFVPYkskgarfrqgkdyvgelsvdlkrrldsitssqssassgfveekSLSDVEEEEAS 990
Cdd:cd14137   74 DEVYL-----NLVM-------EYMPE-------------------------------------------TLYRVIRHYSK 98
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  991 EelyKDFLTLEHLICYSFQVAKGMEFLASRKCIHRDLAARNILL-SEKNVVKICDFGLARDIykDPD----------YVR 1059
Cdd:cd14137   99 N---KQTIPIIYVKLYSYQLFRGLAYLHSLGICHRDIKPQNLLVdPETGVLKLCDFGSAKRL--VPGepnvsyicsrYYR 173
                        250       260       270
                 ....*....|....*....|....*....|..
gi 27777648 1060 kgdarlplkwmAPETIFD-RVYTIQSDVWSFG 1090
Cdd:cd14137  174 -----------APELIFGaTDYTTAIDIWSAG 194
STKc_TAO1 cd06635
Catalytic domain of the Serine/Threonine Kinase, Thousand-and-One Amino acids 1; STKs catalyze ...
1012-1158 4.17e-10

Catalytic domain of the Serine/Threonine Kinase, Thousand-and-One Amino acids 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TAO1 is sometimes referred to as prostate-derived sterile 20-like kinase 2 (PSK2). TAO1 activates the p38 MAPK through direct interaction with and activation of MEK3. TAO1 is highly expressed in the brain and may play a role in neuronal apoptosis. TAO1 interacts with the checkpoint proteins BubR1 and Mad2, and plays an important role in regulating mitotic progression, which is required for both chromosome congression and checkpoint-induced anaphase delay. TAO1 may play a role in protecting genomic stability. TAO proteins possess MAPK kinase kinase activity. MAPK signaling cascades are important in mediating cellular responses to extracellular signals. The TAO1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270805 [Multi-domain]  Cd Length: 317  Bit Score: 62.76  E-value: 4.17e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1012 KGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIYKDPDYVRKgdarlPLkWMAPETIF---DRVYTIQSDVWS 1088
Cdd:cd06635  136 QGLAYLHSHNMIHRDIKAGNILLTEPGQVKLADFGSASIASPANSFVGT-----PY-WMAPEVILamdEGQYDGKVDVWS 209
                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 27777648 1089 FGVLLWEIFSLGASPYPGVKIDEEFCRRLKEGTRMRAPDYTtpEMYQTMLD-CWHEDPNQRPSFSELVEHL 1158
Cdd:cd06635  210 LGITCIELAERKPPLFNMNAMSALYHIAQNESPTLQSNEWS--DYFRNFVDsCLQKIPQDRPTSEELLKHM 278
STKc_GAK_like cd13985
Catalytic domain of cyclin G-Associated Kinase-like proteins; STKs catalyze the transfer of ...
836-1158 4.63e-10

Catalytic domain of cyclin G-Associated Kinase-like proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily includes cyclin G-Associated Kinase (GAK), Drosophila melanogaster Numb-Associated Kinase (NAK)-like proteins, and similar protein kinases. GAK plays regulatory roles in clathrin-mediated membrane trafficking, the maintenance of centrosome integrity and chromosome congression, neural patterning, survival of neurons, and immune responses. NAK plays a role in asymmetric cell division through its association with Numb. It also regulates the localization of Dlg, a protein essential for septate junction formation. The GAK-like subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270887 [Multi-domain]  Cd Length: 272  Bit Score: 61.97  E-value: 4.63e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  836 KPLGRGAFGQVIEADafgidKTATCKTVAVKMLKEGATHSEhRALMSELKILIHIGHHLNVVNLLGA--CTKPGGPLMVI 913
Cdd:cd13985    6 KQLGEGGFSYVYLAH-----DVNTGRRYALKRMYFNDEEQL-RVAIKEIEIMKRLCGHPNIVQYYDSaiLSSEGRKEVLL 79
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  914 V-EFCKfGNLSTYLRgkrnefvpykskgarfrqgKDYVGELSVdlkrrldsitssqssassgfveekslsdveeeeasee 992
Cdd:cd13985   80 LmEYCP-GSLVDILE-------------------KSPPSPLSE------------------------------------- 102
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  993 lykdfltlEHLICYSFQVAKGMEFL--ASRKCIHRDLAARNILLSEKNVVKICDFGLARDIykDPDYVRKGDA------- 1063
Cdd:cd13985  103 --------EEVLRIFYQICQAVGHLhsQSPPIIHRDIKIENILFSNTGRFKLCDFGSATTE--HYPLERAEEVniieeei 172
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1064 --RLPLKWMAPETI--FDRvYTI--QSDVWSFGVLLWEI--FSLgasPYpgvkiDEEFCRRLKEGT-RMRAPDYTTPEMY 1134
Cdd:cd13985  173 qkNTTPMYRAPEMIdlYSK-KPIgeKADIWALGCLLYKLcfFKL---PF-----DESSKLAIVAGKySIPEQPRYSPELH 243
                        330       340
                 ....*....|....*....|....
gi 27777648 1135 QTMLDCWHEDPNQRPSFSELVEHL 1158
Cdd:cd13985  244 DLIRHMLTPDPAERPDIFQVINII 267
STKc_STK33 cd14097
Catalytic domain of Serine/Threonine Kinase 33; STKs catalyze the transfer of the ...
1002-1157 4.81e-10

Catalytic domain of Serine/Threonine Kinase 33; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. STK33 is highly expressed in the testis and is present in low levels in most tissues. It may be involved in spermatogenesis and organ ontogenesis. It interacts with and phosphorylates vimentin and may be involved in regulating intermediate filament cytoskeletal dynamics. Its role in promoting the cell viability of KRAS-dependent cancer cells is under debate; some studies have found STK33 to promote cancer cell viability, while other studies have found it to be non-essential. KRAS is the most commonly mutated human oncogene, thus, studies on the role of STK33 in KRAS mutant cancer cells are important. The STK33 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270999 [Multi-domain]  Cd Length: 266  Bit Score: 61.80  E-value: 4.81e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1002 HLICysfQVAKGMEFLASRKCIHRDLAARNILLSEKNV-------VKICDFGLARDIYKDPDYVRKGDARLPLkWMAPET 1074
Cdd:cd14097  104 HIIQ---SLASAVAYLHKNDIVHRDLKLENILVKSSIIdnndklnIKVTDFGLSVQKYGLGEDMLQETCGTPI-YMAPEV 179
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1075 IFDRVYTIQSDVWSFGVLLWeIFSLGASPYpgVKIDEEfcrRLKEGTRMRAPDYTTpEMYQTMLDCWHE--------DPN 1146
Cdd:cd14097  180 ISAHGYSQQCDIWSIGVIMY-MLLCGEPPF--VAKSEE---KLFEEIRKGDLTFTQ-SVWQSVSDAAKNvlqqllkvDPA 252
                        170
                 ....*....|.
gi 27777648 1147 QRPSFSELVEH 1157
Cdd:cd14097  253 HRMTASELLDN 263
IgI_3_Robo cd05725
Third immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of ...
673-746 5.04e-10

Third immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, Robo3), and three mammalian Slit homologs (Slit-1,Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, and Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409390 [Multi-domain]  Cd Length: 83  Bit Score: 57.02  E-value: 5.04e-10
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 27777648  673 NQTTTIGETIEVTCPASGNPTPHITWFKDNETLVEDSGIVLRDgnRNLTIRRVRKEDGGLYTCQACNVLGCARA 746
Cdd:cd05725    6 NQVVLVDDSAEFQCEVGGDPVPTVRWRKEDGELPKGRYEILDD--HSLKIRKVTAGDMGSYTCVAENMVGKIEA 77
STKc_SnRK3 cd14663
Catalytic domain of the Serine/Threonine Kinases, Sucrose nonfermenting 1-related protein ...
1006-1157 5.10e-10

Catalytic domain of the Serine/Threonine Kinases, Sucrose nonfermenting 1-related protein kinase subfamily 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The SnRKs form three different subfamilies designated SnRK1-3. SnRK3 is represented in this cd. The SnRK3 group contains members also known as CBL-interacting protein kinase, salt overly sensitive 2, SOS3-interacting proteins and protein kinase S. These kinases interact with calcium-binding proteins such as SOS3, SCaBPs, and CBL proteins, and are involved in responses to salt stress and in sugar and ABA signaling. The SnRKs belong to a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271133 [Multi-domain]  Cd Length: 256  Bit Score: 61.65  E-value: 5.10e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1006 YSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLArdIYKDPdyvRKGDARL------PlKWMAPETIFDRV 1079
Cdd:cd14663  105 YFQQLIDAVDYCHSRGVFHRDLKPENLLLDEDGNLKISDFGLS--ALSEQ---FRQDGLLhttcgtP-NYVAPEVLARRG 178
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1080 YT-IQSDVWSFGVLLWEIFSlGASPYPGVKIDEEFcRRLKEGtRMRAPDYTTPE---MYQTMLDcwhEDPNQRPSFSELV 1155
Cdd:cd14663  179 YDgAKADIWSCGVILFVLLA-GYLPFDDENLMALY-RKIMKG-EFEYPRWFSPGaksLIKRILD---PNPSTRITVEQIM 252

                 ..
gi 27777648 1156 EH 1157
Cdd:cd14663  253 AS 254
STKc_CDK2_3 cd07860
Catalytic domain of the Serine/Threonine Kinases, Cyclin-Dependent protein Kinase 2 and 3; ...
1006-1172 5.24e-10

Catalytic domain of the Serine/Threonine Kinases, Cyclin-Dependent protein Kinase 2 and 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK2 is regulated by cyclin E or cyclin A. Upon activation by cyclin E, it phosphorylates the retinoblastoma (pRb) protein which activates E2F mediated transcription and allows cells to move into S phase. The CDK2/cyclin A complex plays a role in regulating DNA replication. CDK2, together with CDK4, also regulates embryonic cell proliferation. Despite these important roles, mice deleted for the cdk2 gene are viable and normal except for being sterile. This may be due to compensation provided by CDK1 (also called Cdc2), which can also bind cyclin E and drive the G1 to S phase transition. CDK3 is regulated by cyclin C and it phosphorylates pRB specifically during the G0/G1 transition. This phosphorylation is required for cells to exit G0 efficiently and enter the G1 phase. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK2/3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270844 [Multi-domain]  Cd Length: 284  Bit Score: 62.14  E-value: 5.24e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1006 YSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARdIYKDPdyVRKGDARLPLKWM-APETIFD-RVYTIQ 1083
Cdd:cd07860  105 YLFQLLQGLAFCHSHRVLHRDLKPQNLLINTEGAIKLADFGLAR-AFGVP--VRTYTHEVVTLWYrAPEILLGcKYYSTA 181
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1084 SDVWSFGVLLWEIFSLGASpYPG-VKIDEEF--CRRLKEGTRMRAPDYTTPEMYQTMLDCWhedpnQRPSFSELVEHLgn 1160
Cdd:cd07860  182 VDIWSLGCIFAEMVTRRAL-FPGdSEIDQLFriFRTLGTPDEVVWPGVTSMPDYKPSFPKW-----ARQDFSKVVPPL-- 253
                        170
                 ....*....|..
gi 27777648 1161 llqanaQQDGKD 1172
Cdd:cd07860  254 ------DEDGRD 259
STKc_PCTAIRE2 cd07872
Catalytic domain of the Serine/Threonine Kinase, PCTAIRE-2 kinase; STKs catalyze the transfer ...
996-1113 5.32e-10

Catalytic domain of the Serine/Threonine Kinase, PCTAIRE-2 kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PCTAIRE-2 is specifically expressed in neurons in the central nervous system, mainly in terminally differentiated neurons. It associates with Trap (Tudor repeat associator with PCTAIRE-2) and could play a role in regulating mitochondrial function in neurons. PCTAIRE-2 shares sequence similarity with Cyclin-Dependent Kinases (CDKs), which belong to a large family of STKs that are regulated by their cognate cyclins. Together, CDKs and cyclins are involved in the control of cell-cycle progression, transcription, and neuronal function. The PCTAIRE-2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 143377 [Multi-domain]  Cd Length: 309  Bit Score: 62.32  E-value: 5.32e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  996 DFLTLEHLICYSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARdiYKDPDYVRKGDARLPLKWMAPETI 1075
Cdd:cd07872   99 NIMSMHNVKIFLYQILRGLAYCHRRKVLHRDLKPQNLLINERGELKLADFGLAR--AKSVPTKTYSNEVVTLWYRPPDVL 176
                         90       100       110
                 ....*....|....*....|....*....|....*....
gi 27777648 1076 F-DRVYTIQSDVWSFGVLLWEIFSlGASPYPGVKIDEEF 1113
Cdd:cd07872  177 LgSSEYSTQIDMWGVGCIFFEMAS-GRPLFPGSTVEDEL 214
Ig_3 pfam13927
Immunoglobulin domain; This family contains immunoglobulin-like domains.
339-404 5.56e-10

Immunoglobulin domain; This family contains immunoglobulin-like domains.


Pssm-ID: 464046 [Multi-domain]  Cd Length: 78  Bit Score: 56.80  E-value: 5.56e-10
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 27777648    339 KSLVEATVGSQVRIPVKYLSYPAPDIKWYRNGRPIESNYTMIVGDE-----LTIMEVTERDAGNYTVILTN 404
Cdd:pfam13927    8 PSSVTVREGETVTLTCEATGSPPPTITWYKNGEPISSGSTRSRSLSgsnstLTISNVTRSDAGTYTCVASN 78
STKc_PKA_like cd05580
Catalytic subunit of the Serine/Threonine Kinases, cAMP-dependent protein kinases; STKs ...
832-1096 5.87e-10

Catalytic subunit of the Serine/Threonine Kinases, cAMP-dependent protein kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of the cAMP-dependent protein kinases, PKA and PRKX, and similar proteins. The inactive PKA holoenzyme is a heterotetramer composed of two phosphorylated and active catalytic subunits with a dimer of regulatory (R) subunits. Activation is achieved through the binding of the important second messenger cAMP to the R subunits, which leads to the dissociation of PKA into the R dimer and two active subunits. PKA is present ubiquitously in cells and interacts with many different downstream targets. It plays a role in the regulation of diverse processes such as growth, development, memory, metabolism, gene expression, immunity, and lipolysis. PRKX is also reulated by the R subunit and is is present in many tissues including fetal and adult brain, kidney, and lung. It is implicated in granulocyte/macrophage lineage differentiation, renal cell epithelial migration, and tubular morphogenesis in the developing kidney. The PKA-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270732 [Multi-domain]  Cd Length: 290  Bit Score: 61.83  E-value: 5.87e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  832 LKLGKPLGRGAFGQVIEADafgidKTATCKTVAVKMLKEGAT----HSEHraLMSELKILIHIGHHLnVVNLLGAcTKPG 907
Cdd:cd05580    3 FEFLKTLGTGSFGRVRLVK-----HKDSGKYYALKILKKAKIiklkQVEH--VLNEKRILSEVRHPF-IVNLLGS-FQDD 73
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  908 GPLMVIVEFCKFGNLSTYLRgKRNEFvpyKSKGARFrqgkdyvgelsvdlkrrldsitssqssassgfveekslsdveee 987
Cdd:cd05580   74 RNLYMVMEYVPGGELFSLLR-RSGRF---PNDVAKF-------------------------------------------- 105
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  988 easeelykdfltlehlicYSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIYK-------DPDYvrk 1060
Cdd:cd05580  106 ------------------YAAEVVLALEYLHSLDIVYRDLKPENLLLDSDGHIKITDFGFAKRVKDrtytlcgTPEY--- 164
                        250       260       270
                 ....*....|....*....|....*....|....*.
gi 27777648 1061 gdarlplkwMAPETIFDRVYTIQSDVWSFGVLLWEI 1096
Cdd:cd05580  165 ---------LAPEIILSKGHGKAVDWWALGILIYEM 191
STKc_ERK5 cd07855
Catalytic domain of the Serine/Threonine Kinase, Extracellular signal-Regulated Kinase 5; ...
998-1157 5.95e-10

Catalytic domain of the Serine/Threonine Kinase, Extracellular signal-Regulated Kinase 5; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. ERK5 (also called Big MAPK1 (BMK1) or MAPK7) has a unique C-terminal extension, making it approximately twice as big as other MAPKs. This extension contains transcriptional activation capability which is inhibited by the N-terminal half. ERK5 is activated in response to growth factors and stress by a cascade that leads to its phosphorylation by the MAP2K MEK5, which in turn is regulated by the MAP3Ks MEKK2 and MEKK3. Activated ERK5 phosphorylates its targets including myocyte enhancer factor 2 (MEF2), Sap1a, c-Myc, and RSK. It plays a role in EGF-induced cell proliferation during the G1/S phase transition. Studies on knockout mice revealed that ERK5 is essential for cardiovascular development and plays an important role in angiogenesis. It is also critical for neural differentiation and survival. The ERK5 pathway has been implicated in the pathogenesis of many diseases including cancer, cardiac hypertrophy, and atherosclerosis. MAPKs are important mediators of cellular responses to extracellular signals. The ERK5 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270842 [Multi-domain]  Cd Length: 336  Bit Score: 62.38  E-value: 5.95e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  998 LTLEHLICYSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIYKDPD--------YVrkgdARLPLKw 1069
Cdd:cd07855  106 LTLEHIRYFLYQLLRGLKYIHSANVIHRDLKPSNLLVNENCELKIGDFGMARGLCTSPEehkyfmteYV----ATRWYR- 180
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1070 mAPETIF--DRvYTIQSDVWSFGVLLWE-------------------IFSLGASPYPGV--KIDEEFCRRLKEGTRMRAP 1126
Cdd:cd07855  181 -APELMLslPE-YTQAIDMWSVGCIFAEmlgrrqlfpgknyvhqlqlILTVLGTPSQAVinAIGADRVRRYIQNLPNKQP 258
                        170       180       190
                 ....*....|....*....|....*....|....*...
gi 27777648 1127 -DYTT--PEMYQTMLDCWHE----DPNQRPSFSELVEH 1157
Cdd:cd07855  259 vPWETlyPKADQQALDLLSQmlrfDPSERITVAEALQH 296
PK_ILK cd14057
Pseudokinase domain of Integrin Linked Kinase; The pseudokinase domain shows similarity to ...
1006-1155 5.96e-10

Pseudokinase domain of Integrin Linked Kinase; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. ILK contains N-terminal ankyrin repeats, a Pleckstrin Homology (PH) domain, and a C-terminal pseudokinase domain. It is a component of the IPP (ILK/PINCH/Parvin) complex that couples beta integrins to the actin cytoskeleton, and plays important roles in cell adhesion, spreading, invasion, and migration. ILK was initially thought to be an active kinase despite the lack of key conserved residues because of in vitro studies showing that it can phosphorylate certain protein substrates. However, in vivo experiments in Caenorhabditis elegans, Drosophila melanogaster, and mice (ILK-null and knock-in) proved that ILK is not an active kinase. In addition to actin cytoskeleton regulation, ILK also influences the microtubule network and mitotic spindle orientation. The pseudokinase domain of ILK binds several adaptor proteins including the parvins and paxillin. The ILK subfamily is part of a larger superfamily that includes the catalytic domains of protein serine/threonine kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270959 [Multi-domain]  Cd Length: 251  Bit Score: 61.35  E-value: 5.96e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1006 YSFQVAKGMEFLAS-RKCIHR-DLAARNILLSEKNVVKIcDFGLARDIYKDPdyvrkGDARLPlKWMAPETIFDRVYTIQ 1083
Cdd:cd14057   99 FALDIARGMAFLHTlEPLIPRhHLNSKHVMIDEDMTARI-NMADVKFSFQEP-----GKMYNP-AWMAPEALQKKPEDIN 171
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1084 ---SDVWSFGVLLWEI------FSLGASPYPGVKIdeefcrrLKEGTRMRAPDYTTPEMYQTMLDCWHEDPNQRPSFSEL 1154
Cdd:cd14057  172 rrsADMWSFAILLWELvtrevpFADLSNMEIGMKI-------ALEGLRVTIPPGISPHMCKLMKICMNEDPGKRPKFDMI 244

                 .
gi 27777648 1155 V 1155
Cdd:cd14057  245 V 245
ig pfam00047
Immunoglobulin domain; Members of the immunoglobulin superfamily are found in hundreds of ...
673-742 6.45e-10

Immunoglobulin domain; Members of the immunoglobulin superfamily are found in hundreds of proteins of different functions. Examples include antibodies, the giant muscle kinase titin and receptor tyrosine kinases. Immunoglobulin-like domains may be involved in protein-protein and protein-ligand interactions.


Pssm-ID: 395002  Cd Length: 86  Bit Score: 57.20  E-value: 6.45e-10
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 27777648    673 NQTTTIGETIEVTCPAS-GNPTPHITWFKDNETLVEDSGIVLRDGNR---NLTIRRVRKEDGGLYTCQACNVLG 742
Cdd:pfam00047    5 TVTVLEGDSATLTCSAStGSPGPDVTWSKEGGTLIESLKVKHDNGRTtqsSLLISNVTKEDAGTYTCVVNNPGG 78
STKc_CaMKK2 cd14199
Catalytic domain of the Serine/Threonine kinase, Calmodulin Dependent Protein Kinase Kinase 2; ...
1006-1104 6.50e-10

Catalytic domain of the Serine/Threonine kinase, Calmodulin Dependent Protein Kinase Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CaMKKs are upstream kinases of the CaM kinase cascade that phosphorylate and activate CaMKI and CamKIV. They may also phosphorylate other substrates including PKB and AMP-activated protein kinase (AMPK). CaMKK2, also called CaMKK beta, is one of the most versatile CaMKs. It is involved in regulating energy balance, glucose metabolism, adiposity, hematopoiesis, inflammation, and cancer. CaMKK2 contains unique N- and C-terminal domains and a central catalytic kinase domain that is followed by a regulatory domain that bears overlapping autoinhibitory and CaM-binding regions. It can be activated by signaling through G-coupled receptors, IP3 receptors, plasma membrane ion channels, and Toll-like receptors. Thus, CaMKK2 acts as a molecular hub that is capable of receiving and decoding signals from diverse pathways. The CaMKK2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271101 [Multi-domain]  Cd Length: 286  Bit Score: 61.91  E-value: 6.50e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1006 YSFQ-VAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDiYKDPDYVRKGDARLPlKWMAPETIFD--RVYTI 1082
Cdd:cd14199  130 FYFQdLIKGIEYLHYQKIIHRDVKPSNLLVGEDGHIKIADFGVSNE-FEGSDALLTNTVGTP-AFMAPETLSEtrKIFSG 207
                         90       100
                 ....*....|....*....|...
gi 27777648 1083 QS-DVWSFGVLLWeIFSLGASPY 1104
Cdd:cd14199  208 KAlDVWAMGVTLY-CFVFGQCPF 229
PTK_Jak3_rpt1 cd14208
Pseudokinase (repeat 1) domain of the Protein Tyrosine Kinase, Janus kinase 3; Jak3 is ...
1009-1158 6.92e-10

Pseudokinase (repeat 1) domain of the Protein Tyrosine Kinase, Janus kinase 3; Jak3 is expressed only in hematopoietic cells. It binds the shared receptor subunit, common gamma chain and thus, is essential in the signaling of cytokines that use it such as IL-2, IL-4, IL-7, IL-9, IL-15, and IL-21. Jak3 is important in lymphoid development and myeloid cell differentiation. Inactivating mutations in Jak3 have been reported in humans with severe combined immunodeficiency (SCID). Jak3 is a cytoplasmic (or nonreceptor) PTK containing an N-terminal FERM domain, followed by a Src homology 2 (SH2) domain, a pseudokinase domain, and a C-terminal tyr kinase domain. The pseudokinase domain shows similarity to tyr kinases but lacks crucial residues for catalytic activity and ATP binding. It modulates the kinase activity of the C-terminal catalytic domain. Jaks are activated by autophosphorylation upon cytokine-induced receptor aggregation, and subsequently trigger downstream signaling events such as the phosphorylation of signal transducers and activators of transcription (STATs). The Jak3 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271110 [Multi-domain]  Cd Length: 260  Bit Score: 61.46  E-value: 6.92e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1009 QVAKGMEFLASRKCIHRDLAARNILLSEKN------VVKICDFGLARDIYKDPDYVRkgdaRLPlkWMAPETIFD-RVYT 1081
Cdd:cd14208  112 QLAYALNYLEDKQLVHGNVSAKKVLLSREGdkgsppFIKLSDPGVSIKVLDEELLAE----RIP--WVAPECLSDpQNLA 185
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1082 IQSDVWSFGVLLWEIFSLGASPY----PGVKIdeEFCRRLKEgtrMRAPDYTtpEMYQTMLDCWHEDPNQRPSFSELVEH 1157
Cdd:cd14208  186 LEADKWGFGATLWEIFSGGHMPLsaldPSKKL--QFYNDRKQ---LPAPHWI--ELASLIQQCMSYNPLLRPSFRAIIRD 258

                 .
gi 27777648 1158 L 1158
Cdd:cd14208  259 L 259
STKc_MOK cd07831
Catalytic domain of the Serine/Threonine Kinase, MAPK/MAK/MRK Overlapping Kinase; STKs ...
1006-1157 8.15e-10

Catalytic domain of the Serine/Threonine Kinase, MAPK/MAK/MRK Overlapping Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MOK, also called Renal tumor antigen 1 (RAGE-1), is widely expressed and is enriched in testis, kidney, lung, and brain. It is expressed in approximately 50% of renal cell carcinomas (RCC) and is a potential target for immunotherapy. MOK is stabilized by its association with the HSP90 molecular chaperone. It is induced by the transcription factor Cdx2 and may be involved in regulating intestinal epithelial development and differentiation. The MOK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270825 [Multi-domain]  Cd Length: 282  Bit Score: 61.52  E-value: 8.15e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1006 YSFQVAKGMEFLASRKCIHRDLAARNILLsEKNVVKICDFGLARDIYKDPDYVRKGDARlplkWM-APETIF-DRVYTIQ 1083
Cdd:cd07831  105 YMYQLLKSLDHMHRNGIFHRDIKPENILI-KDDILKLADFGSCRGIYSKPPYTEYISTR----WYrAPECLLtDGYYGPK 179
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1084 SDVWSFGVLLWEIFSLgaSP-YPGV-------KI-------DEEFCRRLKEGTRM-----------------RAPDYTTP 1131
Cdd:cd07831  180 MDIWAVGCVFFEILSL--FPlFPGTneldqiaKIhdvlgtpDAEVLKKFRKSRHMnynfpskkgtglrkllpNASAEGLD 257
                        170       180
                 ....*....|....*....|....*.
gi 27777648 1132 EMYQTMLdcwhEDPNQRPSFSELVEH 1157
Cdd:cd07831  258 LLKKLLA----YDPDERITAKQALRH 279
STKc_PASK cd14004
Catalytic domain of the Serine/Threonine kinase, Per-ARNT-Sim (PAS) domain Kinase; STKs ...
1001-1157 8.20e-10

Catalytic domain of the Serine/Threonine kinase, Per-ARNT-Sim (PAS) domain Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PASK (or PASKIN) is a nutrient and energy sensor and thus, plays an important role in maintaining cellular energy homeostasis. It coordinates the utilization of glucose in response to metabolic demand. It contains an N-terminal PAS domain which directly interacts and inhibits a C-terminal catalytic kinase domain. The PAS domain serves as a sensory module for different environmental signals such as light, redox state, and various metabolites. Binding of ligands to the PAS domain causes structural changes which leads to kinase activation and the phosphorylation of substrates to trigger the appropriate cellular response. The PASK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270906 [Multi-domain]  Cd Length: 256  Bit Score: 60.86  E-value: 8.20e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1001 EHLICYSF-QVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIYKDPDYVRKGDarlpLKWMAPETIFDRV 1079
Cdd:cd14004  108 EKEAKYIFrQVADAVKHLHDQGIVHRDIKDENVILDGNGTIKLIDFGSAAYIKSGPFDTFVGT----IDYAAPEVLRGNP 183
                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 27777648 1080 YTIQS-DVWSFGVLLWEIFsLGASPYpgVKIDEEFCRRLkegtrmRAPDYTTPEMYQTMLDCWHEDPNQRPSFSELVEH 1157
Cdd:cd14004  184 YGGKEqDIWALGVLLYTLV-FKENPF--YNIEEILEADL------RIPYAVSEDLIDLISRMLNRDVGDRPTIEELLTD 253
PK_GC_unk cd14045
Pseudokinase domain of the unknown subfamily of membrane Guanylate Cyclase receptors; The ...
1005-1154 9.12e-10

Pseudokinase domain of the unknown subfamily of membrane Guanylate Cyclase receptors; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. Membrane (or particulate) GCs consist of an extracellular ligand-binding domain, a single transmembrane region, and an intracellular tail that contains a PK-like domain, an amphiphatic region and a catalytic GC domain that catalyzes the conversion of GTP into cGMP and pyrophosphate. Membrane GCs act as receptors that transduce an extracellular signal to the intracellular production of cGMP, which has been implicated in many processes including cell proliferation, phototransduction, and muscle contractility, through its downstream effectors such as PKG. The PK-like domain of GCs lack a critical aspartate involved in ATP binding and does not exhibit kinase activity. It functions as a negative regulator of the catalytic GC domain and may also act as a docking site for interacting proteins such as GC-activating proteins. The GC subfamily is part of a larger superfamily that includes the catalytic domains of protein serine/threonine kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270947 [Multi-domain]  Cd Length: 269  Bit Score: 61.03  E-value: 9.12e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1005 CYSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLArdIYKDPDYVRKGDA---RLPLKWMAPE--TIFDRV 1079
Cdd:cd14045  107 SFATDIARGMAYLHQHKIYHGRLKSSNCVIDDRWVCKIADYGLT--TYRKEDGSENASGyqqRLMQVYLPPEnhSNTDTE 184
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1080 YTIQSDVWSFGVLLWEIFSLgASPYPG--VKIDEEFCRRLKE----GTRMRAPdytTPEMYQTMLD-CWHEDPNQRPSFS 1152
Cdd:cd14045  185 PTQATDVYSYAIILLEIATR-NDPVPEddYSLDEAWCPPLPElisgKTENSCP---CPADYVELIRrCRKNNPAQRPTFE 260

                 ..
gi 27777648 1153 EL 1154
Cdd:cd14045  261 QI 262
STKc_WNK cd13983
Catalytic domain of the Serine/Threonine kinase, With No Lysine (WNK) kinase; STKs catalyze ...
1009-1157 9.23e-10

Catalytic domain of the Serine/Threonine kinase, With No Lysine (WNK) kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. WNKs comprise a subfamily of STKs with an unusual placement of a catalytic lysine relative to all other protein kinases. They are critical in regulating ion balance and are thus, important components in the control of blood pressure. They are also involved in cell signaling, survival, proliferation, and organ development. WNKs are activated by hyperosmotic or low-chloride hypotonic stress and they function upstream of SPAK and OSR1 kinases, which regulate the activity of cation-chloride cotransporters through direct interaction and phosphorylation. There are four vertebrate WNKs which show varying expression patterns. WNK1 and WNK2 are widely expressed while WNK3 and WNK4 show a more restricted expression pattern. Because mutations in human WNK1 and WNK4 cause PseudoHypoAldosteronism type II (PHAII), characterized by hypertension (due to increased sodium reabsorption) and hyperkalemia (due to impaired renal potassium secretion), there are more studies conducted on these two proteins, compared to WNK2 and WNK3. The WNK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270885 [Multi-domain]  Cd Length: 258  Bit Score: 61.09  E-value: 9.23e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1009 QVAKGMEFLASRK--CIHRDLAARNILL-SEKNVVKICDFGLARDIYKD--------PDYvrkgdarlplkwMAPEtIFD 1077
Cdd:cd13983  110 QILEGLNYLHTRDppIIHRDLKCDNIFInGNTGEVKIGDLGLATLLRQSfaksvigtPEF------------MAPE-MYE 176
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1078 RVYTIQSDVWSFGVLLWEIFSlGASPYPGVKIDEEFCRRLKEGTRMRAPDYTT-PEMYQTMLDCWhEDPNQRPSFSELVE 1156
Cdd:cd13983  177 EHYDEKVDIYAFGMCLLEMAT-GEYPYSECTNAAQIYKKVTSGIKPESLSKVKdPELKDFIEKCL-KPPDERPSARELLE 254

                 .
gi 27777648 1157 H 1157
Cdd:cd13983  255 H 255
STKc_MEKK3_like_u1 cd06653
Catalytic domain of an Uncharacterized subfamily of Mitogen-Activated Protein (MAP) ...
833-1157 9.39e-10

Catalytic domain of an Uncharacterized subfamily of Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase Kinase 3-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of uncharacterized proteins with similarity to MEKK3, MEKK2, and related proteins; they contain an N-terminal PB1 domain, which mediates oligomerization, and a C-terminal catalytic domain. MEKK2 and MEKK3 are MAPK kinase kinases (MAPKKKs or MKKKs), proteins that phosphorylate and activate MAPK kinases (MAPKKs or MKKs), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. MEKK2 and MEKK3 activate MEK5 (also called MKK5), which activates ERK5. The ERK5 cascade plays roles in promoting cell proliferation, differentiation, neuronal survival, and neuroprotection. MEKK3 plays an essential role in embryonic angiogenesis and early heart development. MEKK2 and MEKK3 can also activate the MAPKs, c-Jun N-terminal kinase (JNK) and p38, through their respective MAPKKs. The MEKK3-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270819 [Multi-domain]  Cd Length: 264  Bit Score: 61.19  E-value: 9.39e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  833 KLGKPLGRGAFGQVI---EADafgidktaTCKTVAVKML----KEGATHSEHRALMSELKILIHIGHHLnvvnllgactk 905
Cdd:cd06653    5 RLGKLLGRGAFGEVYlcyDAD--------TGRELAVKQVpfdpDSQETSKEVNALECEIQLLKNLRHDR----------- 65
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  906 pggplmvIVEFckFGNLSTYLRGKRNEFVPYKSKGARFRQGKDYvGELSVDLKRRldsitssqssassgfveekslsdve 985
Cdd:cd06653   66 -------IVQY--YGCLRDPEEKKLSIFVEYMPGGSVKDQLKAY-GALTENVTRR------------------------- 110
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  986 eeeaseelykdfltlehlicYSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIYKdpdYVRKGDARL 1065
Cdd:cd06653  111 --------------------YTRQILQGVSYLHSNMIVHRDIKGANILRDSAGNVKLGDFGASKRIQT---ICMSGTGIK 167
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1066 PLK----WMAPETIFDRVYTIQSDVWSFGVLLWEIFSlGASPYPGVKIDEEFCRRLKEGTRMRAPDYTTPEMYQTMLDCW 1141
Cdd:cd06653  168 SVTgtpyWMSPEVISGEGYGRKADVWSVACTVVEMLT-EKPPWAEYEAMAAIFKIATQPTKPQLPDGVSDACRDFLRQIF 246
                        330
                 ....*....|....*.
gi 27777648 1142 HEDpNQRPSFSELVEH 1157
Cdd:cd06653  247 VEE-KRRPTAEFLLRH 261
IgI_2_FGFRL1-like cd05856
Second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor_like-1 ...
678-742 1.11e-09

Second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor_like-1(FGFRL1); member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor like-1(FGFRL1). FGFRL1 is comprised of a signal peptide, three extracellular Ig-like modules, a transmembrane segment, and a short intracellular domain. FGFRL1 is expressed preferentially in skeletal tissues. Similar to FGF receptors, the expressed protein interacts specifically with heparin and with FGF2. FGFRL1 does not have a protein tyrosine kinase domain at its C-terminus; neither does its cytoplasmic domain appear to interact with a signaling partner. It has been suggested that FGFRL1 may not have any direct signaling function, but instead acts as a decoy receptor trapping FGFs and preventing them from binding other receptors.


Pssm-ID: 409442  Cd Length: 92  Bit Score: 56.41  E-value: 1.11e-09
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 27777648  678 IGETIEVTCPASGNPTPHITWFKDNETLVEDSGIVLRDGNRNLTIRRVRKEDGGLYTCQACNVLG 742
Cdd:cd05856   18 VGSSVRLKCVASGNPRPDITWLKDNKPLTPPEIGENKKKKWTLSLKNLKPEDSGKYTCHVSNRAG 82
IgI_2_FGFR_like cd05729
Second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor, and similar ...
679-742 1.23e-09

Second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor, and similar domains; member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor. FGF receptors bind FGF signaling polypeptides. FGFs participate in multiple processes such as morphogenesis, development, and angiogenesis. FGFs bind to four FGF receptor tyrosine kinases (FGFR1, FGFR2, FGFR3, FGFR4). Receptor diversity is controlled by alternative splicing producing splice variants with different ligand binding characteristics and different expression patterns. FGFRs have an extracellular region comprised of three Ig-like domains, a single transmembrane helix, and an intracellular tyrosine kinase domain. Ligand binding and specificity reside in the Ig-like domains 2 and 3, and the linker region that connects these two. FGFR activation and signaling depend on FGF-induced dimerization, a process involving cell surface heparin or heparin sulfate proteoglycans. This group also contains fibroblast growth factor (FGF) receptor like-1(FGFRL1). FGFRL1 does not have a protein tyrosine kinase domain at its C-terminus; neither does its cytoplasmic domain appear to interact with a signaling partner. It has been suggested that FGFRL1 may not have any direct signaling function, but instead acts as a decoy receptor trapping FGFs and preventing them from binding other receptors.


Pssm-ID: 409393 [Multi-domain]  Cd Length: 95  Bit Score: 56.46  E-value: 1.23e-09
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 27777648  679 GETIEVTCPASGNPTPHITWFKDNETLVEDSGI---VLRDGNRNLTIRRVRKEDGGLYTCQACNVLG 742
Cdd:cd05729   19 ANKVRLECGAGGNPMPNITWLKDGKEFKKEHRIggtKVEEKGWSLIIERAIPRDKGKYTCIVENEYG 85
STKc_obscurin_rpt2 cd14110
Catalytic kinase domain, second repeat, of the Giant Serine/Threonine Kinase Obscurin; STKs ...
1006-1120 1.30e-09

Catalytic kinase domain, second repeat, of the Giant Serine/Threonine Kinase Obscurin; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Obscurin, approximately 800 kDa in size, is one of three giant proteins expressed in vetebrate striated muscle, together with titin and nebulin. It is a multidomain protein composed of tandem adhesion and signaling domains, including 49 immunoglobulin (Ig) and 2 fibronectin type III (FN3) domains at the N-terminus followed by a more complex region containing more Ig domains, a conserved SH3 domain near a RhoGEF and PH domains, non-modular regions, as well as IQ and phosphorylation motifs. The obscurin gene also encode two kinase domains, which are not expressed as part of the 800 kDa protein, but as a smaller, alternatively spliced product present mainly in the heart muscle, also called obscurin-MLCK. Obscurin is localized at the peripheries of Z-disks and M-lines, where it is able to communicate with the surrounding myoplasm. It interacts with diverse proteins including sAnk1, myosin, titin, and MyBP-C. It may act as a scaffold for the assembly of elements of the contractile apparatus. The obscurin subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271012 [Multi-domain]  Cd Length: 257  Bit Score: 60.32  E-value: 1.30e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1006 YSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIykDPDYV----RKGDARLPlkwMAPETIFDRVYT 1081
Cdd:cd14110  104 YLWQILSAVDYLHSRRILHLDLRSENMIITEKNLLKIVDLGNAQPF--NQGKVlmtdKKGDYVET---MAPELLEGQGAG 178
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|
gi 27777648 1082 IQSDVWSFGVLlweIFSLGASPYP-GVKIDEEFCRRLKEG 1120
Cdd:cd14110  179 PQTDIWAIGVT---AFIMLSADYPvSSDLNWERDRNIRKG 215
PKc_MEK1 cd06650
Catalytic domain of the dual-specificity Protein Kinase, Mitogen-Activated Protein (MAP) ...
1007-1105 1.38e-09

Catalytic domain of the dual-specificity Protein Kinase, Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase 1; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. MEK1 is a dual-specificity PK and a MAPK kinase (MAPKK or MKK) that phosphorylates and activates the downstream targets, ERK1 and ERK2, on specific threonine and tyrosine residues. The ERK cascade starts with extracellular signals including growth factors, hormones, and neurotransmitters, which act through receptors and ion channels to initiate intracellular signaling that leads to the activation at the MAPKKK (Raf-1 or MOS) level, which leads to the transmission of signals to MEK1, and finally to ERK1/2. The ERK cascade plays an important role in cell proliferation, differentiation, oncogenic transformation, and cell cycle control, as well as in apoptosis and cell survival under certain conditions. Gain-of-function mutations in genes encoding ERK cascade proteins, including MEK1, cause cardiofaciocutaneous (CFC) syndrome, a condition leading to multiple congenital anomalies and mental retardation in patients. MEK1 also plays a role in cell cycle control. The MEK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270816 [Multi-domain]  Cd Length: 319  Bit Score: 61.22  E-value: 1.38e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1007 SFQVAKGMEFLASR-KCIHRDLAARNILLSEKNVVKICDFGLARDIYKDPDYVRKGDArlplKWMAPETIFDRVYTIQSD 1085
Cdd:cd06650  109 SIAVIKGLTYLREKhKIMHRDVKPSNILVNSRGEIKLCDFGVSGQLIDSMANSFVGTR----SYMSPERLQGTHYSVQSD 184
                         90       100
                 ....*....|....*....|
gi 27777648 1086 VWSFGVLLWEIfSLGASPYP 1105
Cdd:cd06650  185 IWSMGLSLVEM-AVGRYPIP 203
Ig_Perlecan_like cd05743
Immunoglobulin (Ig)-like domain of the human basement membrane heparan sulfate proteoglycan ...
679-742 1.41e-09

Immunoglobulin (Ig)-like domain of the human basement membrane heparan sulfate proteoglycan perlecan and similar proteins; The members here are composed of the immunoglobulin (Ig)-like domain of the human basement membrane heparan sulfate proteoglycan perlecan, also known as HSPG2, and similar proteins. Perlecan consists of five domains: domain I has three putative heparan sulfate attachment sites, domain II has four LDL receptor-like repeats, and one Ig-like repeat, domain III resembles the short arm of laminin chains, domain IV has multiple Ig-like repeats (21 repeats in human perlecan), and domain V resembles the globular G domain of the laminin A chain and internal repeats of EGF. Perlecan may participate in a variety of biological functions including cell binding, LDL-metabolism, basement membrane assembly and selective permeability, calcium binding, and growth- and neurite-promoting activities.


