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 414144880   1 MDLLGPSLEDLFNFCSRRFTMKTVLMLADQMISRIEYVHTKNFIHRDIKPDNFLMGIGRHCNKclespvgkrkrsmtvst 80
Cdd:cd14128   75 MDLLGPSLEDLFNFCSRRFTMKTVLMLADQMIGRIEYVHNKNFIHRDIKPDNFLMGIGRHCNK----------------- 137

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 414144880  81 sqdpsfsglnqLFLIDFGLAKKYRDNRTRQHIPYREDKNLTGTARYASINAHLGIEQSRRDDMESLGYVLMYFNRTSLPW 160
Cdd:cd14128  138 -----------LFLIDFGLAKKYRDSRTRQHIPYREDKNLTGTARYASINAHLGIEQSRRDDMESLGYVLMYFNRGSLPW 206

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 414144880 161 QGLKAATKKQKYEKISEKKMSTPVEVLCKGFPAEFAMYLNYCRGLRFEEAPDYMYLRQLF 220
Cdd:cd14128  207 QGLKAATKKQKYEKISEKKMSTPVEVLCKGFPAEFAMYLNYCRGLRFEEAPDYMYLRQLF 266

Catalytic domain of the Serine/Threonine protein kinases, Casein Kinase 1 alpha; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CK1 phosphorylates a variety of substrates including enzymes, transcription and splice factors, cytoskeletal proteins, viral oncogenes, receptors, and membrane-associated proteins. There are mutliple isoforms of CK1 and in mammals, seven isoforms (alpha, beta, gamma1-3, delta, and epsilon) have been characterized. These isoforms differ mainly in the length and structure of their C-terminal non-catalytic region. CK1alpha plays a role in cell cycle progression, spindle dynamics, and chromosome segregation. It is also involved in regulating apoptosis mediated by Fas or the retinoid X receptor (RXR), and is a positive regulator of Wnt signaling. CK1alpha phosphorylates the NS5A protein of flaviviruses such as the Hepatitis C virus (HCV) and yellow fever virus (YFV), and influences flaviviral replication. The CK1 alpha subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 414144880   1 MDLLGPSLEDLFNFCSRRFTMKTVLMLADQMISRIEYVHTKNFIHRDIKPDNFLMGIGRHCNKclespvgkrkrsmtvst 80
Cdd:cd14128   75 MDLLGPSLEDLFNFCSRRFTMKTVLMLADQMIGRIEYVHNKNFIHRDIKPDNFLMGIGRHCNK----------------- 137

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 414144880  81 sqdpsfsglnqLFLIDFGLAKKYRDNRTRQHIPYREDKNLTGTARYASINAHLGIEQSRRDDMESLGYVLMYFNRTSLPW 160
Cdd:cd14128  138 -----------LFLIDFGLAKKYRDSRTRQHIPYREDKNLTGTARYASINAHLGIEQSRRDDMESLGYVLMYFNRGSLPW 206

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 414144880 161 QGLKAATKKQKYEKISEKKMSTPVEVLCKGFPAEFAMYLNYCRGLRFEEAPDYMYLRQLF 220
Cdd:cd14128  207 QGLKAATKKQKYEKISEKKMSTPVEVLCKGFPAEFAMYLNYCRGLRFEEAPDYMYLRQLF 266

Serine/threonine protein kinase [Signal transduction mechanisms];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 414144880   1 MDLL-GPSLEDLFNFcSRRFTMKTVLMLADQMISRIEYVHTKNFIHRDIKPDNFLMgigrhcnkclespvgkrkrsmtvs 79
Cdd:COG0515   86 MEYVeGESLADLLRR-RGPLPPAEALRILAQLAEALAAAHAAGIVHRDIKPANILL------------------------ 140

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 414144880  80 tSQDpsfsglNQLFLIDFGLAKKYRDNR-TRQHIpyredknLTGTARYASINAHLGIEQSRRDDMESLGyVLMYF 153
Cdd:COG0515  141 -TPD------GRVKLIDFGIARALGGATlTQTGT-------VVGTPGYMAPEQARGEPVDPRSDVYSLG-VTLYE 200

Fungal protein kinase; This domain appears to be a variant of the protein kinase domain that is found in a variety of fungal species.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 414144880   41 KNFIHRDIKPDNFlmgigrhcnkclespvgkrkrsMTVSTSQDPSFSGlnqlFLIDFGLAKKYRDNRTRQhipyreDKNL 120
Cdd:pfam17667 306 AGILHRDISINNI----------------------MITEPEQEGGRRG----FLIDLDLAKELSRSSASG------ARER 353

                          90       100       110
                  ....*....|....*....|....*....|..
gi 414144880  121 TGTARYASINAHLGIEQSRRDDMESLGYVLMY 152
Cdd:pfam17667 354 TGTLPFMAIELLRGEDHTYRHDLESFFYVLLW 385

