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Conserved domains on  [gi|4504217|ref|NP_000171|]
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retinal guanylyl cyclase 1 precursor [Homo sapiens]

Protein Classification

receptor-type guanylate cyclase( domain architecture ID 11570897)

receptor-type guanylate cyclase that catalyzes the conversion of guanosine triphosphate (GTP) to 3',5'-cyclic guanosine monophosphate (cGMP) and pyrophosphate, such as retinal and olfactory guanylyl cyclases; contains PBP1-type ligand binding, pseudokinase and guanylyl cyclase catalytic domains

Graphical summary

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List of domain hits

Name Accession Description Interval E-value
PBP1_sensory_GC_DEF-like cd06371
ligand-binding domain of membrane guanylyl cyclases (GC-D, GC-E, and GC-F) that are ...
55-431 0e+00

ligand-binding domain of membrane guanylyl cyclases (GC-D, GC-E, and GC-F) that are specifically expressed in sensory tissues; This group includes the ligand-binding domain of membrane guanylyl cyclases (GC-D, GC-E, and GC-F) that are specifically expressed in sensory tissues. They share a similar topology with an N-terminal extracellular ligand-binding domain, a single transmembrane domain, and a C-terminal cytosolic region that contains kinase-like and catalytic domains. GC-D is specifically expressed in a subpopulation of olfactory sensory neurons. GC-E and GC-F are colocalized within the same photoreceptor cells of the retina and have important roles in phototransduction. Unlike the other family members, GC-E and GC-F have no known extracellular ligands. Instead, they are activated under low calcium conditions by guanylyl cyclase activating proteins called GCAPs. GC-D expressing neurons have been implicated in pheromone detection and GC-D is phylogenetically more similar to the Ca2+-regulated GC-E and GC-F than to receptor GC-A, -B and -C which are activated by peptide ligands. Moreover, these olfactory GCs and retinal GCs share characteristic sequence similarity in a regulatory domain that is involved in the binding of GCAPs, suggesting GC-D activity may be regulated by an unknown extracellular ligand and intracellular Ca2+. Rodent GC-D-expressing neurons have been implicated in pheromone detection and were recently shown to respond to atmospheric CO2 which is an olfactory stimulus for many invertebrates and regulates some insect innate behavior, such as the location of food and hosts.


:

Pssm-ID: 380594 [Multi-domain]  Cd Length: 379  Bit Score: 586.59  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217    55 TVGVLGPWACDPIFSRARPDLAARLAAARLNRDPGLAGGPRFEVALLPEPCRTPGSLGAVSSALARVSGLVGPVNPAACR 134
Cdd:cd06371    1 KVGVVGPWTCDPIFAKALPDLAARLAVSRINKDPSLDLGYWFDYVILPEDCETSKALAAFSSAEGRASGFVGPVNPGYCE 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   135 PAELLAEEAGIALVPWGCPWT--QAEGTTAPAVTPAADALYALLRAFGWARVALVTAPQDLWVEAGRSLSTALRARGLPV 212
Cdd:cd06371   81 AASLLAQEWDKALFSWGCVNHelNSYPTFARTLPPPADVLYTVLRYFRWAHVAVVSSPQDLWVETGRELASALRARGLPV 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   213 ASVTSMEPLDlSGAREALRKVRDGPRVTAVIMVMHSVLLGGEEQRYLLEAAEELGLTDGSLVFLPFDTIHYALSPGPEAL 292
Cdd:cd06371  161 GLVTSMEPSD-SGAREALKRIRDADRVRVVIMCMHSVLIGGEEQRTLLEAAHDMGLTDGSYVFVPYDTLLYSLPYKHEPY 239
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   293 AALANSSQLRRAHDAVLTLTRHcPSEGSVLDSLRRAQERRELPSDLNLQQVSPLFGTIYDAVFLLarGVAEARAAAGGRW 372
Cdd:cd06371  240 AVLRNNSKLRRAYDAVLTITME-SPEGSFYEAFRRAQERGELPSDLDPEQVSPLFGTIYNSIYLL--AGAVENARAAGGG 316
                        330       340       350       360       370       380
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 4504217   373 VSGAAVARHIRDAQVPGFCGDL----GGDEEPPFVLLDTDAAGDRLFATYMLDPARGSFLSAG 431
Cdd:cd06371  317 VSGASLARHARNAQFPGFNQLLrtdsGGNGQPSYVILDTDGKGWRLFPTYTLDMTTGLLRFLG 379
PK_GC-2D cd14043
Pseudokinase domain of the membrane Guanylate Cyclase receptor, GC-2D; The pseudokinase domain ...
536-811 8.71e-174

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: 510.03  E-value: 8.71e-174
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   536 MSDIRSGPSQHLDSPNIGV-YEGDRVWLKKFPGDQHIAIRPATKTAFSKLQELRHENVALYLGLFLARGaegpaalwegN 614
Cdd:cd14043    1 PSSPSSTSSVNATSSNTGVaYEGDWVWLKKFPGGSHTELRPSTKNVFSKLRELRHENVNLFLGLFVDCG----------I 70
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   615 LAVVSEHCTRGSLQDLLAQREIKLDWMFKSSLLLDLIKGIRYLHHRGVAHGRLKSRNCIVDGRFVLKITDHGHGRLLEAQ 694
Cdd:cd14043   71 LAIVSEHCSRGSLEDLLRNDDMKLDWMFKSSLLLDLIKGMRYLHHRGIVHGRLKSRNCVVDGRFVLKITDYGYNEILEAQ 150
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   695 KVLPEPPRAEDQLWTAPELLRDPALERRGTLAGDVFSLAIIMQEVVCRSAPYAMLELTPEEVVQRVRSPPPLCRPLVSMD 774
Cdd:cd14043  151 NLPLPEPAPEELLWTAPELLRDPRLERRGTFPGDVFSFAIIMQEVIVRGAPYCMLGLSPEEIIEKVRSPPPLCRPSVSMD 230
                        250       260       270
                 ....*....|....*....|....*....|....*..
gi 4504217   775 QAPVECILLMKQCWAEQPELRPSMDHTFDLFKNINKG 811
Cdd:cd14043  231 QAPLECIQLMKQCWSEAPERRPTFDQIFDQFKSINKG 267
CYCc smart00044
Adenylyl- / guanylyl cyclase, catalytic domain; Present in two copies in mammalian adenylyl ...
846-1036 1.53e-88

Adenylyl- / guanylyl cyclase, catalytic domain; Present in two copies in mammalian adenylyl cyclases. Eubacterial homologues are known. Two residues (Asn, Arg) are thought to be involved in catalysis. These cyclases have important roles in a diverse range of cellular processes.


:

Pssm-ID: 214485  Cd Length: 194  Bit Score: 282.99  E-value: 1.53e-88
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217      846 KQKTDRLLTQMLPPSVAEALKTG-TPVEPEYFEQVTLYFSDIVGFTTISAMSEPIEVVDLLNDLYTLFDAIIGSHDVYKV 924
Cdd:smart00044    3 KKKTDRLLDQLLPASVAEQLKRGgSPVPAESYDNVTILFSDIVGFTSLCSTSTPEQVVNLLNDLYSRFDQIIDRHGGYKV 82
                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217      925 ETIGDAYMVASGLPQRNGQRHAAEIANMSLDILSAVGTFrMRHMPEVPVRIRIGLHSGPCVAGVVGLTMPRYCLFGDTVN 1004
Cdd:smart00044   83 KTIGDAYMVASGLPEEALVDHAELIADEALDMVEELKTV-LVQHREEGLRVRIGIHTGPVVAGVVGIRMPRYCLFGDTVN 161
                           170       180       190
                    ....*....|....*....|....*....|..
gi 4504217     1005 TASRMESTGLPYRIHVNLSTVGILRALDSGYQ 1036
Cdd:smart00044  162 LASRMESAGDPGQIQVSEETYSLLARRGGQFV 193
HNOBA super family cl06648
Heme NO binding associated; The HNOBA domain is found associated with the HNOB domain and ...
820-865 6.45e-05

Heme NO binding associated; The HNOBA domain is found associated with the HNOB domain and pfam00211 in soluble cyclases and signalling proteins. The HNOB domain is predicted to function as a heme-dependent sensor for gaseous ligands, and transduce diverse downstream signals, in both bacteria and animals.


The actual alignment was detected with superfamily member pfam07701:

Pssm-ID: 462234  Cd Length: 214  Bit Score: 45.26  E-value: 6.45e-05
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*.
gi 4504217     820 MLRMLEQYSSNLEDLIRERTEEleleKQKTDRLLTQMLPPSVAEAL 865
Cdd:pfam07701  173 ALDQLEQKSAELEESMRELEEE----KKKTDELLYSMLPKSVADRL 214
 
Name Accession Description Interval E-value
PBP1_sensory_GC_DEF-like cd06371
ligand-binding domain of membrane guanylyl cyclases (GC-D, GC-E, and GC-F) that are ...
55-431 0e+00

ligand-binding domain of membrane guanylyl cyclases (GC-D, GC-E, and GC-F) that are specifically expressed in sensory tissues; This group includes the ligand-binding domain of membrane guanylyl cyclases (GC-D, GC-E, and GC-F) that are specifically expressed in sensory tissues. They share a similar topology with an N-terminal extracellular ligand-binding domain, a single transmembrane domain, and a C-terminal cytosolic region that contains kinase-like and catalytic domains. GC-D is specifically expressed in a subpopulation of olfactory sensory neurons. GC-E and GC-F are colocalized within the same photoreceptor cells of the retina and have important roles in phototransduction. Unlike the other family members, GC-E and GC-F have no known extracellular ligands. Instead, they are activated under low calcium conditions by guanylyl cyclase activating proteins called GCAPs. GC-D expressing neurons have been implicated in pheromone detection and GC-D is phylogenetically more similar to the Ca2+-regulated GC-E and GC-F than to receptor GC-A, -B and -C which are activated by peptide ligands. Moreover, these olfactory GCs and retinal GCs share characteristic sequence similarity in a regulatory domain that is involved in the binding of GCAPs, suggesting GC-D activity may be regulated by an unknown extracellular ligand and intracellular Ca2+. Rodent GC-D-expressing neurons have been implicated in pheromone detection and were recently shown to respond to atmospheric CO2 which is an olfactory stimulus for many invertebrates and regulates some insect innate behavior, such as the location of food and hosts.


Pssm-ID: 380594 [Multi-domain]  Cd Length: 379  Bit Score: 586.59  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217    55 TVGVLGPWACDPIFSRARPDLAARLAAARLNRDPGLAGGPRFEVALLPEPCRTPGSLGAVSSALARVSGLVGPVNPAACR 134
Cdd:cd06371    1 KVGVVGPWTCDPIFAKALPDLAARLAVSRINKDPSLDLGYWFDYVILPEDCETSKALAAFSSAEGRASGFVGPVNPGYCE 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   135 PAELLAEEAGIALVPWGCPWT--QAEGTTAPAVTPAADALYALLRAFGWARVALVTAPQDLWVEAGRSLSTALRARGLPV 212
Cdd:cd06371   81 AASLLAQEWDKALFSWGCVNHelNSYPTFARTLPPPADVLYTVLRYFRWAHVAVVSSPQDLWVETGRELASALRARGLPV 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   213 ASVTSMEPLDlSGAREALRKVRDGPRVTAVIMVMHSVLLGGEEQRYLLEAAEELGLTDGSLVFLPFDTIHYALSPGPEAL 292
Cdd:cd06371  161 GLVTSMEPSD-SGAREALKRIRDADRVRVVIMCMHSVLIGGEEQRTLLEAAHDMGLTDGSYVFVPYDTLLYSLPYKHEPY 239
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   293 AALANSSQLRRAHDAVLTLTRHcPSEGSVLDSLRRAQERRELPSDLNLQQVSPLFGTIYDAVFLLarGVAEARAAAGGRW 372
Cdd:cd06371  240 AVLRNNSKLRRAYDAVLTITME-SPEGSFYEAFRRAQERGELPSDLDPEQVSPLFGTIYNSIYLL--AGAVENARAAGGG 316
                        330       340       350       360       370       380
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 4504217   373 VSGAAVARHIRDAQVPGFCGDL----GGDEEPPFVLLDTDAAGDRLFATYMLDPARGSFLSAG 431
Cdd:cd06371  317 VSGASLARHARNAQFPGFNQLLrtdsGGNGQPSYVILDTDGKGWRLFPTYTLDMTTGLLRFLG 379
PK_GC-2D cd14043
Pseudokinase domain of the membrane Guanylate Cyclase receptor, GC-2D; The pseudokinase domain ...
536-811 8.71e-174

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: 510.03  E-value: 8.71e-174
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   536 MSDIRSGPSQHLDSPNIGV-YEGDRVWLKKFPGDQHIAIRPATKTAFSKLQELRHENVALYLGLFLARGaegpaalwegN 614
Cdd:cd14043    1 PSSPSSTSSVNATSSNTGVaYEGDWVWLKKFPGGSHTELRPSTKNVFSKLRELRHENVNLFLGLFVDCG----------I 70
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   615 LAVVSEHCTRGSLQDLLAQREIKLDWMFKSSLLLDLIKGIRYLHHRGVAHGRLKSRNCIVDGRFVLKITDHGHGRLLEAQ 694
Cdd:cd14043   71 LAIVSEHCSRGSLEDLLRNDDMKLDWMFKSSLLLDLIKGMRYLHHRGIVHGRLKSRNCVVDGRFVLKITDYGYNEILEAQ 150
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   695 KVLPEPPRAEDQLWTAPELLRDPALERRGTLAGDVFSLAIIMQEVVCRSAPYAMLELTPEEVVQRVRSPPPLCRPLVSMD 774
Cdd:cd14043  151 NLPLPEPAPEELLWTAPELLRDPRLERRGTFPGDVFSFAIIMQEVIVRGAPYCMLGLSPEEIIEKVRSPPPLCRPSVSMD 230
                        250       260       270
                 ....*....|....*....|....*....|....*..
gi 4504217   775 QAPVECILLMKQCWAEQPELRPSMDHTFDLFKNINKG 811
Cdd:cd14043  231 QAPLECIQLMKQCWSEAPERRPTFDQIFDQFKSINKG 267
CYCc smart00044
Adenylyl- / guanylyl cyclase, catalytic domain; Present in two copies in mammalian adenylyl ...
846-1036 1.53e-88

Adenylyl- / guanylyl cyclase, catalytic domain; Present in two copies in mammalian adenylyl cyclases. Eubacterial homologues are known. Two residues (Asn, Arg) are thought to be involved in catalysis. These cyclases have important roles in a diverse range of cellular processes.


Pssm-ID: 214485  Cd Length: 194  Bit Score: 282.99  E-value: 1.53e-88
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217      846 KQKTDRLLTQMLPPSVAEALKTG-TPVEPEYFEQVTLYFSDIVGFTTISAMSEPIEVVDLLNDLYTLFDAIIGSHDVYKV 924
Cdd:smart00044    3 KKKTDRLLDQLLPASVAEQLKRGgSPVPAESYDNVTILFSDIVGFTSLCSTSTPEQVVNLLNDLYSRFDQIIDRHGGYKV 82
                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217      925 ETIGDAYMVASGLPQRNGQRHAAEIANMSLDILSAVGTFrMRHMPEVPVRIRIGLHSGPCVAGVVGLTMPRYCLFGDTVN 1004
Cdd:smart00044   83 KTIGDAYMVASGLPEEALVDHAELIADEALDMVEELKTV-LVQHREEGLRVRIGIHTGPVVAGVVGIRMPRYCLFGDTVN 161
                           170       180       190
                    ....*....|....*....|....*....|..
gi 4504217     1005 TASRMESTGLPYRIHVNLSTVGILRALDSGYQ 1036
Cdd:smart00044  162 LASRMESAGDPGQIQVSEETYSLLARRGGQFV 193
Guanylate_cyc pfam00211
Adenylate and Guanylate cyclase catalytic domain;
871-1058 1.34e-77

Adenylate and Guanylate cyclase catalytic domain;


Pssm-ID: 425528  Cd Length: 183  Bit Score: 252.55  E-value: 1.34e-77
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217     871 VEPEYFEQVTLYFSDIVGFTTISAMSEPIEVVDLLNDLYTLFDAIIGSHDVYKVETIGDAYMVASGLPqRNGQRHAAEIA 950
Cdd:pfam00211    1 VYAQPYDNVTILFADIVGFTALSSRHSPEQVVRLLNELYTRFDRLLDKHKVYKVKTIGDAYMVVSGLP-EPSPAHARKIA 79
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217     951 NMSLDILSAVGTFRMRHMPevPVRIRIGLHSGPCVAGVVGLTMPRYCLFGDTVNTASRMESTGLPYRIHVNLSTVGILRa 1030
Cdd:pfam00211   80 EMALDMLEAIGEVNVESSE--GLRVRVGIHTGPVVAGVIGARMPRYDLWGNTVNLASRMESTGVPGKIHVSEETYRLLK- 156
                          170       180
                   ....*....|....*....|....*...
gi 4504217    1031 lDSGYQVELRGRTELKGKGAEDTFWLVG 1058
Cdd:pfam00211  157 -TEGFEFTERGEIEVKGKGKMKTYFLNG 183
CHD cd07302
cyclase homology domain; Catalytic domains of the mononucleotidyl cyclases (MNC's), also ...
878-1056 1.77e-62

cyclase homology domain; Catalytic domains of the mononucleotidyl cyclases (MNC's), also called cyclase homology domains (CHDs), are part of the class III nucleotidyl cyclases. This class includes eukaryotic and prokaryotic adenylate cyclases (AC's) and guanylate cyclases (GC's). They seem to share a common catalytic mechanism in their requirement for two magnesium ions to bind the polyphosphate moiety of the nucleotide.


Pssm-ID: 143636 [Multi-domain]  Cd Length: 177  Bit Score: 210.13  E-value: 1.77e-62
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   878 QVTLYFSDIVGFTTISAMSEPIEVVDLLNDLYTLFDAIIGSHDVYKVETIGDAYMVASGLPQRNgQRHAAEIANMSLDIL 957
Cdd:cd07302    1 EVTVLFADIVGFTALSERLGPEELVELLNEYFSAFDEIIERHGGTVDKTIGDAVMAVFGLPGAH-EDHAERAVRAALEMQ 79
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   958 SAVGTFRMRHMPEVPVRIRIGLHSGPCVAGVVGLTMPRYCLFGDTVNTASRMESTGLPYRIHVNLSTVGILRalDSGYQV 1037
Cdd:cd07302   80 EALAELNAEREGGPPLRLRIGIHTGPVVAGVVGSERPEYTVIGDTVNLAARLESLAKPGQILVSEATYELLG--DAGFEF 157
                        170       180
                 ....*....|....*....|
gi 4504217  1038 ELRGRTELKGK-GAEDTFWL 1056
Cdd:cd07302  158 EELGEVELKGKsGPVRVYRL 177
ANF_receptor pfam01094
Receptor family ligand binding region; This family includes extracellular ligand binding ...
87-420 4.93e-44

Receptor family ligand binding region; This family includes extracellular ligand binding domains of a wide range of receptors. This family also includes the bacterial amino acid binding proteins of known structure.


Pssm-ID: 460062 [Multi-domain]  Cd Length: 347  Bit Score: 163.33  E-value: 4.93e-44
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217      87 DPGLAGGPRFEVALLPEPCRTPGSLGAVSSALA-RVSGLVGPVNPAACRPAELLAEEAGIALVPWGC-PWTQAEGT---- 160
Cdd:pfam01094   16 DPGLLPGTKLEYIILDTCCDPSLALAAALDLLKgEVVAIIGPSCSSVASAVASLANEWKVPLISYGStSPALSDLNrypt 95
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217     161 ---TAPAVTPAADALYALLRAFGWARVALVTAPQDLWVEAGRSLSTALRARGLPVASVTSMEPL--DLSGAREALRKVRD 235
Cdd:pfam01094   96 flrTTPSDTSQADAIVDILKHFGWKRVALIYSDDDYGESGLQALEDALRERGIRVAYKAVIPPAqdDDEIARKLLKEVKS 175
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217     236 GPRVtaVIMVMHSvllggEEQRYLLEAAEELGLTDGSLVFLPFDTIHYALSPgpealaalaNSSQLRRAHDAVLTLTRHC 315
Cdd:pfam01094  176 RARV--IVVCCSS-----ETARRLLKAARELGMMGEGYVWIATDGLTTSLVI---------LNPSTLEAAGGVLGFRLHP 239
                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217     316 PSEGSVLDSL-RRAQERRELPSDLNLQQVSPLFgTIYDAVFLL--------ARGVAEARAAAGGRWVSGAAVARHIRDAQ 386
Cdd:pfam01094  240 PDSPEFSEFFwEKLSDEKELYENLGGLPVSYGA-LAYDAVYLLahalhnllRDDKPGRACGALGPWNGGQKLLRYLKNVN 318
                          330       340       350
                   ....*....|....*....|....*....|....
gi 4504217     387 VPGFCGDlggdeeppfvlLDTDAAGDRLFATYML 420
Cdd:pfam01094  319 FTGLTGN-----------VQFDENGDRINPDYDI 341
AcyC COG2114
Adenylate cyclase, class 3 [Signal transduction mechanisms];
816-1061 1.58e-41

Adenylate cyclase, class 3 [Signal transduction mechanisms];


Pssm-ID: 441717 [Multi-domain]  Cd Length: 407  Bit Score: 158.04  E-value: 1.58e-41
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   816 IIDSMLRMLEQYSSNLEDLIRERTEELELEKQKTDRLLTQMLPPSVAEALKTGTPVEP--EYFEQVTLYFSDIVGFTTIS 893
Cdd:COG2114  158 VALLLLALLLLLLLLLLLALLLLLLLALRERERLRDLLGRYLPPEVAERLLAGGEELRlgGERREVTVLFADIVGFTALS 237
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   894 AMSEPIEVVDLLNDLYTLFDAIIGSHDVYKVETIGDAYMVASGLPQRNGQrHAAEIANMSLDILSAVGTFRMRHMPE--V 971
Cdd:COG2114  238 ERLGPEELVELLNRYFSAMVEIIERHGGTVDKFIGDGVMAVFGAPVARED-HAERAVRAALAMQEALAELNAELPAEggP 316
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   972 PVRIRIGLHSGPCVAGVVGLTMPR-YCLFGDTVNTASRMESTGLPYRIHVNLSTVgilRALDSGYQVELRGRTELKGKGA 1050
Cdd:COG2114  317 PLRVRIGIHTGEVVVGNIGSEDRLdYTVIGDTVNLAARLESLAKPGEILVSEATY---DLLRDRFEFRELGEVRLKGKAE 393
                        250
                 ....*....|..
gi 4504217  1051 E-DTFWLVGRRG 1061
Cdd:COG2114  394 PvEVYELLGAKE 405
PK_Tyr_Ser-Thr pfam07714
Protein tyrosine and serine/threonine kinase; Protein phosphorylation, which plays a key role ...
554-798 4.12e-29

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: 117.21  E-value: 4.12e-29
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217     554 VYEGdrvWLKKFPGDQHI--AI-------RPATKTAF----SKLQELRHENVALYLGlflargaegpAALWEGNLAVVSE 620
Cdd:pfam07714   15 VYKG---TLKGEGENTKIkvAVktlkegaDEEEREDFleeaSIMKKLDHPNIVKLLG----------VCTQGEPLYIVTE 81
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217     621 HCTRGSLQDLLAQREIKLDWMFKSSLLLDLIKGIRYLHHRGVAHGRLKSRNCIVDGRFVLKITDHGHGRLLE------AQ 694
Cdd:pfam07714   82 YMPGGDLLDFLRKHKRKLTLKDLLSMALQIAKGMEYLESKNFVHRDLAARNCLVSENLVVKISDFGLSRDIYdddyyrKR 161
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217     695 KVLPEPPRaedqlWTAPELLRDpaleRRGTLAGDVFSLAIIMQEVVCRSA-PYAmlELTPEEVVQRVRSPPPLCRPlvsm 773
Cdd:pfam07714  162 GGGKLPIK-----WMAPESLKD----GKFTSKSDVWSFGVLLWEIFTLGEqPYP--GMSNEEVLEFLEDGYRLPQP---- 226
                          250       260
                   ....*....|....*....|....*
gi 4504217     774 DQAPVECILLMKQCWAEQPELRPSM 798
Cdd:pfam07714  227 ENCPDELYDLMKQCWAYDPEDRPTF 251
TyrKc smart00219
Tyrosine kinase, catalytic domain; Phosphotransferases. Tyrosine-specific kinase subfamily.
584-798 1.44e-27

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


Pssm-ID: 197581 [Multi-domain]  Cd Length: 257  Bit Score: 113.01  E-value: 1.44e-27
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217      584 LQELRHENVALYLGlflargaegpAALWEGNLAVVSEHCTRGSLQDLLAQREIKLDWMFKSSLLLDLIKGIRYLHHRGVA 663
Cdd:smart00219   55 MRKLDHPNVVKLLG----------VCTEEEPLYIVMEYMEGGDLLSYLRKNRPKLSLSDLLSFALQIARGMEYLESKNFI 124
                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217      664 HGRLKSRNCIVDGRFVLKITDHGHGRLLE-----AQKVLPEPPRaedqlWTAPELLRdpalERRGTLAGDVFSLAIIMQE 738
Cdd:smart00219  125 HRDLAARNCLVGENLVVKISDFGLSRDLYdddyyRKRGGKLPIR-----WMAPESLK----EGKFTSKSDVWSFGVLLWE 195
                           170       180       190       200       210       220
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 4504217      739 VVCR-SAPYAmlELTPEEVVQRVRS-----PPPLCrplvsmdqaPVECILLMKQCWAEQPELRPSM 798
Cdd:smart00219  196 IFTLgEQPYP--GMSNEEVLEYLKNgyrlpQPPNC---------PPELYDLMLQCWAEDPEDRPTF 250
SPS1 COG0515
Serine/threonine protein kinase [Signal transduction mechanisms];
584-765 5.66e-11

Serine/threonine protein kinase [Signal transduction mechanisms];


Pssm-ID: 440281 [Multi-domain]  Cd Length: 482  Bit Score: 66.19  E-value: 5.66e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   584 LQELRHENVALYLGLFLARGAegpaalwegnLAVVSEHCTRGSLQDLLAQREiKLDWMFKSSLLLDLIKGIRYLHHRGVA 663
Cdd:COG0515   61 LARLNHPNIVRVYDVGEEDGR----------PYLVMEYVEGESLADLLRRRG-PLPPAEALRILAQLAEALAAAHAAGIV 129
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   664 HGRLKSRNCIVDGRFVLKITDHGHGRLLEAQKVLPEPPRAEDQLWTAPELLRDpaleRRGTLAGDVFSLAIIMQEVVCRS 743
Cdd:COG0515  130 HRDIKPANILLTPDGRVKLIDFGIARALGGATLTQTGTVVGTPGYMAPEQARG----EPVDPRSDVYSLGVTLYELLTGR 205
                        170       180
                 ....*....|....*....|..
gi 4504217   744 APYAmlELTPEEVVQRVRSPPP 765
Cdd:COG0515  206 PPFD--GDSPAELLRAHLREPP 225
PHA02988 PHA02988
hypothetical protein; Provisional
535-746 1.18e-08

hypothetical protein; Provisional


Pssm-ID: 165291 [Multi-domain]  Cd Length: 283  Bit Score: 57.44  E-value: 1.18e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217    535 SMSDIRSGPSQHLDSPNI-------------GVYEGDRVWLKKFPGDQ--HIAIRPATKTAFSKLQELRHENVALYLGLF 599
Cdd:PHA02988    8 YINDIKCIESDDIDKYTSvlikendqnsiykGIFNNKEVIIRTFKKFHkgHKVLIDITENEIKNLRRIDSNNILKIYGFI 87
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217    600 LARGAEGPaalwegNLAVVSEHCTRGSLQDLLaQREIKLDWMFKSSLLLDLIKGIRYLH-HRGVAHGRLKSRNCIVDGRF 678
Cdd:PHA02988   88 IDIVDDLP------RLSLILEYCTRGYLREVL-DKEKDLSFKTKLDMAIDCCKGLYNLYkYTNKPYKNLTSVSFLVTENY 160
                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217    679 VLKITDHGhgrlLEaqKVLPEPP--RAEDQLWTAPELLRDPALERrgTLAGDVFSLAIIMQEVVCRSAPY 746
Cdd:PHA02988  161 KLKIICHG----LE--KILSSPPfkNVNFMVYFSYKMLNDIFSEY--TIKDDIYSLGVVLWEIFTGKIPF 222
HNOBA pfam07701
Heme NO binding associated; The HNOBA domain is found associated with the HNOB domain and ...
820-865 6.45e-05

Heme NO binding associated; The HNOBA domain is found associated with the HNOB domain and pfam00211 in soluble cyclases and signalling proteins. The HNOB domain is predicted to function as a heme-dependent sensor for gaseous ligands, and transduce diverse downstream signals, in both bacteria and animals.


Pssm-ID: 462234  Cd Length: 214  Bit Score: 45.26  E-value: 6.45e-05
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*.
gi 4504217     820 MLRMLEQYSSNLEDLIRERTEEleleKQKTDRLLTQMLPPSVAEAL 865
Cdd:pfam07701  173 ALDQLEQKSAELEESMRELEEE----KKKTDELLYSMLPKSVADRL 214
LivK COG0683
ABC-type branched-chain amino acid transport system, periplasmic component [Amino acid ...
120-269 2.32e-04

ABC-type branched-chain amino acid transport system, periplasmic component [Amino acid transport and metabolism];


Pssm-ID: 440447 [Multi-domain]  Cd Length: 314  Bit Score: 44.54  E-value: 2.32e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   120 RVSGLVGPVNPAACRPAELLAEEAGIALVpwgcpwtqAEGTTAPAVTP-----------AADALYA------LLRAFGWA 182
Cdd:COG0683   71 KVDAIVGPLSSGVALAVAPVAEEAGVPLI--------SPSATAPALTGpecspyvfrtaPSDAQQAealadyLAKKLGAK 142
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   183 RVALVTAPQDLWVEAGRSLSTALRARGLPVASVTSMePLDLSGAREALRKVRDGpRVTAVIMVMHsvllgGEEQRYLLEA 262
Cdd:COG0683  143 KVALLYDDYAYGQGLAAAFKAALKAAGGEVVGEEYY-PPGTTDFSAQLTKIKAA-GPDAVFLAGY-----GGDAALFIKQ 215

                 ....*..
gi 4504217   263 AEELGLT 269
Cdd:COG0683  216 AREAGLK 222
 
Name Accession Description Interval E-value
PBP1_sensory_GC_DEF-like cd06371
ligand-binding domain of membrane guanylyl cyclases (GC-D, GC-E, and GC-F) that are ...
55-431 0e+00

ligand-binding domain of membrane guanylyl cyclases (GC-D, GC-E, and GC-F) that are specifically expressed in sensory tissues; This group includes the ligand-binding domain of membrane guanylyl cyclases (GC-D, GC-E, and GC-F) that are specifically expressed in sensory tissues. They share a similar topology with an N-terminal extracellular ligand-binding domain, a single transmembrane domain, and a C-terminal cytosolic region that contains kinase-like and catalytic domains. GC-D is specifically expressed in a subpopulation of olfactory sensory neurons. GC-E and GC-F are colocalized within the same photoreceptor cells of the retina and have important roles in phototransduction. Unlike the other family members, GC-E and GC-F have no known extracellular ligands. Instead, they are activated under low calcium conditions by guanylyl cyclase activating proteins called GCAPs. GC-D expressing neurons have been implicated in pheromone detection and GC-D is phylogenetically more similar to the Ca2+-regulated GC-E and GC-F than to receptor GC-A, -B and -C which are activated by peptide ligands. Moreover, these olfactory GCs and retinal GCs share characteristic sequence similarity in a regulatory domain that is involved in the binding of GCAPs, suggesting GC-D activity may be regulated by an unknown extracellular ligand and intracellular Ca2+. Rodent GC-D-expressing neurons have been implicated in pheromone detection and were recently shown to respond to atmospheric CO2 which is an olfactory stimulus for many invertebrates and regulates some insect innate behavior, such as the location of food and hosts.


Pssm-ID: 380594 [Multi-domain]  Cd Length: 379  Bit Score: 586.59  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217    55 TVGVLGPWACDPIFSRARPDLAARLAAARLNRDPGLAGGPRFEVALLPEPCRTPGSLGAVSSALARVSGLVGPVNPAACR 134
Cdd:cd06371    1 KVGVVGPWTCDPIFAKALPDLAARLAVSRINKDPSLDLGYWFDYVILPEDCETSKALAAFSSAEGRASGFVGPVNPGYCE 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   135 PAELLAEEAGIALVPWGCPWT--QAEGTTAPAVTPAADALYALLRAFGWARVALVTAPQDLWVEAGRSLSTALRARGLPV 212
Cdd:cd06371   81 AASLLAQEWDKALFSWGCVNHelNSYPTFARTLPPPADVLYTVLRYFRWAHVAVVSSPQDLWVETGRELASALRARGLPV 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   213 ASVTSMEPLDlSGAREALRKVRDGPRVTAVIMVMHSVLLGGEEQRYLLEAAEELGLTDGSLVFLPFDTIHYALSPGPEAL 292
Cdd:cd06371  161 GLVTSMEPSD-SGAREALKRIRDADRVRVVIMCMHSVLIGGEEQRTLLEAAHDMGLTDGSYVFVPYDTLLYSLPYKHEPY 239
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   293 AALANSSQLRRAHDAVLTLTRHcPSEGSVLDSLRRAQERRELPSDLNLQQVSPLFGTIYDAVFLLarGVAEARAAAGGRW 372
Cdd:cd06371  240 AVLRNNSKLRRAYDAVLTITME-SPEGSFYEAFRRAQERGELPSDLDPEQVSPLFGTIYNSIYLL--AGAVENARAAGGG 316
                        330       340       350       360       370       380
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 4504217   373 VSGAAVARHIRDAQVPGFCGDL----GGDEEPPFVLLDTDAAGDRLFATYMLDPARGSFLSAG 431
Cdd:cd06371  317 VSGASLARHARNAQFPGFNQLLrtdsGGNGQPSYVILDTDGKGWRLFPTYTLDMTTGLLRFLG 379
PK_GC-2D cd14043
Pseudokinase domain of the membrane Guanylate Cyclase receptor, GC-2D; The pseudokinase domain ...
536-811 8.71e-174

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: 510.03  E-value: 8.71e-174
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   536 MSDIRSGPSQHLDSPNIGV-YEGDRVWLKKFPGDQHIAIRPATKTAFSKLQELRHENVALYLGLFLARGaegpaalwegN 614
Cdd:cd14043    1 PSSPSSTSSVNATSSNTGVaYEGDWVWLKKFPGGSHTELRPSTKNVFSKLRELRHENVNLFLGLFVDCG----------I 70
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   615 LAVVSEHCTRGSLQDLLAQREIKLDWMFKSSLLLDLIKGIRYLHHRGVAHGRLKSRNCIVDGRFVLKITDHGHGRLLEAQ 694
Cdd:cd14043   71 LAIVSEHCSRGSLEDLLRNDDMKLDWMFKSSLLLDLIKGMRYLHHRGIVHGRLKSRNCVVDGRFVLKITDYGYNEILEAQ 150
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   695 KVLPEPPRAEDQLWTAPELLRDPALERRGTLAGDVFSLAIIMQEVVCRSAPYAMLELTPEEVVQRVRSPPPLCRPLVSMD 774
Cdd:cd14043  151 NLPLPEPAPEELLWTAPELLRDPRLERRGTFPGDVFSFAIIMQEVIVRGAPYCMLGLSPEEIIEKVRSPPPLCRPSVSMD 230
                        250       260       270
                 ....*....|....*....|....*....|....*..
gi 4504217   775 QAPVECILLMKQCWAEQPELRPSMDHTFDLFKNINKG 811
Cdd:cd14043  231 QAPLECIQLMKQCWSEAPERRPTFDQIFDQFKSINKG 267
PK_GC cd13992
Pseudokinase domain of membrane Guanylate Cyclase receptors; The pseudokinase domain shows ...
537-807 2.91e-109

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: 341.29  E-value: 2.91e-109
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   537 SDIRSGPSQHLDSPNIGVYEGdrvwlkkFPGDQHIAIRPAT---------KTAFSKLQELRHENVALYLGLFLARGaegp 607
Cdd:cd13992    1 ASCGSGASSHTGEPKYVKKVG-------VYGGRTVAIKHITfsrtekrtiLQELNQLKELVHDNLNKFIGICINPP---- 69
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   608 aalwegNLAVVSEHCTRGSLQDLLAQREIKLDWMFKSSLLLDLIKGIRYLH-HRGVAHGRLKSRNCIVDGRFVLKITDHG 686
Cdd:cd13992   70 ------NIAVVTEYCTRGSLQDVLLNREIKMDWMFKSSFIKDIVKGMNYLHsSSIGYHGRLKSSNCLVDSRWVVKLTDFG 143
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   687 HGRLLEAQKV--LPEPPRAEDQLWTAPELLRDPALERRGTLAGDVFSLAIIMQEVVCRSAPYAML-ELTPEEVVQRVRSP 763
Cdd:cd13992  144 LRNLLEEQTNhqLDEDAQHKKLLWTAPELLRGSLLEVRGTQKGDVYSFAIILYEILFRSDPFALErEVAIVEKVISGGNK 223
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|....*
gi 4504217   764 PPLCRPLVSMDQAPVECILLMKQCWAEQPELRPSM-DHTFDLFKN 807
Cdd:cd13992  224 PFRPELAVLLDEFPPRLVLLVKQCWAENPEKRPSFkQIKKTLTEN 268
CYCc smart00044
Adenylyl- / guanylyl cyclase, catalytic domain; Present in two copies in mammalian adenylyl ...
846-1036 1.53e-88

Adenylyl- / guanylyl cyclase, catalytic domain; Present in two copies in mammalian adenylyl cyclases. Eubacterial homologues are known. Two residues (Asn, Arg) are thought to be involved in catalysis. These cyclases have important roles in a diverse range of cellular processes.


Pssm-ID: 214485  Cd Length: 194  Bit Score: 282.99  E-value: 1.53e-88
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217      846 KQKTDRLLTQMLPPSVAEALKTG-TPVEPEYFEQVTLYFSDIVGFTTISAMSEPIEVVDLLNDLYTLFDAIIGSHDVYKV 924
Cdd:smart00044    3 KKKTDRLLDQLLPASVAEQLKRGgSPVPAESYDNVTILFSDIVGFTSLCSTSTPEQVVNLLNDLYSRFDQIIDRHGGYKV 82
                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217      925 ETIGDAYMVASGLPQRNGQRHAAEIANMSLDILSAVGTFrMRHMPEVPVRIRIGLHSGPCVAGVVGLTMPRYCLFGDTVN 1004
Cdd:smart00044   83 KTIGDAYMVASGLPEEALVDHAELIADEALDMVEELKTV-LVQHREEGLRVRIGIHTGPVVAGVVGIRMPRYCLFGDTVN 161
                           170       180       190
                    ....*....|....*....|....*....|..
gi 4504217     1005 TASRMESTGLPYRIHVNLSTVGILRALDSGYQ 1036
Cdd:smart00044  162 LASRMESAGDPGQIQVSEETYSLLARRGGQFV 193
Guanylate_cyc pfam00211
Adenylate and Guanylate cyclase catalytic domain;
871-1058 1.34e-77

Adenylate and Guanylate cyclase catalytic domain;


Pssm-ID: 425528  Cd Length: 183  Bit Score: 252.55  E-value: 1.34e-77
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217     871 VEPEYFEQVTLYFSDIVGFTTISAMSEPIEVVDLLNDLYTLFDAIIGSHDVYKVETIGDAYMVASGLPqRNGQRHAAEIA 950
Cdd:pfam00211    1 VYAQPYDNVTILFADIVGFTALSSRHSPEQVVRLLNELYTRFDRLLDKHKVYKVKTIGDAYMVVSGLP-EPSPAHARKIA 79
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217     951 NMSLDILSAVGTFRMRHMPevPVRIRIGLHSGPCVAGVVGLTMPRYCLFGDTVNTASRMESTGLPYRIHVNLSTVGILRa 1030
Cdd:pfam00211   80 EMALDMLEAIGEVNVESSE--GLRVRVGIHTGPVVAGVIGARMPRYDLWGNTVNLASRMESTGVPGKIHVSEETYRLLK- 156
                          170       180
                   ....*....|....*....|....*...
gi 4504217    1031 lDSGYQVELRGRTELKGKGAEDTFWLVG 1058
Cdd:pfam00211  157 -TEGFEFTERGEIEVKGKGKMKTYFLNG 183
PK_GC-A_B cd14042
Pseudokinase domain of the membrane Guanylate Cyclase receptors, GC-A and GC-B; The ...
528-811 5.27e-70

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: 235.18  E-value: 5.27e-70
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   528 RSSLGARSMSDIrsGPSQHLDSPNIGVYEGDRVWLKKFPgDQHIAIRPATKTAFSKLQELRHENVALYLGlflargaegp 607
Cdd:cd14042    3 SSSSYGSLMTAA--SFDQSQIFTKTGYYKGNLVAIKKVN-KKRIDLTREVLKELKHMRDLQHDNLTRFIG---------- 69
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   608 AALWEGNLAVVSEHCTRGSLQDLLAQREIKLDWMFKSSLLLDLIKGIRYLHHRG-VAHGRLKSRNCIVDGRFVLKITDHG 686
Cdd:cd14042   70 ACVDPPNICILTEYCPKGSLQDILENEDIKLDWMFRYSLIHDIVKGMHYLHDSEiKSHGNLKSSNCVVDSRFVLKITDFG 149
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   687 hgrlLEAQKVLPEPPR-----AEDQLWTAPELLRDPALERRGTLAGDVFSLAIIMQEVVCRSAPYA--MLELTPEE-VVQ 758
Cdd:cd14042  150 ----LHSFRSGQEPPDdshayYAKLLWTAPELLRDPNPPPPGTQKGDVYSFGIILQEIATRQGPFYeeGPDLSPKEiIKK 225
                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 4504217   759 RVRS--PPPLcRPLVSMDQAPVECILLMKQCWAEQPELRPSMDHTFDLFKNINKG 811
Cdd:cd14042  226 KVRNgeKPPF-RPSLDELECPDEVLSLMQRCWAEDPEERPDFSTLRNKLKKLNKG 279
CHD cd07302
cyclase homology domain; Catalytic domains of the mononucleotidyl cyclases (MNC's), also ...
878-1056 1.77e-62

cyclase homology domain; Catalytic domains of the mononucleotidyl cyclases (MNC's), also called cyclase homology domains (CHDs), are part of the class III nucleotidyl cyclases. This class includes eukaryotic and prokaryotic adenylate cyclases (AC's) and guanylate cyclases (GC's). They seem to share a common catalytic mechanism in their requirement for two magnesium ions to bind the polyphosphate moiety of the nucleotide.


Pssm-ID: 143636 [Multi-domain]  Cd Length: 177  Bit Score: 210.13  E-value: 1.77e-62
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   878 QVTLYFSDIVGFTTISAMSEPIEVVDLLNDLYTLFDAIIGSHDVYKVETIGDAYMVASGLPQRNgQRHAAEIANMSLDIL 957
Cdd:cd07302    1 EVTVLFADIVGFTALSERLGPEELVELLNEYFSAFDEIIERHGGTVDKTIGDAVMAVFGLPGAH-EDHAERAVRAALEMQ 79
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   958 SAVGTFRMRHMPEVPVRIRIGLHSGPCVAGVVGLTMPRYCLFGDTVNTASRMESTGLPYRIHVNLSTVGILRalDSGYQV 1037
Cdd:cd07302   80 EALAELNAEREGGPPLRLRIGIHTGPVVAGVVGSERPEYTVIGDTVNLAARLESLAKPGQILVSEATYELLG--DAGFEF 157
                        170       180
                 ....*....|....*....|
gi 4504217  1038 ELRGRTELKGK-GAEDTFWL 1056
Cdd:cd07302  158 EELGEVELKGKsGPVRVYRL 177
ANF_receptor pfam01094
Receptor family ligand binding region; This family includes extracellular ligand binding ...
87-420 4.93e-44

Receptor family ligand binding region; This family includes extracellular ligand binding domains of a wide range of receptors. This family also includes the bacterial amino acid binding proteins of known structure.


Pssm-ID: 460062 [Multi-domain]  Cd Length: 347  Bit Score: 163.33  E-value: 4.93e-44
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217      87 DPGLAGGPRFEVALLPEPCRTPGSLGAVSSALA-RVSGLVGPVNPAACRPAELLAEEAGIALVPWGC-PWTQAEGT---- 160
Cdd:pfam01094   16 DPGLLPGTKLEYIILDTCCDPSLALAAALDLLKgEVVAIIGPSCSSVASAVASLANEWKVPLISYGStSPALSDLNrypt 95
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217     161 ---TAPAVTPAADALYALLRAFGWARVALVTAPQDLWVEAGRSLSTALRARGLPVASVTSMEPL--DLSGAREALRKVRD 235
Cdd:pfam01094   96 flrTTPSDTSQADAIVDILKHFGWKRVALIYSDDDYGESGLQALEDALRERGIRVAYKAVIPPAqdDDEIARKLLKEVKS 175
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217     236 GPRVtaVIMVMHSvllggEEQRYLLEAAEELGLTDGSLVFLPFDTIHYALSPgpealaalaNSSQLRRAHDAVLTLTRHC 315
Cdd:pfam01094  176 RARV--IVVCCSS-----ETARRLLKAARELGMMGEGYVWIATDGLTTSLVI---------LNPSTLEAAGGVLGFRLHP 239
                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217     316 PSEGSVLDSL-RRAQERRELPSDLNLQQVSPLFgTIYDAVFLL--------ARGVAEARAAAGGRWVSGAAVARHIRDAQ 386
Cdd:pfam01094  240 PDSPEFSEFFwEKLSDEKELYENLGGLPVSYGA-LAYDAVYLLahalhnllRDDKPGRACGALGPWNGGQKLLRYLKNVN 318
                          330       340       350
                   ....*....|....*....|....*....|....
gi 4504217     387 VPGFCGDlggdeeppfvlLDTDAAGDRLFATYML 420
Cdd:pfam01094  319 FTGLTGN-----------VQFDENGDRINPDYDI 341
AcyC COG2114
Adenylate cyclase, class 3 [Signal transduction mechanisms];
816-1061 1.58e-41

Adenylate cyclase, class 3 [Signal transduction mechanisms];


Pssm-ID: 441717 [Multi-domain]  Cd Length: 407  Bit Score: 158.04  E-value: 1.58e-41
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   816 IIDSMLRMLEQYSSNLEDLIRERTEELELEKQKTDRLLTQMLPPSVAEALKTGTPVEP--EYFEQVTLYFSDIVGFTTIS 893
Cdd:COG2114  158 VALLLLALLLLLLLLLLLALLLLLLLALRERERLRDLLGRYLPPEVAERLLAGGEELRlgGERREVTVLFADIVGFTALS 237
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   894 AMSEPIEVVDLLNDLYTLFDAIIGSHDVYKVETIGDAYMVASGLPQRNGQrHAAEIANMSLDILSAVGTFRMRHMPE--V 971
Cdd:COG2114  238 ERLGPEELVELLNRYFSAMVEIIERHGGTVDKFIGDGVMAVFGAPVARED-HAERAVRAALAMQEALAELNAELPAEggP 316
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   972 PVRIRIGLHSGPCVAGVVGLTMPR-YCLFGDTVNTASRMESTGLPYRIHVNLSTVgilRALDSGYQVELRGRTELKGKGA 1050
Cdd:COG2114  317 PLRVRIGIHTGEVVVGNIGSEDRLdYTVIGDTVNLAARLESLAKPGEILVSEATY---DLLRDRFEFRELGEVRLKGKAE 393
                        250
                 ....*....|..
gi 4504217  1051 E-DTFWLVGRRG 1061
Cdd:COG2114  394 PvEVYELLGAKE 405
PK_GC-C cd14044
Pseudokinase domain of the membrane Guanylate Cyclase receptor, GC-C; The pseudokinase domain ...
618-796 9.08e-36

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: 137.32  E-value: 9.08e-36
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   618 VSEHCTRGSLQDLLAQR-----EIKLDWMFKSSLLLDLIKGIRYLHHRGVA-HGRLKSRNCIVDGRFVLKITDHGHGRLL 691
Cdd:cd14044   81 VIEYCERGSLRDVLNDKisypdGTFMDWEFKISVMYDIAKGMSYLHSSKTEvHGRLKSTNCVVDSRMVVKITDFGCNSIL 160
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   692 eaqkvlpePPRAEdqLWTAPELLRDPALERRgtlaGDVFSLAIIMQEVVCRSAPYAMLELTP-EEVVQRVRSPPPLC--R 768
Cdd:cd14044  161 --------PPSKD--LWTAPEHLRQAGTSQK----GDVYSYGIIAQEIILRKETFYTAACSDrKEKIYRVQNPKGMKpfR 226
                        170       180       190
                 ....*....|....*....|....*....|.
gi 4504217   769 PLVSMDQA---PVECILLMKQCWAEQPELRP 796
Cdd:cd14044  227 PDLNLESAgerEREVYGLVKNCWEEDPEKRP 257
Nucleotidyl_cyc_III cd07556
Class III nucleotidyl cyclases; Class III nucleotidyl cyclases are the largest, most diverse ...
878-1019 1.21e-35

Class III nucleotidyl cyclases; Class III nucleotidyl cyclases are the largest, most diverse group of nucleotidyl cyclases (NC's) containing prokaryotic and eukaryotic proteins. They can be divided into two major groups; the mononucleotidyl cyclases (MNC's) and the diguanylate cyclases (DGC's). The MNC's, which include the adenylate cyclases (AC's) and the guanylate cyclases (GC's), have a conserved cyclase homology domain (CHD), while the DGC's have a conserved GGDEF domain, named after a conserved motif within this subgroup. Their products, cyclic guanylyl and adenylyl nucleotides, are second messengers that play important roles in eukaryotic signal transduction and prokaryotic sensory pathways.