Pssm-ID: 143220  Cd Length: 78  Bit Score: 55.96  E-value: 1.41e-09
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 27777648  679 GETIEVTCPASGNPTPHITWfKDNETLVEDSGIVL---RDGNRNLTIRRVRKEDGGLYTCQACNVLG 742
Cdd:cd05743    1 GETVEFTCVATGVPTPIINW-RLNWGHVPDSARVSitsEGGYGTLTIRDVKESDQGAYTCEAINTRG 66
STKc_TSSK-like cd14080
Catalytic domain of testis-specific serine/threonine kinases and similar proteins; STKs ...
834-1093 1.48e-09

Catalytic domain of testis-specific serine/threonine kinases and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TSSK proteins are almost exclusively expressed postmeiotically in the testis and play important roles in spermatogenesis and/or spermiogenesis. There are five mammalian TSSK proteins which show differences in their localization and timing of expression. TSSK1 and TSSK2 are expressed specifically in meiotic and postmeiotic spermatogenic cells, respectively. TSSK3 has been reported to be expressed in the interstitial Leydig cells of adult testis. TSSK4, also called TSSK5, is expressed in testis from haploid round spermatids to mature spermatozoa. TSSK6, also called SSTK, is expressed at the head of elongated sperm. TSSK1/TSSK2 double knock-out and TSSK6 null mice are sterile without manifesting other defects, making these kinases viable targets for male contraception. The TSSK-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270982 [Multi-domain]  Cd Length: 262  Bit Score: 60.27  E-value: 1.48e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  834 LGKPLGRGAFGQVIEADAFgidKTATCKTVAVKML-KEGATHSE-HRALMSELKILIHIgHHLNVVNLLGACTKpGGPLM 911
Cdd:cd14080    4 LGKTIGEGSYSKVKLAEYT---KSGLKEKVACKIIdKKKAPKDFlEKFLPRELEILRKL-RHPNIIQVYSIFER-GSKVF 78
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  912 VIVEFCKFGNLSTYLRGKrnefvpykskgarfrqgkdyvGELSVDLKRRLdsitssqssassgfveekslsdveeeease 991
Cdd:cd14080   79 IFMEYAEHGDLLEYIQKR---------------------GALSESQARIW------------------------------ 107
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  992 elykdFLtlehlicysfQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARdiykdpdYVRKGDARLPLK--- 1068
Cdd:cd14080  108 -----FR----------QLALAVQYLHSLDIAHRDLKCENILLDSNNNVKLSDFGFAR-------LCPDDDGDVLSKtfc 165
                        250       260       270
                 ....*....|....*....|....*....|
gi 27777648 1069 ----WMAPETIFDRVYTIQ-SDVWSFGVLL 1093
Cdd:cd14080  166 gsaaYAAPEILQGIPYDPKkYDIWSLGVIL 195
STKc_cPKC_alpha cd05615
Catalytic domain of the Serine/Threonine Kinase, Classical Protein Kinase C alpha; STKs ...
1006-1113 1.59e-09

Catalytic domain of the Serine/Threonine Kinase, Classical Protein Kinase C alpha; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKC-alpha is expressed in many tissues and is associated with cell proliferation, apoptosis, and cell motility. It plays a role in the signaling of the growth factors PDGF, VEGF, EGF, and FGF. Abnormal levels of PKC-alpha have been detected in many transformed cell lines and several human tumors. In addition, PKC-alpha is required for HER2 dependent breast cancer invasion. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. PKCs undergo three phosphorylations in order to take mature forms. In addition, cPKCs depend on calcium, DAG (1,2-diacylglycerol), and in most cases, phosphatidylserine (PS) for activation. The cPKC-alpha subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270766 [Multi-domain]  Cd Length: 341  Bit Score: 61.17  E-value: 1.59e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1006 YSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIYKD----------PDYVrkgdarlplkwmAPETI 1075
Cdd:cd05615  116 YAAEISVGLFFLHKKGIIYRDLKLDNVMLDSEGHIKIADFGMCKEHMVEgvttrtfcgtPDYI------------APEII 183
                         90       100       110
                 ....*....|....*....|....*....|....*...
gi 27777648 1076 FDRVYTIQSDVWSFGVLLWEIFSlGASPYPGVKIDEEF 1113
Cdd:cd05615  184 AYQPYGRSVDWWAYGVLLYEMLA-GQPPFDGEDEDELF 220
IgI_4_MYLK-like cd20976
Fourth Ig-like domain from smooth muscle myosin light chain kinase and similar domains ; a ...
664-748 1.76e-09

Fourth Ig-like domain from smooth muscle myosin light chain kinase and similar domains ; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain from smooth muscle myosin light chain kinase (MYLK) and similar domains. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of this group shows that the fourth Ig-like domain from myosin light chain kinase lacks this strand and thus belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409568 [Multi-domain]  Cd Length: 90  Bit Score: 56.10  E-value: 1.76e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  664 APMITGNLENQTTTIGETIEVTCPASGNPTPHITWFKDNETLVEDSGIVLRD-GNRNLTIRRVRKEDGGLYTCQACNVLG 742
Cdd:cd20976    1 APSFSSVPKDLEAVEGQDFVAQCSARGKPVPRITWIRNAQPLQYAADRSTCEaGVGELHIQDVLPEDHGTYTCLAKNAAG 80

                 ....*.
gi 27777648  743 CARAET 748
Cdd:cd20976   81 QVSCSA 86
STKc_SIK cd14071
Catalytic domain of the Serine/Threonine Kinases, Salt-Inducible kinases; STKs catalyze the ...
1009-1157 1.96e-09

Catalytic domain of the Serine/Threonine Kinases, Salt-Inducible kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SIKs are part of a complex network that regulates Na,K-ATPase to maintain sodium homeostasis and blood pressure. Vertebrates contain three forms of SIKs (SIK1-3) from three distinct genes, which display tissue-specific effects. SIK1, also called SNF1LK, controls steroidogenic enzyme production in adrenocortical cells. In the brain, both SIK1 and SIK2 regulate energy metabolism. SIK2, also called QIK or SNF1LK2, is involved in the regulation of gluconeogenesis in the liver and lipogenesis in adipose tissues, where it phosphorylates the insulin receptor substrate-1. In the liver, SIK3 (also called QSK) regulates cholesterol and bile acid metabolism. In addition, SIK2 plays an important role in the initiation of mitosis and regulates the localization of C-Nap1, a centrosome linker protein. The SIK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270973 [Multi-domain]  Cd Length: 253  Bit Score: 59.71  E-value: 1.96e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1009 QVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLArDIYKDPDYVRKGDARLPlkWMAPETIFDRVYT-IQSDVW 1087
Cdd:cd14071  107 QILSAVEYCHKRHIVHRDLKAENLLLDANMNIKIADFGFS-NFFKPGELLKTWCGSPP--YAAPEVFEGKEYEgPQLDIW 183
                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 27777648 1088 SFGVLLWeIFSLGASPYPGVKIdEEFCRRLKEGtRMRAPDYTTPE---MYQTMLDCwheDPNQRPSFSELVEH 1157
Cdd:cd14071  184 SLGVVLY-VLVCGALPFDGSTL-QTLRDRVLSG-RFRIPFFMSTDcehLIRRMLVL---DPSKRLTIEQIKKH 250
IgC_1_Robo cd07693
First immunoglobulin (Ig)-like constant domain in Robo (roundabout) receptors, and similar ...
665-746 2.01e-09

First immunoglobulin (Ig)-like constant domain in Robo (roundabout) receptors, and similar domains; The members here are composed of the first immunoglobulin (Ig)-like domain in Roundabout (Robo) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, and Robo3), and three mammalian Slit homologs (Slit1, Slit2, Slit3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit1, Slit2,and Slit3 are expressed at the ventral midline. Robo3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be is the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site.


Pssm-ID: 409490 [Multi-domain]  Cd Length: 99  Bit Score: 56.02  E-value: 2.01e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  665 PMITGNLENQTTTIGETIEVTCPASGNPTPHITWFKDNETLVEDSG------IVLRDGNR---NLTIRRVRKEDGGLYTC 735
Cdd:cd07693    1 PRIVEHPSDLIVSKGDPATLNCKAEGRPTPTIQWLKNGQPLETDKDdprshrIVLPSGSLfflRVVHGRKGRSDEGVYVC 80
                         90
                 ....*....|.
gi 27777648  736 QACNVLGCARA 746
Cdd:cd07693   81 VAHNSLGEAVS 91
STKc_LRRK1 cd14067
Catalytic domain of the Serine/Threonine Kinase, Leucine-Rich Repeat Kinase 1; STKs catalyze ...
997-1158 2.31e-09

Catalytic domain of the Serine/Threonine Kinase, Leucine-Rich Repeat Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. LRRK1 is one of two vertebrate LRRKs which show complementary expression in the brain. It can form heterodimers with LRRK2, and may influence the age of onset of LRRK2-associated Parkinson's disease. LRRKs are also classified as ROCO proteins because they contain a ROC (Ras of complex proteins)/GTPase domain followed by a COR (C-terminal of ROC) domain of unknown function. In addition, LRRKs contain a catalytic kinase domain and protein-protein interaction motifs including a WD40 domain, LRRs and ankyrin (ANK) repeats. LRRKs possess both GTPase and kinase activities, with the ROC domain acting as a molecular switch for the kinase domain, cycling between a GTP-bound state which drives kinase activity and a GDP-bound state which decreases the activity. The LRRK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270969 [Multi-domain]  Cd Length: 276  Bit Score: 59.98  E-value: 2.31e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  997 FLTLEHLICY--SFQVAKGMEFLASRKCIHRDLAARNILLSEKNV-----VKICDFGLARDIYKDPDYVRKGDArlplKW 1069
Cdd:cd14067  108 FMPLGHMLTFkiAYQIAAGLAYLHKKNIIFCDLKSDNILVWSLDVqehinIKLSDYGISRQSFHEGALGVEGTP----GY 183
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1070 MAPETIFDRVYTIQSDVWSFGVLLWEIFSlGASPYPGVKiDEEFCRRLKEGTRmraPDYTTPEMYQ------TMLDCWHE 1143
Cdd:cd14067  184 QAPEIRPRIVYDEKVDMFSYGMVLYELLS-GQRPSLGHH-QLQIAKKLSKGIR---PVLGQPEEVQffrlqaLMMECWDT 258
                        170
                 ....*....|....*
gi 27777648 1144 DPNQRPSFSELVEHL 1158
Cdd:cd14067  259 KPEKRPLACSVVEQM 273
PK_KSR2 cd14153
Pseudokinase domain of Kinase Suppressor of Ras 2; The pseudokinase domain shows similarity to ...
831-1161 2.37e-09

Pseudokinase domain of Kinase Suppressor of Ras 2; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. KSR2 interacts with the protein phosphatase calcineurin and functions in calcium-mediated ERK signaling. It also functions in energy metabolism by regulating AMP kinase and AMPK-dependent processes such as glucose uptake and fatty acid oxidation. KSR proteins act as scaffold proteins that function downstream of Ras and upstream of Raf in the Extracellular signal-Regulated Kinase (ERK) pathway that regulates many cellular processes including cycle regulation, proliferation, differentiation, survival, and apoptosis. KSR proteins regulate the assembly and activation of the Raf/MEK/ERK module upon Ras activation at the membrane by direct association of its components. They are widely regarded as pseudokinases. The KSR2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271055 [Multi-domain]  Cd Length: 270  Bit Score: 60.02  E-value: 2.37e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  831 RLKLGKPLGRGAFGQVIEADAFGidkTATCKTVAVKMLKEGATHSEHRALMSELKIlihigHHLNVVNLLGACTKPggP- 909
Cdd:cd14153    1 QLEIGELIGKGRFGQVYHGRWHG---EVAIRLIDIERDNEEQLKAFKREVMAYRQT-----RHENVVLFMGACMSP--Ph 70
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  910 LMVIVEFCKFGNLSTYLRgkrnefvpykskgarfrqgkDYVGELSVDLKRRLdsitssqssassgfveekslsdveeeea 989
Cdd:cd14153   71 LAIITSLCKGRTLYSVVR--------------------DAKVVLDVNKTRQI---------------------------- 102
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  990 seelykdfltlehlicySFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVkICDFGLARDIYKDPDYVRKGDARLPLKW 1069
Cdd:cd14153  103 -----------------AQEIVKGMGYLHAKGILHKDLKSKNVFYDNGKVV-ITDFGLFTISGVLQAGRREDKLRIQSGW 164
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1070 M-----------APETIFDRV-YTIQSDVWSFGVLLWEifsLGASPYPgVKIDEEFCRRLKEGTRMRaPDYTT----PEM 1133
Cdd:cd14153  165 LchlapeiirqlSPETEEDKLpFSKHSDVFAFGTIWYE---LHAREWP-FKTQPAEAIIWQVGSGMK-PNLSQigmgKEI 239
                        330       340
                 ....*....|....*....|....*...
gi 27777648 1134 YQTMLDCWHEDPNQRPSFSELVEHLGNL 1161
Cdd:cd14153  240 SDILLFCWAYEQEERPTFSKLMEMLEKL 267
IgI_2_Follistatin_like cd05736
Second immunoglobulin (Ig)-like domain of a Follistatin-related protein 5, and similar domains; ...
665-751 2.44e-09

Second immunoglobulin (Ig)-like domain of a Follistatin-related protein 5, and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the second immunoglobulin (Ig)-like domain found in human Follistatin-related protein 5 (FSTL5) and a follistatin-like molecule encoded by the CNS-related Mahya gene. Mahya genes have been retained in certain Bilaterian branches during evolution. They are conserved in Hymenoptera and Deuterostomes, but are absent from other metazoan species such as fruit fly and nematode. Mahya proteins are secretory, with a follistatin-like domain (Kazal-type serine/threonine protease inhibitor domain and EF-hand calcium-binding domain), two Ig-like domains, and a novel C-terminal domain. Mahya may be involved in learning and memory and in processing of sensory information in Hymenoptera and vertebrates. Follistatin is a secreted, multidomain protein that binds activins with high affinity and antagonizes their signaling.


Pssm-ID: 409399 [Multi-domain]  Cd Length: 93  Bit Score: 55.73  E-value: 2.44e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  665 PMITGNLENQTTTIGETIEVTCPASGNPTPHITWFKDNETLVED--SGIVLRDGNRNLTIRRVRKEDGGLYTCQACNVLG 742
Cdd:cd05736    1 PVIRVYPEFQAKEPGVEASLRCHAEGIPLPRVQWLKNGMDINPKlsKQLTLIANGSELHISNVRYEDTGAYTCIAKNEGG 80
                         90
                 ....*....|
gi 27777648  743 CAR-AETLFI 751
Cdd:cd05736   81 VDEdISSLFV 90
I-set pfam07679
Immunoglobulin I-set domain;
342-419 2.45e-09

Immunoglobulin I-set domain;


Pssm-ID: 400151 [Multi-domain]  Cd Length: 90  Bit Score: 55.34  E-value: 2.45e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648    342 VEATVGSQVRIPVKYLSYPAPDIKWYRNGRPI-ESNYTMIVGDE----LTIMEVTERDAGNYTVILTNPIsmEKQSHMVS 416
Cdd:pfam07679   10 VEVQEGESARFTCTVTGTPDPEVSWFKDGQPLrSSDRFKVTYEGgtytLTISNVQPDDSGKYTCVATNSA--GEAEASAE 87

                   ...
gi 27777648    417 LVV 419
Cdd:pfam07679   88 LTV 90
PTK_Tyk2_rpt1 cd05076
Pseudokinase (repeat 1) domain of the Protein Tyrosine Kinase, Tyrosine kinase 2; Tyk2 is ...
1009-1158 2.55e-09

Pseudokinase (repeat 1) domain of the Protein Tyrosine Kinase, Tyrosine kinase 2; Tyk2 is widely expressed in many tissues. It is involved in signaling via the cytokine receptors IFN-alphabeta, IL-6, IL-10, IL-12, IL-13, and IL-23. It mediates cell surface urokinase receptor (uPAR) signaling and plays a role in modulating vascular smooth muscle cell (VSMC) functional behavior in response to injury. Tyk2 is also important in dendritic cell function and T helper (Th)1 cell differentiation. A homozygous mutation of Tyk2 was found in a patient with hyper-IgE syndrome (HIES), a primary immunodeficiency characterized by recurrent skin abscesses, pneumonia, and elevated serum IgE. This suggests that Tyk2 may play important roles in multiple cytokine signaling involved in innate and adaptive immunity. Tyk2 is a member of the Janus kinase (Jak) subfamily of proteins, which are cytoplasmic (or nonreceptor) PTKs containing an N-terminal FERM domain, followed by a Src homology 2 (SH2) domain, a pseudokinase domain, and a C-terminal tyr kinase domain. The pseudokinase domain shows similarity to tyr kinases but lacks crucial residues for catalytic activity and ATP binding. It modulates the kinase activity of the C-terminal catalytic domain. The Tyk2 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270661 [Multi-domain]  Cd Length: 273  Bit Score: 59.92  E-value: 2.55e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1009 QVAKGMEFLASRKCIHRDLAARNILLSEKNV-------VKICDFGLARDIYKDPDYVRkgdaRLPlkWMAPETIfDRVYT 1081
Cdd:cd05076  124 QLASALSYLENKNLVHGNVCAKNILLARLGLeegtspfIKLSDPGVGLGVLSREERVE----RIP--WIAPECV-PGGNS 196
                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 27777648 1082 IQS--DVWSFGVLLWEIFSLGASPYPGVKIDEEfcRRLKEgTRMRAPDYTTPEMYQTMLDCWHEDPNQRPSFSELVEHL 1158
Cdd:cd05076  197 LSTaaDKWGFGATLLEICFNGEAPLQSRTPSEK--ERFYQ-RQHRLPEPSCPELATLISQCLTYEPTQRPSFRTILRDL 272
STKc_MLCK cd14103
Catalytic domain of the Serine/Threonine Kinase, Myosin Light Chain Kinase; STKs catalyze the ...
1009-1106 2.75e-09

Catalytic domain of the Serine/Threonine Kinase, Myosin Light Chain Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MLCK phosphorylates myosin regulatory light chain and controls the contraction of all muscle types. In vertebrates, different MLCKs function in smooth (MLCK1), skeletal (MLCK2), and cardiac (MLCK3) muscles. A fourth protein, MLCK4, has also been identified through comprehensive genome analysis although it has not been biochemically characterized. The MLCK1 gene expresses three transcripts in a cell-specific manner: a short MLCK1 which contains three immunoglobulin (Ig)-like and one fibronectin type III (FN3) domains, PEVK and actin-binding regions, and a kinase domain near the C-terminus; a long MLCK1 containing six additional Ig-like domains at the N-terminus compared to the short MLCK1; and the C-terminal Ig module. MLCK2, MLCK3, and MLCK4 share a simpler domain architecture of a single kinase domain near the C-terminus and the absence of Ig-like or FN3 domains. The MLCK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271005 [Multi-domain]  Cd Length: 250  Bit Score: 59.16  E-value: 2.75e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1009 QVAKGMEFLASRKCIHRDLAARNILLSEK--NVVKICDFGLArdiykdpdyvRKGDARLPLK-------WMAPETI-FDR 1078
Cdd:cd14103   99 QICEGVQYMHKQGILHLDLKPENILCVSRtgNQIKIIDFGLA----------RKYDPDKKLKvlfgtpeFVAPEVVnYEP 168
                         90       100
                 ....*....|....*....|....*...
gi 27777648 1079 VyTIQSDVWSFGVLLWEIFSlGASPYPG 1106
Cdd:cd14103  169 I-SYATDMWSVGVICYVLLS-GLSPFMG 194
Ig3_L1-CAM_like cd05731
Third immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM), and similar ...
674-745 2.92e-09

Third immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM), and similar domains; The members here are composed of the third immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM). L1 belongs to the L1 subfamily of cell adhesion molecules (CAMs) and is comprised of an extracellular region having six Ig-like domains and five fibronectin type III domains, a transmembrane region and an intracellular domain. L1 is primarily expressed in the nervous system and is involved in its development and function. L1 is associated with an X-linked recessive disorder, X-linked hydrocephalus, MASA syndrome, and spastic paraplegia type 1, that involves abnormalities of axonal growth. This group also contains the chicken neuron-glia cell adhesion molecule, Ng-CAM and human neurofascin.


Pssm-ID: 409394 [Multi-domain]  Cd Length: 83  Bit Score: 55.11  E-value: 2.92e-09
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 27777648  674 QTTTI---GETIEVTCPASGNPTPHITWFKDNETLVEDSGiVLRDGNRNLTIRRVRKEDGGLYTCQACNVLGCAR 745
Cdd:cd05731    2 ESSTMvlrGGVLLLECIAEGLPTPDIRWIKLGGELPKGRT-KFENFNKTLKIENVSEADSGEYQCTASNTMGSAR 75
STKc_Trio_C cd14113
C-terminal kinase domain of the Large Serine/Threonine Kinase and Rho Guanine Nucleotide ...
998-1150 2.92e-09

C-terminal kinase domain of the Large Serine/Threonine Kinase and Rho Guanine Nucleotide Exchange Factor, Triple functional domain protein; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Triple functional domain protein (Trio), also called PTPRF-interacting protein, is a large multidomain protein containing a series of spectrin-like repeats, two each of RhoGEF and SH3 domains, an immunoglobulin-like (Ig) domain and a C-terminal kinase. Trio plays important roles in neuronal cell migration and axon guidance. It was originally identified as an interacting partner of the of the receptor-like tyrosine phosphatase (RPTP) LAR (leukocyte-antigen-related protein), a family of receptors that function in the signaling to the actin cytoskeleton during development. Trio functions as a GEF for Rac1, RhoG, and RhoA, and is involved in the regulation of lamellipodia formation, mediating Rac1-dependent cell spreading and migration. The Trio subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271015 [Multi-domain]  Cd Length: 263  Bit Score: 59.60  E-value: 2.92e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  998 LTLEHLICYSFQVAKGMEFLASRKCIHRDLAARNILLSE---KNVVKICDFGLARDIYKDPdYVRK--GDArlplKWMAP 1072
Cdd:cd14113  100 LTEEKIRFYLREILEALQYLHNCRIAHLDLKPENILVDQslsKPTIKLADFGDAVQLNTTY-YIHQllGSP----EFAAP 174
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1073 ETIFDRVYTIQSDVWSFGVLLWEIFSlGASPYPGVKIDE---EFCRRlkegtrmrapDYTTPEMY-----QTMLD--CW- 1141
Cdd:cd14113  175 EIILGNPVSLTSDLWSIGVLTYVLLS-GVSPFLDESVEEtclNICRL----------DFSFPDDYfkgvsQKAKDfvCFl 243
                        170
                 ....*....|
gi 27777648 1142 -HEDPNQRPS 1150
Cdd:cd14113  244 lQMDPAKRPS 253
STKc_GRK2 cd14223
Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase 2; STKs ...
1006-1148 3.07e-09

Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. GRK2, also called beta-adrenergic receptor kinase (beta-ARK) or beta-ARK1, is important in regulating several cardiac receptor responses. It plays a role in cardiac development and in hypertension. Deletion of GRK2 in mice results in embryonic lethality, caused by hypoplasia of the ventricular myocardium. GRK2 also plays important roles in the liver (as a regulator of portal blood pressure), in immune cells, and in the nervous system. Altered GRK2 expression has been reported in several disorders including major depression, schizophrenia, bipolar disorder, and Parkinsonism. GRK2 contains an N-terminal RGS homology (RH) domain, a central catalytic domain, and C-terminal pleckstrin homology (PH) domain that mediates PIP2 and G protein betagamma-subunit translocation to the membrane. GRKs phosphorylate and regulate G protein-coupled receptors (GPCRs), the largest superfamily of cell surface receptors which regulate some part of nearly all physiological functions. Phosphorylated GPCRs bind to arrestins, which prevents further G protein signaling despite the presence of activating ligand. TheGRK2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271125 [Multi-domain]  Cd Length: 321  Bit Score: 60.06  E-value: 3.07e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1006 YSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIYKDPDYVRKGDArlplKWMAPETIFDRV-YTIQS 1084
Cdd:cd14223  108 YAAEIILGLEHMHSRFVVYRDLKPANILLDEFGHVRISDLGLACDFSKKKPHASVGTH----GYMAPEVLQKGVaYDSSA 183
                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 27777648 1085 DVWSFGVLLWEIFSlGASPYPGVKI-DEEFCRRLKEGTRMRAPDYTTPEMYQTMLDCWHEDPNQR 1148
Cdd:cd14223  184 DWFSLGCMLFKLLR-GHSPFRQHKTkDKHEIDRMTLTMAVELPDSFSPELRSLLEGLLQRDVNRR 247
STKc_Unc-89_rpt2 cd14112
Catalytic kinase domain, second repeat, of the Giant Serine/Threonine Kinase Uncoordinated ...
975-1157 3.07e-09

Catalytic kinase domain, second repeat, of the Giant Serine/Threonine Kinase Uncoordinated protein 89; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The nematode Unc-89 gene, through alternative promoter use and splicing, encodes at least six major isoforms (Unc-89A to Unc-89F) of giant muscle proteins that are homologs for the vetebrate obscurin. In flies, five isoforms of Unc-89 have been detected: four in the muscles of adult flies (two in the indirect flight muscle and two in other muscles) and another isoform in the larva. Unc-89 in nematodes is required for normal muscle cell architecture. In flies, it is necessary for the development of a symmetrical sarcomere in the flight muscles. Unc-89 proteins contain several adhesion and signaling domains including multiple copies of the immunoglobulin (Ig) domain, as well as fibronectin type III (FN3), SH3, RhoGEF, and PH domains. The nematode Unc-89 isoforms D, C, D, and F contain two kinase domain with B and F having two complete kinase domains while the first repeat of C and D are partial domains. Homology modeling suggests that the first kinase repeat of Unc-89 may be catalytically inactive, a pseudokinase, while the second kinase repeat may be active. The Unc-89 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271014 [Multi-domain]  Cd Length: 259  Bit Score: 59.47  E-value: 3.07e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  975 FVEEKSLSDVEEEEAseelYKDFLTLEHLICYSFQVAKGMEFLASRKCIHRDLAARNILLSEKN--VVKICDFGLARDIY 1052
Cdd:cd14112   77 LVMEKLQEDVFTRFS----SNDYYSEEQVATTVRQILDALHYLHFKGIAHLDVQPDNIMFQSVRswQVKLVDFGRAQKVS 152
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1053 KDPDYVRKGDarlpLKWMAPETIFDRVY-TIQSDVWSFGVLLWEIFSlGASPYPGVKIDEEFCRRLKEGTRMRaPDY--- 1128
Cdd:cd14112  153 KLGKVPVDGD----TDWASPEFHNPETPiTVQSDIWGLGVLTFCLLS-GFHPFTSEYDDEEETKENVIFVKCR-PNLifv 226
                        170       180       190
                 ....*....|....*....|....*....|
gi 27777648 1129 -TTPEMYQTMLDCWHEDPNQRPSFSELVEH 1157
Cdd:cd14112  227 eATQEALRFATWALKKSPTRRMRTDEALEH 256
STKc_DAPK3 cd14195
Catalytic domain of the Serine/Threonine Kinase, Death-Associated Protein Kinase 3; STKs ...
995-1157 3.10e-09

Catalytic domain of the Serine/Threonine Kinase, Death-Associated Protein Kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. DAPKs mediate cell death and act as tumor suppressors. They are necessary to induce cell death and their overexpression leads to death-associated changes including membrane blebbing, cell rounding, and formation of autophagic vesicles. Vertebrates contain three subfamily members with different domain architecture, localization, and function. DAPK3, also called DAP-like kinase (DLK) and zipper-interacting protein kinase (ZIPk), contains an N-terminal kinase domain and a C-terminal region with nuclear localization signals (NLS) and a leucine zipper motif that mediates homodimerization and interaction with other leucine zipper proteins. It interacts with Par-4, a protein that contains a death domain and interacts with actin filaments. DAPK3 is present in both the cytoplasm and nucleus. Its co-expression with Par-4 results in the co-localization of the two proteins to actin filaments. In addition to cell death, DAPK3 is also implicated in mediating cell motility and the contraction of smooth muscles. The DAPK3 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271097 [Multi-domain]  Cd Length: 271  Bit Score: 59.63  E-value: 3.10e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  995 KDFLTLEHLICYSFQVAKGMEFLASRKCIHRDLAARNILLSEKNV----VKICDFGLA---------RDIYKDPDYVrkg 1061
Cdd:cd14195  102 KESLTEEEATQFLKQILDGVHYLHSKRIAHFDLKPENIMLLDKNVpnprIKLIDFGIAhkieagnefKNIFGTPEFV--- 178
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1062 darlplkwmAPETIFDRVYTIQSDVWSFGVLLWEIFSlGASPYPGVKIDEEFcrrlkegTRMRAPDYTTPEMYQT----- 1136
Cdd:cd14195  179 ---------APEIVNYEPLGLEADMWSIGVITYILLS-GASPFLGETKQETL-------TNISAVNYDFDEEYFSntsel 241
                        170       180
                 ....*....|....*....|....*
gi 27777648 1137 ----MLDCWHEDPNQRPSFSELVEH 1157
Cdd:cd14195  242 akdfIRRLLVKDPKKRMTIAQSLEH 266
STKc_TSSK6-like cd14164
Catalytic domain of testis-specific serine/threonine kinase 6 and similar proteins; STKs ...
1009-1122 3.11e-09

Catalytic domain of testis-specific serine/threonine kinase 6 and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TSSK proteins are almost exclusively expressed postmeiotically in the testis and play important roles in spermatogenesis and/or spermiogenesis. There are five mammalian TSSK proteins which show differences in their localization and timing of expression. TSSK6, also called SSTK, is expressed at the head of elongated sperm. It can phosphorylate histones and associate with heat shock protens HSP90 and HSC70. Male mice deficient in TSSK6 are infertile, showing spermatogenic impairment including reduced sperm counts, impaired DNA condensation, abnormal morphology and decreased motility rates. The TSSK6-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271066 [Multi-domain]  Cd Length: 256  Bit Score: 59.49  E-value: 3.11e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1009 QVAKGMEFLASRKCIHRDLAARNILLS-EKNVVKICDFGLARDIYKDPDYVRK--GDArlplKWMAPETIFDRVYTIQS- 1084
Cdd:cd14164  108 QMVGAVNYLHDMNIVHRDLKCENILLSaDDRKIKIADFGFARFVEDYPELSTTfcGSR----AYTPPEVILGTPYDPKKy 183
                         90       100       110
                 ....*....|....*....|....*....|....*...
gi 27777648 1085 DVWSFGVLLWEIFSlGASPYpgvkiDEEFCRRLKEGTR 1122
Cdd:cd14164  184 DVWSLGVVLYVMVT-GTMPF-----DETNVRRLRLQQR 215
STKc_CaMKII cd14086
Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase ...
993-1157 3.33e-09

Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase Type II; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CaMKs are multifunctional calcium and calmodulin (CaM) stimulated STKs involved in cell cycle regulation. There are several types of CaMKs including CaMKI, CaMKII, and CaMKIV. CaMKs contain an N-terminal catalytic domain followed by a regulatory domain that harbors a CaM binding site. In addition, CaMKII contains a C-terminal association domain that facilitates oligomerization. There are four CaMKII proteins (alpha, beta, gamma, delta) encoded by different genes; each gene undergoes alternative splicing to produce more than 30 isoforms. CaMKII-alpha and -beta are enriched in neurons while CaMKII-gamma and -delta are predominant in myocardium. CaMKII is a signaling molecule that translates upstream calcium and reactive oxygen species (ROS) signals into downstream responses that play important roles in synaptic function and cardiovascular physiology. It is a major component of the postsynaptic density and is critical in regulating synaptic plasticity including long-term potentiation. It is critical in regulating ion channels and proteins involved in myocardial excitation-contraction and excitation-transcription coupling. Excessive CaMKII activity promotes processes that contribute to heart failure and arrhythmias. The CaMKII subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270988 [Multi-domain]  Cd Length: 292  Bit Score: 59.74  E-value: 3.33e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  993 LYKDFLTLEHlicYS--------FQVAKGMEFLASRKCIHRDLAARNILLSEKN---VVKICDFGLARDIYKDPDyVRKG 1061
Cdd:cd14086   87 LFEDIVAREF---YSeadashciQQILESVNHCHQNGIVHRDLKPENLLLASKSkgaAVKLADFGLAIEVQGDQQ-AWFG 162
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1062 DARLPlKWMAPETIFDRVYTIQSDVWSFGVLLWeIFSLGASPYpgvkIDEEFcRRLKEGTRMRAPDYTTPE--------- 1132
Cdd:cd14086  163 FAGTP-GYLSPEVLRKDPYGKPVDIWACGVILY-ILLVGYPPF----WDEDQ-HRLYAQIKAGAYDYPSPEwdtvtpeak 235
                        170       180
                 ....*....|....*....|....*.
gi 27777648 1133 -MYQTMLDCwheDPNQRPSFSELVEH 1157
Cdd:cd14086  236 dLINQMLTV---NPAKRITAAEALKH 258
STKc_Rad53_Cds1 cd14098
Catalytic domain of the yeast Serine/Threonine Kinases, Rad53 and Cds1; STKs catalyze the ...
1009-1157 4.11e-09

Catalytic domain of the yeast Serine/Threonine Kinases, Rad53 and Cds1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Rad53 and Cds1 are the checkpoint kinase 2 (Chk2) homologs found in budding and fission yeast, respectively. They play a central role in the cell's response to DNA lesions to prevent genome rearrangements and maintain genome integrity. They are phosphorylated in response to DNA damage and incomplete replication, and are essential for checkpoint control. They help promote DNA repair by stalling the cell cycle prior to mitosis in the presence of DNA damage. The Rad53/Cds1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271000 [Multi-domain]  Cd Length: 265  Bit Score: 59.03  E-value: 4.11e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1009 QVAKGMEFLASRKCIHRDLAARNILLSEKN--VVKICDFGLARdiykdpdyVRKGDARL-----PLKWMAPETIFDR--- 1078
Cdd:cd14098  109 QILEAMAYTHSMGITHRDLKPENILITQDDpvIVKISDFGLAK--------VIHTGTFLvtfcgTMAYLAPEILMSKeqn 180
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1079 ---VYTIQSDVWSFGVLLWEIFSlGASPYPGVKiDEEFCRRLKEGTRMRAP--DYTTPEMYQTMLDCWHE-DPNQRPSFS 1152
Cdd:cd14098  181 lqgGYSNLVDMWSVGCLVYVMLT-GALPFDGSS-QLPVEKRIRKGRYTQPPlvDFNISEEAIDFILRLLDvDPEKRMTAA 258

                 ....*
gi 27777648 1153 ELVEH 1157
Cdd:cd14098  259 QALDH 263
STKc_DRAK1 cd14197
Catalytic domain of the Serine/Threonine Kinase, Death-associated protein kinase-Related ...
1009-1113 4.20e-09

Catalytic domain of the Serine/Threonine Kinase, Death-associated protein kinase-Related Apoptosis-inducing protein Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. DRAKs were named based on their similarity (around 50% identity) to the kinase domain of DAPKs. They contain an N-terminal kinase domain and a C-terminal regulatory domain. Vertebrates contain two subfamily members, DRAK1 (also called STK17A) and DRAK2. Both DRAKs are localized to the nucleus, autophosphorylate themselves, and phosphorylate myosin light chain as a substrate. Rabbit DRAK1 has been shown to induce apoptosis in osteoclasts and overexpressio of human DRAK1 induces apoptosis in cultured fibroblast cells. DRAK1 may be involved in apoptotic signaling. The DRAK1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271099 [Multi-domain]  Cd Length: 271  Bit Score: 59.18  E-value: 4.20e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1009 QVAKGMEFLASRKCIHRDLAARNILLSEKNV---VKICDFGLAR---------DIYKDPDYVrkgdarlplkwmAPETIF 1076
Cdd:cd14197  119 QILEGVSFLHNNNVVHLDLKPQNILLTSESPlgdIKIVDFGLSRilknseelrEIMGTPEYV------------APEILS 186
                         90       100       110
                 ....*....|....*....|....*....|....*..
gi 27777648 1077 DRVYTIQSDVWSFGVLLWEIFSlGASPYPGVKIDEEF 1113
Cdd:cd14197  187 YEPISTATDMWSIGVLAYVMLT-GISPFLGDDKQETF 222
PK_eIF2AK_GCN2_rpt1 cd14012
Pseudokinase domain, repeat 1, of eukaryotic translation Initiation Factor 2-Alpha Kinase 4 or ...
1006-1157 4.62e-09

Pseudokinase domain, repeat 1, of eukaryotic translation Initiation Factor 2-Alpha Kinase 4 or General Control Non-derepressible-2; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. EIF2AKs phosphorylate the alpha subunit of eIF-2, resulting in the overall downregulation of protein synthesis. eIF-2 phosphorylation is induced in response to cellular stresses including virus infection, heat shock, nutrient deficiency, and the accummulation of unfolded proteins, among others. There are four distinct kinases that phosphorylate eIF-2 and control protein synthesis under different stress conditions: GCN2, protein kinase regulated by RNA (PKR), heme-regulated inhibitor kinase (HRI), and PKR-like endoplasmic reticulum kinase (PERK). GCN2 is activated by amino acid or serum starvation and UV irradiation. It induces GCN4, a transcriptional activator of amino acid biosynthetic genes, leading to increased production of amino acids under amino acid-deficient conditions. In serum-starved cells, GCN2 activation induces translation of the stress-responsive transcription factor ATF4, while under UV stress, GCN2 triggers transcriptional rescue via NF-kappaB signaling. GCN2 contains an N-terminal RWD, a degenerate kinase-like (repeat 1), the catalytic kinase (repeat 2), a histidyl-tRNA synthetase (HisRS)-like, and a C-terminal ribosome-binding and dimerization (RB/DD) domains. The degenerate pseudokinase domain of GCN2 may function as a regulatory domain. The GCN2 subfamily is part of a larger superfamily that includes the catalytic domains of serine/threonine kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270914 [Multi-domain]  Cd Length: 254  Bit Score: 58.91  E-value: 4.62e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1006 YSFQVAKGMEFLASRKCIHRDLAARNILLSEKN---VVKICDFGLARDIyKDPDYVRKGDARLPLKWMAPETI-FDRVYT 1081
Cdd:cd14012  109 WTLQLLEALEYLHRNGVVHKSLHAGNVLLDRDAgtgIVKLTDYSLGKTL-LDMCSRGSLDEFKQTYWLPPELAqGSKSPT 187
                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 27777648 1082 IQSDVWSFGVLLWEIFslgaspyPGVKIDEEFcrrlkEGTRMRAPDYTTPEMYQTMLD-CWHEDPNQRPSFSELVEH 1157
Cdd:cd14012  188 RKTDVWDLGLLFLQML-------FGLDVLEKY-----TSPNPVLVSLDLSASLQDFLSkCLSLDPKKRPTALELLPH 252
STKc_Kin1_2 cd14077
Catalytic domain of Kin1, Kin2, and simlar Serine/Threonine Kinases; STKs catalyze the ...
1006-1157 4.73e-09

Catalytic domain of Kin1, Kin2, and simlar Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of yeast Kin1, Kin2, and similar proteins. Fission yeast Kin1 is a membrane-associated kinase that is involved in regulating cell surface cohesiveness during interphase. It also plays a role during mitosis, linking actomyosin ring assembly with septum synthesis and membrane closure to ensure separation of daughter cells. Budding yeast Kin1 and Kin2 act downstream of the Rab-GTPase Sec4 and are associated with the exocytic apparatus; they play roles in the secretory pathway. The Kin1/2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270979 [Multi-domain]  Cd Length: 267  Bit Score: 59.00  E-value: 4.73e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1006 YSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLArDIYKDPDYVRK--GDarlpLKWMAPETIFDRVYT-I 1082
Cdd:cd14077  118 FARQIASALDYLHRNSIVHRDLKIENILISKSGNIKIIDFGLS-NLYDPRRLLRTfcGS----LYFAAPELLQAQPYTgP 192
                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 27777648 1083 QSDVWSFGVLLWEIFSlGASPYpgvkiDEEFCRRL----KEGTrMRAPDYTTPEMYQTMLDCWHEDPNQRPSFSELVEH 1157
Cdd:cd14077  193 EVDVWSFGVVLYVLVC-GKVPF-----DDENMPALhakiKKGK-VEYPSYLSSECKSLISRMLVVDPKKRATLEQVLNH 264
STKc_CaMKK1 cd14200
Catalytic domain of the Serine/Threonine kinase, Calmodulin Dependent Protein Kinase Kinase 1; ...
1006-1111 4.83e-09

Catalytic domain of the Serine/Threonine kinase, Calmodulin Dependent Protein Kinase Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CaMKKs are upstream kinases of the CaM kinase cascade that phosphorylate and activate CaMKI and CamKIV. They may also phosphorylate other substrates including PKB and AMP-activated protein kinase (AMPK). CaMKK1, also called CaMKK alpha, is involved in the regulation of glucose uptake in skeletal muscles, independently of AMPK and PKB activation. It also play roles in learning and memory. Studies on CaMKK1 knockout mice reveal deficits in fear conditioning. The CaMKK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271102 [Multi-domain]  Cd Length: 284  Bit Score: 59.19  E-value: 4.83e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1006 YSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDiYKDPDYVRKGDARLPlKWMAPETIFDRVYTIQS- 1084
Cdd:cd14200  129 YFRDIVLGIEYLHYQKIVHRDIKPSNLLLGDDGHVKIADFGVSNQ-FEGNDALLSSTAGTP-AFMAPETLSDSGQSFSGk 206
                         90       100
                 ....*....|....*....|....*....
gi 27777648 1085 --DVWSFGVLLWeIFSLGASPYpgvkIDE 1111
Cdd:cd14200  207 alDVWAMGVTLY-CFVYGKCPF----IDE 230
PKc_MEK cd06615
Catalytic domain of the dual-specificity Protein Kinase, Mitogen-Activated Protein (MAP) ...
1007-1105 5.05e-09

Catalytic domain of the dual-specificity Protein Kinase, Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. MEK1 and MEK2 are MAPK kinases (MAPKKs or MKKs), and are dual-specificity PKs that phosphorylate and activate the downstream targets, ERK1 and ERK2, on specific threonine and tyrosine residues. The ERK cascade starts with extracellular signals including growth factors, hormones, and neurotransmitters, which act through receptors and ion channels to initiate intracellular signaling that leads to the activation at the MAPKKK (Raf-1 or MOS) level, which leads to the transmission of signals to MEK1/2, and finally to ERK1/2. The ERK cascade plays an important role in cell proliferation, differentiation, oncogenic transformation, and cell cycle control, as well as in apoptosis and cell survival under certain conditions. This cascade has also been implicated in synaptic plasticity, migration, morphological determination, and stress response immunological reactions. Gain-of-function mutations in genes encoding ERK cascade proteins, including MEK1/2, cause cardiofaciocutaneous (CFC) syndrome, a condition leading to multiple congenital anomalies and mental retardation in patients. The MEK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 132946 [Multi-domain]  Cd Length: 308  Bit Score: 59.37  E-value: 5.05e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1007 SFQVAKGMEFLAS-RKCIHRDLAARNILLSEKNVVKICDFG--------LARDIYKDPDYvrkgdarlplkwMAPETIFD 1077
Cdd:cd06615  105 SIAVLRGLTYLREkHKIMHRDVKPSNILVNSRGEIKLCDFGvsgqlidsMANSFVGTRSY------------MSPERLQG 172
                         90       100
                 ....*....|....*....|....*...
gi 27777648 1078 RVYTIQSDVWSFGVLLWEIfSLGASPYP 1105
Cdd:cd06615  173 THYTVQSDIWSLGLSLVEM-AIGRYPIP 199
STKc_Nek10 cd08528
Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase ...
1020-1155 5.11e-09

Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase 10; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. No function has yet been ascribed to Nek10. The gene encoding Nek10 is a putative causative gene for breast cancer; it is located within a breast cancer susceptibility loci on chromosome 3p24. Nek10 is one in a family of 11 different Neks (Nek1-11) that are involved in cell cycle control. The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270867 [Multi-domain]  Cd Length: 270  Bit Score: 59.05  E-value: 5.11e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1020 RKCIHRDLAARNILLSEKNVVKICDFGLARDiyKDPDYVRKGDARLPLKWMAPETIFDRVYTIQSDVWSFGVLLWEIFSL 1099
Cdd:cd08528  133 KQIVHRDLKPNNIMLGEDDKVTITDFGLAKQ--KGPESSKMTSVVGTILYSCPEIVQNEPYGEKADIWALGCILYQMCTL 210
                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 27777648 1100 gASPYPGVKIdeefcrrLKEGTRMRAPDYT-TPE------MYQTMLDCWHEDPNQRPSFSELV 1155
Cdd:cd08528  211 -QPPFYSTNM-------LTLATKIVEAEYEpLPEgmysddITFVIRSCLTPDPEARPDIVEVS 265
IgI_5_Dscam cd20958
Fifth immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; ...
671-739 5.29e-09

Fifth immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fifth immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. This group is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.