Catalytic domain of the Serine/Threonine protein kinases, Casein Kinase 1 alpha; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CK1 phosphorylates a variety of substrates including enzymes, transcription and splice factors, cytoskeletal proteins, viral oncogenes, receptors, and membrane-associated proteins. There are mutliple isoforms of CK1 and in mammals, seven isoforms (alpha, beta, gamma1-3, delta, and epsilon) have been characterized. These isoforms differ mainly in the length and structure of their C-terminal non-catalytic region. CK1alpha plays a role in cell cycle progression, spindle dynamics, and chromosome segregation. It is also involved in regulating apoptosis mediated by Fas or the retinoid X receptor (RXR), and is a positive regulator of Wnt signaling. CK1alpha phosphorylates the NS5A protein of flaviviruses such as the Hepatitis C virus (HCV) and yellow fever virus (YFV), and influences flaviviral replication. The CK1 alpha subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 414144880   1 MDLLGPSLEDLFNFCSRRFTMKTVLMLADQMISRIEYVHTKNFIHRDIKPDNFLMGIGRHCNKclespvgkrkrsmtvst 80
Cdd:cd14128   75 MDLLGPSLEDLFNFCSRRFTMKTVLMLADQMIGRIEYVHNKNFIHRDIKPDNFLMGIGRHCNK----------------- 137

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 414144880  81 sqdpsfsglnqLFLIDFGLAKKYRDNRTRQHIPYREDKNLTGTARYASINAHLGIEQSRRDDMESLGYVLMYFNRTSLPW 160
Cdd:cd14128  138 -----------LFLIDFGLAKKYRDSRTRQHIPYREDKNLTGTARYASINAHLGIEQSRRDDMESLGYVLMYFNRGSLPW 206

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 414144880 161 QGLKAATKKQKYEKISEKKMSTPVEVLCKGFPAEFAMYLNYCRGLRFEEAPDYMYLRQLF 220
Cdd:cd14128  207 QGLKAATKKQKYEKISEKKMSTPVEVLCKGFPAEFAMYLNYCRGLRFEEAPDYMYLRQLF 266

Catalytic domain of the Serine/Threonine protein kinase, Casein Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CK1 phosphorylates a variety of substrates including enzymes, transcription and splice factors, cytoskeletal proteins, viral oncogenes, receptors, and membrane-associated proteins. There are mutliple isoforms of CK1 and in mammals, seven isoforms (alpha, beta, gamma1-3, delta, and epsilon) have been characterized. These isoforms differ mainly in the length and structure of their C-terminal non-catalytic region. Some isoforms have several splice variants such as the long (L) and short (S) variants of CK1alpha. CK1 proteins are involved in the regulation of many cellular processes including membrane transport processes, circadian rhythm, cell division, apoptosis, and the development of cancer and neurodegenerative diseases. The CK1 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 414144880   1 MDLLGPSLEDLFNFCSRRFTMKTVLMLADQMISRIEYVHTKNFIHRDIKPDNFLMGIGRHCNkclespvgkrkrsmtvst 80
Cdd:cd14016   75 MDLLGPSLEDLFNKCGRKFSLKTVLMLADQMISRLEYLHSKGYIHRDIKPENFLMGLGKNSN------------------ 136

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 414144880  81 sqdpsfsglnQLFLIDFGLAKKYRDNRTRQHIPYREDKNLTGTARYASINAHLGIEQSRRDDMESLGYVLMYFNRTSLPW 160
Cdd:cd14016  137 ----------KVYLIDFGLAKKYRDPRTGKHIPYREGKSLTGTARYASINAHLGIEQSRRDDLESLGYVLIYFLKGSLPW 206

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 414144880 161 QGLKAATKKQKYEKISEKKMSTPVEVLCKGFPAEFAMYLNYCRGLRFEEAPDYMYLRQLF 220
Cdd:cd14016  207 QGLKAQSKKEKYEKIGEKKMNTSPEELCKGLPKEFAKYLEYVRSLKFEEEPDYDYLRQLF 266