Pssm-ID: 143637 [Multi-domain]  Cd Length: 133  Bit Score: 131.71  E-value: 1.21e-35
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   878 QVTLYFSDIVGFTTISAMSEPIEVVDLLNDLYTLFDAIIGSHDVYKVETIGDAYMVASGLPqrngqrHAAEIANMSLDIL 957
Cdd:cd07556    1 PVTILFADIVGFTSLADALGPDEGDELLNELAGRFDSLIRRSGDLKIKTIGDEFMVVSGLD------HPAAAVAFAEDMR 74
                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 4504217   958 SAVGtfRMRHMPEVPVRIRIGLHSGPCVAGVVGLtMPRYCLFGDTVNTASRMESTGLPYRIH 1019
Cdd:cd07556   75 EAVS--ALNQSEGNPVRVRIGIHTGPVVVGVIGS-RPQYDVWGALVNLASRMESQAKAGQVL 133
STKc_MAP3K-like cd13999
Catalytic domain of Mitogen-Activated Protein Kinase (MAPK) Kinase Kinase-like Serine ...
584-800 1.42e-35

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: 135.74  E-value: 1.42e-35
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   584 LQELRHENVALYLGlflargaegpAALWEGNLAVVSEHCTRGSLQDLLAQREIKLDWMFKSSLLLDLIKGIRYLHHRGVA 663
Cdd:cd13999   44 LSKLRHPNIVQFIG----------ACLSPPPLCIVTEYMPGGSLYDLLHKKKIPLSWSLRLKIALDIARGMNYLHSPPII 113
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   664 HGRLKSRNCIVDGRFVLKITDHGHGRLL----EAQKVLPEPPRaedqlWTAPELLRdpalERRGTLAGDVFSLAIIMQEV 739
Cdd:cd13999  114 HRDLKSLNILLDENFTVKIADFGLSRIKnsttEKMTGVVGTPR-----WMAPEVLR----GEPYTEKADVYSFGIVLWEL 184
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 4504217   740 VCRSAPYAmlELTPEEVVQRVRSPPPlcRPLVSMDqAPVECILLMKQCWAEQPELRPSMDH 800
Cdd:cd13999  185 LTGEVPFK--ELSPIQIAAAVVQKGL--RPPIPPD-CPPELSKLIKRCWNEDPEKRPSFSE 240
PK_GC_unk cd14045
Pseudokinase domain of the unknown subfamily of membrane Guanylate Cyclase receptors; The ...
553-799 1.60e-32

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: 127.67  E-value: 1.60e-32
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   553 GVYEGdrvwlkkfpgdQHIAIRPATKTAFS----------KLQELRHENVALYLGLFLargaEGPaalwegNLAVVSEHC 622
Cdd:cd14045   26 GIYDG-----------RTVAIKKIAKKSFTlskrirkevkQVRELDHPNLCKFIGGCI----EVP------NVAIITEYC 84
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   623 TRGSLQDLLAQREIKLDWMFKSSLLLDLIKGIRYLHHRGVAHGRLKSRNCIVDGRFVLKITDHGHgRLLEAQKvLPEPPR 702
Cdd:cd14045   85 PKGSLNDVLLNEDIPLNWGFRFSFATDIARGMAYLHQHKIYHGRLKSSNCVIDDRWVCKIADYGL-TTYRKED-GSENAS 162
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   703 AED----QLWTAPELLRDPALERrgTLAGDVFSLAIIMQEVVCRSAPyamlelTPEEVvqrvrspPPL----CRPLVSMD 774
Cdd:cd14045  163 GYQqrlmQVYLPPENHSNTDTEP--TQATDVYSYAIILLEIATRNDP------VPEDD-------YSLdeawCPPLPELI 227
                        250       260       270
                 ....*....|....*....|....*....|...
gi 4504217   775 QA--------PVECILLMKQCWAEQPELRPSMD 799
Cdd:cd14045  228 SGktenscpcPADYVELIRRCRKNNPAQRPTFE 260
PK_Tyr_Ser-Thr pfam07714
Protein tyrosine and serine/threonine kinase; Protein phosphorylation, which plays a key role ...
554-798 4.12e-29

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: 117.21  E-value: 4.12e-29
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217     554 VYEGdrvWLKKFPGDQHI--AI-------RPATKTAF----SKLQELRHENVALYLGlflargaegpAALWEGNLAVVSE 620
Cdd:pfam07714   15 VYKG---TLKGEGENTKIkvAVktlkegaDEEEREDFleeaSIMKKLDHPNIVKLLG----------VCTQGEPLYIVTE 81
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217     621 HCTRGSLQDLLAQREIKLDWMFKSSLLLDLIKGIRYLHHRGVAHGRLKSRNCIVDGRFVLKITDHGHGRLLE------AQ 694
Cdd:pfam07714   82 YMPGGDLLDFLRKHKRKLTLKDLLSMALQIAKGMEYLESKNFVHRDLAARNCLVSENLVVKISDFGLSRDIYdddyyrKR 161
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217     695 KVLPEPPRaedqlWTAPELLRDpaleRRGTLAGDVFSLAIIMQEVVCRSA-PYAmlELTPEEVVQRVRSPPPLCRPlvsm 773
Cdd:pfam07714  162 GGGKLPIK-----WMAPESLKD----GKFTSKSDVWSFGVLLWEIFTLGEqPYP--GMSNEEVLEFLEDGYRLPQP---- 226
                          250       260
                   ....*....|....*....|....*
gi 4504217     774 DQAPVECILLMKQCWAEQPELRPSM 798
Cdd:pfam07714  227 ENCPDELYDLMKQCWAYDPEDRPTF 251
TyrKc smart00219
Tyrosine kinase, catalytic domain; Phosphotransferases. Tyrosine-specific kinase subfamily.
584-798 1.44e-27

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


Pssm-ID: 197581 [Multi-domain]  Cd Length: 257  Bit Score: 113.01  E-value: 1.44e-27
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217      584 LQELRHENVALYLGlflargaegpAALWEGNLAVVSEHCTRGSLQDLLAQREIKLDWMFKSSLLLDLIKGIRYLHHRGVA 663
Cdd:smart00219   55 MRKLDHPNVVKLLG----------VCTEEEPLYIVMEYMEGGDLLSYLRKNRPKLSLSDLLSFALQIARGMEYLESKNFI 124
                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217      664 HGRLKSRNCIVDGRFVLKITDHGHGRLLE-----AQKVLPEPPRaedqlWTAPELLRdpalERRGTLAGDVFSLAIIMQE 738
Cdd:smart00219  125 HRDLAARNCLVGENLVVKISDFGLSRDLYdddyyRKRGGKLPIR-----WMAPESLK----EGKFTSKSDVWSFGVLLWE 195
                           170       180       190       200       210       220
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 4504217      739 VVCR-SAPYAmlELTPEEVVQRVRS-----PPPLCrplvsmdqaPVECILLMKQCWAEQPELRPSM 798
Cdd:smart00219  196 IFTLgEQPYP--GMSNEEVLEYLKNgyrlpQPPNC---------PPELYDLMLQCWAEDPEDRPTF 250
STYKc smart00221
Protein kinase; unclassified specificity; Phosphotransferases. The specificity of this class ...
584-798 2.30e-26

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: 109.56  E-value: 2.30e-26
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217      584 LQELRHENVALYLGlflargaegpAALWEGNLAVVSEHCTRGSLQD-LLAQREIKLDWMFKSSLLLDLIKGIRYLHHRGV 662
Cdd:smart00221   55 MRKLDHPNIVKLLG----------VCTEEEPLMIVMEYMPGGDLLDyLRKNRPKELSLSDLLSFALQIARGMEYLESKNF 124
                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217      663 AHGRLKSRNCIVDGRFVLKITDHGHGRLLE-----AQKVLPEPPRaedqlWTAPELLRDpaleRRGTLAGDVFSLAIIMQ 737
Cdd:smart00221  125 IHRDLAARNCLVGENLVVKISDFGLSRDLYdddyyKVKGGKLPIR-----WMAPESLKE----GKFTSKSDVWSFGVLLW 195
                           170       180       190       200       210       220
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 4504217      738 EVVCR-SAPYAmlELTPEEVVQRVRS-----PPPLCrplvsmdqaPVECILLMKQCWAEQPELRPSM 798
Cdd:smart00221  196 EIFTLgEEPYP--GMSNAEVLEYLKKgyrlpKPPNC---------PPELYKLMLQCWAEDPEDRPTF 251
PTKc cd00192
Catalytic domain of Protein Tyrosine Kinases; PTKs catalyze the transfer of the ...
584-799 1.32e-25

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: 107.24  E-value: 1.32e-25
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   584 LQELRHENVALYLGlflargaegpAALWEGNLAVVSEHCTRGSLQDLLAQREIKLDWMFKSSL-LLDLI-------KGIR 655
Cdd:cd00192   50 MKKLGHPNVVRLLG----------VCTEEEPLYLVMEYMEGGDLLDFLRKSRPVFPSPEPSTLsLKDLLsfaiqiaKGME 119
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   656 YLHHRGVAHGRLKSRNCIVDGRFVLKITDHGHGRLLEAQKVL------PEPPRaedqlWTAPELLRDpaleRRGTLAGDV 729
Cdd:cd00192  120 YLASKKFVHRDLAARNCLVGEDLVVKISDFGLSRDIYDDDYYrkktggKLPIR-----WMAPESLKD----GIFTSKSDV 190
                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 4504217   730 FSLAIIMQEVVCRSA-PYAmlELTPEEVVQRVRSPPPLCRPlvsmDQAPVECILLMKQCWAEQPELRPSMD 799
Cdd:cd00192  191 WSFGVLLWEIFTLGAtPYP--GLSNEEVLEYLRKGYRLPKP----ENCPDELYELMLSCWQLDPEDRPTFS 255
PKc cd00180
Catalytic domain of Protein Kinases; PKs catalyze the transfer of the gamma-phosphoryl group ...
555-755 5.22e-25

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: 104.27  E-value: 5.22e-25
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   555 YEGDRVWLKKFPGDQHIAIRPATKTAFSKLQELRHENVALYLGLFLargaegpaalWEGNLAVVSEHCTRGSLQDLLAQR 634
Cdd:cd00180   16 ETGKKVAVKVIPKEKLKKLLEELLREIEILKKLNHPNIVKLYDVFE----------TENFLYLVMEYCEGGSLKDLLKEN 85
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   635 EIKLDWMFKSSLLLDLIKGIRYLHHRGVAHGRLKSRNCIVDGRFVLKITDHGHGRLLEAQKVLPEPPRAEDQLWTAPELL 714
Cdd:cd00180   86 KGPLSEEEALSILRQLLSALEYLHSNGIIHRDLKPENILLDSDGTVKLADFGLAKDLDSDDSLLKTTGGTTPPYYAPPEL 165
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|..
gi 4504217   715 rdpALERRGTLAGDVFSLAIIMQEV-VCRSAPYAMLELTPEE 755
Cdd:cd00180  166 ---LGGRYYGPKVDIWSLGVILYELeELKDLIRRMLQYDPKK 204
STKc_RIP cd13978
Catalytic domain of the Serine/Threonine kinase, Receptor Interacting Protein; STKs catalyze ...
583-800 1.92e-23

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: 100.99  E-value: 1.92e-23
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   583 KLQELRHENVALYLGLFLargaegpaalWEGNLAVVSEHCTRGSLQDLLAQREIKLDWMFKSSLLLDLIKGIRYLHH--R 660
Cdd:cd13978   45 KMERARHSYVLPLLGVCV----------ERRSLGLVMEYMENGSLKSLLEREIQDVPWSLRFRIIHEIALGMNFLHNmdP 114
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   661 GVAHGRLKSRNCIVDGRFVLKITDHGHGRL----LEAQKVLPEPPRAEDQLWTAPELLRDpaLERRGTLAGDVFSLAIIM 736
Cdd:cd13978  115 PLLHHDLKPENILLDNHFHVKISDFGLSKLgmksISANRRRGTENLGGTPIYMAPEAFDD--FNKKPTSKSDVYSFAIVI 192
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 4504217   737 QEVVCRSAPYAMLELTPEEVVQRVR----SPPPLCRPLVsmDQAPVECILLMKQCWAEQPELRPSMDH 800
Cdd:cd13978  193 WAVLTRKEPFENAINPLLIMQIVSKgdrpSLDDIGRLKQ--IENVQELISLMIRCWDGNPDARPTFLE 258
S_TKc smart00220
Serine/Threonine protein kinases, catalytic domain; Phosphotransferases. Serine or ...
584-802 2.94e-20

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


Pssm-ID: 214567 [Multi-domain]  Cd Length: 254  Bit Score: 91.44  E-value: 2.94e-20
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217      584 LQELRHENVALYLGLFLArgaegpaalwEGNLAVVSEHCTRGSLQDLLaQREIKLDWMFKSSLLLDLIKGIRYLHHRGVA 663
Cdd:smart00220   51 LKKLKHPNIVRLYDVFED----------EDKLYLVMEYCEGGDLFDLL-KKRGRLSEDEARFYLRQILSALEYLHSKGIV 119
                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217      664 HGRLKSRNCIVDGRFVLKITDHGHGRLLEAQKVL------PEppraedqlWTAPELLRdpaleRRG-TLAGDVFSLAIIM 736
Cdd:smart00220  120 HRDLKPENILLDEDGHVKLADFGLARQLDPGEKLttfvgtPE--------YMAPEVLL-----GKGyGKAVDIWSLGVIL 186
                           170       180       190       200       210       220       230
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217      737 QEVVCRSAPYAMlELTPEEVVQRVRSPPPLCRPlvSMDQAPVECILLMKQCWAEQPELRPS----MDHTF 802
Cdd:smart00220  187 YELLTGKPPFPG-DDQLLELFKKIGKPKPPFPP--PEWDISPEAKDLIRKLLVKDPEKRLTaeeaLQHPF 253
PTKc_Csk cd05082
Catalytic domain of the Protein Tyrosine Kinase, C-terminal Src kinase; PTKs catalyze the ...
552-797 8.55e-20

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: 90.43  E-value: 8.55e-20
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   552 IGVYEGDRVWLKKFPGDqhiairpATKTAF----SKLQELRHENVALYLGLFLARgaegpaalwEGNLAVVSEHCTRGSL 627
Cdd:cd05082   24 LGDYRGNKVAVKCIKND-------ATAQAFlaeaSVMTQLRHSNLVQLLGVIVEE---------KGGLYIVTEYMAKGSL 87
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   628 QDLLAQRE---IKLDWMFKSSLllDLIKGIRYLHHRGVAHGRLKSRNCIVDGRFVLKITDHGHGRLLEAQKVLPEPPRAe 704
Cdd:cd05082   88 VDYLRSRGrsvLGGDCLLKFSL--DVCEAMEYLEGNNFVHRDLAARNVLVSEDNVAKVSDFGLTKEASSTQDTGKLPVK- 164
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   705 dqlWTAPELLRdpalERRGTLAGDVFSLAIIMQEVVC-RSAPYAMLELtpEEVVQRVRSPPPLCRPlvsmDQAPVECILL 783
Cdd:cd05082  165 ---WTAPEALR----EKKFSTKSDVWSFGILLWEIYSfGRVPYPRIPL--KDVVPRVEKGYKMDAP----DGCPPAVYDV 231
                        250
                 ....*....|....
gi 4504217   784 MKQCWAEQPELRPS 797
Cdd:cd05082  232 MKNCWHLDAAMRPS 245
STKc_RIP1 cd14027
Catalytic domain of the Serine/Threonine kinase, Receptor Interacting Protein 1; STKs catalyze ...
584-797 1.23e-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: 1.23e-18
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   584 LQELRHENVALYLGLFLArgaegpaalwEGNLAVVSEHCTRGSLQDLLAQREIKLDwmFKSSLLLDLIKGIRYLHHRGVA 663
Cdd:cd14027   45 MNRLRHSRVVKLLGVILE----------EGKYSLVMEYMEKGNLMHVLKKVSVPLS--VKGRIILEIIEGMAYLHGKGVI 112
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   664 HGRLKSRNCIVDGRFVLKITDHGHGRLLEAQKVLPEPPRAEDQL------------WTAPELLRDpaLERRGTLAGDVFS 731
Cdd:cd14027  113 HKDLKPENILVDNDFHIKIADLGLASFKMWSKLTKEEHNEQREVdgtakknagtlyYMAPEHLND--VNAKPTEKSDVYS 190
                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 4504217   732 LAIIMQEVVCRSAPYamleltpeevvQRVRSPPPLC-------RPLVSM--DQAPVECILLMKQCWAEQPELRPS 797
Cdd:cd14027  191 FAIVLWAIFANKEPY-----------ENAINEDQIImciksgnRPDVDDitEYCPREIIDLMKLCWEANPEARPT 254
PK_KSR cd14063
Pseudokinase domain of Kinase Suppressor of Ras; The pseudokinase domain shows similarity to ...
588-797 2.19e-18

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: 86.63  E-value: 2.19e-18
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   588 RHENVALYLGlflargaegpAALWEGNLAVVSEHCTRGSLQDLLAQREIKLDWMFKSSLLLDLIKGIRYLHHRGVAHGRL 667
Cdd:cd14063   54 RHDNLVLFMG----------ACMDPPHLAIVTSLCKGRTLYSLIHERKEKFDFNKTVQIAQQICQGMGYLHAKGIIHKDL 123
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   668 KSRNCIVD-GRFVlkITDHGhgrLLEAQKVLPePPRAEDQL-----WT---APELLR--DPALERRGTL----AGDVFSL 732
Cdd:cd14063  124 KSKNIFLEnGRVV--ITDFG---LFSLSGLLQ-PGRREDTLvipngWLcylAPEIIRalSPDLDFEESLpftkASDVYAF 197
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 4504217   733 AIIMQEVVCRSAPYAmlELTPEEVVQRVRS--PPPLcrplvSMDQAPVECILLMKQCWAEQPELRPS 797
Cdd:cd14063  198 GTVWYELLAGRWPFK--EQPAESIIWQVGCgkKQSL-----SQLDIGREVKDILMQCWAYDPEKRPT 257
PTKc_Tec_like cd05059
Catalytic domain of Tec-like Protein Tyrosine Kinases; PTKs catalyze the transfer of the ...
559-796 2.64e-18

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: 85.96  E-value: 2.64e-18
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   559 RVWLKKFPGDQHIAIRPATKTAFSK---------LQELRHEN-VALYlGLFLARGAegpaalwegnLAVVSEHCTRGSLQ 628
Cdd:cd05059   19 VVHLGKWRGKIDVAIKMIKEGSMSEddfieeakvMMKLSHPKlVQLY-GVCTKQRP----------IFIVTEYMANGCLL 87
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   629 DLLAQREIKldwmFKSSLLL----DLIKGIRYLHHRGVAHGRLKSRNCIVDGRFVLKITDHGHGR-LLEAQKVLPEPPRA 703
Cdd:cd05059   88 NYLRERRGK----FQTEQLLemckDVCEAMEYLESNGFIHRDLAARNCLVGEQNVVKVSDFGLARyVLDDEYTSSVGTKF 163
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   704 EDQlWTAPELLrdpaLERRGTLAGDVFSLAIIMQEV-VCRSAPYAmlELTPEEVVQRVRSPPPLCRPlvsmDQAPVECIL 782
Cdd:cd05059  164 PVK-WSPPEVF----MYSKFSSKSDVWSFGVLMWEVfSEGKMPYE--RFSNSEVVEHISQGYRLYRP----HLAPTEVYT 232
                        250
                 ....*....|....
gi 4504217   783 LMKQCWAEQPELRP 796
Cdd:cd05059  233 IMYSCWHEKPEERP 246
PTKc_Src_Fyn_like cd14203
Catalytic domain of a subset of Src kinase-like Protein Tyrosine Kinases; PTKs catalyze the ...
560-800 5.57e-18

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: 84.58  E-value: 5.57e-18
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   560 VWLKKFPGDQHIAIR---PATKTAFSKLQE------LRHEN-VALYlglflargaegpAALWEGNLAVVSEHCTRGSLQD 629
Cdd:cd14203   11 VWMGTWNGTTKVAIKtlkPGTMSPEAFLEEaqimkkLRHDKlVQLY------------AVVSEEPIYIVTEFMSKGSLLD 78
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   630 LLAQREIKldwMFKSSLLLDL----IKGIRYLHHRGVAHGRLKSRNCIVDGRFVLKITDHGHGRLLEAQKVLPEPPRAED 705
Cdd:cd14203   79 FLKDGEGK---YLKLPQLVDMaaqiASGMAYIERMNYIHRDLRAANILVGDNLVCKIADFGLARLIEDNEYTARQGAKFP 155
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   706 QLWTAPEllrdPALERRGTLAGDVFSLAIIMQEVVCRS-APYAmlELTPEEVVQRV----RSP-PPLCrplvsmdqaPVE 779
Cdd:cd14203  156 IKWTAPE----AALYGRFTIKSDVWSFGILLTELVTKGrVPYP--GMNNREVLEQVergyRMPcPPGC---------PES 220
                        250       260
                 ....*....|....*....|.
gi 4504217   780 CILLMKQCWAEQPELRPSMDH 800
Cdd:cd14203  221 LHELMCQCWRKDPEERPTFEY 241
STKc_Mos cd13979
Catalytic domain of the Serine/Threonine kinase, Oocyte maturation factor Mos; STKs catalyze ...
553-799 1.32e-17

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: 83.97  E-value: 1.32e-17
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   553 GVYEGDRVWLKKfpgdqhiaIRPATKTAFSK--------LQELRHENVALYLGlflARGAEGPAALWegnlAVVSEHCTR 624
Cdd:cd13979   22 ATYKGETVAVKI--------VRRRRKNRASRqsfwaelnAARLRHENIVRVLA---AETGTDFASLG----LIIMEYCGN 86
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   625 GSLQDLLAQREIKLDWMFKSSLLLDLIKGIRYLHHRGVAHGRLKSRNCIVDGRFVLKITDHGHGRLLEAQKVLPEPPRAE 704
Cdd:cd13979   87 GTLQQLIYEGSEPLPLAHRILISLDIARALRFCHSHGIVHLDVKPANILISEQGVCKLCDFGCSVKLGEGNEVGTPRSHI 166
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   705 DQLWT--APELLRDpaleRRGTLAGDVFSLAIIMQEVVCRSAPYAML-----------ELTPE-------EVVQRVRSPP 764
Cdd:cd13979  167 GGTYTyrAPELLKG----ERVTPKADIYSFGITLWQMLTRELPYAGLrqhvlyavvakDLRPDlsgledsEFGQRLRSLI 242
                        250       260       270
                 ....*....|....*....|....*....|....*
gi 4504217   765 plcrplvsmdqapvecillmKQCWAEQPELRPSMD 799
Cdd:cd13979  243 --------------------SRCWSAQPAERPNAD 257
PTKc_Jak2_rpt2 cd14205
Catalytic (repeat 2) domain of the Protein Tyrosine Kinase, Janus kinase 2; PTKs catalyze the ...
584-797 2.36e-17

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: 83.91  E-value: 2.36e-17
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   584 LQELRHENVALYLGLFLARGAEgpaalwegNLAVVSEHCTRGSLQDLLAQREIKLDWmfkSSLLL---DLIKGIRYLHHR 660
Cdd:cd14205   59 LKSLQHDNIVKYKGVCYSAGRR--------NLRLIMEYLPYGSLRDYLQKHKERIDH---IKLLQytsQICKGMEYLGTK 127
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   661 GVAHGRLKSRNCIVDGRFVLKITDHGhgrlleAQKVLPE--------PPRAEDQLWTAPELLRdpalERRGTLAGDVFSL 732
Cdd:cd14205  128 RYIHRDLATRNILVENENRVKIGDFG------LTKVLPQdkeyykvkEPGESPIFWYAPESLT----ESKFSVASDVWSF 197
                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 4504217   733 AIIMQEVVC-----RSAPYAMLELTPEE---------VVQRVRSPPPLCRPlvsmDQAPVECILLMKQCWAEQPELRPS 797
Cdd:cd14205  198 GVVLYELFTyieksKSPPAEFMRMIGNDkqgqmivfhLIELLKNNGRLPRP----DGCPDEIYMIMTECWNNNVNQRPS 272
PKc_LIMK_like cd14065
Catalytic domain of the LIM domain kinase-like protein kinases; PKs catalyze the transfer of ...
584-797 2.62e-17

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: 82.92  E-value: 2.62e-17
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   584 LQELRHENVALYLGLFLArgaegpaalwEGNLAVVSEHCTRGSLQDLLAQREIKLDWMFKSSLLLDLIKGIRYLHHRGVA 663
Cdd:cd14065   42 MRRLSHPNILRFIGVCVK----------DNKLNFITEYVNGGTLEELLKSMDEQLPWSQRVSLAKDIASGMAYLHSKNII 111
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   664 HGRLKSRNCIV---DGRFVLKITDHGHGRLLEAQKVlPEPPRAE------DQLWTAPELLRDPALERRgtlaGDVFSLAI 734
Cdd:cd14065  112 HRDLNSKNCLVreaNRGRNAVVADFGLAREMPDEKT-KKPDRKKrltvvgSPYWMAPEMLRGESYDEK----VDVFSFGI 186
                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 4504217   735 IMQEVVCRsapyamLELTPEEV---------VQRVRSPPPlcrplvsmDQAPVECILLMKQCWAEQPELRPS 797
Cdd:cd14065  187 VLCEIIGR------VPADPDYLprtmdfgldVRAFRTLYV--------PDCPPSFLPLAIRCCQLDPEKRPS 244
PTKc_Csk_like cd05039
Catalytic domain of C-terminal Src kinase-like Protein Tyrosine Kinases; PTKs catalyze the ...
553-801 3.17e-17

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: 82.78  E-value: 3.17e-17
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   553 GVYEGDRVWLKKFPGDQhiairpATKTAF----SKLQELRHENVALYLGLflargaegpaALWEGNLAVVSEHCTRGSLQ 628
Cdd:cd05039   25 GDYRGQKVAVKCLKDDS------TAAQAFlaeaSVMTTLRHPNLVQLLGV----------VLEGNGLYIVTEYMAKGSLV 88
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   629 DLLAQRE---IKLD--WMFKssllLDLIKGIRYLHHRGVAHGRLKSRNCIVDGRFVLKITDHGHGRL----LEAQKvLPE 699
Cdd:cd05039   89 DYLRSRGravITRKdqLGFA----LDVCEGMEYLESKKFVHRDLAARNVLVSEDNVAKVSDFGLAKEassnQDGGK-LPI 163
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   700 PpraedqlWTAPELLRdpalERRGTLAGDVFSLAIIMQEVVC--RsAPYAMLELtpEEVVQRV----RSPPPlcrplvsm 773
Cdd:cd05039  164 K-------WTAPEALR----EKKFSTKSDVWSFGILLWEIYSfgR-VPYPRIPL--KDVVPHVekgyRMEAP-------- 221
                        250       260
                 ....*....|....*....|....*...
gi 4504217   774 DQAPVECILLMKQCWAEQPELRPSMDHT 801
Cdd:cd05039  222 EGCPPEVYKVMKNCWELDPAKRPTFKQL 249
STKc_MLTK cd14060
Catalytic domain of the Serine/Threonine Kinase, Mixed lineage kinase-Like mitogen-activated ...
566-797 5.08e-17

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: 81.93  E-value: 5.08e-17
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   566 PGDQHIAIRPATKTAFSK--LQELRHENVALYLGLFLargaEGPaalwegNLAVVSEHCTRGSLQDLLAQREI-KLDWMF 642
Cdd:cd14060   16 SQDKEVAVKKLLKIEKEAeiLSVLSHRNIIQFYGAIL----EAP------NYGIVTEYASYGSLFDYLNSNESeEMDMDQ 85
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   643 KSSLLLDLIKGIRYLHHRG---VAHGRLKSRNCIVDGRFVLKITDHGHGRLLEAQKVL------PeppraedqlWTAPEL 713
Cdd:cd14060   86 IMTWATDIAKGMHYLHMEApvkVIHRDLKSRNVVIAADGVLKICDFGASRFHSHTTHMslvgtfP---------WMAPEV 156
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   714 LRD-PALErrgtlAGDVFSLAIIMQEVVCRSAPYAMLE--LTPEEVVQRVRSP--PPLCrplvsmdqaPVECILLMKQCW 788
Cdd:cd14060  157 IQSlPVSE-----TCDTYSYGVVLWEMLTREVPFKGLEglQVAWLVVEKNERPtiPSSC---------PRSFAELMRRCW 222

                 ....*....
gi 4504217   789 AEQPELRPS 797
Cdd:cd14060  223 EADVKERPS 231
STKc_RIP2 cd14026
Catalytic domain of the Serine/Threonine kinase, Receptor Interacting Protein 2; STKs catalyze ...
615-800 5.49e-17

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: 82.66  E-value: 5.49e-17
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   615 LAVVSEHCTRGSLQDLLAQREIKLD--WMFKSSLLLDLIKGIRYLHHRG--VAHGRLKSRNCIVDGRFVLKITDHGHG-- 688
Cdd:cd14026   72 LGIVTEYMTNGSLNELLHEKDIYPDvaWPLRLRILYEIALGVNYLHNMSppLLHHDLKTQNILLDGEFHVKIADFGLSkw 151
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   689 RLLEAQKVLPEPPRAEDQ--LWTAPELLrDPALERRGTLAGDVFSLAIIMQEVVCRSAPYamleltpEEVV---QRVRSP 763
Cdd:cd14026  152 RQLSISQSRSSKSAPEGGtiIYMPPEEY-EPSQKRRASVKHDIYSYAIIMWEVLSRKIPF-------EEVTnplQIMYSV 223
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|...
gi 4504217   764 PPLCRPLVSMDQAPVE------CILLMKQCWAEQPELRPSMDH 800
Cdd:cd14026  224 SQGHRPDTGEDSLPVDiphratLINLIESGWAQNPDERPSFLK 266
PTKc_Tyk2_rpt2 cd05080
Catalytic (repeat 2) domain of the Protein Tyrosine Kinase, Tyrosine kinase 2; PTKs catalyze ...
557-808 8.65e-17

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: 81.87  E-value: 8.65e-17
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   557 GDRVWLKKFPGDQHIAIRPATKTAFSKLQELRHENVALYLGLFLARGAEGpaalwegnLAVVSEHCTRGSLQDLLAQREI 636
Cdd:cd05080   33 GEMVAVKALKADCGPQHRSGWKQEIDILKTLYHENIVKYKGCCSEQGGKS--------LQLIMEYVPLGSLRDYLPKHSI 104
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   637 KLdwmfkSSLLL---DLIKGIRYLHHRGVAHGRLKSRNCIVDGRFVLKITDHGhgrlleAQKVLPEPPR----AEDQ--- 706
Cdd:cd05080  105 GL-----AQLLLfaqQICEGMAYLHSQHYIHRDLAARNVLLDNDRLVKIGDFG------LAKAVPEGHEyyrvREDGdsp 173
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   707 -LWTAPELLRdpalERRGTLAGDVFSLAIIMQEVVCRSAPY--------AMLELTPEEVVQ---------RVRSPPPlcr 768
Cdd:cd05080  174 vFWYAPECLK----EYKFYYASDVWSFGVTLYELLTHCDSSqspptkflEMIGIAQGQMTVvrliellerGERLPCP--- 246
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|
gi 4504217   769 plvsmDQAPVECILLMKQCWAEQPELRPSMDHTFDLFKNI 808
Cdd:cd05080  247 -----DKCPQEVYHLMKNCWETEASFRPTFENLIPILKTV 281
PBP1_NPR_GC-like cd06352
ligand-binding domain of membrane guanylyl-cyclase receptors; Ligand-binding domain of ...
96-435 8.66e-17

ligand-binding domain of membrane guanylyl-cyclase receptors; Ligand-binding domain of membrane guanylyl-cyclase receptors. Membrane guanylyl cyclases (GC) have a single membrane-spanning region and are activated by endogenous and exogenous peptides. This family can be divided into three major subfamilies: the natriuretic peptide receptors (NPRs), sensory organ-specific membrane GCs, and the enterotoxin/guanylin receptors. The binding of peptide ligands to the receptor results in the activation of the cytosolic catalytic domain. Three types of NPRs have been cloned from mammalian tissues: NPR-A/GC-A, NPR-B/ GC-B, and NPR-C. In addition, two of the GCs, GC-D and GC-G, appear to be pseudogenes in humans. Atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) are produced in the heart, and both bind to the NPR-A. NPR-C, also termed the clearance receptor, binds each of the natriuretic peptides and can alter circulating levels of these peptides. The ligand binding domain of the NPRs exhibits strong structural similarity to the type 1 periplasmic binding fold protein family.


Pssm-ID: 380575 [Multi-domain]  Cd Length: 391  Bit Score: 83.94  E-value: 8.66e-17
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217    96 FEVALLPEPCRTPGSLGAVSSALA--RVSGLVGPVNPAACRPAELLAEEAGIALVPWGCPWTQAEG--------TTAPAV 165
Cdd:cd06352   43 FEFTYRDSCCDESEAVGAAADLIYkrNVDVFIGPACSAAADAVGRLATYWNIPIITWGAVSASFLDksryptltRTSPNS 122
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   166 TPAADALYALLRAFGWARVA-LVTAPQDLWVEAGRSLSTALRAR-GLPVASVTSMEPLDLSGAREALRKVRDGPRVtaVI 243
Cdd:cd06352  123 LSLAEALLALLKQFNWKRAAiIYSDDDSKCFSIANDLEDALNQEdNLTISYYEFVEVNSDSDYSSILQEAKKRARI--IV 200
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   244 MVMHSvllggEEQRYLLEAAEELGLTDGSLVFLPFDT--IHYALSPGPEALAALANSSQLRRAHDAVLTLTRHcPSEGSV 321
Cdd:cd06352  201 LCFDS-----ETVRQFMLAAHDLGMTNGEYVFIFIELfkDGFGGNSTDGWERNDGRDEDAKQAYESLLVISLS-RPSNPE 274
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   322 LDS-----LRRAQERRELPSDLNLQQVSPLFGTIYDAVFLLARGVAEARAAAGGRwVSGAAVARHIRDAQVPGFCGDlgg 396
Cdd:cd06352  275 YDNfskevKARAKEPPFYCYDASEEEVSPYAAALYDAVYLYALALNETLAEGGNY-RNGTAIAQRMWNRTFQGITGP--- 350
                        330       340       350       360
                 ....*....|....*....|....*....|....*....|.
gi 4504217   397 deeppfVLLDTDaaGDR--LFATYMLDPARGSFLSAGTRMH 435
Cdd:cd06352  351 ------VTIDSN--GDRdpDYALLDLDPSTGKFVVVLTYDG 383
PKc_LIMK_like_unk cd14156
Catalytic domain of an unknown subfamily of LIM domain kinase-like protein kinases; PKs ...
568-742 9.33e-17

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: 81.41  E-value: 9.33e-17
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   568 DQHIAIRpatktAFSKLQELRHENVALYLGlflargaegpAALWEGNLAVVSEHCTRGSLQDLLAQREIKLDWMFKSSLL 647
Cdd:cd14156   31 DQHKIVR-----EISLLQKLSHPNIVRYLG----------ICVKDEKLHPILEYVSGGCLEELLAREELPLSWREKVELA 95
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   648 LDLIKGIRYLHHRGVAHGRLKSRNCIV----DGRFVLkITDHGHGRlleaqKVLPEPPRAEDQ--------LWTAPELLR 715
Cdd:cd14156   96 CDISRGMVYLHSKNIYHRDLNSKNCLIrvtpRGREAV-VTDFGLAR-----EVGEMPANDPERklslvgsaFWMAPEMLR 169
                        170       180
                 ....*....|....*....|....*..
gi 4504217   716 DPALERRgtlaGDVFSLAIIMQEVVCR 742
Cdd:cd14156  170 GEPYDRK----VDVFSFGIVLCEILAR 192
PTKc_Fes_like cd05041
Catalytic domain of Fes-like Protein Tyrosine Kinases; Protein Tyrosine Kinase (PTK) family; ...
617-799 1.32e-16

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: 80.95  E-value: 1.32e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   617 VVSEHCTRGSLQDLLAQREIKLDWMFKSSLLLDLIKGIRYLHHRGVAHGRLKSRNCIVDGRFVLKITDHG-----HGRLL 691
Cdd:cd05041   70 IVMELVPGGSLLTFLRKKGARLTVKQLLQMCLDAAAGMEYLESKNCIHRDLAARNCLVGENNVLKISDFGmsreeEDGEY 149
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   692 EAQKVLPEPPRAedqlWTAPELLRdpalERRGTLAGDVFSLAIIMQEVVCR-SAPYAML--ELTPEEVVQRVRSPPPlcr 768
Cdd:cd05041  150 TVSDGLKQIPIK----WTAPEALN----YGRYTSESDVWSFGILLWEIFSLgATPYPGMsnQQTREQIESGYRMPAP--- 218
                        170       180       190
                 ....*....|....*....|....*....|.
gi 4504217   769 plvsmDQAPVECILLMKQCWAEQPELRPSMD 799
Cdd:cd05041  219 -----ELCPEAVYRLMLQCWAYDPENRPSFS 244
PTKc_Jak_rpt2 cd05038
Catalytic (repeat 2) domain of the Protein Tyrosine Kinases, Janus kinases; The Jak subfamily ...
546-799 2.90e-16

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: 80.50  E-value: 2.90e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   546 HLDSPNIGvyEGDRVWLKKFPGDQHIAIRPATKTAFSKLQELRHENVALYLGLflargAEGPAalwEGNLAVVSEHCTRG 625
Cdd:cd05038   24 RYDPLGDN--TGEQVAVKSLQPSGEEQHMSDFKREIEILRTLDHEYIVKYKGV-----CESPG---RRSLRLIMEYLPSG 93
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   626 SLQDLLAQREIKLDwmfKSSLLL---DLIKGIRYLHHRGVAHGRLKSRNCIVDGRFVLKITDHGHGRLLEAQK--VLPEP 700
Cdd:cd05038   94 SLRDYLQRHRDQID---LKRLLLfasQICKGMEYLGSQRYIHRDLAARNILVESEDLVKISDFGLAKVLPEDKeyYYVKE 170
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   701 PRAEDQLWTAPELLRdpalERRGTLAGDVFSLAIIMQEVV--CRS-----------APYAMLELTPEEVVQRVRSPPPLC 767
Cdd:cd05038  171 PGESPIFWYAPECLR----ESRFSSASDVWSFGVTLYELFtyGDPsqsppalflrmIGIAQGQMIVTRLLELLKSGERLP 246
                        250       260       270
                 ....*....|....*....|....*....|..
gi 4504217   768 RPlvsmDQAPVECILLMKQCWAEQPELRPSMD 799
Cdd:cd05038  247 RP----PSCPDEVYDLMKECWEYEPQDRPSFS 274
PTKc_Lck_Blk cd05067
Catalytic domain of the Protein Tyrosine Kinases, Lymphocyte-specific kinase and Blk; PTKs ...
560-808 4.31e-16

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: 79.55  E-value: 4.31e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   560 VWLKKFPGDQHIAIR---PATKTAFSKLQE------LRHEN-VALYlglflargaegpAALWEGNLAVVSEHCTRGSLQD 629
Cdd:cd05067   23 VWMGYYNGHTKVAIKslkQGSMSPDAFLAEanlmkqLQHQRlVRLY------------AVVTQEPIYIITEYMENGSLVD 90
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   630 LLAQRE-IKLdwmfKSSLLLDLI----KGIRYLHHRGVAHGRLKSRNCIVDGRFVLKITDHGHGRLLEAQKVLPEPPRAE 704
Cdd:cd05067   91 FLKTPSgIKL----TINKLLDMAaqiaEGMAFIEERNYIHRDLRAANILVSDTLSCKIADFGLARLIEDNEYTAREGAKF 166
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   705 DQLWTAPELLRDPALerrgTLAGDVFSLAIIMQEVVCRS-APYAmlELTPEEVVQRVRSPPPLCRPlvsmDQAPVECILL 783
Cdd:cd05067  167 PIKWTAPEAINYGTF----TIKSDVWSFGILLTEIVTHGrIPYP--GMTNPEVIQNLERGYRMPRP----DNCPEELYQL 236
                        250       260
                 ....*....|....*....|....*
gi 4504217   784 MKQCWAEQPELRPsmdhTFDLFKNI 808
Cdd:cd05067  237 MRLCWKERPEDRP----TFEYLRSV 257
PTKc_Src_like cd05034
Catalytic domain of Src kinase-like Protein Tyrosine Kinases; PTKs catalyze the transfer of ...
560-805 5.44e-16

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: 78.86  E-value: 5.44e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   560 VWLKKFPGDQHIAI---RPATKTAFSKLQE------LRHEN-VALYlglflargaegpaalwegnlAVVS---------E 620
Cdd:cd05034   11 VWMGVWNGTTKVAVktlKPGTMSPEAFLQEaqimkkLRHDKlVQLY--------------------AVCSdeepiyivtE 70
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   621 HCTRGSLQDLLAQREIKldwMFKSSLLLDLI----KGIRYLHHRGVAHGRLKSRNCIVDGRFVLKITDHGHGRLLEAQKV 696
Cdd:cd05034   71 LMSKGSLLDYLRTGEGR---ALRLPQLIDMAaqiaSGMAYLESRNYIHRDLAARNILVGENNVCKVADFGLARLIEDDEY 147
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   697 LPE-----PPRaedqlWTAPEllrdPALERRGTLAGDVFSLAIIMQEVVCRS-APYAmlELTPEEVVQRV----RSP-PP 765
Cdd:cd05034  148 TARegakfPIK-----WTAPE----AALYGRFTIKSDVWSFGILLYEIVTYGrVPYP--GMTNREVLEQVergyRMPkPP 216
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|
gi 4504217   766 LCrplvsmdqaPVECILLMKQCWAEQPELRPSMDHTFDLF 805
Cdd:cd05034  217 GC---------PDELYDIMLQCWKKEPEERPTFEYLQSFL 247
PTKc_Jak3_rpt2 cd05081
Catalytic (repeat 2) domain of the Protein Tyrosine Kinase, Janus kinase 3; PTKs catalyze the ...
584-797 5.95e-16

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: 79.55  E-value: 5.95e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   584 LQELRHENVALYLGLFLARGAEGpaalwegnLAVVSEHCTRGSLQDLLAQREIKLDwmfKSSLLL---DLIKGIRYLHHR 660
Cdd:cd05081   59 LKALHSDFIVKYRGVSYGPGRRS--------LRLVMEYLPSGCLRDFLQRHRARLD---ASRLLLyssQICKGMEYLGSR 127
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   661 GVAHGRLKSRNCIVDGRFVLKITDHGHGRLLEAQK---VLPEPPRAEdQLWTAPELLRDPALERrgtlAGDVFSLAIIMQ 737
Cdd:cd05081  128 RCVHRDLAARNILVESEAHVKIADFGLAKLLPLDKdyyVVREPGQSP-IFWYAPESLSDNIFSR----QSDVWSFGVVLY 202
                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 4504217   738 EVV-----CRSAPYAMLELT-PEEVVQRV-----------RSP-PPLCrplvsmdqaPVECILLMKQCWAEQPELRPS 797
Cdd:cd05081  203 ELFtycdkSCSPSAEFLRMMgCERDVPALcrllelleegqRLPaPPAC---------PAEVHELMKLCWAPSPQDRPS 271
PTKc_Fes cd05084
Catalytic domain of the Protein Tyrosine Kinase, Fes; PTKs catalyze the transfer of the ...
642-797 8.76e-16

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: 78.43  E-value: 8.76e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   642 FKSSLLLDLIK----GIRYLHHRGVAHGRLKSRNCIVDGRFVLKITDHGHGRllEAQKVLPEPPRAEDQL---WTAPELL 714
Cdd:cd05084   92 LKVKELIRMVEnaaaGMEYLESKHCIHRDLAARNCLVTEKNVLKISDFGMSR--EEEDGVYAATGGMKQIpvkWTAPEAL 169
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   715 RdpalERRGTLAGDVFSLAIIMQEVVCRSA-PYAML--ELTPEEVVQRVRSPPPlcrplvsmDQAPVECILLMKQCWAEQ 791
Cdd:cd05084  170 N----YGRYSSESDVWSFGILLWETFSLGAvPYANLsnQQTREAVEQGVRLPCP--------ENCPDEVYRLMEQCWEYD 237

                 ....*.
gi 4504217   792 PELRPS 797
Cdd:cd05084  238 PRKRPS 243
PKc_TESK cd14155
Catalytic domain of the Dual-specificity protein kinase, Testicular protein kinase; ...
584-742 1.19e-15

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: 77.90  E-value: 1.19e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   584 LQELRHENVALYLGLflargaegpaALWEGNLAVVSEHCTRGSLQDLLAQREIkLDWMFKSSLLLDLIKGIRYLHHRGVA 663
Cdd:cd14155   42 MNRLSHPNILRFMGV----------CVHQGQLHALTEYINGGNLEQLLDSNEP-LSWTVRVKLALDIARGLSYLHSKGIF 110
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   664 HGRLKSRNCIVD----------GRFVL--KITDHGHGRllEAQKVLPEPpraedqLWTAPELLRDPALERRgtlaGDVFS 731
Cdd:cd14155  111 HRDLTSKNCLIKrdengytavvGDFGLaeKIPDYSDGK--EKLAVVGSP------YWMAPEVLRGEPYNEK----ADVFS 178
                        170
                 ....*....|.
gi 4504217   732 LAIIMQEVVCR 742
Cdd:cd14155  179 YGIILCEIIAR 189
PTKc_Chk cd05083
Catalytic domain of the Protein Tyrosine Kinase, Csk homologous kinase; PTKs catalyze the ...
553-797 2.73e-15

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: 76.84  E-value: 2.73e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   553 GVYEGDRVWLKKFPGDqhiairpATKTAF----SKLQELRHENVALYLGLFLARGaegpaalwegnLAVVSEHCTRGSLQ 628
Cdd:cd05083   25 GEYMGQKVAVKNIKCD-------VTAQAFleetAVMTKLQHKNLVRLLGVILHNG-----------LYIVMELMSKGNLV 86
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   629 DLLAQR---EIKLDWMFKSSLllDLIKGIRYLHHRGVAHGRLKSRNCIVDGRFVLKITDHGHGRlleaqkvlPEPPRAED 705
Cdd:cd05083   87 NFLRSRgraLVPVIQLLQFSL--DVAEGMEYLESKKLVHRDLAARNILVSEDGVAKISDFGLAK--------VGSMGVDN 156
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   706 QL----WTAPELLRDPALERRgtlaGDVFSLAIIMQEVVCRS-APYAMLEL--TPEEVVQRVRSPPPlcrplvsmDQAPV 778
Cdd:cd05083  157 SRlpvkWTAPEALKNKKFSSK----SDVWSYGVLLWEVFSYGrAPYPKMSVkeVKEAVEKGYRMEPP--------EGCPP 224
                        250
                 ....*....|....*....
gi 4504217   779 ECILLMKQCWAEQPELRPS 797
Cdd:cd05083  225 DVYSIMTSCWEAEPGKRPS 243
STKc_MAP3K12_13 cd14059
Catalytic domain of the Serine/Threonine Kinases, Mitogen-Activated Protein Kinase Kinase ...
553-801 3.73e-15