Pssm-ID: 409550 [Multi-domain]  Cd Length: 89  Bit Score: 54.50  E-value: 5.29e-09
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 27777648  671 LENQTTTIGETIEVTCPASGNPTPHITWFKDNETL-VEDSGIVLRDGnrNLTIRRV-RKEDGGLYTCQACN 739
Cdd:cd20958    7 MGNLTAVAGQTLRLHCPVAGYPISSITWEKDGRRLpLNHRQRVFPNG--TLVIENVqRSSDEGEYTCTARN 75
STKc_RSK_C cd14091
C-terminal catalytic domain of the Serine/Threonine Kinases, Ribosomal S6 kinases; STKs ...
1010-1157 5.35e-09

C-terminal catalytic domain of the Serine/Threonine Kinases, Ribosomal S6 kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. RSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family. They are activated by signaling inputs from extracellular regulated kinase (ERK) and phosphoinositide dependent kinase 1 (PDK1). ERK phosphorylates and activates the CTD of RSK, serving as a docking site for PDK1, which phosphorylates and activates the NTD, which in turn phosphorylates all known RSK substrates. RSKs act as downstream effectors of mitogen-activated protein kinase (MAPK) and play key roles in mitogen-activated cell growth, differentiation, and survival. Mammals possess four RSK isoforms (RSK1-4) from distinct genes. RSK proteins are also referred to as MAP kinase-activated protein kinases (MAPKAPKs), 90 kDa ribosomal protein S6 kinases (p90-RSKs), or p90S6Ks. The RSK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270993 [Multi-domain]  Cd Length: 291  Bit Score: 59.18  E-value: 5.35e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1010 VAKGMEFLASRKCIHRDLAARNILLSEK----NVVKICDFGLARDIYKD------PDYVRkgdarlplKWMAPETIFDRV 1079
Cdd:cd14091  103 LTKTVEYLHSQGVVHRDLKPSNILYADEsgdpESLRICDFGFAKQLRAEngllmtPCYTA--------NFVAPEVLKKQG 174
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1080 YTIQSDVWSFGVLLWEIFSlGASPYPGVKID--EEFCRRLKEGtrmrAPDYTTP----------EMYQTMLdcwHEDPNQ 1147
Cdd:cd14091  175 YDAACDIWSLGVLLYTMLA-GYTPFASGPNDtpEVILARIGSG----KIDLSGGnwdhvsdsakDLVRKML---HVDPSQ 246
                        170
                 ....*....|
gi 27777648 1148 RPSFSELVEH 1157
Cdd:cd14091  247 RPTAAQVLQH 256
STKc_PhKG cd14093
Catalytic domain of the Serine/Threonine Kinase, Phosphorylase kinase Gamma subunit; STKs ...
1009-1104 5.48e-09

Catalytic domain of the Serine/Threonine Kinase, Phosphorylase kinase Gamma subunit; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Phosphorylase kinase (PhK) catalyzes the phosphorylation of inactive phosphorylase b to form the active phosphorylase a. It coordinates hormonal, metabolic, and neuronal signals to initiate the breakdown of glycogen stores, which enables the maintenance of blood-glucose homeostasis during fasting, and is also used as a source of energy for muscle contraction. PhK is one of the largest and most complex protein kinases, composed of a heterotetramer containing four molecules each of four subunit types: one catalytic (gamma) and three regulatory (alpha, beta, and delta). Each subunit has tissue-specific isoforms or splice variants. Vertebrates contain two isoforms of the gamma subunit (gamma 1 and gamma 2). The gamma subunit, when isolated, is constitutively active and does not require phosphorylation of the A-loop for activity. The regulatory subunits restrain this kinase activity until signals are received to relieve this inhibition. For example, the kinase is activated in response to hormonal stimulation, after autophosphorylation or phosphorylation by cAMP-dependent kinase of the alpha and beta subunits. The high-affinity binding of ADP to the beta subunit also stimulates kinase activity, whereas calcium relieves inhibition by binding to the delta (calmodulin) subunit. The PhKG subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270995 [Multi-domain]  Cd Length: 272  Bit Score: 58.90  E-value: 5.48e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1009 QVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIyKDPDYVRK-----GdarlplkWMAPETI----FDRV 1079
Cdd:cd14093  117 QLFEAVEFLHSLNIVHRDLKPENILLDDNLNVKISDFGFATRL-DEGEKLRElcgtpG-------YLAPEVLkcsmYDNA 188
                         90       100
                 ....*....|....*....|....*..
gi 27777648 1080 --YTIQSDVWSFGVLLWEIFSlGASPY 1104
Cdd:cd14093  189 pgYGKEVDMWACGVIMYTLLA-GCPPF 214
STKc_PIM cd14005
Catalytic domain of the Serine/Threonine kinase, Proviral Integration Moloney virus (PIM) ...
1008-1157 5.85e-09

Catalytic domain of the Serine/Threonine kinase, Proviral Integration Moloney virus (PIM) kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The PIM gene locus was discovered as a result of the cloning of retroviral intergration sites in murine Moloney leukemia virus, leading to the identification of PIM kinases. They are constitutively active STKs with a broad range of cellular targets and are overexpressed in many haematopoietic malignancies and solid cancers. Vertebrates contain three distinct PIM kinase genes (PIM1-3); each gene may result in mutliple protein isoforms. There are two PIM1 and three PIM2 isoforms as a result of alternative translation initiation sites, while there is only one PIM3 protein. Compound knockout mice deficient of all three PIM kinases that survive the perinatal period show a profound reduction in body size, indicating that PIMs are important for body growth. The PIM subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270907 [Multi-domain]  Cd Length: 255  Bit Score: 58.40  E-value: 5.85e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1008 FQVAKGMEFLASRKCIHRDLAARNILLSEKNV-VKICDFG----LARDIYKDPDYVRKGdarlplkwMAPETIFDRVYTI 1082
Cdd:cd14005  114 RQVVEAVRHCHQRGVLHRDIKDENLLINLRTGeVKLIDFGcgalLKDSVYTDFDGTRVY--------SPPEWIRHGRYHG 185
                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 27777648 1083 QS-DVWSFGVLLWEIFSlGASPYpgvKIDEEFCRRLKEGTRMRapdytTPEMYQTMLDCWHEDPNQRPSFSELVEH 1157
Cdd:cd14005  186 RPaTVWSLGILLYDMLC-GDIPF---ENDEQILRGNVLFRPRL-----SKECCDLISRCLQFDPSKRPSLEQILSH 252
STKc_GRK7 cd05607
Catalytic domain of the Protein Serine/Threonine Kinase, G protein-coupled Receptor Kinase 7; ...
998-1131 6.32e-09

Catalytic domain of the Protein Serine/Threonine Kinase, G protein-coupled Receptor Kinase 7; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. GRK7 (also called iodopsin kinase) belongs to the visual group of GRKs. It is primarily found in the retina and plays a role in the regulation of opsin light receptors. GRK7 is located in retinal cone outer segments and plays an important role in regulating photoresponse of the cones. GRKs phosphorylate and regulate G protein-coupled receptors (GPCRs), the largest superfamily of cell surface receptors, which regulate some part of nearly all physiological functions. Phosphorylated GPCRs bind to arrestins, which prevents further G protein signaling despite the presence of activating ligand. The GRK7 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270758 [Multi-domain]  Cd Length: 286  Bit Score: 58.76  E-value: 6.32e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  998 LTLEHLICYSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIYKDPDYVRKGDARlplKWMAPETIFD 1077
Cdd:cd05607  101 IEMERVIFYSAQITCGILHLHSLKIVYRDMKPENVLLDDNGNCRLSDLGLAVEVKEGKPITQRAGTN---GYMAPEILKE 177
                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 27777648 1078 RVYTIQSDVWSFGVLLWEIFSlGASPY--PGVKID-EEFCRR-LKEGTRMRAPDYTTP 1131
Cdd:cd05607  178 ESYSYPVDWFAMGCSIYEMVA-GRTPFrdHKEKVSkEELKRRtLEDEVKFEHQNFTEE 234
STKc_SnRK2-3 cd14665
Catalytic domain of the Serine/Threonine Kinases, Sucrose nonfermenting 1-related protein ...
1009-1157 6.99e-09

Catalytic domain of the Serine/Threonine Kinases, Sucrose nonfermenting 1-related protein kinase subfamily 2, group 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The SnRKs form three different subfamilies designated SnRK1-3. SnRK2 is represented in this cd. SnRK2s are involved in plant response to abiotic stresses and abscisic acid (ABA)-dependent plant development. The SnRK2s subfamily is in turn classed into three subgroups, all 3 of which are represented in this CD. Group 1 comprises kinases not activated by ABA, group 2 - kinases not activated or activated very weakly by ABA (depending on plant species), and group 3 - kinases strongly activated by ABA. The SnRKs belong to a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271135 [Multi-domain]  Cd Length: 257  Bit Score: 58.46  E-value: 6.99e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1009 QVAKGMEFLASRKCIHRDLAARNILL--SEKNVVKICDFGLARD--IYKDPdyvrKGDARLPlKWMAPETIFDRVYTIQ- 1083
Cdd:cd14665  104 QLISGVSYCHSMQICHRDLKLENTLLdgSPAPRLKICDFGYSKSsvLHSQP----KSTVGTP-AYIAPEVLLKKEYDGKi 178
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1084 SDVWSFGVLLWeIFSLGASPYPGVKIDEEFCRRLKegtRMRAPDYTTPEMYQTMLDCWH-------EDPNQRPSFSELVE 1156
Cdd:cd14665  179 ADVWSCGVTLY-VMLVGAYPFEDPEEPRNFRKTIQ---RILSVQYSIPDYVHISPECRHlisrifvADPATRITIPEIRN 254

                 .
gi 27777648 1157 H 1157
Cdd:cd14665  255 H 255
STKc_IKK_alpha cd14039
Catalytic domain of the Serine/Threonine kinase, Inhibitor of Nuclear Factor-KappaB Kinase ...
1010-1095 7.18e-09

Catalytic domain of the Serine/Threonine kinase, Inhibitor of Nuclear Factor-KappaB Kinase (IKK) alpha; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. IKKalpha is involved in the non-canonical or alternative pathway of regulating Nuclear Factor-KappaB (NF-kB) proteins, a family of transcription factors which are critical in many cellular functions including inflammatory responses, immune development, cell survival, and cell proliferation, among others. The non-canonical pathway functions in cells lacking NEMO (NF-kB Essential MOdulator) and IKKbeta. It is induced by a subset of TNFR family members including CD40, RANK, and B cell-activating factor receptor. IKKalpha processes the Inhibitor of NF-kB (IkB)-like C-terminus of NF-kB2/p100 to produce p52, allowing the p52/RelB dimer to migrate to the nucleus. This pathway is dependent on NIK (NF-kB Inducing Kinase) which phosphorylates and activates IKKalpha. The IKKalpha subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270941 [Multi-domain]  Cd Length: 289  Bit Score: 58.78  E-value: 7.18e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1010 VAKGMEFLASRKCIHRDLAARNILLSEKN---VVKICDFGLARDIYKDP---DYVRKgdarlpLKWMAPETIFDRVYTIQ 1083
Cdd:cd14039  108 IGSGIQYLHENKIIHRDLKPENIVLQEINgkiVHKIIDLGYAKDLDQGSlctSFVGT------LQYLAPELFENKSYTVT 181
                         90
                 ....*....|..
gi 27777648 1084 SDVWSFGVLLWE 1095
Cdd:cd14039  182 VDYWSFGTMVFE 193
Ig3_Peroxidasin cd05745
Third immunoglobulin (Ig)-like domain of peroxidasin; The members here are composed of the ...
679-752 7.43e-09

Third immunoglobulin (Ig)-like domain of peroxidasin; The members here are composed of the third immunoglobulin (Ig)-like domain in peroxidasin. Peroxidasin has a peroxidase domain and interacting extracellular motifs containing four Ig-like domains. It has been suggested that peroxidasin is secreted and has functions related to the stabilization of the extracellular matrix. It may play a part in various other important processes such as removal and destruction of cells which have undergone programmed cell death and protection of the organism against non-self.


Pssm-ID: 143222 [Multi-domain]  Cd Length: 74  Bit Score: 53.79  E-value: 7.43e-09
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 27777648  679 GETIEVTCPASGNPTPHITWFKDNETL-VEDSGIVLRDGnrNLTIRRVRKEDGGLYTCQACNVLGCARAETLFII 752
Cdd:cd05745    2 GQTVDFLCEAQGYPQPVIAWTKGGSQLsVDRRHLVLSSG--TLRISRVALHDQGQYECQAVNIVGSQRTVAQLTV 74
STKc_YPK1_like cd05585
Catalytic domain of Yeast Protein Kinase 1-like Serine/Threonine Kinases; STKs catalyze the ...
1006-1148 7.43e-09

Catalytic domain of Yeast Protein Kinase 1-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of fungal proteins with similarity to the AGC STKs, Saccharomyces cerevisiae YPK1 and Schizosaccharomyces pombe Gad8p. YPK1 is required for cell growth and acts as a downstream kinase in the sphingolipid-mediated signaling pathway of yeast. It also plays a role in efficient endocytosis and in the maintenance of cell wall integrity. Gad8p is a downstream target of Tor1p, the fission yeast homolog of mTOR. It plays a role in cell growth and sexual development. The YPK1-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270737 [Multi-domain]  Cd Length: 313  Bit Score: 58.74  E-value: 7.43e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1006 YSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIYKDPDyvRKGDARLPLKWMAPETIFDRVYTIQSD 1085
Cdd:cd05585   99 YTAELLCALECLHKFNVIYRDLKPENILLDYTGHIALCDFGLCKLNMKDDD--KTNTFCGTPEYLAPELLLGHGYTKAVD 176
                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 27777648 1086 VWSFGVLLWEIFSlGASPYPGVKIDEEFCRRLKEgtRMRAPDYTTPEMYQTMLDCWHEDPNQR 1148
Cdd:cd05585  177 WWTLGVLLYEMLT-GLPPFYDENTNEMYRKILQE--PLRFPDGFDRDAKDLLIGLLNRDPTKR 236
STKc_MEKK3 cd06651
Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein (MAP)/Extracellular ...
1006-1157 7.96e-09

Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase Kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MEKK3 is a MAPK kinase kinase (MAPKKK or MKKK), that phosphorylates and activates the MAPK kinase MEK5 (or MKK5), which in turn phosphorylates and activates ERK5. The ERK5 cascade plays roles in promoting cell proliferation, differentiation, neuronal survival, and neuroprotection. MEKK3 plays an essential role in embryonic angiogenesis and early heart development. In addition, MEKK3 is involved in interleukin-1 receptor and Toll-like receptor 4 signaling. It is also a specific regulator of the proinflammatory cytokines IL-6 and GM-CSF in some immune cells. MEKK3 also regulates calcineurin, which plays a critical role in T cell activation, apoptosis, skeletal myocyte differentiation, and cardiac hypertrophy. The MEKK3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270817 [Multi-domain]  Cd Length: 271  Bit Score: 58.17  E-value: 7.96e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1006 YSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIYKdpdYVRKGDARLPLK----WMAPETIFDRVYT 1081
Cdd:cd06651  116 YTRQILEGMSYLHSNMIVHRDIKGANILRDSAGNVKLGDFGASKRLQT---ICMSGTGIRSVTgtpyWMSPEVISGEGYG 192
                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 27777648 1082 IQSDVWSFGVLLWEIFSlGASPYPGVKIDEEFCRRLKEGTRMRAPDYTTpEMYQTMLDCWHEDPNQRPSFSELVEH 1157
Cdd:cd06651  193 RKADVWSLGCTVVEMLT-EKPPWAEYEAMAAIFKIATQPTNPQLPSHIS-EHARDFLGCIFVEARHRPSAEELLRH 266
STKc_TSSK1_2-like cd14165
Catalytic domain of testis-specific serine/threonine kinase 1, TSSK2, and similar proteins; ...
1005-1157 8.23e-09

Catalytic domain of testis-specific serine/threonine kinase 1, TSSK2, and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TSSK proteins are almost exclusively expressed postmeiotically in the testis and play important roles in spermatogenesis and/or spermiogenesis. There are five mammalian TSSK proteins which show differences in their localization and timing of expression. TSSK1 and TSSK2 are expressed specifically in meiotic and postmeiotic spermatogenic cells, respectively. TSSK2 is localized in the sperm neck, equatorial segment, and mid-piece of the sperm tail. Both TSSK1 and TSSK2 phosphorylate their common substrate TSKS (testis-specific-kinase-substrate). TSSK1/TSSK2 double knock-out mice are sterile without manifesting other defects, making these kinases viable targets for male contraception. The TSSK1/2-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271067 [Multi-domain]  Cd Length: 263  Bit Score: 58.25  E-value: 8.23e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1005 CYSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIykdpdyVRKGDARLPLK--------WMAPETIF 1076
Cdd:cd14165  106 KMFHQLSSAIKYCHELDIVHRDLKCENLLLDKDFNIKLTDFGFSKRC------LRDENGRIVLSktfcgsaaYAAPEVLQ 179
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1077 DRVYTIQ-SDVWSFGVLLWeIFSLGASPYPGVKIDEEFcrRLKEGTRMRAPD--YTTPEMYQTMLDCWHEDPNQRPSFSE 1153
Cdd:cd14165  180 GIPYDPRiYDIWSLGVILY-IMVCGSMPYDDSNVKKML--KIQKEHRVRFPRskNLTSECKDLIYRLLQPDVSQRLCIDE 256

                 ....
gi 27777648 1154 LVEH 1157
Cdd:cd14165  257 VLSH 260
STKc_CDK1_CdkB_like cd07835
Catalytic domain of Cyclin-Dependent protein Kinase 1-like Serine/Threonine Kinases and of ...
1006-1113 8.55e-09

Catalytic domain of Cyclin-Dependent protein Kinase 1-like Serine/Threonine Kinases and of Plant B-type Cyclin-Dependent protein Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of CDK, CDK2, and CDK3. CDK1 is also called Cell division control protein 2 (Cdc2) or p34 protein kinase, and is regulated by cyclins A, B, and E. The CDK1/cyclin A complex controls G2 phase entry and progression while the CDK1/cyclin B complex is critical for G2 to M phase transition. CDK2 is regulated by cyclin E or cyclin A. Upon activation by cyclin E, it phosphorylates the retinoblastoma (pRb) protein which activates E2F mediated transcription and allows cells to move into S phase. The CDK2/cyclin A complex plays a role in regulating DNA replication. Studies in knockout mice revealed that CDK1 can compensate for the loss of the cdk2 gene as it can also bind cyclin E and drive G1 to S phase transition. CDK3 is regulated by cyclin C and it phosphorylates pRB specifically during the G0/G1 transition. This phosphorylation is required for cells to exit G0 efficiently and enter the G1 phase. The plant-specific B-type CDKs are expressed from the late S to the M phase of the cell cycle. They are characterized by the cyclin binding motif PPT[A/T]LRE. They play a role in controlling mitosis and integrating developmental pathways, such as stomata and leaf development. CdkB has been shown to associate with both cyclin B, which controls G2/M transition, and cyclin D, which acts as a mediator in linking extracellular signals to the cell cycle. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270829 [Multi-domain]  Cd Length: 283  Bit Score: 58.46  E-value: 8.55e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1006 YSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIykdpdyvrkgdaRLPLK---------WM-APETI 1075
Cdd:cd07835  104 YLYQLLQGIAFCHSHRVLHRDLKPQNLLIDTEGALKLADFGLARAF------------GVPVRtythevvtlWYrAPEIL 171
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|
gi 27777648 1076 F-DRVYTIQSDVWSFGVLLWEIfSLGASPYPG-VKIDEEF 1113
Cdd:cd07835  172 LgSKHYSTPVDIWSVGCIFAEM-VTRRPLFPGdSEIDQLF 210
STKc_IKK cd13989
Catalytic domain of the Serine/Threonine kinase, Inhibitor of Nuclear Factor-KappaB Kinase ...
1010-1116 8.79e-09

Catalytic domain of the Serine/Threonine kinase, Inhibitor of Nuclear Factor-KappaB Kinase (IKK); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The IKK complex functions as a master regulator of Nuclear Factor-KappaB (NF-kB) proteins, a family of transcription factors which are critical in many cellular functions including inflammatory responses, immune development, cell survival, and cell proliferation, among others. It is composed of two kinases, IKKalpha and IKKbeta, and the regulatory subunit IKKgamma or NEMO (NF-kB Essential MOdulator). IKKs facilitate the release of NF-kB dimers from an inactive state, allowing them to migrate to the nucleus where they regulate gene transcription. There are two IKK pathways that regulate NF-kB signaling, called the classical (involving IKKbeta and NEMO) and non-canonical (involving IKKalpha) pathways. The classical pathway regulates the majority of genes activated by NF-kB. The IKK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase (PI3K).


Pssm-ID: 270891 [Multi-domain]  Cd Length: 289  Bit Score: 58.23  E-value: 8.79e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1010 VAKGMEFLASRKCIHRDLAARNILLSEKN---VVKICDFGLARDIYKDP---DYVRKgdarlpLKWMAPETIFDRVYTIQ 1083
Cdd:cd13989  111 ISSAISYLHENRIIHRDLKPENIVLQQGGgrvIYKLIDLGYAKELDQGSlctSFVGT------LQYLAPELFESKKYTCT 184
                         90       100       110
                 ....*....|....*....|....*....|....*..
gi 27777648 1084 SDVWSFGVLLWEIFSlGASP----YPGVKIDEEFCRR 1116
Cdd:cd13989  185 VDYWSFGTLAFECIT-GYRPflpnWQPVQWHGKVKQK 220
STKc_CDK12 cd07864
Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 12; STKs ...
1001-1098 9.42e-09

Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 12; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK12 is also called Cdc2-related protein kinase 7 (CRK7) or Cdc2-related kinase arginine/serine-rich (CrkRS). It is a unique CDK that contains an RS domain, which is predominantly found in splicing factors. CDK12 is widely expressed in tissues. It interacts with cyclins L1 and L2, and plays roles in regulating transcription and alternative splicing. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK12 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270847 [Multi-domain]  Cd Length: 302  Bit Score: 58.28  E-value: 9.42e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1001 EHLICYSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARdIYKDPDYVRKGDARLPLKWMAPETIF-DRV 1079
Cdd:cd07864  116 DHIKSFMKQLLEGLNYCHKKNFLHRDIKCSNILLNNKGQIKLADFGLAR-LYNSEESRPYTNKVITLWYRPPELLLgEER 194
                         90
                 ....*....|....*....
gi 27777648 1080 YTIQSDVWSFGVLLWEIFS 1098
Cdd:cd07864  195 YGPAIDVWSCGCILGELFT 213
STKc_nPKC_eta cd05590
Catalytic domain of the Serine/Threonine Kinase, Novel Protein Kinase C eta; STKs catalyze the ...
1006-1113 9.53e-09

Catalytic domain of the Serine/Threonine Kinase, Novel Protein Kinase C eta; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKC-eta is predominantly expressed in squamous epithelia, where it plays a crucial role in the signaling of cell-type specific differentiation. It is also expressed in pro-B cells and early-stage thymocytes, and acts as a key regulator in early B-cell development. PKC-eta increases glioblastoma multiforme (GBM) proliferation and resistance to radiation, and is being developed as a therapeutic target for the management of GBM. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. nPKCs are calcium-independent, but require DAG (1,2-diacylglycerol) and phosphatidylserine (PS) for activity. The nPKC-eta subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270742 [Multi-domain]  Cd Length: 323  Bit Score: 58.77  E-value: 9.53e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1006 YSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIYKD----------PDYVrkgdarlplkwmAPETI 1075
Cdd:cd05590  101 YAAEITSALMFLHDKGIIYRDLKLDNVLLDHEGHCKLADFGMCKEGIFNgkttstfcgtPDYI------------APEIL 168
                         90       100       110
                 ....*....|....*....|....*....|....*...
gi 27777648 1076 FDRVYTIQSDVWSFGVLLWEIFSlGASPYPGVKIDEEF 1113
Cdd:cd05590  169 QEMLYGPSVDWWAMGVLLYEMLC-GHAPFEAENEDDLF 205
STKc_obscurin_rpt1 cd14107
Catalytic kinase domain, first repeat, of the Giant Serine/Threonine Kinase Obscurin; STKs ...
932-1157 1.05e-08

Catalytic kinase domain, first repeat, of the Giant Serine/Threonine Kinase Obscurin; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Obscurin, approximately 800 kDa in size, is one of three giant proteins expressed in vetebrate striated muscle, together with titin and nebulin. It is a multidomain protein composed of tandem adhesion and signaling domains, including 49 immunoglobulin (Ig) and 2 fibronectin type III (FN3) domains at the N-terminus followed by a more complex region containing more Ig domains, a conserved SH3 domain near a RhoGEF and PH domains, non-modular regions, as well as IQ and phosphorylation motifs. The obscurin gene also encode two kinase domains, which are not expressed as part of the 800 kDa protein, but as a smaller, alternatively spliced product present mainly in the heart muscle, also called obscurin-MLCK. Obscurin is localized at the peripheries of Z-disks and M-lines, where it is able to communicate with the surrounding myoplasm. It interacts with diverse proteins including sAnk1, myosin, titin, and MyBP-C. It may act as a scaffold for the assembly of elements of the contractile apparatus. The obscurin subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271009 [Multi-domain]  Cd Length: 257  Bit Score: 57.59  E-value: 1.05e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  932 EFVPYKSKG-ARFRQGKDYVGELSVD-LKRRLDSitssqssassgFVEEKSLSDVEEEEASEELY-----KDFLTLEHLI 1004
Cdd:cd14107   33 KFIPLRSSTrARAFQERDILARLSHRrLTCLLDQ-----------FETRKTLILILELCSSEELLdrlflKGVVTEAEVK 101
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1005 CYSFQVAKGMEFLASRKCIHRDLAARNILL--SEKNVVKICDFGLARDIYK-DPDYVRKGDArlplKWMAPETIFDRVYT 1081
Cdd:cd14107  102 LYIQQVLEGIGYLHGMNILHLDIKPDNILMvsPTREDIKICDFGFAQEITPsEHQFSKYGSP----EFVAPEIVHQEPVS 177
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1082 IQSDVWSFGVLLWeiFSLG-ASPYPGvKIDEEFCRRLKEGTRmrapDYTTPEMYQTMLDC-------WHEDPNQRPSFSE 1153
Cdd:cd14107  178 AATDIWALGVIAY--LSLTcHSPFAG-ENDRATLLNVAEGVV----SWDTPEITHLSEDAkdfikrvLQPDPEKRPSASE 250

                 ....
gi 27777648 1154 LVEH 1157
Cdd:cd14107  251 CLSH 254
IG_like smart00410
Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.
233-326 1.09e-08

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.


Pssm-ID: 214653 [Multi-domain]  Cd Length: 85  Bit Score: 53.66  E-value: 1.09e-08
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648     233 PHEIELSAGEKLVLNCTARTELNVglDFTWH----SPPSKSHHKKIVNRDvkpfpgtvakmFLSTLTIESVTKSDQGEYT 308
Cdd:smart00410    1 PPSVTVKEGESVTLSCEASGSPPP--EVTWYkqggKLLAESGRFSVSRSG-----------STSTLTISNVTPEDSGTYT 67
                            90
                    ....*....|....*...
gi 27777648     309 CVASSGRMIKRNRTFVRV 326
Cdd:smart00410   68 CAATNSSGSASSGTTLTV 85
STKc_PCTAIRE_like cd07844
Catalytic domain of PCTAIRE-like Serine/Threonine Kinases; STKs catalyze the transfer of the ...
1005-1112 1.16e-08

Catalytic domain of PCTAIRE-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PCTAIRE-like proteins show unusual expression patterns with high levels in post-mitotic tissues, suggesting that they may be involved in regulating post-mitotic cellular events. They share sequence similarity with Cyclin-Dependent Kinases (CDKs), which belong to a large family of STKs that are regulated by their cognate cyclins. Together, CDKs and cyclins are involved in the control of cell-cycle progression, transcription, and neuronal function. The association of PCTAIRE-like proteins with cyclins has not been widely studied, although PFTAIRE-1 has been shown to function as a CDK which is regulated by cyclin D3 as well as the membrane-associated cyclin Y. The PCTAIRE-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270835 [Multi-domain]  Cd Length: 286  Bit Score: 58.16  E-value: 1.16e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1005 CYSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARdiykdpdyvrkgdAR-LPLK---------WMAPET 1074
Cdd:cd07844  102 LFLFQLLRGLAYCHQRRVLHRDLKPQNLLISERGELKLADFGLAR-------------AKsVPSKtysnevvtlWYRPPD 168
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|
gi 27777648 1075 IF--DRVYTIQSDVWSFGVLLWEIFSlGASPYPGVKIDEE 1112
Cdd:cd07844  169 VLlgSTEYSTSLDMWGVGCIFYEMAT-GRPLFPGSTDVED 207
STKc_EIF2AK1_HRI cd14049
Catalytic domain of the Serine/Threonine kinase, eukaryotic translation Initiation Factor ...
996-1156 1.19e-08

Catalytic domain of the Serine/Threonine kinase, eukaryotic translation Initiation Factor 2-Alpha Kinase 2 or Heme-Regulated Inhibitor kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. HRI (or EIF2AK1) contains an N-terminal regulatory heme-binding domain and a C-terminal catalytic kinase domain. It is suppressed under normal conditions by binding of the heme iron, and is activated during heme deficiency. It functions as a critical regulator that ensures balanced synthesis of globins and heme, in order to form stable hemoglobin during erythroid differentiation and maturation. HRI also protects cells and enhances survival under iron-deficient conditions. EIF2AKs phosphorylate the alpha subunit of eIF-2, resulting in the downregulation of protein synthesis. The HRI subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270951 [Multi-domain]  Cd Length: 284  Bit Score: 57.90  E-value: 1.19e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  996 DFLTLEHLICYSFQVAKGMEFLASRKCIHRDLAARNILLSEKNV-VKICDFGLA--RDIYKDPDYVRKGDARLPLK---- 1068
Cdd:cd14049  115 TPVDVDVTTKILQQLLEGVTYIHSMGIVHRDLKPRNIFLHGSDIhVRIGDFGLAcpDILQDGNDSTTMSRLNGLTHtsgv 194
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1069 ----WMAPETIFDRVYTIQSDVWSFGVLLWEIFslgaSPYpGVKIDE-EFCRRLKEGTRMRAPDYTTPEMYQTMLDCWHE 1143
Cdd:cd14049  195 gtclYAAPEQLEGSHYDFKSDMYSIGVILLELF----QPF-GTEMERaEVLTQLRNGQIPKSLCKRWPVQAKYIKLLTST 269
                        170
                 ....*....|...
gi 27777648 1144 DPNQRPSFSELVE 1156
Cdd:cd14049  270 EPSERPSASQLLE 282
STKc_EIF2AK4_GCN2_rpt2 cd14046
Catalytic domain, repeat 2, of the Serine/Threonine kinase, eukaryotic translation Initiation ...
1009-1157 1.19e-08

Catalytic domain, repeat 2, of the Serine/Threonine kinase, eukaryotic translation Initiation Factor 2-Alpha Kinase 4 or General Control Non-derepressible-2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. GCN2 (or EIF2AK4) is activated by amino acid or serum starvation and UV irradiation. It induces GCN4, a transcriptional activator of amino acid biosynthetic genes, leading to increased production of amino acids under amino acid-deficient conditions. In serum-starved cells, GCN2 activation induces translation of the stress-responsive transcription factor ATF4, while under UV stress, GCN2 triggers transcriptional rescue via NF-kB signaling. GCN2 contains an N-terminal RWD, a degenerate kinase-like (repeat 1), the catalytic kinase (repeat 2), a histidyl-tRNA synthetase (HisRS)-like, and a C-terminal ribosome-binding and dimerization (RB/DD) domains. Its kinase domain is activated via conformational changes as a result of the binding of uncharged tRNA to the HisRS-like domain. EIF2AKs phosphorylate the alpha subunit of eIF-2, resulting in the overall downregulation of protein synthesis. The GCN2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270948 [Multi-domain]  Cd Length: 278  Bit Score: 57.76  E-value: 1.19e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1009 QVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARD----IYKDPDYVRKGDARLPLK------------WMAP 1072
Cdd:cd14046  112 QILEGLAYIHSQGIIHRDLKPVNIFLDSNGNVKIGDFGLATSnklnVELATQDINKSTSAALGSsgdltgnvgtalYVAP 191
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1073 ETI--FDRVYTIQSDVWSFGVLLWE-----------IFSLGASPYPGVKIDEEFCRRLKEgtrmrapdyTTPEMYQTMLD 1139
Cdd:cd14046  192 EVQsgTKSTYNEKVDMYSLGIIFFEmcypfstgmerVQILTALRSVSIEFPPDFDDNKHS---------KQAKLIRWLLN 262
                        170
                 ....*....|....*...
gi 27777648 1140 cwhEDPNQRPSFSELVEH 1157
Cdd:cd14046  263 ---HDPAKRPSAQELLKS 277
PK_Unc-89_rpt1 cd14109
Pseudokinase domain, first repeat, of the Giant Serine/Threonine Kinase Uncoordinated protein ...
995-1120 1.25e-08

Pseudokinase domain, first repeat, of the Giant Serine/Threonine Kinase Uncoordinated protein 89; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. The nematode Unc-89 gene, through alternative promoter use and splicing, encodes at least six major isoforms (Unc-89A to Unc-89F) of giant muscle proteins that are homologs for the vetebrate obscurin. In flies, five isoforms of Unc-89 have been detected: four in the muscles of adult flies (two in the indirect flight muscle and two in other muscles) and another isoform in the larva. Unc-89 in nematodes is required for normal muscle cell architecture. In flies, it is necessary for the development of a symmetrical sarcomere in the flight muscles. Unc-89 proteins contain several adhesion and signaling domains including multiple copies of the immunoglobulin (Ig) domain, as well as fibronectin type III (FN3), SH3, RhoGEF, and PH domains. The nematode Unc-89 isoforms D, C, D, and F contain two kinase domain with B and F having two complete kinase domains while the first repeat of C and D are partial domains. Homology modeling suggests that the first kinase repeat of Unc-89 may be catalytically inactive, a pseudokinase, while the second kinase repeat may be active. The pseudokinase domain may function as a regulatory domain or a protein interaction domain. The Unc-89 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271011 [Multi-domain]  Cd Length: 255  Bit Score: 57.52  E-value: 1.25e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  995 KDFLTLEHLICYSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVvKICDFGLARDIYKDPDYVRkgDARLPlKWMAPET 1074
Cdd:cd14109   93 KDYYTERQVAVFVRQLLLALKHMHDLGIAHLDLRPEDILLQDDKL-KLADFGQSRRLLRGKLTTL--IYGSP-EFVSPEI 168
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*.
gi 27777648 1075 IFDRVYTIQSDVWSFGVLLWEIFSlGASPYPGVKiDEEFCRRLKEG 1120
Cdd:cd14109  169 VNSYPVTLATDMWSVGVLTYVLLG-GISPFLGDN-DRETLTNVRSG 212
PTZ00263 PTZ00263
protein kinase A catalytic subunit; Provisional
1006-1104 1.49e-08

protein kinase A catalytic subunit; Provisional


Pssm-ID: 140289 [Multi-domain]  Cd Length: 329  Bit Score: 57.91  E-value: 1.49e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  1006 YSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIyKDPDYVRKGDArlplKWMAPETIFDRVYTIQSD 1085
Cdd:PTZ00263  123 YHAELVLAFEYLHSKDIIYRDLKPENLLLDNKGHVKVTDFGFAKKV-PDRTFTLCGTP----EYLAPEVIQSKGHGKAVD 197
                          90
                  ....*....|....*....
gi 27777648  1086 VWSFGVLLWEiFSLGASPY 1104
Cdd:PTZ00263  198 WWTMGVLLYE-FIAGYPPF 215
Ig3_L1-CAM cd05876
Third immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM); The members here ...
674-745 1.63e-08

Third immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM); The members here are composed of the third immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM). L1 belongs to the L1 subfamily of cell adhesion molecules (CAMs) and is comprised of an extracellular region having six Ig-like domains, five fibronectin type III domains, a transmembrane region and an intracellular domain. L1 is primarily expressed in the nervous system and is involved in its development and function. L1 is associated with an X-linked recessive disorder, X-linked hydrocephalus, MASA syndrome, or spastic paraplegia type 1, that involves abnormalities of axonal growth. This group also contains the chicken neuron-glia cell adhesion molecule, Ng-CAM.


