Protein Kinases, catalytic domain; The protein kinase superfamily is mainly composed of the catalytic domains of serine/threonine-specific and tyrosine-specific protein kinases. It also includes RIO kinases, which are atypical serine protein kinases, aminoglycoside phosphotransferases, and choline kinases. These proteins catalyze the transfer of the gamma-phosphoryl group from ATP to hydroxyl groups in specific substrates such as serine, threonine, or tyrosine residues of proteins.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755556245  69 LVKIGDLFNGRYHVIRKLGWGHFSTVWLSWDIQGKKFVAMKVVKSAEHYTETALDEIRLLKSVRNSDPNDPNGEMVVQLL 148
Cdd:cd14216    1 LVKIGDLFNGRYHVIRKLGWGHFSTVWLSWDIQGKRFVAMKVVKSAEHYTETALDEIKLLKSVRNSDPNDPNREMVVQLL 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755556245 149 DDFKISGVNGTHICMVFEVLGHHLLKWIIKSNYQGLPLPCVKKIIQQVLQGLDYLHTKCRIIHTDIKPENILLSVNEQYI 228
Cdd:cd14216   81 DDFKISGVNGTHICMVFEVLGHHLLKWIIKSNYQGLPLPCVKKIIRQVLQGLDYLHTKCRIIHTDIKPENILLSVNEQYI 160

                        170
                 ....*....|...
gi 755556245 229 RRLAAEATEWQRS 241
Cdd:cd14216  161 RRLAAEATEWQRN 173

Catalytic domain of the Serine/Threonine Kinase, Serine-aRginine Protein Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SRPK1 binds with high affinity the alternative splicing factor, SRSF1 (serine/arginine-rich splicing factor 1), and regiospecifically phosphorylates 10-12 serines in its RS domain. It plays a role in the regulation of pre-mRNA splicing, chromatin structure, and germ cell development. SRPKs phosphorylate and regulate splicing factors from the SR protein family by specifically phosphorylating multiple serine residues residing in SR/RS dipeptide motifs (also known as RS domains). Phosphorylation of the RS domains enhances interaction with transportin SR and facilitates entry of the SR proteins into the nucleus. SRPKs contain a nonconserved insert domain, within the well-conserved catalytic kinase domain, that regulates their subcellular localization. The SRPK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755556245  69 LVKIGDLFNGRYHVIRKLGWGHFSTVWLSWDIQGKKFVAMKVVKSAEHYTETALDEIRLLKSVRNSDPNDPNGEMVVQLL 148
Cdd:cd14216    1 LVKIGDLFNGRYHVIRKLGWGHFSTVWLSWDIQGKRFVAMKVVKSAEHYTETALDEIKLLKSVRNSDPNDPNREMVVQLL 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755556245 149 DDFKISGVNGTHICMVFEVLGHHLLKWIIKSNYQGLPLPCVKKIIQQVLQGLDYLHTKCRIIHTDIKPENILLSVNEQYI 228
Cdd:cd14216   81 DDFKISGVNGTHICMVFEVLGHHLLKWIIKSNYQGLPLPCVKKIIRQVLQGLDYLHTKCRIIHTDIKPENILLSVNEQYI 160

                        170
                 ....*....|...
gi 755556245 229 RRLAAEATEWQRS 241
Cdd:cd14216  161 RRLAAEATEWQRN 173

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755556245    80 YHVIRKLGWGHFSTVWLSWDIQGKKFVAMKVVK--SAEHYTETALDEIRLLKSVrnsdpNDPNgemVVQLLDDFkisgVN 157
Cdd:smart00220   1 YEILEKLGEGSFGKVYLARDKKTGKLVAIKVIKkkKIKKDRERILREIKILKKL-----KHPN---IVRLYDVF----ED 68

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 755556245   158 GTHICMVFEVLGHHLLKWIIKSNyQGLPLPCVKKIIQQVLQGLDYLHtKCRIIHTDIKPENILLSVN 224
Cdd:smart00220  69 EDKLYLVMEYCEGGDLFDLLKKR-GRLSEDEARFYLRQILSALEYLH-SKGIVHRDLKPENILLDED 133

protein kinase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755556245  59 PNDYCKGGYHLVKIG---DLFNGRYHVIRKLGWGHFSTVWLSWDIQGKKFVAMKVVKSAEHYTETALDEIRLLKSVRNSD 135
Cdd:PTZ00284 107 PNQSREEGHFYVVLGediDVSTQRFKILSLLGEGTFGKVVEAWDRKRKEYCAVKIVRNVPKYTRDAKIEIQFMEKVRQAD 186