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: 76.38  E-value: 3.73e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   553 GVYEGDRVWLKKfpgdqhiaIRPATKTAFSKLQELRHENVALYLGLFlargAEGPAalwegnLAVVSEHCTRGSLQDLL- 631
Cdd:cd14059   12 GKFRGEEVAVKK--------VRDEKETDIKHLRKLNHPNIIKFKGVC----TQAPC------YCILMEYCPYGQLYEVLr 73
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   632 AQREIKldwmfkSSLLLDLIKGI----RYLHHRGVAHGRLKSRNCIVDGRFVLKITDHGHGRLLEAQKVlpEPPRAEDQL 707
Cdd:cd14059   74 AGREIT------PSLLVDWSKQIasgmNYLHLHKIIHRDLKSPNVLVTYNDVLKISDFGTSKELSEKST--KMSFAGTVA 145
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   708 WTAPELLR-DPALERRgtlagDVFSLAIIMQEVVCRSAPYAmlELTPEEVVQRVRS-----PPPlcrplvsmDQAPVECI 781
Cdd:cd14059  146 WMAPEVIRnEPCSEKV-----DIWSFGVVLWELLTGEIPYK--DVDSSAIIWGVGSnslqlPVP--------STCPDGFK 210
                        250       260
                 ....*....|....*....|
gi 4504217   782 LLMKQCWAEQPELRPSMDHT 801
Cdd:cd14059  211 LLMKQCWNSKPRNRPSFRQI 230
PTKc_Fyn cd05070
Catalytic domain of the Protein Tyrosine Kinase, Fyn; PTKs catalyze the transfer of the ...
560-800 4.47e-15

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: 76.65  E-value: 4.47e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   560 VWLKKFPGDQHIAIR---PATKTAFSKLQE------LRHEN-VALYlglflargaegpAALWEGNLAVVSEHCTRGSLQD 629
Cdd:cd05070   25 VWMGTWNGNTKVAIKtlkPGTMSPESFLEEaqimkkLKHDKlVQLY------------AVVSEEPIYIVTEYMSKGSLLD 92
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   630 LLAQ---REIKLDWMFksSLLLDLIKGIRYLHHRGVAHGRLKSRNCIVDGRFVLKITDHGHGRLLEAQKVLPEPPRAEDQ 706
Cdd:cd05070   93 FLKDgegRALKLPNLV--DMAAQVAAGMAYIERMNYIHRDLRSANILVGNGLICKIADFGLARLIEDNEYTARQGAKFPI 170
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   707 LWTAPEllrdPALERRGTLAGDVFSLAIIMQEVVCRS-APYAmlELTPEEVVQRV----RSPPPlcrplvsmDQAPVECI 781
Cdd:cd05070  171 KWTAPE----AALYGRFTIKSDVWSFGILLTELVTKGrVPYP--GMNNREVLEQVergyRMPCP--------QDCPISLH 236
                        250
                 ....*....|....*....
gi 4504217   782 LLMKQCWAEQPELRPSMDH 800
Cdd:cd05070  237 ELMIHCWKKDPEERPTFEY 255
PK_eIF2AK_GCN2_rpt1 cd14012
Pseudokinase domain, repeat 1, of eukaryotic translation Initiation Factor 2-Alpha Kinase 4 or ...
579-804 1.14e-14

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: 75.09  E-value: 1.14e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   579 TAFSKLQELRHENVALYLGLFLARGAEGPAalWEgnLAVVSEHCTRGSLQDLLaQREIKLDWMFKSSLLLDLIKGIRYLH 658
Cdd:cd14012   47 KELESLKKLRHPNLVSYLAFSIERRGRSDG--WK--VYLLTEYAPGGSLSELL-DSVGSVPLDTARRWTLQLLEALEYLH 121
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   659 HRGVAHGRLKSRNCIVD---GRFVLKITDHGHGRLLEAQKVLPEPPRAEDQLWTAPELLRDPAlerRGTLAGDVFSLAII 735
Cdd:cd14012  122 RNGVVHKSLHAGNVLLDrdaGTGIVKLTDYSLGKTLLDMCSRGSLDEFKQTYWLPPELAQGSK---SPTRKTDVWDLGLL 198
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 4504217   736 MQEVVCRSapyamleltpeEVVQRVRSPPPLCRPlVSMDQAPVEcilLMKQCWAEQPELRPSmdhTFDL 804
Cdd:cd14012  199 FLQMLFGL-----------DVLEKYTSPNPVLVS-LDLSASLQD---FLSKCLSLDPKKRPT---ALEL 249
PTKc_Yes cd05069
Catalytic domain of the Protein Tyrosine Kinase, Yes; PTKs catalyze the transfer of the ...
560-800 1.18e-14

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: 75.49  E-value: 1.18e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   560 VWLKKFPGDQHIAIR---PATKTAFSKLQE------LRHEN-VALYlglflargaegpAALWEGNLAVVSEHCTRGSLQD 629
Cdd:cd05069   28 VWMGTWNGTTKVAIKtlkPGTMMPEAFLQEaqimkkLRHDKlVPLY------------AVVSEEPIYIVTEFMGKGSLLD 95
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   630 LLAQREIKldwMFKSSLLLDLIK----GIRYLHHRGVAHGRLKSRNCIVDGRFVLKITDHGHGRLLEAQKVLPEPPRAED 705
Cdd:cd05069   96 FLKEGDGK---YLKLPQLVDMAAqiadGMAYIERMNYIHRDLRAANILVGDNLVCKIADFGLARLIEDNEYTARQGAKFP 172
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   706 QLWTAPEllrdPALERRGTLAGDVFSLAIIMQEVVCRS-APY-AMLELTPEEVVQR-VRSPPPlcrplvsmDQAPVECIL 782
Cdd:cd05069  173 IKWTAPE----AALYGRFTIKSDVWSFGILLTELVTKGrVPYpGMVNREVLEQVERgYRMPCP--------QGCPESLHE 240
                        250
                 ....*....|....*...
gi 4504217   783 LMKQCWAEQPELRPSMDH 800
Cdd:cd05069  241 LMKLCWKKDPDERPTFEY 258
PTKc_Src cd05071
Catalytic domain of the Protein Tyrosine Kinase, Src; PTKs catalyze the transfer of the ...
560-800 2.79e-14

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: 74.34  E-value: 2.79e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   560 VWLKKFPGDQHIAIR---PATKTAFSKLQE------LRHEN-VALYlglflargaegpAALWEGNLAVVSEHCTRGSLQD 629
Cdd:cd05071   25 VWMGTWNGTTRVAIKtlkPGTMSPEAFLQEaqvmkkLRHEKlVQLY------------AVVSEEPIYIVTEYMSKGSLLD 92
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   630 LLAQREIKldwMFKSSLLLD----LIKGIRYLHHRGVAHGRLKSRNCIVDGRFVLKITDHGHGRLLEAQKVLPEPPRAED 705
Cdd:cd05071   93 FLKGEMGK---YLRLPQLVDmaaqIASGMAYVERMNYVHRDLRAANILVGENLVCKVADFGLARLIEDNEYTARQGAKFP 169
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   706 QLWTAPEllrdPALERRGTLAGDVFSLAIIMQEVVCRS-APY-AMLELTPEEVVQR-VRSP-PPLCrplvsmdqaPVECI 781
Cdd:cd05071  170 IKWTAPE----AALYGRFTIKSDVWSFGILLTELTTKGrVPYpGMVNREVLDQVERgYRMPcPPEC---------PESLH 236
                        250
                 ....*....|....*....
gi 4504217   782 LLMKQCWAEQPELRPSMDH 800
Cdd:cd05071  237 DLMCQCWRKEPEERPTFEY 255
PTKc_Jak1_rpt2 cd05079
Catalytic (repeat 2) domain of the Protein Tyrosine Kinase, Janus kinase 1; PTKs catalyze the ...
556-811 3.41e-14

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: 74.20  E-value: 3.41e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   556 EGDRVW-------LKKFPGDQHIAirpATKTAFSKLQELRHENVALYLGLFLARGAEGpaalwegnLAVVSEHCTRGSLQ 628
Cdd:cd05079   28 EGDNTGeqvavksLKPESGGNHIA---DLKKEIEILRNLYHENIVKYKGICTEDGGNG--------IKLIMEFLPSGSLK 96
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   629 DLLAQREIKLDWMFKSSLLLDLIKGIRYLHHRGVAHGRLKSRNCIVDGRFVLKITDHGHGRLLEAQKvlpEPPRAEDQL- 707
Cdd:cd05079   97 EYLPRNKNKINLKQQLKYAVQICKGMDYLGSRQYVHRDLAARNVLVESEHQVKIGDFGLTKAIETDK---EYYTVKDDLd 173
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   708 ----WTAPELLrdpaLERRGTLAGDVFSLAIIMQEVV--CRS--APYAML---------ELTPEEVVQRVRSPPPLCRPl 770
Cdd:cd05079  174 spvfWYAPECL----IQSKFYIASDVWSFGVTLYELLtyCDSesSPMTLFlkmigpthgQMTVTRLVRVLEEGKRLPRP- 248
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|.
gi 4504217   771 vsmDQAPVECILLMKQCWAEQPELRPSmdhtfdlFKNINKG 811
Cdd:cd05079  249 ---PNCPEEVYQLMRKCWEFQPSKRTT-------FQNLIEG 279
STKc_IRAK cd14066
Catalytic domain of the Serine/Threonine kinases, Interleukin-1 Receptor Associated Kinases ...
583-798 4.96e-14

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: 73.46  E-value: 4.96e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   583 KLQELRHENVALYLGLFLARGaegpaalwegNLAVVSEHCTRGSLQDLL-AQREIK-LDWMFKSSLLLDLIKGIRYLHHR 660
Cdd:cd14066   43 MLGRLRHPNLVRLLGYCLESD----------EKLLVYEYMPNGSLEDRLhCHKGSPpLPWPQRLKIAKGIARGLEYLHEE 112
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   661 G---VAHGRLKSRNCIVDGRFVLKITDHGHGRLLEaqkvlPEPPRAEDQL------WTAPELLRDpaleRRGTLAGDVFS 731
Cdd:cd14066  113 CpppIIHGDIKSSNILLDEDFEPKLTDFGLARLIP-----PSESVSKTSAvkgtigYLAPEYIRT----GRVSTKSDVYS 183
                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 4504217   732 LAIIMQEVVCRSAPY-----AMLELTPEEVVQRVRSP-------PPLCRPLVSMDQAPVECILLMKQCWAEQPELRPSM 798
Cdd:cd14066  184 FGVVLLELLTGKPAVdenreNASRKDLVEWVESKGKEeledildKRLVDDDGVEEEEVEALLRLALLCTRSDPSLRPSM 262
PTKc_Lyn cd05072
Catalytic domain of the Protein Tyrosine Kinase, Lyn; PTKs catalyze the transfer of the ...
552-800 7.31e-14

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: 73.15  E-value: 7.31e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   552 IGVYEGDRVWLKKFPGDQHIAIR---PATKTAFSKLQE------LRHENValyLGLFLARGAEGPaalwegnLAVVSEHC 622
Cdd:cd05072   15 LGAGQFGEVWMGYYNNSTKVAVKtlkPGTMSVQAFLEEanlmktLQHDKL---VRLYAVVTKEEP-------IYIITEYM 84
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   623 TRGSLQDLLAQRE---IKLDWMFKSSLllDLIKGIRYLHHRGVAHGRLKSRNCIVDGRFVLKITDHGHGRLLEAQKVLPE 699
Cdd:cd05072   85 AKGSLLDFLKSDEggkVLLPKLIDFSA--QIAEGMAYIERKNYIHRDLRAANVLVSESLMCKIADFGLARVIEDNEYTAR 162
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   700 PPRAEDQLWTAPELLRDPALerrgTLAGDVFSLAIIMQEVVCRSA-PYAmlELTPEEVVQRVRSPPPLCRplvsMDQAPV 778
Cdd:cd05072  163 EGAKFPIKWTAPEAINFGSF----TIKSDVWSFGILLYEIVTYGKiPYP--GMSNSDVMSALQRGYRMPR----MENCPD 232
                        250       260
                 ....*....|....*....|..
gi 4504217   779 ECILLMKQCWAEQPELRPSMDH 800
Cdd:cd05072  233 ELYDIMKTCWKEKAEERPTFDY 254
PTKc_Srm_Brk cd05148
Catalytic domain of the Protein Tyrosine Kinases, Src-related kinase lacking C-terminal ...
617-797 9.62e-14

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: 72.47  E-value: 9.62e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   617 VVSEHCTRGSLQDLLAQREIKldwMFKSSLLLDL----IKGIRYLHHRGVAHGRLKSRNCIVDGRFVLKITDHGHGRLLE 692
Cdd:cd05148   79 IITELMEKGSLLAFLRSPEGQ---VLPVASLIDMacqvAEGMAYLEEQNSIHRDLAARNILVGEDLVCKVADFGLARLIK 155
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   693 AQKVLPE----PPRaedqlWTAPEllrdPALERRGTLAGDVFSLAIIMQEVVCRSA-PYAmlELTPEEVVQRVRSPPPLC 767
Cdd:cd05148  156 EDVYLSSdkkiPYK-----WTAPE----AASHGTFSTKSDVWSFGILLYEMFTYGQvPYP--GMNNHEVYDQITAGYRMP 224
                        170       180       190
                 ....*....|....*....|....*....|
gi 4504217   768 RPLvsmdQAPVECILLMKQCWAEQPELRPS 797
Cdd:cd05148  225 CPA----KCPQEIYKIMLECWAAEPEDRPS 250
PTKc_EphR cd05033
Catalytic domain of Ephrin Receptor Protein Tyrosine Kinases; PTKs catalyze the transfer of ...
617-796 9.78e-14

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: 72.79  E-value: 9.78e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   617 VVSEHCTRGSLQDLLAQREIKLDWMFKSSLLLDLIKGIRYLHHRGVAHGRLKSRNCIVDGRFVLKITDHGHGRLLEAQKV 696
Cdd:cd05033   82 IVTEYMENGSLDKFLRENDGKFTVTQLVGMLRGIASGMKYLSEMNYVHRDLAARNILVNSDLVCKVSDFGLSRRLEDSEA 161
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   697 LPE------PPRaedqlWTAPELLRdpalERRGTLAGDVFSLAIIMQEVVCRSA-PYamLELTPEEVVQRV----RSPPP 765
Cdd:cd05033  162 TYTtkggkiPIR-----WTAPEAIA----YRKFTSASDVWSFGIVMWEVMSYGErPY--WDMSNQDVIKAVedgyRLPPP 230
                        170       180       190
                 ....*....|....*....|....*....|.
gi 4504217   766 lcrplvsMDqAPVECILLMKQCWAEQPELRP 796
Cdd:cd05033  231 -------MD-CPSALYQLMLDCWQKDRNERP 253
PTKc_InsR_like cd05032
Catalytic domain of Insulin Receptor-like Protein Tyrosine Kinases; PTKs catalyze the transfer ...
617-797 1.17e-13

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: 72.76  E-value: 1.17e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   617 VVSEHCTRGSLQDLL-AQREIKLDWMFKSSLLLDLI--------KGIRYLHHRGVAHGRLKSRNCIVDGRFVLKITDHGH 687
Cdd:cd05032   86 VVMELMAKGDLKSYLrSRRPEAENNPGLGPPTLQKFiqmaaeiaDGMAYLAAKKFVHRDLAARNCMVAEDLTVKIGDFGM 165
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   688 GRLL--------EAQKVLpePPRaedqlWTAPELLRDPALerrgTLAGDVFSLAIIMQEVVCRSA-PYamLELTPEEVVQ 758
Cdd:cd05032  166 TRDIyetdyyrkGGKGLL--PVR-----WMAPESLKDGVF----TTKSDVWSFGVVLWEMATLAEqPY--QGLSNEEVLK 232
                        170       180       190
                 ....*....|....*....|....*....|....*....
gi 4504217   759 RVRSPPPLCRPlvsmDQAPVECILLMKQCWAEQPELRPS 797
Cdd:cd05032  233 FVIDGGHLDLP----ENCPDKLLELMRMCWQYNPKMRPT 267
PTKc_DDR cd05051
Catalytic domain of the Protein Tyrosine Kinases, Discoidin Domain Receptors; PTKs catalyze ...
573-802 1.54e-13

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: 72.75  E-value: 1.54e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   573 IRP-ATKTA---FSK----LQELRHENVALYLGlflargaegpAALWEGNLAVVSEHCTRGSLQDLLAQREIK---LDWM 641
Cdd:cd05051   54 LRPdASKNAredFLKevkiMSQLKDPNIVRLLG----------VCTRDEPLCMIVEYMENGDLNQFLQKHEAEtqgASAT 123
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   642 FKSSL----LLDLIK----GIRYLHHRGVAHGRLKSRNCIVDGRFVLKITDHGHGRLL--------EAQKVLpePPRaed 705
Cdd:cd05051  124 NSKTLsygtLLYMATqiasGMKYLESLNFVHRDLATRNCLVGPNYTIKIADFGMSRNLysgdyyriEGRAVL--PIR--- 198
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   706 qlWTAPELLrdpaLERRGTLAGDVFSLAIIMQEV--VCRSAPYAmlELTPEEVV------------QRVRSPPPLCrplv 771
Cdd:cd05051  199 --WMAWESI----LLGKFTTKSDVWAFGVTLWEIltLCKEQPYE--HLTDEQVIenageffrddgmEVYLSRPPNC---- 266
                        250       260       270
                 ....*....|....*....|....*....|...
gi 4504217   772 smdqaPVECILLMKQCWAEQPELRPSMD--HTF 802
Cdd:cd05051  267 -----PKEIYELMLECWRRDEEDRPTFReiHLF 294
PTKc_EphR_A2 cd05063
Catalytic domain of the Protein Tyrosine Kinase, Ephrin Receptor A2; PTKs catalyze the ...
554-796 1.72e-13

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: 71.93  E-value: 1.72e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   554 VYEGdrvwLKKFPGDQHIAIRPAT-KTAFSKLQELRHENVALYLGLFLARGA---EGPAALWEgNLAVVSEHCTRGSLQD 629
Cdd:cd05063   21 VFRG----ILKMPGRKEVAVAIKTlKPGYTEKQRQDFLSEASIMGQFSHHNIirlEGVVTKFK-PAMIITEYMENGALDK 95
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   630 LLAQReiklDWMFKSSLLLDLIKGI----RYLHHRGVAHGRLKSRNCIVDGRFVLKITDHGHGRLLEAQkvlPE------ 699
Cdd:cd05063   96 YLRDH----DGEFSSYQLVGMLRGIaagmKYLSDMNYVHRDLAARNILVNSNLECKVSDFGLSRVLEDD---PEgtytts 168
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   700 ----PPRaedqlWTAPELLRdpalERRGTLAGDVFSLAIIMQEVVCRSA-PYamLELTPEEVVQRV----RSPPPlcrpl 770
Cdd:cd05063  169 ggkiPIR-----WTAPEAIA----YRKFTSASDVWSFGIVMWEVMSFGErPY--WDMSNHEVMKAIndgfRLPAP----- 232
                        250       260
                 ....*....|....*....|....*.
gi 4504217   771 vsMDqAPVECILLMKQCWAEQPELRP 796
Cdd:cd05063  233 --MD-CPSAVYQLMLQCWQQDRARRP 255
PTKc_EphR_A10 cd05064
Catalytic domain of the Protein Tyrosine Kinase, Ephrin Receptor A10; PTKs catalyze the ...
613-805 1.93e-13

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: 71.88  E-value: 1.93e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   613 GN-LAVVSEHCTRGSLQDLLAQREIKLDWMFKSSLLLDLIKGIRYLHHRGVAHGRLKSRNCIVDGRFVLKITDHGHGRLL 691
Cdd:cd05064   78 GNtMMIVTEYMSNGALDSFLRKHEGQLVAGQLMGMLPGLASGMKYLSEMGYVHKGLAAHKVLVNSDLVCKISGFRRLQED 157
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   692 EAQKVLPEPPRAEDQLWTAPELLRdpalERRGTLAGDVFSLAIIMQEVVCRSA-PYamLELTPEEVVQRV----RSPPPL 766
Cdd:cd05064  158 KSEAIYTTMSGKSPVLWAAPEAIQ----YHHFSSASDVWSFGIVMWEVMSYGErPY--WDMSGQDVIKAVedgfRLPAPR 231
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|
gi 4504217   767 -CRPLVSMdqapvecilLMKQCWAEQPELRPSMDHTFDLF 805
Cdd:cd05064  232 nCPNLLHQ---------LMLDCWQKERGERPRFSQIHSIL 262
PTKc_c-ros cd05044
Catalytic domain of the Protein Tyrosine Kinase, C-ros; PTKs catalyze the transfer of the ...
645-799 2.10e-13

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: 71.68  E-value: 2.10e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   645 SLLLDLIKGIRYLHHRGVAHGRLKSRNCIV---DGRF-VLKITDHGHGRLL--------EAQKVLPeppraedQLWTAPE 712
Cdd:cd05044  110 SICVDVAKGCVYLEDMHFVHRDLAARNCLVsskDYRErVVKIGDFGLARDIykndyyrkEGEGLLP-------VRWMAPE 182
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   713 LLRDPALerrgTLAGDVFSLAIIMQEVVCR-SAPYAmlELTPEEVVQRVRSPPPLCRPlvsmDQAPVECILLMKQCWAEQ 791
Cdd:cd05044  183 SLVDGVF----TTQSDVWAFGVLMWEILTLgQQPYP--ARNNLEVLHFVRAGGRLDQP----DNCPDDLYELMLRCWSTD 252

                 ....*...
gi 4504217   792 PELRPSMD 799
Cdd:cd05044  253 PEERPSFA 260
PTKc_Itk cd05112
Catalytic domain of the Protein Tyrosine Kinase, Interleukin-2-inducible T-cell Kinase; PTKs ...
544-797 2.72e-13

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: 71.13  E-value: 2.72e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   544 SQHLDSPNIGVyegdrVWLKKFPGDQHIAIRPATKTAFSK---------LQELRHENVALYLGLFLARGAegpaalwegn 614
Cdd:cd05112    9 VQEIGSGQFGL-----VHLGYWLNKDKVAIKTIREGAMSEedfieeaevMMKLSHPKLVQLYGVCLEQAP---------- 73
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   615 LAVVSEHCTRGSLQDLLAQREIKLDwmfKSSLL---LDLIKGIRYLHHRGVAHGRLKSRNCIVDGRFVLKITDHGHGRLL 691
Cdd:cd05112   74 ICLVFEFMEHGCLSDYLRTQRGLFS---AETLLgmcLDVCEGMAYLEEASVIHRDLAARNCLVGENQVVKVSDFGMTRFV 150
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   692 EAQKVLPEPPRAEDQLWTAPELLRdpalERRGTLAGDVFSLAIIMQEVVCRS-APYAmlELTPEEVVQRVRSPPPLCRPL 770
Cdd:cd05112  151 LDDQYTSSTGTKFPVKWSSPEVFS----FSRYSSKSDVWSFGVLMWEVFSEGkIPYE--NRSNSEVVEDINAGFRLYKPR 224
                        250       260
                 ....*....|....*....|....*..
gi 4504217   771 VsmdqAPVECILLMKQCWAEQPELRPS 797
Cdd:cd05112  225 L----ASTHVYEIMNHCWKERPEDRPS 247
PK_KSR2 cd14153
Pseudokinase domain of Kinase Suppressor of Ras 2; The pseudokinase domain shows similarity to ...
585-810 5.47e-13

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: 70.42  E-value: 5.47e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   585 QELRHENVALYLGlflargaegpAALWEGNLAVVSEHCTRGSLQDLLAQREIKLDWMFKSSLLLDLIKGIRYLHHRGVAH 664
Cdd:cd14153   51 RQTRHENVVLFMG----------ACMSPPHLAIITSLCKGRTLYSVVRDAKVVLDVNKTRQIAQEIVKGMGYLHAKGILH 120
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   665 GRLKSRNCIVD-GRFVlkITDHGhgrLLEAQKVLpEPPRAEDQL-----W---TAPELLR--DPALERRG---TLAGDVF 730
Cdd:cd14153  121 KDLKSKNVFYDnGKVV--ITDFG---LFTISGVL-QAGRREDKLriqsgWlchLAPEIIRqlSPETEEDKlpfSKHSDVF 194
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   731 SLAIIMQEVVCRSAPYamlELTPEEVV--QRVRSPPPLCRPlVSMDQAPVECILLmkqCWAEQPELRPSMDHTFDLFKNI 808
Cdd:cd14153  195 AFGTIWYELHAREWPF---KTQPAEAIiwQVGSGMKPNLSQ-IGMGKEISDILLF---CWAYEQEERPTFSKLMEMLEKL 267

                 ..
gi 4504217   809 NK 810
Cdd:cd14153  268 PK 269
PTKc_EphR_A cd05066
Catalytic domain of the Protein Tyrosine Kinases, Class EphA Ephrin Receptors; PTKs catalyze ...
617-799 6.90e-13

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: 70.28  E-value: 6.90e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   617 VVSEHCTRGSLQDLLAQREIKLDWMFKSSLLLDLIKGIRYLHHRGVAHGRLKSRNCIVDGRFVLKITDHGHGRLLEAQkv 696
Cdd:cd05066   82 IVTEYMENGSLDAFLRKHDGQFTVIQLVGMLRGIASGMKYLSDMGYVHRDLAARNILVNSNLVCKVSDFGLSRVLEDD-- 159
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   697 lPE----------PPRaedqlWTAPELLRdpalERRGTLAGDVFSLAIIMQEVVCRSA-PYamLELTPEEVVQRV----R 761
Cdd:cd05066  160 -PEaayttrggkiPIR-----WTAPEAIA----YRKFTSASDVWSYGIVMWEVMSYGErPY--WEMSNQDVIKAIeegyR 227
                        170       180       190
                 ....*....|....*....|....*....|....*...
gi 4504217   762 SPPPlcrplvsMDqAPVECILLMKQCWAEQPELRPSMD 799
Cdd:cd05066  228 LPAP-------MD-CPAALHQLMLDCWQKDRNERPKFE 257
STKc_KSR1 cd14152
Catalytic domain of the Serine/Threonine Kinase, Kinase Suppressor of Ras 1; STKs catalyze the ...
585-810 8.09e-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: 70.00  E-value: 8.09e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   585 QELRHENVALYLGlflargaegpAALWEGNLAVVSEHCTRGSLQDLLAQREIKLDWMFKSSLLLDLIKGIRYLHHRGVAH 664
Cdd:cd14152   51 RQTRHENVVLFMG----------ACMHPPHLAIITSFCKGRTLYSFVRDPKTSLDINKTRQIAQEIIKGMGYLHAKGIVH 120
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   665 GRLKSRNCIVDGRFVLkITDHGhgrLLEAQKVLPEpPRAEDQL--------WTAPELLRDPALERRG-----TLAGDVFS 731
Cdd:cd14152  121 KDLKSKNVFYDNGKVV-ITDFG---LFGISGVVQE-GRRENELklphdwlcYLAPEIVREMTPGKDEdclpfSKAADVYA 195
                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 4504217   732 LAIIMQEVVCRSAPyaMLELTPEEVVQRVRSPPPLCRPLVSMDQAPvECILLMKQCWAEQPELRPSMDHTFDLFKNINK 810
Cdd:cd14152  196 FGTIWYELQARDWP--LKNQPAEALIWQIGSGEGMKQVLTTISLGK-EVTEILSACWAFDLEERPSFTLLMDMLEKLPK 271
PKc_Wee1_like cd13997
Catalytic domain of the Wee1-like Protein Kinases; PKs catalyze the transfer of the ...
611-799 9.14e-13

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: 69.33  E-value: 9.14e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   611 WE--GNLAVVSEHCTRGSLQDLLAQ--REIKLDWMFKSSLLLDLIKGIRYLHHRGVAHGRLKSRNCIVDGRFVLKITDHG 686
Cdd:cd13997   69 WEegGHLYIQMELCENGSLQDALEElsPISKLSEAEVWDLLLQVALGLAFIHSKGIVHLDIKPDNIFISNKGTCKIGDFG 148
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   687 HGRLLEAQkvlpePPRAE-DQLWTAPELLRDpalERRGTLAGDVFSLAIIMQEVVCRsapyamLELtPE--EVVQRVRS- 762
Cdd:cd13997  149 LATRLETS-----GDVEEgDSRYLAPELLNE---NYTHLPKADIFSLGVTVYEAATG------EPL-PRngQQWQQLRQg 213
                        170       180       190
                 ....*....|....*....|....*....|....*...
gi 4504217   763 -PPPLCRPLVSMDQAPvecilLMKQCWAEQPELRPSMD 799
Cdd:cd13997  214 kLPLPPGLVLSQELTR-----LLKVMLDPDPTRRPTAD 246
STKc_MEKK4 cd06626
Catalytic domain of the Protein Serine/Threonine Kinase, Mitogen-Activated Protein (MAP) ...
584-802 1.23e-12

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: 69.25  E-value: 1.23e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   584 LQELRHENVALYLGLFLARGaegpaalwegNLAVVSEHCTRGSLQDLLAQREIkLDWMFKSSLLLDLIKGIRYLHHRGVA 663
Cdd:cd06626   53 LEGLDHPNLVRYYGVEVHRE----------EVYIFMEYCQEGTLEELLRHGRI-LDEAVIRVYTLQLLEGLAYLHENGIV 121
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   664 HGRLKSRNCIVDGRFVLKITDHGHGRLLEAQKVLPEPPRAED----QLWTAPELLRDPALERRGTlAGDVFSLAIIMQEV 739
Cdd:cd06626  122 HRDIKPANIFLDSNGLIKLGDFGSAVKLKNNTTTMAPGEVNSlvgtPAYMAPEVITGNKGEGHGR-AADIWSLGCVVLEM 200
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 4504217   740 VCRSAPYAMLElTPEEVVQRVRS--PPPLCRPLvsmdQAPVECILLMKQCWAEQPELRPS----MDHTF 802
Cdd:cd06626  201 ATGKRPWSELD-NEWAIMYHVGMghKPPIPDSL----QLSPEGKDFLSRCLESDPKKRPTaselLDHPF 264
PTKc_EphR_B cd05065
Catalytic domain of the Protein Tyrosine Kinases, Class EphB Ephrin Receptors; PTKs catalyze ...
617-796 1.47e-12

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: 69.13  E-value: 1.47e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   617 VVSEHCTRGSLQDLLAQREIKLDWMFKSSLLLDLIKGIRYLHHRGVAHGRLKSRNCIVDGRFVLKITDHGHGRLLEAQKV 696
Cdd:cd05065   82 IITEFMENGALDSFLRQNDGQFTVIQLVGMLRGIAAGMKYLSEMNYVHRDLAARNILVNSNLVCKVSDFGLSRFLEDDTS 161
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   697 LPE---------PPRaedqlWTAPELLRdpalERRGTLAGDVFSLAIIMQEVVCRSA-PYamLELTPEEVV----QRVRS 762
Cdd:cd05065  162 DPTytsslggkiPIR-----WTAPEAIA----YRKFTSASDVWSYGIVMWEVMSYGErPY--WDMSNQDVInaieQDYRL 230
                        170       180       190
                 ....*....|....*....|....*....|....
gi 4504217   763 PPPlcrplvsMDqAPVECILLMKQCWAEQPELRP 796
Cdd:cd05065  231 PPP-------MD-CPTALHQLMLDCWQKDRNLRP 256
PTK_Ryk cd05043
Pseudokinase domain of Ryk (Receptor related to tyrosine kinase); Ryk is a receptor tyr kinase ...
582-797 1.54e-12

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: 69.40  E-value: 1.54e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   582 SKLQELRHENVaLYLGLFLARGAEGPAALWE----GNLAVVSEHCTRGSLQDLLAQREIKLdwmfkSSLLLDLIKGIRYL 657
Cdd:cd05043   59 SLLYGLSHQNL-LPILHVCIEDGEKPMVLYPymnwGNLKLFLQQCRLSEANNPQALSTQQL-----VHMALQIACGMSYL 132
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   658 HHRGVAHGRLKSRNCIVDGRFVLKITDHGHGRLLeaqkvLP-----------EPPRaedqlWTAPELLrdpaLERRGTLA 726
Cdd:cd05043  133 HRRGVIHKDIAARNCVIDDELQVKITDNALSRDL-----FPmdyhclgdnenRPIK-----WMSLESL----VNKEYSSA 198
                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 4504217   727 GDVFSLAIIMQEVVCRSA-PYAmlELTPEEVVQRVRSPPPLCRPLvsmdQAPVECILLMKQCWAEQPELRPS 797
Cdd:cd05043  199 SDVWSFGVLLWELMTLGQtPYV--EIDPFEMAAYLKDGYRLAQPI----NCPDELFAVMACCWALDPEERPS 264
STKc_MAPKKK cd06606
Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein Kinase Kinase ...
584-797 1.66e-12

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: 68.70  E-value: 1.66e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   584 LQELRHENVALYLGLFLArgaegpaalwEGNLAVVSEHCTRGSLQDLLAqreikldwMFKS-------SLLLDLIKGIRY 656
Cdd:cd06606   53 LSSLKHPNIVRYLGTERT----------ENTLNIFLEYVPGGSLASLLK--------KFGKlpepvvrKYTRQILEGLEY 114
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   657 LHHRGVAHGRLKSRNCIVDGRFVLKITDHGHGRLLEAQKVLPEP------PRaedqlWTAPELLRDpalERRGTlAGDVF 730
Cdd:cd06606  115 LHSNGIVHRDIKGANILVDSDGVVKLADFGCAKRLAEIATGEGTkslrgtPY-----WMAPEVIRG---EGYGR-AADIW 185
                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   731 SLAIIMQEVVCRSAPYAMLElTPEEVVQRV---RSPPPLcrPlvsmDQAPVECILLMKQCWAEQPELRPS 797
Cdd:cd06606  186 SLGCTVIEMATGKPPWSELG-NPVAALFKIgssGEPPPI--P----EHLSEEAKDFLRKCLQRDPKKRPT 248
PKc_TNNI3K cd14064
Catalytic domain of the Dual-specificity protein kinase, TNNI3-interacting kinase; ...
582-797 1.80e-12

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: 68.71  E-value: 1.80e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   582 SKLQELRHENVALYLGLFLargaEGPAalwegNLAVVSEHCTRGSLQDLLAQREIKLDWMFKSSLLLDLIKGIRYLHH-- 659
Cdd:cd14064   43 SILCRLNHPCVIQFVGACL----DDPS-----QFAIVTQYVSGGSLFSLLHEQKRVIDLQSKLIIAVDVAKGMEYLHNlt 113
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   660 RGVAHGRLKSRNCIV--DGRFVlkITDHGHGRLLEAqkvlpeppRAEDQL--------WTAPELLRDPAlerRGTLAGDV 729
Cdd:cd14064  114 QPIIHRDLNSHNILLyeDGHAV--VADFGESRFLQS--------LDEDNMtkqpgnlrWMAPEVFTQCT---RYSIKADV 180
                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 4504217   730 FSLAIIMQEVVCRSAPYAMLE---LTPEEVVQRVRSPPPLCRPlvsmdqAPVeCILLMkQCWAEQPELRPS 797
Cdd:cd14064  181 FSYALCLWELLTGEIPFAHLKpaaAAADMAYHHIRPPIGYSIP------KPI-SSLLM-RGWNAEPESRPS 243
PTKc_DDR_like cd05097
Catalytic domain of Discoidin Domain Receptor-like Protein Tyrosine Kinases; PTKs catalyze the ...
573-802 2.15e-12

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: 69.23  E-value: 2.15e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   573 IRP-ATKTA---FSK----LQELRHENVALYLGLFLArgaegpaalwEGNLAVVSEHCTRGSLQDLLAQREIK------- 637
Cdd:cd05097   52 LRAdVTKTArndFLKeikiMSRLKNPNIIRLLGVCVS----------DDPLCMITEYMENGDLNQFLSQREIEstfthan 121
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   638 -LDWMFKSSLL---LDLIKGIRYLHHRGVAHGRLKSRNCIVDGRFVLKITDHGHGRLL--------EAQKVLPeppraed 705
Cdd:cd05097  122 nIPSVSIANLLymaVQIASGMKYLASLNFVHRDLATRNCLVGNHYTIKIADFGMSRNLysgdyyriQGRAVLP------- 194
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   706 QLWTAPELLrdpaLERRGTLAGDVFSLAIIMQEV--VCRSAPYAMleLTPEEVV------------QRVRSPPPLCrplv 771
Cdd:cd05097  195 IRWMAWESI----LLGKFTTASDVWAFGVTLWEMftLCKEQPYSL--LSDEQVIentgeffrnqgrQIYLSQTPLC---- 264
                        250       260       270
                 ....*....|....*....|....*....|...
gi 4504217   772 smdqaPVECILLMKQCWAEQPELRPSMD--HTF 802
Cdd:cd05097  265 -----PSPVFKLMMRCWSRDIKDRPTFNkiHHF 292
STKc_PAK cd06614
Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase; STKs catalyze the ...
584-797 2.34e-12

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: 68.39  E-value: 2.34e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   584 LQELRHENVALYLGLFLARGAegpaaLWegnlaVVSEHCTRGSLQDLLAQREIKLDWMFKSSLLLDLIKGIRYLHHRGVA 663
Cdd:cd06614   50 MKECKHPNIVDYYDSYLVGDE-----LW-----VVMEYMDGGSLTDIITQNPVRMNESQIAYVCREVLQGLEYLHSQNVI 119
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   664 HGRLKSRNCIVDGRFVLKITDHGHGRLLEAQK-----VLPEPpraedqLWTAPELLRDpalERRGTLAgDVFSLAIIMQE 738
Cdd:cd06614  120 HRDIKSDNILLSKDGSVKLADFGFAAQLTKEKskrnsVVGTP------YWMAPEVIKR---KDYGPKV-DIWSLGIMCIE 189
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 4504217   739 VVCRSAPYamLELTPEEVVQRVRS--PPPLcRPLVSMDQapvECILLMKQCWAEQPELRPS 797
Cdd:cd06614  190 MAEGEPPY--LEEPPLRALFLITTkgIPPL-KNPEKWSP---EFKDFLNKCLVKDPEKRPS 244
STKc_Byr2_like cd06628
Catalytic domain of the Serine/Threonine Kinases, fungal Byr2-like Mitogen-Activated Protein ...
568-806 2.91e-12

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: 68.33  E-value: 2.91e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   568 DQHIAIRPATKTAFSKLQELRHENVALYLGlflargaegpAALWEGNLAVVSEHCTRGSLQDLLAQREikldwMFKSSLL 647
Cdd:cd06628   44 DRKKSMLDALQREIALLRELQHENIVQYLG----------SSSDANHLNIFLEYVPGGSVATLLNNYG-----AFEESLV 108
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   648 LDLI----KGIRYLHHRGVAHGRLKSRNCIVDGRFVLKITDHGHGRLLEAQKVLPEPPRAEDQL-----WTAPELLRDPA 718
Cdd:cd06628  109 RNFVrqilKGLNYLHNRGIIHRDIKGANILVDNKGGIKISDFGISKKLEANSLSTKNNGARPSLqgsvfWMAPEVVKQTS 188
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   719 LERRgtlaGDVFSLAIIMQEVVCRSAPYAmlELTPEEVVQRVRSpppLCRPLVSmDQAPVECILLMKQCWAEQPELRPSM 798
Cdd:cd06628  189 YTRK----ADIWSLGCLVVEMLTGTHPFP--DCTQMQAIFKIGE---NASPTIP-SNISSEARDFLEKTFEIDHNKRPTA 258

                 ....*...
gi 4504217   799 DhtfDLFK 806
Cdd:cd06628  259 D---ELLK 263
STKc_TAK1 cd14058
Catalytic domain of the Serine/Threonine Kinase, Transforming Growth Factor beta Activated ...
572-799 3.15e-12

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: 67.85  E-value: 3.15e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   572 AIRPATKTAFSKLQELRHENVALYLGlflargaegpAALWEGNLAVVSEHCTRGSLQDLLAQREIK--------LDWMFK 643
Cdd:cd14058   28 SEKKAFEVEVRQLSRVDHPNIIKLYG----------ACSNQKPVCLVMEYAEGGSLYNVLHGKEPKpiytaahaMSWALQ 97
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   644 SSllldliKGIRYLHH---RGVAHGRLKSRNCI-VDGRFVLKITDHGHGRLLEAQKVLPEPPRAedqlWTAPELLRDpal 719
Cdd:cd14058   98 CA------KGVAYLHSmkpKALIHRDLKPPNLLlTNGGTVLKICDFGTACDISTHMTNNKGSAA----WMAPEVFEG--- 164
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   720 eRRGTLAGDVFSLAIIMQEVVCRSAPYAMLELTPEEVVQRVRS--PPPLCRPLvsmdQAPVECilLMKQCWAEQPELRPS 797
Cdd:cd14058  165 -SKYSEKCDVFSWGIILWEVITRRKPFDHIGGPAFRIMWAVHNgeRPPLIKNC----PKPIES--LMTRCWSKDPEKRPS 237

                 ..
gi 4504217   798 MD 799
Cdd:cd14058  238 MK 239
PKc_STE cd05122
Catalytic domain of STE family Protein Kinases; PKs catalyze the transfer of the ...
584-765 3.59e-12

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: 67.61  E-value: 3.59e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   584 LQELRHENVALYLGLFLArgaegpaalwEGNLAVVSEHCTRGSLQDLLAQREIKLDWMFKSSLLLDLIKGIRYLHHRGVA 663
Cdd:cd05122   51 LKKCKHPNIVKYYGSYLK----------KDELWIVMEFCSGGSLKDLLKNTNKTLTEQQIAYVCKEVLKGLEYLHSHGII 120
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   664 HGRLKSRNCIVDGRFVLKITDHGhgrlLEAQKvlpEPPRAEDQL-----WTAPELLRDpalERRGTLAgDVFSLAIIMQE 738
Cdd:cd05122  121 HRDIKAANILLTSDGEVKLIDFG----LSAQL---SDGKTRNTFvgtpyWMAPEVIQG---KPYGFKA-DIWSLGITAIE 189
                        170       180
                 ....*....|....*....|....*...
gi 4504217   739 VVCRSAPYAmlELTPEEVVQRV-RSPPP 765
Cdd:cd05122  190 MAEGKPPYS--ELPPMKALFLIaTNGPP 215
PTKc_Hck cd05073
Catalytic domain of the Protein Tyrosine Kinase, Hematopoietic cell kinase; PTKs catalyze the ...
617-800 4.07e-12

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: 67.74  E-value: 4.07e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   617 VVSEHCTRGSLQDLLAQREIKLDWMFKsslLLD----LIKGIRYLHHRGVAHGRLKSRNCIVDGRFVLKITDHGHGRLLE 692
Cdd:cd05073   82 IITEFMAKGSLLDFLKSDEGSKQPLPK---LIDfsaqIAEGMAFIEQRNYIHRDLRAANILVSASLVCKIADFGLARVIE 158
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   693 AQKVLPEPPRAEDQLWTAPELLRDPALerrgTLAGDVFSLAIIMQEVVCRS-APYAmlELTPEEVVQRVRSPPPLCRplv 771
Cdd:cd05073  159 DNEYTAREGAKFPIKWTAPEAINFGSF----TIKSDVWSFGILLMEIVTYGrIPYP--GMSNPEVIRALERGYRMPR--- 229
                        170       180
                 ....*....|....*....|....*....
gi 4504217   772 sMDQAPVECILLMKQCWAEQPELRPSMDH 800
Cdd:cd05073  230 -PENCPEELYNIMMRCWKNRPEERPTFEY 257
STKc_MLK cd14061
Catalytic domain of the Serine/Threonine Kinases, Mixed Lineage Kinases; STKs catalyze the ...
576-808 5.62e-12

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: 67.42  E-value: 5.62e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   576 ATKTAFSKLQE------LRHENVALYLGLFLArgaegpaalwEGNLAVVSEHCTRGSLQDLLAQREIK----LDWMfkss 645
Cdd:cd14061   33 ISVTLENVRQEarlfwmLRHPNIIALRGVCLQ----------PPNLCLVMEYARGGALNRVLAGRKIPphvlVDWA---- 98
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   646 llLDLIKGIRYLHHRG---VAHGRLKSRNCIVDGRF--------VLKITDHGHGRllEAQKVlPEPPRAEDQLWTAPELL 714
Cdd:cd14061   99 --IQIARGMNYLHNEApvpIIHRDLKSSNILILEAIenedlenkTLKITDFGLAR--EWHKT-TRMSAAGTYAWMAPEVI 173
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   715 RDPALERrgtlAGDVFSLAIIMQEVVCRSAPYAMLEltPEEVVQRVRS-----PPPlcrplvsmDQAPVECILLMKQCWA 789
Cdd:cd14061  174 KSSTFSK----ASDVWSYGVLLWELLTGEVPYKGID--GLAVAYGVAVnkltlPIP--------STCPEPFAQLMKDCWQ 239
                        250
                 ....*....|....*....
gi 4504217   790 EQPELRPSMDHTFDLFKNI 808
Cdd:cd14061  240 PDPHDRPSFADILKQLENI 258
STKc_ULK4 cd14010
Catalytic domain of the Serine/Threonine kinase, Unc-51-like kinase 4; STKs catalyze the ...
584-785 6.75e-12

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: 67.32  E-value: 6.75e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   584 LQELRHENV----ALYlglflargaEGPAALWegnlaVVSEHCTRGSLQDLLAQrEIKLDWMFKSSLLLDLIKGIRYLHH 659
Cdd:cd14010   48 THELKHPNVlkfyEWY---------ETSNHLW-----LVVEYCTGGDLETLLRQ-DGNLPESSVRKFGRDLVRGLHYIHS 112
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   660 RGVAHGRLKSRNCIVDGRFVLKITDHGHGRLL-EAQKVLPEPPRAEDQ--------------LWTAPELLRDPALerrgT 724
Cdd:cd14010  113 KGIIYCDLKPSNILLDGNGTLKLSDFGLARREgEILKELFGQFSDEGNvnkvskkqakrgtpYYMAPELFQGGVH----S 188
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 4504217   725 LAGDVFSLAIIMQEVVCRSAPYAMLELTpEEVVQRVRSPPPLCRPLVSmDQAPVECILLMK 785
Cdd:cd14010  189 FASDLWALGCVLYEMFTGKPPFVAESFT-ELVEKILNEDPPPPPPKVS-SKPSPDFKSLLK 247
STKc_HAL4_like cd13994
Catalytic domain of Fungal Halotolerance protein 4-like Serine/Threonine kinases; STKs ...
581-799 1.07e-11

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: 66.56  E-value: 1.07e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   581 FSKLQELRHENVALYLGLFLARGAEgpaalwegnLAVVSEHCTRGSLQDLLAQREiKLDWMFKSSLLLDLIKGIRYLHHR 660
Cdd:cd13994   48 YIISSKLHHPNIVKVLDLCQDLHGK---------WCLVMEYCPGGDLFTLIEKAD-SLSLEEKDCFFKQILRGVAYLHSH 117
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   661 GVAHGRLKSRNCIVDGRFVLKITDHGHGRLLeaqKVLPEP-PRAEDQL-----WTAPELLR----DPalerrgtLAGDVF 730
Cdd:cd13994  118 GIAHRDLKPENILLDEDGVLKLTDFGTAEVF---GMPAEKeSPMSAGLcgsepYMAPEVFTsgsyDG-------RAVDVW 187
                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 4504217   731 SLAIIMQEVVCRSAPYAMLELTPEE----VVQRVRSPPPLCRPLVSMdqaPVECILLMKQCWAEQPELRPSMD 799
Cdd:cd13994  188 SCGIVLFALFTGRFPWRSAKKSDSAykayEKSGDFTNGPYEPIENLL---PSECRRLIYRMLHPDPEKRITID 257
STKc_TGFbR_I cd14056
Catalytic domain of the Serine/Threonine Kinases, Transforming Growth Factor beta family Type ...
552-798 1.10e-11

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: 66.91  E-value: 1.10e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   552 IGVYEGDRVWLKKFPgdqhiairpaTKTAFSKLQE--------LRHENValyLGlFLA---RGAEGPAALWegnlaVVSE 620
Cdd:cd14056   13 LGKYRGEKVAVKIFS----------SRDEDSWFREteiyqtvmLRHENI---LG-FIAadiKSTGSWTQLW-----LITE 73
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   621 HCTRGSLQDLLAQREIKLDWMFKssLLLDLIKGIRYLHHR--------GVAHGRLKSRNCIVDGRFVLKITDHGHG-RLL 691
Cdd:cd14056   74 YHEHGSLYDYLQRNTLDTEEALR--LAYSAASGLAHLHTEivgtqgkpAIAHRDLKSKNILVKRDGTCCIADLGLAvRYD 151
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   692 EAQKVLPEP--PRAEDQLWTAPELLRDpaleRRGTL------AGDVFSLAIIMQEVVCRSA----------PYamLELTP 753
Cdd:cd14056  152 SDTNTIDIPpnPRVGTKRYMAPEVLDD----SINPKsfesfkMADIYSFGLVLWEIARRCEiggiaeeyqlPY--FGMVP 225
                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 4504217   754 -----EE-----VVQRVRSPPPlcrPLVSMDQAPVECILLMKQCWAEQPELRPSM 798
Cdd:cd14056  226 sdpsfEEmrkvvCVEKLRPPIP---NRWKSDPVLRSMVKLMQECWSENPHARLTA 277
PTKc_Tec_Rlk cd05114
Catalytic domain of the Protein Tyrosine Kinases, Tyrosine kinase expressed in hepatocellular ...
615-808 1.14e-11