Catalytic domain of the Serine/Threonine protein kinase, Fungal Casein Kinase 1 homolog 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CK1 phosphorylates a variety of substrates including enzymes, transcription and splice factors, cytoskeletal proteins, viral oncogenes, receptors, and membrane-associated proteins. There are mutliple isoforms of CK1 and in mammals, seven isoforms (alpha, beta, gamma1-3, delta, and epsilon) have been characterized. These isoforms differ mainly in the length and structure of their C-terminal non-catalytic region. This subfamily is composed of fungal CK1 homolog 1 proteins, also called Yck1 in Saccharomyces cerevisiae and Cki1 in Schizosaccharomyces pombe. Yck1 (or Yck1p) and Cki1 are plasma membrane-anchored proteins. Yck1 phosphorylates and regulates Khd1p, a RNA-binding protein that represses translation of bud-localized mRNA. Cki1 phosphorylates and regulates phosphatidylinositol (PI)-(4)P-5-kinase, which catalyzes the last step in the sythesis of PI(4,5)P2, which is involved in actin cytoskeleton remodeling and membrane traffic. The fungal CK1 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 414144880   1 MDLLGPSLEDLFNFCSRRFTMKTVLMLADQMISRIEYVHTKNFIHRDIKPDNFLMGigrhcnkclespvgkrkrsmtvst 80
Cdd:cd14127   75 IDLLGPSLEDLFDLCGRKFSVKTVVMVAKQMLTRVQTIHEKNLIYRDIKPDNFLIG------------------------ 130

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 414144880  81 sqDPSFSGLNQLFLIDFGLAKKYRDNRTRQHIPYREDKNLTGTARYASINAHLGIEQSRRDDMESLGYVLMYFNRTSLPW 160
Cdd:cd14127  131 --RPGTKNANVIHVVDFGMAKQYRDPKTKQHIPYREKKSLSGTARYMSINTHLGREQSRRDDLEALGHVFMYFLRGSLPW 208

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 414144880 161 QGLKAATKKQKYEKISEKKMSTPVEVLCKGFPAEFAMYLNYCRGLRFEEAPDYMYLRQLFRILFRTLN 228
Cdd:cd14127  209 QGLKAATNKQKYEKIGEKKQSTPIRDLCEGFPEEFAQYLEYVRNLGFDETPDYDYLRGLFSKALKDLG 276

Catalytic domain of the Serine/Threonine protein kinase, Vaccinia Related Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. VRKs were initially discovered due to its similarity to vaccinia virus B1R STK, which is important for viral replication. They play important roles in cell signaling, nuclear envelope dynamics, apoptosis, and stress responses. Vertebrates contain three VRK proteins (VRK1, VRK2, and VRK3) while invertebrates, specifically fruit flies and nematodes, seem to carry only a single ortholog. Mutations of VRK in Drosophila and Caenorhabditis elegans showed varying phenotypes ranging from embryonic lethality to mitotic and meiotic defects resulting in sterility. In vertebrates, VRK1 is implicated in cell cycle progression and proliferation, nuclear envelope assembly, and chromatin condensation. VRK2 is involved in modulating JNK signaling. VRK3 is an inactive pseudokinase that inhibits ERK signaling. The VRK 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 414144880   1 MDLLGPSLEDLFNFCSRRFTMKTVLMLADQMISRIEYVHTKNFIHRDIKPDNFLMGIGRhcNKclespvgkrkrsmtvst 80
Cdd:cd14015  106 MPRFGRDLQKIFEKNGKRFPEKTVLQLALRILDVLEYIHENGYVHADIKASNLLLGFGK--NK----------------- 166

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 414144880  81 sqdpsfsglNQLFLIDFGLAKKYRDNRtrQHIPYRED--KNLTGTARYASINAHLGIEQSRRDDMESLGYVLMYFNRTSL 158
Cdd:cd14015  167 ---------DQVYLVDYGLASRYCPNG--KHKEYKEDprKAHNGTIEFTSRDAHKGVAPSRRGDLEILGYNMLQWLCGKL 235

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 414144880 159 PWQGLKAATKKQKYEKisEKKMSTPVEVLCKGF-----PAEFAMYLNYCRGLRFEEAPDYMYLRQLF 220
Cdd:cd14015  236 PWEDNLKNPEYVQKQK--EKYMDDIPLLLKKCFpgkdvPEELQKYLKYVASLEYEEKPDYEKLRKIL 300

Catalytic domain of the Serine/Threonine protein kinase, Tau-Tubulin Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TTBK is a neuron-specific kinase that phosphorylates the microtubule-associated protein tau and promotes its aggregation. Higher vertebrates contain two TTBK proteins, TTBK1 and TTBK2, both of which have been implicated in neurodegeneration. Genetic variations in TTBK1 are linked to Alzheimer's disease (AD). Hyperphosphorylated tau is a major component of paired helical filaments that accumulate in the brain of AD patients. Studies in transgenic mice show that TTBK1 is involved in the phosphorylation-dependent pathogenic aggregation of tau. The TTBK1 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 414144880   1 MDLLGPSLEDLFNFCSR-RFTMKTVLMLADQMISRIEYVHTKNFIHRDIKPDNFLMG-IGRHCNKClespvgkrkrsmtv 78
Cdd:cd14130   75 MQLQGRNLADLRRSQPRgTFTLSTTLRLGKQILESIEAIHSVGFLHRDIKPSNFAMGrLPSTYRKC-------------- 140