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755556245 136 PNDPNGEMVVQLLddFKisgvNGT-HICMVFEVLGHHLLKWIIKS---NYQGLplpcvKKIIQQVLQGLDYLHTKCRIIH 211
Cdd:PTZ00284 187 PADRFPLMKIQRY--FQ----NETgHMCIVMPKYGPCLLDWIMKHgpfSHRHL-----AQIIFQTGVALDYFHTELHLMH 255

                        170
                 ....*....|....*..
gi 755556245 212 TDIKPENILLSVNEQYI 228
Cdd:PTZ00284 256 TDLKPENILMETSDTVV 272

Protein kinase domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755556245   80 YHVIRKLGWGHFSTVWLSWDIQGKKFVAMKVVK---SAEHYTETALDEIRLLKSVRNsdPNdpngemVVQLLDDFkisgV 156
Cdd:pfam00069   1 YEVLRKLGSGSFGTVYKAKHRDTGKIVAIKKIKkekIKKKKDKNILREIKILKKLNH--PN------IVRLYDAF----E 68

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*.
gi 755556245  157 NGTHICMVFE-VLGHHLLKWIikSNYQGLPLPCVKKIIQQVLQGLD 201
Cdd:pfam00069  69 DKDNLYLVLEyVEGGSLFDLL--SEKGAFSEREAKFIMKQILEGLE 112

protein kinase; Provisional

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 755556245 485 QVKIADLGNACWVHKHFTEDIQTRQYRSLEVLIGSGYNTPADIWSTACMTWDA-TGRML 542
Cdd:PTZ00284 286 RVRICDLGGCCDERHSRTAIVSTRHYRSPEVVLGLGWMYSTDMWSMGCIIYELyTGKLL 344

Catalytic domain of the Serine/Threonine Kinase, Serine-aRginine Protein Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SRPK1 binds with high affinity the alternative splicing factor, SRSF1 (serine/arginine-rich splicing factor 1), and regiospecifically phosphorylates 10-12 serines in its RS domain. It plays a role in the regulation of pre-mRNA splicing, chromatin structure, and germ cell development. SRPKs phosphorylate and regulate splicing factors from the SR protein family by specifically phosphorylating multiple serine residues residing in SR/RS dipeptide motifs (also known as RS domains). Phosphorylation of the RS domains enhances interaction with transportin SR and facilitates entry of the SR proteins into the nucleus. SRPKs contain a nonconserved insert domain, within the well-conserved catalytic kinase domain, that regulates their subcellular localization. The SRPK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755556245  69 LVKIGDLFNGRYHVIRKLGWGHFSTVWLSWDIQGKKFVAMKVVKSAEHYTETALDEIRLLKSVRNSDPNDPNGEMVVQLL 148
Cdd:cd14216    1 LVKIGDLFNGRYHVIRKLGWGHFSTVWLSWDIQGKRFVAMKVVKSAEHYTETALDEIKLLKSVRNSDPNDPNREMVVQLL 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755556245 149 DDFKISGVNGTHICMVFEVLGHHLLKWIIKSNYQGLPLPCVKKIIQQVLQGLDYLHTKCRIIHTDIKPENILLSVNEQYI 228
Cdd:cd14216   81 DDFKISGVNGTHICMVFEVLGHHLLKWIIKSNYQGLPLPCVKKIIRQVLQGLDYLHTKCRIIHTDIKPENILLSVNEQYI 160