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: 66.42  E-value: 1.14e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   615 LAVVSEHCTRGSLQDLLAQREIKLDWMFKSSLLLDLIKGIRYLHHRGVAHGRLKSRNCIVDGRFVLKITDHGHGR-LLEA 693
Cdd:cd05114   74 IYIVTEFMENGCLLNYLRQRRGKLSRDMLLSMCQDVCEGMEYLERNNFIHRDLAARNCLVNDTGVVKVSDFGMTRyVLDD 153
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   694 QKVLPEPPRAEDQlWTAPELLrdpaLERRGTLAGDVFSLAIIMQEVVCRSA-PYAmlELTPEEVVQRVRSPPPLCRPLVs 772
Cdd:cd05114  154 QYTSSSGAKFPVK-WSPPEVF----NYSKFSSKSDVWSFGVLMWEVFTEGKmPFE--SKSNYEVVEMVSRGHRLYRPKL- 225
                        170       180       190
                 ....*....|....*....|....*....|....*.
gi 4504217   773 mdqAPVECILLMKQCWAEQPELRPSMDhtfDLFKNI 808
Cdd:cd05114  226 ---ASKSVYEVMYSCWHEKPEGRPTFA---DLLRTI 255
STKc_LRRK cd14000
Catalytic domain of the Serine/Threonine kinase, Leucine-Rich Repeat Kinase; STKs catalyze the ...
615-797 1.24e-11

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: 66.48  E-value: 1.24e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   615 LAVVSEHCTRGSLQDLLAQ---REIKLDWMFKSSLLLDLIKGIRYLHHRGVAHGRLKSRNCIVdgrFVLKITDHGHGRLL 691
Cdd:cd14000   83 LMLVLELAPLGSLDHLLQQdsrSFASLGRTLQQRIALQVADGLRYLHSAMIIYRDLKSHNVLV---WTLYPNSAIIIKIA 159
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   692 E---AQKVLPEPPRAEDQL--WTAPELLRDpalERRGTLAGDVFSLAIIMQEVVCRSAPYAMLELTPEEVVQRVRSPPPL 766
Cdd:cd14000  160 DygiSRQCCRMGAKGSEGTpgFRAPEIARG---NVIYNEKVDVFSFGMLLYEILSGGAPMVGHLKFPNEFDIHGGLRPPL 236
                        170       180       190
                 ....*....|....*....|....*....|.
gi 4504217   767 CRPlvsMDQAPVECILLMKQCWAEQPELRPS 797
Cdd:cd14000  237 KQY---ECAPWPEVEVLMKKCWKENPQQRPT 264
PTKc_FGFR cd05053
Catalytic domain of the Protein Tyrosine Kinases, Fibroblast Growth Factor Receptors; PTKs ...
588-797 1.49e-11

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: 66.67  E-value: 1.49e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   588 RHENVALYLGlflargaegpAALWEGNLAVVSEHCTRGSLQDLL-AQREIKLDWMFKSSLLL-------DLI-------K 652
Cdd:cd05053   75 KHKNIINLLG----------ACTQDGPLYVVVEYASKGNLREFLrARRPPGEEASPDDPRVPeeqltqkDLVsfayqvaR 144
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   653 GIRYLHHRGVAHGRLKSRNCIVDGRFVLKITDHGHGRLLEAQKVLPEppRAEDQL---WTAPELLRDpaleRRGTLAGDV 729
Cdd:cd05053  145 GMEYLASKKCIHRDLAARNVLVTEDNVMKIADFGLARDIHHIDYYRK--TTNGRLpvkWMAPEALFD----RVYTHQSDV 218
                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 4504217   730 FSLAIIMQEVVCRS-APYAMLELtpEEVVQRVRS-----PPPLCrplvsmdqaPVECILLMKQCWAEQPELRPS 797
Cdd:cd05053  219 WSFGVLLWEIFTLGgSPYPGIPV--EELFKLLKEghrmeKPQNC---------TQELYMLMRDCWHEVPSQRPT 281
PTKc_FGFR4 cd05099
Catalytic domain of the Protein Tyrosine Kinase, Fibroblast Growth Factor Receptor 4; PTKs ...
588-828 2.05e-11

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: 66.53  E-value: 2.05e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   588 RHENVALYLGLflargaegpaALWEGNLAVVSEHCTRGSLQDLL-AQREIKLDWMFKS--------------SLLLDLIK 652
Cdd:cd05099   76 KHKNIINLLGV----------CTQEGPLYVIVEYAAKGNLREFLrARRPPGPDYTFDItkvpeeqlsfkdlvSCAYQVAR 145
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   653 GIRYLHHRGVAHGRLKSRNCIVDGRFVLKITDHGHGRLLEAQKVLPEPPRAEDQL-WTAPELLRDpaleRRGTLAGDVFS 731
Cdd:cd05099  146 GMEYLESRRCIHRDLAARNVLVTEDNVMKIADFGLARGVHDIDYYKKTSNGRLPVkWMAPEALFD----RVYTHQSDVWS 221
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   732 LAIIMQEV-VCRSAPYAMLELtpEEVVQRVRSPPPLCRPlvsmDQAPVECILLMKQCWAEQPELRPSMDHTFDLFKNINK 810
Cdd:cd05099  222 FGILMWEIfTLGGSPYPGIPV--EELFKLLREGHRMDKP----SNCTHELYMLMRECWHAVPTQRPTFKQLVEALDKVLA 295
                        250
                 ....*....|....*....
gi 4504217   811 GRKTNIIDsmLRM-LEQYS 828
Cdd:cd05099  296 AVSEEYLD--LSMpFEQYS 312
STKc_RIP4_like cd14025
Catalytic domain of the Serine/Threonine kinases, Receptor Interacting Protein 4 and similar ...
615-797 2.09e-11

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: 65.59  E-value: 2.09e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   615 LAVVSEHCTRGSLQDLLAQReiKLDWMFKSSLLLDLIKGIRYLH--HRGVAHGRLKSRNCIVDGRFVLKITDHGHGRLLE 692
Cdd:cd14025   68 VGLVMEYMETGSLEKLLASE--PLPWELRFRIIHETAVGMNFLHcmKPPLLHLDLKPANILLDAHYHVKISDFGLAKWNG 145
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   693 -AQKVLPEPPRAEDQL-WTAPELLRDPalERRGTLAGDVFSLAIIMQEVVCRSAPYA----MLELTPEeVVQRVR-SPPP 765
Cdd:cd14025  146 lSHSHDLSRDGLRGTIaYLPPERFKEK--NRCPDTKHDVYSFAIVIWGILTQKKPFAgennILHIMVK-VVKGHRpSLSP 222
                        170       180       190
                 ....*....|....*....|....*....|....*
gi 4504217   766 LCRplvsmdQAPVEC---ILLMKQCWAEQPELRPS 797
Cdd:cd14025  223 IPR------QRPSECqqmICLMKRCWDQDPRKRPT 251
STKc_PknB_like cd14014
Catalytic domain of bacterial Serine/Threonine kinases, PknB and similar proteins; STKs ...
584-797 3.78e-11

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: 64.92  E-value: 3.78e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   584 LQELRHENVALYLGLFLargaegpaalWEGNLAVVSEHCTRGSLQDLLAQReIKLDWMFKSSLLLDLIKGIRYLHHRGVA 663
Cdd:cd14014   54 LARLSHPNIVRVYDVGE----------DDGRPYIVMEYVEGGSLADLLRER-GPLPPREALRILAQIADALAAAHRAGIV 122
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   664 HGRLKSRNCIVDGRFVLKITDHGHGRLLEAQKVLPEPPRAEDQLWTAPELLRDPALerrgTLAGDVFSLAIIMQEVVCRS 743
Cdd:cd14014  123 HRDIKPANILLTEDGRVKLTDFGIARALGDSGLTQTGSVLGTPAYMAPEQARGGPV----DPRSDIYSLGVVLYELLTGR 198
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....
gi 4504217   744 APYAMLElTPEEVVQRVRSPPPLCRPLVSMDQAPVECILLmkQCWAEQPELRPS 797
Cdd:cd14014  199 PPFDGDS-PAAVLAKHLQEAPPPPSPLNPDVPPALDAIIL--RALAKDPEERPQ 249
PTKc_Frk_like cd05068
Catalytic domain of Fyn-related kinase-like Protein Tyrosine Kinases; PTKs catalyze the ...
617-797 4.88e-11

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: 64.74  E-value: 4.88e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   617 VVSEHCTRGSLQDLLAQREIKLdwmfKSSLLLDL----IKGIRYLHHRGVAHGRLKSRNCIVDGRFVLKITDHGHGRLLE 692
Cdd:cd05068   80 IITELMKHGSLLEYLQGKGRSL----QLPQLIDMaaqvASGMAYLESQNYIHRDLAARNVLVGENNICKVADFGLARVIK 155
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   693 AQKVLPEPPRAEDQL-WTAPEllrdPALERRGTLAGDVFSLAIIMQEVVCRSA-PYAmlELTPEEVVQRV----RSP-PP 765
Cdd:cd05068  156 VEDEYEAREGAKFPIkWTAPE----AANYNRFSIKSDVWSFGILLTEIVTYGRiPYP--GMTNAEVLQQVergyRMPcPP 229
                        170       180       190
                 ....*....|....*....|....*....|..
gi 4504217   766 LCrplvsmdqaPVECILLMKQCWAEQPELRPS 797
Cdd:cd05068  230 NC---------PPQLYDIMLECWKADPMERPT 252
PTKc_DDR1 cd05096
Catalytic domain of the Protein Tyrosine Kinase, Discoidin Domain Receptor 1; PTKs catalyze ...
645-802 5.13e-11

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: 64.96  E-value: 5.13e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   645 SLLLDLIKGIRYLHHRGVAHGRLKSRNCIVDGRFVLKITDHGHGRLLEAQKVLPEPPRAEDQL-WTAPELLrdpaLERRG 723
Cdd:cd05096  142 HVALQIASGMKYLSSLNFVHRDLATRNCLVGENLTIKIADFGMSRNLYAGDYYRIQGRAVLPIrWMAWECI----LMGKF 217
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   724 TLAGDVFSLAIIMQEV--VCRSAPYAmlELTPEEVVQR-------------VRSPPPLCRPLVSmdqapvecilLMKQCW 788
Cdd:cd05096  218 TTASDVWAFGVTLWEIlmLCKEQPYG--ELTDEQVIENageffrdqgrqvyLFRPPPCPQGLYE----------LMLQCW 285
                        170
                 ....*....|....*.
gi 4504217   789 AEQPELRPSMD--HTF 802
Cdd:cd05096  286 SRDCRERPSFSdiHAF 301
PTKc_Ror cd05048
Catalytic Domain of the Protein Tyrosine Kinases, Receptor tyrosine kinase-like Orphan ...
554-797 5.41e-11

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: 64.70  E-value: 5.41e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   554 VYEGDRVWLKKFPGDQHIAIRPATKTAFSKLQ-----------ELRHENVALYLGLFLArgaEGPaalwegnLAVVSEHC 622
Cdd:cd05048   21 VYKGELLGPSSEESAISVAIKTLKENASPKTQqdfrreaelmsDLQHPNIVCLLGVCTK---EQP-------QCMLFEYM 90
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   623 TRGSLQDLLAQRE-------IKLDWMFKSSLL-LDLI-------KGIRYLHHRGVAHGRLKSRNCIVDGRFVLKITDHGH 687
Cdd:cd05048   91 AHGDLHEFLVRHSphsdvgvSSDDDGTASSLDqSDFLhiaiqiaAGMEYLSSHHYVHRDLAARNCLVGDGLTVKISDFGL 170
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   688 GRLLEA------QKVLPEPPRaedqlWTAPELLrdpaLERRGTLAGDVFSLAIIMQEVVCRSA-PYamLELTPEEVVQRV 760
Cdd:cd05048  171 SRDIYSsdyyrvQSKSLLPVR-----WMPPEAI----LYGKFTTESDVWSFGVVLWEIFSYGLqPY--YGYSNQEVIEMI 239
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|.
gi 4504217   761 RSppplcRPLVSmdqAPVEC----ILLMKQCWAEQPELRPS 797
Cdd:cd05048  240 RS-----RQLLP---CPEDCparvYSLMVECWHEIPSRRPR 272
SPS1 COG0515
Serine/threonine protein kinase [Signal transduction mechanisms];
584-765 5.66e-11

Serine/threonine protein kinase [Signal transduction mechanisms];


Pssm-ID: 440281 [Multi-domain]  Cd Length: 482  Bit Score: 66.19  E-value: 5.66e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   584 LQELRHENVALYLGLFLARGAegpaalwegnLAVVSEHCTRGSLQDLLAQREiKLDWMFKSSLLLDLIKGIRYLHHRGVA 663
Cdd:COG0515   61 LARLNHPNIVRVYDVGEEDGR----------PYLVMEYVEGESLADLLRRRG-PLPPAEALRILAQLAEALAAAHAAGIV 129
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   664 HGRLKSRNCIVDGRFVLKITDHGHGRLLEAQKVLPEPPRAEDQLWTAPELLRDpaleRRGTLAGDVFSLAIIMQEVVCRS 743
Cdd:COG0515  130 HRDIKPANILLTPDGRVKLIDFGIARALGGATLTQTGTVVGTPGYMAPEQARG----EPVDPRSDVYSLGVTLYELLTGR 205
                        170       180
                 ....*....|....*....|..
gi 4504217   744 APYAmlELTPEEVVQRVRSPPP 765
Cdd:COG0515  206 PPFD--GDSPAELLRAHLREPP 225
STKc_LIMK cd14154
Catalytic domain of the Serine/Threonine Kinase, LIM domain kinase; STKs catalyze the transfer ...
584-742 7.75e-11

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: 64.07  E-value: 7.75e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   584 LQELRHENVALYLGLflargaegpaaLWEGN-LAVVSEHCTRGSLQDLLAQREIKLDWMFKSSLLLDLIKGIRYLHHRGV 662
Cdd:cd14154   44 MRSLDHPNVLKFIGV-----------LYKDKkLNLITEYIPGGTLKDVLKDMARPLPWAQRVRFAKDIASGMAYLHSMNI 112
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   663 AHGRLKSRNCIVDGRFVLKITDHGHGRLLEAQKVLPEPPRAEDQL-------------------WTAPELLRDPALERRg 723
Cdd:cd14154  113 IHRDLNSHNCLVREDKTVVVADFGLARLIVEERLPSGNMSPSETLrhlkspdrkkrytvvgnpyWMAPEMLNGRSYDEK- 191
                        170
                 ....*....|....*....
gi 4504217   724 tlaGDVFSLAIIMQEVVCR 742
Cdd:cd14154  192 ---VDIFSFGIVLCEIIGR 207
STKc_A-Raf cd14150
Catalytic domain of the Serine/Threonine Kinase, A-Raf (Rapidly Accelerated Fibrosarcoma) ...
576-747 7.93e-11

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: 63.88  E-value: 7.93e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   576 ATKTAFSKLQELRHENVALYLGlFLARGaegpaalwegNLAVVSEHCTRGSLQDLLAQREIKLDWMFKSSLLLDLIKGIR 655
Cdd:cd14150   42 AFKNEMQVLRKTRHVNILLFMG-FMTRP----------NFAIITQWCEGSSLYRHLHVTETRFDTMQLIDVARQTAQGMD 110
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   656 YLHHRGVAHGRLKSRNCIVDGRFVLKITDHG----HGRLLEAQKVlpEPPRAEdQLWTAPELLR--DPALErrgTLAGDV 729
Cdd:cd14150  111 YLHAKNIIHRDLKSNNIFLHEGLTVKIGDFGlatvKTRWSGSQQV--EQPSGS-ILWMAPEVIRmqDTNPY---SFQSDV 184
                        170
                 ....*....|....*...
gi 4504217   730 FSLAIIMQEVVCRSAPYA 747
Cdd:cd14150  185 YAYGVVLYELMSGTLPYS 202
STKc_BMPR2_AMHR2 cd14054
Catalytic domain of the Serine/Threonine Kinases, Bone Morphogenetic Protein and ...
553-795 1.56e-10

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: 63.53  E-value: 1.56e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   553 GVYEGDRVWLKKFPGDQHIAIrpATKTAFSKLQELRHENVALYLGlflarGAEGP-AALWEGNLAVVSEHcTRGSLQDLL 631
Cdd:cd14054   14 GSLDERPVAVKVFPARHRQNF--QNEKDIYELPLMEHSNILRFIG-----ADERPtADGRMEYLLVLEYA-PKGSLCSYL 85
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   632 aqREIKLDWMFKSSLLLDLIKGIRYLH---HRG------VAHGRLKSRNCIV--DGRFVlkITDHGHGRLLEAQKVLPEP 700
Cdd:cd14054   86 --RENTLDWMSSCRMALSLTRGLAYLHtdlRRGdqykpaIAHRDLNSRNVLVkaDGSCV--ICDFGLAMVLRGSSLVRGR 161
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   701 PRAEDQL---------WTAPELLrDPALERRGT----LAGDVFSLAIIMQEVVCR-------------SAPY-AMLELTP 753
Cdd:cd14054  162 PGAAENAsisevgtlrYMAPEVL-EGAVNLRDCesalKQVDVYALGLVLWEIAMRcsdlypgesvppyQMPYeAELGNHP 240
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|....*..
gi 4504217   754 --EEV---VQRVRSPPPLCRPLVSMDQAPVECILLMKQCWAEQPELR 795
Cdd:cd14054  241 tfEDMqllVSREKARPKFPDAWKENSLAVRSLKETIEDCWDQDAEAR 287
PTK_Jak_rpt1 cd05037
Pseudokinase (repeat 1) domain of the Protein Tyrosine Kinases, Janus kinases; The Jak ...
529-797 1.59e-10

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: 62.88  E-value: 1.59e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   529 SSLGARSMSDIRSGPSQhldSPNIGVYEGDRVWLKKFPGDQHIAIRPATKTAfSKLQELRHENVALYLGLFLARGAEgpa 608
Cdd:cd05037    5 EHLGQGTFTNIYDGILR---EVGDGRVQEVEVLLKVLDSDHRDISESFFETA-SLMSQISHKHLVKLYGVCVADENI--- 77
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   609 alwegnlaVVSEHCTRGSLqDLLAQREIKLDWM-FKSSLLLDLIKGIRYLHHRGVAHGRLKSRNCIV-------DGRFVl 680
Cdd:cd05037   78 --------MVQEYVRYGPL-DKYLRRMGNNVPLsWKLQVAKQLASALHYLEDKKLIHGNVRGRNILLaregldgYPPFI- 147
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   681 KITDHGHGRlleaqKVLPEPPRAEDQLWTAPELLRDPAleRRGTLAGDVFSLAIIMQEVVCRS-APYAMLELTPEEVVQR 759
Cdd:cd05037  148 KLSDPGVPI-----TVLSREERVDRIPWIAPECLRNLQ--ANLTIAADKWSFGTTLWEICSGGeEPLSALSSQEKLQFYE 220
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|
gi 4504217   760 VRS--PPPLCRPLVsmdqapveciLLMKQCWAEQPELRPS 797
Cdd:cd05037  221 DQHqlPAPDCAELA----------ELIMQCWTYEPTKRPS 250
STKc_MST1_2 cd06612
Catalytic domain of the Serine/Threonine Kinases, Mammalian STe20-like protein kinase 1 and 2; ...
584-802 2.25e-10

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: 62.28  E-value: 2.25e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   584 LQELRHENVALYLGLFLArgaegpaalwEGNLAVVSEHCTRGSLQDLLAQREIKLDWMFKSSLLLDLIKGIRYLHHRGVA 663
Cdd:cd06612   52 LKQCDSPYIVKYYGSYFK----------NTDLWIVMEYCGAGSVSDIMKITNKTLTEEEIAAILYQTLKGLEYLHSNKKI 121
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   664 HGRLKSRNCIVDGRFVLKITDHG-----HGRLLEAQKVLPEPpraedqLWTAPELLrdpaLERRGTLAGDVFSLAIIMQE 738
Cdd:cd06612  122 HRDIKAGNILLNEEGQAKLADFGvsgqlTDTMAKRNTVIGTP------FWMAPEVI----QEIGYNNKADIWSLGITAIE 191
                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   739 VVCRSAPYAmlELTPEEVVQRV--RSPPPLCRPlvsmDQAPVECILLMKQCWAEQPELRPS----MDHTF 802
Cdd:cd06612  192 MAEGKPPYS--DIHPMRAIFMIpnKPPPTLSDP----EKWSPEFNDFVKKCLVKDPEERPSaiqlLQHPF 255
STKc_Raf cd14062
Catalytic domain of the Serine/Threonine Kinases, Raf (Rapidly Accelerated Fibrosarcoma) ...
576-796 4.83e-10

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: 61.26  E-value: 4.83e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   576 ATKTAFSKLQELRHENVALYLGlflargaegpaALWEGNLAVVSEHCTRGSLQDLLAQREIKldwmFKSSLLLDLIK--- 652
Cdd:cd14062   35 AFKNEVAVLRKTRHVNILLFMG-----------YMTKPQLAIVTQWCEGSSLYKHLHVLETK----FEMLQLIDIARqta 99
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   653 -GIRYLHHRGVAHGRLKSRNCIVDGRFVLKITDHGhgrlLEAQKVLPEPPRAEDQ-----LWTAPELLRDPALERRGTLA 726
Cdd:cd14062  100 qGMDYLHAKNIIHRDLKSNNIFLHEDLTVKIGDFG----LATVKTRWSGSQQFEQptgsiLWMAPEVIRMQDENPYSFQS 175
                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 4504217   727 gDVFSLAIIMQEVVCRSAPYAMLElTPEEVVQRVRSppPLCRPLVSM--DQAPVECILLMKQCWAEQPELRP 796
Cdd:cd14062  176 -DVYAFGIVLYELLTGQLPYSHIN-NRDQILFMVGR--GYLRPDLSKvrSDTPKALRRLMEDCIKFQRDERP 243
STKc_ACVR2 cd14053
Catalytic domain of the Serine/Threonine Kinase, Activin Type II Receptor; STKs catalyze the ...
560-797 5.47e-10

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: 61.57  E-value: 5.47e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   560 VWLKKFPgDQHIAIR---PATKTAFS------KLQELRHENVALYLGLfLARGAEGPAALWegnlaVVSEHCTRGSLQDL 630
Cdd:cd14053   11 VWKAQYL-NRLVAVKifpLQEKQSWLtereiySLPGMKHENILQFIGA-EKHGESLEAEYW-----LITEFHERGSLCDY 83
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   631 LAQREIKLDWMFKssLLLDLIKGIRYLH------HRG----VAHGRLKSRNCIVDGRFVLKITDHGHGRLLEAQKVLPEp 700
Cdd:cd14053   84 LKGNVISWNELCK--IAESMARGLAYLHedipatNGGhkpsIAHRDFKSKNVLLKSDLTACIADFGLALKFEPGKSCGD- 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   701 prAEDQLWT----APELLrDPALE--RRGTLAGDVFSLAIIMQEVVCRS-----------APYAM-------LELTPEEV 756
Cdd:cd14053  161 --THGQVGTrrymAPEVL-EGAINftRDAFLRIDMYAMGLVLWELLSRCsvhdgpvdeyqLPFEEevgqhptLEDMQECV 237
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|..
gi 4504217   757 VQR-VRsppPLCRPLVSMDQAPVECILLMKQCWAEQPELRPS 797
Cdd:cd14053  238 VHKkLR---PQIRDEWRKHPGLAQLCETIEECWDHDAEARLS 276
PBP1_GC_G-like cd06372
Ligand-binding domain of membrane guanylyl cyclase G; This group includes the ligand-binding ...
55-356 7.57e-10

Ligand-binding domain of membrane guanylyl cyclase G; This group includes the ligand-binding domain of membrane guanylyl cyclase G (GC-G) which is a sperm surface receptor and might function, similar to its sea urchin counterpart, in the early signaling event that regulates the Ca2+ influx/efflux and subsequent motility response in sperm. GC-G appears to be a pseudogene in human. Furthermore, in contrast to the other orphan receptor GCs, GC-G has a broad tissue distribution in rat, including lung, intestine, kidney, and skeletal muscle.


Pssm-ID: 380595 [Multi-domain]  Cd Length: 390  Bit Score: 62.12  E-value: 7.57e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217    55 TVGVLGPWACDPIFSRARPDLAARLAAARLNRDPGLAGGPRFEVALLPEPCRTPGSLGAVSSALAR--VSGLVGPVNPAA 132
Cdd:cd06372    1 TVGFQAPWNLSHPFSAQRLGSAIQLAVDKVNSEPSLLGNYSLDFVYTDCGCNAKESLGAFIDQVQKenISALFGPACPEA 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   133 CRPAELLAEEagialvpWGCPWTQAEGTTA---------------PAVTPAADALYALLRAFGWARVALVTAP------- 190
Cdd:cd06372   81 AEVTGLLASE-------WNIPMFGFVGQSPklddrdvydtyvklvPPLQRIGEVLVKTLQFFGWTHVAMFGGSsatstwd 153
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   191 --QDLWveagRSLSTALRARGLPVASVtSMEPLDLSGAREALRKVrdgPRVTAVIMVMHSvllgGEEQRYLLEAAEELGL 268
Cdd:cd06372  154 kvDELW----KSVENQLKFNFNVTAKV-KYDTSNPDLLQENLRYI---SSVARVIVLICS----SEDARSILLEAEKLGL 221
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   269 TDGSLVFLPFDtiHYALSPGPEALAALANSSQLrRAHDAVLTLTRHcpSEGSVLDS---------LRRAQERRELPSDln 339
Cdd:cd06372  222 MDGEYVFFLLQ--QFEDSFWKEVLNDEKNQVFL-KAYEMVFLIAQS--SYGTYGYSdfrkqvhqkLRRAPFYSSISSE-- 294
                        330
                 ....*....|....*..
gi 4504217   340 lQQVSPLFGTIYDAVFL 356
Cdd:cd06372  295 -DQVSPYSAYLHDAVLL 310
PTKc_Fer cd05085
Catalytic domain of the Protein Tyrosine Kinase, Fer; Protein Tyrosine Kinase (PTK) family; ...
584-796 7.63e-10

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: 60.79  E-value: 7.63e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   584 LQELRHENVALYLGLFLARGAegpaalwegnLAVVSEHCTRGSLQDLLAQR--EIKLDWMFKSSLllDLIKGIRYLHHRG 661
Cdd:cd05085   47 LKQYDHPNIVKLIGVCTQRQP----------IYIVMELVPGGDFLSFLRKKkdELKTKQLVKFSL--DAAAGMAYLESKN 114
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   662 VAHGRLKSRNCIVDGRFVLKITDHGHGRL----LEAQKVLPEPPRAedqlWTAPELLRdpalERRGTLAGDVFSLAIIMQ 737
Cdd:cd05085  115 CIHRDLAARNCLVGENNALKISDFGMSRQeddgVYSSSGLKQIPIK----WTAPEALN----YGRYSSESDVWSFGILLW 186
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 4504217   738 EV----VCrsaPY-AMLELTPEEVVQR--VRSPPPLCrplvsmdqaPVECILLMKQCWAEQPELRP 796
Cdd:cd05085  187 ETfslgVC---PYpGMTNQQAREQVEKgyRMSAPQRC---------PEDIYKIMQRCWDYNPENRP 240
PTKc_Musk cd05050
Catalytic domain of the Protein Tyrosine Kinase, Muscle-specific kinase; PTKs catalyze the ...
645-797 8.54e-10

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: 61.00  E-value: 8.54e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   645 SLLLDLIKGIRYLHHRGVAHGRLKSRNCIVDGRFVLKITDHGHGRLLEAQKVLPE------PPRaedqlWTAPELLrdpa 718
Cdd:cd05050  134 CIAKQVAAGMAYLSERKFVHRDLATRNCLVGENMVVKIADFGLSRNIYSADYYKAsendaiPIR-----WMPPESI---- 204
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   719 LERRGTLAGDVFSLAIIMQEVVCRS-APYamLELTPEEVVQRVRSPPPLCRPlvsmDQAPVECILLMKQCWAEQPELRPS 797
Cdd:cd05050  205 FYNRYTTESDVWAYGVVLWEIFSYGmQPY--YGMAHEEVIYYVRDGNVLSCP----DNCPLELYNLMRLCWSKLPSDRPS 278
STKc_TSSK-like cd14080
Catalytic domain of testis-specific serine/threonine kinases and similar proteins; STKs ...
650-803 1.03e-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: 60.66  E-value: 1.03e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   650 LIKGIRYLHHRGVAHGRLKSRNCIVDGRFVLKITDHGHGRLLeaqkvlpePPRAEDQL---------WTAPELLR----D 716
Cdd:cd14080  111 LALAVQYLHSLDIAHRDLKCENILLDSNNNVKLSDFGFARLC--------PDDDGDVLsktfcgsaaYAAPEILQgipyD 182
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   717 PALerrgtlaGDVFSLAIIMQEVVCRSAPY--AMLELTPEEVVQRVRSPPPLCRPLVSmdqapvECILLMKQCWAEQPEL 794
Cdd:cd14080  183 PKK-------YDIWSLGVILYIMLCGSMPFddSNIKKMLKDQQNRKVRFPSSVKKLSP------ECKDLIDQLLEPDPTK 249

                 ....*....
gi 4504217   795 RPSMDHTFD 803
Cdd:cd14080  250 RATIEEILN 258
PKc_TOPK cd14001
Catalytic domain of the Dual-specificity protein kinase, Lymphokine-activated killer ...
584-807 1.26e-09

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: 60.88  E-value: 1.26e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   584 LQELRHENVALYLGLflargaegpAALWEGNLAVVSEHCTRgSLQDLLAQR-EIKLDWMFKSSLL---LDLIKGIRYLHH 659
Cdd:cd14001   59 LKSLNHPNIVGFRAF---------TKSEDGSLCLAMEYGGK-SLNDLIEERyEAGLGPFPAATILkvaLSIARALEYLHN 128
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   660 -RGVAHGRLKSRNCIVDGRF-VLKITDHGHGRLLEAQKVLPEPPRAE---DQLWTAPEllrdpALERRG--TLAGDVFSL 732
Cdd:cd14001  129 eKKILHGDIKSGNVLIKGDFeSVKLCDFGVSLPLTENLEVDSDPKAQyvgTEPWKAKE-----ALEEGGviTDKADIFAY 203
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   733 AIIMQEVVCRSAPYamLELTPEE-----------------VVQRVRSPPPLcrPLVSMDQAPVECILLMKQCWAEQPELR 795
Cdd:cd14001  204 GLVLWEMMTLSVPH--LNLLDIEdddedesfdedeedeeaYYGTLGTRPAL--NLGELDDSYQKVIELFYACTQEDPKDR 279
                        250
                 ....*....|..
gi 4504217   796 PSMDHTFDLFKN 807
Cdd:cd14001  280 PSAAHIVEALEA 291
PTKc_VEGFR cd05054
Catalytic domain of the Protein Tyrosine Kinases, Vascular Endothelial Growth Factor Receptors; ...
612-797 1.57e-09

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: 60.58  E-value: 1.57e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   612 EGNLAVVSEHCTRGSLQDLL--------AQREIKL---------DWMFKSSLLL-DLI-------KGIRYLHHRGVAHGR 666
Cdd:cd05054   84 GGPLMVIVEFCKFGNLSNYLrskreefvPYRDKGArdveeeeddDELYKEPLTLeDLIcysfqvaRGMEFLASRKCIHRD 163
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   667 LKSRNCIVDGRFVLKITDHGHGRLLEAQkvlPEPPRAEDQL----WTAPELLRDPALerrgTLAGDVFSLAIIMQEVVCR 742
Cdd:cd05054  164 LAARNILLSENNVVKICDFGLARDIYKD---PDYVRKGDARlplkWMAPESIFDKVY----TTQSDVWSFGVLLWEIFSL 236
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 4504217   743 SA-PYAMLELTpEEVVQRVRSPPPLCRPlvsmDQAPVECILLMKQCWAEQPELRPS 797
Cdd:cd05054  237 GAsPYPGVQMD-EEFCRRLKEGTRMRAP----EYTTPEIYQIMLDCWHGEPKERPT 287
PTKc_InsR cd05061
Catalytic domain of the Protein Tyrosine Kinase, Insulin Receptor; PTKs catalyze the transfer ...
649-807 1.83e-09

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: 59.98  E-value: 1.83e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   649 DLIKGIRYLHHRGVAHGRLKSRNCIVDGRFVLKITDHGHGRLLE--------AQKVLPEPpraedqlWTAPELLRDPALe 720
Cdd:cd05061  127 EIADGMAYLNAKKFVHRDLAARNCMVAHDFTVKIGDFGMTRDIYetdyyrkgGKGLLPVR-------WMAPESLKDGVF- 198
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   721 rrgTLAGDVFSLAIIMQEVVCRS-APYAmlELTPEEVVQRVRSPPPLCRPlvsmDQAPVECILLMKQCWAEQPELRPSMD 799
Cdd:cd05061  199 ---TTSSDMWSFGVVLWEITSLAeQPYQ--GLSNEQVLKFVMDGGYLDQP----DNCPERVTDLMRMCWQFNPKMRPTFL 269

                 ....*...
gi 4504217   800 HTFDLFKN 807
Cdd:cd05061  270 EIVNLLKD 277
PTKc_Tyro3 cd05074
Catalytic domain of the Protein Tyrosine Kinase, Tyro3; PTKs catalyze the transfer of the ...
584-808 2.11e-09

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: 59.93  E-value: 2.11e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   584 LQELRHENVALYLGLFLARGAEG--PAALwegnlaVVSEHCTRGSLQD-LLAQR----EIKLDWMFKSSLLLDLIKGIRY 656
Cdd:cd05074   65 MKEFDHPNVIKLIGVSLRSRAKGrlPIPM------VILPFMKHGDLHTfLLMSRigeePFTLPLQTLVRFMIDIASGMEY 138
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   657 LHHRGVAHGRLKSRNCIVDGRFVLKITDHGHGRLLEA-----QKVLPEPPRAedqlWTAPELLRDPALerrgTLAGDVFS 731
Cdd:cd05074  139 LSSKNFIHRDLAARNCMLNENMTVCVADFGLSKKIYSgdyyrQGCASKLPVK----WLALESLADNVY----TTHSDVWA 210
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   732 LAIIMQEVVCR-SAPYAMLEltPEEVV------QRVRSPPplcrplvsmdQAPVECILLMKQCWAEQPELRPSMDHTFDL 804
Cdd:cd05074  211 FGVTMWEIMTRgQTPYAGVE--NSEIYnylikgNRLKQPP----------DCLEDVYELMCQCWSPEPKCRPSFQHLRDQ 278

                 ....
gi 4504217   805 FKNI 808
Cdd:cd05074  279 LELI 282
STKc_LIMK1 cd14221
Catalytic domain of the Serine/Threonine Kinase, LIM domain kinase 1; STKs catalyze the ...
587-742 2.40e-09

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: 59.58  E-value: 2.40e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   587 LRHENVALYLGLFLArgaegpaalwEGNLAVVSEHCTRGSLQDLLAQREIKLDWMFKSSLLLDLIKGIRYLHHRGVAHGR 666
Cdd:cd14221   47 LEHPNVLKFIGVLYK----------DKRLNFITEYIKGGTLRGIIKSMDSHYPWSQRVSFAKDIASGMAYLHSMNIIHRD 116
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   667 LKSRNCIVDGRFVLKITDHGHGRLLEAQKVLPEPPRAE-------------DQLWTAPELLRDPALERRgtlaGDVFSLA 733
Cdd:cd14221  117 LNSHNCLVRENKSVVVADFGLARLMVDEKTQPEGLRSLkkpdrkkrytvvgNPYWMAPEMINGRSYDEK----VDVFSFG 192

                 ....*....
gi 4504217   734 IIMQEVVCR 742
Cdd:cd14221  193 IVLCEIIGR 201
PK_ILK cd14057
Pseudokinase domain of Integrin Linked Kinase; The pseudokinase domain shows similarity to ...
581-799 2.44e-09

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: 59.42  E-value: 2.44e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   581 FSKLQELRHENVALYLGlflargaegpAALWEGNLAVVSEHCTRGSLQDLL-AQREIKLDWMFKSSLLLDLIKGIRYLH- 658
Cdd:cd14057   43 YPRLRIFSHPNVLPVLG----------ACNSPPNLVVISQYMPYGSLYNVLhEGTGVVVDQSQAVKFALDIARGMAFLHt 112
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   659 -HRGVAHGRLKSRNCIVDGRFVLKITdhghgrLLEAQKVLPEPPRAEDQLWTAPELL-RDPalERRGTLAGDVFSLAIIM 736
Cdd:cd14057  113 lEPLIPRHHLNSKHVMIDEDMTARIN------MADVKFSFQEPGKMYNPAWMAPEALqKKP--EDINRRSADMWSFAILL 184
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 4504217   737 QEVVCRSAPYAmlELTPEEVVQRVR------SPPPLCRPLVSMdqapvecilLMKQCWAEQPELRPSMD 799
Cdd:cd14057  185 WELVTREVPFA--DLSNMEIGMKIAleglrvTIPPGISPHMCK---------LMKICMNEDPGKRPKFD 242
PTKc_Btk_Bmx cd05113
Catalytic domain of the Protein Tyrosine Kinases, Bruton's tyrosine kinase and Bone marrow ...
617-797 3.08e-09

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: 59.12  E-value: 3.08e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   617 VVSEHCTRGSLQDLLAQREIKLDWMFKSSLLLDLIKGIRYLHHRGVAHGRLKSRNCIVDGRFVLKITDHGHGR-LLEAQK 695
Cdd:cd05113   76 IITEYMANGCLLNYLREMRKRFQTQQLLEMCKDVCEAMEYLESKQFLHRDLAARNCLVNDQGVVKVSDFGLSRyVLDDEY 155
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   696 VLPE----PPRaedqlWTAPELLrdpaLERRGTLAGDVFSLAIIMQEVVCRSA-PYAMleLTPEEVVQRVRSPPPLCRPl 770
Cdd:cd05113  156 TSSVgskfPVR-----WSPPEVL----MYSKFSSKSDVWAFGVLMWEVYSLGKmPYER--FTNSETVEHVSQGLRLYRP- 223
                        170       180
                 ....*....|....*....|....*..
gi 4504217   771 vsmDQAPVECILLMKQCWAEQPELRPS 797
Cdd:cd05113  224 ---HLASEKVYTIMYSCWHEKADERPT 247
STKc_CDK_like cd07829
Catalytic domain of Cyclin-Dependent protein Kinase-like Serine/Threonine Kinases; STKs ...
560-740 3.20e-09

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: 59.42  E-value: 3.20e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   560 VWLKKFPGDQHI------AIRpatktAFSKLQELRHENVALYLGLFLArgaegpaalwEGNLAVVSEHCTRgSLQDLLAQ 633
Cdd:cd07829   27 VALKKIRLDNEEegipstALR-----EISLLKELKHPNIVKLLDVIHT----------ENKLYLVFEYCDQ-DLKKYLDK 90
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   634 REIKLDWMFKSSLLLDLIKGIRYLHHRGVAHGRLKSRNCIVDGRFVLKITDHGHGRLLEaqkvlpEPPRAEDQ----LW- 708
Cdd:cd07829   91 RPGPLPPNLIKSIMYQLLRGLAYCHSHRILHRDLKPQNLLINRDGVLKLADFGLARAFG------IPLRTYTHevvtLWy 164
                        170       180       190
                 ....*....|....*....|....*....|...
gi 4504217   709 TAPELLrdpaL-ERRGTLAGDVFSLAIIMQEVV 740
Cdd:cd07829  165 RAPEIL----LgSKHYSTAVDIWSVGCIFAELI 193
STKc_C-Raf cd14149
Catalytic domain of the Serine/Threonine Kinase, C-Raf (Rapidly Accelerated Fibrosarcoma) ...
576-749 4.08e-09

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: 58.89  E-value: 4.08e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   576 ATKTAFSKLQELRHENVALYLGLflargaegpaaLWEGNLAVVSEHCTRGSLQDLLAQREIKLDwMFKsslLLDLIK--- 652
Cdd:cd14149   54 AFRNEVAVLRKTRHVNILLFMGY-----------MTKDNLAIVTQWCEGSSLYKHLHVQETKFQ-MFQ---LIDIARqta 118
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   653 -GIRYLHHRGVAHGRLKSRNCIVDGRFVLKITDHG----HGRLLEAQKVlpEPPRAEdQLWTAPELLR----DPAlerrg 723
Cdd:cd14149  119 qGMDYLHAKNIIHRDMKSNNIFLHEGLTVKIGDFGlatvKSRWSGSQQV--EQPTGS-ILWMAPEVIRmqdnNPF----- 190
                        170       180
                 ....*....|....*....|....*.
gi 4504217   724 TLAGDVFSLAIIMQEVVCRSAPYAML 749
Cdd:cd14149  191 SFQSDVYSYGIVLYELMTGELPYSHI 216
STKc_MLK4 cd14146
Catalytic domain of the Serine/Threonine Kinase, Mixed Lineage Kinase 4; STKs catalyze the ...
552-797 4.27e-09

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: 58.90  E-value: 4.27e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   552 IGVYEGDRVWLKKFPGdQHIAIRPA--------TKTAFSKLQE------LRHENVALYLGLflargaegpaALWEGNLAV 617
Cdd:cd14146    2 IGVGGFGKVYRATWKG-QEVAVKAArqdpdediKATAESVRQEaklfsmLRHPNIIKLEGV----------CLEEPNLCL 70
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   618 VSEHCTRGSLQDLLAQR--------------EIKLDWMfkssllLDLIKGIRYLHHRGVA---HGRLKSRNCIV------ 674
Cdd:cd14146   71 VMEFARGGTLNRALAAAnaapgprrarrippHILVNWA------VQIARGMLYLHEEAVVpilHRDLKSSNILLlekieh 144
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   675 --DGRFVLKITDHGHGRllEAQKVlPEPPRAEDQLWTAPELLRDpALERRGTlagDVFSLAIIMQEVVCRSAPYAM---L 749
Cdd:cd14146  145 ddICNKTLKITDFGLAR--EWHRT-TKMSAAGTYAWMAPEVIKS-SLFSKGS---DIWSYGVLLWELLTGEVPYRGidgL 217
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|....*...
gi 4504217   750 ELTPEEVVQRVRSPPPlcrplvsmDQAPVECILLMKQCWAEQPELRPS 797
Cdd:cd14146  218 AVAYGVAVNKLTLPIP--------STCPEPFAKLMKECWEQDPHIRPS 257
PTKc_FGFR2 cd05101
Catalytic domain of the Protein Tyrosine Kinase, Fibroblast Growth Factor Receptor 2; PTKs ...
588-797 5.16e-09

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: 59.26  E-value: 5.16e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   588 RHENVALYLGlflargaegpAALWEGNLAVVSEHCTRGSLQDLL-AQREIKLDWMFKSSLLLD--------------LIK 652
Cdd:cd05101   88 KHKNIINLLG----------ACTQDGPLYVIVEYASKGNLREYLrARRPPGMEYSYDINRVPEeqmtfkdlvsctyqLAR 157
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   653 GIRYLHHRGVAHGRLKSRNCIVDGRFVLKITDHGHGRLLEAQKVLPEPPRAEDQL-WTAPELLRDpaleRRGTLAGDVFS 731
Cdd:cd05101  158 GMEYLASQKCIHRDLAARNVLVTENNVMKIADFGLARDINNIDYYKKTTNGRLPVkWMAPEALFD----RVYTHQSDVWS 233
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 4504217   732 LAIIMQEV-VCRSAPYAMLELtpEEVVQRVRSPPPLCRPLVSMDqapvECILLMKQCWAEQPELRPS 797
Cdd:cd05101  234 FGVLMWEIfTLGGSPYPGIPV--EELFKLLKEGHRMDKPANCTN----ELYMMMRDCWHAVPSQRPT 294
STKc_CDK9_like cd07840
Catalytic domain of Cyclin-Dependent protein Kinase 9-like Serine/Threonine Kinases; STKs ...
557-744 6.40e-09

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: 58.34  E-value: 6.40e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   557 GDRVWLKKFPGDQH------IAIRpatktAFSKLQELRHENVALYLGLFLARGAEGpaalWEGNLAVVSEHCTRgSLQDL 630
Cdd:cd07840   24 GELVALKKIRMENEkegfpiTAIR-----EIKLLQKLDHPNVVRLKEIVTSKGSAK----YKGSIYMVFEYMDH-DLTGL 93
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   631 LAQREIKLDWMFKSSLLLDLIKGIRYLHHRGVAHGRLKSRNCIVDGRFVLKITDHGHGRLLEAQKVLPEPPRAEdQLW-T 709
Cdd:cd07840   94 LDNPEVKFTESQIKCYMKQLLEGLQYLHSNGILHRDIKGSNILINNDGVLKLADFGLARPYTKENNADYTNRVI-TLWyR 172
                        170       180       190
                 ....*....|....*....|....*....|....*.
gi 4504217   710 APELLrdpaL-ERRGTLAGDVFSLAIIMQEVVCRSA 744
Cdd:cd07840  173 PPELL----LgATRYGPEVDMWSVGCILAELFTGKP 204
STKc_TSSK3-like cd14163
Catalytic domain of testis-specific serine/threonine kinase 3 and similar proteins; STKs ...
645-746 7.24e-09

Catalytic domain of testis-specific serine/threonine kinase 3 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. TSSK3 has been reported to be expressed in the interstitial Leydig cells of adult testis. Its mRNA levels is low at birth, increases at puberty, and remains high throughout adulthood. The TSSK3-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: 271065 [Multi-domain]  Cd Length: 257  Bit Score: 58.08  E-value: 7.24e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   645 SLLLDLIKGIRYLHHRGVAHGRLKSRNCIVDGrFVLKITDHGHGrlleaqKVLPEPPRAEDQL------WTAPELLRDPA 718
Cdd:cd14163  105 ALFRQLVEAIRYCHGCGVAHRDLKCENALLQG-FTLKLTDFGFA------KQLPKGGRELSQTfcgstaYAAPEVLQGVP 177
                         90       100
                 ....*....|....*....|....*...
gi 4504217   719 LERRgtlAGDVFSLAIIMQEVVCRSAPY 746
Cdd:cd14163  178 HDSR---KGDIWSMGVVLYVMLCAQLPF 202
PTKc_Met_Ron cd05058
Catalytic domain of the Protein Tyrosine Kinases, Met and Ron; PTKs catalyze the transfer of ...
648-797 7.92e-09

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: 57.87  E-value: 7.92e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   648 LDLIKGIRYLHHRGVAHGRLKSRNCIVDGRFVLKITDHGHGRLLEAQKVLPEPPRAEDQL---WTAPELLRdpalERRGT 724
Cdd:cd05058  105 LQVAKGMEYLASKKFVHRDLAARNCMLDESFTVKVADFGLARDIYDKEYYSVHNHTGAKLpvkWMALESLQ----TQKFT 180
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   725 LAGDVFSLAIIMQEVVCRSA-PYAmlELTPEEVV------QRVRSPPPLCRPLVSmdqapvecilLMKQCWAEQPELRPS 797
Cdd:cd05058  181 TKSDVWSFGVLLWELMTRGApPYP--DVDSFDITvyllqgRRLLQPEYCPDPLYE----------VMLSCWHPKPEMRPT 248
STKc_MLK3 cd14147
Catalytic domain of the Serine/Threonine Kinase, Mixed Lineage Kinase 3; STKs catalyze the ...
610-797 8.52e-09

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: 57.73  E-value: 8.52e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   610 LWEGNLAVVSEHCTRGSLQDLLAQREIK----LDWMfkssllLDLIKGIRYLHHRG---VAHGRLKSRNCIVDGRFV--- 679
Cdd:cd14147   72 LEEPNLCLVMEYAAGGPLSRALAGRRVPphvlVNWA------VQIARGMHYLHCEAlvpVIHRDLKSNNILLLQPIEndd 145
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   680 -----LKITDHGHGRllEAQKVlPEPPRAEDQLWTAPELLRDPALerrgTLAGDVFSLAIIMQEVVCRSAPYA---MLEL 751
Cdd:cd14147  146 mehktLKITDFGLAR--EWHKT-TQMSAAGTYAWMAPEVIKASTF----SKGSDVWSFGVLLWELLTGEVPYRgidCLAV 218
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*.
gi 4504217   752 TPEEVVQRVRSPPPlcrplvsmDQAPVECILLMKQCWAEQPELRPS 797
Cdd:cd14147  219 AYGVAVNKLTLPIP--------STCPEPFAQLMADCWAQDPHRRPD 256
STKc_LIMK2 cd14222
Catalytic domain of the Serine/Threonine Kinase, LIM domain kinase 2; STKs catalyze the ...
584-740 8.76e-09