Pssm-ID: 409460 [Multi-domain]  Cd Length: 83  Bit Score: 52.99  E-value: 1.63e-08
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 27777648  674 QTTTI---GETIEVTCPASGNPTPHITWFKDNETLVEDSGIVLrDGNRNLTIRRVRKEDGGLYTCQACNVLGCAR 745
Cdd:cd05876    2 SSSLValrGQSLVLECIAEGLPTPTVKWLRPSGPLPPDRVKYQ-NHNKTLQLLNVGESDDGEYVCLAENSLGSAR 75
STKc_Nek3 cd08219
Catalytic domain of the Protein Serine/Threonine Kinase, Never In Mitosis gene A (NIMA) ...
1003-1155 1.78e-08

Catalytic domain of the Protein Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Nek3 is primarily localized in the cytoplasm and shows no cell cycle-dependent changes in its activity. It is present in the axons of neurons and affects morphogenesis and polarity through its regulation of microtubule acetylation. Nek3 modulates the signaling of the prolactin receptor through its activation of Vav2 and contributes to prolactin-mediated motility of breast cancer cells. It is one in a family of 11 different Neks (Nek1-11) that are involved in cell cycle control. The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173759 [Multi-domain]  Cd Length: 255  Bit Score: 56.91  E-value: 1.78e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1003 LICYSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARdIYKDPDYVRKGDARLPLkWMAPETIFDRVYTI 1082
Cdd:cd08219  102 ILQWFVQMCLGVQHIHEKRVLHRDIKSKNIFLTQNGKVKLGDFGSAR-LLTSPGAYACTYVGTPY-YVPPEIWENMPYNN 179
                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 27777648 1083 QSDVWSFGVLLWEIFSLgASPYPGVKIdEEFCRRLKEGTRMRAPDYTTPEMYQTMLDCWHEDPNQRPSFSELV 1155
Cdd:cd08219  180 KSDIWSLGCILYELCTL-KHPFQANSW-KNLILKVCQGSYKPLPSHYSYELRSLIKQMFKRNPRSRPSATTIL 250
PHA03209 PHA03209
serine/threonine kinase US3; Provisional
998-1112 1.79e-08

serine/threonine kinase US3; Provisional


Pssm-ID: 177557 [Multi-domain]  Cd Length: 357  Bit Score: 57.96  E-value: 1.79e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648   998 LTLEHLICYSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIYKDPDYVrkGDARlPLKWMAPETIFD 1077
Cdd:PHA03209  154 LPIDQALIIEKQILEGLRYLHAQRIIHRDVKTENIFINDVDQVCIGDLGAAQFPVVAPAFL--GLAG-TVETNAPEVLAR 230
                          90       100       110
                  ....*....|....*....|....*....|....*
gi 27777648  1078 RVYTIQSDVWSFGVLLWEIFSlgaspYPGVKIDEE 1112
Cdd:PHA03209  231 DKYNSKADIWSAGIVLFEMLA-----YPSTIFEDP 260
Ig4_L1-NrCAM_like cd04978
Fourth immunoglobulin (Ig)-like domain of L1, Ng-CAM (Neuron-glia CAM cell adhesion molecule), ...
673-746 1.81e-08

Fourth immunoglobulin (Ig)-like domain of L1, Ng-CAM (Neuron-glia CAM cell adhesion molecule), and NrCAM (Ng-CAM-related); The members here are composed of the fourth immunoglobulin (Ig)-like domain of L1, Ng-CAM (Neuron-glia CAM cell adhesion molecule), and NrCAM (Ng-CAM-related). These proteins belong to the L1 subfamily of cell adhesion molecules (CAMs) and are comprised of an extracellular region having six Ig-like domains and five fibronectin type III domains, a transmembrane region and an intracellular domain. These molecules are primarily expressed in the nervous system. L1 is associated with an X-linked recessive disorder, X-linked hydrocephalus, MASA syndrome, or spastic paraplegia type 1, that involves abnormalities of axonal growth.


Pssm-ID: 409367 [Multi-domain]  Cd Length: 89  Bit Score: 52.84  E-value: 1.81e-08
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 27777648  673 NQTTTIGETIEVTCPASGNPTPHITWfKDNETLVEDSG--IVLRDGNRNLTIRRVRKEDGGLYTCQACNVLGCARA 746
Cdd:cd04978    8 SLVLSPGETGELICEAEGNPQPTITW-RLNGVPIEPAPedMRRTVDGRTLIFSNLQPNDTAVYQCNASNVHGYLLA 82
STKc_Mnk cd14090
Catalytic domain of the Serine/Threonine kinases, Mitogen-activated protein kinase ...
835-1106 1.91e-08

Catalytic domain of the Serine/Threonine kinases, Mitogen-activated protein kinase signal-integrating kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAPK signal-integrating kinases (Mnks) are MAPK-activated protein kinases and is comprised by a group of four proteins, produced by alternative splicing from two genes (Mnk1 and Mnk2). The isoforms of Mnk1 (1a/1b) and Mnk2 (2a/2b) differ at their C-termini, with the a-form having a longer C-terminus containing a MAPK-binding region. All Mnks contain a catalytic kinase domain and a polybasic region at the N-terminus which binds importin and the eukaryotic initiation factor eIF4G. The best characterized Mnk substrate is eIF4G, whose phosphorylation may promote the export of certain mRNAs from the nucleus. Mnk also phosphorylate substrates that bind to AU-rich elements that regulate mRNA stability and translation. Mnks have also been implicated in tyrosine kinase receptor signaling, inflammation, and cell prolieration or survival. The Mnk subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270992 [Multi-domain]  Cd Length: 289  Bit Score: 57.42  E-value: 1.91e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  835 GKPLGRGAFGQVieadaFGIDKTATCKTVAVKMLKEGATHSEHRaLMSELKILIHIGHHLNVVNLlgactkpggplmviV 914
Cdd:cd14090    7 GELLGEGAYASV-----QTCINLYTGKEYAVKIIEKHPGHSRSR-VFREVETLHQCQGHPNILQL--------------I 66
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  915 EFCKfGNLSTYLrgkrnefVPYKSKGarfrqgkdyvGELSVDLKRRldsitssqssassGFVEEKSLSDVEeeeaseely 994
Cdd:cd14090   67 EYFE-DDERFYL-------VFEKMRG----------GPLLSHIEKR-------------VHFTEQEASLVV--------- 106
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  995 KDfltlehlicysfqVAKGMEFLASRKCIHRDLAARNILLSEKNV---VKICDFGLARDIYKDPDY---VRKGDARLPL- 1067
Cdd:cd14090  107 RD-------------IASALDFLHDKGIAHRDLKPENILCESMDKvspVKICDFDLGSGIKLSSTSmtpVTTPELLTPVg 173
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|....*.
gi 27777648 1068 --KWMAPETI--F---DRVYTIQSDVWSFGVLLWeIFSLGASPYPG 1106
Cdd:cd14090  174 saEYMAPEVVdaFvgeALSYDKRCDLWSLGVILY-IMLCGYPPFYG 218
IgI_1_MuSK cd20970
agrin-responsive first immunoglobulin-like domains (Ig1) of the MuSK ectodomain; a member of ...
342-411 2.03e-08

agrin-responsive first immunoglobulin-like domains (Ig1) of the MuSK ectodomain; a member of the I-set of IgSF domains; The members here are composed of the first immunoglobulin-like domains (Ig1) of the Muscle-specific kinase (MuSK). MuSK is a receptor tyrosine kinase specifically expressed in skeletal muscle, where it plays a central role in the formation and maintenance of the neuromuscular junction (NMJ). MuSK is activated by agrin, a neuron-derived heparan sulfate proteoglycan. The activation of MUSK in myotubes regulates the formation of NMJs through the regulation of different processes including the specific expression of genes in subsynaptic nuclei, the reorganization of the actin cytoskeleton and the clustering of the acetylcholine receptors (AChR) in the postsynaptic membrane. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the MuSK lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409562 [Multi-domain]  Cd Length: 92  Bit Score: 52.90  E-value: 2.03e-08
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 27777648  342 VEATVGSQVRIPVKYLSYPAPDIKWYRNG-RPIESNYTMIV---GDELTIMEVTERDAGNYTVILTN--PISMEKQ 411
Cdd:cd20970   12 VTAREGENATFMCRAEGSPEPEISWTRNGnLIIEFNTRYIVrenGTTLTIRNIRRSDMGIYLCIASNgvPGSVEKR 87
STKc_NUAK2 cd14161
Catalytic domain of the Serine/Threonine Kinase, novel (nua) kinase family NUAK 2; STKs ...
1009-1106 2.07e-08

Catalytic domain of the Serine/Threonine Kinase, novel (nua) kinase family NUAK 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. NUAK proteins are classified as AMP-activated protein kinase (AMPK)-related kinases, which like AMPK are activated by the major tumor suppressor LKB1. Vertebrates contain two NUAK proteins, called NUAK1 and NUAK2. NUAK2, also called SNARK (Sucrose, non-fermenting 1/AMP-activated protein kinase-related kinase), is involved in energy metabolism. It is activated by hyperosmotic stress, DNA damage, and nutrients such as glucose and glutamine. NUAK2-knockout mice develop obesity, altered serum lipid profiles, hyperinsulinaemia, hyperglycaemia, and impaired glucose tolerance. NUAK2 is implicated in regulating actin stress fiber assembly through its association with myosin phosphatase Rho-interacting protein (MRIP), which leads to an increase in myosin regulatory light chain (MLC) phosphorylation. It is also associated with tumor growth, migration, and oncogenicity of melanoma cells. The NUAK2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271063 [Multi-domain]  Cd Length: 255  Bit Score: 56.89  E-value: 2.07e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1009 QVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLArDIYKDPDYVRKGDARlPLkWMAPETIFDRVYT-IQSDVW 1087
Cdd:cd14161  110 QIVSAVHYCHANGIVHRDLKLENILLDANGNIKIADFGLS-NLYNQDKFLQTYCGS-PL-YASPEIVNGRPYIgPEVDSW 186
                         90
                 ....*....|....*....
gi 27777648 1088 SFGVLLWeIFSLGASPYPG 1106
Cdd:cd14161  187 SLGVLLY-ILVHGTMPFDG 204
IgI_telokin-like cd20973
immunoglobulin-like domain of telokin and similar proteins; a member of the I-set of IgSF ...
671-744 2.34e-08

immunoglobulin-like domain of telokin and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin (Ig) domain in telokin, the C-terminal domain of myosin light chain kinase which is identical to telokin, and similar proteins. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the telokin Ig domain lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409565 [Multi-domain]  Cd Length: 88  Bit Score: 52.58  E-value: 2.34e-08
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 27777648  671 LENQTTTIGETIEVTCPASGNPTPHITWFKDNETLVEDSGIVL---RDGNRNLTIRRVRKEDGGLYTCQACNVLGCA 744
Cdd:cd20973    4 LRDKEVVEGSAARFDCKVEGYPDPEVKWMKDDNPIVESRRFQIdqdEDGLCSLIISDVCGDDSGKYTCKAVNSLGEA 80
IgI_4_Robo cd05726
Fourth immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of ...
672-755 2.38e-08

Fourth immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; Members here are composed the fourth immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, Robo3), and three mammalian Slit homologs (Slit-1, Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, and Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409391 [Multi-domain]  Cd Length: 98  Bit Score: 53.04  E-value: 2.38e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  672 ENQTTTIGETIEVTCPASGNPTPHITWFKD-NETLV------EDSGIVLRDGNRNLTIRRVRKEDGGLYTCQACNVLGCA 744
Cdd:cd05726    7 RDQVVALGRTVTFQCETKGNPQPAIFWQKEgSQNLLfpyqppQPSSRFSVSPTGDLTITNVQRSDVGYYICQALNVAGSI 86
                         90
                 ....*....|.
gi 27777648  745 RAETLFIIEGA 755
Cdd:cd05726   87 LAKAQLEVTDV 97
STKc_CDK1_euk cd07861
Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 1 from higher ...
953-1144 2.76e-08

Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 1 from higher eukaryotes; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK1 is also called Cell division control protein 2 (Cdc2) or p34 protein kinase, and is regulated by cyclins A, B, and E. The CDK1/cyclin A complex controls G2 phase entry and progression. CDK1/cyclin A2 has also been implicated as an important regulator of S phase events. The CDK1/cyclin B complex is critical for G2 to M phase transition. It induces mitosis by activating nuclear enzymes that regulate chromatin condensation, nuclear membrane degradation, mitosis-specific microtubule and cytoskeletal reorganization. CDK1 also associates with cyclin E and plays a role in the entry into S phase. CDK1 transcription is stable throughout the cell cycle but is modulated in some pathological conditions. It may play a role in regulating apoptosis under these conditions. In breast cancer cells, HER2 can mediate apoptosis by inactivating CDK1. Activation of CDK1 may contribute to HIV-1 induced apoptosis as well as neuronal apoptosis in neurodegenerative diseases. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270845 [Multi-domain]  Cd Length: 285  Bit Score: 56.66  E-value: 2.76e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  953 LSVDLKRRLDSITSSqssassgfveekslsdveeeeaseelykDFLTLEHLICYSFQVAKGMEFLASRKCIHRDLAARNI 1032
Cdd:cd07861   81 LSMDLKKYLDSLPKG----------------------------KYMDAELVKSYLYQILQGILFCHSRRVLHRDLKPQNL 132
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1033 LLSEKNVVKICDFGLARdIYKDPDYVRKGDArLPLKWMAPETIFDRV-YTIQSDVWSFGVLLWEIFSLGASPYPGVKIDE 1111
Cdd:cd07861  133 LIDNKGVIKLADFGLAR-AFGIPVRVYTHEV-VTLWYRAPEVLLGSPrYSTPVDIWSIGTIFAEMATKKPLFHGDSEIDQ 210
                        170       180       190
                 ....*....|....*....|....*....|....*
gi 27777648 1112 EF--CRRLKEGTRMRAPDYTTPEMYQTMLDCWHED 1144
Cdd:cd07861  211 LFriFRILGTPTEDIWPGVTSLPDYKNTFPKWKKG 245
PKc_MEK2 cd06649
Catalytic domain of the dual-specificity Protein Kinase, Mitogen-Activated Protein (MAP) ...
1007-1105 3.03e-08

Catalytic domain of the dual-specificity Protein Kinase, Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase 2; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. MEK2 is a dual-specificity PK and a MAPK kinase (MAPKK or MKK) that phosphorylates and activates the downstream targets, ERK1 and ERK2, on specific threonine and tyrosine residues. The ERK cascade starts with extracellular signals including growth factors, hormones, and neurotransmitters, which act through receptors and ion channels to initiate intracellular signaling that leads to the activation at the MAPKKK (Raf-1 or MOS) level, which leads to the transmission of signals to MEK2, and finally to ERK1/2. The ERK cascade plays an important role in cell proliferation, differentiation, oncogenic transformation, and cell cycle control, as well as in apoptosis and cell survival under certain conditions. Gain-of-function mutations in genes encoding ERK cascade proteins, including MEK2, cause cardiofaciocutaneous (CFC) syndrome, a condition leading to multiple congenital anomalies and mental retardation in patients. The MEK subfamily is part of a larger superfamily that includes the catalytic domains of other protein serine/threonine kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 132980 [Multi-domain]  Cd Length: 331  Bit Score: 56.98  E-value: 3.03e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1007 SFQVAKGMEFLASR-KCIHRDLAARNILLSEKNVVKICDFGLARDIYKDPDYVRKGDArlplKWMAPETIFDRVYTIQSD 1085
Cdd:cd06649  109 SIAVLRGLAYLREKhQIMHRDVKPSNILVNSRGEIKLCDFGVSGQLIDSMANSFVGTR----SYMSPERLQGTHYSVQSD 184
                         90       100
                 ....*....|....*....|
gi 27777648 1086 VWSFGVLLWEIfSLGASPYP 1105
Cdd:cd06649  185 IWSMGLSLVEL-AIGRYPIP 203
STKc_MLCK3 cd14192
Catalytic domain of the Serine/Threonine Kinase, Myosin Light Chain Kinase 3; STKs catalyze ...
998-1106 3.08e-08

Catalytic domain of the Serine/Threonine Kinase, Myosin Light Chain Kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MLCK3 (or MYLK3) phosphorylates myosin regulatory light chain 2 and controls the contraction of cardiac muscles. It is expressed specifically in both the atrium and ventricle of the heart and its expression is regulated by the cardiac protein Nkx2-5. MLCK3 plays an important role in cardiogenesis by regulating the assembly of cardiac sarcomeres, the repeating contractile unit of striated muscle. MLCK3 contains a single kinase domain near the C-terminus and a unique N-terminal half, and unlike MLCK1/2, it does not appear to be regulated by Ca2+/calmodulin. The MLCK3 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271094 [Multi-domain]  Cd Length: 261  Bit Score: 56.51  E-value: 3.08e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  998 LTLEHLICYSFQVAKGMEFLASRKCIHRDLAARNILL--SEKNVVKICDFGLARDiYKdPDYVRKGDARLPlKWMAPETI 1075
Cdd:cd14192   99 LTELDAILFTRQICEGVHYLHQHYILHLDLKPENILCvnSTGNQIKIIDFGLARR-YK-PREKLKVNFGTP-EFLAPEVV 175
                         90       100       110
                 ....*....|....*....|....*....|.
gi 27777648 1076 FDRVYTIQSDVWSFGVLLWEIFSlGASPYPG 1106
Cdd:cd14192  176 NYDFVSFPTDMWSVGVITYMLLS-GLSPFLG 205
pknD PRK13184
serine/threonine-protein kinase PknD;
995-1167 3.10e-08

serine/threonine-protein kinase PknD;


Pssm-ID: 183880 [Multi-domain]  Cd Length: 932  Bit Score: 58.24  E-value: 3.10e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648   995 KDFLTLEHLICysfqvaKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIYKDPDYVRKGDARLP-------- 1066
Cdd:PRK13184  113 GAFLSIFHKIC------ATIEYVHSKGVLHRDLKPDNILLGLFGEVVILDWGAAIFKKLEEEDLLDIDVDERnicyssmt 186
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  1067 --------LKWMAPETIFDRVYTIQSDVWSFGVLLWEIFSLgASPYpgvkideefcrRLKEGTRMRAPDYTT-------- 1130
Cdd:PRK13184  187 ipgkivgtPDYMAPERLLGVPASESTDIYALGVILYQMLTL-SFPY-----------RRKKGRKISYRDVILspievapy 254
                         170       180       190       200
                  ....*....|....*....|....*....|....*....|..
gi 27777648  1131 ----PEMYQTMLDCWHEDPNQR-PSFSELVEHLGNLLQANAQ 1167
Cdd:PRK13184  255 reipPFLSQIAMKALAVDPAERySSVQELKQDLEPHLQGSPE 296
STKc_Twitchin_like cd14114
The catalytic domain of the Giant Serine/Threonine Kinases, Twitchin and Projectin; STKs ...
998-1157 3.41e-08

The catalytic domain of the Giant Serine/Threonine Kinases, Twitchin and Projectin; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of Caenorhabditis elegans and Aplysia californica Twitchin, Drosophila melanogaster Projectin, and similar proteins. These are very large muscle proteins containing multiple immunoglobulin (Ig)-like and fibronectin type III (FN3) domains and a single kinase domain near the C-terminus. Twitchin and Projectin are both associated with thick filaments. Twitchin is localized in the outer parts of A-bands and is involved in regulating muscle contraction. It interacts with the myofibrillar proteins myosin and actin in a phosphorylation-dependent manner, and may be involved in regulating the myosin cross-bridge cycle. The kinase activity of Twitchen is activated by Ca2+ and the Ca2+ binding protein S100A1. Projectin is associated with the end of thick filaments and is a component of flight muscle connecting filaments. The kinase domain of Projectin may play roles in autophosphorylation and transphosphorylation, which impact the formation of myosin filaments. The Twitchin-like subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271016 [Multi-domain]  Cd Length: 259  Bit Score: 56.05  E-value: 3.41e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  998 LTLEHLICYSFQVAKGMEFLASRKCIHRDLAARNILLSEK--NVVKICDFGLARDIykDPDYVRK---GDArlplKWMAP 1072
Cdd:cd14114   97 MSEAEVINYMRQVCEGLCHMHENNIVHLDIKPENIMCTTKrsNEVKLIDFGLATHL--DPKESVKvttGTA----EFAAP 170
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1073 ETIFDRVYTIQSDVWSFGVLLWEIFSlGASPYPGvKIDEEFCRRLKE---GTRMRAPDYTTPEMYQTMLDCWHEDPNQRP 1149
Cdd:cd14114  171 EIVEREPVGFYTDMWAVGVLSYVLLS-GLSPFAG-ENDDETLRNVKScdwNFDDSAFSGISEEAKDFIRKLLLADPNKRM 248

                 ....*...
gi 27777648 1150 SFSELVEH 1157
Cdd:cd14114  249 TIHQALEH 256
STKc_MLCK1 cd14191
Catalytic domain of the Serine/Threonine Kinase, Myosin Light Chain Kinase 1; STKs catalyze ...
995-1106 3.58e-08

Catalytic domain of the Serine/Threonine Kinase, Myosin Light Chain Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MLCK1 (or MYLK1) phosphorylates myosin regulatory light chain and controls the contraction of smooth muscles. The MLCK1 gene expresses three transcripts in a cell-specific manner: a short MLCK1 which contains three immunoglobulin (Ig)-like and one fibronectin type III (FN3) domains, PEVK and actin-binding regions, and a kinase domain near the C-terminus followed by a regulatory segment containing an autoinhibitory Ca2+/calmodulin binding site; a long MLCK1 containing six additional Ig-like domains at the N-terminus compared to the short MLCK1; and the C-terminal Ig module which results in the expression of telokin in phasic smooth muscles, leading to Ca2+ desensitization by cyclic nucleotides of smooth muscle force. MLCK1 is also responsible for myosin regulatory light chain phosphorylation in nonmuscle cells and may play a role in regulating myosin II ATPase activity. The MLCK1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271093 [Multi-domain]  Cd Length: 259  Bit Score: 56.17  E-value: 3.58e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  995 KDF-LTLEHLICYSFQVAKGMEFLASRKCIHRDLAARNILLSEK--NVVKICDFGLARD---------IYKDPDYVrkgd 1062
Cdd:cd14191   93 EDFeLTERECIKYMRQISEGVEYIHKQGIVHLDLKPENIMCVNKtgTKIKLIDFGLARRlenagslkvLFGTPEFV---- 168
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....
gi 27777648 1063 arlplkwmAPETIFDRVYTIQSDVWSFGVLLWEIFSlGASPYPG 1106
Cdd:cd14191  169 --------APEVINYEPIGYATDMWSIGVICYILVS-GLSPFMG 203
STKc_Pho85 cd07836
Catalytic domain of the Serine/Threonine Kinase, Fungal Cyclin-Dependent protein Kinase Pho85; ...
1006-1106 3.74e-08

Catalytic domain of the Serine/Threonine Kinase, Fungal Cyclin-Dependent protein Kinase Pho85; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Pho85 is a multifunctional CDK in yeast. It is regulated by 10 different cyclins (Pcls) and plays a role in G1 progression, cell polarity, phosphate and glycogen metabolism, gene expression, and in signaling changes in the environment. It is not essential for yeast viability and is the functional homolog of mammalian CDK5, which plays a role in central nervous system development. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The Pho85 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 143341 [Multi-domain]  Cd Length: 284  Bit Score: 56.33  E-value: 3.74e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1006 YSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDiYKDPdyVRKGDARLPLKWM-APETIF-DRVYTIQ 1083
Cdd:cd07836  105 FTYQLLKGIAFCHENRVLHRDLKPQNLLINKRGELKLADFGLARA-FGIP--VNTFSNEVVTLWYrAPDVLLgSRTYSTS 181
                         90       100
                 ....*....|....*....|...
gi 27777648 1084 SDVWSFGVLLWEIFSlGASPYPG 1106
Cdd:cd07836  182 IDIWSVGCIMAEMIT-GRPLFPG 203
Ig4_PDGFR cd05859
Fourth immunoglobulin (Ig)-like domain of platelet-derived growth factor receptor (PDGFR); The ...
692-739 3.74e-08

Fourth immunoglobulin (Ig)-like domain of platelet-derived growth factor receptor (PDGFR); The members here are composed of the fourth immunoglobulin (Ig)-like domain of platelet-derived growth factor receptor (PDGFR; also known as cluster of differentiation (CD) 140a) alpha and beta. PDGF is a potent mitogen for connective tissue cells. PDGF-stimulated processes are mediated by three different PDGFs (PDGF-A,PDGF-B, and PDGF-C). PDGFR alpha binds to all three PDGFs, whereas the PDGFR beta binds only to PDGF-B. PDGF alpha is organized as an extracellular component having five Ig-like domains, a transmembrane segment, and a cytoplasmic portion having protein tyrosine kinase activity. In mice, PDGFR alpha and PDGFR beta are essential for normal development.


Pssm-ID: 409445  Cd Length: 101  Bit Score: 52.56  E-value: 3.74e-08
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 27777648  692 PTPHITWFKDNETLVEDSGIVLRDGNR--------NLTIRRVRKEDGGLYTCQACN 739
Cdd:cd05859   31 PPPQIRWLKDNRTLIENLTEITTSTRNvqetryvsKLKLIRAKEEDSGLYTALAQN 86
STKc_PKB_alpha cd05594
Catalytic domain of the Serine/Threonine Kinase, Protein Kinase B alpha (also called Akt1); ...
1006-1148 3.77e-08

Catalytic domain of the Serine/Threonine Kinase, Protein Kinase B alpha (also called Akt1); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKB-alpha is predominantly expressed in endothelial cells. It is critical for the regulation of angiogenesis and the maintenance of vascular integrity. It also plays a role in adipocyte differentiation. Mice deficient in PKB-alpha exhibit perinatal morbidity, growth retardation, reduction in body weight accompanied by reduced sizes of multiple organs, and enhanced apoptosis in some cell types. PKB-alpha activity has been reported to be frequently elevated in breast and prostate cancers. In some cancer cells, PKB-alpha may act as a suppressor of metastasis. PKB contains an N-terminal pleckstrin homology (PH) domain and a C-terminal catalytic domain. The PKB-alpha subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270746 [Multi-domain]  Cd Length: 356  Bit Score: 56.96  E-value: 3.77e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1006 YSFQVAKGMEFL-ASRKCIHRDLAARNILLSEKNVVKICDFGLARDIYKDpDYVRKGDARLPlKWMAPETIFDRVYTIQS 1084
Cdd:cd05594  130 YGAEIVSALDYLhSEKNVVYRDLKLENLMLDKDGHIKITDFGLCKEGIKD-GATMKTFCGTP-EYLAPEVLEDNDYGRAV 207
                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 27777648 1085 DVWSFGVLLWEIFSlGASPYPGVKIDEEFCRRLKEgtRMRAPDYTTPEMYQTMLDCWHEDPNQR 1148
Cdd:cd05594  208 DWWGLGVVMYEMMC-GRLPFYNQDHEKLFELILME--EIRFPRTLSPEAKSLLSGLLKKDPKQR 268
IgI_2_MuSK cd20968
agrin-responsive second immunoglobulin-like domains (Ig2) of the Muscle-specific kinase (MuSK) ...
673-744 3.78e-08

agrin-responsive second immunoglobulin-like domains (Ig2) of the Muscle-specific kinase (MuSK) ectodomain; a member of the I-set of Ig superfamily domains; The members here are composed of the second immunoglobulin-like (Ig) domains of the Muscle-specific kinase (MuSK) ectodomain. MuSK is a receptor tyrosine kinase specifically expressed in skeletal muscle, where it plays a central role in the formation and maintenance of the neuromuscular junction (NMJ). MuSK is activated by agrin, a neuron-derived heparan sulfate proteoglycan. The activation of MUSK in myotubes regulates the formation of NMJs through the regulation of different processes including the specific expression of genes in subsynaptic nuclei, the reorganization of the actin cytoskeleton and the clustering of the acetylcholine receptors (AChR) in the postsynaptic membrane. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the MuSK lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409560 [Multi-domain]  Cd Length: 88  Bit Score: 52.24  E-value: 3.78e-08
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 27777648  673 NQTTTIGETIEVTCPASGNPTPHITWFKDNETLVEDSGI-VLRDGNrnLTIRRVRKEDGGLYTCQACNVLGCA 744
Cdd:cd20968    8 NVTIIEGLKAVLPCTTMGNPKPSVSWIKGDDLIKENNRIaVLESGS--LRIHNVQKEDAGQYRCVAKNSLGIA 78
STKc_TSSK4-like cd14162
Catalytic domain of testis-specific serine/threonine kinase 4 and similar proteins; STKs ...
1009-1094 4.00e-08

Catalytic domain of testis-specific serine/threonine kinase 4 and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TSSK proteins are almost exclusively expressed postmeiotically in the testis and play important roles in spermatogenesis and/or spermiogenesis. There are five mammalian TSSK proteins which show differences in their localization and timing of expression. TSSK4, also called TSSK5, is expressed in testis from haploid round spermatids to mature spermatozoa. It phosphorylates Cre-Responsive Element Binding protein (CREB), facilitating the binding of CREB to the specific cis cAMP responsive element (CRE), which is important in activating genes related to germ cell differentiation. Mutations in the human TSSK4 gene is associated with infertile Chinese men with impaired spermatogenesis. The TSSK4-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271064 [Multi-domain]  Cd Length: 259  Bit Score: 56.15  E-value: 4.00e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1009 QVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIYKDPdyvrkgDARLPLK--------WMAPETIFDRVY 1080
Cdd:cd14162  108 QLVAGVEYCHSKGVVHRDLKCENLLLDKNNNLKITDFGFARGVMKTK------DGKPKLSetycgsyaYASPEILRGIPY 181
                         90
                 ....*....|....*
gi 27777648 1081 TIQ-SDVWSFGVLLW 1094
Cdd:cd14162  182 DPFlSDIWSMGVVLY 196
STKc_p38delta cd07879
Catalytic domain of the Serine/Threonine Kinase, p38delta Mitogen-Activated Protein Kinase ...
825-1098 4.05e-08

Catalytic domain of the Serine/Threonine Kinase, p38delta Mitogen-Activated Protein Kinase (also called MAPK13); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. p38delta/MAPK13 is found in skeletal muscle, heart, lung, testis, pancreas, and small intestine. It regulates microtubule function by phosphorylating Tau. It activates the c-jun promoter and plays a role in G2 cell cycle arrest. It also controls the degration of c-Myb, which is associated with myeloid leukemia and poor prognosis in colorectal cancer. p38delta is the main isoform involved in regulating the differentiation and apoptosis of keratinocytes. p38 kinases are MAPKs, serving as important mediators of cellular responses to extracellular signals. They are activated by the MAPK kinases MKK3 and MKK6, which in turn are activated by upstream MAPK kinase kinases including TAK1, ASK1, and MLK3, in response to cellular stresses or inflammatory cytokines. The p38delta subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 143384 [Multi-domain]  Cd Length: 342  Bit Score: 56.83  E-value: 4.05e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  825 WEFPRDRLKLgKPLGRGAFGQVIEAdafgIDKTaTCKTVAVKMLkegathseHRALMSE---------LKILIHIGHHlN 895
Cdd:cd07879   11 WELPERYTSL-KQVGSGAYGSVCSA----IDKR-TGEKVAIKKL--------SRPFQSEifakrayreLTLLKHMQHE-N 75
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  896 VVNLLGACTkpggPLMVIVEFCKFgnlstYLrgkrneFVPYkskgarfrqgkdyvgeLSVDLKRRLDSItssqssassgF 975
Cdd:cd07879   76 VIGLLDVFT----SAVSGDEFQDF-----YL------VMPY----------------MQTDLQKIMGHP----------L 114
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  976 VEEKslsdveeeeaseelykdfltLEHLIcysFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLArdiykdp 1055
Cdd:cd07879  115 SEDK--------------------VQYLV---YQMLCGLKYIHSAGIIHRDLKPGNLAVNEDCELKILDFGLA------- 164
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|....*....
gi 27777648 1056 dyvRKGDARLP----LKWM-APETIFDRV-YTIQSDVWSFGVLLWEIFS 1098
Cdd:cd07879  165 ---RHADAEMTgyvvTRWYrAPEVILNWMhYNQTVDIWSVGCIMAEMLT 210
IgI_hCEACAM_2_4_6_like cd05740
Immunoglobulin (Ig)-like domain of human carcinoembryonic antigen (CEA) related cell adhesion ...
664-739 4.35e-08

Immunoglobulin (Ig)-like domain of human carcinoembryonic antigen (CEA) related cell adhesion molecule (CEACAM) domains 2, 4, and 6, and similar domains; The members here are composed of the second, fourth, and sixth immunoglobulin (Ig)-like domains in human carcinoembryonic antigen (CEA) related cell adhesion molecule (CEACAM) protein subfamily. The CEA family is a group of anchored or secreted glycoproteins expressed by epithelial cells, leukocytes, endothelial cells, and placenta. The CEA family is divided into the CEACAM and pregnancy-specific glycoprotein (PSG) subfamilies. This group represents the CEACAM subfamily. CEACAM1 has many important cellular functions; it is a cell adhesion molecule and a signaling molecule that regulates the growth of tumor cells, an angiogenic factor, and a receptor for bacterial and viral pathogens, including mouse hepatitis virus (MHV). In mice, four isoforms of CEACAM1 generated by alternative splicing have either two [D1, D4] or four [D1-D4] Ig-like domains on the cell surface.


Pssm-ID: 409402 [Multi-domain]  Cd Length: 89  Bit Score: 52.01  E-value: 4.35e-08
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 27777648  664 APMITGNleNQTTTIGE-TIEVTCPASGNPTpHITWFKDNETLVEDSGIVLRDGNRNLTIRRVRKEDGGLYTCQACN 739
Cdd:cd05740    1 KPFISSN--NSNPVEDKdAVTLTCEPETQNT-SYLWWFNGQSLPVTPRLTLSNGNRTLTLLNVTREDAGAYQCEISN 74
STKc_ACVR2 cd14053
Catalytic domain of the Serine/Threonine Kinase, Activin Type II Receptor; STKs catalyze the ...
998-1163 4.49e-08

Catalytic domain of the Serine/Threonine Kinase, Activin Type II Receptor; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. ACVR2 belongs to a group of receptors for the TGFbeta family of secreted signaling molecules that includes TGFbeta, bone morphogenetic proteins (BMPs), activins, growth and differentiation factors (GDFs), and anti-Mullerian hormone, among others. These receptors contain an extracellular domain that binds ligands, a single transmembrane region, and a cytoplasmic catalytic kinase domain. Type II receptors, such as ACVR2, are high-affinity receptors which bind ligands, autophosphorylate, as well as trans-phosphorylate and activate low-affinity type I receptors. ACVR2 acts primarily as the receptors for activins, nodal, myostatin, GDF11, and a subset of BMPs. ACVR2 signaling impacts many cellular and physiological processes including reproductive and gonadal functions, myogenesis, bone remodeling and tooth development, kidney organogenesis, apoptosis, fibrosis, inflammation, and neurogenesis. Vertebrates contain two ACVR2 proteins, ACVR2a (or ActRIIA) and ACVR2b (or ActRIIB). The ACVR2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270955 [Multi-domain]  Cd Length: 290  Bit Score: 56.18  E-value: 4.49e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  998 LTLEHLICYSFQVAKGMEFL---------ASRKCI-HRDLAARNILLSEKNVVKICDFGLARdIYkDPDYVrKGDARLPL 1067
Cdd:cd14053   89 ISWNELCKIAESMARGLAYLhedipatngGHKPSIaHRDFKSKNVLLKSDLTACIADFGLAL-KF-EPGKS-CGDTHGQV 165
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1068 ---KWMAPETI-----FDRVYTIQSDVWSFGVLLWEI-----------------FSLGASPYPGVKIDEEFCRRLKEgtR 1122
Cdd:cd14053  166 gtrRYMAPEVLegainFTRDAFLRIDMYAMGLVLWELlsrcsvhdgpvdeyqlpFEEEVGQHPTLEDMQECVVHKKL--R 243
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*.
gi 27777648 1123 MRAPDYTTP-----EMYQTMLDCWHEDPNQRPSFSELVEHLGNLLQ 1163
Cdd:cd14053  244 PQIRDEWRKhpglaQLCETIEECWDHDAEARLSAGCVEERLSQLSR 289
STKc_MELK cd14078
Catalytic domain of the Serine/Threonine Kinase, Maternal Embryonic Leucine zipper Kinase; ...
1009-1157 4.52e-08

Catalytic domain of the Serine/Threonine Kinase, Maternal Embryonic Leucine zipper Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MELK is a cell cycle dependent protein which functions in cytokinesis, cell cycle, apoptosis, cell proliferation, and mRNA processing. It is found upregulated in many types of cancer cells, playing an indispensable role in cancer cell survival. It makes an attractive target in the design of inhibitors for use in the treatment of a wide range of human cancer. The MELK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270980 [Multi-domain]  Cd Length: 257  Bit Score: 55.85  E-value: 4.52e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1009 QVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIYKDPDYVRKGDARLPlKWMAPETIFDRVYT-IQSDVW 1087
Cdd:cd14078  109 QIVSAVAYVHSQGYAHRDLKPENLLLDEDQNLKLIDFGLCAKPKGGMDHHLETCCGSP-AYAAPELIQGKPYIgSEADVW 187
                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 27777648 1088 SFGVLLWEIFSlGASPYPGVKIdEEFCRRLKEGtRMRAPDYTTP---EMYQTMLDCwheDPNQRPSFSELVEH 1157
Cdd:cd14078  188 SMGVLLYALLC-GFLPFDDDNV-MALYRKIQSG-KYEEPEWLSPsskLLLDQMLQV---DPKKRITVKELLNH 254
STKc_beta_ARK cd05606
Catalytic domain of the Serine/Threonine Kinase, beta-adrenergic receptor kinase; STKs ...
1006-1148 4.54e-08

Catalytic domain of the Serine/Threonine Kinase, beta-adrenergic receptor kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The beta-ARK group is composed of GRK2, GRK3, and similar proteins. GRK2 and GRK3 are both widely expressed in many tissues, although GRK2 is present at higher levels. They contain an N-terminal RGS homology (RH) domain, a central catalytic domain, and C-terminal pleckstrin homology (PH) domain that mediates PIP2 and G protein betagamma-subunit translocation to the membrane. GRK2 (also called beta-ARK or beta-ARK1) is important in regulating several cardiac receptor responses. It plays a role in cardiac development and in hypertension. Deletion of GRK2 in mice results in embryonic lethality, caused by hypoplasia of the ventricular myocardium. GRK2 also plays important roles in the liver (as a regulator of portal blood pressure), in immune cells, and in the nervous system. Altered GRK2 expression has been reported in several disorders including major depression, schizophrenia, bipolar disorder, and Parkinsonism. GRKs phosphorylate and regulate G protein-coupled receptors (GPCRs), the largest superfamily of cell surface receptors which regulate some part of nearly all physiological functions. Phosphorylated GPCRs bind to arrestins, which prevents further G protein signaling despite the presence of activating ligand. The beta-ARK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270757 [Multi-domain]  Cd Length: 279  Bit Score: 55.91  E-value: 4.54e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1006 YSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIYKDPDYVRKGDArlplKWMAPETIFDRV-YTIQS 1084
Cdd:cd05606  103 YAAEVILGLEHMHNRFIVYRDLKPANILLDEHGHVRISDLGLACDFSKKKPHASVGTH----GYMAPEVLQKGVaYDSSA 178
                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 27777648 1085 DVWSFGVLLWEIFSlGASPYPGVKI-DEEFCRRLKEGTRMRAPDYTTPEMYQTMLDCWHEDPNQR 1148
Cdd:cd05606  179 DWFSLGCMLYKLLK-GHSPFRQHKTkDKHEIDRMTLTMNVELPDSFSPELKSLLEGLLQRDVSKR 242
Ig_Pro_neuregulin cd05750
Immunoglobulin (Ig)-like domain in neuregulins; The members here are composed of the ...
671-742 4.56e-08

Immunoglobulin (Ig)-like domain in neuregulins; The members here are composed of the immunoglobulin (Ig)-like domain in neuregulins (NRGs). NRGs are signaling molecules which participate in cell-cell interactions in the nervous system, breast, heart, and other organ systems, and are implicated in the pathology of diseases including schizophrenia, multiple sclerosis, and breast cancer. There are four members of the neuregulin gene family (NRG-1, NRG-2, NRG-3, and NRG-4). The NRG-1 protein, binds to and activates the tyrosine kinases receptors ErbB3 and ErbB4, initiating signaling cascades. The other NRGs proteins bind one or the other or both of these ErbBs. NRG-1 has multiple functions: in the brain it regulates various processes such as radial glia formation and neuronal migration, dendritic development, and expression of neurotransmitters receptors, while in the peripheral nervous system NRG-1 regulates processes such as target cell differentiation, and Schwann cell survival. There are many NRG-1 isoforms which arise from the alternative splicing of mRNA. Less is known of the functions of the other NRGs. NRG-2 and NRG-3 are expressed predominantly in the nervous system. NRG-2 is expressed by motor neurons and terminal Schwann cells, and is concentrated near synaptic sites and may be a signal that regulates synaptic differentiation. NRG-4 has been shown to direct pancreatic islet cell development towards the delta-cell lineage.