                        170
                 ....*....|...
gi 755556245 229 RRLAAEATEWQRS 241
Cdd:cd14216  161 RRLAAEATEWQRN 173

Catalytic domain of the Serine/Threonine Kinase, Serine-aRginine Protein Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SRPK2 mediates neuronal cell cycle and cell death through regulation of nuclear cyclin D1. It has also been found to promote leukemia cell proliferation by regulating cyclin A1. SRPK2 also plays a role in regulating pre-mRNA splicing and is required for spliceosomal B complex formation. SRPKs phosphorylate and regulate splicing factors from the SR protein family by specifically phosphorylating multiple serine residues residing in SR/RS dipeptide motifs (also known as RS domains). Phosphorylation of the RS domains enhances interaction with transportin SR and facilitates entry of the SR proteins into the nucleus. SRPKs contain a nonconserved insert domain, within the well-conserved catalytic kinase domain, that regulates their subcellular localization. The SRPK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755556245  67 YHLVKIGDLFNGRYHVIRKLGWGHFSTVWLSWDIQGKKFVAMKVVKSAEHYTETALDEIRLLKSVRNSDPNDPNGEMVVQ 146
Cdd:cd14217    1 YHPVKIGDLFNGRYHVIRKLGWGHFSTVWLCWDMQGKRFVAMKVVKSAQHYTETALDEIKLLRCVRESDPEDPNKDMVVQ 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755556245 147 LLDDFKISGVNGTHICMVFEVLGHHLLKWIIKSNYQGLPLPCVKKIIQQVLQGLDYLHTKCRIIHTDIKPENILLSVNEQ 226
Cdd:cd14217   81 LIDDFKISGMNGIHVCMVFEVLGHHLLKWIIKSNYQGLPIRCVKSIIRQVLQGLDYLHSKCKIIHTDIKPENILMCVDDA 160

                        170       180
                 ....*....|....*....|....*....
gi 755556245 227 YIRRLAAEATEWQRSGAPPPSGSAVSTAP 255
Cdd:cd14217  161 YVRRMAAEATEWQKAGAPPPSGSAVSTAP 189

Catalytic domain of the Dual-specificity protein kinases, CDC-like kinases; Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (S/T) as well as tyrosine residues on protein substrates. CLKs are involved in the phosphorylation and regulation of serine/arginine-rich (SR) proteins, which play a crucial role in pre-mRNA splicing by directing splice site selection. SR proteins are phosphorylated first by SR protein kinases (SRPKs) at the N-terminus, which leads to its assembly into nuclear speckles where splicing factors are stored. CLKs phosphorylate the C-terminal part of SR proteins, causing the nuclear speckles to dissolve and splicing factors to be recruited at sites of active transcription. Based on a conserved "EHLAMMERILG" signature motif which may be crucial for substrate specificity, CLKs are also referred to as LAMMER kinases. CLKs autophosphorylate at tyrosine residues and phosphorylate their substrates exclusively on S/T residues. In Drosophila, the CLK homolog DOA (Darkener of apricot) is essential for embryogenesis and its mutation leads to defects in sexual differentiation, eye formation, and neuronal development. In fission yeast, the CLK homolog Lkh1 is a negative regulator of filamentous growth and asexual flocculation, and is also involved in oxidative stress response. Vertebrates contain mutliple CLK proteins and mammals have four (CLK1-4). The CLK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755556245  68 HL-VKIGDLFNGRYHVIRKLGWGHFSTVWLSWDIQGKKFVAMKVVKSAEHYTETALDEIRLLKSVRNSDPNDPNgeMVVQ 146
Cdd:cd14134    1 HLiYKPGDLLTNRYKILRLLGEGTFGKVLECWDRKRKRYVAVKIIRNVEKYREAAKIEIDVLETLAEKDPNGKS--HCVQ 78

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755556245 147 LLDDFKISGvngtHICMVFEVLGHHLLKWIIKSNYQGLPLPCVKKIIQQVLQGLDYLHtKCRIIHTDIKPENILLsVNEQ 226
Cdd:cd14134   79 LRDWFDYRG----HMCIVFELLGPSLYDFLKKNNYGPFPLEHVQHIAKQLLEAVAFLH-DLKLTHTDLKPENILL-VDSD 152