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: 58.03  E-value: 8.76e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   584 LQELRHENVALYLGLFLArgaegpaalwEGNLAVVSEHCTRGSLQDLLaQREIKLDWMFKSSLLLDLIKGIRYLHHRGVA 663
Cdd:cd14222   44 MRSLDHPNVLKFIGVLYK----------DKRLNLLTEFIEGGTLKDFL-RADDPFPWQQKVSFAKGIASGMAYLHSMSII 112
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   664 HGRLKSRNCIVDGRFVLKITDHGHGRLLEAQKVLPEPPRAEDQ-------------------LWTAPELLRDPALERRgt 724
Cdd:cd14222  113 HRDLNSHNCLIKLDKTVVVADFGLSRLIVEEKKKPPPDKPTTKkrtlrkndrkkrytvvgnpYWMAPEMLNGKSYDEK-- 190
                        170
                 ....*....|....*.
gi 4504217   725 laGDVFSLAIIMQEVV 740
Cdd:cd14222  191 --VDIFSFGIVLCEII 204
PTKc_FAK cd05056
Catalytic domain of the Protein Tyrosine Kinase, Focal Adhesion Kinase; PTKs catalyze the ...
617-799 8.85e-09

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: 57.82  E-value: 8.85e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   617 VVSEHCTRGSLQDLLAQREiklDWMFKSSLLL---DLIKGIRYLHHRGVAHGRLKSRNCIVDGRFVLKITDHGHGRLLEA 693
Cdd:cd05056   83 IVMELAPLGELRSYLQVNK---YSLDLASLILyayQLSTALAYLESKRFVHRDIAARNVLVSSPDCVKLGDFGLSRYMED 159
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   694 QKVLPEPPRAEDQLWTAPELLRdpalERRGTLAGDVFSLAIIMQEVVCRSA-PYAMLEltPEEVVQRV----RSP-PPLC 767
Cdd:cd05056  160 ESYYKASKGKLPIKWMAPESIN----FRRFTSASDVWMFGVCMWEILMLGVkPFQGVK--NNDVIGRIengeRLPmPPNC 233
                        170       180       190
                 ....*....|....*....|....*....|...
gi 4504217   768 RP-LVSmdqapvecilLMKQCWAEQPELRPSMD 799
Cdd:cd05056  234 PPtLYS----------LMTKCWAYDPSKRPRFT 256
STKc_MLK2 cd14148
Catalytic domain of the Serine/Threonine Kinase, Mixed Lineage Kinase 2; STKs catalyze the ...
553-797 8.99e-09

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: 57.69  E-value: 8.99e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   553 GVYEGDRVWLK--KFPGDQHIAIrpatkTAFSKLQE------LRHENVALYLGlflargaegpAALWEGNLAVVSEHCTR 624
Cdd:cd14148   13 GLWRGEEVAVKaaRQDPDEDIAV-----TAENVRQEarlfwmLQHPNIIALRG----------VCLNPPHLCLVMEYARG 77
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   625 GSLQDLLAQREIK----LDWMfkssllLDLIKGIRYLHHRG---VAHGRLKSRNCIVDGRF--------VLKITDHGHGR 689
Cdd:cd14148   78 GALNRALAGKKVPphvlVNWA------VQIARGMNYLHNEAivpIIHRDLKSSNILILEPIenddlsgkTLKITDFGLAR 151
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   690 llEAQKVlPEPPRAEDQLWTAPELLRDPALERrgtlAGDVFSLAIIMQEVVCRSAPYAmlELTPEEVVQRVrSPPPLCRP 769
Cdd:cd14148  152 --EWHKT-TKMSAAGTYAWMAPEVIRLSLFSK----SSDVWSFGVLLWELLTGEVPYR--EIDALAVAYGV-AMNKLTLP 221
                        250       260
                 ....*....|....*....|....*...
gi 4504217   770 LVSMDQAPVECILlmKQCWAEQPELRPS 797
Cdd:cd14148  222 IPSTCPEPFARLL--EECWDPDPHGRPD 247
STKc_AMPK-like cd14003
Catalytic domain of AMP-activated protein kinase-like Serine/Threonine Kinases; STKs catalyze ...
584-799 9.05e-09

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: 57.53  E-value: 9.05e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   584 LQELRHENVALYLGLFLArgaegpaalwEGNLAVVSEHCTRGSLQDLLAQREiKLD-----WMFKSsllldLIKGIRYLH 658
Cdd:cd14003   53 MKLLNHPNIIKLYEVIET----------ENKIYLVMEYASGGELFDYIVNNG-RLSedearRFFQQ-----LISAVDYCH 116
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   659 HRGVAHGRLKSRNCIVDGRFVLKITDHGHGRLLEAQKVLPE----PPRAedqlwtAPELLRDPalERRGTLAgDVFSLAI 734
Cdd:cd14003  117 SNGIVHRDLKLENILLDKNGNLKIIDFGLSNEFRGGSLLKTfcgtPAYA------APEVLLGR--KYDGPKA-DVWSLGV 187
                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 4504217   735 IMQEVVCRSAPY------AMLELTPEEVVQRVRSPPPlcrplvsmdqapvECILLMKQCWAEQPELRPSMD 799
Cdd:cd14003  188 ILYAMLTGYLPFdddndsKLFRKILKGKYPIPSHLSP-------------DARDLIRRMLVVDPSKRITIE 245
STKc_MEKK1_plant cd06632
Catalytic domain of the Serine/Threonine Kinase, Plant Mitogen-Activated Protein (MAP) ...
584-802 9.16e-09

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: 57.80  E-value: 9.16e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   584 LQELRHENVALYLGlflargaegpAALWEGNLAVVSEHCTRGSLQDLLaQREIKLDWMFKSSLLLDLIKGIRYLHHRGVA 663
Cdd:cd06632   56 LSKLRHPNIVQYYG----------TEREEDNLYIFLEYVPGGSIHKLL-QRYGAFEEPVIRLYTRQILSGLAYLHSRNTV 124
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   664 HGRLKSRNCIVDGRFVLKITDHGHGRLLEAQ---KVLPEPPraedqLWTAPELLRdPALERRGtLAGDVFSLAIIMQEVV 740
Cdd:cd06632  125 HRDIKGANILVDTNGVVKLADFGMAKHVEAFsfaKSFKGSP-----YWMAPEVIM-QKNSGYG-LAVDIWSLGCTVLEMA 197
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 4504217   741 CRSAPYAmlELTPEEVVQRVRSPPPLcrPLVSMDQAPvECILLMKQCWAEQPELRPS----MDHTF 802
Cdd:cd06632  198 TGKPPWS--QYEGVAAIFKIGNSGEL--PPIPDHLSP-DAKDFIRLCLQRDPEDRPTasqlLEHPF 258
STKc_myosinIIIB_N cd06639
N-terminal Catalytic domain of the Serine/Threonine Kinase, Class IIIB myosin; STKs catalyze ...
581-803 9.74e-09

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: 58.08  E-value: 9.74e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   581 FSKLQEL-RHENVALYLGLFLARGAEGPAALWegnlaVVSEHCTRGSLQDL---LAQREIKLDWMFKSSLLLDLIKGIRY 656
Cdd:cd06639   69 YNILRSLpNHPNVVKFYGMFYKADQYVGGQLW-----LVLELCNGGSVTELvkgLLKCGQRLDEAMISYILYGALLGLQH 143
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   657 LHHRGVAHGRLKSRNCIVDGRFVLKITDHGHGRLLEAQKvLPEPPRAEDQLWTAPELLR-----DPALERRgtlaGDVFS 731
Cdd:cd06639  144 LHNNRIIHRDVKGNNILLTTEGGVKLVDFGVSAQLTSAR-LRRNTSVGTPFWMAPEVIAceqqyDYSYDAR----CDVWS 218
                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 4504217   732 LAIIMQEVVCRSAPyaMLELTPEEVVQRV-RSPPPlcrPLVSMDQAPVECILLMKQCWAEQPELRPSMDHTFD 803
Cdd:cd06639  219 LGITAIELADGDPP--LFDMHPVKALFKIpRNPPP---TLLNPEKWCRGFSHFISQCLIKDFEKRPSVTHLLE 286
PHA02988 PHA02988
hypothetical protein; Provisional
535-746 1.18e-08

hypothetical protein; Provisional


Pssm-ID: 165291 [Multi-domain]  Cd Length: 283  Bit Score: 57.44  E-value: 1.18e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217    535 SMSDIRSGPSQHLDSPNI-------------GVYEGDRVWLKKFPGDQ--HIAIRPATKTAFSKLQELRHENVALYLGLF 599
Cdd:PHA02988    8 YINDIKCIESDDIDKYTSvlikendqnsiykGIFNNKEVIIRTFKKFHkgHKVLIDITENEIKNLRRIDSNNILKIYGFI 87
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217    600 LARGAEGPaalwegNLAVVSEHCTRGSLQDLLaQREIKLDWMFKSSLLLDLIKGIRYLH-HRGVAHGRLKSRNCIVDGRF 678
Cdd:PHA02988   88 IDIVDDLP------RLSLILEYCTRGYLREVL-DKEKDLSFKTKLDMAIDCCKGLYNLYkYTNKPYKNLTSVSFLVTENY 160
                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217    679 VLKITDHGhgrlLEaqKVLPEPP--RAEDQLWTAPELLRDPALERrgTLAGDVFSLAIIMQEVVCRSAPY 746
Cdd:PHA02988  161 KLKIICHG----LE--KILSSPPfkNVNFMVYFSYKMLNDIFSEY--TIKDDIYSLGVVLWEIFTGKIPF 222
STKc_MLK1 cd14145
Catalytic domain of the Serine/Threonine Kinase, Mixed Lineage Kinase 1; STKs catalyze the ...
587-808 1.27e-08

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: 57.36  E-value: 1.27e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   587 LRHENVALYLGLflargaegpaALWEGNLAVVSEHCTRGSLQDLLAQREIKLDWMFKSSLllDLIKGIRYLHHRG---VA 663
Cdd:cd14145   62 LKHPNIIALRGV----------CLKEPNLCLVMEFARGGPLNRVLSGKRIPPDILVNWAV--QIARGMNYLHCEAivpVI 129
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   664 HGRLKSRNCIVDGRF--------VLKITDHGHGRLLEAQKVLPEpprAEDQLWTAPELLRDPALERrgtlAGDVFSLAII 735
Cdd:cd14145  130 HRDLKSSNILILEKVengdlsnkILKITDFGLAREWHRTTKMSA---AGTYAWMAPEVIRSSMFSK----GSDVWSYGVL 202
                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 4504217   736 MQEVVCRSAPYAM---LELTPEEVVQRVRSPPPlcrplvsmDQAPVECILLMKQCWAEQPELRPSMDHTFDLFKNI 808
Cdd:cd14145  203 LWELLTGEVPFRGidgLAVAYGVAMNKLSLPIP--------STCPEPFARLMEDCWNPDPHSRPPFTNILDQLTAI 270
PTKc_TAM cd05035
Catalytic Domain of TAM (Tyro3, Axl, Mer) Protein Tyrosine Kinases; PTKs catalyze the transfer ...
584-808 1.34e-08

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: 57.16  E-value: 1.34e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   584 LQELRHENVALYLGL-FLARGAEGPAALwegnlAVVSEHCTRGSLQD-LLAQREIKLDWMFKSSLLL----DLIKGIRYL 657
Cdd:cd05035   55 MKDFDHPNVMRLIGVcFTASDLNKPPSP-----MVILPFMKHGDLHSyLLYSRLGGLPEKLPLQTLLkfmvDIAKGMEYL 129
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   658 HHRGVAHGRLKSRNCIVDGRFVLKITDHGHGRLLEA-----QKVLPEPPRAedqlWTAPELLRDpaleRRGTLAGDVFSL 732
Cdd:cd05035  130 SNRNFIHRDLAARNCMLDENMTVCVADFGLSRKIYSgdyyrQGRISKMPVK----WIALESLAD----NVYTSKSDVWSF 201
                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 4504217   733 AIIMQEVVCRS-APYAMLEltPEEVVQRVRSPPPLCRPLVSMDqapvECILLMKQCWAEQPELRPSMDHTFDLFKNI 808
Cdd:cd05035  202 GVTMWEIATRGqTPYPGVE--NHEIYDYLRNGNRLKQPEDCLD----EVYFLMYFCWTVDPKDRPTFTKLREVLENI 272
PTKc_RET cd05045
Catalytic domain of the Protein Tyrosine Kinase, REarranged during Transfection protein; PTKs ...
562-810 1.40e-08

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: 57.67  E-value: 1.40e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   562 LKKFPGDQHIAIRPATKTA-----------FSKLQELRHENVALYLGlflargaegpAALWEGNLAVVSEHCTRGSLQDL 630
Cdd:cd05045   24 LKGRAGYTTVAVKMLKENAssselrdllseFNLLKQVNHPHVIKLYG----------ACSQDGPLLLIVEYAKYGSLRSF 93
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   631 LAQRE------IKLDWMFKSSLLL----------DLI-------KGIRYLHHRGVAHGRLKSRNCIV-DGRfVLKITDHG 686
Cdd:cd05045   94 LRESRkvgpsyLGSDGNRNSSYLDnpderaltmgDLIsfawqisRGMQYLAEMKLVHRDLAARNVLVaEGR-KMKISDFG 172
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   687 HGR-LLEAQKVLPeppRAEDQL---WTAPELLRDPALerrgTLAGDVFSLAIIMQEVVCRSA-PYAmlELTPEEVVQRVR 761
Cdd:cd05045  173 LSRdVYEEDSYVK---RSKGRIpvkWMAIESLFDHIY----TTQSDVWSFGVLLWEIVTLGGnPYP--GIAPERLFNLLK 243
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|....*....
gi 4504217   762 SPPPLCRPlvsmDQAPVECILLMKQCWAEQPELRPSmdhtfdlFKNINK 810
Cdd:cd05045  244 TGYRMERP----ENCSEEMYNLMLTCWKQEPDKRPT-------FADISK 281
PTKc_FGFR3 cd05100
Catalytic domain of the Protein Tyrosine Kinase, Fibroblast Growth Factor Receptor 3; PTKs ...
588-833 1.47e-08

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: 57.72  E-value: 1.47e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   588 RHENVALYLGlflargaegpAALWEGNLAVVSEHCTRGSLQDLL-AQREIKLDWMFKSSLL-------LDLI-------K 652
Cdd:cd05100   76 KHKNIINLLG----------ACTQDGPLYVLVEYASKGNLREYLrARRPPGMDYSFDTCKLpeeqltfKDLVscayqvaR 145
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   653 GIRYLHHRGVAHGRLKSRNCIVDGRFVLKITDHGHGRLLEAQKVLPEPPRAEDQL-WTAPELLRDpaleRRGTLAGDVFS 731
Cdd:cd05100  146 GMEYLASQKCIHRDLAARNVLVTEDNVMKIADFGLARDVHNIDYYKKTTNGRLPVkWMAPEALFD----RVYTHQSDVWS 221
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   732 LAIIMQEVVCRS-APYAMLELtpEEVVQRVRSPPPLCRPLvsmdQAPVECILLMKQCWAEQPELRPSMDHtfdLFKNINK 810
Cdd:cd05100  222 FGVLLWEIFTLGgSPYPGIPV--EELFKLLKEGHRMDKPA----NCTHELYMIMRECWHAVPSQRPTFKQ---LVEDLDR 292
                        250       260
                 ....*....|....*....|....*.
gi 4504217   811 GRKTNIIDSMLRM---LEQYSSNLED 833
Cdd:cd05100  293 VLTVTSTDEYLDLsvpFEQYSPGCPD 318
STKc_LRRK2 cd14068
Catalytic domain of the Serine/Threonine Kinase, Leucine-Rich Repeat Kinase 2; STKs catalyze ...
553-805 1.81e-08

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: 56.50  E-value: 1.81e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   553 GVYEGDRVWLKKFpgDQHIAIRpATKTAFSKLQELRHENVALYLglflargAEGPAALwegnlAVVSEHCTRGSLQDLLA 632
Cdd:cd14068   13 AVYRGEDVAVKIF--NKHTSFR-LLRQELVVLSHLHHPSLVALL-------AAGTAPR-----MLVMELAPKGSLDALLQ 77
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   633 QREIKLDWMFKSSLLLDLIKGIRYLHHRGVAHGRLKSRNCIV-----DGRFVLKITDHGHGRLLEAQKVLPEPPRAEdql 707
Cdd:cd14068   78 QDNASLTRTLQHRIALHVADGLRYLHSAMIIYRDLKPHNVLLftlypNCAIIAKIADYGIAQYCCRMGIKTSEGTPG--- 154
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   708 WTAPELLRDPALERRgtlAGDVFSLAIIMQEVVCRSAPYAMLELTPEE----VVQRvRSPPPL----CRPLVSMDQapve 779
Cdd:cd14068  155 FRAPEVARGNVIYNQ---QADVYSFGLLLYDILTCGERIVEGLKFPNEfdelAIQG-KLPDPVkeygCAPWPGVEA---- 226
                        250       260
                 ....*....|....*....|....*.
gi 4504217   780 cilLMKQCWAEQPELRPSMDHTFDLF 805
Cdd:cd14068  227 ---LIKDCLKENPQCRPTSAQVFDIL 249
PTKc_Syk_like cd05060
Catalytic domain of Spleen Tyrosine Kinase-like Protein Tyrosine Kinases; PTKs catalyze the ...
615-808 2.07e-08

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: 56.59  E-value: 2.07e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   615 LAVVSEHCTRGSLQDLLAQR------EIKLdWMFKSSLlldlikGIRYLHHRGVAHGRLKSRNCIVDGRFVLKITDHGHG 688
Cdd:cd05060   70 LMLVMELAPLGPLLKYLKKRreipvsDLKE-LAHQVAM------GMAYLESKHFVHRDLAARNVLLVNRHQAKISDFGMS 142
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   689 RLLEAQKvlpEPPRAEDQ-----LWTAPELLRdpalERRGTLAGDVFSLAIIMQEVVCRSA-PYAmlELTPEEVVQRVRS 762
Cdd:cd05060  143 RALGAGS---DYYRATTAgrwplKWYAPECIN----YGKFSSKSDVWSYGVTLWEAFSYGAkPYG--EMKGPEVIAMLES 213
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*.
gi 4504217   763 PPPLCRPlvsmDQAPVECILLMKQCWAEQPELRPSMDHTFDLFKNI 808
Cdd:cd05060  214 GERLPRP----EECPQEIYSIMLSCWKYRPEDRPTFSELESTFRRD 255
PTKc_Ack_like cd05040
Catalytic domain of the Protein Tyrosine Kinase, Activated Cdc42-associated kinase; PTKs ...
584-797 2.14e-08

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: 56.58  E-value: 2.14e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   584 LQELRHEN-VALYlGLFLARgaegpaalwegNLAVVSEHCTRGSLQDLLAQReikldwmfKSSLLLDLI--------KGI 654
Cdd:cd05040   52 MHSLDHPNlIRLY-GVVLSS-----------PLMMVTELAPLGSLLDRLRKD--------QGHFLISTLcdyavqiaNGM 111
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   655 RYLHHRGVAHGRLKSRNCIVDGRFVLKITDHGHGRLL---------EAQKVLPEPpraedqlWTAPELLRdpalERRGTL 725
Cdd:cd05040  112 AYLESKRFIHRDLAARNILLASKDKVKIGDFGLMRALpqnedhyvmQEHRKVPFA-------WCAPESLK----TRKFSH 180
                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 4504217   726 AGDVFSLAIIMQEVVCRSA-PYamLELTPEEVVQRV-----RSPPPlcrplvsmDQAPVECILLMKQCWAEQPELRPS 797
Cdd:cd05040  181 ASDVWMFGVTLWEMFTYGEePW--LGLNGSQILEKIdkegeRLERP--------DDCPQDIYNVMLQCWAHKPADRPT 248
STKc_Cdc7_like cd06627
Catalytic domain of Cell division control protein 7-like Serine/Threonine Kinases; STKs ...
584-797 2.32e-08

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: 56.46  E-value: 2.32e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   584 LQELRHENVALYLGLFLARGaegpaalwegNLAVVSEHCTRGSLQDLLAQREI---KLDWMFKSSLLldliKGIRYLHHR 660
Cdd:cd06627   53 LKKLNHPNIVKYIGSVKTKD----------SLYIILEYVENGSLASIIKKFGKfpeSLVAVYIYQVL----EGLAYLHEQ 118
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   661 GVAHGRLKSRNCIVDGRFVLKITDHGhgrllEAQKVLPEPPRAEDQL----WTAPEllrdpALERRG-TLAGDVFSLAII 735
Cdd:cd06627  119 GVIHRDIKGANILTTKDGLVKLADFG-----VATKLNEVEKDENSVVgtpyWMAPE-----VIEMSGvTTASDIWSVGCT 188
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 4504217   736 MQEVVCRSAPYAmlELTPEEVVQR-VRSPPPlcrPLVSMDQApvECILLMKQCWAEQPELRPS 797
Cdd:cd06627  189 VIELLTGNPPYY--DLQPMAALFRiVQDDHP---PLPENISP--ELRDFLLQCFQKDPTLRPS 244
STKc_MST3_like cd06609
Catalytic domain of Mammalian Ste20-like protein kinase 3-like Serine/Threonine Kinases; STKs ...
584-827 2.62e-08

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: 56.48  E-value: 2.62e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   584 LQELRHENVALYLGLFLARgaegpAALWegnlaVVSEHCTRGSLQDLLaqREIKLDWMFKSSLLLDLIKGIRYLHHRGVA 663
Cdd:cd06609   53 LSQCDSPYITKYYGSFLKG-----SKLW-----IIMEYCGGGSVLDLL--KPGPLDETYIAFILREVLLGLEYLHSEGKI 120
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   664 HGRLKSRNCIVDGRFVLKITDHG-HGRLLEAQKVL------PeppraedqLWTAPELLRDPALErrgtLAGDVFSLAIIM 736
Cdd:cd06609  121 HRDIKAANILLSEEGDVKLADFGvSGQLTSTMSKRntfvgtP--------FWMAPEVIKQSGYD----EKADIWSLGITA 188
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   737 QEVVCRSAPYAmlELTPEEVVQRV--RSPPPLCRPLVSMD-QAPVECillmkqCWAEQPELRPS----MDHTFdlfknIN 809
Cdd:cd06609  189 IELAKGEPPLS--DLHPMRVLFLIpkNNPPSLEGNKFSKPfKDFVEL------CLNKDPKERPSakelLKHKF-----IK 255
                        250
                 ....*....|....*...
gi 4504217   810 KGRKTNIIDSMLRMLEQY 827
Cdd:cd06609  256 KAKKTSYLTLLIERIKKW 273
STKc_LKB1_CaMKK cd14008
Catalytic domain of the Serine/Threonine kinases, Liver Kinase B1, Calmodulin Dependent ...
584-799 2.82e-08

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: 56.41  E-value: 2.82e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   584 LQELRHENVA-------------LYLGLFLARGaeGPAALWEGNlavvsehCTRGSLQDLLAQReikldwMFKsslllDL 650
Cdd:cd14008   58 MKKLDHPNIVrlyeviddpesdkLYLVLEYCEG--GPVMELDSG-------DRVPPLPEETARK------YFR-----DL 117
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   651 IKGIRYLHHRGVAHGRLKSRNCIVDGRFVLKITDHGHGRLLEAQKVLPEP----PraedqLWTAPELLRDPALERRGtLA 726
Cdd:cd14008  118 VLGLEYLHENGIVHRDIKPENLLLTADGTVKISDFGVSEMFEDGNDTLQKtagtP-----AFLAPELCDGDSKTYSG-KA 191
                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 4504217   727 GDVFSLAIIMQEVVCRSAP-YAMLELTPEEVVQRVRSPPPLCRPLvsmdqaPVECILLMKQCWAEQPELRPSMD 799
Cdd:cd14008  192 ADIWALGVTLYCLVFGRLPfNGDNILELYEAIQNQNDEFPIPPEL------SPELKDLLRRMLEKDPEKRITLK 259
PTKc_VEGFR2 cd05103
Catalytic domain of the Protein Tyrosine Kinase, Vascular Endothelial Growth Factor Receptor 2; ...
626-797 3.02e-08

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: 56.91  E-value: 3.02e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   626 SLQDLLAQREIKLDwMFKSSLLL-DLI-------KGIRYLHHRGVAHGRLKSRNCIVDGRFVLKITDHGHGRLLEAQkvl 697
Cdd:cd05103  157 SLSDVEEEEAGQED-LYKDFLTLeDLIcysfqvaKGMEFLASRKCIHRDLAARNILLSENNVVKICDFGLARDIYKD--- 232
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   698 PEPPRAEDQL----WTAPELLRDpaleRRGTLAGDVFSLAIIMQEVVCRSA-PYAMLELTpEEVVQRVRSPPPLCRPlvs 772
Cdd:cd05103  233 PDYVRKGDARlplkWMAPETIFD----RVYTIQSDVWSFGVLLWEIFSLGAsPYPGVKID-EEFCRRLKEGTRMRAP--- 304
                        170       180
                 ....*....|....*....|....*
gi 4504217   773 mDQAPVECILLMKQCWAEQPELRPS 797
Cdd:cd05103  305 -DYTTPEMYQTMLDCWHGEPSQRPT 328
PTKc_Ror2 cd05091
Catalytic domain of the Protein Tyrosine Kinase, Receptor tyrosine kinase-like Orphan Receptor ...
566-814 3.26e-08

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: 56.18  E-value: 3.26e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   566 PGDQH--IAIRPATKTAFSKLQE-----------LRHENVALYLGLFLArgaegpaalwEGNLAVVSEHCTRGSLQDLLA 632
Cdd:cd05091   32 PGEQTqaVAIKTLKDKAEGPLREefrheamlrsrLQHPNIVCLLGVVTK----------EQPMSMIFSYCSHGDLHEFLV 101
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   633 QRE-------IKLDWMFKSSL--------LLDLIKGIRYLHHRGVAHGRLKSRNCIVDGRFVLKITDHGHGRLLEAQ--- 694
Cdd:cd05091  102 MRSphsdvgsTDDDKTVKSTLepadflhiVTQIAAGMEYLSSHHVVHKDLATRNVLVFDKLNVKISDLGLFREVYAAdyy 181
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   695 KVL---PEPPRaedqlWTAPELLrdpaLERRGTLAGDVFSLAIIMQEVVCRS-APYAmlELTPEEVVQRVRSPPPLCRPl 770
Cdd:cd05091  182 KLMgnsLLPIR-----WMSPEAI----MYGKFSIDSDIWSYGVVLWEVFSYGlQPYC--GYSNQDVIEMIRNRQVLPCP- 249
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|....
gi 4504217   771 vsmDQAPVECILLMKQCWAEQPELRPSmdhtfdlFKNINKGRKT 814
Cdd:cd05091  250 ---DDCPAWVYTLMLECWNEFPSRRPR-------FKDIHSRLRT 283
PTKc_IGF-1R cd05062
Catalytic domain of the Protein Tyrosine Kinase, Insulin-like Growth Factor-1 Receptor; PTKs ...
617-797 3.81e-08

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: 56.19  E-value: 3.81e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   617 VVSEHCTRGSLQDLLaqREIKLDWMFKSSLLLDLIK-----------GIRYLHHRGVAHGRLKSRNCIVDGRFVLKITDH 685
Cdd:cd05062   86 VIMELMTRGDLKSYL--RSLRPEMENNPVQAPPSLKkmiqmageiadGMAYLNANKFVHRDLAARNCMVAEDFTVKIGDF 163
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   686 GHGR-LLEAQKVLPEPPRAEDQLWTAPELLRDPALerrgTLAGDVFSLAIIMQEVVCRS-APYAmlELTPEEVVQRVRSP 763
Cdd:cd05062  164 GMTRdIYETDYYRKGGKGLLPVRWMSPESLKDGVF----TTYSDVWSFGVVLWEIATLAeQPYQ--GMSNEQVLRFVMEG 237
                        170       180       190
                 ....*....|....*....|....*....|....
gi 4504217   764 PPLCRPlvsmDQAPVECILLMKQCWAEQPELRPS 797
Cdd:cd05062  238 GLLDKP----DNCPDMLFELMRMCWQYNPKMRPS 267
PTKc_Tie cd05047
Catalytic domain of Tie Protein Tyrosine Kinases; PTKs catalyze the transfer of the ...
613-797 3.82e-08

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: 55.82  E-value: 3.82e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   613 GNLAVVSEHCTRGSLQDLLAQ-REIKLDWMF----------KSSLLL----DLIKGIRYLHHRGVAHGRLKSRNCIVDGR 677
Cdd:cd05047   69 GYLYLAIEYAPHGNLLDFLRKsRVLETDPAFaianstastlSSQQLLhfaaDVARGMDYLSQKQFIHRDLAARNILVGEN 148
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   678 FVLKITDHG--HGRLLEAQKVLPEPPRAedqlWTAPELLRDPALerrgTLAGDVFSLAIIMQEVVCRSA-PYAmlELTPE 754
Cdd:cd05047  149 YVAKIADFGlsRGQEVYVKKTMGRLPVR----WMAIESLNYSVY----TTNSDVWSYGVLLWEIVSLGGtPYC--GMTCA 218
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|...
gi 4504217   755 EVVQRVRSPPPLCRPLVSMDqapvECILLMKQCWAEQPELRPS 797
Cdd:cd05047  219 ELYEKLPQGYRLEKPLNCDD----EVYDLMRQCWREKPYERPS 257
STKc_CDKL cd07833
Catalytic domain of Cyclin-Dependent protein Kinase Like Serine/Threonine Kinases; STKs ...
557-714 3.83e-08

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: 56.17  E-value: 3.83e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   557 GDRVWLKKF---PGDQHIairpaTKTAF---SKLQELRHENVALYLGLFLargaegpaalWEGNLAVVSEHCTRGSLQDL 630
Cdd:cd07833   26 GEIVAIKKFkesEDDEDV-----KKTALrevKVLRQLRHENIVNLKEAFR----------RKGRLYLVFEYVERTLLELL 90
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   631 LAQREiKLDWMFKSSLLLDLIKGIRYLHHRGVAHGRLKSRNCIVDGRFVLKITDHGHGRLLEAQKVLPEPPRAEDQLWTA 710
Cdd:cd07833   91 EASPG-GLPPDAVRSYIWQLLQAIAYCHSHNIIHRDIKPENILVSESGVLKLCDFGFARALTARPASPLTDYVATRWYRA 169

                 ....
gi 4504217   711 PELL 714
Cdd:cd07833  170 PELL 173
PTKc_EGFR_like cd05057
Catalytic domain of Epidermal Growth Factor Receptor-like Protein Tyrosine Kinases; PTKs ...
615-797 5.13e-08

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: 55.50  E-value: 5.13e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   615 LAVVSEHCTRGSLQDLLAQREIKLDwmfkSSLLLD----LIKGIRYLHHRGVAHGRLKSRNCIVDGRFVLKITDHGHGRL 690
Cdd:cd05057   83 VQLITQLMPLGCLLDYVRNHRDNIG----SQLLLNwcvqIAKGMSYLEEKRLVHRDLAARNVLVKTPNHVKITDFGLAKL 158
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   691 LEaqkvlpeppRAEDQL----------WTAPELLRdpalERRGTLAGDVFSLAIIMQEVVCRSA-PYAMLELT--PEEVV 757
Cdd:cd05057  159 LD---------VDEKEYhaeggkvpikWMALESIQ----YRIYTHKSDVWSYGVTVWELMTFGAkPYEGIPAVeiPDLLE 225
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|.
gi 4504217   758 QRVRSP-PPLCRPLVSMdqapvecilLMKQCWAEQPELRPS 797
Cdd:cd05057  226 KGERLPqPPICTIDVYM---------VLVKCWMIDAESRPT 257
PTKc_FGFR1 cd05098
Catalytic domain of the Protein Tyrosine Kinase, Fibroblast Growth Factor Receptor 1; PTKs ...
588-800 5.92e-08

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: 55.79  E-value: 5.92e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   588 RHENVALYLGlflargaegpAALWEGNLAVVSEHCTRGSLQDLL-AQREIKLDWMFKSSL-------LLDLI-------K 652
Cdd:cd05098   77 KHKNIINLLG----------ACTQDGPLYVIVEYASKGNLREYLqARRPPGMEYCYNPSHnpeeqlsSKDLVscayqvaR 146
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   653 GIRYLHHRGVAHGRLKSRNCIVDGRFVLKITDHGHGRLLEAQKVLPEPPRAEDQL-WTAPELLRDpaleRRGTLAGDVFS 731
Cdd:cd05098  147 GMEYLASKKCIHRDLAARNVLVTEDNVMKIADFGLARDIHHIDYYKKTTNGRLPVkWMAPEALFD----RIYTHQSDVWS 222
                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   732 LAIIMQEV-VCRSAPYAMLELtpEEVVQRVRSPPPLCRPLVSMDqapvECILLMKQCWAEQPELRPSMDH 800
Cdd:cd05098  223 FGVLLWEIfTLGGSPYPGVPV--EELFKLLKEGHRMDKPSNCTN----ELYMMMRDCWHAVPSQRPTFKQ 286
PTK_CCK4 cd05046
Pseudokinase domain of the Protein Tyrosine Kinase, Colon Carcinoma Kinase 4; CCK4, also ...
581-799 6.51e-08

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: 55.16  E-value: 6.51e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   581 FSKLQelrHENVALYLGLflARGAEgPAALwegnlavVSEHCTRGSLQDLLAQREIKLDWMF--------KSSLLLDLIK 652
Cdd:cd05046   62 FRKLS---HKNVVRLLGL--CREAE-PHYM-------ILEYTDLGDLKQFLRATKSKDEKLKppplstkqKVALCTQIAL 128
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   653 GIRYLHHRGVAHGRLKSRNCIVDGRFVLKITDHGHGR--------LLEAQKVlpePPRaedqlWTAPELLRDPALerrgT 724
Cdd:cd05046  129 GMDHLSNARFVHRDLAARNCLVSSQREVKVSLLSLSKdvynseyyKLRNALI---PLR-----WLAPEAVQEDDF----S 196
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   725 LAGDVFSLAIIMQEVVCRSA-PYAmlELTPEEVVQRVRS-----PPPlcrplvsmDQAPVECILLMKQCWAEQPELRPSM 798
Cdd:cd05046  197 TKSDVWSFGVLMWEVFTQGElPFY--GLSDEEVLNRLQAgklelPVP--------EGCPSRLYKLMTRCWAVNPKDRPSF 266

                 .
gi 4504217   799 D 799
Cdd:cd05046  267 S 267
STKc_ULK3 cd14121
Catalytic domain of the Serine/Threonine kinase, Unc-51-like kinase 3; STKs catalyze the ...
584-803 7.12e-08

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: 54.99  E-value: 7.12e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   584 LQELRHENVALYLGLFlargaegpaalW-EGNLAVVSEHCTRGSLQDLLAQREIKLDWMFKSsLLLDLIKGIRYLHHRGV 662
Cdd:cd14121   49 LKKLKHPHIVELKDFQ-----------WdEEHIYLIMEYCSGGDLSRFIRSRRTLPESTVRR-FLQQLASALQFLREHNI 116
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   663 AHGRLKSRNCIVDGRF--VLKITDHG---HGRLLEAQKVLPEPPraedqLWTAPELLRDPALERRgtlaGDVFSLAIIMQ 737
Cdd:cd14121  117 SHMDLKPQNLLLSSRYnpVLKLADFGfaqHLKPNDEAHSLRGSP-----LYMAPEMILKKKYDAR----VDLWSVGVILY 187
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 4504217   738 EVVCRSAPYAmlELTPEEVVQRVRSPPPL---CRPLVSMDqapveCILLMKQCWAEQPELRPSMDHTFD 803
Cdd:cd14121  188 ECLFGRAPFA--SRSFEELEEKIRSSKPIeipTRPELSAD-----CRDLLLRLLQRDPDRRISFEEFFA 249
STKc_B-Raf cd14151
Catalytic domain of the Serine/Threonine Kinase, B-Raf (Rapidly Accelerated Fibrosarcoma) ...
576-797 7.53e-08

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: 55.07  E-value: 7.53e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   576 ATKTAFSKLQELRHENVALYLGLflargAEGPaalwegNLAVVSEHCTRGSLQDLLAQREIKLDWMFKSSLLLDLIKGIR 655
Cdd:cd14151   50 AFKNEVGVLRKTRHVNILLFMGY-----STKP------QLAIVTQWCEGSSLYHHLHIIETKFEMIKLIDIARQTAQGMD 118
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   656 YLHHRGVAHGRLKSRNCIVDGRFVLKITDHGhgrlLEAQKVLPEPPRAEDQ-----LWTAPELLRdpaLERRG--TLAGD 728
Cdd:cd14151  119 YLHAKSIIHRDLKSNNIFLHEDLTVKIGDFG----LATVKSRWSGSHQFEQlsgsiLWMAPEVIR---MQDKNpySFQSD 191
                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 4504217   729 VFSLAIIMQEVVCRSAPYAMLELTPE--EVVQRVRSPPPLCRplvSMDQAPVECILLMKQCWAEQPELRPS 797
Cdd:cd14151  192 VYAFGIVLYELMTGQLPYSNINNRDQiiFMVGRGYLSPDLSK---VRSNCPKAMKRLMAECLKKKRDERPL 259
PTKc_PDGFR_alpha cd05105
Catalytic domain of the Protein Tyrosine Kinase, Platelet Derived Growth Factor Receptor alpha; ...
639-808 8.36e-08

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: 55.80  E-value: 8.36e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   639 DWMFKSSLLLDLI-------KGIRYLHHRGVAHGRLKSRNCIVDGRFVLKITDHGHGR-LLEAQKVLPEPPRAEDQLWTA 710
Cdd:cd05105  228 DDGSEGLTTLDLLsftyqvaRGMEFLASKNCVHRDLAARNVLLAQGKIVKICDFGLARdIMHDSNYVSKGSTFLPVKWMA 307
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   711 PELLRDPALerrgTLAGDVFSLAIIMQEVVCRSA-PYAMLeLTPEEVVQRVRSPPPLCRPlvsmDQAPVECILLMKQCWA 789
Cdd:cd05105  308 PESIFDNLY----TTLSDVWSYGILLWEIFSLGGtPYPGM-IVDSTFYNKIKSGYRMAKP----DHATQEVYDIMVKCWN 378
                        170
                 ....*....|....*....
gi 4504217   790 EQPELRPSMDHTFDLFKNI 808
Cdd:cd05105  379 SEPEKRPSFLHLSDIVESL 397
PK_STRAD cd08216
Pseudokinase domain of STE20-related kinase adapter protein; The pseudokinase domain shows ...
563-818 1.03e-07

Pseudokinase domain of STE20-related kinase adapter protein; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. STRAD forms a complex with the scaffolding protein MO25, and the serine/threonine kinase (STK), LKB1, resulting in the activation of the kinase. In the complex, LKB1 phosphorylates and activates adenosine monophosphate-activated protein kinases (AMPKs), which regulate cell energy metabolism and cell polarity. LKB1 is a tumor suppressor linked to the rare inherited disease, Peutz-Jeghers syndrome, which is characterized by a predisposition to benign polyps and hyperpigmentation of the buccal mucosa. There are two forms of STRAD, alpha and beta, that complex with LKB1 and MO25. The structure of STRAD-alpha is available and shows that this protein binds ATP, has an ordered activation loop, and adopts a closed conformation typical of fully active protein kinases. It does not possess activity due to nonconservative substitutions of essential catalytic residues. ATP binding enhances the affinity of STRAD for MO25. The conformation of STRAD-alpha stabilized through ATP and MO25 may be needed to activate LKB1. The STRAD 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: 270856 [Multi-domain]  Cd Length: 315  Bit Score: 54.99  E-value: 1.03e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   563 KKFPGDQHIAIR-----PATKTAFSKLQE-------LRHENVALYLGLFLARGAegpaaLWegnlaVVSEHCTRGSLQDL 630
Cdd:cd08216   20 KHKPTNTLVAVKkinleSDSKEDLKFLQQeiltsrqLQHPNILPYVTSFVVDND-----LY-----VVTPLMAYGSCRDL 89
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   631 LAQReikldwmFKSSL--------LLDLIKGIRYLHHRGVAHGRLKSRNCIVDG---------RFVLKITDHGhgrllEA 693
Cdd:cd08216   90 LKTH-------FPEGLpelaiafiLRDVLNALEYIHSKGYIHRSVKASHILISGdgkvvlsglRYAYSMVKHG-----KR 157
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   694 QKVLPEPPR--AEDQLWTAPELLRDpalerrgTLAG-----DVFSLAIIMQEVVCRSAPYAMLELTpEEVVQRVRSPPP- 765
Cdd:cd08216  158 QRVVHDFPKssEKNLPWLSPEVLQQ-------NLLGyneksDIYSVGITACELANGVVPFSDMPAT-QMLLEKVRGTTPq 229
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   766 ------LCRPLVSMDQAPVECIL----------------------LMKQCWAEQPELRPS----MDHTFdlFKNInKGRK 813
Cdd:cd08216  230 lldcstYPLEEDSMSQSEDSSTEhpnnrdtrdipyqrtfseafhqFVELCLQRDPELRPSasqlLAHSF--FKQC-RRSN 306

                 ....*
gi 4504217   814 TNIID 818
Cdd:cd08216  307 TSLLD 311
STKc_NAK1_like cd06917
Catalytic domain of Fungal Nak1-like Serine/Threonine Kinases; STKs catalyze the transfer of ...
584-765 1.08e-07

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: 54.79  E-value: 1.08e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   584 LQELRH---ENVALYLGLFLargaEGPaalwegNLAVVSEHCTRGSLQDLLaqREIKLDWMFKSSLLLDLIKGIRYLHHR 660
Cdd:cd06917   53 LSQLKLgqpKNIIKYYGSYL----KGP------SLWIIMDYCEGGSIRTLM--RAGPIAERYIAVIMREVLVALKFIHKD 120
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   661 GVAHGRLKSRNCIVDGRFVLKITDHGHGRLLeAQKVLPEPPRAEDQLWTAPELLRDpalERRGTLAGDVFSLAIIMQEVV 740
Cdd:cd06917  121 GIIHRDIKAANILVTNTGNVKLCDFGVAASL-NQNSSKRSTFVGTPYWMAPEVITE---GKYYDTKADIWSLGITTYEMA 196
                        170       180
                 ....*....|....*....|....*.
gi 4504217   741 CRSAPYAMLEltPEEVVQRV-RSPPP 765
Cdd:cd06917  197 TGNPPYSDVD--ALRAVMLIpKSKPP 220
PTKc_DDR2 cd05095
Catalytic domain of the Protein Tyrosine Kinase, Discoidin Domain Receptor 2; PTKs catalyze ...
615-797 1.28e-07

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: 54.61  E-value: 1.28e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   615 LAVVSEHCTRGSLQDLLAQREIKLDWMFKSSLLL-----------DLIKGIRYLHHRGVAHGRLKSRNCIVDGRFVLKIT 683
Cdd:cd05095   94 LCMITEYMENGDLNQFLSRQQPEGQLALPSNALTvsysdlrfmaaQIASGMKYLSSLNFVHRDLATRNCLVGKNYTIKIA 173
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   684 DHGHGRLL--------EAQKVLPeppraedQLWTAPELLrdpaLERRGTLAGDVFSLAIIMQEVV--CRSAPYAmlELTP 753
Cdd:cd05095  174 DFGMSRNLysgdyyriQGRAVLP-------IRWMSWESI----LLGKFTTASDVWAFGVTLWETLtfCREQPYS--QLSD 240
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 4504217   754 EEVVQ-----------RVRSPPP-LCrplvsmdqaPVECILLMKQCWAEQPELRPS 797
Cdd:cd05095  241 EQVIEntgeffrdqgrQTYLPQPaLC---------PDSVYKLMLSCWRRDTKDRPS 287
STKc_SnRK3 cd14663
Catalytic domain of the Serine/Threonine Kinases, Sucrose nonfermenting 1-related protein ...
614-736 1.30e-07

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: 53.95  E-value: 1.30e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   614 NLAVVSEHCTRGSLQDLLAQ----REIKLDWMFKSsllldLIKGIRYLHHRGVAHGRLKSRNCIVDGRFVLKITDHGhgr 689
Cdd:cd14663   74 KIFFVMELVTGGELFSKIAKngrlKEDKARKYFQQ-----LIDAVDYCHSRGVFHRDLKPENLLLDEDGNLKISDFG--- 145
                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 4504217   690 lLEAqkvLPEPPRAEDQLWT--------APELLRdpaleRRG--TLAGDVFSLAIIM 736
Cdd:cd14663  146 -LSA---LSEQFRQDGLLHTtcgtpnyvAPEVLA-----RRGydGAKADIWSCGVIL 193
PTKc_Axl cd05075
Catalytic domain of the Protein Tyrosine Kinase, Axl; PTKs catalyze the transfer of the ...
646-810 1.38e-07

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: 54.24  E-value: 1.38e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   646 LLLDLIKGIRYLHHRGVAHGRLKSRNCIVDGRFVLKITDHG------HGRLLEAQKVLPEPPRaedqlWTAPELLRDpal 719
Cdd:cd05075  118 FMTDIASGMEYLSSKNFIHRDLAARNCMLNENMNVCVADFGlskkiyNGDYYRQGRISKMPVK-----WIAIESLAD--- 189
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   720 eRRGTLAGDVFSLAIIMQEVVCR-SAPYAMLELTpeEVVQRVRSPPPLCRPLVSMDqapveCIL-LMKQCWAEQPELRPS 797
Cdd:cd05075  190 -RVYTTKSDVWSFGVTMWEIATRgQTPYPGVENS--EIYDYLRQGNRLKQPPDCLD-----GLYeLMSSCWLLNPKDRPS 261
                        170
                 ....*....|...
gi 4504217   798 MDHTFDLFKNINK 810
Cdd:cd05075  262 FETLRCELEKILK 274
PKc_MAPKK cd06605
Catalytic domain of the dual-specificity Protein Kinase, Mitogen-Activated Protein Kinase ...
612-802 1.52e-07

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: 53.89  E-value: 1.52e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   612 EGNLAVVSEHCTRGSLQDLLAQ-REIKLDWMFKSSllLDLIKGIRYLHH-RGVAHGRLKSRNCIVDGRFVLKITDHG-HG 688
Cdd:cd06605   71 EGDISICMEYMDGGSLDKILKEvGRIPERILGKIA--VAVVKGLIYLHEkHKIIHRDVKPSNILVNSRGQVKLCDFGvSG 148
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   689 RLLEAQkvlpepprAED----QLWTAPELLRDPALerrgTLAGDVFSLAIIMQEVVCRSAPY----AMLELTPEEVVQRV 760
Cdd:cd06605  149 QLVDSL--------AKTfvgtRSYMAPERISGGKY----TVKSDIWSLGLSLVELATGRFPYpppnAKPSMMIFELLSYI 216
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*.
gi 4504217   761 RSPPPlcrPLVSMDQAPVECILLMKQCWAEQPELRPS----MDHTF 802
Cdd:cd06605  217 VDEPP---PLLPSGKFSPDFQDFVSQCLQKDPTERPSykelMEHPF 259
STKc_Unc-89_rpt2 cd14112
Catalytic kinase domain, second repeat, of the Giant Serine/Threonine Kinase Uncoordinated ...
563-803 1.69e-07

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: 53.69  E-value: 1.69e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   563 KKFPGDQHIA--IRPATKTA------FSKLQELRHENVAlylGLFLARGAEGPAALWEGNLAvvSEHCTRGSLQDLLAQR 634
Cdd:cd14112   25 STTETDAHCAvkIFEVSDEAseavreFESLRTLQHENVQ---RLIAAFKPSNFAYLVMEKLQ--EDVFTRFSSNDYYSEE 99
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   635 EIkldwmfkSSLLLDLIKGIRYLHHRGVAHGRLKSRNCIVDGR--FVLKITDHGhgrllEAQKVLPE--PPRAEDQLWTA 710
Cdd:cd14112  100 QV-------ATTVRQILDALHYLHFKGIAHLDVQPDNIMFQSVrsWQVKLVDFG-----RAQKVSKLgkVPVDGDTDWAS 167
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   711 PELLRDpalERRGTLAGDVFSLAIIMQEVVCRSAPYAMLELTPEEVVQRVRSPPplCRPLVSMDQAPVECILLMKQCWAE 790
Cdd:cd14112  168 PEFHNP---ETPITVQSDIWGLGVLTFCLLSGFHPFTSEYDDEEETKENVIFVK--CRPNLIFVEATQEALRFATWALKK 242
                        250
                 ....*....|...
gi 4504217   791 QPELRPSMDHTFD 803
Cdd:cd14112  243 SPTRRMRTDEALE 255
PTKc_Aatyk3 cd14206
Catalytic domain of the Protein Tyrosine Kinases, Apoptosis-associated tyrosine kinase 3; PTKs ...
617-802 2.05e-07