Pssm-ID: 409408 [Multi-domain]  Cd Length: 92  Bit Score: 52.13  E-value: 4.56e-08
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 27777648  671 LENQTTTIGETIEVTCPA-SGNPTPHITWFKDNETL--VEDSGIVLRDGNRN--LTIRRVRKEDGGLYTCQACNVLG 742
Cdd:cd05750    6 MKSQTVQEGSKLVLKCEAtSENPSPRYRWFKDGKELnrKRPKNIKIRNKKKNseLQINKAKLEDSGEYTCVVENILG 82
ig pfam00047
Immunoglobulin domain; Members of the immunoglobulin superfamily are found in hundreds of ...
231-312 5.27e-08

Immunoglobulin domain; Members of the immunoglobulin superfamily are found in hundreds of proteins of different functions. Examples include antibodies, the giant muscle kinase titin and receptor tyrosine kinases. Immunoglobulin-like domains may be involved in protein-protein and protein-ligand interactions.


Pssm-ID: 395002  Cd Length: 86  Bit Score: 51.43  E-value: 5.27e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648    231 SPPHEIELSAGEKLVLNCTARTeLNVGLDFTWH----SPPSKSHHKKIVNRdvkpfpgtvakMFLSTLTIESVTKSDQGE 306
Cdd:pfam00047    1 SAPPTVTVLEGDSATLTCSAST-GSPGPDVTWSkeggTLIESLKVKHDNGR-----------TTQSSLLISNVTKEDAGT 68

                   ....*.
gi 27777648    307 YTCVAS 312
Cdd:pfam00047   69 YTCVVN 74
STKc_PRP4 cd14135
Catalytic domain of the Serine/Threonine Kinase, Pre-mRNA-Processing factor 4; STKs catalyze ...
1005-1098 5.58e-08

Catalytic domain of the Serine/Threonine Kinase, Pre-mRNA-Processing factor 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PRP4 phosphorylates a number of factors involved in the formation of active spliceosomes, which catalyze pre-mRNA splicing. It phosphorylates PRP6 and PRP31, components of the U4/U6-U5 tri-small nuclear ribonucleoprotein (snRNP), during spliceosomal complex formation. In fission yeast, PRP4 phosphorylates the splicing factor PRP1 (U5-102 kD in mammals). Thus, PRP4 plays a key role in regulating spliceosome assembly and pre-mRNA splicing. It also plays an important role in mitosis by acting as a spindle assembly checkpoint kinase that is required for chromosome alignment and the recruitment of the checkpoint proteins MPS1, MAD1, and MAD2 at kinetochores. The PRP4 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271037 [Multi-domain]  Cd Length: 318  Bit Score: 56.08  E-value: 5.58e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1005 CYSFQVakgmeFLA---SRKC--IHRDLAARNILLSE-KNVVKICDFGLARDIYKD---PDYVrkgdARLplkWMAPETI 1075
Cdd:cd14135  109 SYAQQL-----FLAlkhLKKCniLHADIKPDNILVNEkKNTLKLCDFGSASDIGENeitPYLV----SRF---YRAPEII 176
                         90       100
                 ....*....|....*....|...
gi 27777648 1076 FDRVYTIQSDVWSFGVLLWEIFS 1098
Cdd:cd14135  177 LGLPYDYPIDMWSVGCTLYELYT 199
STKc_Aurora-B_like cd14117
Catalytic domain of the Serine/Threonine kinase, Aurora-B kinase and similar proteins; STKs ...
1009-1122 5.79e-08

Catalytic domain of the Serine/Threonine kinase, Aurora-B kinase and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Aurora kinases are key regulators of mitosis and are essential for the accurate and equal division of genomic material from parent to daughter cells. Vertebrates contain at least 2 Aurora kinases (A and B); mammals contains a third Aurora kinase gene (C). This subfamily includes Aurora-B and Aurora-C. Aurora-B is most active at the transition during metaphase to the end of mitosis. It associates with centromeres, relocates to the midzone of the central spindle, and concentrates at the midbody during cell division. It is critical for accurate chromosomal segregation, cytokinesis, protein localization to the centrosome and kinetochore, correct microtubule-kinetochore attachments, and regulation of the mitotic checkpoint. Aurora-C is mainly expressed in meiotically dividing cells; it was originally discovered in mice as a testis-specific STK called Aie1. Both Aurora-B and -C are chromosomal passenger proteins that can form complexes with INCENP and survivin, and they may have redundant cellular functions. INCENP participates in the activation of Aurora-B in a two-step process: first by binding to form an intermediate state of activation and the phosphorylation of its C-terminal TSS motif to generate the fully active kinase. The Aurora-B subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271019 [Multi-domain]  Cd Length: 270  Bit Score: 55.64  E-value: 5.79e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1009 QVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLArdiYKDPDYVRKGDARlPLKWMAPETIFDRVYTIQSDVWS 1088
Cdd:cd14117  114 ELADALHYCHEKKVIHRDIKPENLLMGYKGELKIADFGWS---VHAPSLRRRTMCG-TLDYLPPEMIEGRTHDEKVDLWC 189
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....
gi 27777648 1089 FGVLLWEIFsLGASPYPG----------VKIDEEFCRRLKEGTR 1122
Cdd:cd14117  190 IGVLCYELL-VGMPPFESashtetyrriVKVDLKFPPFLSDGSR 232
STKc_MSK_N cd05583
N-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated ...
1006-1104 5.97e-08

N-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family. MSKs are activated by two major signaling cascades, the Ras-MAPK and p38 stress kinase pathways, in response to various stimuli such as growth factors, hormones, neurotransmitters, cellular stress, and pro-inflammatory cytokines. This triggers phosphorylation in the activation loop (A-loop) of the CTD of MSK. The active CTD phosphorylates the hydrophobic motif (HM) in the C-terminal extension of NTD, which facilitates the phosphorylation of the A-loop and activates the NTD, which in turn phosphorylates downstream targets. MSKs are predominantly nuclear proteins. They are widely expressed in many tissues including heart, brain, lung, liver, kidney, and pancreas. There are two isoforms of MSK, called MSK1 and MSK2. The MSK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270735 [Multi-domain]  Cd Length: 268  Bit Score: 55.48  E-value: 5.97e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1006 YSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIYKDPDYvRKGDARLPLKWMAPETIF--DRVYTIQ 1083
Cdd:cd05583  104 YIGEIVLALEHLHKLGIIYRDIKLENILLDSEGHVVLTDFGLSKEFLPGEND-RAYSFCGTIEYMAPEVVRggSDGHDKA 182
                         90       100
                 ....*....|....*....|.
gi 27777648 1084 SDVWSFGVLLWEIFSlGASPY 1104
Cdd:cd05583  183 VDWWSLGVLTYELLT-GASPF 202
STKc_CaMKI_alpha cd14167
Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase ...
829-1157 6.24e-08

Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase Type I alpha; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CaMKs are multifunctional calcium and calmodulin (CaM) stimulated STKs involved in cell cycle regulation. The CaMK family includes CaMKI, CaMKII, CaMKIV, and CaMK kinase (CaMKK). In vertebrates, there are four CaMKI proteins encoded by different genes (alpha, beta, gamma, and delta), each producing at least one variant. CaMKs contain an N-terminal catalytic domain and a C-terminal regulatory domain that harbors a CaM binding site. CaMKI proteins are monomeric and they play pivotal roles in the nervous system, including long-term potentiation, dendritic arborization, neurite outgrowth, and the formation of spines, synapses, and axons. In addition, they may be involved in osteoclast differentiation and bone resorption. The CaMKI-alpha subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271069 [Multi-domain]  Cd Length: 263  Bit Score: 55.42  E-value: 6.24e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  829 RDRLKLGKPLGRGAFGQVIEADafgidKTATCKTVAVKMLKEGATHSEHRALMSELKILiHIGHHLNVVNLlGACTKPGG 908
Cdd:cd14167    2 RDIYDFREVLGTGAFSEVVLAE-----EKRTQKLVAIKCIAKKALEGKETSIENEIAVL-HKIKHPNIVAL-DDIYESGG 74
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  909 PLMVIVEFCKFGNLSTYLRGKrnefvpykskgarfrqgkdyvgelsvdlkrrldsitssqssassGFVEEKSLSdveeee 988
Cdd:cd14167   75 HLYLIMQLVSGGELFDRIVEK--------------------------------------------GFYTERDAS------ 104
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  989 aseelykdfltleHLICysfQVAKGMEFLASRKCIHRDLAARNIL---LSEKNVVKICDFGLARdiYKDPDYVRKGDARL 1065
Cdd:cd14167  105 -------------KLIF---QILDAVKYLHDMGIVHRDLKPENLLyysLDEDSKIMISDFGLSK--IEGSGSVMSTACGT 166
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1066 PlKWMAPETIFDRVYTIQSDVWSFGVLLWeIFSLGASPYPGVKIDEEFCRRLKEGTRMRAP--DYTTPEMYQTMLDCWHE 1143
Cdd:cd14167  167 P-GYVAPEVLAQKPYSKAVDCWSIGVIAY-ILLCGYPPFYDENDAKLFEQILKAEYEFDSPywDDISDSAKDFIQHLMEK 244
                        330
                 ....*....|....
gi 27777648 1144 DPNQRPSFSELVEH 1157
Cdd:cd14167  245 DPEKRFTCEQALQH 258
STKc_MLCK2 cd14190
Catalytic domain of the Serine/Threonine Kinase, Myosin Light Chain Kinase 2; STKs catalyze ...
1009-1106 6.71e-08

Catalytic domain of the Serine/Threonine Kinase, Myosin Light Chain Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MLCK2 (or MYLK2) phosphorylates myosin regulatory light chain and controls the contraction of skeletal muscles. MLCK2 contains a single kinase domain near the C-terminus followed by a regulatory segment containing an autoinhibitory Ca2+/calmodulin binding site. The MLCK2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271092 [Multi-domain]  Cd Length: 261  Bit Score: 55.31  E-value: 6.71e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1009 QVAKGMEFLASRKCIHRDLAARNILL--SEKNVVKICDFGLARDiYKdPDYVRKGDARLPlKWMAPETI-FDRVyTIQSD 1085
Cdd:cd14190  110 QICEGIQFMHQMRVLHLDLKPENILCvnRTGHQVKIIDFGLARR-YN-PREKLKVNFGTP-EFLSPEVVnYDQV-SFPTD 185
                         90       100
                 ....*....|....*....|.
gi 27777648 1086 VWSFGVLLWEIFSlGASPYPG 1106
Cdd:cd14190  186 MWSMGVITYMLLS-GLSPFLG 205
IgI_Myotilin_C cd05892
C-terminal immunoglobulin (Ig)-like domain of myotilin; member of the I-set of Ig superfamily ...
665-744 7.25e-08

C-terminal immunoglobulin (Ig)-like domain of myotilin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of myotilin. Mytolin belongs to the palladin-myotilin-myopalladin family. Proteins belonging to the latter family contain multiple Ig-like domains and function as scaffolds, modulating the actin cytoskeleton. Myotilin is most abundant in skeletal and cardiac muscle and is involved in maintaining sarcomere integrity. It binds to alpha-actinin, filamin, and actin. Mutations in myotilin lead to muscle disorders. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409473  Cd Length: 92  Bit Score: 51.31  E-value: 7.25e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  665 PMITGNLENQTTTIGETIEVTCPASGNPTPHITWFKDNETLVEDSGIV--LRD--GNRNLTIRRVRKEDGGLYTCQACNV 740
Cdd:cd05892    1 PMFIQKPQNKKVLEGDPVRLECQISAIPPPQIFWKKNNEMLQYNTDRIslYQDncGRICLLIQNANKKDAGWYTVSAVNE 80

                 ....
gi 27777648  741 LGCA 744
Cdd:cd05892   81 AGVV 84
STKc_TAO2 cd06634
Catalytic domain of the Serine/Threonine Kinase, Thousand-and-One Amino acids 2; STKs catalyze ...
1012-1157 7.65e-08

Catalytic domain of the Serine/Threonine Kinase, Thousand-and-One Amino acids 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Human TAO2 is also known as prostate-derived Ste20-like kinase (PSK) and was identified in a screen for overexpressed RNAs in prostate cancer. TAO2 possesses mitogen-activated protein kinase (MAPK) kinase kinase activity and activates both p38 and c-Jun N-terminal kinase (JNK), by phosphorylating and activating their respective MAP/ERK kinases, MEK3/MEK6 and MKK4/MKK7. It contains a long C-terminal extension with autoinhibitory segments, and is activated by the release of this inhibition and the phosphorylation of its activation loop serine. TAO2 functions as a regulator of actin cytoskeletal and microtubule organization. In addition, it regulates the transforming growth factor-activated kinase 1 (TAK1), which is a MAPKKK that plays an essential role in the signaling pathways of tumor necrosis factor, interleukin 1, and Toll-like receptor. The TAO2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270804 [Multi-domain]  Cd Length: 308  Bit Score: 55.80  E-value: 7.65e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1012 KGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIYKDPDYVRKgdarlPLkWMAPETIF---DRVYTIQSDVWS 1088
Cdd:cd06634  126 QGLAYLHSHNMIHRDVKAGNILLTEPGLVKLGDFGSASIMAPANSFVGT-----PY-WMAPEVILamdEGQYDGKVDVWS 199
                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1089 FGVLLWEIFSLGASPYPGVKIDEEFCRRLKEGTRMRAPDYTtpEMYQTMLD-CWHEDPNQRPSFSELVEH 1157
Cdd:cd06634  200 LGITCIELAERKPPLFNMNAMSALYHIAQNESPALQSGHWS--EYFRNFVDsCLQKIPQDRPTSDVLLKH 267
STKc_SnRK2 cd14662
Catalytic domain of the Serine/Threonine Kinases, Sucrose nonfermenting 1-related protein ...
1009-1157 7.83e-08

Catalytic domain of the Serine/Threonine Kinases, Sucrose nonfermenting 1-related protein kinase subfamily 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The SnRKs form three different subfamilies designated SnRK1-3. SnRK2 is represented in this cd. SnRK2s are involved in plant response to abiotic stresses and abscisic acid (ABA)-dependent plant development. The SnRK2s subfamily is in turn classed into three subgroups, all 3 of which are represented in this CD. Group 1 comprises kinases not activated by ABA, group 2 - kinases not activated or activated very weakly by ABA (depending on plant species), and group 3 - kinases strongly activated by ABA. The SnRKs belong to a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271132 [Multi-domain]  Cd Length: 257  Bit Score: 55.16  E-value: 7.83e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1009 QVAKGMEFLASRKCIHRDLAARNILL--SEKNVVKICDFGLARD--IYKDPdyvrKGDARLPlKWMAPETIFDRVYTIQ- 1083
Cdd:cd14662  104 QLISGVSYCHSMQICHRDLKLENTLLdgSPAPRLKICDFGYSKSsvLHSQP----KSTVGTP-AYIAPEVLSRKEYDGKv 178
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1084 SDVWSFGVLLWeIFSLGASPYPGVKIDEEFCRRLkegTRMRAPDYTTPEMYQTMLDCWH-------EDPNQRPSFSELVE 1156
Cdd:cd14662  179 ADVWSCGVTLY-VMLVGAYPFEDPDDPKNFRKTI---QRIMSVQYKIPDYVRVSQDCRHllsrifvANPAKRITIPEIKN 254

                 .
gi 27777648 1157 H 1157
Cdd:cd14662  255 H 255
Ig cd00096
Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found ...
350-412 7.94e-08

Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins, including T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, including butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E, and D strands in one sheet and A', G, F, C, C' and C" in the other. The structures in C1-set are smaller than those in the V-set; they have one beta sheet that is formed by strands A, B, E, and D and the other by strands G, F, C, and C'. Moreover, a C1-set Ig domain contains a short C' strand (three residues) and lacks A' and C" strand. Unlike other Ig domain sets, C2-set structures do not have a D strand. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409353 [Multi-domain]  Cd Length: 70  Bit Score: 50.41  E-value: 7.94e-08
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 27777648  350 VRIPVKYLSYPAPDIKWYRNGRPIESNYTMIVGDE-----LTIMEVTERDAGNYTVILTNPISMEKQS 412
Cdd:cd00096    1 VTLTCSASGNPPPTITWYKNGKPLPPSSRDSRRSElgngtLTISNVTLEDSGTYTCVASNSAGGSASA 68
STKc_CDK8_like cd07842
Catalytic domain of Cyclin-Dependent protein Kinase 8-like Serine/Threonine Kinases; STKs ...
1008-1099 8.39e-08

Catalytic domain of Cyclin-Dependent protein Kinase 8-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of CDK8, CDC2L6, and similar proteins. CDK8 functions as a negative or positive regulator of transcription, depending on the scenario. Together with its regulator, cyclin C, it reversibly associates with the multi-subunit core Mediator complex, a cofactor that is involved in regulating RNA polymerase II-dependent transcription. CDC2L6 also associates with Mediator in complexes lacking CDK8. In VP16-dependent transcriptional activation, CDK8 and CDC2L6 exerts opposing effects by positive and negative regulation, respectively, in similar conditions. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK8-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270834 [Multi-domain]  Cd Length: 316  Bit Score: 55.75  E-value: 8.39e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1008 FQVAKGMEFLASRKCIHRDLAARNILL----SEKNVVKICDFGLARDIYKDPDYVRKGDARLPLKWM-APETIFD-RVYT 1081
Cdd:cd07842  115 WQILNGIHYLHSNWVLHRDLKPANILVmgegPERGVVKIGDLGLARLFNAPLKPLADLDPVVVTIWYrAPELLLGaRHYT 194
                         90
                 ....*....|....*...
gi 27777648 1082 IQSDVWSFGVLLWEIFSL 1099
Cdd:cd07842  195 KAIDIWAIGCIFAELLTL 212
STKc_GRK3 cd05633
Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase 3; STKs ...
1006-1148 8.50e-08

Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. GRK3, also called beta-adrenergic receptor kinase 2 (beta-ARK2), is widely expressed in many tissues. It is involved in modulating the cholinergic response of airway smooth muscles, and also plays a role in dopamine receptor regulation. GRK3-deficient mice show a lack of olfactory receptor desensitization and altered regulation of the M2 muscarinic airway. GRK3 promoter polymorphisms may also be associated with bipolar disorder. GRK3 contains an N-terminal RGS homology (RH) domain, a central catalytic domain, and C-terminal pleckstrin homology (PH) domain that mediates PIP2 and G protein betagamma-subunit translocation to the membrane. GRKs phosphorylate and regulate G protein-coupled receptors (GPCRs), the largest superfamily of cell surface receptors which regulate some part of nearly all physiological functions. Phosphorylated GPCRs bind to arrestins, which prevents further G protein signaling despite the presence of activating ligand. The GRK3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270781 [Multi-domain]  Cd Length: 346  Bit Score: 55.84  E-value: 8.50e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1006 YSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIYKDPDYVRKGDArlplKWMAPETIFD-RVYTIQS 1084
Cdd:cd05633  113 YATEIILGLEHMHNRFVVYRDLKPANILLDEHGHVRISDLGLACDFSKKKPHASVGTH----GYMAPEVLQKgTAYDSSA 188
                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 27777648 1085 DVWSFGVLLWEIFSlGASPYPGVKI-DEEFCRRLKEGTRMRAPDYTTPEMYQTMLDCWHEDPNQR 1148
Cdd:cd05633  189 DWFSLGCMLFKLLR-GHSPFRQHKTkDKHEIDRMTLTVNVELPDSFSPELKSLLEGLLQRDVSKR 252
PTZ00036 PTZ00036
glycogen synthase kinase; Provisional
1006-1128 8.74e-08

glycogen synthase kinase; Provisional


Pssm-ID: 173333 [Multi-domain]  Cd Length: 440  Bit Score: 56.20  E-value: 8.74e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  1006 YSFQVAKGMEFLASRKCIHRDLAARNILLSEK-NVVKICDFGLARDIYKDPDYVRKGDARLplkWMAPETIFDRV-YTIQ 1083
Cdd:PTZ00036  175 YSYQLCRALAYIHSKFICHRDLKPQNLLIDPNtHTLKLCDFGSAKNLLAGQRSVSYICSRF---YRAPELMLGATnYTTH 251
                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|.
gi 27777648  1084 SDVWSFGVLLWE------IFSLGASPYPGVKIDEEFCRRLKEGTRMRAPDY 1128
Cdd:PTZ00036  252 IDLWSLGCIIAEmilgypIFSGQSSVDQLVRIIQVLGTPTEDQLKEMNPNY 302
IgI_1_Titin_Z1z2-like cd20974
First Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and ...
665-746 9.71e-08

First Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the first immunoglobulin (Ig)-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the titin Z1z2 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409566 [Multi-domain]  Cd Length: 93  Bit Score: 51.20  E-value: 9.71e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  665 PMITGNLENQTTTIGETIEVTCPASGNPTPHITWFKDNE----TLVEDSGIVLRDGNRNLTIRRVRKEDGGLYTCQACNV 740
Cdd:cd20974    1 PVFTQPLQSVVVLEGSTATFEAHVSGKPVPEVSWFRDGQvistSTLPGVQISFSDGRAKLSIPAVTKANSGRYSLTATNG 80

                 ....*.
gi 27777648  741 LGCARA 746
Cdd:cd20974   81 SGQATS 86
IgI_3_WFIKKN-like cd05765
Third immunoglobulin-like domain of the human WFIKKN (WAP, follistatin, immunoglobulin, Kunitz ...
665-747 9.97e-08

Third immunoglobulin-like domain of the human WFIKKN (WAP, follistatin, immunoglobulin, Kunitz and NTR domain-containing protein), and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin-like domain of the human WFIKKN (WAP, follistatin, immunoglobulin, Kunitz and NTR domain-containing protein) and similar proteins. WFIKKN is a secreted protein that consists of multiple types of protease inhibitory modules, including two tandem Kunitz-type protease inhibitor-domains. The Ig superfamily is a heterogenous group of proteins built on a common fold comprised of a sandwich of two beta sheets. Members of the Ig superfamily are components of immunoglobulin, neuroglia, cell surface glycoproteins, such as T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, such as butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409422 [Multi-domain]  Cd Length: 95  Bit Score: 51.01  E-value: 9.97e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  665 PMITGNLENQTTTIGETIEVTCPASGNPTPHITWFK---DNETLV----EDSGIVLRDGNRNLTIRRVRKEDGGLYTCQA 737
Cdd:cd05765    1 PALVNSPTHQTVKVGETASFHCDVTGRPQPEITWEKqvpGKENLImrpnHVRGNVVVTNIGQLVIYNAQPQDAGLYTCTA 80
                         90
                 ....*....|
gi 27777648  738 CNVLGCARAE 747
Cdd:cd05765   81 RNSGGLLRAN 90
STKc_GAK cd14036
Catalytic domain of the Serine/Threonine protein kinase, cyclin G-Associated Kinase; STKs ...
1008-1164 1.03e-07

Catalytic domain of the Serine/Threonine protein kinase, cyclin G-Associated Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. GAK, also called auxilin-2, contains an N-terminal kinase domain that phosphorylates the mu subunits of adaptor protein (AP) 1 and AP2. In addition, it contains an auxilin-1-like domain structure consisting of PTEN-like, clathrin-binding, and J domains. Like auxilin-1, GAK facilitates Hsc70-mediated dissociation of clathrin from clathrin-coated vesicles. GAK is expressed ubiquitously and is enriched in the Golgi, unlike auxilin-1 which is nerve-specific. GAK also plays regulatory roles outside of clathrin-mediated membrane traffic including the maintenance of centrosome integrity and chromosome congression, neural patterning, survival of neurons, and immune responses through interaction with the interleukin 12 receptor. It also interacts with the androgen receptor, acting as a transcriptional coactivator, and its expression is significantly increased with the progression of prostate cancer. The GAK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270938 [Multi-domain]  Cd Length: 282  Bit Score: 55.21  E-value: 1.03e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1008 FQVAKGMEFLASRK--CIHRDLAARNILLSEKNVVKICDFGLARDIYKDPDYVRKGDARLPLK----------WMAPETI 1075
Cdd:cd14036  115 YQTCRAVQHMHKQSppIIHRDLKIENLLIGNQGQIKLCDFGSATTEAHYPDYSWSAQKRSLVEdeitrnttpmYRTPEMI 194
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1076 fdRVY-----TIQSDVWSFGVLLWeIFSLGASPYpgvkideefcrrlKEGTRMRA--PDYTTPEM---YQTMLD----CW 1141
Cdd:cd14036  195 --DLYsnypiGEKQDIWALGCILY-LLCFRKHPF-------------EDGAKLRIinAKYTIPPNdtqYTVFHDlirsTL 258
                        170       180
                 ....*....|....*....|...
gi 27777648 1142 HEDPNQRPSFSELVEHLGNLLQA 1164
Cdd:cd14036  259 KVNPEERLSITEIVEQLQELAAA 281
STKc_MSK1_C cd14179
C-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated ...
1023-1154 1.07e-07

C-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MSK1 plays a role in the regulation of translational control and transcriptional activation. It phosphorylates the transcription factors, CREB and NFkB. It also phosphorylates the nucleosomal proteins H3 and HMG-14. Increased phosphorylation of MSK1 is associated with the development of cerebral ischemic/hypoxic preconditioning. MSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family. MSKs are activated by two major signaling cascades, the Ras-MAPK and p38 stress kinase pathways, which trigger phosphorylation in the activation loop (A-loop) of the CTD of MSK. The active CTD phosphorylates the hydrophobic motif (HM) of NTD, which facilitates the phosphorylation of the A-loop and activates the NTD, which in turn phosphorylates downstream targets. The MSK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271081 [Multi-domain]  Cd Length: 310  Bit Score: 55.43  E-value: 1.07e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1023 IHRDLAARNILLSEKN---VVKICDFGLARdiYKDPDYVRKGDARLPLKWMAPETIFDRVYTIQSDVWSFGVLLWEIFSl 1099
Cdd:cd14179  124 VHRDLKPENLLFTDESdnsEIKIIDFGFAR--LKPPDNQPLKTPCFTLHYAAPELLNYNGYDESCDLWSLGVILYTMLS- 200
                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 27777648 1100 GASPYPG------VKIDEEFCRRLK------EGTRMRAPDYTTPEMYQTMLDCwheDPNQRPSFSEL 1154
Cdd:cd14179  201 GQVPFQChdksltCTSAEEIMKKIKqgdfsfEGEAWKNVSQEAKDLIQGLLTV---DPNKRIKMSGL 264
IgI_3_FGFR cd04974
Third immunoglobulin (Ig)-like domain of fibroblast growth factor receptor (FGFR); member of ...
665-742 1.07e-07

Third immunoglobulin (Ig)-like domain of fibroblast growth factor receptor (FGFR); member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig)-like domain of fibroblast growth factor receptor (FGFR). Fibroblast growth factors (FGFs) participate in morphogenesis, development, angiogenesis, and wound healing. These FGF-stimulated processes are mediated by four FGFR tyrosine kinases (FGRF1-4). FGFRs are comprised of an extracellular portion consisting of three Ig-like domains, a transmembrane helix, and a cytoplasmic portion having protein tyrosine kinase activity. The highly conserved Ig-like domains 2 and 3, and the linker region between D2 and D3 define a general binding site for FGFs. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409363  Cd Length: 102  Bit Score: 51.27  E-value: 1.07e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  665 PMITGNL-ENQTTTIGETIEVTCPASGNPTPHITWFKDNET-------------LVEDSGIVLRDGNRN-LTIRRVRKED 729
Cdd:cd04974    1 PILQAGLpANQTVVLGSDVEFHCKVYSDAQPHIQWLKHVEVngskygpdglpyvTVLKVAGVNTTGEENtLTISNVTFDD 80
                         90
                 ....*....|...
gi 27777648  730 GGLYTCQACNVLG 742
Cdd:cd04974   81 AGEYICLAGNSIG 93
STKc_aPKC_zeta cd05617
Catalytic domain of the Serine/Threonine Kinase, Atypical Protein Kinase C zeta; STKs catalyze ...
1001-1148 1.18e-07

Catalytic domain of the Serine/Threonine Kinase, Atypical Protein Kinase C zeta; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKC-zeta plays a critical role in activating the glucose transport response. It is activated by glucose, insulin, and exercise through diverse pathways. PKC-zeta also plays a central role in maintaining cell polarity in yeast and mammalian cells. In addition, it affects actin remodeling in muscle cells. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. aPKCs only require phosphatidylserine (PS) for activation. The aPKC-zeta subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270768 [Multi-domain]  Cd Length: 357  Bit Score: 55.41  E-value: 1.18e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1001 EHLICYSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARdiykdpDYVRKGDARLPL----KWMAPETIF 1076
Cdd:cd05617  116 EHARFYAAEICIALNFLHERGIIYRDLKLDNVLLDADGHIKLTDYGMCK------EGLGPGDTTSTFcgtpNYIAPEILR 189
                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 27777648 1077 DRVYTIQSDVWSFGVLLWEIFSlGASPY------PGVKIDEEFCRRLKEGTrMRAPDYTTPEMYQTMLDCWHEDPNQR 1148
Cdd:cd05617  190 GEEYGFSVDWWALGVLMFEMMA-GRSPFdiitdnPDMNTEDYLFQVILEKP-IRIPRFLSVKASHVLKGFLNKDPKER 265
PLN00009 PLN00009
cyclin-dependent kinase A; Provisional
996-1113 1.21e-07

cyclin-dependent kinase A; Provisional


Pssm-ID: 177649 [Multi-domain]  Cd Length: 294  Bit Score: 54.82  E-value: 1.21e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648   996 DFLTLEHLI-CYSFQVAKGMEFLASRKCIHRDLAARNILLSEK-NVVKICDFGLARdIYKDPdyVRKGDARLPLKWM-AP 1072
Cdd:PLN00009   96 DFAKNPRLIkTYLYQILRGIAYCHSHRVLHRDLKPQNLLIDRRtNALKLADFGLAR-AFGIP--VRTFTHEVVTLWYrAP 172
                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 27777648  1073 ETIF-DRVYTIQSDVWSFGVLLWEIFSlgASP-YPG-VKIDEEF 1113
Cdd:PLN00009  173 EILLgSRHYSTPVDIWSVGCIFAEMVN--QKPlFPGdSEIDELF 214
STKc_PFTAIRE1 cd07869
Catalytic domain of the Serine/Threonine Kinase, PFTAIRE-1 kinase; STKs catalyze the transfer ...
1006-1108 1.29e-07

Catalytic domain of the Serine/Threonine Kinase, PFTAIRE-1 kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PFTAIRE-1 is widely expressed except in the spleen and thymus. It is highly expressed in the brain, heart, pancreas, testis, and ovary, and is localized in the cytoplasm. It is regulated by cyclin D3 and is inhibited by the p21 cell cycle inhibitor. It has also been shown to interact with the membrane-associated cyclin Y, which recruits the protein to the plasma membrane. PFTAIRE-1 shares sequence similarity with Cyclin-Dependent Kinases (CDKs), which belong to a large family of STKs that are regulated by their cognate cyclins. Together, CDKs and cyclins are involved in the control of cell-cycle progression, transcription, and neuronal function. The PFTAIRE-1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 143374 [Multi-domain]  Cd Length: 303  Bit Score: 55.08  E-value: 1.29e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1006 YSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARdIYKDPDYVRKGDArLPLKWMAPETIFDRV-YTIQS 1084
Cdd:cd07869  108 FLFQLLRGLSYIHQRYILHRDLKPQNLLISDTGELKLADFGLAR-AKSVPSHTYSNEV-VTLWYRPPDVLLGSTeYSTCL 185
                         90       100
                 ....*....|....*....|....
gi 27777648 1085 DVWSFGVLLWEIFSlGASPYPGVK 1108
Cdd:cd07869  186 DMWGVGCIFVEMIQ-GVAAFPGMK 208
I-set pfam07679
Immunoglobulin I-set domain;
228-312 1.35e-07

Immunoglobulin I-set domain;


Pssm-ID: 400151 [Multi-domain]  Cd Length: 90  Bit Score: 50.33  E-value: 1.35e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648    228 VILSPPHEIELSAGEKLVLNCTARtelnvG---LDFTWH---SPPSKSHHKKIVNRDVKpfpgtvakmflSTLTIESVTK 301
Cdd:pfam07679    2 KFTQKPKDVEVQEGESARFTCTVT-----GtpdPEVSWFkdgQPLRSSDRFKVTYEGGT-----------YTLTISNVQP 65
                           90
                   ....*....|.
gi 27777648    302 SDQGEYTCVAS 312
Cdd:pfam07679   66 DDSGKYTCVAT 76
PTKc_Wee1a cd14138
Catalytic domain of the Protein Tyrosine Kinase, Wee1a; PTKs catalyze the transfer of the ...
980-1157 1.36e-07

Catalytic domain of the Protein Tyrosine Kinase, Wee1a; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. This subfamily is composed of human Wee1a, Xenopus laevis Wee1b (XeWee1b) and similar vertebrate proteins. Members of this subfamily show a wide expression pattern. XeWee1b functions after the first zygotic cell divisions. It is expressed in all tissues and is also present after the gastrulation stage of embryos. Wee1 is a cell cycle checkpoint kinase that helps keep the cyclin-dependent kinase CDK1 in an inactive state through phosphorylation of an N-terminal tyr (Y15) residue. During the late G2 phase, CDK1 is activated and mitotic entry is promoted by the removal of this inhibitory phosphorylation by the phosphatase Cdc25. Although Wee1 is functionally a tyr kinase, it is more closely related to serine/threonine kinases (STKs). It contains a catalytic kinase domain sandwiched in between N- and C-terminal regulatory domains. It is regulated by phosphorylation and degradation, and its expression levels are also controlled by circadian clock proteins. The Wee1a subfamily is part of a larger superfamily that includes the catalytic domains of STKs, other PTKs, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271040 [Multi-domain]  Cd Length: 276  Bit Score: 54.64  E-value: 1.36e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  980 SLSDVEEEEASEELYKDFLTLEHLIcysFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKIC-------DFGLARDIY 1052
Cdd:cd14138   91 SLADAISENYRIMSYFTEPELKDLL---LQVARGLKYIHSMSLVHMDIKPSNIFISRTSIPNAAseegdedEWASNKVIF 167
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1053 KDPDY----------VRKGDARlplkWMAPEtIFDRVYT--IQSDVWSFGVLLWEifSLGASPYPgvkIDEEFCRRLKEG 1120
Cdd:cd14138  168 KIGDLghvtrvsspqVEEGDSR----FLANE-VLQENYThlPKADIFALALTVVC--AAGAEPLP---TNGDQWHEIRQG 237
                        170       180       190
                 ....*....|....*....|....*....|....*..
gi 27777648 1121 TRMRAPDYTTPEMYQTMLDCWHEDPNQRPSFSELVEH 1157
Cdd:cd14138  238 KLPRIPQVLSQEFLDLLKVMIHPDPERRPSAVALVKH 274
STKc_Mnk2 cd14173
Catalytic domain of the Serine/Threonine kinase, Mitogen-activated protein kinase ...
1010-1106 1.39e-07

Catalytic domain of the Serine/Threonine kinase, Mitogen-activated protein kinase signal-integrating kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAPK signal-integrating kinases (Mnks) are MAPK-activated protein kinases and is comprised by a group of four proteins, produced by alternative splicing from two genes (Mnk1 and Mnk2). The isoforms of Mnk1 (1a/1b) and Mnk2 (2a/2b) differ at their C-termini, with the a-form having a longer C-terminus containing a MAPK-binding region. All Mnks contain a catalytic kinase domain and a polybasic region at the N-terminus which binds importin and the eukaryotic initiation factor eIF4G. The best characterized Mnk substrate is eIF4G, whose phosphorylation may promote the export of certain mRNAs from the nucleus. Mnk also phosphorylate substrates that bind to AU-rich elements that regulate mRNA stability and translation. Mnks have also been implicated in tyrosine kinase receptor signaling, inflammation, and cell prolieration or survival. The Mnk subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271075 [Multi-domain]  Cd Length: 288  Bit Score: 54.65  E-value: 1.39e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1010 VAKGMEFLASRKCIHRDLAARNILLSEKNV---VKICDFGLARDIYKDPDYVRKGDARL-----PLKWMAPETI--FDR- 1078
Cdd:cd14173  109 IASALDFLHNKGIAHRDLKPENILCEHPNQvspVKICDFDLGSGIKLNSDCSPISTPELltpcgSAEYMAPEVVeaFNEe 188
                         90       100       110
                 ....*....|....*....|....*....|
gi 27777648 1079 --VYTIQSDVWSFGVLLWEIFSlGASPYPG 1106
Cdd:cd14173  189 asIYDKRCDLWSLGVILYIMLS-GYPPFVG 217
STKc_HUNK cd14070
Catalytic domain of the Serine/Threonine Kinase, Hormonally up-regulated Neu-associated kinase ...
1006-1104 1.39e-07

Catalytic domain of the Serine/Threonine Kinase, Hormonally up-regulated Neu-associated kinase (also called MAK-V); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. HUNK/MAK-V was identified from a mammary tumor in an MMTV-neu transgenic mouse. It is required for the metastasis of c-myc-induced mammary tumors, but is not necessary for c-myc-induced primary tumor formation or normal development. It is required for HER2/neu-induced tumor formation and maintenance of the cells' tumorigenic phenotype. It is over-expressed in aggressive subsets of ovary, colon, and breast carcinomas. HUNK interacts with synaptopodin, and may also play a role in synaptic plasticity. The HUNK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270972 [Multi-domain]  Cd Length: 262  Bit Score: 54.44  E-value: 1.39e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1006 YSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDI----YKDPDYVRKGDArlplKWMAPETIFDRVYT 1081
Cdd:cd14070  108 YIRQLVSAVEHLHRAGVVHRDLKIENLLLDENDNIKLIDFGLSNCAgilgYSDPFSTQCGSP----AYAAPELLARKKYG 183
                         90       100
                 ....*....|....*....|...
gi 27777648 1082 IQSDVWSFGVLLWEIFSlGASPY 1104
Cdd:cd14070  184 PKVDVWSIGVNMYAMLT-GTLPF 205
STKc_BMPR2_AMHR2 cd14054
Catalytic domain of the Serine/Threonine Kinases, Bone Morphogenetic Protein and ...
1010-1106 1.41e-07

Catalytic domain of the Serine/Threonine Kinases, Bone Morphogenetic Protein and Anti-Muellerian Hormone Type II Receptors; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. BMPR2 and AMHR2 belong to a group of receptors for the TGFbeta family of secreted signaling molecules that includes TGFbeta, BMPs, activins, growth and differentiation factors (GDFs), and AMH, among others. These receptors contain an extracellular domain that binds ligands, a single transmembrane region, and a cytoplasmic catalytic kinase domain. Type II receptors are high-affinity receptors which bind ligands, autophosphorylate, as well as trans-phosphorylate and activate low-affinity type I receptors. BMPR2 and AMHR2 act primarily as a receptor for BMPs and AMH, respectively. BMPs induce bone and cartilage formation, as well as regulate tooth, kidney, skin, hair, haematopoietic, and neuronal development. Mutations in BMPR2A is associated with familial pulmonary arterial hypertension. AMH is mainly responsible for the regression of Mullerian ducts during male sex differentiation. It is expressed exclusively by somatic cells of the gonads. Mutations in either AMH or AMHR2 cause persistent Mullerian duct syndrome (PMDS), a rare form of male pseudohermaphroditism characterized by the presence of Mullerian derivatives (ovary and tubes) in otherwise normally masculine males. The BMPR2/AMHR2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270956 [Multi-domain]  Cd Length: 300  Bit Score: 54.67  E-value: 1.41e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1010 VAKGMEFLAS--------RKCI-HRDLAARNILLSEKNVVKICDFGLA---RDIYKDPDYVRKGDARLP-----LKWMAP 1072
Cdd:cd14054  102 LTRGLAYLHTdlrrgdqyKPAIaHRDLNSRNVLVKADGSCVICDFGLAmvlRGSSLVRGRPGAAENASIsevgtLRYMAP 181
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|.
gi 27777648 1073 ETIFDRV-------YTIQSDVWSFGVLLWEIFSLGASPYPG 1106
Cdd:cd14054  182 EVLEGAVnlrdcesALKQVDVYALGLVLWEIAMRCSDLYPG 222
STKc_TGFbR-like cd13998
Catalytic domain of Transforming Growth Factor beta Receptor-like Serine/Threonine Kinases; ...
1024-1098 1.51e-07

Catalytic domain of Transforming Growth Factor beta Receptor-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of receptors for the TGFbeta family of secreted signaling molecules including TGFbeta, bone morphogenetic proteins (BMPs), activins, growth and differentiation factors (GDFs), and anti-Mullerian hormone, among others. These receptors contain an extracellular domain that binds ligands, a single transmembrane (TM) region, and a cytoplasmic catalytic kinase domain. There are two types of TGFbeta receptors included in this subfamily, I and II, that play different roles in signaling. For signaling to occur, the ligand first binds to the high-affinity type II receptor, which is followed by the recruitment of the low-affinity type I receptor to the complex and its activation through trans-phosphorylation by the type II receptor. The active type I receptor kinase starts intracellular signaling to the nucleus by phosphorylating SMAD proteins. Type I receptors contain an additional domain located between the TM and kinase domains called the the GS domain, which contains the activating phosphorylation site and confers preference for specific SMAD proteins. Different ligands interact with various combinations of types I and II receptors to elicit a specific signaling pathway. Activins primarily signal through combinations of ACVR1b/ALK7 and ACVR2a/b; myostatin and GDF11 through TGFbR1/ALK4 and ACVR2a/b; BMPs through ACVR1/ALK1 and BMPR2; and TGFbeta through TGFbR1 and TGFbR2. The TGFbR-like subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270900 [Multi-domain]  Cd Length: 289  Bit Score: 54.75  E-value: 1.51e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1024 HRDLAARNILLSEKNVVKICDFGLA------RDIYKDPDYVRKGDARlplkWMAPETIFDRVYT------IQSDVWSFGV 1091
Cdd:cd13998  124 HRDLKSKNILVKNDGTCCIADFGLAvrlspsTGEEDNANNGQVGTKR----YMAPEVLEGAINLrdfesfKRVDIYAMGL 199

                 ....*..
gi 27777648 1092 LLWEIFS 1098
Cdd:cd13998  200 VLWEMAS 206
STKc_NIK cd13991
Catalytic domain of the Serine/Threonine kinase, NF-kappaB Inducing Kinase (NIK); STKs ...
1006-1164 1.63e-07

Catalytic domain of the Serine/Threonine kinase, NF-kappaB Inducing Kinase (NIK); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. NIK, also called mitogen activated protein kinase kinase kinase 14 (MAP3K14), phosphorylates and activates Inhibitor of NF-KappaB Kinase (IKK) alpha, which is a regulator of NF-kB proteins, a family of transcription factors which are critical in many cellular functions including inflammatory responses, immune development, cell survival, and cell proliferation, among others. NIK is essential in the IKKalpha-mediated non-canonical NF-kB signaling pathway, in which IKKalpha processes the IkB-like C-terminus of NF-kB2/p100 to produce p52, allowing the p52/RelB dimer to migrate to the nucleus where it regulates gene transcription. NIK also plays an important role in Toll-like receptor 7/9 signaling cascades. The NIK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270893 [Multi-domain]  Cd Length: 268  Bit Score: 54.44  E-value: 1.63e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1006 YSFQVAKGMEFLASRKCIHRDLAARNILLSEK-NVVKICDFGLARDIYKD---PDYVRKGDARLPLKWMAPETIFDRVYT 1081
Cdd:cd13991  103 YLGQALEGLEYLHSRKILHGDVKADNVLLSSDgSDAFLCDFGHAECLDPDglgKSLFTGDYIPGTETHMAPEVVLGKPCD 182
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1082 IQSDVWSFGVLLWEIFSlGASPYPGVKIDEEFCRRLKEGTRMRA-PDYTTPEMYQTMLDCWHEDPNQRPSFSELVEHLGN 1160
Cdd:cd13991  183 AKVDVWSSCCMMLHMLN-GCHPWTQYYSGPLCLKIANEPPPLREiPPSCAPLTAQAIQAGLRKEPVHRASAAELRRKTNR 261

                 ....
gi 27777648 1161 LLQA 1164
Cdd:cd13991  262 ALQE 265
Ig_3 pfam13927
Immunoglobulin domain; This family contains immunoglobulin-like domains.
228-312 1.68e-07

Immunoglobulin domain; This family contains immunoglobulin-like domains.