                 ...
gi 755556245 227 YIR 229
Cdd:cd14134  153 YVK 155

Catalytic domain of the Serine/Threonine Kinase, Serine-aRginine Protein Kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SRPK3 is highly expressed in the heart and skeletal muscles, and is controlled by a muscle-specific enhancer that is regulated by MEF2. It may play an important role in muscle development. SRPKs phosphorylate and regulate splicing factors from the SR protein family by specifically phosphorylating multiple serine residues residing in SR/RS dipeptide motifs (also known as RS domains). Phosphorylation of the RS domains enhances interaction with transportin SR and facilitates entry of the SR proteins into the nucleus. SRPKs contain a nonconserved insert domain, within the well-conserved catalytic kinase domain, that regulates their subcellular localization. The SRPK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755556245 456 PNGALDSkgkFSAGNFLINPLEPKNAEKLQVKIADLGNACWVHKHFTEDIQTRQYRSLEVLIGSGYNTPADIWSTACMTW 535
Cdd:cd14218  178 PSGSSVS---FGASDFLVNPLEPQNADKIRVKIADLGNACWVHKHFTEDIQTRQYRALEVLIGAEYGTPADIWSTACMAF 254

                 ....*...
gi 755556245 536 D-ATGRML 542
Cdd:cd14218  255 ElATGDYL 262

Catalytic domain of the protein kinase, Dual-specificity tYrosine-phosphorylated and -Regulated Kinase; Protein Kinases (PKs), Dual-specificity tYrosine-phosphorylated and -Regulated Kinase (DYRK) subfamily, catalytic (c) domain. Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (S/T) as well as tyrosine residues on protein substrates. The DYRK subfamily is part of a larger superfamily that includes the catalytic domains of other protein S/T PKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase (PI3K). DYRKs autophosphorylate themselves on tyrosine residues and phosphorylate their substrates exclusively on S/T residues. They play important roles in cell proliferation, differentiation, survival, and development. Vertebrates contain multiple DYRKs (DYRK1-4) and mammals contain two types of DYRK1 proteins, DYRK1A and DYRK1B. DYRK1A is involved in neuronal differentiation and is implicated in the pathogenesis of DS (Down syndrome). DYRK1B plays a critical role in muscle differentiation by regulating transcription, cell motility, survival, and cell cycle progression. It is overexpressed in many solid tumors where it acts as a tumor survival factor. DYRK2 promotes apoptosis in response to DNA damage by phosphorylating the tumor suppressor p53, while DYRK3 promotes cell survival by phosphorylating SIRT1 and promoting p53 deacetylation. DYRK4 is a testis-specific kinase that may function during spermiogenesis.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755556245  66 GYHLVKIGDLFNGRYHVIRKLGWGHFSTVWLSWDIQGKKFVAMKVVKSAEHYTETALDEIRLLKSVRNSDPNDPNGemVV 145
Cdd:cd14210    1 GDYKVVLGDHIAYRYEVLSVLGKGSFGQVVKCLDHKTGQLVAIKIIRNKKRFHQQALVEVKILKHLNDNDPDDKHN--IV 78

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 755556245 146 QLLDDFKISGvngtHICMVFEVLGHHLLKWIIKSNYQGLPLPCVKKIIQQVLQGLDYLHtKCRIIHTDIKPENILLS 222
Cdd:cd14210   79 RYKDSFIFRG----HLCIVFELLSINLYELLKSNNFQGLSLSLIRKFAKQILQALQFLH-KLNIIHCDLKPENILLK 150

Catalytic domain of the Serine/Threonine Kinase, Serine-aRginine Protein Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SRPK2 mediates neuronal cell cycle and cell death through regulation of nuclear cyclin D1. It has also been found to promote leukemia cell proliferation by regulating cyclin A1. SRPK2 also plays a role in regulating pre-mRNA splicing and is required for spliceosomal B complex formation. SRPKs phosphorylate and regulate splicing factors from the SR protein family by specifically phosphorylating multiple serine residues residing in SR/RS dipeptide motifs (also known as RS domains). Phosphorylation of the RS domains enhances interaction with transportin SR and facilitates entry of the SR proteins into the nucleus. SRPKs contain a nonconserved insert domain, within the well-conserved catalytic kinase domain, that regulates their subcellular localization. The SRPK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 755556245 467 SAGNFLINPLEPKNAEKLQVKIADLGNACWVHKHFTEDIQTRQYRSLEVLIGSGYNTPADIWSTACMTWD-ATGRML 542
Cdd:cd14217  187 TAPDLLVNPLDPRNADKIRVKIADLGNACWVHKHFTEDIQTRQYRSIEVLIGAGYSTPADIWSTACMAFElATGDYL 263