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: 53.80  E-value: 2.05e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   617 VVSEHCTRGSLQDLL-AQReiKLDWMFKSSLLLDLI----------KGIRYLHHRGVAHGRLKSRNCIVDGRFVLKITDH 685
Cdd:cd14206   74 LIMEFCQLGDLKRYLrAQR--KADGMTPDLPTRDLRtlqrmayeitLGLLHLHKNNYIHSDLALRNCLLTSDLTVRIGDY 151
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   686 G--HGRLLEAQKVLPE----PPRaedqlWTAPELLRdpalERRGTL-------AGDVFSLAIIMQEVV-CRSAPYAmlEL 751
Cdd:cd14206  152 GlsHNNYKEDYYLTPDrlwiPLR-----WVAPELLD----ELHGNLivvdqskESNVWSLGVTIWELFeFGAQPYR--HL 220
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|...
gi 4504217   752 TPEEVVQRV--RSPPPLCRPLVSMDQAPVeCILLMKQCWAEqPELRPSMDHTF 802
Cdd:cd14206  221 SDEEVLTFVvrEQQMKLAKPRLKLPYADY-WYEIMQSCWLP-PSQRPSVEELH 271
PKc_Dusty cd13975
Catalytic domain of the Dual-specificity Protein Kinase, Dusty; Dual-specificity PKs catalyze ...
638-796 2.25e-07

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: 53.65  E-value: 2.25e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   638 LDWMFKSSLLLDLIKGIRYLHHRGVAHGRLKSRNCIVDGRFVLKITDHGHGRlleaqkvlPEPPRAEDQLWT----APEL 713
Cdd:cd13975   99 LSLEERLQIALDVVEGIRFLHSQGLVHRDIKLKNVLLDKKNRAKITDLGFCK--------PEAMMSGSIVGTpihmAPEL 170
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   714 LR---DPALerrgtlagDVFSLAIIMQEVVCRSA--PYAMLELTPEEVVQR-VRSPpplCRP--LVSMDQapvECILLMK 785
Cdd:cd13975  171 FSgkyDNSV--------DVYAFGILFWYLCAGHVklPEAFEQCASKDHLWNnVRKG---VRPerLPVFDE---ECWNLME 236
                        170
                 ....*....|.
gi 4504217   786 QCWAEQPELRP 796
Cdd:cd13975  237 ACWSGDPSQRP 247
PTKc_HER2 cd05109
Catalytic domain of the Protein Tyrosine Kinase, HER2; PTKs catalyze the transfer of the ...
617-810 3.34e-07

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: 53.10  E-value: 3.34e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   617 VVSEHCTRGSLQDLLAQREIKLDWMFKSSLLLDLIKGIRYLHHRGVAHGRLKSRNCIVDGRFVLKITDHGHGRLLEAQKV 696
Cdd:cd05109   85 LVTQLMPYGCLLDYVRENKDRIGSQDLLNWCVQIAKGMSYLEEVRLVHRDLAARNVLVKSPNHVKITDFGLARLLDIDET 164
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   697 LPEPPRAEDQL-WTAPELLrdpaLERRGTLAGDVFSLAIIMQEVVCRSA-PYAMLEL--TPEEVVQRVRSP-PPLCrplv 771
Cdd:cd05109  165 EYHADGGKVPIkWMALESI----LHRRFTHQSDVWSYGVTVWELMTFGAkPYDGIPAreIPDLLEKGERLPqPPIC---- 236
                        170       180       190
                 ....*....|....*....|....*....|....*....
gi 4504217   772 smdqaPVECILLMKQCWAEQPELRPSMDHTFDLFKNINK 810
Cdd:cd05109  237 -----TIDVYMIMVKCWMIDSECRPRFRELVDEFSRMAR 270
STKc_MAP4K3_like cd06613
Catalytic domain of Mitogen-activated protein kinase kinase kinase kinase (MAP4K) 3-like ...
584-802 3.42e-07

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: 52.69  E-value: 3.42e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   584 LQELRHENVALYLGLFLARGAegpaaLWegnlaVVSEHCTRGSLQDLLAQ----REIKLDWMFKSSLlldliKGIRYLHH 659
Cdd:cd06613   51 LKECRHPNIVAYFGSYLRRDK-----LW-----IVMEYCGGGSLQDIYQVtgplSELQIAYVCRETL-----KGLAYLHS 115
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   660 RGVAHGRLKSRNCIvdgrfvlkITDHGHGRL----LEAQ--------KVLPEPPraedqLWTAPELLrdpALERRGTLAG 727
Cdd:cd06613  116 TGKIHRDIKGANIL--------LTEDGDVKLadfgVSAQltatiakrKSFIGTP-----YWMAPEVA---AVERKGGYDG 179
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   728 --DVFSLAIIMQEVVCRSAPyaMLELTPEEVVQ---RVRSPPPlcrPLVSMDQAPVECILLMKQCWAEQPELRPS----M 798
Cdd:cd06613  180 kcDIWALGITAIELAELQPP--MFDLHPMRALFlipKSNFDPP---KLKDKEKWSPDFHDFIKKCLTKNPKKRPTatklL 254

                 ....
gi 4504217   799 DHTF 802
Cdd:cd06613  255 QHPF 258
PTKc_VEGFR3 cd05102
Catalytic domain of the Protein Tyrosine Kinase, Vascular Endothelial Growth Factor Receptor 3; ...
632-812 3.68e-07

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: 53.44  E-value: 3.68e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   632 AQREIKLDWMFKSSLLL-DLI-------KGIRYLHHRGVAHGRLKSRNCIVDGRFVLKITDHGHGRLLEAQKVLPEPPRA 703
Cdd:cd05102  155 NQPRQEVDDLWQSPLTMeDLIcysfqvaRGMEFLASRKCIHRDLAARNILLSENNVVKICDFGLARDIYKDPDYVRKGSA 234
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   704 EDQL-WTAPELLRDPALerrgTLAGDVFSLAIIMQEVVCRSA-PYAMLELTpEEVVQRVRSPPPLCRPlvsmDQAPVECI 781
Cdd:cd05102  235 RLPLkWMAPESIFDKVY----TTQSDVWSFGVLLWEIFSLGAsPYPGVQIN-EEFCQRLKDGTRMRAP----EYATPEIY 305
                        170       180       190
                 ....*....|....*....|....*....|.
gi 4504217   782 LLMKQCWAEQPELRPSMDHTFDLFKNINKGR 812
Cdd:cd05102  306 RIMLSCWHGDPKERPTFSDLVEILGDLLQEN 336
PTKc_Wee1_fungi cd14052
Catalytic domain of the Protein Tyrosine Kinases, Fungal Wee1 proteins; PTKs catalyze the ...
611-739 3.82e-07

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: 52.81  E-value: 3.82e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   611 WE--GNLAVVSEHCTRGSLQDLLAQREIK--LD----WmfksSLLLDLIKGIRYLHHRGVAHGRLKSRNCIVDGRFVLKI 682
Cdd:cd14052   72 WEyhGHLYIQTELCENGSLDVFLSELGLLgrLDefrvW----KILVELSLGLRFIHDHHFVHLDLKPANVLITFEGTLKI 147
                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 4504217   683 TDHGHGRLLEAQKVLpepPRAEDQLWTAPELLRDPALERrgtlAGDVFSLAIIMQEV 739
Cdd:cd14052  148 GDFGMATVWPLIRGI---EREGDREYIAPEILSEHMYDK----PADIFSLGLILLEA 197
STKc_TSSK4-like cd14162
Catalytic domain of testis-specific serine/threonine kinase 4 and similar proteins; STKs ...
650-799 4.48e-07

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: 52.68  E-value: 4.48e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   650 LIKGIRYLHHRGVAHGRLKSRNCIVDGRFVLKITDHGHGRLleaqkvLPEPPRAEDQL---------WTAPELLR----D 716
Cdd:cd14162  109 LVAGVEYCHSKGVVHRDLKCENLLLDKNNNLKITDFGFARG------VMKTKDGKPKLsetycgsyaYASPEILRgipyD 182
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   717 PALerrgtlaGDVFSLAIIMQEVVCRSAPY------AMLeltpEEVVQRVRSPPplcRPLVSMdqapvECILLMKQCWAE 790
Cdd:cd14162  183 PFL-------SDIWSMGVVLYTMVYGRLPFddsnlkVLL----KQVQRRVVFPK---NPTVSE-----ECKDLILRMLSP 243

                 ....*....
gi 4504217   791 QPElRPSMD 799
Cdd:cd14162  244 VKK-RITIE 251
PTKc_Trk cd05049
Catalytic domain of the Protein Tyrosine Kinases, Tropomyosin Related Kinases; PTKs catalyze ...
653-807 4.50e-07

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: 52.85  E-value: 4.50e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   653 GIRYLHHRGVAHGRLKSRNCIVDGRFVLKITDHGHGR--------LLEAQKVLPeppraedQLWTAPELLrdpaLERRGT 724
Cdd:cd05049  134 GMVYLASQHFVHRDLATRNCLVGTNLVVKIGDFGMSRdiystdyyRVGGHTMLP-------IRWMPPESI----LYRKFT 202
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   725 LAGDVFSLAIIMQEVVCRS-APYamLELTPEEVVQRVRSPPPLCRPLVsmdqAPVECILLMKQCWAEQPELRPSMDHTFD 803
Cdd:cd05049  203 TESDVWSFGVVLWEIFTYGkQPW--FQLSNTEVIECITQGRLLQRPRT----CPSEVYAVMLGCWKREPQQRLNIKDIHK 276

                 ....
gi 4504217   804 LFKN 807
Cdd:cd05049  277 RLQE 280
STKc_PIM1 cd14100
Catalytic domain of the Serine/Threonine kinase, Proviral Integration Moloney virus (PIM) ...
624-799 4.52e-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: 52.28  E-value: 4.52e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   624 RGSLQDLLAQreikldwmfksSLLLDLIKGIRYLHHRGVAHGRLKSRNCIVD-GRFVLKITDHGHGRLLEaQKVLPEPPR 702
Cdd:cd14100  100 RGALPEELAR-----------SFFRQVLEAVRHCHNCGVLHRDIKDENILIDlNTGELKLIDFGSGALLK-DTVYTDFDG 167
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   703 AedQLWTAPELLRdpaLERRGTLAGDVFSLAIIMQEVVCRSAPYAM-LELTPEEVVQRVRSPPplcrplvsmdqapvECI 781
Cdd:cd14100  168 T--RVYSPPEWIR---FHRYHGRSAAVWSLGILLYDMVCGDIPFEHdEEIIRGQVFFRQRVSS--------------ECQ 228
                        170
                 ....*....|....*...
gi 4504217   782 LLMKQCWAEQPELRPSMD 799
Cdd:cd14100  229 HLIKWCLALRPSDRPSFE 246
PTKc_Tie2 cd05088
Catalytic domain of the Protein Tyrosine Kinase, Tie2; PTKs catalyze the transfer of the ...
649-816 4.82e-07

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: 53.08  E-value: 4.82e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   649 DLIKGIRYLHHRGVAHGRLKSRNCIVDGRFVLKITDHG--HGRLLEAQKVLPEPPRAedqlWTAPELLRDPALerrgTLA 726
Cdd:cd05088  132 DVARGMDYLSQKQFIHRDLAARNILVGENYVAKIADFGlsRGQEVYVKKTMGRLPVR----WMAIESLNYSVY----TTN 203
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   727 GDVFSLAIIMQEVVCRSA-PYAmlELTPEEVVQRVRSPPPLCRPLVSMDqapvECILLMKQCWAEQPELRPSMDHTFDLF 805
Cdd:cd05088  204 SDVWSYGVLLWEIVSLGGtPYC--GMTCAELYEKLPQGYRLEKPLNCDD----EVYDLMRQCWREKPYERPSFAQILVSL 277
                        170
                 ....*....|.
gi 4504217   806 KNINKGRKTNI 816
Cdd:cd05088  278 NRMLEERKTYV 288
PTKc_Aatyk cd05042
Catalytic domain of the Protein Tyrosine Kinases, Apoptosis-associated tyrosine kinases; PTKs ...
617-797 1.01e-06

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: 51.43  E-value: 1.01e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   617 VVSEHCTRGSLQDLL-AQREIKL---DWMFKSSLLLDLIKGIRYLHHRGVAHGRLKSRNCIVDGRFVLKITDHG--HGRL 690
Cdd:cd05042   72 LVMEFCDLGDLKAYLrSEREHERgdsDTRTLQRMACEVAAGLAHLHKLNFVHSDLALRNCLLTSDLTVKIGDYGlaHSRY 151
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   691 LEAQKVLPE----PPRaedqlWTAPELL---RDPALERRGTLAGDVFSLAIIMQEVVCRSA-PYAmlELTPEEVV----- 757
Cdd:cd05042  152 KEDYIETDDklwfPLR-----WTAPELVtefHDRLLVVDQTKYSNIWSLGVTLWELFENGAqPYS--NLSDLDVLaqvvr 224
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|.
gi 4504217   758 -QRVRSPPPLCRPLVSMDQAPVecillMKQCWAeQPELRPS 797
Cdd:cd05042  225 eQDTKLPKPQLELPYSDRWYEV-----LQFCWL-SPEQRPA 259
PTKc_EGFR cd05108
Catalytic domain of the Protein Tyrosine Kinase, Epidermal Growth Factor Receptor; PTKs ...
625-796 1.03e-06

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: 51.95  E-value: 1.03e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   625 GSLQDLLAQREIKLDWMFKSSLLLDLIKGIRYLHHRGVAHGRLKSRNCIVDGRFVLKITDHGHGRLLEAQKVLPEPPRAE 704
Cdd:cd05108   93 GCLLDYVREHKDNIGSQYLLNWCVQIAKGMNYLEDRRLVHRDLAARNVLVKTPQHVKITDFGLAKLLGAEEKEYHAEGGK 172
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   705 DQL-WTAPELLrdpaLERRGTLAGDVFSLAIIMQEVVC-RSAPYamlELTPEEVVQRV-----RSP-PPLCrplvsmdqa 776
Cdd:cd05108  173 VPIkWMALESI----LHRIYTHQSDVWSYGVTVWELMTfGSKPY---DGIPASEISSIlekgeRLPqPPIC--------- 236
                        170       180
                 ....*....|....*....|
gi 4504217   777 PVECILLMKQCWAEQPELRP 796
Cdd:cd05108  237 TIDVYMIMVKCWMIDADSRP 256
PTKc_Abl cd05052
Catalytic domain of the Protein Tyrosine Kinase, Abelson kinase; PTKs catalyze the transfer of ...
584-808 1.04e-06

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: 51.27  E-value: 1.04e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   584 LQELRHENVALYLGLflargaegpaALWEGNLAVVSEHCTRGSLQDLLAQR-EIKLDWMFKSSLLLDLIKGIRYLHHRGV 662
Cdd:cd05052   56 MKEIKHPNLVQLLGV----------CTREPPFYIITEFMPYGNLLDYLRECnREELNAVVLLYMATQIASAMEYLEKKNF 125
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   663 AHGRLKSRNCIVDGRFVLKITDHGHGRLLE-----AQKVLPEPPRaedqlWTAPELLrdpALERRGTlAGDVFSLAIIMQ 737
Cdd:cd05052  126 IHRDLAARNCLVGENHLVKVADFGLSRLMTgdtytAHAGAKFPIK-----WTAPESL---AYNKFSI-KSDVWAFGVLLW 196
                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 4504217   738 EVVCRS-APYAMLELTpeEVVQRVRSPPPLCRPlvsmDQAPVECILLMKQCWAEQPELRPSMDHTFDLFKNI 808
Cdd:cd05052  197 EIATYGmSPYPGIDLS--QVYELLEKGYRMERP----EGCPPKVYELMRACWQWNPSDRPSFAEIHQALETM 262
PTKc_PDGFR cd05055
Catalytic domain of the Protein Tyrosine Kinases, Platelet Derived Growth Factor Receptors; ...
589-797 1.04e-06

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: 51.72  E-value: 1.04e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   589 HENVALYLGlflargaegpAALWEGNLAVVSEHCTRGSLQDLL-AQREIKLDWMFKSSLLLDLIKGIRYLHHRGVAHGRL 667
Cdd:cd05055   98 HENIVNLLG----------ACTIGGPILVITEYCCYGDLLNFLrRKRESFLTLEDLLSFSYQVAKGMAFLASKNCIHRDL 167
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   668 KSRNCIVDGRFVLKITDHGHGR--------LLEAQKVLPEPpraedqlWTAPELLRDPALerrgTLAGDVFSLAIIMQEV 739
Cdd:cd05055  168 AARNVLLTHGKIVKICDFGLARdimndsnyVVKGNARLPVK-------WMAPESIFNCVY----TFESDVWSYGILLWEI 236
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 4504217   740 VCR-SAPYAMLeLTPEEVVQRVRSPPPLCRPlvsmDQAPVECILLMKQCWAEQPELRPS 797
Cdd:cd05055  237 FSLgSNPYPGM-PVDSKFYKLIKEGYRMAQP----EHAPAEIYDIMKTCWDADPLKRPT 290
STKc_STK25 cd06642
Catalytic domain of Serine/Threonine Kinase 25 (also called Yeast Sps1/Ste20-related kinase 1); ...
615-827 1.13e-06

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: 51.60  E-value: 1.13e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   615 LAVVSEHCTRGSLQDLLaqREIKLDWMFKSSLLLDLIKGIRYLHHRGVAHGRLKSRNCIVDGRFVLKITDHG-HGRLLEA 693
Cdd:cd06642   77 LWIIMEYLGGGSALDLL--KPGPLEETYIATILREILKGLDYLHSERKIHRDIKAANVLLSEQGDVKLADFGvAGQLTDT 154
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   694 QkvLPEPPRAEDQLWTAPELLRDPALErrgtLAGDVFSLAIIMQEVVCRSAPYAmlELTPEEVVQRV--RSPPPL----C 767
Cdd:cd06642  155 Q--IKRNTFVGTPFWMAPEVIKQSAYD----FKADIWSLGITAIELAKGEPPNS--DLHPMRVLFLIpkNSPPTLegqhS 226
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   768 RPLVSMDQApvecillmkqCWAEQPELRPSMDhtfDLFKNINKGRKTNIIDSMLRMLEQY 827
Cdd:cd06642  227 KPFKEFVEA----------CLNKDPRFRPTAK---ELLKHKFITRYTKKTSFLTELIDRY 273
PTKc_TrkB cd05093
Catalytic domain of the Protein Tyrosine Kinase, Tropomyosin Related Kinase B; PTKs catalyze ...
653-811 1.19e-06

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: 51.58  E-value: 1.19e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   653 GIRYLHHRGVAHGRLKSRNCIVDGRFVLKITDHGHGR--------LLEAQKVLPeppraedQLWTAPELLrdpaLERRGT 724
Cdd:cd05093  132 GMVYLASQHFVHRDLATRNCLVGENLLVKIGDFGMSRdvystdyyRVGGHTMLP-------IRWMPPESI----MYRKFT 200
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   725 LAGDVFSLAIIMQEVVCR-SAPYamLELTPEEVVQRVRSPPPLCRPLVsmdqAPVECILLMKQCWAEQPELRPSMDHTFD 803
Cdd:cd05093  201 TESDVWSLGVVLWEIFTYgKQPW--YQLSNNEVIECITQGRVLQRPRT----CPKEVYDLMLGCWQREPHMRLNIKEIHS 274

                 ....*...
gi 4504217   804 LFKNINKG 811
Cdd:cd05093  275 LLQNLAKA 282
STKc_Nek cd08215
Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase; ...
584-799 1.27e-06

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: 50.92  E-value: 1.27e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   584 LQELRHENVALYLGLFLARGaegpaalwegNLAVVSEHCTRGSLQDLLAQREIK---------LDWMFKSSLlldlikGI 654
Cdd:cd08215   53 LSKLKHPNIVKYYESFEENG----------KLCIVMEYADGGDLAQKIKKQKKKgqpfpeeqiLDWFVQICL------AL 116
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   655 RYLHHRGVAHGRLKSRNCIVDGRFVLKITDHGHGRLLE-----AQKVLPEPpraedqLWTAPELLRDpaleRRGTLAGDV 729
Cdd:cd08215  117 KYLHSRKILHRDLKTQNIFLTKDGVVKLGDFGISKVLEsttdlAKTVVGTP------YYLSPELCEN----KPYNYKSDI 186
                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 4504217   730 FSLAIIMQEVVCRSAPYA---MLELtpeeVVQRVRSPPPlcrPLVSmdQAPVECILLMKQCWAEQPELRPSMD 799
Cdd:cd08215  187 WALGCVLYELCTLKHPFEannLPAL----VYKIVKGQYP---PIPS--QYSSELRDLVNSMLQKDPEKRPSAN 250
STKc_PIM3 cd14102
Catalytic domain of the Serine/Threonine kinase, Proviral Integration Moloney virus (PIM) ...
650-803 1.34e-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: 51.11  E-value: 1.34e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   650 LIKGIRYLHHRGVAHGRLKSRNCIVDGRF-VLKITDHGHGRLLEaQKVLPEPPRAedQLWTAPELLRdpaLERRGTLAGD 728
Cdd:cd14102  114 VLEAVRHCYSCGVVHRDIKDENLLVDLRTgELKLIDFGSGALLK-DTVYTDFDGT--RVYSPPEWIR---YHRYHGRSAT 187
                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 4504217   729 VFSLAIIMQEVVCRSAPYAMleltpEEVVQRVRsppplcrpLVSMDQAPVECILLMKQCWAEQPELRPSMDHTFD 803
Cdd:cd14102  188 VWSLGVLLYDMVCGDIPFEQ-----DEEILRGR--------LYFRRRVSPECQQLIKWCLSLRPSDRPTLEQIFD 249
PTKc_Aatyk1 cd05087
Catalytic domain of the Protein Tyrosine Kinases, Apoptosis-associated tyrosine kinase 1; PTKs ...
617-799 1.34e-06

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: 51.14  E-value: 1.34e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   617 VVSEHCTRGSLQDLL----AQREIKLDWMFKSSLLLDLIKGIRYLHHRGVAHGRLKSRNCIVDGRFVLKITDHG--HGRL 690
Cdd:cd05087   74 LVMEFCPLGDLKGYLrscrAAESMAPDPLTLQRMACEVACGLLHLHRNNFVHSDLALRNCLLTADLTVKIGDYGlsHCKY 153
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   691 LEAQKVlpepprAEDQL-----WTAPELLRD---PALERRGTLAGDVFSLAIIMQEVV-CRSAPY------AMLELTPEE 755
Cdd:cd05087  154 KEDYFV------TADQLwvplrWIAPELVDEvhgNLLVVDQTKQSNVWSLGVTIWELFeLGNQPYrhysdrQVLTYTVRE 227
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....
gi 4504217   756 vvQRVRSPPPLCRplVSMDQAPVEcilLMKQCWAeQPELRPSMD 799
Cdd:cd05087  228 --QQLKLPKPQLK--LSLAERWYE---VMQFCWL-QPEQRPTAE 263
STKc_MLCK-like cd14006
Catalytic kinase domain of Myosin Light Chain Kinase-like Serine/Threonine Kinases; STKs ...
558-762 1.42e-06

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: 50.73  E-value: 1.42e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   558 DRVWLKKFpgdqhIAIRPATKTA----FSKLQELRHENValyLGLFLArgAEGPAALWegnlaVVSEHCTRGSLQDLLAQ 633
Cdd:cd14006   18 GREFAAKF-----IPKRDKKKEAvlreISILNQLQHPRI---IQLHEA--YESPTELV-----LILELCSGGELLDRLAE 82
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   634 REIKLDWMFKSsLLLDLIKGIRYLHHRGVAHGRLKSRNCIVDGRFV--LKITDHGHGRLLEAQKVL------PEppraed 705
Cdd:cd14006   83 RGSLSEEEVRT-YMRQLLEGLQYLHNHHILHLDLKPENILLADRPSpqIKIIDFGLARKLNPGEELkeifgtPE------ 155
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 4504217   706 qlWTAPELLR-DPAlerrgTLAGDVFSLAIIMqeVVCRSAPYAMLELTPEEVVQRVRS 762
Cdd:cd14006  156 --FVAPEIVNgEPV-----SLATDMWSIGVLT--YVLLSGLSPFLGEDDQETLANISA 204
PTK_HER3 cd05111
Pseudokinase domain of the Protein Tyrosine Kinase, HER3; HER3 (ErbB3) is a member of the EGFR ...
614-797 1.50e-06

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: 51.11  E-value: 1.50e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   614 NLAVVSEHCTRGSLQDLLAQREIKLDWMFKSSLLLDLIKGIRYLHHRGVAHGRLKSRNCIVDGRFVLKITDHGHGRLL-- 691
Cdd:cd05111   82 SLQLVTQLLPLGSLLDHVRQHRGSLGPQLLLNWCVQIAKGMYYLEEHRMVHRNLAARNVLLKSPSQVQVADFGVADLLyp 161
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   692 EAQKVLPEPPRAEDQlWTAPELLrdpaLERRGTLAGDVFSLAIIMQEVVCRSA-PYAMLEltPEEVVQRVRSPPPLCRPL 770
Cdd:cd05111  162 DDKKYFYSEAKTPIK-WMALESI----HFGKYTHQSDVWSYGVTVWEMMTFGAePYAGMR--LAEVPDLLEKGERLAQPQ 234
                        170       180
                 ....*....|....*....|....*..
gi 4504217   771 VsmdqAPVECILLMKQCWAEQPELRPS 797
Cdd:cd05111  235 I----CTIDVYMVMVKCWMIDENIRPT 257
STKc_CCRK cd07832
Catalytic domain of the Serine/Threonine Kinase, Cell Cycle-Related Kinase; STKs catalyze the ...
645-738 1.58e-06

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: 51.18  E-value: 1.58e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   645 SLLLDLIKGIRYLHHRGVAHGRLKSRNCIVDGRFVLKITDHGHGRLLEAQKVLPEPPRAEDQLWTAPELLRDpalERRGT 724
Cdd:cd07832  104 RYMRMLLKGVAYMHANRIMHRDLKPANLLISSTGVLKIADFGLARLFSEEDPRLYSHQVATRWYRAPELLYG---SRKYD 180
                         90
                 ....*....|....
gi 4504217   725 LAGDVFSLAIIMQE 738
Cdd:cd07832  181 EGVDLWAVGCIFAE 194
STKc_obscurin_rpt2 cd14110
Catalytic kinase domain, second repeat, of the Giant Serine/Threonine Kinase Obscurin; STKs ...
571-714 1.72e-06

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: 50.69  E-value: 1.72e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   571 IAIRPATKTA----FSKLQELRHENVALYLGLFLArgaegpaalwEGNLAVVSEHCTRGSLQDLLAQREIKLDWMFKSsL 646
Cdd:cd14110   36 IPYKPEDKQLvlreYQVLRRLSHPRIAQLHSAYLS----------PRHLVLIEELCSGPELLYNLAERNSYSEAEVTD-Y 104
                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 4504217   647 LLDLIKGIRYLHHRGVAHGRLKSRNCIVDGRFVLKITDHGHGRLLEAQKVLPEPPRAEDQLWTAPELL 714
Cdd:cd14110  105 LWQILSAVDYLHSRRILHLDLRSENMIITEKNLLKIVDLGNAQPFNQGKVLMTDKKGDYVETMAPELL 172
STKc_Rad53_Cds1 cd14098
Catalytic domain of the yeast Serine/Threonine Kinases, Rad53 and Cds1; STKs catalyze the ...
584-798 1.75e-06

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: 50.94  E-value: 1.75e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   584 LQELRHENVALYLGLFlargaEGPAALWegnlaVVSEHCTRGSLQDLLAQREiKLDWMFKSSLLLDLIKGIRYLHHRGVA 663
Cdd:cd14098   55 LKSLEHPGIVRLIDWY-----EDDQHIY-----LVMEYVEGGDLMDFIMAWG-AIPEQHARELTKQILEAMAYTHSMGIT 123
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   664 HGRLKSRNCIV--DGRFVLKITDHGHGRLLEAQKVLPEppRAEDQLWTAPELLRDPALERRGTLAG--DVFSLAIIMQEV 739
Cdd:cd14098  124 HRDLKPENILItqDDPVIVKISDFGLAKVIHTGTFLVT--FCGTMAYLAPEILMSKEQNLQGGYSNlvDMWSVGCLVYVM 201
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 4504217   740 VCRSAPYAmlELTPEEVVQRVRSPPPLCRPLVSMDQAPvECILLMKQCWAEQPELRPSM 798
Cdd:cd14098  202 LTGALPFD--GSSQLPVEKRIRKGRYTQPPLVDFNISE-EAIDFILRLLDVDPEKRMTA 257
PKc_MKK3_6 cd06617
Catalytic domain of the dual-specificity Protein Kinases, Mitogen-activated protein Kinase ...
648-802 1.85e-06

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: 50.89  E-value: 1.85e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   648 LDLIKGIRYLHHR-GVAHGRLKSRNCIVDGRFVLKITDHG-HGRLLEAqkvLPEPPRAEDQLWTAPELLrDPALERRG-T 724
Cdd:cd06617  110 VSIVKALEYLHSKlSVIHRDVKPSNVLINRNGQVKLCDFGiSGYLVDS---VAKTIDAGCKPYMAPERI-NPELNQKGyD 185
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   725 LAGDVFSLAIIMQEVVCRSAPYAMLELTPEEVVQRVRSPPplcrPLVSMDQAPVECILLMKQCWAEQPELRPS----MDH 800
Cdd:cd06617  186 VKSDVWSLGITMIELATGRFPYDSWKTPFQQLKQVVEEPS----PQLPAEKFSPEFQDFVNKCLKKNYKERPNypelLQH 261

                 ..
gi 4504217   801 TF 802
Cdd:cd06617  262 PF 263
STKc_CDK7 cd07841
Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 7; STKs ...
584-714 2.04e-06

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: 51.03  E-value: 2.04e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   584 LQELRHENVALYLGLFLARGaegpaalwegNLAVVSEHCTrGSLQDLLAQREIKLDWMFKSSLLLDLIKGIRYLHHRGVA 663
Cdd:cd07841   56 LQELKHPNIIGLLDVFGHKS----------NINLVFEFME-TDLEKVIKDKSIVLTPADIKSYMLMTLRGLEYLHSNWIL 124
                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 4504217   664 HGRLKSRNCIVDGRFVLKITDHGHGRlleaqkVLPEPPRA-EDQLWT----APELL 714
Cdd:cd07841  125 HRDLKPNNLLIASDGVLKLADFGLAR------SFGSPNRKmTHQVVTrwyrAPELL 174
STKc_Nek11 cd08222
Catalytic domain of the Protein Serine/Threonine Kinase, Never In Mitosis gene A (NIMA) ...
584-797 2.19e-06

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: 50.50  E-value: 2.19e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   584 LQELRHENVALYLGLFLARGaegpaalwegNLAVVSEHCTRGSLQD----------LLAQREIkLDWmfksslLLDLIKG 653
Cdd:cd08222   56 LSKLDHPAIVKFHDSFVEKE----------SFCIVTEYCEGGDLDDkiseykksgtTIDENQI-LDW------FIQLLLA 118
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   654 IRYLHHRGVAHGRLKSRNcIVDGRFVLKITDHGHGRLL-----EAQKVLPEPpraedqLWTAPELLRDPALERRgtlaGD 728
Cdd:cd08222  119 VQYMHERRILHRDLKAKN-IFLKNNVIKVGDFGISRILmgtsdLATTFTGTP------YYMSPEVLKHEGYNSK----SD 187
                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 4504217   729 VFSLAIIMQEVVCRS---APYAMLELTPEEVVQRVRSPPplcrplvsmDQAPVECILLMKQCWAEQPELRPS 797
Cdd:cd08222  188 IWSLGCILYEMCCLKhafDGQNLLSVMYKIVEGETPSLP---------DKYSKELNAIYSRMLNKDPALRPS 250
STKc_Chk1 cd14069
Catalytic domain of the Serine/Threonine kinase, Checkpoint kinase 1; STKs catalyze the ...
587-736 2.39e-06

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: 50.41  E-value: 2.39e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   587 LRHENVALYLGLflargAEGPAALWegnlaVVSEHCTRGSLQDLLAQrEIKLDWMFKSSLLLDLIKGIRYLHHRGVAHGR 666
Cdd:cd14069   57 LSHKNVVRFYGH-----RREGEFQY-----LFLEYASGGELFDKIEP-DVGMPEDVAQFYFQQLMAGLKYLHSCGITHRD 125
                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 4504217   667 LKSRNCIVDGRFVLKITDHG-------HGRLLEAQKVLPEPPraedqlWTAPELLRDPALerRGTLAgDVFSLAIIM 736
Cdd:cd14069  126 IKPENLLLDENDNLKISDFGlatvfryKGKERLLNKMCGTLP------YVAPELLAKKKY--RAEPV-DVWSCGIVL 193
STKc_PAK_I cd06647
Catalytic domain of the Serine/Threonine Kinase, Group I p21-activated kinase; STKs catalyze ...
584-746 2.84e-06

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: 49.93  E-value: 2.84e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   584 LQELRHENVALYLGLFLArGAEgpaaLWegnlaVVSEHCTRGSLQDLLAqrEIKLDWMFKSSLLLDLIKGIRYLHHRGVA 663
Cdd:cd06647   58 MRENKNPNIVNYLDSYLV-GDE----LW-----VVMEYLAGGSLTDVVT--ETCMDEGQIAAVCRECLQALEFLHSNQVI 125
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   664 HGRLKSRNCIVDGRFVLKITDHGHgrlleAQKVLPEPPRAEDQL----WTAPELLRDPALERRgtlaGDVFSLAIIMQEV 739
Cdd:cd06647  126 HRDIKSDNILLGMDGSVKLTDFGF-----CAQITPEQSKRSTMVgtpyWMAPEVVTRKAYGPK----VDIWSLGIMAIEM 196

                 ....*..
gi 4504217   740 VCRSAPY 746
Cdd:cd06647  197 VEGEPPY 203
STKc_IRAK1 cd14159
Catalytic domain of the Serine/Threonine kinase, Interleukin-1 Receptor Associated Kinase 1; ...
562-740 3.08e-06

Catalytic domain of the Serine/Threonine kinase, Interleukin-1 Receptor Associated Kinase 1; 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. IRAK1 plays a role in the activation of IRF3/7, STAT, and NFkB. It mediates IL-6 and IFN-gamma responses following IL-1 and IL-18 stimulation, respectively. It also plays an essential role in IFN-alpha induction downstream of TLR7 and TLR9. The IRAK1 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: 271061 [Multi-domain]  Cd Length: 296  Bit Score: 50.21  E-value: 3.08e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   562 LKKFPGDQHI---AIRPATKTAFSKLQELRHENVALYLGLFLARGaegpaalwegNLAVVSEHCTRGSLQDLL--AQREI 636
Cdd:cd14159   21 VKRLKEDSELdwsVVKNSFLTEVEKLSRFRHPNIVDLAGYSAQQG----------NYCLIYVYLPNGSLEDRLhcQVSCP 90
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   637 KLDWMFKSSLLLDLIKGIRYLHHRGVA--HGRLKSRNCIVDGRFVLKITDHGHGRLLEAQKvlpEPPRAEDQLWTA---- 710
Cdd:cd14159   91 CLSWSQRLHVLLGTARAIQYLHSDSPSliHGDVKSSNILLDAALNPKLGDFGLARFSRRPK---QPGMSSTLARTQtvrg 167
                        170       180       190
                 ....*....|....*....|....*....|....*.
gi 4504217   711 ------PELLRDPALerrgTLAGDVFSLAIIMQEVV 740
Cdd:cd14159  168 tlaylpEEYVKTGTL----SVEIDVYSFGVVLLELL 199
STKc_MAP4K5 cd06646
Catalytic domain of the Serine/Threonine Kinase, Mitogen-activated protein kinase kinase ...
584-753 3.20e-06

Catalytic domain of the Serine/Threonine Kinase, Mitogen-activated protein kinase kinase kinase kinase 5; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAP4K5, also called germinal center kinase-related enzyme (GCKR), has been shown to activate the MAPK c-Jun N-terminal kinase (JNK). MAP4K5 also facilitates Wnt signaling in B cells, and may therefore be implicated in the control of cell fate, proliferation, and polarity. MAP4Ks are involved in some MAPK signaling pathways by activating a MAPK kinase kinase. 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 MAP3K to start the triple kinase core cascade or indirectly through a mediator kinase, a MAP4K. Members of this subfamily contain an N-terminal catalytic domain and a C-terminal citron homology (CNH) regulatory domain. The MAP4K5 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: 270813 [Multi-domain]  Cd Length: 268  Bit Score: 50.03  E-value: 3.20e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   584 LQELRHENVALYLGLFLARgaegpAALWegnlaVVSEHCTRGSLQDLL----AQREIKLDWMFKSSLlldliKGIRYLHH 659
Cdd:cd06646   60 VKECKHCNIVAYFGSYLSR-----EKLW-----ICMEYCGGGSLQDIYhvtgPLSELQIAYVCRETL-----QGLAYLHS 124
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   660 RGVAHGRLKSRNCIvdgrfvlkITDHGHGRLLE---AQKVLPEPPRAEDQL----WTAPELlrdPALERRGTLAG--DVF 730
Cdd:cd06646  125 KGKMHRDIKGANIL--------LTDNGDVKLADfgvAAKITATIAKRKSFIgtpyWMAPEV---AAVEKNGGYNQlcDIW 193
                        170       180
                 ....*....|....*....|...
gi 4504217   731 SLAIIMQEVVCRSAPyaMLELTP 753
Cdd:cd06646  194 AVGITAIELAELQPP--MFDLHP 214
STKc_CDC2L1 cd07843
Catalytic domain of the Serine/Threonine Kinase, Cell Division Cycle 2-like 1; STKs catalyze ...
627-738 3.36e-06

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: 50.30  E-value: 3.36e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   627 LQDLL-------AQREIKldwmfksSLLLDLIKGIRYLHHRGVAHGRLKSRNCIVDGRFVLKITDHGHGRLleaqkvLPE 699
Cdd:cd07843   92 LKSLMetmkqpfLQSEVK-------CLMLQLLSGVAHLHDNWILHRDLKTSNLLLNNRGILKICDFGLARE------YGS 158
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....
gi 4504217   700 PPRAEDQ----LW-TAPELLRDpalERRGTLAGDVFSLAIIMQE 738
Cdd:cd07843  159 PLKPYTQlvvtLWyRAPELLLG---AKEYSTAIDMWSVGCIFAE 199
PTKc_Ror1 cd05090
Catalytic domain of the Protein Tyrosine Kinase, Receptor tyrosine kinase-like Orphan Receptor ...
548-796 3.57e-06

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: 50.01  E-value: 3.57e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   548 DSPNIGVYEGdRVWLKKFPGDQHIAIR-------PATKTAFSK----LQELRHENVALYLGlflargaegpAALWEGNLA 616
Cdd:cd05090   15 ECAFGKIYKG-HLYLPGMDHAQLVAIKtlkdynnPQQWNEFQQeaslMTELHHPNIVCLLG----------VVTQEQPVC 83
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   617 VVSEHCTRGSLQDLLAQRE--------IKLDWMFKSSL--------LLDLIKGIRYLHHRGVAHGRLKSRNCIVDGRFVL 680
Cdd:cd05090   84 MLFEFMNQGDLHEFLIMRSphsdvgcsSDEDGTVKSSLdhgdflhiAIQIAAGMEYLSSHFFVHKDLAARNILVGEQLHV 163
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   681 KITDHGHGR-LLEAQKVLPEPPRAEDQLWTAPELLrdpaLERRGTLAGDVFSLAIIMQEVVCRS-APYamLELTPEEVVQ 758
Cdd:cd05090  164 KISDLGLSReIYSSDYYRVQNKSLLPIRWMPPEAI----MYGKFSSDSDIWSFGVVLWEIFSFGlQPY--YGFSNQEVIE 237
                        250       260       270
                 ....*....|....*....|....*....|....*...
gi 4504217   759 RVRSPPPLCRPlvsmDQAPVECILLMKQCWAEQPELRP 796
Cdd:cd05090  238 MVRKRQLLPCS----EDCPPRMYSLMTECWQEIPSRRP 271
PBP1_SAP_GC-like cd06370
Ligand-binding domain of membrane bound guanylyl cyclases; Ligand-binding domain of membrane ...
161-356 3.82e-06

Ligand-binding domain of membrane bound guanylyl cyclases; Ligand-binding domain of membrane bound guanylyl cyclases (GCs), which are known to be activated by sperm-activating peptides (SAPs), such as speract or resact. These ligand peptides are released by a range of invertebrates to stimulate the metabolism and motility of spermatozoa and are also potent chemoattractants. These GCs contain a single transmembrane segment, an extracellular ligand binding domain, and intracellular protein kinase-like and cyclase catalytic domains. GCs of insect and nematodes, which exhibit high sequence similarity to the speract receptor are also included in this model.


Pssm-ID: 380593 [Multi-domain]  Cd Length: 400  Bit Score: 50.71  E-value: 3.82e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   161 TAPAVTPAADALYALLRAFGWARVALVTAPQDLWVEAGRSLSTALRARGLPVASVTSMEPLDLSGA------REALRKVR 234
Cdd:cd06370  117 TIPPDSQISKSVIALLKHFNWNKVSIVYENETKWSKIADTIKELLELNNIEINHEEYFPDPYPYTTshgnpfDKIVEETK 196
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   235 DGPRVtaVIMVMHSVLLggeeqRYLLEAAEELGLTD-GSLVFL-----PFDTIHYALSPGPEALAALANSSQ-LRRAHDA 307
Cdd:cd06370  197 EKTRI--YVFLGDYSLL-----REFMYYAEDLGLLDnGDYVVIgveldQYDVDDPAKYPNFLSGDYTKNDTKeALEAFRS 269
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 4504217   308 VLTLTRHCPSEGSVLDSLRRAQERRELP-------SDLNLQQVSPLFGT-IYDAVFL 356
Cdd:cd06370  270 VLIVTPSPPTNPEYEKFTKKVKEYNKLPpfnfpnpEGIEKTKEVPIYAAyLYDAVML 326
PTKc_VEGFR1 cd14207
Catalytic domain of the Protein Tyrosine Kinases, Vascular Endothelial Growth Factor Receptors; ...
626-796 4.24e-06

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: 50.00  E-value: 4.24e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   626 SLQDLlAQREIKLDWMFKSSLLL-DLI-------KGIRYLHHRGVAHGRLKSRNCIVDGRFVLKITDHGHGRLLEAQkvl 697
Cdd:cd14207  158 SLSDV-EEEEEDSGDFYKRPLTMeDLIsysfqvaRGMEFLSSRKCIHRDLAARNILLSENNVVKICDFGLARDIYKN--- 233
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   698 PEPPRAEDQL----WTAPELLRDPALERRGtlagDVFSLAIIMQEVVCRSA-PYAMLELTpEEVVQRVRSPPPLCRPlvs 772
Cdd:cd14207  234 PDYVRKGDARlplkWMAPESIFDKIYSTKS----DVWSYGVLLWEIFSLGAsPYPGVQID-EDFCSKLKEGIRMRAP--- 305
                        170       180
                 ....*....|....*....|....
gi 4504217   773 mDQAPVECILLMKQCWAEQPELRP 796
Cdd:cd14207  306 -EFATSEIYQIMLDCWQGDPNERP 328
STKc_CDK10 cd07845
Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 10; STKs ...
584-738 4.51e-06

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: 50.06  E-value: 4.51e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   584 LQELRHENVALYLGLFLARGAEgpaalwegNLAVVSEHCTrgslQDLLAQreikLDWM---FKSS----LLLDLIKGIRY 656
Cdd:cd07845   60 LLNLRHPNIVELKEVVVGKHLD--------SIFLVMEYCE----QDLASL----LDNMptpFSESqvkcLMLQLLRGLQY 123
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   657 LHHRGVAHGRLKSRNCIVDGRFVLKITDHGHGRLLEaqkvLPEPPRAED--QLW-TAPELLRDpalERRGTLAGDVFSLA 733
Cdd:cd07845  124 LHENFIIHRDLKVSNLLLTDKGCLKIADFGLARTYG----LPAKPMTPKvvTLWyRAPELLLG---CTTYTTAIDMWAVG 196

                 ....*
gi 4504217   734 IIMQE 738
Cdd:cd07845  197 CILAE 201
PKc_Myt1 cd14050
Catalytic domain of the Dual-specificity protein kinase, Myt1; Dual-specificity PKs catalyze ...
611-741 5.11e-06

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: 49.23  E-value: 5.11e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   611 WE--GNLAVVSEHCtRGSLQDLLAQ------REIkldWMFksslLLDLIKGIRYLHHRGVAHGRLKSRNCIVDGRFVLKI 682
Cdd:cd14050   70 WEekGILYIQTELC-DTSLQQYCEEthslpeSEV---WNI----LLDLLKGLKHLHDHGLIHLDIKPANIFLSKDGVCKL 141
                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 4504217   683 TDHGhgrlleaqkVLPEPPRAE-------DQLWTAPELLRDpalerRGTLAGDVFSLAIIMQEVVC 741
Cdd:cd14050  142 GDFG---------LVVELDKEDihdaqegDPRYMAPELLQG-----SFTKAADIFSLGITILELAC 193
STKc_Rim15_like cd05611
Catalytic domain of fungal Rim15-like Protein Serine/Threonine Kinases; STKs catalyze the ...
614-762 5.73e-06

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: 49.02  E-value: 5.73e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   614 NLAVVSEHCTRGSLQDLLAQR-EIKLDWMFKssLLLDLIKGIRYLHHRGVAHGRLKSRNCIVDGRFVLKITDHGHGRLLE 692
Cdd:cd05611   71 YLYLVMEYLNGGDCASLIKTLgGLPEDWAKQ--YIAEVVLGVEDLHQRGIIHRDIKPENLLIDQTGHLKLTDFGLSRNGL 148
                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 4504217   693 AQKvlpEPPR---AEDQLwtAPELLrdpaLERRGTLAGDVFSLAIIMQEVVCRSAPYAmlELTPEEVVQRVRS 762
Cdd:cd05611  149 EKR---HNKKfvgTPDYL--APETI----LGVGDDKMSDWWSLGCVIFEFLFGYPPFH--AETPDAVFDNILS 210
PTKc_Tie1 cd05089
Catalytic domain of the Protein Tyrosine Kinase, Tie1; Protein Tyrosine Kinase (PTK) family; ...
613-796 7.39e-06

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: 49.23  E-value: 7.39e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   613 GNLAVVSEHCTRGSLQDLLAQ-REIKLDWMF----------KSSLLL----DLIKGIRYLHHRGVAHGRLKSRNCIVDGR 677
Cdd:cd05089   76 GYLYIAIEYAPYGNLLDFLRKsRVLETDPAFakehgtastlTSQQLLqfasDVAKGMQYLSEKQFIHRDLAARNVLVGEN 155
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   678 FVLKITDHG--HGRLLEAQKVLPEPPRAedqlWTAPELLRDPALerrgTLAGDVFSLAIIMQEVVCRSA-PYAmlELTPE 754
Cdd:cd05089  156 LVSKIADFGlsRGEEVYVKKTMGRLPVR----WMAIESLNYSVY----TTKSDVWSFGVLLWEIVSLGGtPYC--GMTCA 225
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|..
gi 4504217   755 EVVQRVRSPPPLCRPLVSMDqapvECILLMKQCWAEQPELRP 796
Cdd:cd05089  226 ELYEKLPQGYRMEKPRNCDD----EVYELMRQCWRDRPYERP 263
STKc_Bck1_like cd06629
Catalytic domain of the Serine/Threonine Kinases, fungal Bck1-like Mitogen-Activated Protein ...
576-802 7.95e-06

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: 48.92  E-value: 7.95e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   576 ATKTAFSKLQELRHENVALYLGlflargaegpaalWEGNLAVVS---EHCTRGSLQDLLaQREIKLDWMFKSSLLLDLIK 652
Cdd:cd06629   54 ALKSEIDTLKDLDHPNIVQYLG-------------FEETEDYFSiflEYVPGGSIGSCL-RKYGKFEEDLVRFFTRQILD 119
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   653 GIRYLHHRGVAHGRLKSRNCIVDGRFVLKITDHGHGRlleaqkvlpeppRAEDQ-------------LWTAPELLRdpaL 719
Cdd:cd06629  120 GLAYLHSKGILHRDLKADNILVDLEGICKISDFGISK------------KSDDIygnngatsmqgsvFWMAPEVIH---S 184
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   720 ERRGTLAG-DVFSLAIIMQEVVCRSAPYamlelTPEEVVQRV------RSPPPLcRPLVSMDQapvECILLMKQCWAEQP 792
Cdd:cd06629  185 QGQGYSAKvDIWSLGCVVLEMLAGRRPW-----SDDEAIAAMfklgnkRSAPPV-PEDVNLSP---EALDFLNACFAIDP 255
                        250
                 ....*....|....
gi 4504217   793 ELRPS----MDHTF 802
Cdd:cd06629  256 RDRPTaaelLSHPF 269
STKc_IRAK2 cd14157
Catalytic domain of the Serine/Threonine kinase, Interleukin-1 Receptor Associated Kinase 2; ...
625-695 1.13e-05