Pssm-ID: 464046 [Multi-domain]  Cd Length: 78  Bit Score: 49.87  E-value: 1.68e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648    228 VILSPPHEIELSAGEKLVLNCTArtELNVGLDFTWHSPPSKSHHKKIVNRDVKPFPgtvakmflSTLTIESVTKSDQGEY 307
Cdd:pfam13927    3 VITVSPSSVTVREGETVTLTCEA--TGSPPPTITWYKNGEPISSGSTRSRSLSGSN--------STLTISNVTRSDAGTY 72

                   ....*
gi 27777648    308 TCVAS 312
Cdd:pfam13927   73 TCVAS 77
IgI_telokin-like cd20973
immunoglobulin-like domain of telokin and similar proteins; a member of the I-set of IgSF ...
339-404 1.75e-07

immunoglobulin-like domain of telokin and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin (Ig) domain in telokin, the C-terminal domain of myosin light chain kinase which is identical to telokin, and similar proteins. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the telokin Ig domain lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409565 [Multi-domain]  Cd Length: 88  Bit Score: 50.27  E-value: 1.75e-07
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 27777648  339 KSLVEATV--GSQVRIPVKYLSYPAPDIKWYRNGRPI-ESNYTMIVGDE-----LTIMEVTERDAGNYTVILTN 404
Cdd:cd20973    2 QTLRDKEVveGSAARFDCKVEGYPDPEVKWMKDDNPIvESRRFQIDQDEdglcsLIISDVCGDDSGKYTCKAVN 75
IG_like smart00410
Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.
342-419 1.82e-07

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.


Pssm-ID: 214653 [Multi-domain]  Cd Length: 85  Bit Score: 50.20  E-value: 1.82e-07
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648     342 VEATVGSQVRIPVKYLSYPAPDIKWYRNGR--PIESNYTMIVGD----ELTIMEVTERDAGNYTVILTNPISMEKQShmV 415
Cdd:smart00410    4 VTVKEGESVTLSCEASGSPPPEVTWYKQGGklLAESGRFSVSRSgstsTLTISNVTPEDSGTYTCAATNSSGSASSG--T 81

                    ....
gi 27777648     416 SLVV 419
Cdd:smart00410   82 TLTV 85
STKc_BMPR1 cd14144
Catalytic domain of the Serine/Threonine Kinase, Bone Morphogenetic Protein Type I Receptor; ...
1024-1148 1.85e-07

Catalytic domain of the Serine/Threonine Kinase, Bone Morphogenetic Protein Type I Receptor; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. BMPR1 functions as a receptor for morphogenetic proteins (BMPs), which are involved in the regulation of cell proliferation, survival, differentiation, and apoptosis. BMPs are able to induce bone, cartilage, ligament, and tendon formation, and may play roles in bone diseases and tumors. Vertebrates contain two type I BMP receptors, BMPR1a and BMPR1b. BMPR1 belongs to a group of receptors for the TGFbeta family of secreted signaling molecules that also includes TGFbeta, activins, growth and differentiation factors, and anti-Mullerian hormone, among others. These receptors contain an extracellular domain that binds ligands, a single transmembrane (TM) region, and a cytoplasmic catalytic kinase domain. Type I receptors, like BMPR1, are low-affinity receptors that bind ligands only after they are recruited by the ligand/type II high-affinity receptor complex. Following activation, they start intracellular signaling to the nucleus by phosphorylating SMAD proteins. Type I receptors contain an additional domain located between the TM and kinase domains called the GS domain, which contains the activating phosphorylation site and confers preference for specific SMAD proteins. The BMPR1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271046 [Multi-domain]  Cd Length: 287  Bit Score: 54.40  E-value: 1.85e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1024 HRDLAARNILLSEKNVVKICDFGLARDIYKDPDYVRKG-DARLPLK-WMAPETI--------FDRVytIQSDVWSFGVLL 1093
Cdd:cd14144  123 HRDIKSKNILVKKNGTCCIADLGLAVKFISETNEVDLPpNTRVGTKrYMAPEVLdeslnrnhFDAY--KMADMYSFGLVL 200
                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 27777648 1094 WEIFSLGASP----------YPGVKIDEEF--CRRLKEGTRMRAP---DYTTPEMYQTML----DCWHEDPNQR 1148
Cdd:cd14144  201 WEIARRCISGgiveeyqlpyYDAVPSDPSYedMRRVVCVERRRPSipnRWSSDEVLRTMSklmsECWAHNPAAR 274
Ig_Titin_like cd05748
Immunoglobulin (Ig)-like domain of titin and similar proteins; The members here are composed ...
346-419 1.95e-07

Immunoglobulin (Ig)-like domain of titin and similar proteins; The members here are composed of the immunoglobulin (Ig)-like domain found in titin-like proteins and similar proteins. Titin (also called connectin) is a fibrous sarcomeric protein specifically found in vertebrate striated muscle. Titin is a giant protein; depending on isoform composition, it ranges from 2970 to 3700 kDa, and is of a length that spans half a sarcomere. Titin largely consists of multiple repeats of Ig-like and fibronectin type 3 (FN-III)-like domains. Titin connects the ends of myosin thick filaments to Z disks and extends along the thick filament to the H zone. It appears to function similarly to an elastic band, keeping the myosin filaments centered in the sarcomere during muscle contraction or stretching. Within the sarcomere, titin is also attached to or is associated with myosin binding protein C (MyBP-C). MyBP-C appears to contribute to the generation of passive tension by titin and like titin has repeated Ig-like and FN-III domains. Also included in this group are worm twitchin and insect projectin, thick filament proteins of invertebrate muscle which also have repeated Ig-like and FN-III domains.


Pssm-ID: 409406 [Multi-domain]  Cd Length: 82  Bit Score: 49.90  E-value: 1.95e-07
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 27777648  346 VGSQVRIPVKYLSYPAPDIKWYRNGRPIESN--YTMIVGDE---LTIMEVTERDAGNYTVILTNPiSMEKQSHmVSLVV 419
Cdd:cd05748    6 AGESLRLDIPIKGRPTPTVTWSKDGQPLKETgrVQIETTASstsLVIKNAKRSDSGKYTLTLKNS-AGEKSAT-INVKV 82
Ig4_PDGFR cd05859
Fourth immunoglobulin (Ig)-like domain of platelet-derived growth factor receptor (PDGFR); The ...
331-421 2.12e-07

Fourth immunoglobulin (Ig)-like domain of platelet-derived growth factor receptor (PDGFR); The members here are composed of the fourth immunoglobulin (Ig)-like domain of platelet-derived growth factor receptor (PDGFR; also known as cluster of differentiation (CD) 140a) alpha and beta. PDGF is a potent mitogen for connective tissue cells. PDGF-stimulated processes are mediated by three different PDGFs (PDGF-A,PDGF-B, and PDGF-C). PDGFR alpha binds to all three PDGFs, whereas the PDGFR beta binds only to PDGF-B. PDGF alpha is organized as an extracellular component having five Ig-like domains, a transmembrane segment, and a cytoplasmic portion having protein tyrosine kinase activity. In mice, PDGFR alpha and PDGFR beta are essential for normal development.


Pssm-ID: 409445  Cd Length: 101  Bit Score: 50.25  E-value: 2.12e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  331 FIAFGSGMKSLVEATVGSQVRIPVKYLSYPAPDIKWYRNGRPIESNYTMIVGD-----------ELTIMEVTERDAGNYT 399
Cdd:cd05859    2 FIALKPTFGQLEFANLHEVKEFVVEVEAYPPPQIRWLKDNRTLIENLTEITTStrnvqetryvsKLKLIRAKEEDSGLYT 81
                         90       100
                 ....*....|....*....|..
gi 27777648  400 VILTNpiSMEKQSHMVSLVVNV 421
Cdd:cd05859   82 ALAQN--EDAVKSYTFALQIQV 101
STKc_TGFbR2_like cd14055
Catalytic domain of the Serine/Threonine Kinase, Transforming Growth Factor beta Type II ...
1024-1161 2.17e-07

Catalytic domain of the Serine/Threonine Kinase, Transforming Growth Factor beta Type II Receptor; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TGFbR2 belongs to a group of receptors for the TGFbeta family of secreted signaling molecules that includes TGFbeta, bone morphogenetic proteins, activins, growth and differentiation factors, and anti-Mullerian hormone, among others. These receptors contain an extracellular domain that binds ligands, a single transmembrane region, and a cytoplasmic catalytic kinase domain. Type II receptors, such as TGFbR2, are high-affinity receptors which bind ligands, autophosphorylate, as well as trans-phosphorylate and activate low-affinity type I receptors. TGFbR2 acts as the receptor for TGFbeta, which is crucial in growth control and homeostasis in many different tissues. It plays roles in regulating apoptosis and in maintaining the balance between self renewal and cell loss. It also plays a key role in maintaining vascular integrity and in regulating responses to genotoxic stress. Mutations in TGFbR2 can cause aortic aneurysm disorders such as Loeys-Dietz and Marfan syndromes. The TGFbR2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270957 [Multi-domain]  Cd Length: 295  Bit Score: 54.31  E-value: 2.17e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1024 HRDLAARNILLSEKNVVKICDFGLArdIYKDP-----DYVRKGDARLPlKWMAPETIFDRVYTI------QSDVWSFGVL 1092
Cdd:cd14055  130 HRDLKSSNILVKNDGTCVLADFGLA--LRLDPslsvdELANSGQVGTA-RYMAPEALESRVNLEdlesfkQIDVYSMALV 206
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1093 LWEIFS----LG-ASPYP---GVKIDEEFCRR------LKEGTRMRAPD-YTTPE----MYQTMLDCWHEDPNQRPSFSE 1153
Cdd:cd14055  207 LWEMASrceaSGeVKPYElpfGSKVRERPCVEsmkdlvLRDRGRPEIPDsWLTHQgmcvLCDTITECWDHDPEARLTASC 286

                 ....*...
gi 27777648 1154 LVEHLGNL 1161
Cdd:cd14055  287 VAERFNEL 294
STKc_MLCK4 cd14193
Catalytic domain of the Serine/Threonine Kinase, Myosin Light Chain Kinase 4; STKs catalyze ...
998-1106 2.19e-07

Catalytic domain of the Serine/Threonine Kinase, Myosin Light Chain Kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MLCK phosphorylates myosin regulatory light chain and controls the contraction of all muscle types. In vertebrates, different MLCKs function in smooth (MLCK1), skeletal (MLCK2), and cardiac (MLCK3) muscles. A fourth protein, MLCK4, has also been identified through comprehensive genome analysis although it has not been biochemically characterized. MLCK4 (or MYLK4 or SgK085) contains a single kinase domain near the C-terminus. The MLCK4 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271095 [Multi-domain]  Cd Length: 261  Bit Score: 53.76  E-value: 2.19e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  998 LTLEHLICYSFQVAKGMEFLASRKCIHRDLAARNILL--SEKNVVKICDFGLARDiYKdPDYVRKGDARLPlKWMAPETI 1075
Cdd:cd14193   99 LTELDTILFIKQICEGIQYMHQMYILHLDLKPENILCvsREANQVKIIDFGLARR-YK-PREKLRVNFGTP-EFLAPEVV 175
                         90       100       110
                 ....*....|....*....|....*....|.
gi 27777648 1076 FDRVYTIQSDVWSFGVLLWEIFSlGASPYPG 1106
Cdd:cd14193  176 NYEFVSFPTDMWSLGVIAYMLLS-GLSPFLG 205
Ig4_Contactin-2-like cd05728
Fourth Ig domain of the neural cell adhesion molecule contactin-2, and similar domains; The ...
678-747 2.21e-07

Fourth Ig domain of the neural cell adhesion molecule contactin-2, and similar domains; The members here are composed of the fourth Ig domain of the neural cell adhesion molecule contactin-2. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-2 (also called TAG-1, axonin-1) facilitates cell adhesion by homophilic binding between molecules in apposed membranes. The first four Ig domains form the intermolecular binding fragment which arranges as a compact U-shaped module by contacts between Ig domains 1 and 4, and domains 2 and 3. It has been proposed that a linear zipper-like array forms, from contactin-2 molecules alternatively provided by the two apposed membranes.


Pssm-ID: 143205 [Multi-domain]  Cd Length: 85  Bit Score: 49.91  E-value: 2.21e-07
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 27777648  678 IGETIEVTCPASGNPTPHITWFKDNETLVEDSGIVLRDGnrNLTIRRVRKEDGGLYTCQACNVLGC--ARAE 747
Cdd:cd05728   13 IGSSLRWECKASGNPRPAYRWLKNGQPLASENRIEVEAG--DLRITKLSLSDSGMYQCVAENKHGTiyASAE 82
STKc_PIM1 cd14100
Catalytic domain of the Serine/Threonine kinase, Proviral Integration Moloney virus (PIM) ...
996-1157 2.56e-07

Catalytic domain of the Serine/Threonine kinase, Proviral Integration Moloney virus (PIM) kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The PIM gene locus was discovered as a result of the cloning of retroviral intergration sites in murine Moloney leukemia virus, leading to the identification of PIM kinases. They are constitutively active STKs with a broad range of cellular targets and are overexpressed in many haematopoietic malignancies and solid cancers. Vertebrates contain three distinct PIM kinase genes (PIM1-3); each gene may result in mutliple protein isoforms. There are two PIM1 isoforms resulting from alternative translation initiation sites. PIM1 is the founding member of the PIM subfamily. It is involved in regulating cell growth, differentiation, and apoptosis. It promotes cancer development when overexpressed by inhibiting apoptosis, promoting cell proliferation, and promoting genomic instability. The PIM1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271002 [Multi-domain]  Cd Length: 254  Bit Score: 53.43  E-value: 2.56e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  996 DFLT----LEHLICYSF--QVAKGMEFLASRKCIHRDLAARNILLS-EKNVVKICDFG---LARD-IYKDPDYVRkgdAR 1064
Cdd:cd14100   95 DFITergaLPEELARSFfrQVLEAVRHCHNCGVLHRDIKDENILIDlNTGELKLIDFGsgaLLKDtVYTDFDGTR---VY 171
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1065 LPLKWMApetiFDRVYTIQSDVWSFGVLLWEIFSlGASPYpgvKIDEEFCRRlKEGTRMRapdyTTPEMYQTMLDCWHED 1144
Cdd:cd14100  172 SPPEWIR----FHRYHGRSAAVWSLGILLYDMVC-GDIPF---EHDEEIIRG-QVFFRQR----VSSECQHLIKWCLALR 238
                        170
                 ....*....|...
gi 27777648 1145 PNQRPSFSELVEH 1157
Cdd:cd14100  239 PSDRPSFEDIQNH 251
STKc_p38gamma cd07880
Catalytic domain of the Serine/Threonine Kinase, p38gamma Mitogen-Activated Protein Kinase ...
1008-1098 2.70e-07

Catalytic domain of the Serine/Threonine Kinase, p38gamma Mitogen-Activated Protein Kinase (also called MAPK12); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. p38gamma/MAPK12 is predominantly expressed in skeletal muscle. Unlike p38alpha and p38beta, p38gamma is insensitive to pyridinylimidazoles. It displays an antagonizing function compared to p38alpha. p38gamma inhibits, while p38alpha stimulates, c-Jun phosphorylation and AP-1 mediated transcription. p38gamma also plays a role in the signaling between Ras and the estrogen receptor and has been implicated to increase cell invasion and breast cancer progression. In Xenopus, p38gamma is critical in the meiotic maturation of oocytes. p38 kinases are MAPKs, serving as important mediators of cellular responses to extracellular signals. They are activated by the MAPK kinases MKK3 and MKK6, which in turn are activated by upstream MAPK kinase kinases including TAK1, ASK1, and MLK3, in response to cellular stresses or inflammatory cytokines. The p38gamma subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 143385 [Multi-domain]  Cd Length: 343  Bit Score: 54.19  E-value: 2.70e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1008 FQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARdiYKDPDYVrkgdARLPLKWM-APETIFDRV-YTIQSD 1085
Cdd:cd07880  125 YQMLKGLKYIHAAGIIHRDLKPGNLAVNEDCELKILDFGLAR--QTDSEMT----GYVVTRWYrAPEVILNWMhYTQTVD 198
                         90
                 ....*....|...
gi 27777648 1086 VWSFGVLLWEIFS 1098
Cdd:cd07880  199 IWSVGCIMAEMLT 211
STKc_CDK9 cd07865
Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 9; STKs ...
1009-1095 2.71e-07

Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 9; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK9, together with a cyclin partner (cyclin T1, T2a, T2b, or K), is the main component of distinct positive transcription elongation factors (P-TEFb), which function as Ser2 C-terminal domain kinases of RNA polymerase II. P-TEFb participates in multiple steps of gene expression including transcription elongation, mRNA synthesis, processing, export, and translation. It also plays a role in mediating cytokine induced transcription networks such as IL6-induced STAT3 signaling. In addition, the CDK9/cyclin T2a complex promotes muscle differentiation and enhances the function of some myogenic regulatory factors. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK9 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270848 [Multi-domain]  Cd Length: 310  Bit Score: 53.91  E-value: 2.71e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1009 QVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLAR--DIYKDPDYVRKGDARLPLKWMAPETIF-DRVYTIQSD 1085
Cdd:cd07865  127 MLLNGLYYIHRNKILHRDMKAANILITKDGVLKLADFGLARafSLAKNSQPNRYTNRVVTLWYRPPELLLgERDYGPPID 206
                         90
                 ....*....|
gi 27777648 1086 VWSFGVLLWE 1095
Cdd:cd07865  207 MWGAGCIMAE 216
STKc_MEKK2 cd06652
Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein (MAP)/Extracellular ...
833-1157 2.83e-07

Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MEKK2 is a MAPK kinase kinase (MAPKKK or MKKK), that phosphorylates and activates the MAPK kinase MEK5 (or MKK5), which in turn phosphorylates and activates ERK5. The ERK5 cascade plays roles in promoting cell proliferation, differentiation, neuronal survival, and neuroprotection. MEKK2 also activates ERK1/2, c-Jun N-terminal kinase (JNK) and p38 through their respective MAPKKs MEK1/2, JNK-activating kinase 2 (JNKK2), and MKK3/6. MEKK2 plays roles in T cell receptor signaling, immune synapse formation, cytokine gene expression, as well as in EGF and FGF receptor signaling. The MEKK2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270818 [Multi-domain]  Cd Length: 264  Bit Score: 53.51  E-value: 2.83e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  833 KLGKPLGRGAFGQVI---EADafgidktaTCKTVAVKMLK----EGATHSEHRALMSELKILIHIGHHlNVVNLLGACTK 905
Cdd:cd06652    5 RLGKLLGQGAFGRVYlcyDAD--------TGRELAVKQVQfdpeSPETSKEVNALECEIQLLKNLLHE-RIVQYYGCLRD 75
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  906 PGGPLMVIvefckfgnlstylrgkrneFVPYKSKGARFRQGKDYvGELSVDLKRRldsitssqssassgfveekslsdve 985
Cdd:cd06652   76 PQERTLSI-------------------FMEYMPGGSIKDQLKSY-GALTENVTRK------------------------- 110
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  986 eeeaseelykdfltlehlicYSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIYKdpdYVRKGDARL 1065
Cdd:cd06652  111 --------------------YTRQILEGVHYLHSNMIVHRDIKGANILRDSVGNVKLGDFGASKRLQT---ICLSGTGMK 167
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1066 PLK----WMAPETIFDRVYTIQSDVWSFGVLLWEIFSlGASPYPGVKIDEEFCRRLKEGTRMRAPDYTTpEMYQTMLDCW 1141
Cdd:cd06652  168 SVTgtpyWMSPEVISGEGYGRKADIWSVGCTVVEMLT-EKPPWAEFEAMAAIFKIATQPTNPQLPAHVS-DHCRDFLKRI 245
                        330
                 ....*....|....*.
gi 27777648 1142 HEDPNQRPSFSELVEH 1157
Cdd:cd06652  246 FVEAKLRPSADELLRH 261
STKc_NIM1 cd14075
Catalytic domain of the Serine/Threonine Kinase, NIM1; STKs catalyze the transfer of the ...
1009-1157 3.27e-07

Catalytic domain of the Serine/Threonine Kinase, NIM1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. NIM1 is a widely-expressed kinase belonging to the AMP-activated protein kinase (AMPK) subfamily. Although present in most tissues, NIM1 kinase activity is only observed in the brain and testis. NIM1 is capable of autophosphorylating and activating itself, but may be present in other tissues in the inactive form. The physiological function of NIM1 has yet to be elucidated. The NIM1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270977 [Multi-domain]  Cd Length: 255  Bit Score: 53.11  E-value: 3.27e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1009 QVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIYKD---------PDYVrkgdarlplkwmAPETIFDRV 1079
Cdd:cd14075  109 QIVSAVKHMHENNIIHRDLKAENVFYASNNCVKVGDFGFSTHAKRGetlntfcgsPPYA------------APELFKDEH 176
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1080 YT-IQSDVWSFGVLLWeiFSL-GASPY-----PGVKideefcRRLKEGTrMRAPDYTTP---EMYQTMLdcwHEDPNQRP 1149
Cdd:cd14075  177 YIgIYVDIWALGVLLY--FMVtGVMPFraetvAKLK------KCILEGT-YTIPSYVSEpcqELIRGIL---QPVPSDRY 244

                 ....*...
gi 27777648 1150 SFSELVEH 1157
Cdd:cd14075  245 SIDEIKNS 252
STKc_IKK_beta cd14038
Catalytic domain of the Serine/Threonine kinase, Inhibitor of Nuclear Factor-KappaB Kinase ...
1010-1104 3.47e-07

Catalytic domain of the Serine/Threonine kinase, Inhibitor of Nuclear Factor-KappaB Kinase (IKK) beta; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. IKKbeta is involved in the classical pathway of regulating Nuclear Factor-KappaB (NF-kB) proteins, a family of transcription factors which are critical in many cellular functions including inflammatory responses, immune development, cell survival, and cell proliferation, among others. The classical pathway regulates the majority of genes activated by NF-kB including those encoding cytokines, chemokines, leukocyte adhesion molecules, and anti-apoptotic factors. It involves NEMO (NF-kB Essential MOdulator)- and IKKbeta-dependent phosphorylation and degradation of the Inhibitor of NF-kB (IkB), which liberates NF-kB dimers (typified by the p50-p65 heterodimer) from an inactive IkB/dimeric NF-kB complex, enabling them to migrate to the nucleus where they regulate gene transcription. The IKKbeta subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270940 [Multi-domain]  Cd Length: 290  Bit Score: 53.43  E-value: 3.47e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1010 VAKGMEFLASRKCIHRDLAARNILLS--EKNVV-KICDFGLARDIYKDP---DYVRKgdarlpLKWMAPETIFDRVYTIQ 1083
Cdd:cd14038  110 ISSALRYLHENRIIHRDLKPENIVLQqgEQRLIhKIIDLGYAKELDQGSlctSFVGT------LQYLAPELLEQQKYTVT 183
                         90       100
                 ....*....|....*....|.
gi 27777648 1084 SDVWSFGVLLWEIFSlGASPY 1104
Cdd:cd14038  184 VDYWSFGTLAFECIT-GFRPF 203
IgI_2_Titin_Z1z2-like cd20972
Second Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk, and ...
343-412 3.48e-07

Second Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the titin Z1z2 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409564 [Multi-domain]  Cd Length: 91  Bit Score: 49.50  E-value: 3.48e-07
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 27777648  343 EATVGSQVRIPVKYLSYPAPDIKWYRNGRPIESNYTMIVGDE-----LTIMEVTERDAGNYTVILTNPISMEKQS 412
Cdd:cd20972   12 EVAEGSKVRLECRVTGNPTPVVRWFCEGKELQNSPDIQIHQEgdlhsLIIAEAFEEDTGRYSCLATNSVGSDTTS 86
STKc_PKB_gamma cd05593
Catalytic domain of the Serine/Threonine Kinase, Protein Kinase B gamma (also called Akt3); ...
1006-1148 3.66e-07

Catalytic domain of the Serine/Threonine Kinase, Protein Kinase B gamma (also called Akt3); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKB-gamma is predominantly expressed in neuronal tissues. Mice deficient in PKB-gamma show a reduction in brain weight due to the decreases in cell size and cell number. PKB-gamma has also been shown to be upregulated in estrogen-deficient breast cancer cells, androgen-independent prostate cancer cells, and primary ovarian tumors. It acts as a key mediator in the genesis of ovarian cancer. PKB contains an N-terminal pleckstrin homology (PH) domain and a C-terminal catalytic domain. The PKB-gamma subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270745 [Multi-domain]  Cd Length: 348  Bit Score: 53.93  E-value: 3.66e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1006 YSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIYKDPDYVrKGDARLPlKWMAPETIFDRVYTIQSD 1085
Cdd:cd05593  120 YGAEIVSALDYLHSGKIVYRDLKLENLMLDKDGHIKITDFGLCKEGITDAATM-KTFCGTP-EYLAPEVLEDNDYGRAVD 197
                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 27777648 1086 VWSFGVLLWEIFSlGASPYPGVKIDEEFCRRLKEGTRMraPDYTTPEMYQTMLDCWHEDPNQR 1148
Cdd:cd05593  198 WWGLGVVMYEMMC-GRLPFYNQDHEKLFELILMEDIKF--PRTLSADAKSLLSGLLIKDPNKR 257
STKc_JNK cd07850
Catalytic domain of the Serine/Threonine Kinase, c-Jun N-terminal Kinase; STKs catalyze the ...
1008-1123 3.71e-07

Catalytic domain of the Serine/Threonine Kinase, c-Jun N-terminal Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. JNKs are mitogen-activated protein kinases (MAPKs) that are involved in many stress-activated responses including those during inflammation, neurodegeneration, apoptosis, and persistent pain sensitization, among others. They are also essential regulators of physiological and pathological processes and are involved in the pathogenesis of several diseases such as diabetes, atherosclerosis, stroke, Parkinson's and Alzheimer's. Vetebrates harbor three different JNK genes (Jnk1, Jnk2, and Jnk3) that are alternatively spliced to produce at least 10 isoforms. JNKs are specifically activated by the MAPK kinases MKK4 and MKK7, which are in turn activated by upstream MAPK kinase kinases as a result of different stimuli including stresses such as ultraviolet (UV) irradiation, hyperosmolarity, heat shock, or cytokines. JNKs activate a large number of different substrates based on specific stimulus, cell type, and cellular condition, and may be implicated in seemingly contradictory functions. The JNK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270840 [Multi-domain]  Cd Length: 337  Bit Score: 53.96  E-value: 3.71e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1008 FQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLAR---DIYKDPDYVRKGDARlplkwmAPETIFDRVYTIQS 1084
Cdd:cd07850  109 YQMLCGIKHLHSAGIIHRDLKPSNIVVKSDCTLKILDFGLARtagTSFMMTPYVVTRYYR------APEVILGMGYKENV 182
                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|...
gi 27777648 1085 DVWSFGVLLWEIFsLGASPYPGV-------KI-------DEEFCRRLKEGTRM 1123
Cdd:cd07850  183 DIWSVGCIMGEMI-RGTVLFPGTdhidqwnKIieqlgtpSDEFMSRLQPTVRN 234
STKc_MSK1_N cd05613
N-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated ...
1006-1104 3.80e-07

N-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MSK1 plays a role in the regulation of translational control and transcriptional activation. It phosphorylates the transcription factors, CREB and NFkB. It also phosphorylates the nucleosomal proteins H3 and HMG-14. Increased phosphorylation of MSK1 is associated with the development of cerebral ischemic/hypoxic preconditioning. MSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family. MSKs are activated by two major signaling cascades, the Ras-MAPK and p38 stress kinase pathways, which trigger phosphorylation in the activation loop (A-loop) of the CTD of MSK. The active CTD phosphorylates the hydrophobic motif (HM) of NTD, which facilitates the phosphorylation of the A-loop and activates the NTD, which in turn phosphorylates downstream targets. The MSK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270764 [Multi-domain]  Cd Length: 290  Bit Score: 53.47  E-value: 3.80e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1006 YSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIYKDpDYVRKGDARLPLKWMAPETIF--DRVYTIQ 1083
Cdd:cd05613  110 YIGEIVLALEHLHKLGIIYRDIKLENILLDSSGHVVLTDFGLSKEFLLD-ENERAYSFCGTIEYMAPEIVRggDSGHDKA 188
                         90       100
                 ....*....|....*....|.
gi 27777648 1084 SDVWSFGVLLWEIFSlGASPY 1104
Cdd:cd05613  189 VDWWSLGVLMYELLT-GASPF 208
PHA02785 PHA02785
IL-beta-binding protein; Provisional
142-401 3.90e-07

IL-beta-binding protein; Provisional


Pssm-ID: 165149 [Multi-domain]  Cd Length: 326  Bit Score: 53.48  E-value: 3.90e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648   142 ENKNKTVVIPCrgsiSNLNvSLCARYP------EKRFVPDGNRISWDSEIGFTLPSYMISYAGMVFCEAKinDETYQSIM 215
Cdd:PHA02785   38 ELENEPVILPC----PQIN-TLSSGYNildilwEKRGADNDRIIPIDNGSNMLILNPTQSDSGIYICITK--NETYCDMM 110
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648   216 YI---VVVVGYRIYDVILSPPHEIELSAGEKLVLNCTARTELNVGLDFTWhsppskSHHKKIVNRDVKPFPGTVakmfls 292
Cdd:PHA02785  111 SLnltIVSVSESNIDLISYPQIVNERSTGEMVCPNINAFIASNVNADIIW------SGHRRLRNKRLKQRTPGI------ 178
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648   293 tLTIESVTKSDQGEYTCVAssgRMIKRNRTF-----VRVHTKP-FIAFGSGMKSLVEATVGSQVRIPVKYLSYPA---PD 363
Cdd:PHA02785  179 -ITIEDVRKNDAGYYTCVL---KYIYGDKTYnvtriVKLEVRDrIIPPTMQLPEGVVTSIGSNLTIACRVSLRPPttdAD 254
                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 27777648   364 IKWYRNGRPIESN--------------YTM----IVGDELTIMEVTERDAGNYTVI 401
Cdd:PHA02785  255 VFWISNGMYYEEDdedgdgrisvankiYTTdkrrVITSRLNINPVKEEDATTFTCM 310
STKc_MAST cd05609
Catalytic domain of the Protein Serine/Threonine Kinase, Microtubule-associated serine ...
1013-1113 3.93e-07

Catalytic domain of the Protein Serine/Threonine Kinase, Microtubule-associated serine/threonine kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAST kinases contain an N-terminal domain of unknown function, a central catalytic domain, and a C-terminal PDZ domain that mediates protein-protein interactions. There are four mammalian MAST kinases, named MAST1-MAST4. MAST1 is also called syntrophin-associated STK (SAST) while MAST2 is also called MAST205. MAST kinases are cytoskeletal associated kinases of unknown function that are also expressed at neuromuscular junctions and postsynaptic densities. MAST1, MAST2, and MAST3 bind and phosphorylate the tumor suppressor PTEN, and may contribute to the regulation and stabilization of PTEN. MAST2 is involved in the regulation of the Fc-gamma receptor of the innate immune response in macrophages, and may also be involved in the regulation of the Na+/H+ exchanger NHE3. The MAST kinase subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270760 [Multi-domain]  Cd Length: 280  Bit Score: 53.18  E-value: 3.93e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1013 GMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLAR--------DIYKD------PDYVRKGDARLPlKWMAPETIFDR 1078
Cdd:cd05609  112 ALEYLHSYGIVHRDLKPDNLLITSMGHIKLTDFGLSKiglmslttNLYEGhiekdtREFLDKQVCGTP-EYIAPEVILRQ 190
                         90       100       110
                 ....*....|....*....|....*....|....*
gi 27777648 1079 VYTIQSDVWSFGVLLWEiFSLGASPYPGVKIDEEF 1113
Cdd:cd05609  191 GYGKPVDWWAMGIILYE-FLVGCVPFFGDTPEELF 224
STKc_MAPKAPK3 cd14172
Catalytic domain of the Serine/Threonine kinase, Mitogen-activated protein kinase-activated ...
1010-1157 3.96e-07

Catalytic domain of the Serine/Threonine kinase, Mitogen-activated protein kinase-activated protein kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAPK-activated protein kinase 3 (MAPKAP3 or MK3) contains an N-terminal proline-rich region that can bind to SH3 domains, a catalytic kinase domain followed by a C-terminal autoinhibitory region that contains nuclear localization (NLS) and nuclear export (NES) signals with a p38 MAPK docking motif that overlaps the NLS. MK3 is a bonafide substrate for the MAPK p38. It is closely related to MK2 and thus far, MK2/3 show indistinguishable substrate specificity. They are mainly involved in the regulation of gene expression and they participate in diverse cellular processes such as endocytosis, cytokine production, cytoskeletal reorganization, cell migration, cell cycle control and chromatin remodeling. They are implicated in inflammation and cance and their substrates include mRNA-AU-rich-element (ARE)-binding proteins (TTP and hnRNP A0), Hsp proteins (Hsp27 and Hsp25) and RSK, among others. MK2/3 are both expressed ubiquitously but MK2 is expressed at significantly higher levels. MK3 activity is only significant when MK2 is absent. The MK3 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271074 [Multi-domain]  Cd Length: 267  Bit Score: 53.07  E-value: 3.96e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1010 VAKGMEFLASRKCIHRDLAARNILLSEKN---VVKICDFGLARDI-----YKDPDYVrkgdarlPLkWMAPETIFDRVYT 1081
Cdd:cd14172  112 IGTAIQYLHSMNIAHRDVKPENLLYTSKEkdaVLKLTDFGFAKETtvqnaLQTPCYT-------PY-YVAPEVLGPEKYD 183
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1082 IQSDVWSFGVLLWeIFSLGASPY---PGVKIDEEFCRRLKEGT-RMRAPDYT--TPEMYQTMLDCWHEDPNQRPSFSELV 1155
Cdd:cd14172  184 KSCDMWSLGVIMY-ILLCGFPPFysnTGQAISPGMKRRIRMGQyGFPNPEWAevSEEAKQLIRHLLKTDPTERMTITQFM 262

                 ..
gi 27777648 1156 EH 1157
Cdd:cd14172  263 NH 264
PKc_Mps1 cd14131
Catalytic domain of the Dual-specificity Mitotic checkpoint protein kinase, Monopolar spindle ...
1023-1157 4.02e-07

Catalytic domain of the Dual-specificity Mitotic checkpoint protein kinase, Monopolar spindle 1 (also called TTK); Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine as well as tyrosine residues on protein substrates. TTK/Mps1 is a spindle checkpoint kinase that was first discovered due to its necessity in centrosome duplication in budding yeast. It was later found to function in the spindle assembly checkpoint, which monitors the proper attachment of chromosomes to the mitotic spindle. In yeast, substrates of Mps1 include the spindle pole body components Spc98p, Spc110p, and Spc42p. The TTK/Mps1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein serine/threonine PKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271033 [Multi-domain]  Cd Length: 271  Bit Score: 52.99  E-value: 4.02e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1023 IHRDLAARNILLSEKNVvKICDFGLARDIYKDPDYVRKgDARL-PLKWMAPETIFD--------RVYTI--QSDVWSFGV 1091
Cdd:cd14131  125 VHSDLKPANFLLVKGRL-KLIDFGIAKAIQNDTTSIVR-DSQVgTLNYMSPEAIKDtsasgegkPKSKIgrPSDVWSLGC 202
                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 27777648 1092 LLWEiFSLGASPYPGV-KIDEEFCRRLKEGTRMRAPDYTTPEMYQTMLDCWHEDPNQRPSFSELVEH 1157
Cdd:cd14131  203 ILYQ-MVYGKTPFQHItNPIAKLQAIIDPNHEIEFPDIPNPDLIDVMKRCLQRDPKKRPSIPELLNH 268
STKc_Titin cd14104
Catalytic domain of the Giant Serine/Threonine Kinase Titin; STKs catalyze the transfer of the ...
998-1106 4.04e-07

Catalytic domain of the Giant Serine/Threonine Kinase Titin; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Titin, also called connectin, is a muscle-specific elastic protein and is the largest known protein to date. It contains multiple immunoglobulin (Ig)-like and fibronectin type III (FN3) domains, and a single kinase domain near the C-terminus. It spans half of the sarcomere, the repeating contractile unit of striated muscle, and performs mechanical and catalytic functions. Titin contributes to the passive force generated when muscle is stretched during relaxation. Its kinase domain phosphorylates and regulates the muscle protein telethonin, which is required for sarcomere formation in differentiating myocytes. In addition, titin binds many sarcomere proteins and acts as a molecular scaffold for filament formation during myofibrillogenesis. The Titin subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271006 [Multi-domain]  Cd Length: 277  Bit Score: 53.33  E-value: 4.04e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  998 LTLEHLICYSFQVAKGMEFLASRKCIHRDLAARNILLSEK--NVVKICDFGLARDIyKDPDYVRKgdARLPLKWMAPETI 1075
Cdd:cd14104   94 LNEREIVSYVRQVCEALEFLHSKNIGHFDIRPENIIYCTRrgSYIKIIEFGQSRQL-KPGDKFRL--QYTSAEFYAPEVH 170
                         90       100       110
                 ....*....|....*....|....*....|.
gi 27777648 1076 FDRVYTIQSDVWSFGVLLWEIFSlGASPYPG 1106
Cdd:cd14104  171 QHESVSTATDMWSLGCLVYVLLS-GINPFEA 200
STKc_Sck1_like cd05586
Catalytic domain of Suppressor of loss of cAMP-dependent protein kinase-like Serine/Threonine ...
1014-1104 4.19e-07

Catalytic domain of Suppressor of loss of cAMP-dependent protein kinase-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of Schizosaccharomyces pombe Sck1 and similar fungal proteins. Sck1 plays a role in trehalase activation triggered by glucose and a nitrogen source. Trehalase catalyzes the cleavage of the disaccharide trehalose to glucose. Trehalose, as a carbohydrate reserve and stress metabolite, plays an important role in the response of yeast to environmental changes. The Sck1-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270738 [Multi-domain]  Cd Length: 330  Bit Score: 53.73  E-value: 4.19e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1014 MEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIYKDPDYVRK--GDArlplKWMAPETIFDRV-YTIQSDVWSFG 1090
Cdd:cd05586  109 LEHLHKNDIVYRDLKPENILLDANGHIALCDFGLSKADLTDNKTTNTfcGTT----EYLAPEVLLDEKgYTKMVDFWSLG 184
                         90
                 ....*....|....
gi 27777648 1091 VLLWEIfSLGASPY 1104
Cdd:cd05586  185 VLVFEM-CCGWSPF 197
STKc_MSK_C cd14092
C-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated ...
1009-1104 4.27e-07