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755556245    80 YHVIRKLGWGHFSTVWLSWDIQGKKFVAMKVVK--SAEHYTETALDEIRLLKSVrnsdpNDPNgemVVQLLDDFkisgVN 157
Cdd:smart00220   1 YEILEKLGEGSFGKVYLARDKKTGKLVAIKVIKkkKIKKDRERILREIKILKKL-----KHPN---IVRLYDVF----ED 68

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 755556245   158 GTHICMVFEVLGHHLLKWIIKSNyQGLPLPCVKKIIQQVLQGLDYLHtKCRIIHTDIKPENILLSVN 224
Cdd:smart00220  69 EDKLYLVMEYCEGGDLFDLLKKR-GRLSEDEARFYLRQILSALEYLH-SKGIVHRDLKPENILLDED 133

Catalytic domain of the Dual-specificity protein kinase, YAK1; Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (S/T) as well as tyrosine residues on protein substrates. This subfamily is composed of proteins with similarity to Saccharomyces cerevisiae YAK1 (or Yak1p), a dual-specificity kinase that autophosphorylates at tyrosine residues and phosphorylates substrates on S/T residues. YAK1 phosphorylates and activates the transcription factors Hsf1 and Msn2, which play important roles in cellular homeostasis during stress conditions including heat shock, oxidative stress, and nutrient deficiency. It also phosphorylates the protein POP2, a component of a complex that regulates transcription, under glucose-deprived conditions. It functions as a part of a glucose-sensing system that is involved in controlling growth in yeast. The YAK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755556245  80 YHVIRKLGWGHFSTVWLSWDIQGKKFVAMKVVKSAEHYTETALDEIRLLKSVrNSDPNDPNGEMVVQLLDDFKISGvngt 159
Cdd:cd14212    1 YLVLDLLGQGTFGQVVKCQDLKTNKLVAVKVLKNKPAYFRQAMLEIAILTLL-NTKYDPEDKHHIVRLLDHFMHHG---- 75

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 755556245 160 HICMVFEVLGHHLLKWIIKSNYQGLPLPCVKKIIQQVLQGLDYLHtKCRIIHTDIKPENILLS 222
Cdd:cd14212   76 HLCIVFELLGVNLYELLKQNQFRGLSLQLIRKFLQQLLDALSVLK-DARIIHCDLKPENILLV 137

Catalytic domain of the protein kinases, Dual-specificity tYrosine-phosphorylated and -Regulated Kinases 2 and 3; Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (S/T) as well as tyrosine residues on protein substrates. This subfamily is composed of DYRK2 and DYRK3, and similar proteins. Drosophila DYRK2 interacts and phosphorylates the chromatin remodelling factor, SNR1 (Snf5-related 1), and also interacts with the essential chromatin component, trithorax. It may play a role in chromatin remodelling. Vertebrate DYRK2 phosphorylates and regulates the tumor suppressor p53 to induce apoptosis in response to DNA damage. It can also phosphorylate the transcription factor, nuclear factor of activated T cells (NFAT). DYRK2 is overexpressed in lung adenocarcinoma and esophageal carcinomas, and is a predictor for favorable prognosis in lung adenocarcinoma. DYRK3, also called regulatory erythroid kinase (REDK), is highly expressed in erythroid cells and the testis, and is also present in adult kidney and liver. It promotes cell survival by phosphorylating and activating SIRT1, an NAD(+)-dependent protein deacetylase, which promotes p53 deacetylation, resulting in the inhibition of apoptosis. DYRKs autophosphorylate themselves on tyrosine residues and phosphorylate their substrates exclusively on S/T residues. The DYRK2/3 subfamily is part of a larger superfamily that includes the catalytic domains of other S/T kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755556245  53 DDEQedpndyckGGYHLVkIGDLFNGRYHVIRKLGWGHFSTVWLSWDIQGKKFVAMKVVKSAEHYTETALDEIRLLKSVR 132
Cdd:cd14224   49 DDEQ--------GSYIHV-PHDHIAYRYEVLKVIGKGSFGQVVKAYDHKTHQHVALKMVRNEKRFHRQAAEEIRILEHLK 119

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755556245 133 NSDPNdpNGEMVVQLLDDFKISGvngtHICMVFEVLGHHLLKWIIKSNYQGLPLPCVKKIIQQVLQGLDYLHtKCRIIHT 212
Cdd:cd14224  120 KQDKD--NTMNVIHMLESFTFRN----HICMTFELLSMNLYELIKKNKFQGFSLQLVRKFAHSILQCLDALH-RNKIIHC 192