Catalytic domain of the Serine/Threonine kinase, Interleukin-1 Receptor Associated Kinase 2; 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. IRAK2 plays a role in mediating NFkB activation by TLR3, TLR4, and TLR8. It is specifically targeted by the viral protein A52, which is important for virulence, to inhibit all IL-1/TLR pathways, indicating that IRAK2 has a predominant role in NFkB activation. It is redundant with IRAK1 in early signaling but is critical for late and sustained activation. The IRAK2 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: 271059 [Multi-domain]  Cd Length: 289  Bit Score: 48.68  E-value: 1.13e-05
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 4504217   625 GSLQDLLAQREIK--LDWMFKSSLLLDLIKGIRYLHHRGVAHGRLKSRNCIVDGRFVLKITdHGHGRLLEAQK 695
Cdd:cd14157   77 GSLQDRLQQQGGShpLPWEQRLSISLGLLKAVQHLHNFGILHGNIKSSNVLLDGNLLPKLG-HSGLRLCPVDK 148
STKc_NLK cd07853
Catalytic domain of the Serine/Threonine Kinase, Nemo-Like Kinase; STKs catalyze the transfer ...
556-742 1.15e-05

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: 48.97  E-value: 1.15e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   556 EGDRVWLKKFPGD-QHIAirpATKTAFSKLQEL---RHENV--AL------YLGLFlargaegpaalweGNLAVVSE--- 620
Cdd:cd07853   24 DGKRVALKKMPNVfQNLV---SCKRVFRELKMLcffKHDNVlsALdilqppHIDPF-------------EEIYVVTElmq 87
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   621 ---HCTRGSLQDLLAQrEIKLdwmfkssLLLDLIKGIRYLHHRGVAHGRLKSRNCIVDGRFVLKITDHGHGRLLEAQKVL 697
Cdd:cd07853   88 sdlHKIIVSPQPLSSD-HVKV-------FLYQILRGLKYLHSAGILHRDIKPGNLLVNSNCVLKICDFGLARVEEPDESK 159
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*
gi 4504217   698 PEPPRAEDQLWTAPELLRDpalERRGTLAGDVFSLAIIMQEVVCR 742
Cdd:cd07853  160 HMTQEVVTQYYRAPEILMG---SRHYTSAVDIWSVGCIFAELLGR 201
STKc_CDK9 cd07865
Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 9; STKs ...
584-744 1.18e-05

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: 48.52  E-value: 1.18e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   584 LQELRHENVALYLGLflARGAEGPAALWEGNLAVVSEHCTRgSLQDLLAQREIKLDWMFKSSLLLDLIKGIRYLHHRGVA 663
Cdd:cd07865   65 LQLLKHENVVNLIEI--CRTKATPYNRYKGSIYLVFEFCEH-DLAGLLSNKNVKFTLSEIKKVMKMLLNGLYYIHRNKIL 141
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   664 HGRLKSRNCIVDGRFVLKITDHGHGRLLEAQKVlPEPPRAEDQ---LW-TAPELL---RD--PALerrgtlagDVFSLAI 734
Cdd:cd07865  142 HRDMKAANILITKDGVLKLADFGLARAFSLAKN-SQPNRYTNRvvtLWyRPPELLlgeRDygPPI--------DMWGAGC 212
                        170
                 ....*....|
gi 4504217   735 IMQEVVCRSA 744
Cdd:cd07865  213 IMAEMWTRSP 222
PTKc_TrkA cd05092
Catalytic domain of the Protein Tyrosine Kinase, Tropomyosin Related Kinase A; PTKs catalyze ...
653-795 1.18e-05

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: 48.42  E-value: 1.18e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   653 GIRYLHHRGVAHGRLKSRNCIVDGRFVLKITDHGHGRLLEAQKVLPEPPRAEDQL-WTAPELLrdpaLERRGTLAGDVFS 731
Cdd:cd05092  134 GMVYLASLHFVHRDLATRNCLVGQGLVVKIGDFGMSRDIYSTDYYRVGGRTMLPIrWMPPESI----LYRKFTTESDIWS 209
                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 4504217   732 LAIIMQEVVCR-SAPYAMLELTpeEVVQRVRSPPPLCRPLVsmdqAPVECILLMKQCWAEQPELR 795
Cdd:cd05092  210 FGVVLWEIFTYgKQPWYQLSNT--EAIECITQGRELERPRT----CPPEVYAIMQGCWQREPQQR 268
STKc_PASK cd14004
Catalytic domain of the Serine/Threonine kinase, Per-ARNT-Sim (PAS) domain Kinase; STKs ...
625-799 1.18e-05

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: 48.15  E-value: 1.18e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   625 GSLQDLLAQREIK--LDWMFKSSLLLDLIKGIRYLHHRGVAHGRLKSRNCIVDGRFVLKITDHGHGRLLEAQKVlpeppr 702
Cdd:cd14004   91 GSGMDLFDFIERKpnMDEKEAKYIFRQVADAVKHLHDQGIVHRDIKDENVILDGNGTIKLIDFGSAAYIKSGPF------ 164
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   703 aeDQL-----WTAPELLRDpalERRGTLAGDVFSLAIIMQEVVCRSAPYAMLEltpEEVVQRVRSPPPLCRplvsmdqap 777
Cdd:cd14004  165 --DTFvgtidYAAPEVLRG---NPYGGKEQDIWALGVLLYTLVFKENPFYNIE---EILEADLRIPYAVSE--------- 227
                        170       180
                 ....*....|....*....|..
gi 4504217   778 vECILLMKQCWAEQPELRPSMD 799
Cdd:cd14004  228 -DLIDLISRMLNRDVGDRPTIE 248
STKc_PLK cd14099
Catalytic domain of the Serine/Threonine Kinases, Polo-like kinases; STKs catalyze the ...
587-800 1.37e-05

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: 47.93  E-value: 1.37e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   587 LRHENVALYLGLFlargaEGpaalwEGNLAVVSEHCTRGSLQDLLAQR----EIKLDWmfkssLLLDLIKGIRYLHHRGV 662
Cdd:cd14099   58 LKHPNIVKFHDCF-----ED-----EENVYILLELCSNGSLMELLKRRkaltEPEVRY-----FMRQILSGVKYLHSNRI 122
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   663 AHGRLKSRNCIVDGRFVLKITDHGHGRLL----EAQKVLPEPPRaedqlWTAPELLRDpaleRRG-TLAGDVFSLAIIMq 737
Cdd:cd14099  123 IHRDLKLGNLFLDENMNVKIGDFGLAARLeydgERKKTLCGTPN-----YIAPEVLEK----KKGhSFEVDIWSLGVIL- 192
                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 4504217   738 evvcrsapYAMLELTP-------EEVVQRVRS-----PPPLCRPLvsmdqapvECILLMKQCWAEQPELRPSMDH 800
Cdd:cd14099  193 --------YTLLVGKPpfetsdvKETYKRIKKneysfPSHLSISD--------EAKDLIRSMLQPDPTKRPSLDE 251
PTKc_Aatyk2 cd05086
Catalytic domain of the Protein Tyrosine Kinase, Apoptosis-associated tyrosine kinase 2; PTKs ...
617-760 1.49e-05

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: 47.94  E-value: 1.49e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   617 VVSEHCTRGSLQDLLAQREIKL----DWMFKSSLLLDLIKGIRYLHHRGVAHGRLKSRNCIVDGRFVLKITDHGHG---- 688
Cdd:cd05086   74 LVFEFCDLGDLKTYLANQQEKLrgdsQIMLLQRMACEIAAGLAHMHKHNFLHSDLALRNCYLTSDLTVKVGDYGIGfsry 153
                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 4504217   689 --RLLEAQKVLPEPPRaedqlWTAPELL---RDPALERRGTLAGDVFSLAIIMQEVVCRSA-PYAmlELTPEEVVQRV 760
Cdd:cd05086  154 keDYIETDDKKYAPLR-----WTAPELVtsfQDGLLAAEQTKYSNIWSLGVTLWELFENAAqPYS--DLSDREVLNHV 224
STKc_ULK1 cd14202
Catalytic domain of the Serine/Threonine kinase, Unc-51-like kinase 1; STKs catalyze the ...
584-758 1.51e-05

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: 48.08  E-value: 1.51e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   584 LQELRHEN-VALYLGLFLArgaegpaalweGNLAVVSEHCTRGSLQDLL-AQREIKLDWMfksSLLLDLIKG-IRYLHHR 660
Cdd:cd14202   55 LKELKHENiVALYDFQEIA-----------NSVYLVMEYCNGGDLADYLhTMRTLSEDTI---RLFLQQIAGaMKMLHSK 120
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   661 GVAHGRLKSRNCIVD---GR------FVLKITDHGHGRLLE----AQKVLPEPpraedqLWTAPELLRDPALERRgtlaG 727
Cdd:cd14202  121 GIIHRDLKPQNILLSysgGRksnpnnIRIKIADFGFARYLQnnmmAATLCGSP------MYMAPEVIMSQHYDAK----A 190
                        170       180       190
                 ....*....|....*....|....*....|.
gi 4504217   728 DVFSLAIIMQEVVCRSAPYAmlELTPEEVVQ 758
Cdd:cd14202  191 DLWSIGTIIYQCLTGKAPFQ--ASSPQDLRL 219
STKc_DRAK cd14106
Catalytic domain of the Serine/Threonine Kinase, Death-associated protein kinase-Related ...
615-735 1.52e-05

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: 48.12  E-value: 1.52e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   615 LAVVSEHCTRGSLQDLLAQREikldwMFKSS----LLLDLIKGIRYLHHRGVAHGRLKSRNCIVDGRFV---LKITDHGH 687
Cdd:cd14106   83 LILILELAAGGELQTLLDEEE-----CLTEAdvrrLMRQILEGVQYLHERNIVHLDLKPQNILLTSEFPlgdIKLCDFGI 157
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*....
gi 4504217   688 GRLLEAQKVLPEPPRAEDqlWTAPELLR-DPAlerrgTLAGDVFSLAII 735
Cdd:cd14106  158 SRVIGEGEEIREILGTPD--YVAPEILSyEPI-----SLATDMWSIGVL 199
STKc_PLK2 cd14188
Catalytic domain of the Serine/Threonine Kinase, Polo-like kinase 2; STKs catalyze the ...
614-799 1.59e-05

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: 47.70  E-value: 1.59e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   614 NLAVVSEHCTRGSLQDLLAQREIKLDWMFKSsLLLDLIKGIRYLHHRGVAHGRLKSRNCIVDGRFVLKITDHGHGRLLEa 693
Cdd:cd14188   75 NIYILLEYCSRRSMAHILKARKVLTEPEVRY-YLRQIVSGLKYLHEQEILHRDLKLGNFFINENMELKVGDFGLAARLE- 152
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   694 qkvlPEPPRAEDQLWTaPELLRDPALERRG-TLAGDVFSLAIIMQEVVCRSAPYAMLELtpEEVVQRVRSpPPLCRPLVS 772
Cdd:cd14188  153 ----PLEHRRRTICGT-PNYLSPEVLNKQGhGCESDIWALGCVMYTMLLGRPPFETTNL--KETYRCIRE-ARYSLPSSL 224
                        170       180
                 ....*....|....*....|....*..
gi 4504217   773 MDQAPveciLLMKQCWAEQPELRPSMD 799
Cdd:cd14188  225 LAPAK----HLIASMLSKNPEDRPSLD 247
STKc_TAO2 cd06634
Catalytic domain of the Serine/Threonine Kinase, Thousand-and-One Amino acids 2; STKs catalyze ...
584-745 2.10e-05

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: 47.71  E-value: 2.10e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   584 LQELRHENVALYLGLFLArgaegpaalwEGNLAVVSEHCTrGSLQDLLAQREIKLDWMFKSSLLLDLIKGIRYLHHRGVA 663
Cdd:cd06634   69 LQKLRHPNTIEYRGCYLR----------EHTAWLVMEYCL-GSASDLLEVHKKPLQEVEIAAITHGALQGLAYLHSHNMI 137
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   664 HGRLKSRNCIVDGRFVLKITDHGHGRLLEAQKVLPEPPraedqLWTAPELLRdpALErRGTLAG--DVFSLAIIMQEVVC 741
Cdd:cd06634  138 HRDVKAGNILLTEPGLVKLGDFGSASIMAPANSFVGTP-----YWMAPEVIL--AMD-EGQYDGkvDVWSLGITCIELAE 209

                 ....
gi 4504217   742 RSAP 745
Cdd:cd06634  210 RKPP 213
PTKc_TrkC cd05094
Catalytic domain of the Protein Tyrosine Kinase, Tropomyosin Related Kinase C; PTKs catalyze ...
628-811 2.23e-05

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: 47.70  E-value: 2.23e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   628 QDLLAQREIKLDWMFKssLLLDLIKGIRYLHHRGVAHGRLKSRNCIVDGRFVLKITDHGHGR--------LLEAQKVLPe 699
Cdd:cd05094  112 QPRQAKGELGLSQMLH--IATQIASGMVYLASQHFVHRDLATRNCLVGANLLVKIGDFGMSRdvystdyyRVGGHTMLP- 188
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   700 ppraedQLWTAPELLrdpaLERRGTLAGDVFSLAIIMQEVVCR-SAPYamLELTPEEVVQRVRSPPPLCRPLVsmdqAPV 778
Cdd:cd05094  189 ------IRWMPPESI----MYRKFTTESDVWSFGVILWEIFTYgKQPW--FQLSNTEVIECITQGRVLERPRV----CPK 252
                        170       180       190
                 ....*....|....*....|....*....|...
gi 4504217   779 ECILLMKQCWAEQPELRPSMDHTFDLFKNINKG 811
Cdd:cd05094  253 EVYDIMLGCWQREPQQRLNIKEIYKILHALGKA 285
PTKc_Zap-70 cd05115
Catalytic domain of the Protein Tyrosine Kinase, Zeta-chain-associated protein of 70kDa; PTKs ...
614-796 2.69e-05

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: 47.25  E-value: 2.69e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   614 NLAVVSEHCTRGSLQDLLAQREIKLDWMFKSSLLLDLIKGIRYLHHRGVAHGRLKSRNCIVDGRFVLKITDHGHGRLLEA 693
Cdd:cd05115   77 ALMLVMEMASGGPLNKFLSGKKDEITVSNVVELMHQVSMGMKYLEEKNFVHRDLAARNVLLVNQHYAKISDFGLSKALGA 156
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   694 QKVLPEPPRAEDQ--LWTAPELLrdpaLERRGTLAGDVFSLAIIMQEVVCRSA-PYAMLElTPE-----EVVQRVRSPPp 765
Cdd:cd05115  157 DDSYYKARSAGKWplKWYAPECI----NFRKFSSRSDVWSYGVTMWEAFSYGQkPYKKMK-GPEvmsfiEQGKRMDCPA- 230
                        170       180       190
                 ....*....|....*....|....*....|.
gi 4504217   766 lcrplvsmdQAPVECILLMKQCWAEQPELRP 796
Cdd:cd05115  231 ---------ECPPEMYALMSDCWIYKWEDRP 252
STKc_MAPK cd07834
Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein Kinase; STKs ...
650-799 2.69e-05

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: 47.52  E-value: 2.69e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   650 LIKGIRYLHHRGVAHGRLKSRNCIVDGRFVLKITDHGHGRLLeaqkvlpEPPRAEDQL-------W-TAPELLRDPaleR 721
Cdd:cd07834  112 ILRGLKYLHSAGVIHRDLKPSNILVNSNCDLKICDFGLARGV-------DPDEDKGFLteyvvtrWyRAPELLLSS---K 181
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   722 RGTLAGDVFSLAIIMQEVVCRSA------PYAMLEL------TP-EEVVQRVRSP---------PPLCRPLVS--MDQAP 777
Cdd:cd07834  182 KYTKAIDIWSVGCIFAELLTRKPlfpgrdYIDQLNLivevlgTPsEEDLKFISSEkarnylkslPKKPKKPLSevFPGAS 261
                        170       180
                 ....*....|....*....|..
gi 4504217   778 VECILLMKQCWAEQPELRPSMD 799
Cdd:cd07834  262 PEAIDLLEKMLVFNPKKRITAD 283
STKc_IKK cd13989
Catalytic domain of the Serine/Threonine kinase, Inhibitor of Nuclear Factor-KappaB Kinase ...
620-746 3.02e-05

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: 47.06  E-value: 3.02e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   620 EHCTRGSLQDLLAQ-------REIKLdwmfkSSLLLDLIKGIRYLHHRGVAHGRLKSRNCI---VDGRFVLKITDHGHGR 689
Cdd:cd13989   79 EYCSGGDLRKVLNQpenccglKESEV-----RTLLSDISSAISYLHENRIIHRDLKPENIVlqqGGGRVIYKLIDLGYAK 153
                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 4504217   690 LLEAQKVLPEPPRAEDQLwtAPELLRdpalERRGTLAGDVFSLAIIMQEVVCRSAPY 746
Cdd:cd13989  154 ELDQGSLCTSFVGTLQYL--APELFE----SKKYTCTVDYWSFGTLAFECITGYRPF 204
STKc_MAP4K3 cd06645
Catalytic domain of the Serine/Threonine Kinase, Mitogen-activated protein kinase kinase ...
584-753 4.34e-05

Catalytic domain of the Serine/Threonine Kinase, Mitogen-activated protein kinase kinase kinase kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAP4K3 plays a role in the nutrient-responsive pathway of mTOR (mammalian target of rapamycin) signaling. MAP4K3 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. mTOR regulates ribosome biogenesis and protein translation, and is frequently deregulated in cancer. MAP4Ks are involved in MAPK signaling pathways by activating a MAPK kinase kinase. 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 MAP3K to start the triple kinase core cascade or indirectly through a mediator kinase, a MAP4K. Members of this subfamily contain an N-terminal catalytic domain and a C-terminal citron homology (CNH) regulatory domain. The MAP4K3 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: 270812 [Multi-domain]  Cd Length: 272  Bit Score: 46.58  E-value: 4.34e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   584 LQELRHENVALYLGLFLARGaegpaALWegnlaVVSEHCTRGSLQDLL----AQREIKLDWMFKSSLlldliKGIRYLHH 659
Cdd:cd06645   62 MKDCKHSNIVAYFGSYLRRD-----KLW-----ICMEFCGGGSLQDIYhvtgPLSESQIAYVSRETL-----QGLYYLHS 126
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   660 RGVAHGRLKSRNCIVDGRFVLKITDHGHGRLLEA----QKVLPEPPraedqLWTAPELlrdPALERRGTLAG--DVFSLA 733
Cdd:cd06645  127 KGKMHRDIKGANILLTDNGHVKLADFGVSAQITAtiakRKSFIGTP-----YWMAPEV---AAVERKGGYNQlcDIWAVG 198
                        170       180
                 ....*....|....*....|
gi 4504217   734 IIMQEVVCRSAPyaMLELTP 753
Cdd:cd06645  199 ITAIELAELQPP--MFDLHP 216
PTKc_ALK_LTK cd05036
Catalytic domain of the Protein Tyrosine Kinases, Anaplastic Lymphoma Kinase and Leukocyte ...
646-799 4.85e-05

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: 46.61  E-value: 4.85e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   646 LLLDLIKGIRYLHHRGVAHGRLKSRNCIVD----GRfVLKITDHGHGRLLEAQKVLPEPPRAEDQL-WTAPELLRDPALe 720
Cdd:cd05036  121 LAQDVAKGCRYLEENHFIHRDIAARNCLLTckgpGR-VAKIGDFGMARDIYRADYYRKGGKAMLPVkWMPPEAFLDGIF- 198
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   721 rrgTLAGDVFSLAIIMQEVVCRS-APYAmlELTPEEVVQRVRS-----PPPLCrplvsmdqaPVECILLMKQCWAEQPEL 794
Cdd:cd05036  199 ---TSKTDVWSFGVLLWEIFSLGyMPYP--GKSNQEVMEFVTSggrmdPPKNC---------PGPVYRIMTQCWQHIPED 264

                 ....*
gi 4504217   795 RPSMD 799
Cdd:cd05036  265 RPNFS 269
STKc_PAK2 cd06655
Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 2; STKs catalyze the ...
584-746 5.55e-05

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: 46.26  E-value: 5.55e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   584 LQELRHENVALYLGLFLArGAEgpaalwegnLAVVSEHCTRGSLQDLLAqrEIKLDWMFKSSLLLDLIKGIRYLHHRGVA 663
Cdd:cd06655   70 MKELKNPNIVNFLDSFLV-GDE---------LFVVMEYLAGGSLTDVVT--ETCMDEAQIAAVCRECLQALEFLHANQVI 137
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   664 HGRLKSRNCIVDGRFVLKITDHGHgrlleAQKVLPEPPRAEDQL----WTAPELLRDPALERRgtlaGDVFSLAIIMQEV 739
Cdd:cd06655  138 HRDIKSDNVLLGMDGSVKLTDFGF-----CAQITPEQSKRSTMVgtpyWMAPEVVTRKAYGPK----VDIWSLGIMAIEM 208

                 ....*..
gi 4504217   740 VCRSAPY 746
Cdd:cd06655  209 VEGEPPY 215
PBP1_glutamate_receptors-like cd06269
ligand-binding domain of family C G-protein couples receptors (GPCRs), membrane bound guanylyl ...
161-356 5.80e-05

ligand-binding domain of family C G-protein couples receptors (GPCRs), membrane bound guanylyl cyclases such as natriuretic peptide receptors (NPRs), and N-terminal leucine/isoleucine/valine-binding protein (LIVBP)-like domain of ionotropic glutamate rece; This CD represents the ligand-binding domain of the family C G-protein couples receptors (GPCRs), membrane bound guanylyl cyclases such as the family of natriuretic peptide receptors (NPRs), and the N-terminal leucine-isoleucine-valine binding protein (LIVBP)-like domain of the ionotropic glutamate receptors, all of which are structurally similar and related to the periplasmic-binding fold type 1 family. The family C GPCRs consists of metabotropic glutamate receptor (mGluR), a calcium-sensing receptor (CaSR), gamma-aminobutyric acid receptor (GABAbR), the promiscuous L-alpha-amino acid receptor GPR6A, families of taste and pheromone receptors, and orphan receptors. Truncated splicing variants of the orphan receptors are not included in this CD. The family C GPCRs are activated by endogenous agonists such as amino acids, ions, and sugar based molecules. Their amino terminal ligand-binding region is homologous to the bacterial leucine-isoleucine-valine binding protein (LIVBP) and a leucine binding protein (LBP). The ionotropic glutamate receptors (iGluRs) have an integral ion channel and are subdivided into three major groups based on their pharmacology and structural similarities: NMDA receptors, AMPA receptors, and kainate receptors. The family of membrane bound guanylyl cyclases is further divided into three subfamilies: the ANP receptor (GC-A)/C-type natriuretic peptide receptor (GC-B), the heat-stable enterotoxin receptor (GC-C)/sensory organ specific membrane GCs such as retinal receptors (GC-E, GC-F), and olfactory receptors (GC-D and GC-G).


Pssm-ID: 380493 [Multi-domain]  Cd Length: 332  Bit Score: 46.64  E-value: 5.80e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   161 TAPAVTPAADALYALLRAFGWARVALVTApQDLWVEAG-RSLSTALRARGLPVASVTSMEPLDLSGAREALRKVRD-GPR 238
Cdd:cd06269  116 TVPPDSKQADAMLALVRRLGWNKVVLIYS-DDEYGEFGlEGLEELFQEKGGLITSRQSFDENKDDDLTKLLRNLRDtEAR 194
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   239 VtaVIMvmhsvLLGGEEQRYLLEAAEELGLTDGSLVFLPFDTihyalspgpEALAALANSSQLRRAHDAVLTLTRHCPSE 318
Cdd:cd06269  195 V--IIL-----LASPDTARSLMLEAKRLDMTSKDYVWFVIDG---------EASSSDEHGDEARQAAEGAITVTLIFPVV 258
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|...
gi 4504217   319 GSVLD-----SLRRAQERRELPSDLNLQQVSPLFgtiYDAVFL 356
Cdd:cd06269  259 KEFLKfsmelKLKSSKRKQGLNEEYELNNFAAFF---YDAVLA 298
STKc_MST4 cd06640
Catalytic domain of the Serine/Threonine Kinase, Mammalian Ste20-like protein kinase 4; STKs ...
615-822 5.93e-05

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: 46.20  E-value: 5.93e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   615 LAVVSEHCTRGSLQDLLaqREIKLDWMFKSSLLLDLIKGIRYLHHRGVAHGRLKSRNCIVDGRFVLKITDHG-HGRLLEA 693
Cdd:cd06640   77 LWIIMEYLGGGSALDLL--RAGPFDEFQIATMLKEILKGLDYLHSEKKIHRDIKAANVLLSEQGDVKLADFGvAGQLTDT 154
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   694 QkvLPEPPRAEDQLWTAPELLRDPALERRgtlaGDVFSLAIIMQEVVCRSAPYAmlELTPEEVVQRV-RSPPPLCRPLVS 772
Cdd:cd06640  155 Q--IKRNTFVGTPFWMAPEVIQQSAYDSK----ADIWSLGITAIELAKGEPPNS--DMHPMRVLFLIpKNNPPTLVGDFS 226
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 4504217   773 MDQAPvecilLMKQCWAEQPELRPS----MDHTFdLFKNINKGRK-TNIIDSMLR 822
Cdd:cd06640  227 KPFKE-----FIDACLNKDPSFRPTakelLKHKF-IVKNAKKTSYlTELIDRFKR 275
HNOBA pfam07701
Heme NO binding associated; The HNOBA domain is found associated with the HNOB domain and ...
820-865 6.45e-05

Heme NO binding associated; The HNOBA domain is found associated with the HNOB domain and pfam00211 in soluble cyclases and signalling proteins. The HNOB domain is predicted to function as a heme-dependent sensor for gaseous ligands, and transduce diverse downstream signals, in both bacteria and animals.


Pssm-ID: 462234  Cd Length: 214  Bit Score: 45.26  E-value: 6.45e-05
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*.
gi 4504217     820 MLRMLEQYSSNLEDLIRERTEEleleKQKTDRLLTQMLPPSVAEAL 865
Cdd:pfam07701  173 ALDQLEQKSAELEESMRELEEE----KKKTDELLYSMLPKSVADRL 214
STKc_IRE1 cd13982
Catalytic domain of the Serine/Threonine kinase, Inositol-requiring protein 1; STKs catalyze ...
626-736 6.73e-05

Catalytic domain of the Serine/Threonine kinase, Inositol-requiring protein 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. IRE1, also called Endoplasmic reticulum (ER)-to-nucleus signaling protein (or ERN), is an ER-localized type I transmembrane protein with kinase and endoribonuclease domains in the cytoplasmic side. It acts as an ER stress sensor and is the oldest and most conserved component of the unfolded protein response (UPR) in eukaryotes. The UPR is activated when protein misfolding is detected in the ER in order to decrease the synthesis of new proteins and increase the capacity of the ER to cope with the stress. During ER stress, IRE1 dimerizes and forms oligomers, allowing the kinase domain to undergo trans-autophosphorylation. This leads to a conformational change that stimulates its endoribonuclease activity and results in the cleavage of its mRNA substrate, HAC1 in yeast and XBP1 in metazoans, promoting a splicing event that enables translation into a transcription factor which activates the UPR. Mammals contain two IRE1 proteins, IRE1alpha (or ERN1) and IRE1beta (or ERN2). The Ire1 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: 270884 [Multi-domain]  Cd Length: 269  Bit Score: 46.11  E-value: 6.73e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   626 SLQDLLAQREIKLDWMFKS----SLLLDLIKGIRYLHHRGVAHGRLKSRNCIVD-----GRFVLKITDHGHGRLLEAQK- 695
Cdd:cd13982   80 SLQDLVESPRESKLFLRPGlepvRLLRQIASGLAHLHSLNIVHRDLKPQNILIStpnahGNVRAMISDFGLCKKLDVGRs 159
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....
gi 4504217   696 ---VLPEPPRAEDqlWTAPELLRDPaLERRGTLAGDVFSLAIIM 736
Cdd:cd13982  160 sfsRRSGVAGTSG--WIAPEMLSGS-TKRRQTRAVDIFSLGCVF 200
STKc_IKK_alpha cd14039
Catalytic domain of the Serine/Threonine kinase, Inhibitor of Nuclear Factor-KappaB Kinase ...
620-767 6.88e-05

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: 46.06  E-value: 6.88e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   620 EHCTRGSLQDLLAQRE----IKLDWMFksSLLLDLIKGIRYLHHRGVAHGRLKSRNCI---VDGRFVLKITDHGHGRLLE 692
Cdd:cd14039   76 EYCSGGDLRKLLNKPEnccgLKESQVL--SLLSDIGSGIQYLHENKIIHRDLKPENIVlqeINGKIVHKIIDLGYAKDLD 153
                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 4504217   693 aQKVLPEPPRAEDQlWTAPELLRDPALerrgTLAGDVFSLAIIMQEVVCRSAPYaMLELTPEEVVQRVRSPPPLC 767
Cdd:cd14039  154 -QGSLCTSFVGTLQ-YLAPELFENKSY----TVTVDYWSFGTMVFECIAGFRPF-LHNLQPFTWHEKIKKKDPKH 221
STKc_Nek7 cd08229
Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase ...
584-809 6.93e-05

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: 46.18  E-value: 6.93e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   584 LQELRHENVALYLGLFLArgaegpaalwEGNLAVVSEHCTRGSLQDLL----AQREI---KLDWMFksslLLDLIKGIRY 656
Cdd:cd08229   78 LKQLNHPNVIKYYASFIE----------DNELNIVLELADAGDLSRMIkhfkKQKRLipeKTVWKY----FVQLCSALEH 143
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   657 LHHRGVAHGRLKSRNCIVDGRFVLKITDHGHGRLLEAQKVlpepprAEDQLWTAPELLRDPALERRG-TLAGDVFSLAII 735
Cdd:cd08229  144 MHSRRVMHRDIKPANVFITATGVVKLGDLGLGRFFSSKTT------AAHSLVGTPYYMSPERIHENGyNFKSDIWSLGCL 217
                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 4504217   736 MQEVVCRSAPYAMLELTPEEVVQRVRSP--PPLcrplvSMDQAPVECILLMKQCWAEQPELRPSMDHTFDLFKNIN 809
Cdd:cd08229  218 LYEMAALQSPFYGDKMNLYSLCKKIEQCdyPPL-----PSDHYSEELRQLVNMCINPDPEKRPDITYVYDVAKRMH 288
STKc_PhKG cd14093
Catalytic domain of the Serine/Threonine Kinase, Phosphorylase kinase Gamma subunit; STKs ...
618-746 7.41e-05

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: 45.81  E-value: 7.41e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   618 VSEHCTRGSLQDLLAQReIKLDWMFKSSLLLDLIKGIRYLHHRGVAHGRLKSRNCIVDGRFVLKITDHGHGRLLEAQKVL 697
Cdd:cd14093   87 VFELCRKGELFDYLTEV-VTLSEKKTRRIMRQLFEAVEFLHSLNIVHRDLKPENILLDDNLNVKISDFGFATRLDEGEKL 165
                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 4504217   698 PE----PPraedqlWTAPELLR---DPALERRGtLAGDVFSLAIIMQEVVCRSAPY 746
Cdd:cd14093  166 RElcgtPG------YLAPEVLKcsmYDNAPGYG-KEVDMWACGVIMYTLLAGCPPF 214
PTKc_HER4 cd05110
Catalytic domain of the Protein Tyrosine Kinase, HER4; PTKs catalyze the transfer of the ...
644-796 7.98e-05

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: 45.83  E-value: 7.98e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   644 SSLLLD----LIKGIRYLHHRGVAHGRLKSRNCIVDGRFVLKITDHGHGRLLEAQKVLPEPPRAEDQL-WTAPELLRdpa 718
Cdd:cd05110  108 SQLLLNwcvqIAKGMMYLEERRLVHRDLAARNVLVKSPNHVKITDFGLARLLEGDEKEYNADGGKMPIkWMALECIH--- 184
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   719 lERRGTLAGDVFSLAIIMQEVVCRSA-PYAMLEL--TPEEVVQRVRSP-PPLCrplvsmdqaPVECILLMKQCWAEQPEL 794
Cdd:cd05110  185 -YRKFTHQSDVWSYGVTIWELMTFGGkPYDGIPTreIPDLLEKGERLPqPPIC---------TIDVYMVMVKCWMIDADS 254

                 ..
gi 4504217   795 RP 796
Cdd:cd05110  255 RP 256
STKc_Nek3 cd08219
Catalytic domain of the Protein Serine/Threonine Kinase, Never In Mitosis gene A (NIMA) ...
584-797 8.69e-05

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: 45.35  E-value: 8.69e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   584 LQELRHENVALYLGLFLArgaegpaalwEGNLAVVSEHCTRGSLQDLLAQREIKLdwmFKSSLLLD----LIKGIRYLHH 659
Cdd:cd08219   52 LAKMKHPNIVAFKESFEA----------DGHLYIVMEYCDGGDLMQKIKLQRGKL---FPEDTILQwfvqMCLGVQHIHE 118
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   660 RGVAHGRLKSRNCIVDGRFVLKITDHGHGRLLeAQKVLPEPPRAEDQLWTAPELLRDPALERRgtlaGDVFSLAIIMQEV 739
Cdd:cd08219  119 KRVLHRDIKSKNIFLTQNGKVKLGDFGSARLL-TSPGAYACTYVGTPYYVPPEIWENMPYNNK----SDIWSLGCILYEL 193
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 4504217   740 VCRSAPYAM-----LELtpeEVVQRVRSPPPLcrplvsmdQAPVECILLMKQCWAEQPELRPS 797
Cdd:cd08219  194 CTLKHPFQAnswknLIL---KVCQGSYKPLPS--------HYSYELRSLIKQMFKRNPRSRPS 245
PTKc_Syk cd05116
Catalytic domain of the Protein Tyrosine Kinase, Spleen tyrosine kinase; PTKs catalyze the ...
653-797 9.98e-05

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: 45.34  E-value: 9.98e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   653 GIRYLHHRGVAHGRLKSRNCIVDGRFVLKITDHGHGRLL-------EAQKVLPEPPRaedqlWTAPELLRDPALERRGtl 725
Cdd:cd05116  107 GMKYLEESNFVHRDLAARNVLLVTQHYAKISDFGLSKALradenyyKAQTHGKWPVK-----WYAPECMNYYKFSSKS-- 179
                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 4504217   726 agDVFSLAIIMQEVVCRS-APYamLELTPEEVVQRVRSPPPLCRPlvsmDQAPVECILLMKQCWAEQPELRPS 797
Cdd:cd05116  180 --DVWSFGVLMWEAFSYGqKPY--KGMKGNEVTQMIEKGERMECP----AGCPPEMYDLMKLCWTYDVDERPG 244
STKc_Nek6 cd08228
Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase ...
584-809 1.59e-04

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: 44.63  E-value: 1.59e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   584 LQELRHENVALYLGLFLArgaegpaalwEGNLAVVSEHCTRGSLQDLL----AQREI---KLDWMFksslLLDLIKGIRY 656
Cdd:cd08228   56 LKQLNHPNVIKYLDSFIE----------DNELNIVLELADAGDLSQMIkyfkKQKRLipeRTVWKY----FVQLCSAVEH 121
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   657 LHHRGVAHGRLKSRNCIVDGRFVLKITDHGHGRLLEAQKVlpepprAEDQLWTAPELLRDPALERRG-TLAGDVFSLAII 735
Cdd:cd08228  122 MHSRRVMHRDIKPANVFITATGVVKLGDLGLGRFFSSKTT------AAHSLVGTPYYMSPERIHENGyNFKSDIWSLGCL 195
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   736 MQEVVCRSAPYAMLELTPEEVVQRVRSP--PPL--------CRPLVSMdqapvecillmkqCWAEQPELRPSMDHTFDLF 805
Cdd:cd08228  196 LYEMAALQSPFYGDKMNLFSLCQKIEQCdyPPLptehysekLRELVSM-------------CIYPDPDQRPDIGYVHQIA 262

                 ....
gi 4504217   806 KNIN 809
Cdd:cd08228  263 KQMH 266
STKc_ACVR2a cd14141
Catalytic domain of the Serine/Threonine Kinase, Activin Type IIA Receptor; STKs catalyze the ...
587-794 1.69e-04

Catalytic domain of the Serine/Threonine Kinase, Activin Type IIA Receptor; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. ACVR2a (or ActRIIA) 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. ACVR2b is one of two ACVR2 receptors found in vertebrates. Type II receptors 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. The ACVR2a 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: 271043 [Multi-domain]  Cd Length: 290  Bit Score: 45.03  E-value: 1.69e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   587 LRHENVALYLGLfLARGAEGPAALWegnlaVVSEHCTRGSLQDLLAQREIKldWMFKSSLLLDLIKGIRYLH-------- 658
Cdd:cd14141   46 MKHENILQFIGA-EKRGTNLDVDLW-----LITAFHEKGSLTDYLKANVVS--WNELCHIAQTMARGLAYLHedipglkd 117
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   659 -HR-GVAHGRLKSRNCIVDGRFVLKITDHGHGRLLEAQKVLPEP-PRAEDQLWTAPELLRDPA-LERRGTLAGDVFSLAI 734
Cdd:cd14141  118 gHKpAIAHRDIKSKNVLLKNNLTACIADFGLALKFEAGKSAGDThGQVGTRRYMAPEVLEGAInFQRDAFLRIDMYAMGL 197
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 4504217   735 IMQEVVCR----SAPYAMLELTPEEVVQRVRSPPPLCRPLVSMDQAPVecillMKQCWAEQPEL 794
Cdd:cd14141  198 VLWELASRctasDGPVDEYMLPFEEEVGQHPSLEDMQEVVVHKKKRPV-----LRECWQKHAGM 256
PTKc_Mer cd14204
Catalytic Domain of the Protein Tyrosine Kinase, Mer; PTKs catalyze the transfer of the ...
584-797 1.76e-04

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: 44.93  E-value: 1.76e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   584 LQELRHENVALYLGLFLARGAEG-PAALwegnlaVVSEHCTRGSLQDLLAQREIKLDWMFKS-----SLLLDLIKGIRYL 657
Cdd:cd14204   63 MKDFNHPNVIRLLGVCLEVGSQRiPKPM------VILPFMKYGDLHSFLLRSRLGSGPQHVPlqtllKFMIDIALGMEYL 136
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   658 HHRGVAHGRLKSRNCIVDGRFVLKITDHG------HGRLLEAQKVLPEPPRaedqlWTAPELLRDpaleRRGTLAGDVFS 731
Cdd:cd14204  137 SSRNFLHRDLAARNCMLRDDMTVCVADFGlskkiySGDYYRQGRIAKMPVK-----WIAVESLAD----RVYTVKSDVWA 207
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 4504217   732 LAIIMQEVVCRS-APYAMLEltPEEVVQRVRSPPPLCRPLVSMDqapvECILLMKQCWAEQPELRPS 797
Cdd:cd14204  208 FGVTMWEIATRGmTPYPGVQ--NHEIYDYLLHGHRLKQPEDCLD----ELYDIMYSCWRSDPTDRPT 268
STKc_Sty1_Hog1 cd07856
Catalytic domain of the Serine/Threonine Kinases, Fungal Mitogen-Activated Protein Kinases ...
584-694 1.88e-04

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: 44.87  E-value: 1.88e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   584 LQELRHENVALYLGLFLArgaegPAAlwegNLAVVSEhCTRGSLQDLLAQReiKLDWMFKSSLLLDLIKGIRYLHHRGVA 663
Cdd:cd07856   63 LKHLRHENIISLSDIFIS-----PLE----DIYFVTE-LLGTDLHRLLTSR--PLEKQFIQYFLYQILRGLKYVHSAGVI 130
                         90       100       110
                 ....*....|....*....|....*....|.
gi 4504217   664 HGRLKSRNCIVDGRFVLKITDHGHGRLLEAQ 694
Cdd:cd07856  131 HRDLKPSNILVNENCDLKICDFGLARIQDPQ 161
STKc_Pho85 cd07836
Catalytic domain of the Serine/Threonine Kinase, Fungal Cyclin-Dependent protein Kinase Pho85; ...
572-689 1.92e-04

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: 44.78  E-value: 1.92e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   572 AIRpatktAFSKLQELRHEN-VALYLGLFLargaegpaalwEGNLAVVSEHCTrgslQDLLAQREIK-----LDWMFKSS 645
Cdd:cd07836   45 AIR-----EISLMKELKHENiVRLHDVIHT-----------ENKLMLVFEYMD----KDLKKYMDTHgvrgaLDPNTVKS 104
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....
gi 4504217   646 LLLDLIKGIRYLHHRGVAHGRLKSRNCIVDGRFVLKITDHGHGR 689
Cdd:cd07836  105 FTYQLLKGIAFCHENRVLHRDLKPQNLLINKRGELKLADFGLAR 148
STKc_PKB_beta cd05595
Catalytic domain of the Serine/Threonine Kinase, Protein Kinase B beta (also called Akt2); ...
649-809 1.94e-04

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: 45.00  E-value: 1.94e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   649 DLIKGIRYLHHRGVAHGRLKSRNCIVDGRFVLKITDHG---HGRLLEA-QKVLPEPPRaedqlWTAPELLRDPALERrgt 724
Cdd:cd05595  103 EIVSALEYLHSRDVVYRDIKLENLMLDKDGHIKITDFGlckEGITDGAtMKTFCGTPE-----YLAPEVLEDNDYGR--- 174
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   725 lAGDVFSLAIIMQEVVCRSAPY------AMLELTPEEVVQRVRSPPPLCRPLVS--MDQAPvecillmKQCWAEQPE-LR 795
Cdd:cd05595  175 -AVDWWGLGVVMYEMMCGRLPFynqdheRLFELILMEEIRFPRTLSPEAKSLLAglLKKDP-------KQRLGGGPSdAK 246
                        170
                 ....*....|....
gi 4504217   796 PSMDHTFdlFKNIN 809
Cdd:cd05595  247 EVMEHRF--FLSIN 258
STKc_JNK1 cd07875
Catalytic domain of the Serine/Threonine Kinase, c-Jun N-terminal Kinase 1; STKs catalyze the ...
635-741 2.03e-04

Catalytic domain of the Serine/Threonine Kinase, c-Jun N-terminal Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. JNK1 is expressed in every cell and tissue type. It specifically binds with JAMP (JNK1-associated membrane protein), which regulates the duration of JNK1 activity in response to stimuli. Specific JNK1 substrates include Itch and SG10, which are implicated in Th2 responses and airway inflammation, and microtubule dynamics and axodendritic length, respectively. Mice deficient in JNK1 are protected against arthritis, obesity, type 2 diabetes, cardiac cell death, and non-alcoholic liver disease, suggesting that JNK1 may play roles in the pathogenesis of these diseases. Initially, it was thought that JNK1 and JNK2 were functionally redundant as mice deficient in either genes could survive but disruption of both genes resulted in lethality. However, recent studies have shown that JNK1 and JNK2 perform distinct functions through specific binding partners and substrates. JNKs are mitogen-activated protein kinases that are involved in many stress-activated responses including those during inflammation, neurodegeneration, apoptosis, and persistent pain sensitization, among others. The JNK1 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: 143380 [Multi-domain]  Cd Length: 364  Bit Score: 45.04  E-value: 2.03e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   635 EIKLDWMFKSSLLLDLIKGIRYLHHRGVAHGRLKSRNCIVDGRFVLKITDHGHGRllEAQKVLPEPPRAEDQLWTAPELL 714
Cdd:cd07875  120 QMELDHERMSYLLYQMLCGIKHLHSAGIIHRDLKPSNIVVKSDCTLKILDFGLAR--TAGTSFMMTPYVVTRYYRAPEVI 197
                         90       100
                 ....*....|....*....|....*..
gi 4504217   715 RDPALERRgtlaGDVFSLAIIMQEVVC 741
Cdd:cd07875  198 LGMGYKEN----VDIWSVGCIMGEMIK 220
STKc_DAPK3 cd14195
Catalytic domain of the Serine/Threonine Kinase, Death-Associated Protein Kinase 3; STKs ...
584-746 2.18e-04

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: 44.22  E-value: 2.18e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   584 LQELRHENVALYLGLFLARGaegpaalwegNLAVVSEHCTRGSLQDLLAQREiKLDWMFKSSLLLDLIKGIRYLHHRGVA 663
Cdd:cd14195   62 LREIQHPNIITLHDIFENKT----------DVVLILELVSGGELFDFLAEKE-SLTEEEATQFLKQILDGVHYLHSKRIA 130
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   664 HGRLKSRNCIVDGRFV----LKITDHGHGRLLEA----QKVLPEPPraedqlWTAPELLRDPALerrgTLAGDVFSLAII 735
Cdd:cd14195  131 HFDLKPENIMLLDKNVpnprIKLIDFGIAHKIEAgnefKNIFGTPE------FVAPEIVNYEPL----GLEADMWSIGVI 200
                        170
                 ....*....|.
gi 4504217   736 MQEVVCRSAPY 746
Cdd:cd14195  201 TYILLSGASPF 211
STKc_MSK_C cd14092
C-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated ...
644-762 2.26e-04

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: 44.60  E-value: 2.26e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   644 SSLLLDLIKGIRYLHHRGVAHGRLKSRNCIvdgrFV-------LKITDHGHGRLLEAQKVLPEP----PRAedqlwtAPE 712
Cdd:cd14092  102 SRIMRQLVSAVSFMHSKGVVHRDLKPENLL----FTdedddaeIKIVDFGFARLKPENQPLKTPcftlPYA------APE 171
                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|..
gi 4504217   713 LLRDPALERRGTLAGDVFSLAIIMQEVVCRSAPY--AMLELTPEEVVQRVRS 762
Cdd:cd14092  172 VLKQALSTQGYDESCDLWSLGVILYTMLSGQVPFqsPSRNESAAEIMKRIKS 223
LivK COG0683
ABC-type branched-chain amino acid transport system, periplasmic component [Amino acid ...
120-269 2.32e-04

ABC-type branched-chain amino acid transport system, periplasmic component [Amino acid transport and metabolism];


Pssm-ID: 440447 [Multi-domain]  Cd Length: 314  Bit Score: 44.54  E-value: 2.32e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   120 RVSGLVGPVNPAACRPAELLAEEAGIALVpwgcpwtqAEGTTAPAVTP-----------AADALYA------LLRAFGWA 182
Cdd:COG0683   71 KVDAIVGPLSSGVALAVAPVAEEAGVPLI--------SPSATAPALTGpecspyvfrtaPSDAQQAealadyLAKKLGAK 142
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   183 RVALVTAPQDLWVEAGRSLSTALRARGLPVASVTSMePLDLSGAREALRKVRDGpRVTAVIMVMHsvllgGEEQRYLLEA 262
Cdd:COG0683  143 KVALLYDDYAYGQGLAAAFKAALKAAGGEVVGEEYY-PPGTTDFSAQLTKIKAA-GPDAVFLAGY-----GGDAALFIKQ 215

                 ....*..
gi 4504217   263 AEELGLT 269
Cdd:COG0683  216 AREAGLK 222
STKc_PAK1 cd06654
Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 1; STKs catalyze the ...
584-746 2.57e-04

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: 44.33  E-value: 2.57e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   584 LQELRHENVALYLGLFLArGAEgpaaLWegnlaVVSEHCTRGSLQDLLAqrEIKLDWMFKSSLLLDLIKGIRYLHHRGVA 663
Cdd:cd06654   71 MRENKNPNIVNYLDSYLV-GDE----LW-----VVMEYLAGGSLTDVVT--ETCMDEGQIAAVCRECLQALEFLHSNQVI 138
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   664 HGRLKSRNCIVDGRFVLKITDHGHgrlleAQKVLPEPPRAEDQL----WTAPELLRDPALERRgtlaGDVFSLAIIMQEV 739
Cdd:cd06654  139 HRDIKSDNILLGMDGSVKLTDFGF-----CAQITPEQSKRSTMVgtpyWMAPEVVTRKAYGPK----VDIWSLGIMAIEM 209

                 ....*..
gi 4504217   740 VCRSAPY 746
Cdd:cd06654  210 IEGEPPY 216
STK_BAK1_like cd14664
Catalytic domain of the Serine/Threonine Kinase, BRI1 associated kinase 1 and related STKs; ...
556-740 2.90e-04