C-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family. MSKs are activated by two major signaling cascades, the Ras-MAPK and p38 stress kinase pathways, in response to various stimuli such as growth factors, hormones, neurotransmitters, cellular stress, and pro-inflammatory cytokines. This triggers phosphorylation in the activation loop (A-loop) of the CTD of MSK. The active CTD phosphorylates the hydrophobic motif (HM) in the C-terminal extension of NTD, which facilitates the phosphorylation of the A-loop and activates the NTD, which in turn phosphorylates downstream targets. MSKs are predominantly nuclear proteins. They are widely expressed in many tissues including heart, brain, lung, liver, kidney, and pancreas. There are two isoforms of MSK, called MSK1 and MSK2. The MSK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270994 [Multi-domain]  Cd Length: 311  Bit Score: 53.46  E-value: 4.27e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1009 QVAKGMEFLASRKCIHRDLAARNILL---SEKNVVKICDFGLARdiyKDPDYVRKGDARLPLKWMAPETIFDRV----YT 1081
Cdd:cd14092  107 QLVSAVSFMHSKGVVHRDLKPENLLFtdeDDDAEIKIVDFGFAR---LKPENQPLKTPCFTLPYAAPEVLKQALstqgYD 183
                         90       100
                 ....*....|....*....|...
gi 27777648 1082 IQSDVWSFGVLLWEIFSlGASPY 1104
Cdd:cd14092  184 ESCDLWSLGVILYTMLS-GQVPF 205
STKc_NUAK cd14073
Catalytic domain of the Serine/Threonine Kinase, novel (nua) kinase family NUAK; STKs catalyze ...
1009-1106 4.50e-07

Catalytic domain of the Serine/Threonine Kinase, novel (nua) kinase family NUAK; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. NUAK proteins are classified as AMP-activated protein kinase (AMPK)-related kinases, which like AMPK are activated by the major tumor suppressor LKB1. Vertebrates contain two NUAK proteins, called NUAK1 and NUAK2. NUAK1, also called ARK5 (AMPK-related protein kinase 5), regulates cell proliferation and displays tumor suppression through direct interaction and phosphorylation of p53. It is also involved in cell senescence and motility. High NUAK1 expression is associated with invasiveness of nonsmall cell lung cancer (NSCLC) and breast cancer cells. NUAK2, also called SNARK (Sucrose, non-fermenting 1/AMP-activated protein kinase-related kinase), is involved in energy metabolism. It is activated by hyperosmotic stress, DNA damage, and nutrients such as glucose and glutamine. NUAK2-knockout mice develop obesity, altered serum lipid profiles, hyperinsulinaemia, hyperglycaemia, and impaired glucose tolerance. The NUAK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270975 [Multi-domain]  Cd Length: 254  Bit Score: 52.78  E-value: 4.50e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1009 QVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLArDIYKDPDYVRK--GDarlPLkWMAPETIFDRVYT-IQSD 1085
Cdd:cd14073  109 QIVSAVHYCHKNGVVHRDLKLENILLDQNGNAKIADFGLS-NLYSKDKLLQTfcGS---PL-YASPEIVNGTPYQgPEVD 183
                         90       100
                 ....*....|....*....|.
gi 27777648 1086 VWSFGVLLWeIFSLGASPYPG 1106
Cdd:cd14073  184 CWSLGVLLY-TLVYGTMPFDG 203
STKc_PFTAIRE2 cd07870
Catalytic domain of the Serine/Threonine Kinase, PFTAIRE-2 kinase; STKs catalyze the transfer ...
1006-1107 4.71e-07

Catalytic domain of the Serine/Threonine Kinase, PFTAIRE-2 kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PFTAIRE-2 is also referred to as ALS2CR7 (amyotrophic lateral sclerosis 2 (juvenile) chromosome region candidate 7). It may be associated with amyotrophic lateral sclerosis 2 (ALS2), an autosomal recessive form of juvenile ALS. The function of PFTAIRE-2 is not yet known. It shares sequence similarity with Cyclin-Dependent Kinases (CDKs), which belong to a large family of STKs that are regulated by their cognate cyclins. Together, CDKs and cyclins are involved in the control of cell-cycle progression, transcription, and neuronal function. The PFTAIRE-2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270852 [Multi-domain]  Cd Length: 286  Bit Score: 53.04  E-value: 4.71e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1006 YSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDiYKDPDYVRKGDArLPLKWMAPETIFDRV-YTIQS 1084
Cdd:cd07870  103 FMFQLLRGLAYIHGQHILHRDLKPQNLLISYLGELKLADFGLARA-KSIPSQTYSSEV-VTLWYRPPDVLLGATdYSSAL 180
                         90       100
                 ....*....|....*....|...
gi 27777648 1085 DVWSFGVLLWEIFSlGASPYPGV 1107
Cdd:cd07870  181 DIWGAGCIFIEMLQ-GQPAFPGV 202
IgI_2_Necl-1-4 cd05761
Second immunoglobulin (Ig)-like domain of the nectin-like molecules Necl-1 - Necl-4; member of ...
665-737 4.73e-07

Second immunoglobulin (Ig)-like domain of the nectin-like molecules Necl-1 - Necl-4; member of the I-set of Ig superfamily domains; The members here are composed of the second immunoglobulin (Ig)-like domain of the nectin-like molecules Necl-1 (also known as cell adhesion molecule 3 or CADM3), Necl-2 (also known as CADM1), Necl-3 (also known as CADM2) and Necl-4 (also known as CADM4). These nectin-like molecules have similar domain structures to those of nectins. At least five nectin-like molecules have been identified (Necl-1 through Necl-5). These have an extracellular region containing three Ig-like domains, one transmembrane region, and one cytoplasmic region. The N-terminal Ig-like domain of the extracellular region belongs to the V-type subfamily of Ig domains, is essential to cell-cell adhesion, and plays a part in the interaction with the envelope glycoprotein D of various viruses. Necl-1 and Necl-2 have Ca(2+)-independent homophilic and heterophilic cell-cell adhesion activity. Necl-1 is specifically expressed in neural tissue and is important to the formation of synapses, axon bundles, and myelinated axons. Necl-2 is expressed in a wide variety of tissues, and is a putative tumour suppressor gene, which is downregulated in aggressive neuroblastoma. Necl-3 has been shown to accumulate in tissues of the central and peripheral nervous system, where it is expressed in ependymal cells and myelinated axons. It is observed at the interface between the axon shaft and the myelin sheath. Necl-4 is expressed on Schwann cells, and plays a key part in initiating peripheral nervous system (PNS) myelination. Necl-4 participates in cell-cell adhesion and is proposed to play a role in tumor suppression.


Pssm-ID: 409418  Cd Length: 102  Bit Score: 49.35  E-value: 4.73e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  665 PMITGnlENQTTTIGETIEVTCPASGN-PTPHITWFKDNETLVEDSGIVlRDGNR-------NLTIRRVRKEDGGLYTCQ 736
Cdd:cd05761    7 PVITG--FTSPVVEGDEITLTCTTSGSkPAADIRWFKNDKELKGVKEVQ-ESGAGktftvtsTLRFRVDRDDDGVAVICR 83

                 .
gi 27777648  737 A 737
Cdd:cd05761   84 V 84
IgI_2_Titin_Z1z2-like cd20972
Second Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk, and ...
664-744 4.94e-07

Second Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the titin Z1z2 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409564 [Multi-domain]  Cd Length: 91  Bit Score: 49.12  E-value: 4.94e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  664 APMITGNLENQTTTIGETIEVTCPASGNPTPHITWFKDNETLVEDSGI-VLRDGN-RNLTIRRVRKEDGGLYTCQACNVL 741
Cdd:cd20972    1 PPQFIQKLRSQEVAEGSKVRLECRVTGNPTPVVRWFCEGKELQNSPDIqIHQEGDlHSLIIAEAFEEDTGRYSCLATNSV 80

                 ...
gi 27777648  742 GCA 744
Cdd:cd20972   81 GSD 83
STKc_SGK3 cd05604
Catalytic domain of the Protein Serine/Threonine Kinase, Serum- and Glucocorticoid-induced ...
1006-1157 5.38e-07

Catalytic domain of the Protein Serine/Threonine Kinase, Serum- and Glucocorticoid-induced Kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SGK3 (also called cytokine-independent survival kinase or CISK) is expressed in most tissues and is most abundant in the embryo and adult heart and spleen. It was originally discovered in a screen for antiapoptotic genes. It phosphorylates and inhibits the proapoptotic proteins, Bad and FKHRL1. SGK3 also regulates many transporters, ion channels, and receptors. It plays a critical role in hair follicle morphogenesis and hair cycling. The SGK3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270755 [Multi-domain]  Cd Length: 326  Bit Score: 53.04  E-value: 5.38e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1006 YSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARdiykdpDYVRKGDARLPL----KWMAPETIFDRVYT 1081
Cdd:cd05604  102 YAAEIASALGYLHSINIVYRDLKPENILLDSQGHIVLTDFGLCK------EGISNSDTTTTFcgtpEYLAPEVIRKQPYD 175
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1082 IQSDVWSFGVLLWEIFSlGASPYPGVKIDEEFCRRLKEGTRMRaPDYTTP--EMYQTMLDcwhEDPNQR----PSFSELV 1155
Cdd:cd05604  176 NTVDWWCLGSVLYEMLY-GLPPFYCRDTAEMYENILHKPLVLR-PGISLTawSILEELLE---KDRQLRlgakEDFLEIK 250

                 ..
gi 27777648 1156 EH 1157
Cdd:cd05604  251 NH 252
IgI_3_Contactin-1 cd05851
Third immunoglobulin (Ig) domain of contactin-1; member of the I-set of Ig superfamily (IgSF) ...
665-742 5.54e-07

Third immunoglobulin (Ig) domain of contactin-1; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig) domain of the neural cell adhesion molecule contactin-1. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-1 is differentially expressed in tumor tissues and may through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma. This group belongs to the I-set of IgSF domains.


Pssm-ID: 143259  Cd Length: 88  Bit Score: 48.86  E-value: 5.54e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  665 PMITGNLENQTTTIGETIEVTCPASGNPTPHITWFKDNETL-----VEDSGIVLRdgnrnltIRRVRKEDGGLYTCQACN 739
Cdd:cd05851    2 ADINVKFKDTYALKGQNVTLECFALGNPVPVIRWRKILEPMpataeISMSGAVLK-------IFNIQPEDEGTYECEAEN 74

                 ...
gi 27777648  740 VLG 742
Cdd:cd05851   75 IKG 77
STKc_RIP2 cd14026
Catalytic domain of the Serine/Threonine kinase, Receptor Interacting Protein 2; STKs catalyze ...
1008-1151 5.67e-07

Catalytic domain of the Serine/Threonine kinase, Receptor Interacting Protein 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. RIP2, also called RICK or CARDIAK, harbors a C-terminal Caspase Activation and Recruitment domain (CARD) belonging to the Death domain (DD) superfamily. It functions as an effector kinase downstream of the pattern recognition receptors from the Nod-like (NLR) family, Nod1 and Nod2, which recognizes bacterial peptidoglycans released upon infection. RIP2 may also be involved in regulating wound healing and keratinocyte proliferation. RIP kinases serve as essential sensors of cellular stress. The RIP2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270928 [Multi-domain]  Cd Length: 284  Bit Score: 52.61  E-value: 5.67e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1008 FQVAKGMEFL--ASRKCIHRDLAARNILLSEKNVVKICDFGLA--RDIykdpdYVRKGDARLPLK------WMAPETI-- 1075
Cdd:cd14026  107 YEIALGVNYLhnMSPPLLHHDLKTQNILLDGEFHVKIADFGLSkwRQL-----SISQSRSSKSAPeggtiiYMPPEEYep 181
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1076 -FDRVYTIQSDVWSFGVLLWEIFSLgASPYPGVKIDEEFCRRLKEGTRMRAPDYTTP-------EMYQTMLDCWHEDPNQ 1147
Cdd:cd14026  182 sQKRRASVKHDIYSYAIIMWEVLSR-KIPFEEVTNPLQIMYSVSQGHRPDTGEDSLPvdiphraTLINLIESGWAQNPDE 260

                 ....
gi 27777648 1148 RPSF 1151
Cdd:cd14026  261 RPSF 264
STKc_DRAK2 cd14198
The catalytic domain of the Serine/Threonine Kinase, Death-associated protein kinase-Related ...
1009-1113 5.85e-07

The catalytic domain of the Serine/Threonine Kinase, Death-associated protein kinase-Related Apoptosis-inducing protein Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. DRAKs were named based on their similarity (around 50% identity) to the kinase domain of DAPKs. They contain an N-terminal kinase domain and a C-terminal regulatory domain. Vertebrates contain two subfamily members, DRAK1 and DRAK2 (also called STK17B). Both DRAKs are localized to the nucleus, autophosphorylate themselves, and phosphorylate myosin light chain as a substrate. DRAK2 has been implicated in inducing or enhancing apoptosis in beta cells, fibroblasts, and lymphoid cells, where it is highly expressed. It is involved in regulating many immune processes including the germinal center (GC) reaction, responses to thymus-dependent antigens, activated T cell survival, memory T cell responses. It may be involved in the development of autoimmunity. The DRAK2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271100 [Multi-domain]  Cd Length: 270  Bit Score: 52.62  E-value: 5.85e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1009 QVAKGMEFLASRKCIHRDLAARNILLSEKNV---VKICDFGLA---------RDIYKDPDYVrkgdarlplkwmAPETIF 1076
Cdd:cd14198  118 QILEGVYYLHQNNIVHLDLKPQNILLSSIYPlgdIKIVDFGMSrkighacelREIMGTPEYL------------APEILN 185
                         90       100       110
                 ....*....|....*....|....*....|....*..
gi 27777648 1077 DRVYTIQSDVWSFGVLLWEIFSlGASPYPGVKIDEEF 1113
Cdd:cd14198  186 YDPITTATDMWNIGVIAYMLLT-HESPFVGEDNQETF 221
STKc_PRKX_like cd05612
Catalytic domain of PRKX-like Protein Serine/Threonine Kinases; STKs catalyze the transfer of ...
1006-1104 5.93e-07

Catalytic domain of PRKX-like Protein Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Members of this group include human PRKX (X chromosome-encoded protein kinase), Drosophila DC2, and similar proteins. PRKX is present in many tissues including fetal and adult brain, kidney, and lung. The PRKX gene is located in the Xp22.3 subregion and has a homolog called PRKY on the Y chromosome. An abnormal interchange between PRKX aand PRKY leads to the sex reversal disorder of XX males and XY females. PRKX is implicated in granulocyte/macrophage lineage differentiation, renal cell epithelial migration, and tubular morphogenesis in the developing kidney. The PRKX-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270763 [Multi-domain]  Cd Length: 292  Bit Score: 52.82  E-value: 5.93e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1006 YSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIyKDPDYVRKGDArlplKWMAPETIFDRVYTIQSD 1085
Cdd:cd05612  106 YASEIVCALEYLHSKEIVYRDLKPENILLDKEGHIKLTDFGFAKKL-RDRTWTLCGTP----EYLAPEVIQSKGHNKAVD 180
                         90
                 ....*....|....*....
gi 27777648 1086 VWSFGVLLWEIFSlGASPY 1104
Cdd:cd05612  181 WWALGILIYEMLV-GYPPF 198
STKc_aPKC cd05588
Catalytic domain of the Serine/Threonine Kinase, Atypical Protein Kinase C; STKs catalyze the ...
1001-1104 6.01e-07

Catalytic domain of the Serine/Threonine Kinase, Atypical Protein Kinase C; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. aPKCs only require phosphatidylserine (PS) for activation. They contain a C2-like region, instead of a calcium-binding (C2) region found in classical PKCs, in their regulatory domain. There are two aPKC isoforms, zeta and iota. aPKCs are involved in many cellular functions including proliferation, migration, apoptosis, polarity maintenance and cytoskeletal regulation. They also play a critical role in the regulation of glucose metabolism and in the pathogenesis of type 2 diabetes. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. The aPKC subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270740 [Multi-domain]  Cd Length: 328  Bit Score: 53.19  E-value: 6.01e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1001 EHLICYSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARdiykdpDYVRKGDARLPL----KWMAPETIF 1076
Cdd:cd05588   96 EHARFYSAEISLALNFLHEKGIIYRDLKLDNVLLDSEGHIKLTDYGMCK------EGLRPGDTTSTFcgtpNYIAPEILR 169
                         90       100
                 ....*....|....*....|....*...
gi 27777648 1077 DRVYTIQSDVWSFGVLLWEIFSlGASPY 1104
Cdd:cd05588  170 GEDYGFSVDWWALGVLMFEMLA-GRSPF 196
IgI_2_FGFR cd05857
Second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor; member of ...
679-742 6.50e-07

Second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor; member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor. FGF receptors bind FGF signaling polypeptides. FGFs participate in multiple processes such as morphogenesis, development, and angiogenesis. FGFs bind to four FGF receptor tyrosine kinases (FGFR1, FGFR2, FGFR3, FGFR4). Receptor diversity is controlled by alternative splicing producing splice variants with different ligand binding characteristics and different expression patterns. FGFRs have an extracellular region comprised of three IG-like domains, a single transmembrane helix, and an intracellular tyrosine kinase domain. Ligand binding and specificity reside in the Ig-like domains 2 and 3, and the linker region that connects these two. FGFR activation and signaling depend on FGF-induced dimerization, a process involving cell surface heparin or heparin sulfate proteoglycans.


Pssm-ID: 409443 [Multi-domain]  Cd Length: 95  Bit Score: 48.70  E-value: 6.50e-07
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 27777648  679 GETIEVTCPASGNPTPHITWFKDNETLVED---SGIVLRDGNRNLTIRRVRKEDGGLYTCQACNVLG 742
Cdd:cd05857   19 ANTVKFRCPAAGNPTPTMRWLKNGKEFKQEhriGGYKVRNQHWSLIMESVVPSDKGNYTCVVENEYG 85
IgI_3_FGFR2 cd05858
Third immunoglobulin (Ig)-like domain of fibroblast growth factor receptor 2 (FGFR2); member ...
665-742 6.70e-07

Third immunoglobulin (Ig)-like domain of fibroblast growth factor receptor 2 (FGFR2); member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig)-like domain of human fibroblast growth factor receptor 2 (FGFR2). Fibroblast growth factors (FGFs) participate in morphogenesis, development, angiogenesis, and wound healing. These FGF-stimulated processes are mediated by four FGFR tyrosine kinases (FGRF1-4). FGFRs are comprised of an extracellular portion consisting of three Ig-like domains, a transmembrane helix, and a cytoplasmic portion having protein tyrosine kinase activity. The highly conserved Ig-like domains 2 and 3, and the linker region between D2 and D3 define a general binding site for FGFs. FGFR2 is required for male sex determination. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409444  Cd Length: 105  Bit Score: 49.19  E-value: 6.70e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  665 PMITGNL-ENQTTTIGETIEVTCPASGNPTPHITWFKD---NETLVEDSGI----VLRDGNRNLT--------IRRVRKE 728
Cdd:cd05858    1 PILQAGLpANTSVVVGTDAEFVCKVYSDAQPHIQWLKHvekNGSKYGPDGLpyveVLKTAGVNTTdkeievlyLRNVTFE 80
                         90
                 ....*....|....
gi 27777648  729 DGGLYTCQACNVLG 742
Cdd:cd05858   81 DAGEYTCLAGNSIG 94
Ig_Titin_like cd05748
Immunoglobulin (Ig)-like domain of titin and similar proteins; The members here are composed ...
679-752 7.08e-07

Immunoglobulin (Ig)-like domain of titin and similar proteins; The members here are composed of the immunoglobulin (Ig)-like domain found in titin-like proteins and similar proteins. Titin (also called connectin) is a fibrous sarcomeric protein specifically found in vertebrate striated muscle. Titin is a giant protein; depending on isoform composition, it ranges from 2970 to 3700 kDa, and is of a length that spans half a sarcomere. Titin largely consists of multiple repeats of Ig-like and fibronectin type 3 (FN-III)-like domains. Titin connects the ends of myosin thick filaments to Z disks and extends along the thick filament to the H zone. It appears to function similarly to an elastic band, keeping the myosin filaments centered in the sarcomere during muscle contraction or stretching. Within the sarcomere, titin is also attached to or is associated with myosin binding protein C (MyBP-C). MyBP-C appears to contribute to the generation of passive tension by titin and like titin has repeated Ig-like and FN-III domains. Also included in this group are worm twitchin and insect projectin, thick filament proteins of invertebrate muscle which also have repeated Ig-like and FN-III domains.


Pssm-ID: 409406 [Multi-domain]  Cd Length: 82  Bit Score: 48.35  E-value: 7.08e-07
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 27777648  679 GETIEVTCPASGNPTPHITWFKDNETLVEDSGIVLRDGNRN--LTIRRVRKEDGGLYTCQACNVLGcARAETLFII 752
Cdd:cd05748    7 GESLRLDIPIKGRPTPTVTWSKDGQPLKETGRVQIETTASStsLVIKNAKRSDSGKYTLTLKNSAG-EKSATINVK 81
STKc_MARK cd14072
Catalytic domain of the Serine/Threonine Kinases, MAP/microtubule affinity-regulating kinases; ...
1009-1132 7.11e-07

Catalytic domain of the Serine/Threonine Kinases, MAP/microtubule affinity-regulating kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MARKs, also called Partitioning-defective 1 (Par1) proteins, function as regulators of diverse cellular processes in nematodes, Drosophila, yeast, and vertebrates. They are involved in embryogenesis, epithelial cell polarization, cell signaling, and neuronal differentiation. MARKs phosphorylate tau and related microtubule-associated proteins (MAPs), and regulates microtubule-based intracellular transport. Vertebrates contain four isoforms, namely MARK1 (or Par1c), MARK2 (or Par1b), MARK3 (Par1a), and MARK4 (or MARKL1). Known substrates of MARKs include the cell cycle-regulating phosphatase Cdc25, tyrosine phosphatase PTPH1, MAPK scaffolding protein KSR1, class IIa histone deacetylases, and plakophilin 2. The MARK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270974 [Multi-domain]  Cd Length: 253  Bit Score: 52.14  E-value: 7.11e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1009 QVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIYK---------DPDYVrkgdarlplkwmAPETIFDRV 1079
Cdd:cd14072  107 QIVSAVQYCHQKRIVHRDLKAENLLLDADMNIKIADFGFSNEFTPgnkldtfcgSPPYA------------APELFQGKK 174
                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....
gi 27777648 1080 YT-IQSDVWSFGVLLWEIFSlGASPYPGVKIDEEFCRRLKegTRMRAPDYTTPE 1132
Cdd:cd14072  175 YDgPEVDVWSLGVILYTLVS-GSLPFDGQNLKELRERVLR--GKYRIPFYMSTD 225
PKc_CLK1_4 cd14213
Catalytic domain of the Dual-specificity protein kinases, CDC-like kinases 1 and 4; ...
829-1105 7.66e-07

Catalytic domain of the Dual-specificity protein kinases, CDC-like kinases 1 and 4; Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine as well as tyrosine residues on protein substrates. CLK1 plays a role in neuronal differentiation. CLKs are involved in the phosphorylation and regulation of serine/arginine-rich (SR) proteins, which play a crucial role in pre-mRNA splicing by directing splice site selection. SR proteins are phosphorylated first by SR protein kinases (SRPKs) at the N-terminus, which leads to its assembly into nuclear speckles where splicing factors are stored. CLKs phosphorylate the C-terminal part of SR proteins, causing the nuclear speckles to dissolve and splicing factors to be recruited at sites of active transcription. Based on a conserved "EHLAMMERILG" signature motif which may be crucial for substrate specificity, CLKs are also referred to as LAMMER kinases. CLKs autophosphorylate at tyrosine residues and phosphorylate their substrates exclusively on serine/threonine residues. The CLK1/4 subfamily is part of a larger superfamily that includes the catalytic domains of other protein serine/threonine PKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271115 [Multi-domain]  Cd Length: 330  Bit Score: 52.93  E-value: 7.66e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  829 RDRLKLGKPLGRGAFGQVIEAdafgIDKTATCKTVAVKMLKEGATHSEhrALMSELKILIHIG-----HHLNVVNLLGAC 903
Cdd:cd14213   11 RARYEIVDTLGEGAFGKVVEC----IDHKMGGMHVAVKIVKNVDRYRE--AARSEIQVLEHLNttdpnSTFRCVQMLEWF 84
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  904 TKPGgplMVIVEFCKFGnLSTYLRGKRNEFVPYKskgarfrqgkdyvgelsvdlkrrldsitssqssassgfveekslsd 983
Cdd:cd14213   85 DHHG---HVCIVFELLG-LSTYDFIKENSFLPFP---------------------------------------------- 114
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  984 veeeeaseelykdfltLEHLICYSFQVAKGMEFLASRKCIHRDLAARNILLSE------------------KNV-VKICD 1044
Cdd:cd14213  115 ----------------IDHIRNMAYQICKSVNFLHHNKLTHTDLKPENILFVQsdyvvkynpkmkrdertlKNPdIKVVD 178
                        250       260       270       280       290       300
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 27777648 1045 FGLArdIYKDPDYVRKGDARlplKWMAPETIFDRVYTIQSDVWSFGVLLWEIFsLGASPYP 1105
Cdd:cd14213  179 FGSA--TYDDEHHSTLVSTR---HYRAPEVILALGWSQPCDVWSIGCILIEYY-LGFTVFQ 233
IgI_3_Contactin cd04968
Third immunoglobulin (Ig) domain of contactin; member of the I-set of Ig superfamily (IgSF) ...
679-742 7.94e-07

Third immunoglobulin (Ig) domain of contactin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig) domain of contactins. Contactins are neural cell adhesion molecules and are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. The first four Ig domains form the intermolecular binding fragment, which arranges as a compact U-shaped module via contacts between Ig domains 1 and 4, and between Ig domains 2 and 3. Contactin-2 (TAG-1, axonin-1) may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. This group also includes contactin-1 and contactin-5. The different contactins show different expression patterns in the central nervous system. During development and in adulthood, contactin-2 is transiently expressed in subsets of central and peripheral neurons. Contactin-5 is expressed specifically in the rat postnatal nervous system, peaking at about 3 weeks postnatal, and a lack of contactin-5 (NB-2) results in an impairment of neuronal activity in the rat auditory system. Contactin-5 is highly expressed in the adult human brain in the occipital lobe and in the amygdala. Contactin-1 is differentially expressed in tumor tissues and may, through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma. This group belongs to the I-set of IgSF domains.


Pssm-ID: 409357 [Multi-domain]  Cd Length: 88  Bit Score: 48.31  E-value: 7.94e-07
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 27777648  679 GETIEVTCPASGNPTPHITWFKDNETLVedSGIVLRDGNRNLTIRRVRKEDGGLYTCQACNVLG 742
Cdd:cd04968   16 GQTVTLECFALGNPVPQIKWRKVDGSPS--SQWEITTSEPVLEIPNVQFEDEGTYECEAENSRG 77
PHA02988 PHA02988
hypothetical protein; Provisional
1024-1158 7.97e-07

hypothetical protein; Provisional


Pssm-ID: 165291 [Multi-domain]  Cd Length: 283  Bit Score: 52.44  E-value: 7.97e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  1024 HRDLAARNILLSEKNVVKICDFGL----ARDIYKDPDYVRKGDARLPLKwmapetIFDRvYTIQSDVWSFGVLLWEIFSl 1099
Cdd:PHA02988  146 YKNLTSVSFLVTENYKLKIICHGLekilSSPPFKNVNFMVYFSYKMLND------IFSE-YTIKDDIYSLGVVLWEIFT- 217
                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 27777648  1100 GASPYPGVKIDEEFCRRLKEGTRMRAPDYTTPEMYQTMLDCWHEDPNQRPSFSELVEHL 1158
Cdd:PHA02988  218 GKIPFENLTTKEIYDLIINKNNSLKLPLDCPLEIKCIVEACTSHDSIKRPNIKEILYNL 276
STKc_MAPKAPK2 cd14170
Catalytic domain of the Serine/Threonine kinase, Mitogen-activated protein kinase-activated ...
1010-1157 8.60e-07

Catalytic domain of the Serine/Threonine kinase, Mitogen-activated protein kinase-activated protein kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAPK-activated protein kinase 2 (MAPKAP2 or MK2) contains an N-terminal proline-rich region that can bind to SH3 domains, a catalytic kinase domain followed by a C-terminal autoinhibitory region that contains nuclear localization (NLS) and nuclear export (NES) signals with a p38 MAPK docking motif that overlaps the NLS. MK2 is a bonafide substrate for the MAPK p38. It is closely related to MK3 and thus far, MK2/3 show indistinguishable substrate specificity. They are mainly involved in the regulation of gene expression and they participate in diverse cellular processes such as endocytosis, cytokine production, cytoskeletal reorganization, cell migration, cell cycle control and chromatin remodeling. They are implicated in inflammation and cance and their substrates include mRNA-AU-rich-element (ARE)-binding proteins (TTP and hnRNP A0), Hsp proteins (Hsp27 and Hsp25) and RSK, among others. MK2/3 are both expressed ubiquitously but MK2 is expressed at significantly higher levels. The MK2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271072 [Multi-domain]  Cd Length: 303  Bit Score: 52.34  E-value: 8.60e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1010 VAKGMEFLASRKCIHRDLAARNILLSEKN---VVKICDFGLARDI-----YKDPDYVrkgdarlPLkWMAPETIFDRVYT 1081
Cdd:cd14170  110 IGEAIQYLHSINIAHRDVKPENLLYTSKRpnaILKLTDFGFAKETtshnsLTTPCYT-------PY-YVAPEVLGPEKYD 181
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1082 IQSDVWSFGVLLWeIFSLGASPY---PGVKIDEEFCRRLKEGT-RMRAPDYT--TPEMYQTMLDCWHEDPNQRPSFSELV 1155
Cdd:cd14170  182 KSCDMWSLGVIMY-ILLCGYPPFysnHGLAISPGMKTRIRMGQyEFPNPEWSevSEEVKMLIRNLLKTEPTQRMTITEFM 260

                 ..
gi 27777648 1156 EH 1157
Cdd:cd14170  261 NH 262
STKc_TLK cd13990
Catalytic domain of the Serine/Threonine kinase, Tousled-Like Kinase; STKs catalyze the ...
1004-1157 8.76e-07

Catalytic domain of the Serine/Threonine kinase, Tousled-Like Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TLKs play important functions during the cell cycle and are implicated in chromatin remodeling, DNA replication and repair, and mitosis. They phosphorylate and regulate Anti-silencing function 1 protein (Asf1), a histone H3/H4 chaperone that helps facilitate the assembly of chromatin following DNA replication during S phase. TLKs also phosphorylate the H3 histone tail and are essential in transcription. Vertebrates contain two subfamily members, TLK1 and TLK2. The TLK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270892 [Multi-domain]  Cd Length: 279  Bit Score: 52.32  E-value: 8.76e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1004 ICYSFQVAKGMEFLASRK--CIHRDLAARNILLSEKNV---VKICDFGLARdIYKDPDYVRKGdarLPLK-------WMA 1071
Cdd:cd13990  108 RSIIMQVVSALKYLNEIKppIIHYDLKPGNILLHSGNVsgeIKITDFGLSK-IMDDESYNSDG---MELTsqgagtyWYL 183
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1072 PETIFDRVYT---IQS--DVWSFGVLLWEIFsLGASPYpGVKIDEEfcRRLKEGTRMRAPDYTTP-------EMYQTMLD 1139
Cdd:cd13990  184 PPECFVVGKTppkISSkvDVWSVGVIFYQML-YGRKPF-GHNQSQE--AILEENTILKATEVEFPskpvvssEAKDFIRR 259
                        170
                 ....*....|....*...
gi 27777648 1140 CWHEDPNQRPSFSELVEH 1157
Cdd:cd13990  260 CLTYRKEDRPDVLQLAND 277
STKc_SRPK cd14136
Catalytic domain of the Serine/Threonine Kinase, Serine-aRginine Protein Kinase; STKs catalyze ...
1009-1095 9.63e-07

Catalytic domain of the Serine/Threonine Kinase, Serine-aRginine Protein Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SRPKs phosphorylate and regulate splicing factors from the SR protein family by specifically phosphorylating multiple serine residues residing in SR/RS dipeptide motifs (also known as RS domains). Phosphorylation of the RS domains enhances interaction with transportin SR and facilitates entry of the SR proteins into the nucleus. SRPKs contain a nonconserved insert domain, within the well-conserved catalytic kinase domain, that regulates their subcellular localization. They play important roles in mediating pre-mRNA processing and mRNA maturation, as well as other cellular functions such as chromatin reorganization, cell cycle and p53 regulation, and metabolic signaling. Vertebrates contain three distinct SRPKs, called SRPK1-3. The SRPK homolog in budding yeast, Sky1p, recognizes and phosphorylates its substrate Npl3p, which lacks a classic RS domain but contains a single RS dipeptide at the C-terminus of its RGG domain. Npl3p is a shuttling heterogeneous nuclear ribonucleoprotein (hnRNP) that exports a distinct class of mRNA from the nucleus to the cytoplasm. The SRPK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271038 [Multi-domain]  Cd Length: 320  Bit Score: 52.19  E-value: 9.63e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1009 QVAKGMEFLaSRKC--IHRDLAARNILLSEKNV-VKICDFGLARDIYKD-PDYVRKGDARlplkwmAPETIFDRVYTIQS 1084
Cdd:cd14136  127 QVLQGLDYL-HTKCgiIHTDIKPENVLLCISKIeVKIADLGNACWTDKHfTEDIQTRQYR------SPEVILGAGYGTPA 199
                         90
                 ....*....|.
gi 27777648 1085 DVWSFGVLLWE 1095
Cdd:cd14136  200 DIWSTACMAFE 210
STKc_PINK1 cd14018
Catalytic domain of the Serine/Threonine protein kinase, Pten INduced Kinase 1; STKs catalyze ...
1009-1150 9.63e-07

Catalytic domain of the Serine/Threonine protein kinase, Pten INduced Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PINK1 contains an N-terminal mitochondrial targeting sequence, a catalytic domain, and a C-terminal regulatory region. It plays an important role in maintaining mitochondrial homeostasis. It protects cells against oxidative stress-induced apoptosis by phosphorylating the chaperone TNFR-associated protein 1 (TRAP1), also called Hsp75. Phosphorylated TRAP1 prevents cytochrome c release and peroxide-induced apoptosis. PINK1 interacts with Omi/HtrA2, a serine protease, and Parkin, an E3 ubiquitin ligase, in different pathways to promote mitochondrial health. The parkin gene is the most commonly mutated gene in autosomal recessive familial parkinsonism. Mutations within the catalytic domain of PINK1 are also associated with Parkinson's disease. The PINK1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270920 [Multi-domain]  Cd Length: 313  Bit Score: 52.50  E-value: 9.63e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1009 QVAKGMEFLASRKCIHRDLAARNILLSEKN----VVKICDFG--LARDI------YKDPDYVRKGDARLplkwMAPETI- 1075
Cdd:cd14018  146 QLLEGVDHLVRHGIAHRDLKSDNILLELDFdgcpWLVIADFGccLADDSiglqlpFSSWYVDRGGNACL----MAPEVSt 221
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1076 -----FDRVYTIQSDVWSFGVLLWEIFSLgASPYPGVKIDEEFCRRLKEGTRMRAPDYTTPEMYQTMLDCWHEDPNQRPS 1150
Cdd:cd14018  222 avpgpGVVINYSKADAWAVGAIAYEIFGL-SNPFYGLGDTMLESRSYQESQLPALPSAVPPDVRQVVKDLLQRDPNKRVS 300
STKc_SPEG_rpt1 cd14108
Catalytic kinase domain, first repeat, of Giant Serine/Threonine Kinase Striated muscle ...
1006-1106 9.99e-07

Catalytic kinase domain, first repeat, of Giant Serine/Threonine Kinase Striated muscle preferentially expressed protein kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The Striated muscle preferentially expressed gene (SPEG) generates 4 different isoforms through alternative promoter use and splicing in a tissue-specific manner: SPEGalpha and SPEGbeta are expressed in cardiac and skeletal striated muscle; Aortic Preferentially Expressed Protein-1 (APEG-1) is expressed in vascular smooth muscle; and Brain preferentially expressed gene (BPEG) is found in the brain and aorta. SPEG proteins have mutliple immunoglobulin (Ig), 2 fibronectin type III (FN3), and two kinase domains. They are necessary for cardiac development and survival. The SPEG subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271010 [Multi-domain]  Cd Length: 255  Bit Score: 51.83  E-value: 9.99e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1006 YSFQVAKGMEFLASRKCIHRDLAARNILLSEKNV--VKICDFGLARDIYKD-PDYVRKGdarLPlKWMAPETIFDRVYTI 1082
Cdd:cd14108  102 YMRQLLEGIEYLHQNDVLHLDLKPENLLMADQKTdqVRICDFGNAQELTPNePQYCKYG---TP-EFVAPEIVNQSPVSK 177
                         90       100
                 ....*....|....*....|....
gi 27777648 1083 QSDVWSFGVLLWEIFSlGASPYPG 1106
Cdd:cd14108  178 VTDIWPVGVIAYLCLT-GISPFVG 200
Ig2_PTK7 cd05760
Second immunoglobulin (Ig)-like domain of protein tyrosine kinase (PTK) 7; The members here ...
681-753 1.04e-06

Second immunoglobulin (Ig)-like domain of protein tyrosine kinase (PTK) 7; The members here are composed of the second immunoglobulin (Ig)-like domain in protein tyrosine kinase (PTK) 7, also known as CCK4. PTK7 is a subfamily of the receptor protein tyrosine kinase family, and is referred to as an RPTK-like molecule. RPTKs transduce extracellular signals across the cell membrane and play important roles in regulating cell proliferation, migration, and differentiation. PTK7 is organized as an extracellular portion having seven Ig-like domains, a single transmembrane region, and a cytoplasmic tyrosine kinase-like domain. PTK7 is considered a pseudokinase as it has several unusual residues in some of the highly conserved tyrosine kinase (TK) motifs; it is predicted to lack TK activity. PTK7 may function as a cell-adhesion molecule. PTK7 mRNA is expressed at high levels in placenta, melanocytes, liver, lung, pancreas, and kidney. PTK7 is overexpressed in several cancers, including melanoma and colon cancer lines.