                 ....*....
gi 755556245 213 DIKPENILL 221
Cdd:cd14224  193 DLKPENILL 201

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755556245  86 LGWGHFSTVWLSWDIQGKKFVAMKVVK--SAEHYTETALDEIRLLKSVRNsdpndPNgemVVQLLDDFKisgvNGTHICM 163
Cdd:cd00180    1 LGKGSFGKVYKARDKETGKKVAVKVIPkeKLKKLLEELLREIEILKKLNH-----PN---IVKLYDVFE----TENFLYL 68

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 755556245 164 VFEVLGHHLLKWIIKSNYQGLPLPCVKKIIQQVLQGLDYLHtKCRIIHTDIKPENILLS 222
Cdd:cd00180   69 VMEYCEGGSLKDLLKENKGPLSEEEALSILRQLLSALEYLH-SNGIIHRDLKPENILLD 126

Catalytic domain of the Serine/Threonine Kinase, Pre-mRNA-Processing factor 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PRP4 phosphorylates a number of factors involved in the formation of active spliceosomes, which catalyze pre-mRNA splicing. It phosphorylates PRP6 and PRP31, components of the U4/U6-U5 tri-small nuclear ribonucleoprotein (snRNP), during spliceosomal complex formation. In fission yeast, PRP4 phosphorylates the splicing factor PRP1 (U5-102 kD in mammals). Thus, PRP4 plays a key role in regulating spliceosome assembly and pre-mRNA splicing. It also plays an important role in mitosis by acting as a spindle assembly checkpoint kinase that is required for chromosome alignment and the recruitment of the checkpoint proteins MPS1, MAD1, and MAD2 at kinetochores. The PRP4 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755556245  79 RYHVIRKLGWGHFSTVWLSWDIQ-GKKFVAMKVVKSAEHYTETALDEIRLLKSVRNSDPNDPngEMVVQLLDDFKISGvn 157
Cdd:cd14135    1 RYRVYGYLGKGVFSNVVRARDLArGNQEVAIKIIRNNELMHKAGLKELEILKKLNDADPDDK--KHCIRLLRHFEHKN-- 76

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 755556245 158 gtHICMVFEVLgHHLLKWIIK--SNYQGLPLPCVKKIIQQVLQGLDYLHtKCRIIHTDIKPENILlsVNEQ 226
Cdd:cd14135   77 --HLCLVFESL-SMNLREVLKkyGKNVGLNIKAVRSYAQQLFLALKHLK-KCNILHADIKPDNIL--VNEK 141

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755556245  79 RYHVIRKLGWGHFSTVWLSWDIQGKKFVAMKVVKSAEHYTETA----LDEIRLLKSVRNsdPNdpngemVVQLLDdfkiS 154
Cdd:cd14014    1 RYRLVRLLGRGGMGEVYRARDTLLGRPVAIKVLRPELAEDEEFrerfLREARALARLSH--PN------IVRVYD----V 68

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 755556245 155 GVNGTHICMVFEVLGHHLLKWIIKSNyQGLPLPCVKKIIQQVLQGLDYLHtKCRIIHTDIKPENILLSVNEQ 226
Cdd:cd14014   69 GEDDGRPYIVMEYVEGGSLADLLRER-GPLPPREALRILAQIADALAAAH-RAGIVHRDIKPANILLTEDGR 138

protein kinase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755556245  59 PNDYCKGGYHLVKIG---DLFNGRYHVIRKLGWGHFSTVWLSWDIQGKKFVAMKVVKSAEHYTETALDEIRLLKSVRNSD 135
Cdd:PTZ00284 107 PNQSREEGHFYVVLGediDVSTQRFKILSLLGEGTFGKVVEAWDRKRKEYCAVKIVRNVPKYTRDAKIEIQFMEKVRQAD 186

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755556245 136 PNDPNGEMVVQLLddFKisgvNGT-HICMVFEVLGHHLLKWIIKS---NYQGLplpcvKKIIQQVLQGLDYLHTKCRIIH 211
Cdd:PTZ00284 187 PADRFPLMKIQRY--FQ----NETgHMCIVMPKYGPCLLDWIMKHgpfSHRHL-----AQIIFQTGVALDYFHTELHLMH 255