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: 44.02  E-value: 2.90e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   556 EGDRVWLKKFPGDQHIAIRPATKTAFSKLQELRHENVALYLGLFLARgaegpaalwEGNLaVVSEHCTRGSLQDLLAQRE 635
Cdd:cd14664   16 NGTLVAVKRLKGEGTQGGDHGFQAEIQTLGMIRHRNIVRLRGYCSNP---------TTNL-LVYEYMPNGSLGELLHSRP 85
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   636 ---IKLDWMFKSSLLLDLIKGIRYLHHR---GVAHGRLKSRNCIVDGRFVLKITDHGHGRLLEAQKVLPEPPRAEDQLWT 709
Cdd:cd14664   86 esqPPLDWETRQRIALGSARGLAYLHHDcspLIIHRDVKSNNILLDEEFEAHVADFGLAKLMDDKDSHVMSSVAGSYGYI 165
                        170       180       190
                 ....*....|....*....|....*....|.
gi 4504217   710 APELlrdpALERRGTLAGDVFSLAIIMQEVV 740
Cdd:cd14664  166 APEY----AYTGKVSEKSDVYSYGVVLLELI 192
PK_IRAK3 cd14160
Pseudokinase domain of Interleukin-1 Receptor Associated Kinase 3; The pseudokinase domain ...
638-799 3.10e-04

Pseudokinase domain of Interleukin-1 Receptor Associated Kinase 3; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. 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 (a pseudokinase in the case of IRAK3), 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. IRAK3 (or IRAK-M) is the only IRAK that does not show kinase activity. It is found only in monocytes and macrophages in humans, and functions as a negative regulator of TLR signaling including TLR-2 induced p38 activation. It also negatively regulates the alternative NFkB pathway in a TLR-2 specific manner. IRAK3 is downregulated in the monocytes of obese people, and is associated with high SOD2, a marker of mitochondrial oxidative stress. It is an important inhibitor of inflammation in association with obesity and metabolic syndrome. The IRAK3 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: 271062 [Multi-domain]  Cd Length: 276  Bit Score: 44.11  E-value: 3.10e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   638 LDWMFKSSLLLDLIKGIRYLHHR---GVAHGRLKSRNCIVDGRFVLKITDHGHGRLleaqkvlpePPRAEDQ-------- 706
Cdd:cd14160   92 LSWHERINILIGIAKAIHYLHNSqpcTVICGNISSANILLDDQMQPKLTDFALAHF---------RPHLEDQsctinmtt 162
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   707 -----LWTAP-ELLRDPALerrgTLAGDVFSLAIIMQEVV--CR-----SAPYAMLELTPEEVVQRV---------RSPP 764
Cdd:cd14160  163 alhkhLWYMPeEYIRQGKL----SVKTDVYSFGIVIMEVLtgCKvvlddPKHLQLRDLLHELMEKRGldsclsfldLKFP 238
                        170       180       190
                 ....*....|....*....|....*....|....*.
gi 4504217   765 PlCRPLVSMdqapveCIL-LMKQCWAEQPELRPSMD 799
Cdd:cd14160  239 P-CPRNFSA------KLFrLAGRCTATKAKLRPDMD 267
STKc_CDK8_like cd07842
Catalytic domain of Cyclin-Dependent protein Kinase 8-like Serine/Threonine Kinases; STKs ...
562-714 3.28e-04

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: 44.20  E-value: 3.28e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   562 LKKFPGDQHiairpaTKTAFSK--------LQELRHENVALYLGLFLARGaegpaalwEGNLAVV---SEHctrgslqDL 630
Cdd:cd07842   32 IKKFKGDKE------QYTGISQsacreialLRELKHENVVSLVEVFLEHA--------DKSVYLLfdyAEH-------DL 90
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   631 LA----QREIKL----DWMFKSsLLLDLIKGIRYLHHRGVAHGRLKSRNCIVDG----RFVLKITDHGHGRLLEAQkvlP 698
Cdd:cd07842   91 WQiikfHRQAKRvsipPSMVKS-LLWQILNGIHYLHSNWVLHRDLKPANILVMGegpeRGVVKIGDLGLARLFNAP---L 166
                        170       180
                 ....*....|....*....|.
gi 4504217   699 EPPRAEDQ----LW-TAPELL 714
Cdd:cd07842  167 KPLADLDPvvvtIWyRAPELL 187
PTKc_PDGFR_beta cd05107
Catalytic domain of the Protein Tyrosine Kinase, Platelet Derived Growth Factor Receptor beta; ...
652-808 3.29e-04

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: 44.23  E-value: 3.29e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   652 KGIRYLHHRGVAHGRLKSRNC-IVDGRFVlKITDHGHGR-LLEAQKVLPEPPRAEDQLWTAPELLrdpaLERRGTLAGDV 729
Cdd:cd05107  250 NGMEFLASKNCVHRDLAARNVlICEGKLV-KICDFGLARdIMRDSNYISKGSTFLPLKWMAPESI----FNNLYTTLSDV 324
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   730 FSLAIIMQEVVCRSA-PYAMLELTpEEVVQRVRSPPPLCRPLVSMDqapvECILLMKQCWAEQPELRPSMDHTFDLFKNI 808
Cdd:cd05107  325 WSFGILLWEIFTLGGtPYPELPMN-EQFYNAIKRGYRMAKPAHASD----EIYEIMQKCWEEKFEIRPDFSQLVHLVGDL 399
STKc_TGFbR1_ACVR1b_ACVR1c cd14143
Catalytic domain of the Serine/Threonine Kinases, Transforming Growth Factor beta Type I ...
587-795 3.33e-04

Catalytic domain of the Serine/Threonine Kinases, Transforming Growth Factor beta Type I Receptor and Activin Type IB/IC Receptors; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TGFbR1, also called Activin receptor-Like Kinase 5 (ALK5), functions as a receptor for TGFbeta and phoshorylates SMAD2/3. TGFbeta proteins are cytokines that regulate cell growth, differentiation, and survival, and are critical in the development and progression of many human cancers. Mutations in TGFbR1 (and TGFbR2) can cause aortic aneurysm disorders such as Loeys-Dietz and Marfan syndromes. ACVR1b (also called ALK4) and ACVR1c (also called ALK7) act as receptors for activin A and B, respectively. TGFbR1, ACVR1b, and ACVR1c belong 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 (TM) region, and a cytoplasmic catalytic kinase domain. Type I receptors, like TGFbR1, ACVR1b, and ACVR1c, 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 TGFbR1 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: 271045 [Multi-domain]  Cd Length: 288  Bit Score: 43.97  E-value: 3.33e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   587 LRHENValyLGLFLARGAEGpaALWEgNLAVVSEHCTRGSLQDLLAQREIKLDWMFKssLLLDLIKGIRYLHHR------ 660
Cdd:cd14143   46 LRHENI---LGFIAADNKDN--GTWT-QLWLVSDYHEHGSLFDYLNRYTVTVEGMIK--LALSIASGLAHLHMEivgtqg 117
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   661 --GVAHGRLKSRNCIVDGRFVLKITDHGHG-RLLEAQKVLPEPP--RAEDQLWTAPELLRDP-------ALERrgtlaGD 728
Cdd:cd14143  118 kpAIAHRDLKSKNILVKKNGTCCIADLGLAvRHDSATDTIDIAPnhRVGTKRYMAPEVLDDTinmkhfeSFKR-----AD 192
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   729 VFSLAIIMQEVVCRSA----------PYAML---ELTPEE---VV--QRVRSPPP----LCRPLVSMDQapvecilLMKQ 786
Cdd:cd14143  193 IYALGLVFWEIARRCSiggihedyqlPYYDLvpsDPSIEEmrkVVceQKLRPNIPnrwqSCEALRVMAK-------IMRE 265

                 ....*....
gi 4504217   787 CWAEQPELR 795
Cdd:cd14143  266 CWYANGAAR 274
COG3473 COG3473
Maleate cis-trans isomerase [Secondary metabolites biosynthesis, transport and catabolism];
157-245 3.69e-04

Maleate cis-trans isomerase [Secondary metabolites biosynthesis, transport and catabolism];


Pssm-ID: 442696  Cd Length: 242  Bit Score: 43.27  E-value: 3.69e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   157 AEGTTAPAVTPAaDALYALLRAFGWARVALVTA-PQDL-------WVEAGRslsTALRARGLPVASVTSMEPLDLSGARE 228
Cdd:COG3473   99 TEATGVPVTTSA-GALVAALRALGARRIALVTPyTDEVnervvayLEAAGF---EVVAVRGLGLPDNAEIARVSPEELRD 174
                         90
                 ....*....|....*..
gi 4504217   229 ALRKVrDGPRVTAVIMV 245
Cdd:COG3473  175 LAREV-DAPDADAIFIS 190
STKc_PAK3 cd06656
Catalytic domain of the Protein Serine/Threonine Kinase, p21-activated kinase 3; Serine ...
584-746 3.72e-04

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: 43.94  E-value: 3.72e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   584 LQELRHENVALYLGLFLArGAEgpaaLWegnlaVVSEHCTRGSLQDLLAqrEIKLDWMFKSSLLLDLIKGIRYLHHRGVA 663
Cdd:cd06656   70 MRENKNPNIVNYLDSYLV-GDE----LW-----VVMEYLAGGSLTDVVT--ETCMDEGQIAAVCRECLQALDFLHSNQVI 137
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   664 HGRLKSRNCIVDGRFVLKITDHGHgrlleAQKVLPEPPRAEDQL----WTAPELLRDPALERRgtlaGDVFSLAIIMQEV 739
Cdd:cd06656  138 HRDIKSDNILLGMDGSVKLTDFGF-----CAQITPEQSKRSTMVgtpyWMAPEVVTRKAYGPK----VDIWSLGIMAIEM 208

                 ....*..
gi 4504217   740 VCRSAPY 746
Cdd:cd06656  209 VEGEPPY 215
STKc_MAPKAPK3 cd14172
Catalytic domain of the Serine/Threonine kinase, Mitogen-activated protein kinase-activated ...
615-746 5.04e-04

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: 43.05  E-value: 5.04e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   615 LAVVSEhCTRGSlqDLLAQREIKLDWMFK----SSLLLDLIKGIRYLHHRGVAHGRLKSRNCIVDGR---FVLKITDHGH 687
Cdd:cd14172   76 LLIIME-CMEGG--ELFSRIQERGDQAFTereaSEIMRDIGTAIQYLHSMNIAHRDVKPENLLYTSKekdAVLKLTDFGF 152
                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 4504217   688 GRLLEAQKVLPEPprAEDQLWTAPELLRDPALERrgtlAGDVFSLAIIMQEVVCRSAPY 746
Cdd:cd14172  153 AKETTVQNALQTP--CYTPYYVAPEVLGPEKYDK----SCDMWSLGVIMYILLCGFPPF 205
STKc_ERK5 cd07855
Catalytic domain of the Serine/Threonine Kinase, Extracellular signal-Regulated Kinase 5; ...
647-762 5.07e-04

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: 43.51  E-value: 5.07e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   647 LLDLIKGIRYLHHRGVAHGRLKSRNCIVDGRFVLKITDHGHGRLLEA----------QKVLPEPPRaedqlwtAPELLRd 716
Cdd:cd07855  115 LYQLLRGLKYIHSANVIHRDLKPSNLLVNENCELKIGDFGMARGLCTspeehkyfmtEYVATRWYR-------APELML- 186
                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 4504217   717 pALERRgTLAGDVFSLAIIMQEVVCRSAPY-------------AMLELTPEEVVQRVRS 762
Cdd:cd07855  187 -SLPEY-TQAIDMWSVGCIFAEMLGRRQLFpgknyvhqlqlilTVLGTPSQAVINAIGA 243
STKc_JNK3 cd07874
Catalytic domain of the Serine/Threonine Kinase, c-Jun N-terminal Kinase 3; STKs catalyze the ...
635-740 5.72e-04

Catalytic domain of the Serine/Threonine Kinase, c-Jun N-terminal Kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. JNK3 is expressed primarily in the brain, and to a lesser extent in the heart and testis. Mice deficient in JNK3 are protected against kainic acid-induced seizures, stroke, sciatic axotomy neural death, and neuronal death due to NGF deprivation, oxidative stress, or exposure to beta-amyloid peptide. This suggests that JNK3 may play roles in the pathogenesis of these diseases. 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. The JNK3 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: 143379 [Multi-domain]  Cd Length: 355  Bit Score: 43.54  E-value: 5.72e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   635 EIKLDWMFKSSLLLDLIKGIRYLHHRGVAHGRLKSRNCIVDGRFVLKITDHGHGRllEAQKVLPEPPRAEDQLWTAPELL 714
Cdd:cd07874  113 QMELDHERMSYLLYQMLCGIKHLHSAGIIHRDLKPSNIVVKSDCTLKILDFGLAR--TAGTSFMMTPYVVTRYYRAPEVI 190
                         90       100
                 ....*....|....*....|....*.
gi 4504217   715 RDPALERRgtlaGDVFSLAIIMQEVV 740
Cdd:cd07874  191 LGMGYKEN----VDIWSVGCIMGEMV 212
PTKc_CSF-1R cd05106
Catalytic domain of the Protein Tyrosine Kinase, Colony-Stimulating Factor-1 Receptor; PTKs ...
652-799 5.79e-04

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: 43.68  E-value: 5.79e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   652 KGIRYLHHRGVAHGRLKSRNCIVDGRFVLKITDHGHGRLLE--AQKVLPEPPRAEDQlWTAPELLRDPALerrgTLAGDV 729
Cdd:cd05106  223 QGMDFLASKNCIHRDVAARNVLLTDGRVAKICDFGLARDIMndSNYVVKGNARLPVK-WMAPESIFDCVY----TVQSDV 297
                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 4504217   730 FSLAIIMQEVVCRS-APYAMLeLTPEEVVQRVRSPPPLCRPlvsmDQAPVECILLMKQCWAEQPELRPSMD 799
Cdd:cd05106  298 WSYGILLWEIFSLGkSPYPGI-LVNSKFYKMVKRGYQMSRP----DFAPPEIYSIMKMCWNLEPTERPTFS 363
STKc_CdkB_plant cd07837
Catalytic domain of the Serine/Threonine Kinase, Plant B-type Cyclin-Dependent protein Kinase; ...
645-689 5.93e-04

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: 43.29  E-value: 5.93e-04
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*.
gi 4504217   645 SLLLDLIKGIRYLHHRGVAHGRLKSRNCIVD-GRFVLKITDHGHGR 689
Cdd:cd07837  113 SFMYQLCKGVAHCHSHGVMHRDLKPQNLLVDkQKGLLKIADLGLGR 158
STKc_LKB1 cd14119
Catalytic domain of the Serine/Threonine kinase, Liver Kinase B1; STKs catalyze the transfer ...
562-686 6.43e-04

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: 42.63  E-value: 6.43e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   562 LKKFP-GDQHIairpatKTAFSKLQELRHENVALYLGLFlaRGAEgpaalwEGNLAVVSEHCTrGSLQDLLAQREIKLDW 640
Cdd:cd14119   31 LRRIPnGEANV------KREIQILRRLNHRNVIKLVDVL--YNEE------KQKLYMVMEYCV-GGLQEMLDSAPDKRLP 95
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*..
gi 4504217   641 MFKS-SLLLDLIKGIRYLHHRGVAHGRLKSRNCIVDGRFVLKITDHG 686
Cdd:cd14119   96 IWQAhGYFVQLIDGLEYLHSQGIIHKDIKPGNLLLTTDGTLKISDFG 142
STKc_TGFbR-like cd13998
Catalytic domain of Transforming Growth Factor beta Receptor-like Serine/Threonine Kinases; ...
587-795 6.46e-04

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: 43.20  E-value: 6.46e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   587 LRHENVALylglFLA---RGAEGPAALWegnlaVVSEHCTRGSLQDLLaQREIkLDWMFKSSLLLDLIKGIRYLHHR--- 660
Cdd:cd13998   46 LKHENILQ----FIAadeRDTALRTELW-----LVTAFHPNGSL*DYL-SLHT-IDWVSLCRLALSVARGLAHLHSEipg 114
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   661 ------GVAHGRLKSRNCIV--DGRFVlkITDHGHGRLLEAQkvLPEPPRAED-QLWT----APELLRDPALERRGT--L 725
Cdd:cd13998  115 ctqgkpAIAHRDLKSKNILVknDGTCC--IADFGLAVRLSPS--TGEEDNANNgQVGTkrymAPEVLEGAINLRDFEsfK 190
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   726 AGDVFSLAIIMQEVV--CRSAPYAMLELTPeEVVQRVRSPPPL--CRPLVSMDQ-------APVECILL------MKQCW 788
Cdd:cd13998  191 RVDIYAMGLVLWEMAsrCTDLFGIVEEYKP-PFYSEVPNHPSFedMQEVVVRDKqrpnipnRWLSHPGLqslaetIEECW 269

                 ....*..
gi 4504217   789 AEQPELR 795
Cdd:cd13998  270 DHDAEAR 276
STKc_JNK2 cd07876
Catalytic domain of the Serine/Threonine Kinase, c-Jun N-terminal Kinase 2; STKs catalyze the ...
636-740 6.51e-04

Catalytic domain of the Serine/Threonine Kinase, c-Jun N-terminal Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. JNK2 is expressed in every cell and tissue type. It is specifically translocated to the mitochondria during dopaminergic cell death. Specific substrates include the microtubule-associated proteins DCX and Tau, as well as TIF-IA which is involved in ribosomal RNA synthesis regulation. Mice deficient in Jnk2 show protection against arthritis, type 1 diabetes, atherosclerosis, abdominal aortic aneurysm, cardiac cell death, TNF-induced liver damage, and tumor growth, indicating that JNK2 may play roles in the pathogenesis of these diseases. Initially it was thought that JNK1 and JNK2 were functionally redundant as mice deficient in either genes could survive but disruption of both genes resulted in lethality. However, recent studies have shown that JNK1 and JNK2 perform distinct functions through specific binding partners and 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. The JNK2 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: 143381 [Multi-domain]  Cd Length: 359  Bit Score: 43.48  E-value: 6.51e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   636 IKLDWMFKSSLLLDLIKGIRYLHHRGVAHGRLKSRNCIVDGRFVLKITDHGHGRLLEAQKVLpePPRAEDQLWTAPELLr 715
Cdd:cd07876  118 MELDHERMSYLLYQMLCGIKHLHSAGIIHRDLKPSNIVVKSDCTLKILDFGLARTACTNFMM--TPYVVTRYYRAPEVI- 194
                         90       100
                 ....*....|....*....|....*
gi 4504217   716 dpaLERRGTLAGDVFSLAIIMQEVV 740
Cdd:cd07876  195 ---LGMGYKENVDIWSVGCIMGELV 216
PBP1_LacI-like cd06299
ligand-binding domain of DNA-binding regulatory protein from Corynebacterium glutamicum ...
157-338 6.64e-04

ligand-binding domain of DNA-binding regulatory protein from Corynebacterium glutamicum produces significant amounts of L-glutamate directly from cheap sugar and ammonia; This group includes the ligand-binding domain of DNA-binding regulatory protein from Corynebacterium glutamicum which has a unique ability to produce significant amounts of L-glutamate directly from cheap sugar and ammonia. This regulatory protein is a member of the LacI-GalR family of bacterial transcription repressors. The LacI-GalR family repressors are composed of two functional domains: an N-terminal HTH (helix-turn-helix) domain, which is responsible for the DNA-binding specificity, and a C-terminal ligand-binding domain, which is homologous to the sugar-binding domain of ABC-type transport systems that contain the type 1 periplasmic binding protein-like fold. As also observed in the periplasmic binding proteins, the C-terminal domain of the bacterial transcription repressor undergoes a conformational change upon ligand binding which in turn changes the DNA binding affinity of the repressor.


Pssm-ID: 380522 [Multi-domain]  Cd Length: 268  Bit Score: 43.04  E-value: 6.64e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   157 AEGTTAPAVT----PAADALYALLRAFGWARVALVTAPQDLWVEAGR--SLSTALRARGLPVASVTSMEP--LDLSGARE 228
Cdd:cd06299   89 EGLGGVPVVTsdnrPGAREAVEYLVSLGHRRIGYISGPLSTSTGRERlaAFRAALTAAGIPIDEELVAFGdfRQDSGAAA 168
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   229 ALRKVRDGPRVTAVIMVMHSVLLGgeeqryLLEAAEELGLTDGSLVFL-PFDTIHYA--LSPgpeALAALANssQLRR-A 304
Cdd:cd06299  169 AHRLLSRGDPPTALIAGDSLMALG------AIQALRELGLRIGDDVSLiSFDDVPWFelLSP---PLTVIAQ--PVERiG 237
                        170       180       190
                 ....*....|....*....|....*....|....
gi 4504217   305 HDAVLTLTRHCPSEGSVldslrraqERRELPSDL 338
Cdd:cd06299  238 RRAVELLLALIENGGRA--------TSIRVPTEL 263
STKc_YSK4 cd06631
Catalytic domain of the Serine/Threonine Kinase, Yeast Sps1/Ste20-related Kinase 4; STKs ...
576-747 6.98e-04

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: 42.81  E-value: 6.98e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   576 ATKTAFSKLQE-------LRHENVALYLGlflargaegpAALWEGNLAVVSEHCTRGSLQDLLAqREIKLDWMFKSSLLL 648
Cdd:cd06631   42 KAEKEYEKLQEevdllktLKHVNIVGYLG----------TCLEDNVVSIFMEFVPGGSIASILA-RFGALEEPVFCRYTK 110
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   649 DLIKGIRYLHHRGVAHGRLKSRNCIVDGRFVLKITDHG-------------HGRLLEAQKVLPeppraedqLWTAPELLR 715
Cdd:cd06631  111 QILEGVAYLHNNNVIHRDIKGNNIMLMPNGVIKLIDFGcakrlcinlssgsQSQLLKSMRGTP--------YWMAPEVIN 182
                        170       180       190
                 ....*....|....*....|....*....|..
gi 4504217   716 DPALERRgtlaGDVFSLAIIMQEVVCRSAPYA 747
Cdd:cd06631  183 ETGHGRK----SDIWSIGCTVFEMATGKPPWA 210
STKc_p38alpha cd07877
Catalytic domain of the Serine/Threonine Kinase, p38alpha Mitogen-Activated Protein Kinase ...
584-740 7.30e-04

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: 43.10  E-value: 7.30e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   584 LQELRHENVALYLGLFlargaeGPA-ALWEGNLAVVSEHCTRGSLQDLLAQREIKLDWMfkSSLLLDLIKGIRYLHHRGV 662
Cdd:cd07877   70 LKHMKHENVIGLLDVF------TPArSLEEFNDVYLVTHLMGADLNNIVKCQKLTDDHV--QFLIYQILRGLKYIHSADI 141
                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 4504217   663 AHGRLKSRNCIVDGRFVLKITDHGHGRLLEAQKVlpepPRAEDQLWTAPELLRDpALERRGTLagDVFSLAIIMQEVV 740
Cdd:cd07877  142 IHRDLKPSNLAVNEDCELKILDFGLARHTDDEMT----GYVATRWYRAPEIMLN-WMHYNQTV--DIWSVGCIMAELL 212
STKc_TSSK6-like cd14164
Catalytic domain of testis-specific serine/threonine kinase 6 and similar proteins; STKs ...
582-798 7.82e-04

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: 42.54  E-value: 7.82e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   582 SKLQELRHENVALYLGLFlargaegpaALWEGNLAVVSEHCTRGSLQDLLAQREIKLDwmFKSSLLLDLIKGIRYLHHRG 661
Cdd:cd14164   52 SILRRVNHPNIVQMFECI---------EVANGRLYIVMEAAATDLLQKIQEVHHIPKD--LARDMFAQMVGAVNYLHDMN 120
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   662 VAHGRLKSRNCIV--DGRFVlKITDHGHGRLLEAQKVLPEpPRAEDQLWTAPELL----RDPAlerrgtlAGDVFSLAII 735
Cdd:cd14164  121 IVHRDLKCENILLsaDDRKI-KIADFGFARFVEDYPELST-TFCGSRAYTPPEVIlgtpYDPK-------KYDVWSLGVV 191
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 4504217   736 MQEVVCRSAPYamleltPEEVVQRVRSPPplcRPLVSMDQAPVE--CILLMKQCWAEQPELRPSM 798
Cdd:cd14164  192 LYVMVTGTMPF------DETNVRRLRLQQ---RGVLYPSGVALEepCRALIRTLLQFNPSTRPSI 247
STKc_Aurora cd14007
Catalytic domain of the Serine/Threonine kinase, Aurora kinase; STKs catalyze the transfer of ...
620-799 8.38e-04

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: 42.46  E-value: 8.38e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   620 EHCTRGSLQDLLaQREIKLDWMFKSSLLLDLIKGIRYLHHRGVAHGRLKSRNCIVDGRFVLKITDHG---Hgrlleaqkv 696
Cdd:cd14007   80 EYAPNGELYKEL-KKQKRFDEKEAAKYIYQLALALDYLHSKNIIHRDIKPENILLGSNGELKLADFGwsvH--------- 149
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   697 LPEPPRAE-----DQLwtAPELLR----DPALerrgtlagDVFSLAIIMQEVVCRSAPYAMleLTPEEVVQRVRS----- 762
Cdd:cd14007  150 APSNRRKTfcgtlDYL--PPEMVEgkeyDYKV--------DIWSLGVLCYELLVGKPPFES--KSHQETYKRIQNvdikf 217
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|
gi 4504217   763 ---PPPLCRPLVSMdqapveciLLMKqcwaeQPELRPSMD 799
Cdd:cd14007  218 pssVSPEAKDLISK--------LLQK-----DPSKRLSLE 244
STKc_EIF2AK2_PKR cd14047
Catalytic domain of the Serine/Threonine kinase, eukaryotic translation Initiation Factor ...
584-808 9.06e-04

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: 42.48  E-value: 9.06e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   584 LQELRHENVALYLGLF------LARGAEGPAALWEGNLAVVSEHCTRGSLQDLLAQRE-IKLDWMFKSSLLLDLIKGIRY 656
Cdd:cd14047   53 LAKLDHPNIVRYNGCWdgfdydPETSSSNSSRSKTKCLFIQMEFCEKGTLESWIEKRNgEKLDKVLALEIFEQITKGVEY 132
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   657 LHHRGVAHGRLKSRNCIVDGRFVLKITDHGhgrLLEAQK-VLPEPPRAEDQLWTAPELLrdpALERRGTLAgDVFSLAII 735
Cdd:cd14047  133 IHSKKLIHRDLKPSNIFLVDTGKVKIGDFG---LVTSLKnDGKRTKSKGTLSYMSPEQI---SSQDYGKEV-DIYALGLI 205
                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 4504217   736 MQEV--VCRSApyamleLTPEEVVQRVRS---PPPLCRplvsmdQAPVECILLMKQCwAEQPELRPsmdHTFDLFKNI 808
Cdd:cd14047  206 LFELlhVCDSA------FEKSKFWTDLRNgilPDIFDK------RYKIEKTIIKKML-SKKPEDRP---NASEILRTL 267
STKc_MAK_like cd07830
Catalytic domain of Male germ cell-Associated Kinase-like Serine/Threonine Kinases; STKs ...
645-740 1.04e-03

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: 42.52  E-value: 1.04e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   645 SLLLDLIKGIRYLHHRGVAHGRLKSRNCIVDGRFVLKITDHGhgrLleAQKVLPEPP-------RaedqlW-TAPE-LLR 715
Cdd:cd07830  103 SIIYQILQGLAHIHKHGFFHRDLKPENLLVSGPEVVKIADFG---L--AREIRSRPPytdyvstR-----WyRAPEiLLR 172
                         90       100
                 ....*....|....*....|....*
gi 4504217   716 DPALERrgtlAGDVFSLAIIMQEVV 740
Cdd:cd07830  173 STSYSS----PVDIWALGCIMAELY 193
STKc_ASK cd06624
Catalytic domain of the Serine/Threonine Kinase, Apoptosis signal-regulating kinase; STKs ...
586-797 1.05e-03

Catalytic domain of the Serine/Threonine Kinase, Apoptosis signal-regulating kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Members of this subfamily are mitogen-activated protein kinase (MAPK) kinase kinases (MAPKKKs or MKKKs) and include ASK1, ASK2, and MAPKKK15. ASK1 (also called MAPKKK5) functions in the c-Jun N-terminal kinase (JNK) and p38 MAPK signaling pathways by directly activating their respective MAPKKs, MKK4/MKK7 and MKK3/MKK6. It plays important roles in cytokine and stress responses, as well as in reactive oxygen species-mediated cellular responses. ASK1 is implicated in various diseases mediated by oxidative stress including inschemic heart disease, hypertension, vessel injury, brain ischemia, Fanconi anemia, asthma, and pulmonary edema, among others. ASK2 (also called MAPKKK6) functions only in a heteromeric complex with ASK1, and can activate ASK1 by direct phosphorylation. The function of MAPKKK15 is still unknown. The ASK 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: 270794 [Multi-domain]  Cd Length: 268  Bit Score: 42.40  E-value: 1.05e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   586 ELRHENVALYLGLFlargAEGpaalweGNLAVVSEHCTRGSLQDLLAQR-------EIKLDWMFKSSLlldliKGIRYLH 658
Cdd:cd06624   61 RLSHKNIVQYLGSV----SED------GFFKIFMEQVPGGSLSALLRSKwgplkdnENTIGYYTKQIL-----EGLKYLH 125
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   659 HRGVAHGRLKSRNCIVD---GrfVLKITDHGHGRLLEAQKVLPEPPRAEDQlWTAPELLrDPALERRGTLAgDVFSLAII 735
Cdd:cd06624  126 DNKIVHRDIKGDNVLVNtysG--VVKISDFGTSKRLAGINPCTETFTGTLQ-YMAPEVI-DKGQRGYGPPA-DIWSLGCT 200
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 4504217   736 MQEVVCRSAPYAMLeLTPEEVVQRV---RSPPPLcrPlvsmDQAPVECILLMKQCWAEQPELRPS 797
Cdd:cd06624  201 IIEMATGKPPFIEL-GEPQAAMFKVgmfKIHPEI--P----ESLSEEAKSFILRCFEPDPDKRAT 258
STKc_TAO1 cd06635
Catalytic domain of the Serine/Threonine Kinase, Thousand-and-One Amino acids 1; STKs catalyze ...
584-745 1.16e-03

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: 42.34  E-value: 1.16e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   584 LQELRHENVALYLGLFLArgaegpaalwEGNLAVVSEHCTrGSLQDLLAQREIKLDWMFKSSLLLDLIKGIRYLHHRGVA 663
Cdd:cd06635   79 LQRIKHPNSIEYKGCYLR----------EHTAWLVMEYCL-GSASDLLEVHKKPLQEIEIAAITHGALQGLAYLHSHNMI 147
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   664 HGRLKSRNCIVDGRFVLKITDHGHGRLLEAQKVLPEPPraedqLWTAPELLRdpALErRGTLAG--DVFSLAIIMQEVVC 741
Cdd:cd06635  148 HRDIKAGNILLTEPGQVKLADFGSASIASPANSFVGTP-----YWMAPEVIL--AMD-EGQYDGkvDVWSLGITCIELAE 219

                 ....
gi 4504217   742 RSAP 745
Cdd:cd06635  220 RKPP 223
STKc_SPEG_rpt2 cd14111
Catalytic kinase domain, second repeat, of Giant Serine/Threonine Kinase Striated muscle ...
645-802 1.24e-03

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: 42.12  E-value: 1.24e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   645 SLLLDLIKGIRYLHHRGVAHGRLKSRNCIVDGRFVLKITDHGHGRLLEAQKVLPEPPRAEDQLWTAPELLR-DPAlerrG 723
Cdd:cd14111  103 GYLVQILQGLEYLHGRRVLHLDIKPDNIMVTNLNAIKIVDFGSAQSFNPLSLRQLGRRTGTLEYMAPEMVKgEPV----G 178
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   724 TlAGDVFSLAIIMQEVVCRSAPYamLELTPEEVVQRV---RSPPPLCRPLVSMDQApveciLLMKQCWAEQPELRPSMDH 800
Cdd:cd14111  179 P-PADIWSIGVLTYIMLSGRSPF--EDQDPQETEAKIlvaKFDAFKLYPNVSQSAS-----LFLKKVLSSYPWSRPTTKD 250

                 ..
gi 4504217   801 TF 802
Cdd:cd14111  251 CF 252
STKc_BUR1 cd07866
Catalytic domain of the Serine/Threonine Kinase, Fungal Cyclin-Dependent protein Kinase (CDK), ...
647-738 1.47e-03

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: 41.92  E-value: 1.47e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   647 LLDLIKGIRYLHHRGVAHGRLKSRNCIVDGRFVLKITDHGHGRLL-EAQKVLPEPPRAEDQLWT---------APELLrd 716
Cdd:cd07866  121 MLQLLEGINYLHENHILHRDIKAANILIDNQGILKIADFGLARPYdGPPPNPKGGGGGGTRKYTnlvvtrwyrPPELL-- 198
                         90       100
                 ....*....|....*....|..
gi 4504217   717 pALERRGTLAGDVFSLAIIMQE 738
Cdd:cd07866  199 -LGERRYTTAVDIWGIGCVFAE 219
STKc_CDK8 cd07868
Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 8; STKs ...
584-740 1.76e-03

Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 8; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK8 can act 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 (RNAP II)-dependent transcription. CDK8 phosphorylates cyclin H, a subunit of the general transcription factor TFIIH, which results in the inhibition of TFIIH-dependent phosphorylation of the C-terminal domain of RNAP II, facilitating the inhibition of transcription. It has also been shown to promote transcription by a mechanism that is likely to involve RNAP II phosphorylation. CDK8 also functions as a stimulus-specific positive coregulator of p53 transcriptional responses. 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 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: 270851 [Multi-domain]  Cd Length: 333  Bit Score: 41.97  E-value: 1.76e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   584 LQELRHENVALYLGLFLARGAEGPAALW---EGNL-AVVSEHctRGSLQDllaQREIKLDWMFKSSLLLDLIKGIRYLHH 659
Cdd:cd07868   68 LRELKHPNVISLQKVFLSHADRKVWLLFdyaEHDLwHIIKFH--RASKAN---KKPVQLPRGMVKSLLYQILDGIHYLHA 142
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   660 RGVAHGRLKSRNCIVDG----RFVLKITDHGHGRLLEAqkvlPEPPRAE-DQL-----WTAPELLRDPaleRRGTLAGDV 729
Cdd:cd07868  143 NWVLHRDLKPANILVMGegpeRGRVKIADMGFARLFNS----PLKPLADlDPVvvtfwYRAPELLLGA---RHYTKAIDI 215
                        170
                 ....*....|.
gi 4504217   730 FSLAIIMQEVV 740
Cdd:cd07868  216 WAIGCIFAELL 226
STKc_JNK cd07850
Catalytic domain of the Serine/Threonine Kinase, c-Jun N-terminal Kinase; STKs catalyze the ...
644-689 2.48e-03

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: 41.25  E-value: 2.48e-03
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*.
gi 4504217   644 SSLLLDLIKGIRYLHHRGVAHGRLKSRNCIVDGRFVLKITDHGHGR 689
Cdd:cd07850  105 SYLLYQMLCGIKHLHSAGIIHRDLKPSNIVVKSDCTLKILDFGLAR 150
PK_STRAD_beta cd08226
Pseudokinase domain of STE20-related kinase adapter protein beta; The pseudokinase domain ...
588-817 2.58e-03

Pseudokinase domain of STE20-related kinase adapter protein beta; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity.STRAD-beta is also referred to as ALS2CR2 (Amyotrophic lateral sclerosis 2 chromosomal region candidate gene 2 protein), since the human gene encoding it is located within the juvenile ALS2 critical region on chromosome 2q33-q34. It is not linked to the development of ALS2. STRAD forms a complex with the scaffolding protein MO25, and the serine/threonine kinase (STK), LKB1, resulting in the activation of the kinase. In the complex, LKB1 phosphorylates and activates adenosine monophosphate-activated protein kinases (AMPKs), which regulate cell energy metabolism and cell polarity. LKB1 is a tumor suppressor linked to the rare inherited disease, Peutz-Jeghers syndrome, which is characterized by a predisposition to benign polyps and hyperpigmentation of the buccal mucosa. The STRAD-beta 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: 270864 [Multi-domain]  Cd Length: 328  Bit Score: 41.39  E-value: 2.58e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   588 RHENVALYLGLFLArGAEgpaaLWegnlaVVSEHCTRGSLQDLLAQREIK-LDWMFKSSLLLDLIKGIRYLHHRGVAHGR 666
Cdd:cd08226   57 RHPNIMTHWTVFTE-GSW----LW-----VISPFMAYGSARGLLKTYFPEgMNEALIGNILYGAIKALNYLHQNGCIHRS 126
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   667 LKSRNCIV--DGRFVLKITDHGHGRLLEAQ--KVLPEPPR--AEDQLWTAPELLRDpalERRG-TLAGDVFSLAIIMQEV 739
Cdd:cd08226  127 VKASHILIsgDGLVSLSGLSHLYSMVTNGQrsKVVYDFPQfsTSVLPWLSPELLRQ---DLHGyNVKSDIYSVGITACEL 203
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   740 VCRSAPYAMLELTpEEVVQRVRSPPplCRPLVS----------------MDQAPVECIL--------------------- 782
Cdd:cd08226  204 ARGQVPFQDMRRT-QMLLQKLKGPP--YSPLDIfpfpelesrmknsqsgMDSGIGESVAtssmtrtmtserlqtpssktf 280
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|....*
gi 4504217   783 ------LMKQCWAEQPELRPS----MDHTFdlFKNINKGRKTNII 817
Cdd:cd08226  281 spafhnLVELCLQQDPEKRPSasslLSHSF--FKQVKEQTQASLL 323
STKc_DAPK2 cd14196
Catalytic domain of the Serine/Threonine Kinase, Death-Associated Protein Kinase 2; STKs ...
573-746 3.01e-03

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: 40.71  E-value: 3.01e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   573 IRPATKTAFSKLQELRHENVALYLGLFLARGaegpaalwegNLAVVSEHCTRGSLQDLLAQREiKLDWMFKSSLLLDLIK 652
Cdd:cd14196   51 SREEIEREVSILRQVLHPNIITLHDVYENRT----------DVVLILELVSGGELFDFLAQKE-SLSEEEATSFIKQILD 119
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   653 GIRYLHHRGVAHGRLKSRNCIVDGRFV----LKITDHGHGRLL----EAQKVLPEPPraedqlWTAPELLRDPALerrgT 724
Cdd:cd14196  120 GVNYLHTKKIAHFDLKPENIMLLDKNIpiphIKLIDFGLAHEIedgvEFKNIFGTPE------FVAPEIVNYEPL----G 189
                        170       180
                 ....*....|....*....|..
gi 4504217   725 LAGDVFSLAIIMQEVVCRSAPY 746
Cdd:cd14196  190 LEADMWSIGVITYILLSGASPF 211
STKc_RSK_C cd14091
C-terminal catalytic domain of the Serine/Threonine Kinases, Ribosomal S6 kinases; STKs ...
612-762 4.35e-03

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: 40.31  E-value: 4.35e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   612 EGNLAVVSEHCTRGSL------QDLLAQREIkldwmfkSSLLLDLIKGIRYLHHRGVAHGRLKSRNCIvdgrFV------ 679
Cdd:cd14091   66 GNSVYLVTELLRGGELldrilrQKFFSEREA-------SAVMKTLTKTVEYLHSQGVVHRDLKPSNIL----YAdesgdp 134
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   680 --LKITDHGHGRLLeaqkvlpeppRAEDQL---------WTAPELLRdpaleRRG-TLAGDVFSLAIIMQEVVCRSAPYA 747
Cdd:cd14091  135 esLRICDFGFAKQL----------RAENGLlmtpcytanFVAPEVLK-----KQGyDAACDIWSLGVLLYTMLAGYTPFA 199
                        170
                 ....*....|....*.
gi 4504217   748 M-LELTPEEVVQRVRS 762
Cdd:cd14091  200 SgPNDTPEVILARIGS 215
PBP1_ABC_ligand_binding-like cd06326
periplasmic ligand-binding domain of uncharacterized ABC-type transport systems predicted to ...
120-245 4.68e-03

periplasmic ligand-binding domain of uncharacterized ABC-type transport systems predicted to be involved in uptake of amino acids, peptides, or inorganic ions; This group includes the type 1 periplasmic ligand-binding domain of uncharacterized ABC (ATPase Binding Cassette)-type transport systems that are predicted to be involved in the uptake of amino acids, peptides, or inorganic ions. This subgroup has high sequence similarity to members of the family of hydrophobic amino acid transporters (HAAT), such as leucine-isoleucine-valine binding protein (LIVBP); its ligand specificity has not been determined experimentally, however.


Pssm-ID: 380549 [Multi-domain]  Cd Length: 339  Bit Score: 40.60  E-value: 4.68e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   120 RVSGLVGPVNPAACRPAELLAEEAGIALVPwgcPWTQAE---GTTAPAVTPA-------ADALYALLRAFGWARVALVTA 189
Cdd:cd06326   68 KVVALFGYVGTANVEAVLPLLEEAGVPLVG---PLTGADslrEPGNPYVFHVrasyadeVEKIVRHLATLGLKRIAVVYQ 144
                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 4504217   190 PQDLWVEAGRSLSTALRARGLPVASVTSMEPlDLSGAREALRKVRDGpRVTAVIMV 245
Cdd:cd06326  145 DDPFGKEGLAAAEAALAARGLEPVATAAVAR-NAADVAAAAAALAAA-KPQAVVLI 198
PK_STRAD_alpha cd08227
Pseudokinase domain of STE20-related kinase adapter protein alpha; The pseudokinase domain ...
582-822 6.01e-03

Pseudokinase domain of STE20-related kinase adapter protein alpha; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. The structure of STRAD-alpha is available and shows that this protein binds ATP, has an ordered activation loop, and adopts a closed conformation typical of fully active protein kinases. It does not possess activity due to nonconservative substitutions of essential catalytic residues. ATP binding enhances the affinity of STRAD for MO25. The conformation of STRAD-alpha, stabilized through ATP and MO25, may be needed to activate LKB1. A mutation which results in a truncation of a C-terminal part of the human STRAD-alpha pseudokinase domain and disrupts its association with LKB1, leads to PMSE (polyhydramnios, megalencephaly, symptomatic epilepsy) syndrome. Several splice variants of STRAD-alpha exist which exhibit different effects on the localization and activation of LKB1. STRAD forms a complex with the scaffolding protein MO25, and the serine/threonine kinase (STK), LKB1, resulting in the activation of the kinase. In the complex, LKB1 phosphorylates and activates adenosine monophosphate-activated protein kinases (AMPKs), which regulate cell energy metabolism and cell polarity. The STRAD alpha 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: 173767 [Multi-domain]  Cd Length: 327  Bit Score: 40.31  E-value: 6.01e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   582 SKLqeLRHENVALYLGLFLArgaegpaalwEGNLAVVSEHCTRGSLQDLLAQREIK-LDWMFKSSLLLDLIKGIRYLHHR 660
Cdd:cd08227   53 SKL--FNHPNIVPYRATFIA----------DNELWVVTSFMAYGSAKDLICTHFMDgMSELAIAYILQGVLKALDYIHHM 120
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   661 GVAHGRLKSRNCI--VDG-------RFVLKITDHGhgrllEAQKVLPEPPRAEDQL--WTAPELLRDpalerrgTLAG-- 727
Cdd:cd08227  121 GYVHRSVKASHILisVDGkvylsglRSNLSMINHG-----QRLRVVHDFPKYSVKVlpWLSPEVLQQ-------NLQGyd 188
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   728 ---DVFSLAIIMQEVVCRSAPYAMLELT---------------------PEEVVQRV-RS--------PPPLCRPLVSMD 774
Cdd:cd08227  189 aksDIYSVGITACELANGHVPFKDMPATqmlleklngtvpclldtttipAEELTMKPsRSgansglgeSTTVSTPRPSNG 268
                        250       260       270       280       290       300
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 4504217   775 QAPVECIL---------LMKQCWAEQPELRPS----MDHTFdlFKNInKGRKTNIIDSMLR 822
Cdd:cd08227  269 ESSSHPYNrtfsphfhhFVEQCLQRNPDARPSastlLNHSF--FKQI-KRRASEALPELLR 326
STKc_DAPK cd14105
Catalytic domain of the Serine/Threonine Kinase, Death-Associated Protein Kinase; STKs ...
584-746 6.37e-03

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: 39.78  E-value: 6.37e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   584 LQELRHENVALYLGLFLARGaegpaalwegNLAVVSEHCTRGSLQDLLAQREiKLDWMFKSSLLLDLIKGIRYLHHRGVA 663
Cdd:cd14105   62 LRQVLHPNIITLHDVFENKT----------DVVLILELVAGGELFDFLAEKE-SLSEEEATEFLKQILDGVNYLHTKNIA 130
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   664 HGRLKSRNCIVDGRFV----LKITDHGHGRLLEAQKVL------PEppraedqlWTAPELLrdpALERRGtLAGDVFSLA 733
Cdd:cd14105  131 HFDLKPENIMLLDKNVpiprIKLIDFGLAHKIEDGNEFknifgtPE--------FVAPEIV---NYEPLG-LEADMWSIG 198
                        170
                 ....*....|...
gi 4504217   734 IIMQEVVCRSAPY 746
Cdd:cd14105  199 VITYILLSGASPF 211
PHA02882 PHA02882
putative serine/threonine kinase; Provisional
645-695 6.75e-03

putative serine/threonine kinase; Provisional


Pssm-ID: 165211 [Multi-domain]  Cd Length: 294  Bit Score: 39.93  E-value: 6.75e-03
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 4504217    645 SLLLDLIKGIRYLHHRGVAHGRLKSRNCIVDGRFVLKITDHG-------HGRLLEAQK 695
Cdd:PHA02882  130 NIMKDMLTTLEYIHEHGISHGDIKPENIMVDGNNRGYIIDYGiashfiiHGKHIEYSK 187
STKc_PKD cd14082
Catalytic domain of the Serine/Threonine kinase, Protein Kinase D; STKs catalyze the transfer ...
569-736 7.77e-03

Catalytic domain of the Serine/Threonine kinase, Protein Kinase D; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKDs are important regulators of many intracellular signaling pathways such as ERK and JNK, and cellular processes including the organization of the trans-Golgi network, membrane trafficking, cell proliferation, migration, and apoptosis. They contain N-terminal cysteine-rich zinc binding C1 (PKC conserved region 1), central PH (Pleckstrin Homology), and C-terminal catalytic kinase domains. Mammals harbor three types of PKDs: PKD1 (or PKCmu), PKD2, and PKD3 (or PKCnu). PKDs are activated in a PKC-dependent manner by many agents including diacylglycerol (DAG), PDGF, neuropeptides, oxidative stress, and tumor-promoting phorbol esters, among others. The PKD 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: 270984 [Multi-domain]  Cd Length: 260  Bit Score: 39.32  E-value: 7.77e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   569 QHIAIRPATKTAFSK------------LQELRHENVALYLGLFlargaEGPAALWegnlaVVSEHCTRGSLQDLLAQREI 636
Cdd:cd14082   29 RDVAIKVIDKLRFPTkqesqlrnevaiLQQLSHPGVVNLECMF-----ETPERVF-----VVMEKLHGDMLEMILSSEKG 98
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   637 KLDWMFKSSLLLDLIKGIRYLHHRGVAHGRLKSRNCIV--DGRF-VLKITDHGHGRLLEAQK----VLPEPPraedqlWT 709
Cdd:cd14082   99 RLPERITKFLVTQILVALRYLHSKNIVHCDLKPENVLLasAEPFpQVKLCDFGFARIIGEKSfrrsVVGTPA------YL 172
                        170       180
                 ....*....|....*....|....*..
gi 4504217   710 APELLRDPALERrgtlAGDVFSLAIIM 736
Cdd:cd14082  173 APEVLRNKGYNR----SLDMWSVGVII 195
PTK_Tyk2_rpt1 cd05076
Pseudokinase (repeat 1) domain of the Protein Tyrosine Kinase, Tyrosine kinase 2; Tyk2 is ...
617-797 8.02e-03

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: 39.51  E-value: 8.02e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   617 VVSEHCTRGSLqDLLAQRE---IKLDWMFksSLLLDLIKGIRYLHHRGVAHGRLKSRNCIVDGRFV-------LKITDHG 686
Cdd:cd05076   92 MVEEFVEHGPL-DVWLRKEkghVPMAWKF--VVARQLASALSYLENKNLVHGNVCAKNILLARLGLeegtspfIKLSDPG 168
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4504217   687 HGRlleaqKVLPEPPRAEDQLWTAPELLRDPAleRRGTlAGDVFSLAIIMQEvVCRSAPYAMLELTPEE----VVQRVRS 762
Cdd:cd05076  169 VGL-----GVLSREERVERIPWIAPECVPGGN--SLST-AADKWGFGATLLE-ICFNGEAPLQSRTPSEkerfYQRQHRL 239
                        170       180       190
                 ....*....|....*....|....*....|....*
gi 4504217   763 PPPLCRPLVSmdqapvecilLMKQCWAEQPELRPS 797
Cdd:cd05076  240 PEPSCPELAT----------LISQCLTYEPTQRPS 264
 
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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