Pssm-ID: 409417  Cd Length: 95  Bit Score: 48.39  E-value: 1.04e-06
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 27777648  681 TIEVTCPASGNPTPHITWFKDNETLVEDSG-IVLRDGNRNLTIRRVRKEDGGLYTCQACNVLG--CA-RAETLFIIE 753
Cdd:cd05760   18 RVTLRCHIDGHPRPTYQWFRDGTPLSDGQGnYSVSSKERTLTLRSAGPDDSGLYYCCAHNAFGsvCSsQNFTLSIID 94
IgI_VEGFR-1 cd07702
Immunoglobulin (Ig)-like domain of vascular endothelial growth factor receptor 1 (VEGFR-1); ...
331-402 1.13e-06

Immunoglobulin (Ig)-like domain of vascular endothelial growth factor receptor 1 (VEGFR-1); member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin (Ig)-like domain of vascular endothelial growth factor receptor 1 (VEGFR-1). VEGFRs have an extracellular component with seven Ig-like domains, a transmembrane segment, and an intracellular tyrosine kinase domain interrupted by a kinase-insert domain. VEGFRs bind VEGFs with high affinity at the Ig-like domains. VEGFR-1 binds VEGF-A strongly; VEGF-A is important to the growth and maintenance of vascular endothelial cells and to the development of new blood- and lymphatic-vessels in physiological and pathological states. VEGFR-1 may play an inhibitory role in the function of VEGFR-2 by binding VEGF-A and interfering with its interaction with VEGFR-2. VEGFR-1 has a signaling role in mediating monocyte chemotaxis and may mediate a chemotactic and a survival signal in hematopoietic stem cells or leukemia cells. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409499  Cd Length: 92  Bit Score: 47.95  E-value: 1.13e-06
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 27777648  331 FIAFGSGMKSLVEATVGSQ-VRIPVKYLSYPAPDIKWYRNGRPIESNYT--MIVGDELTIMEVTERDAGNYTVIL 402
Cdd:cd07702    1 FITVKHRKQQVLETFAGQKsYRLSMKVKAFPSPEVIWLKDGLPATEKCAryLTRGYSLIIKDVTEEDAGNYTILL 75
STKc_NDR_like cd05599
Catalytic domain of Nuclear Dbf2-Related kinase-like Protein Serine/Threonine Kinases; STKs ...
1023-1095 1.14e-06

Catalytic domain of Nuclear Dbf2-Related kinase-like Protein Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. NDR kinases regulate mitosis, cell growth, embryonic development, and neurological processes. They are also required for proper centrosome duplication. Higher eukaryotes contain two NDR isoforms, NDR1 and NDR2. This subfamily also contains fungal NDR-like kinases. NDR kinase contains an N-terminal regulatory (NTR) domain and an insert within the catalytic domain that contains an auto-inhibitory sequence. Like many other AGC kinases, NDR kinase requires phosphorylation at two sites, the activation loop (A-loop) and the hydrophobic motif (HM), for activity. The NDR kinase subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270750 [Multi-domain]  Cd Length: 324  Bit Score: 52.23  E-value: 1.14e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1023 IHRDLAARNILLSEKNVVKICDFGLARDIYKD---------PDYVrkgdarlplkwmAPETIFDRVYTIQSDVWSFGVLL 1093
Cdd:cd05599  123 IHRDIKPDNLLLDARGHIKLSDFGLCTGLKKShlaystvgtPDYI------------APEVFLQKGYGKECDWWSLGVIM 190

                 ..
gi 27777648 1094 WE 1095
Cdd:cd05599  191 YE 192
STKc_CdkB_plant cd07837
Catalytic domain of the Serine/Threonine Kinase, Plant B-type Cyclin-Dependent protein Kinase; ...
1006-1159 1.17e-06

Catalytic domain of the Serine/Threonine Kinase, Plant B-type Cyclin-Dependent protein Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The plant-specific B-type CDKs are expressed from the late S to the M phase of the cell cycle. They are characterized by the cyclin binding motif PPT[A/T]LRE. They play a role in controlling mitosis and integrating developmental pathways, such as stomata and leaf development. CdkB has been shown to associate with both cyclin B, which controls G2/M transition, and cyclin D, which acts as a mediator in linking extracellular signals to the cell cycle. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CdkB subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270830 [Multi-domain]  Cd Length: 294  Bit Score: 51.76  E-value: 1.17e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1006 YSFQVAKGMEFLASRKCIHRDLAARNILL-SEKNVVKICDFGLARDIykdpdyvrkgdaRLPLK----------WMAPET 1074
Cdd:cd07837  114 FMYQLCKGVAHCHSHGVMHRDLKPQNLLVdKQKGLLKIADLGLGRAF------------TIPIKsytheivtlwYRAPEV 181
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1075 IFDRV-YTIQSDVWSFGVLLWEIfSLGASPYPGvkiDEEFCRRLKEGTRMRAPdytTPEMYQ--TMLDCWHEDPNQRP-S 1150
Cdd:cd07837  182 LLGSThYSTPVDMWSVGCIFAEM-SRKQPLFPG---DSELQQLLHIFRLLGTP---NEEVWPgvSKLRDWHEYPQWKPqD 254

                 ....*....
gi 27777648 1151 FSELVEHLG 1159
Cdd:cd07837  255 LSRAVPDLE 263
STKc_MSK2_N cd05614
N-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated ...
993-1104 1.18e-06

N-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MSK2 and MSK1 play nonredundant roles in activating histone H3 kinases, which play pivotal roles in compaction of the chromatin fiber. MSK2 is the required H3 kinase in response to stress stimuli and activation of the p38 MAPK pathway. MSK2 also plays a role in the pathogenesis of psoriasis. MSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family, similar to 90 kDa ribosomal protein S6 kinases (RSKs). MSKs are activated by two major signaling cascades, the Ras-MAPK and p38 stress kinase pathways, which trigger phosphorylation in the activation loop (A-loop) of the CTD of MSK. The active CTD phosphorylates the hydrophobic motif (HM) of NTD, which facilitates the phosphorylation of the A-loop and activates the NTD, which in turn phosphorylates downstream targets. The MSK2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270765 [Multi-domain]  Cd Length: 332  Bit Score: 52.23  E-value: 1.18e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  993 LY-KDFLTLEHLICYSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIYKDpDYVRKGDARLPLKWMA 1071
Cdd:cd05614   96 LYqRDHFSEDEVRFYSGEIILALEHLHKLGIVYRDIKLENILLDSEGHVVLTDFGLSKEFLTE-EKERTYSFCGTIEYMA 174
                         90       100       110
                 ....*....|....*....|....*....|....
gi 27777648 1072 PETIFDRVYTIQS-DVWSFGVLLWEIFSlGASPY 1104
Cdd:cd05614  175 PEIIRGKSGHGKAvDWWSLGILMFELLT-GASPF 207
PKc_DYRK_like cd14133
Catalytic domain of Dual-specificity tYrosine-phosphorylated and -Regulated Kinase-like ...
1009-1157 1.30e-06

Catalytic domain of Dual-specificity tYrosine-phosphorylated and -Regulated Kinase-like protein kinases; Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (S/T) as well as tyrosine residues on protein substrates. This subfamily is composed of the dual-specificity DYRKs and YAK1, as well as the S/T kinases (STKs), HIPKs. DYRKs and YAK1 autophosphorylate themselves on tyrosine residues and phosphorylate their substrates exclusively on S/T residues. Proteins in this subfamily play important roles in cell proliferation, differentiation, survival, growth, and development. The DYRK-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271035 [Multi-domain]  Cd Length: 262  Bit Score: 51.50  E-value: 1.30e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1009 QVAKGMEFLASRKCIHRDLAARNILL---SEKNvVKICDFG----LARDIYKdpdYVRKGDARlplkwmAPETIFDRVYT 1081
Cdd:cd14133  110 QILEALVFLHSLGLIHCDLKPENILLasySRCQ-IKIIDFGsscfLTQRLYS---YIQSRYYR------APEVILGLPYD 179
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1082 IQSDVWSFGVLLWEIFsLGASPYPGVKIDEEFCRRLkeGTRMRAPDY------TTPEMYQTMLD---CWheDPNQRPSFS 1152
Cdd:cd14133  180 EKIDMWSLGCILAELY-TGEPLFPGASEVDQLARII--GTIGIPPAHmldqgkADDELFVDFLKkllEI--DPKERPTAS 254

                 ....*
gi 27777648 1153 ELVEH 1157
Cdd:cd14133  255 QALSH 259
STKc_MSK2_C cd14180
C-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated ...
1016-1108 1.30e-06

C-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MSK2 and MSK1 play nonredundant roles in activating histone H3 kinases, which play pivotal roles in compaction of the chromatin fiber. MSK2 is the required H3 kinase in response to stress stimuli and activation of the p38 MAPK pathway. MSK2 also plays a role in the pathogenesis of psoriasis. MSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family, similar to 90 kDa ribosomal protein S6 kinases (RSKs). MSKs are activated by two major signaling cascades, the Ras-MAPK and p38 stress kinase pathways, which trigger phosphorylation in the activation loop (A-loop) of the CTD of MSK. The active CTD phosphorylates the hydrophobic motif (HM) of NTD, which facilitates the phosphorylation of the A-loop and activates the NTD, which in turn phosphorylates downstream targets. The MSK2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271082 [Multi-domain]  Cd Length: 309  Bit Score: 51.80  E-value: 1.30e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1016 FLASRKCIHRDLAARNILL---SEKNVVKICDFGLARdiykdpdyVRKGDAR------LPLKWMAPETIFDRVYTIQSDV 1086
Cdd:cd14180  116 FMHEAGVVHRDLKPENILYadeSDGAVLKVIDFGFAR--------LRPQGSRplqtpcFTLQYAAPELFSNQGYDESCDL 187
                         90       100
                 ....*....|....*....|..
gi 27777648 1087 WSFGVLLWEIFSlGASPYPGVK 1108
Cdd:cd14180  188 WSLGVILYTMLS-GQVPFQSKR 208
STKc_Mnk1 cd14174
Catalytic domain of the Serine/Threonine kinase, Mitogen-activated protein kinase ...
1010-1106 1.39e-06

Catalytic domain of the Serine/Threonine kinase, Mitogen-activated protein kinase signal-integrating kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAPK signal-integrating kinases (Mnks) are MAPK-activated protein kinases and is comprised by a group of four proteins, produced by alternative splicing from two genes (Mnk1 and Mnk2). The isoforms of Mnk1 (1a/1b) and Mnk2 (2a/2b) differ at their C-termini, with the a-form having a longer C-terminus containing a MAPK-binding region. All Mnks contain a catalytic kinase domain and a polybasic region at the N-terminus which binds importin and the eukaryotic initiation factor eIF4G. The best characterized Mnk substrate is eIF4G, whose phosphorylation may promote the export of certain mRNAs from the nucleus. Mnk also phosphorylate substrates that bind to AU-rich elements that regulate mRNA stability and translation. Mnks have also been implicated in tyrosine kinase receptor signaling, inflammation, and cell prolieration or survival. The Mnk subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271076 [Multi-domain]  Cd Length: 289  Bit Score: 51.57  E-value: 1.39e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1010 VAKGMEFLASRKCIHRDLAARNILLSEKNV---VKICDFGLARDiykdpdyVRKGDARLPL------------KWMAPET 1074
Cdd:cd14174  109 IASALDFLHTKGIAHRDLKPENILCESPDKvspVKICDFDLGSG-------VKLNSACTPIttpelttpcgsaEYMAPEV 181
                         90       100       110
                 ....*....|....*....|....*....|....*....
gi 27777648 1075 IfdRVYTIQS-------DVWSFGVLLWEIFSlGASPYPG 1106
Cdd:cd14174  182 V--EVFTDEAtfydkrcDLWSLGVILYIMLS-GYPPFVG 217
STKc_aPKC_iota cd05618
Catalytic domain of the Serine/Threonine Kinase, Atypical Protein Kinase C iota; STKs catalyze ...
1001-1148 1.59e-06

Catalytic domain of the Serine/Threonine Kinase, Atypical Protein Kinase C iota; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKC-iota is directly implicated in carcinogenesis. It is critical to oncogenic signaling mediated by Ras and Bcr-Abl. The PKC-iota gene is the target of tumor-specific gene amplification in many human cancers, and has been identified as a human oncogene. In addition to its role in transformed growth, PKC-iota also promotes invasion, chemoresistance, and tumor cell survival. Expression profiling of PKC-iota is a prognostic marker of poor clinical outcome in several human cancers. PKC-iota also plays a role in establishing cell polarity, and has critical embryonic functions. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. aPKCs only require phosphatidylserine (PS) for activation. The aPKC subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270769 [Multi-domain]  Cd Length: 364  Bit Score: 51.96  E-value: 1.59e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1001 EHLICYSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARdiykdpDYVRKGDARLPL----KWMAPETIF 1076
Cdd:cd05618  121 EHARFYSAEISLALNYLHERGIIYRDLKLDNVLLDSEGHIKLTDYGMCK------EGLRPGDTTSTFcgtpNYIAPEILR 194
                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 27777648 1077 DRVYTIQSDVWSFGVLLWEIFSlGASPYPGV-------KIDEEFCRRLKEGTRMRAPDYTTPEMYQTMLDCWHEDPNQR 1148
Cdd:cd05618  195 GEDYGFSVDWWALGVLMFEMMA-GRSPFDIVgssdnpdQNTEDYLFQVILEKQIRIPRSLSVKAASVLKSFLNKDPKER 272
STKc_Kin4 cd14076
Catalytic domain of the yeast Serine/Threonine Kinase, Kin4; STKs catalyze the transfer of the ...
1009-1157 1.60e-06

Catalytic domain of the yeast Serine/Threonine Kinase, Kin4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Kin4 is a central component of the spindle position checkpoint (SPOC), which monitors spindle position and regulates the mitotic exit network (MEN). Kin4 associates with spindle pole bodies in mother cells to inhibit MEN signaling and delay mitosis until the anaphase nucleus is properly positioned along the mother-bud axis. Kin4 activity is regulated by both the bud neck-associated kinase Elm1 and protein phosphatase 2A. The Kin4 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270978 [Multi-domain]  Cd Length: 270  Bit Score: 51.33  E-value: 1.60e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1009 QVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIYKDPDYVRKGDARLPLkWMAPE-TIFDRVYT-IQSDV 1086
Cdd:cd14076  114 QLISGVAYLHKKGVVHRDLKLENLLLDKNRNLVITDFGFANTFDHFNGDLMSTSCGSPC-YAAPElVVSDSMYAgRKADI 192
                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 27777648 1087 WSFGVLLWEIFSlGASPY-------PGVKIDEEFcrRLKEGTRMRAPDYTTPEMYQTMLDCWHEDPNQRPSFSELVEH 1157
Cdd:cd14076  193 WSCGVILYAMLA-GYLPFdddphnpNGDNVPRLY--RYICNTPLIFPEYVTPKARDLLRRILVPNPRKRIRLSAIMRH 267
STKc_PDIK1L cd13977
Catalytic domain of the Serine/Threonine kinase, PDLIM1 interacting kinase 1 like; STKs ...
1009-1094 1.77e-06

Catalytic domain of the Serine/Threonine kinase, PDLIM1 interacting kinase 1 like; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PDIK1L is also called STK35 or CLIK-1. It is predominantly a nuclear protein which is capable of autophosphorylation. Through its interaction with the PDZ-LIM protein CLP-36, it is localized to actin stress fibers. The PDIK1L subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase (PI3K).


Pssm-ID: 270879 [Multi-domain]  Cd Length: 322  Bit Score: 51.40  E-value: 1.77e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1009 QVAKGMEFLASRKCIHRDLAARNILLSEKN---VVKICDFGLARdiykdpdyVRKGDARLPLK----------------- 1068
Cdd:cd13977  142 QLSSALAFLHRNQIVHRDLKPDNILISHKRgepILKVADFGLSK--------VCSGSGLNPEEpanvnkhflssacgsdf 213
                         90       100
                 ....*....|....*....|....*.
gi 27777648 1069 WMAPEtIFDRVYTIQSDVWSFGVLLW 1094
Cdd:cd13977  214 YMAPE-VWEGHYTAKADIFALGIIIW 238
STKc_NAK_like cd14037
Catalytic domain of Numb-Associated Kinase (NAK)-like Serine/Threonine kinases; STKs catalyze ...
1009-1158 1.79e-06

Catalytic domain of Numb-Associated Kinase (NAK)-like Serine/Threonine kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of Drosophila melanogaster NAK, human BMP-2-inducible protein kinase (BMP2K or BIKe) and similar vertebrate proteins, as well as the Saccharomyces cerevisiae proteins Prk1, Actin-regulating kinase 1 (Ark1), and Akl1. NAK was the first characterized member of this subfamily. It plays a role in asymmetric cell division through its association with Numb. It also regulates the localization of Dlg, a protein essential for septate junction formation. BMP2K contains a nuclear localization signal and a kinase domain that is capable of phosphorylating itself and myelin basic protein. The expression of the BMP2K gene is increase during BMP-2-induced osteoblast differentiation. It may function to control the rate of differentiation. Prk1, Ark1, and Akl1 comprise a subfamily of yeast proteins that are important regulators of the actin cytoskeleton and endocytosis. They share an N-terminal kinase domain but no significant homology in other regions of their sequences. The NAK-like subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270939 [Multi-domain]  Cd Length: 277  Bit Score: 51.13  E-value: 1.79e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1009 QVAKGMEFLASRK--CIHRDLAARNILLSEKNVVKICDFGLARDIYKDP------DYVRKGDAR-LPLKWMAPETIfdRV 1079
Cdd:cd14037  116 DVCEAVAAMHYLKppLIHRDLKVENVLISDSGNYKLCDFGSATTKILPPqtkqgvTYVEEDIKKyTTLQYRAPEMI--DL 193
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1080 Y-----TIQSDVWSFGVLLWEI--FSLgasPYpgvkidEEFCRRLKEGTRMRAPDYT--TPEMYQTMLDCWHEDPNQRPS 1150
Cdd:cd14037  194 YrgkpiTEKSDIWALGCLLYKLcfYTT---PF------EESGQLAILNGNFTFPDNSrySKRLHKLIRYMLEEDPEKRPN 264

                 ....*...
gi 27777648 1151 FSELVEHL 1158
Cdd:cd14037  265 IYQVSYEA 272
STKc_DCKL1 cd14183
Catalytic domain of the Serine/Threonine Kinase, Doublecortin-like kinase 1 (also called ...
1008-1157 1.86e-06

Catalytic domain of the Serine/Threonine Kinase, Doublecortin-like kinase 1 (also called Doublecortin-like and CAM kinase-like 1); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. DCKL1 (or DCAMKL1) belongs to the doublecortin (DCX) family of proteins which are involved in neuronal migration, neurogenesis, and eye receptor development, among others. Family members typically contain tandem doublecortin (DCX) domains at the N-terminus; DCX domains can bind microtubules and serve as protein-interaction platforms. In addition, DCKL1 contains a serine, threonine, and proline rich domain (SP) and a C-terminal kinase domain with similarity to CAMKs. DCKL1 interacts with tubulin, glucocorticoid receptor, dynein, JIP1/2, caspases (3 and 8), and calpain, among others. It plays roles in neurogenesis, neuronal migration, retrograde transport, and neuronal apoptosis. The DCKL1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271085 [Multi-domain]  Cd Length: 268  Bit Score: 51.15  E-value: 1.86e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1008 FQVAKGMEFLASRKCIHRDLAARNILLSE----KNVVKICDFGLArDIYKDPDYVRKGDArlplKWMAPETIFDRVYTIQ 1083
Cdd:cd14183  111 YNLASAIKYLHSLNIVHRDIKPENLLVYEhqdgSKSLKLGDFGLA-TVVDGPLYTVCGTP----TYVAPEIIAETGYGLK 185
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1084 SDVWSFGVLLWeIFSLGASPYPGVKIDEEFcrrLKEGTRMRAPDYTTP----------EMYQTMLDCwheDPNQRPSFSE 1153
Cdd:cd14183  186 VDIWAAGVITY-ILLCGFPPFRGSGDDQEV---LFDQILMGQVDFPSPywdnvsdsakELITMMLQV---DVDQRYSALQ 258

                 ....
gi 27777648 1154 LVEH 1157
Cdd:cd14183  259 VLEH 262
STKc_PIM3 cd14102
Catalytic domain of the Serine/Threonine kinase, Proviral Integration Moloney virus (PIM) ...
1018-1157 1.87e-06

Catalytic domain of the Serine/Threonine kinase, Proviral Integration Moloney virus (PIM) kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The PIM gene locus was discovered as a result of the cloning of retroviral intergration sites in murine Moloney leukemia virus, leading to the identification of PIM kinases. They are constitutively active STKs with a broad range of cellular targets and are overexpressed in many haematopoietic malignancies and solid cancers. Vertebrates contain three distinct PIM kinase genes (PIM1-3). PIM3 can inhibit apoptosis and promote cell survival and protein translation, therefore, it can enhance the proliferation of normal and cancer cells. Mice deficient with PIM3 show minimal effects, suggesting that PIM3 msy not be essential. Since its expression is enhanced in several cancers, it may make a good molecular target for cancer drugs. The PIM3 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271004 [Multi-domain]  Cd Length: 253  Bit Score: 50.72  E-value: 1.87e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1018 ASRKC-----IHRDLAARNILLSEKN-VVKICDFG----LARDIYKDPDYVRkgdARLPLKWMApetiFDRVYTIQSDVW 1087
Cdd:cd14102  117 AVRHCyscgvVHRDIKDENLLVDLRTgELKLIDFGsgalLKDTVYTDFDGTR---VYSPPEWIR----YHRYHGRSATVW 189
                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 27777648 1088 SFGVLLWEIFSlGASPYpgvKIDEEFCR-RLKEGTRMrapdytTPEMYQTMLDCWHEDPNQRPSFSELVEH 1157
Cdd:cd14102  190 SLGVLLYDMVC-GDIPF---EQDEEILRgRLYFRRRV------SPECQQLIKWCLSLRPSDRPTLEQIFDH 250
STKc_nPKC_epsilon cd05591
Catalytic domain of the Serine/Threonine Kinase, Novel Protein Kinase C epsilon; STKs catalyze ...
1006-1113 2.34e-06

Catalytic domain of the Serine/Threonine Kinase, Novel Protein Kinase C epsilon; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKC-epsilon has been shown to behave as an oncoprotein. Its overexpression contributes to neoplastic transformation depending on the cell type. It contributes to oncogenesis by inducing disordered cell growth and inhibiting cell death. It also plays a role in tumor invasion and metastasis. PKC-epsilon has also been found to confer cardioprotection against ischemia and reperfusion-mediated damage. Other cellular functions include the regulation of gene expression, cell adhesion, and cell motility. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. nPKCs are calcium-independent, but require DAG (1,2-diacylglycerol) and phosphatidylserine (PS) for activity. The nPKC-epsilon subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270743 [Multi-domain]  Cd Length: 321  Bit Score: 51.34  E-value: 2.34e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648 1006 YSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARD-IYKD---------PDYVrkgdarlplkwmAPETI 1075
Cdd:cd05591  101 YAAEVTLALMFLHRHGVIYRDLKLDNILLDAEGHCKLADFGMCKEgILNGkttttfcgtPDYI------------APEIL 168
                         90       100       110
                 ....*....|....*....|....*....|....*...
gi 27777648 1076 FDRVYTIQSDVWSFGVLLWEIFSlGASPYPGVKIDEEF 1113
Cdd:cd05591  169 QELEYGPSVDWWALGVLMYEMMA-GQPPFEADNEDDLF 205
Ig4_Peroxidasin cd05746
Fourth immunoglobulin (Ig)-like domain of peroxidasin; The members here are composed of the ...
682-744 2.35e-06

Fourth immunoglobulin (Ig)-like domain of peroxidasin; The members here are composed of the fourth immunoglobulin (Ig)-like domain in peroxidasin. Peroxidasin has a peroxidase domain and interacting extracellular motifs containing four Ig-like domains. It has been suggested that peroxidasin is secreted, and has functions related to the stabilization of the extracellular matrix. It may play a part in various other important processes such as removal and destruction of cells which have undergone programmed cell death and protection of the organism against non-self.


Pssm-ID: 143223  Cd Length: 69  Bit Score: 46.41  E-value: 2.35e-06
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 27777648  682 IEVTCPASGNPTPHITWFKDNETLVEDSGI-VLRDGnrNLTIRRVRKEDGGLYTCQACNVLGCA 744
Cdd:cd05746    1 VQIPCSAQGDPEPTITWNKDGVQVTESGKFhISPEG--YLAIRDVGVADQGRYECVARNTIGYA 62
IgI_titin_I1-like cd20951
Immunoglobulin domain I1 of the titin I-band and similar proteins; a member of the I-set of ...
665-753 2.58e-06

Immunoglobulin domain I1 of the titin I-band and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin domain I1 of the titin I-band and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. The two sheets are linked together by a conserved disulfide bond between B strand and F strand. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The Ig I1 domain of the titin I-band is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409543 [Multi-domain]  Cd Length: 94  Bit Score: 47.03  E-value: 2.58e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  665 PMITGNLENQTTTIGETIEVTCPASGNPTPHITWFKdNETLVEDSG------IVLRDGNRNLTIRRVRKEDGGLYTCQAC 738
Cdd:cd20951    1 PEFIIRLQSHTVWEKSDAKLRVEVQGKPDPEVKWYK-NGVPIDPSSipgkykIESEYGVHVLHIRRVTVEDSAVYSAVAK 79
                         90
                 ....*....|....*
gi 27777648  739 NVLGCARAETLFIIE 753
Cdd:cd20951   80 NIHGEASSSASVVVE 94
IgI_4_hemolin-like cd20978
Fourth immunoglobulin (Ig)-like domain of hemolin, and similar domains; a member of the I-set ...
334-404 1.32e-05

Fourth immunoglobulin (Ig)-like domain of hemolin, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain of hemolin and similar proteins. Hemolin, an insect immunoglobulin superfamily (IgSF) member containing four Ig-like domains, is a lipopolysaccharide-binding immune protein induced during bacterial infection. Hemolin shares significant sequence similarity with the first four Ig-like domains of the transmembrane cell adhesion molecules (CAMs) of the L1 family. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The fourth Ig-like domain of hemolin is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409570 [Multi-domain]  Cd Length: 88  Bit Score: 44.69  E-value: 1.32e-05
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 27777648  334 FGSGMKSLVEATVGSQVRIPVKYLSYPAPDIKWYRNGRPIESNY-TMIVGD-ELTIMEVTERDAGNYTVILTN 404
Cdd:cd20978    3 FIQKPEKNVVVKGGQDVTLPCQVTGVPQPKITWLHNGKPLQGPMeRATVEDgTLTIINVQPEDTGYYGCVATN 75
IgI_Myotilin_C_like cd05744
Immunoglobulin (Ig)-like domain of myotilin, palladin, and myopalladin; member of the I-set of ...
343-404 1.49e-05

Immunoglobulin (Ig)-like domain of myotilin, palladin, and myopalladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin (Ig)-like domain in myotilin, palladin, and myopalladin. Myotilin, palladin, and myopalladin function as scaffolds that regulate actin organization. Myotilin and myopalladin are most abundant in skeletal and cardiac muscle; palladin is ubiquitously expressed in the organs of developing vertebrates and plays a key role in cellular morphogenesis. The three family members each interact with specific molecular partners with all three binding to alpha-actinin; In addition, palladin also binds to vasodilator-stimulated phosphoprotein (VASP) and ezrin, myotilin binds to filamin and actin, and myopalladin also binds to nebulin and cardiac ankyrin repeat protein (CARP). This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409405 [Multi-domain]  Cd Length: 91  Bit Score: 44.79  E-value: 1.49e-05
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 27777648  343 EATVGSQVRIPVKYLSYPAPDIKWYRNGRPI--ESNYTMIVGD----ELTIMEVTERDAGNYTVILTN 404
Cdd:cd05744   11 EVQEGRLCRFDCKVSGLPTPDLFWQLNGKPVrpDSAHKMLVREngrhSLIIEPVTKRDAGIYTCIARN 78
Ig_3 pfam13927
Immunoglobulin domain; This family contains immunoglobulin-like domains.
549-642 1.50e-05

Immunoglobulin domain; This family contains immunoglobulin-like domains.


Pssm-ID: 464046 [Multi-domain]  Cd Length: 78  Bit Score: 44.48  E-value: 1.50e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648    549 PEITVQPAAQ-PTEQESVSLLCTADRNTFENLTWYKLGSQATSVHMGESltpvcknldalwklngtmFSNSTNDILIVaf 627
Cdd:pfam13927    2 PVITVSPSSVtVREGETVTLTCEATGSPPPTITWYKNGEPISSGSTRSR------------------SLSGSNSTLTI-- 61
                           90
                   ....*....|....*
gi 27777648    628 QNASLQDQGDYVCSA 642
Cdd:pfam13927   62 SNVTRSDAGTYTCVA 76
IgI_3_NCAM-1 cd05730
Third immunoglobulin (Ig)-like domain of Neural Cell Adhesion Molecule 1 (NCAM-1); member of ...
359-404 2.04e-05

Third immunoglobulin (Ig)-like domain of Neural Cell Adhesion Molecule 1 (NCAM-1); member of the I-set of IgSF domains; The members here are composed of the third immunoglobulin (Ig)-like domain of Neural Cell Adhesion Molecule (NCAM-1). NCAM plays important roles in the development and regeneration of the central nervous system, in synaptogenesis and neural migration. NCAM mediates cell-cell and cell-substratum recognition and adhesion via homophilic (NCAM-NCAM), and heterophilic (NCAM-non-NCAM), interactions. NCAM is expressed as three major isoforms having different intracellular extensions. The extracellular portion of NCAM has five N-terminal Ig-like domains and two fibronectin type III domains. The double zipper adhesion complex model for NCAM homophilic binding involves Ig1, Ig2, and Ig3. By this model, Ig1 and Ig2 mediate dimerization of NCAM molecules situated on the same cell surface (cis interactions), and Ig3 domains mediate interactions between NCAM molecules expressed on the surface of opposing cells (trans interactions) through binding to the Ig1 and Ig2 domains. The adhesive ability of NCAM is modulated by the addition of polysialic acid chains to the fifth Ig-like domain.


Pssm-ID: 143207 [Multi-domain]  Cd Length: 95  Bit Score: 44.54  E-value: 2.04e-05
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 27777648  359 YPAPDIKWYRNGRPIESNYTMIV----GDELTIMEVTERDAGNYTVILTN 404
Cdd:cd05730   30 FPEPTMTWTKDGEPIESGEEKYSfnedGSEMTILDVDKLDEAEYTCIAEN 79
Ig_2 pfam13895
Immunoglobulin domain; This domain contains immunoglobulin-like domains.
345-419 3.18e-05

Immunoglobulin domain; This domain contains immunoglobulin-like domains.


Pssm-ID: 464026 [Multi-domain]  Cd Length: 79  Bit Score: 43.54  E-value: 3.18e-05
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 27777648    345 TVGSQVRIPVKYLSYPAPDIKWYRNGRPIESNYtmivgdELTIMEVTERDAGNYTVILTNPISMeKQSHMVSLVV 419
Cdd:pfam13895   12 TEGEPVTLTCSAPGNPPPSYTWYKDGSAISSSP------NFFTLSVSAEDSGTYTCVARNGRGG-KVSNPVELTV 79
Ig cd00096
Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found ...
244-323 1.43e-04

Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins, including T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, including butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E, and D strands in one sheet and A', G, F, C, C' and C" in the other. The structures in C1-set are smaller than those in the V-set; they have one beta sheet that is formed by strands A, B, E, and D and the other by strands G, F, C, and C'. Moreover, a C1-set Ig domain contains a short C' strand (three residues) and lacks A' and C" strand. Unlike other Ig domain sets, C2-set structures do not have a D strand. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409353 [Multi-domain]  Cd Length: 70  Bit Score: 41.55  E-value: 1.43e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  244 LVLNCTARTELNVglDFTWHSPPSKSHHKKIVNRDVKPFPGTvakmflstLTIESVTKSDQGEYTCVASSGRMIKRNRTF 323
Cdd:cd00096    1 VTLTCSASGNPPP--TITWYKNGKPLPPSSRDSRRSELGNGT--------LTISNVTLEDSGTYTCVASNSAGGSASASV 70
ig pfam00047
Immunoglobulin domain; Members of the immunoglobulin superfamily are found in hundreds of ...
338-408 2.96e-04

Immunoglobulin domain; Members of the immunoglobulin superfamily are found in hundreds of proteins of different functions. Examples include antibodies, the giant muscle kinase titin and receptor tyrosine kinases. Immunoglobulin-like domains may be involved in protein-protein and protein-ligand interactions.


Pssm-ID: 395002  Cd Length: 86  Bit Score: 41.03  E-value: 2.96e-04
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 27777648    338 MKSLVEATVGSQVRIPVKY-LSYPAPDIKWYRNG-RPIES-----NYTMIVGDELTIMEVTERDAGNYTVILTNPISM 408
Cdd:pfam00047    2 APPTVTVLEGDSATLTCSAsTGSPGPDVTWSKEGgTLIESlkvkhDNGRTTQSSLLISNVTKEDAGTYTCVVNNPGGS 79
IgI_5_Robo cd20952
Fifth Ig-like domain of Roundabout (Robo) homolog 1/2, and similar domains; a member of the ...
228-313 3.37e-04

Fifth Ig-like domain of Roundabout (Robo) homolog 1/2, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fifth Ig-like domain of Roundabout (Robo) homolog 1/2 and similar domains. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, -2, and -3), and three mammalian Slit homologs (Slit-1,-2, -3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, -2, and -3 are expressed by commissural neurons in the vertebrate spinal cord and Slits 1, -2, -3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of slit responsiveness, antagonizes slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be is the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. The fifth Ig-like domain of Robo 1 and 2 is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors


Pssm-ID: 409544 [Multi-domain]  Cd Length: 87  Bit Score: 40.94  E-value: 3.37e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  228 VILSPPHEIELSAGEKLVLNCTARTE-LNVgldFTWhsppskshhkkivNRDVKPFPGTVAKMFL---STLTIESVTKSD 303
Cdd:cd20952    1 IILQGPQNQTVAVGGTVVLNCQATGEpVPT---ISW-------------LKDGVPLLGKDERITTlenGSLQIKGAEKSD 64
                         90
                 ....*....|
gi 27777648  304 QGEYTCVASS 313
Cdd:cd20952   65 TGEYTCVALN 74
Ig3_L1-CAM_like cd05731
Third immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM), and similar ...
360-419 4.23e-04

Third immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM), and similar domains; The members here are composed of the third immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM). L1 belongs to the L1 subfamily of cell adhesion molecules (CAMs) and is comprised of an extracellular region having six Ig-like domains and five fibronectin type III domains, a transmembrane region and an intracellular domain. L1 is primarily expressed in the nervous system and is involved in its development and function. L1 is associated with an X-linked recessive disorder, X-linked hydrocephalus, MASA syndrome, and spastic paraplegia type 1, that involves abnormalities of axonal growth. This group also contains the chicken neuron-glia cell adhesion molecule, Ng-CAM and human neurofascin.


Pssm-ID: 409394 [Multi-domain]  Cd Length: 83  Bit Score: 40.47  E-value: 4.23e-04
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 27777648  360 PAPDIKWYR------NGRPIESNYtmivGDELTIMEVTERDAGNYTVILTNPisMEKQSHMVSLVV 419
Cdd:cd05731   23 PTPDIRWIKlggelpKGRTKFENF----NKTLKIENVSEADSGEYQCTASNT--MGSARHTISVTV 82
IgI_4_MYLK-like cd20976
Fourth Ig-like domain from smooth muscle myosin light chain kinase and similar domains ; a ...
360-417 7.13e-04

Fourth Ig-like domain from smooth muscle myosin light chain kinase and similar domains ; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain from smooth muscle myosin light chain kinase (MYLK) and similar domains. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of this group shows that the fourth Ig-like domain from myosin light chain kinase lacks this strand and thus belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409568 [Multi-domain]  Cd Length: 90  Bit Score: 39.93  E-value: 7.13e-04
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 27777648  360 PAPDIKWYRNGRPIESNYTMIVGD----ELTIMEVTERDAGNYTVILTNPISMEKQSHMVSL 417
Cdd:cd20976   29 PVPRITWIRNAQPLQYAADRSTCEagvgELHIQDVLPEDHGTYTCLAKNAAGQVSCSAWVTV 90
IgI_5_Dscam cd20958
Fifth immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; ...
293-326 8.47e-04

Fifth immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fifth immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. This group is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.


Pssm-ID: 409550 [Multi-domain]  Cd Length: 89  Bit Score: 39.86  E-value: 8.47e-04
                         10        20        30
                 ....*....|....*....|....*....|....*.
gi 27777648  293 TLTIESVTK-SDQGEYTCVASSGR-MIKRNRTFVRV 326
Cdd:cd20958   54 TLVIENVQRsSDEGEYTCTARNQQgQSASRSVFVKV 89
IgI_5_Dscam cd20958
Fifth immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; ...
344-421 8.56e-04

Fifth immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fifth immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. This group is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.


Pssm-ID: 409550 [Multi-domain]  Cd Length: 89  Bit Score: 39.86  E-value: 8.56e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  344 ATVGSQVRIPVKYLSYPAPDIKWYRNGRPIESNYTMIVGDE--LTIMEVT-ERDAGNYTVILTNPismEKQSHMVSLVVN 420
Cdd:cd20958   12 AVAGQTLRLHCPVAGYPISSITWEKDGRRLPLNHRQRVFPNgtLVIENVQrSSDEGEYTCTARNQ---QGQSASRSVFVK 88

                 .
gi 27777648  421 V 421
Cdd:cd20958   89 V 89
Ig_Pro_neuregulin cd05750
Immunoglobulin (Ig)-like domain in neuregulins; The members here are composed of the ...
237-313 8.64e-04

Immunoglobulin (Ig)-like domain in neuregulins; The members here are composed of the immunoglobulin (Ig)-like domain in neuregulins (NRGs). NRGs are signaling molecules which participate in cell-cell interactions in the nervous system, breast, heart, and other organ systems, and are implicated in the pathology of diseases including schizophrenia, multiple sclerosis, and breast cancer. There are four members of the neuregulin gene family (NRG-1, NRG-2, NRG-3, and NRG-4). The NRG-1 protein, binds to and activates the tyrosine kinases receptors ErbB3 and ErbB4, initiating signaling cascades. The other NRGs proteins bind one or the other or both of these ErbBs. NRG-1 has multiple functions: in the brain it regulates various processes such as radial glia formation and neuronal migration, dendritic development, and expression of neurotransmitters receptors, while in the peripheral nervous system NRG-1 regulates processes such as target cell differentiation, and Schwann cell survival. There are many NRG-1 isoforms which arise from the alternative splicing of mRNA. Less is known of the functions of the other NRGs. NRG-2 and NRG-3 are expressed predominantly in the nervous system. NRG-2 is expressed by motor neurons and terminal Schwann cells, and is concentrated near synaptic sites and may be a signal that regulates synaptic differentiation. NRG-4 has been shown to direct pancreatic islet cell development towards the delta-cell lineage.


Pssm-ID: 409408 [Multi-domain]  Cd Length: 92  Bit Score: 39.80  E-value: 8.64e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  237 ELSAGEKLVLNCTARTElNVGLDFTWHS-----PPSKSHHKKIVNRDVKpfpgtvakmflSTLTIESVTKSDQGEYTCVA 311
Cdd:cd05750   10 TVQEGSKLVLKCEATSE-NPSPRYRWFKdgkelNRKRPKNIKIRNKKKN-----------SELQINKAKLEDSGEYTCVV 77

                 ..
gi 27777648  312 SS 313
Cdd:cd05750   78 EN 79
IgI_titin_I1-like cd20951
Immunoglobulin domain I1 of the titin I-band and similar proteins; a member of the I-set of ...
347-419 9.55e-04

Immunoglobulin domain I1 of the titin I-band and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin domain I1 of the titin I-band and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. The two sheets are linked together by a conserved disulfide bond between B strand and F strand. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The Ig I1 domain of the titin I-band is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409543 [Multi-domain]  Cd Length: 94  Bit Score: 39.71  E-value: 9.55e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648  347 GSQVRIPVKYLSYPAPDIKWYRNGRPI-----------ESNYTMivgDELTIMEVTERDAGNYTVILTNPISMEKQShmV 415
Cdd:cd20951   15 KSDAKLRVEVQGKPDPEVKWYKNGVPIdpssipgkykiESEYGV---HVLHIRRVTVEDSAVYSAVAKNIHGEASSS--A 89

                 ....
gi 27777648  416 SLVV 419
Cdd:cd20951   90 SVVV 93
Ig5_Contactin cd04969
Fifth immunoglobulin (Ig) domain of contactin; The members here are composed of the fifth ...
338-404 1.27e-03

Fifth immunoglobulin (Ig) domain of contactin; The members here are composed of the fifth immunoglobulin (Ig) domain of contactins. Contactins are neural cell adhesion molecules and are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. The first four Ig domains form the intermolecular binding fragment, which arranges as a compact U-shaped module via contacts between Ig domains 1 and 4, and between Ig domains 2 and 3. Contactin-2 (TAG-1, axonin-1) may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. This group also includes contactin-1 and contactin-5. The different contactins show different expression patterns in the central nervous system. During development and in adulthood, contactin-2 is transiently expressed in subsets of central and peripheral neurons. Contactin-5 is expressed specifically in the rat postnatal nervous system, peaking at about 3 weeks postnatal, and a lack of contactin-5 (NB-2) results in an impairment of neuronal activity in the rat auditory system. Contactin-5 is highly expressed in the adult human brain in the occipital lobe and in the amygdala. Contactin-1 is differentially expressed in tumor tissues and may, through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma.


Pssm-ID: 409358 [Multi-domain]  Cd Length: 89  Bit Score: 39.37  E-value: 1.27e-03
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 27777648  338 MKSLVEATVGSQVRIPVKYLSYPAPDIKWYRNGRPI-ESNYTMIVGD-ELTIMEVTERDAGNYTVILTN 404
Cdd:cd04969    8 VKKKILAAKGGDVIIECKPKASPKPTISWSKGTELLtNSSRICILPDgSLKIKNVTKSDEGKYTCFAVN 76
IgI_4_Dscam cd20956
Fourth immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; ...
360-404 2.17e-03

Fourth immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. This group is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.


Pssm-ID: 409548 [Multi-domain]  Cd Length: 96  Bit Score: 38.70  E-value: 2.17e-03
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 27777648  360 PAPDIKWYRNGRPIESNYTMIVGDELT----------IMEVTERDAGNYTVILTN 404
Cdd:cd20956   29 PLPQITWTLDGFPIPESPRFRVGDYVTsdgdvvsyvnISSVRVEDGGEYTCTATN 83
IG_like smart00410
Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.
563-649 2.22e-03

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.


Pssm-ID: 214653 [Multi-domain]  Cd Length: 85  Bit Score: 38.64  E-value: 2.22e-03
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27777648     563 ESVSLLCTADRNTFENLTWYKLGsqatsvhmgesLTPVCKNLDALWKLNGTMFSnstndiLIvaFQNASLQDQGDYVCSA 642
Cdd:smart00410   10 ESVTLSCEASGSPPPEVTWYKQG-----------GKLLAESGRFSVSRSGSTST------LT--ISNVTPEDSGTYTCAA 70

                    ....*..
gi 27777648     643 QDKKTKK 649
Cdd:smart00410   71 TNSSGSA 77
IgI_2_Robo cd05724
Second immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of ...
359-419 3.19e-03

Second immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the second immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of the Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, and Robo3), and three mammalian Slit homologs (Slit-1,Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit-2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409389 [Multi-domain]  Cd Length: 87  Bit Score: 38.15  E-value: 3.19e-03
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 27777648  359 YPAPDIKWYRNGRPI---ESNYTMIVGDELTIMEVTERDAGNYTVILTNPISmEKQSHMVSLVV 419
Cdd:cd05724   25 HPEPTVSWRKDGQPLnldNERVRIVDDGNLLIAEARKSDEGTYKCVATNMVG-ERESRAARLSV 87
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.21
Preset Options:Database: CDSEARCH/cdd   Low complexity filter: no  Composition Based Adjustment: yes   E-value threshold: 0.01

References:

  • Wang J et al. (2023), "The conserved domain database in 2023", Nucleic Acids Res.51(D)384-8.
  • Lu S et al. (2020), "The conserved domain database in 2020", Nucleic Acids Res.48(D)265-8.
  • Marchler-Bauer A et al. (2017), "CDD/SPARCLE: functional classification of proteins via subfamily domain architectures.", Nucleic Acids Res.45(D)200-3.
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