                        170
                 ....*....|....*..
gi 755556245 212 TDIKPENILLSVNEQYI 228
Cdd:PTZ00284 256 TDLKPENILMETSDTVV 272

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755556245  80 YHVIRKLGWGHFSTVWLSWDIQGKKFVAMKVVK----SAEHYTEtaLDEIRLLKSVrNSDPNdpngemVVQLLDDFKISG 155
Cdd:cd07830    1 YKVIKQLGDGTFGSVYLARNKETGELVAIKKMKkkfySWEECMN--LREVKSLRKL-NEHPN------IVKLKEVFREND 71

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 755556245 156 vngtHICMVFEVLGHHLLKWIIKSNYQGLPLPCVKKIIQQVLQGLDYLHtKCRIIHTDIKPENILLS 222
Cdd:cd07830   72 ----ELYFVFEYMEGNLYQLMKDRKGKPFSESVIRSIIYQILQGLAHIH-KHGFFHRDLKPENLLVS 133

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755556245  79 RYHVIRKLGWGHFSTVWLSWDIQGKKFVAMKVV---KSAEHYTETALDEIRLLKSVRNsdpndPNgemVVQLLDDFkisg 155
Cdd:cd14003    1 NYELGKTLGEGSFGKVKLARHKLTGEKVAIKIIdksKLKEEIEEKIKREIEIMKLLNH-----PN---IIKLYEVI---- 68

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 755556245 156 VNGTHICMVFE-VLGHHLLKWIIKSNYqgLPLPCVKKIIQQVLQGLDYLHtKCRIIHTDIKPENILL 221
Cdd:cd14003   69 ETENKIYLVMEyASGGELFDYIVNNGR--LSEDEARRFFQQLISAVDYCH-SNGIVHRDLKLENILL 132

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755556245  80 YHVIRKLGWGHFSTVWLSWDIQGKKFVAMKVVK---SAEHYTETALDEIRLLKSVRNSdpNDPNgemVVQLLDDF-KISG 155
Cdd:cd07838    1 YEEVAEIGEGAYGTVYKARDLQDGRFVALKKVRvplSEEGIPLSTIREIALLKQLESF--EHPN---VVRLLDVChGPRT 75

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 755556245 156 VNGTHICMVFEVLGHHLLKWIIKSNYQGLPLPCVKKIIQQVLQGLDYLHTKcRIIHTDIKPENILLS 222
Cdd:cd07838   76 DRELKLTLVFEHVDQDLATYLDKCPKPGLPPETIKDLMRQLLRGLDFLHSH-RIVHRDLKPQNILVT 141

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755556245  80 YHVIRKLGWGHFSTVWLSWDIQGKKFVAMKVVK--SAEHYtETALDEIRLLKSVRNsdpndPNgemVVQLLDDFkisgVN 157
Cdd:cd05122    2 FEILEKIGKGGFGVVYKARHKKTGQIVAIKKINleSKEKK-ESILNEIAILKKCKH-----PN---IVKYYGSY----LK 68

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 755556245 158 GTHICMVFEVLGHHLLKWIIKSNYQGLPLPCVKKIIQQVLQGLDYLHTKcRIIHTDIKPENILLSVN 224
Cdd:cd05122   69 KDELWIVMEFCSGGSLKDLLKNTNKTLTEQQIAYVCKEVLKGLEYLHSH-GIIHRDIKAANILLTSD 134

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755556245  86 LGWGHFSTVWLSWDIQGKKFVAMKVV-----------KSAEHYTETALD----EIRLLKSVRNsdpndPNgemVVQL--- 147
Cdd:cd14008    1 LGRGSFGKVKLALDTETGQLYAIKIFnksrlrkrregKNDRGKIKNALDdvrrEIAIMKKLDH-----PN---IVRLyev 72

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 755556245 148 LDDfkisgVNGTHICMVFE-VLGHHLLKWIIKSNYQGLPLPCVKKIIQQVLQGLDYLHTKcRIIHTDIKPENILLS 222
Cdd:cd14008   73 IDD-----PESDKLYLVLEyCEGGPVMELDSGDRVPPLPEETARKYFRDLVLGLEYLHEN-GIVHRDIKPENLLLT 142