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 414144880  79 stsqdpsfsglnqlFLIDFGLAKKYrDNRTRQHIPYREDKNLTGTARYASINAHLGIEQSRRDDMESLGYVLMYFNRTSL 158
Cdd:cd14130  141 --------------YMLDFGLARQY-TNTTGEVRPPRNVAGFRGTVRYASVNAHKNREMGRHDDLWSLFYMLVEFAVGQL 205

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 414144880 159 PWQGLKAATKKQKYEKISEKKMstpvevLCKGFPAEFAMYLNYCRGLRFEEAPDYMYLRQLF 220
Cdd:cd14130  206 PWRKIKDKEQVGMIKEKYEHRM------LLKHMPSEFHLFLDHIASLDYFTKPDYQLIMSVF 261

Catalytic domain of the Serine/Threonine protein kinase, Vaccinia Related Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. VRKs were initially discovered due to its similarity to vaccinia virus B1R STK, which is important for viral replication. Vertebrates contain three VRK proteins. Human VRK1 is implicated in the regulation of many cellular processes including cell cycle progression and proliferation, stress responses, nuclear envelope assembly and chromatin condensation. It regulates cell cycle progression during the DNA replication period by inducing cyclin D1 expression. VRK1 also phosphorylates and regulates some transcription factors including p53, c-Jun, ATF2, and nuclear factor BAF. VRK1 stabilizes p53 by interfering with its mdm2-mediated degradation. Accumulation of p53, which blocks cell growth and division, is modulated by an autoregulatory loop between p53 and VRK1 (accumulated p53 downregulates VRK1). This autoregulatory loop has been found to be nonfunctional in some lung carcinomas. The VRK1 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 414144880   1 MDLLGPSLEDLFNFCSRRFTMKTVLMLADQMISRIEYVHTKNFIHRDIKPDNFLMgigrhcnkclespvgkrkrsmtvst 80
Cdd:cd14122  106 MDRFGSDLQKIYEANAKRFSRKTVLQLGLRILDILEYIHEHEYVHGDIKASNLLL------------------------- 160

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 414144880  81 sqdpSFSGLNQLFLIDFGLAKKYRDNRTrqHIPYRED--KNLTGTARYASINAHLGIEQSRRDDMESLGYVLMYFNRTSL 158
Cdd:cd14122  161 ----SYKNPDQVYLVDYGLAYRYCPEGV--HKEYKEDpkRCHDGTIEFTSIDAHKGVAPSRRGDLEILGYCMIQWLCGHL 234

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 414144880 159 PWQGLKAATKKQKYEKISEKKMSTPVEVLC---KGFPAEFAMYLNYCRGLRFEEAPDYMYLRQLF 220
Cdd:cd14122  235 PWEDNLKDPNYVRDSKIRYRDNISELMEKCfpgKNKPGEIRKYMETVKLLGYTEKPLYPHLREIL 299

putative serine/threonine kinase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 414144880  31 MISRIEYVHTKNFIHRDIKPDNFLmgigrhcnkclespVGKRKRSmtvstsqdpsfsglnqlFLIDFGLAKKYRDNRtrQ 110
Cdd:PHA02882 135 MLTTLEYIHEHGISHGDIKPENIM--------------VDGNNRG-----------------YIIDYGIASHFIIHG--K 181

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 414144880 111 HIPY-REDKNL-TGTARYASINAHLGIEQSRRDDMESLGYVLMYFNRTSLPWQGLKAATKKQKYEKISEKKMSTPVEVLC 188
Cdd:PHA02882 182 HIEYsKEQKDLhRGTLYYAGLDAHNGACVTRRGDLESLGYCMLKWAGIKLPWKGFGHNGNLIHAAKCDFIKRLHEGKIKI 261

                        170       180       190
                 ....*....|....*....|....*....|..
gi 414144880 189 KGFPAEFAMYLNYCRGLRFEEAPDYMYLRQLF 220
Cdd:PHA02882 262 KNANKFIYDFIECVTKLSYEEKPDYDALIKIF 293

Serine/threonine protein kinase [Signal transduction mechanisms];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 414144880   1 MDLL-GPSLEDLFNFcSRRFTMKTVLMLADQMISRIEYVHTKNFIHRDIKPDNFLMgigrhcnkclespvgkrkrsmtvs 79
Cdd:COG0515   86 MEYVeGESLADLLRR-RGPLPPAEALRILAQLAEALAAAHAAGIVHRDIKPANILL------------------------ 140

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 414144880  80 tSQDpsfsglNQLFLIDFGLAKKYRDNR-TRQHIpyredknLTGTARYASINAHLGIEQSRRDDMESLGyVLMYF 153
Cdd:COG0515  141 -TPD------GRVKLIDFGIARALGGATlTQTGT-------VVGTPGYMAPEQARGEPVDPRSDVYSLG-VTLYE 200

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 414144880   1 MDLLGPSLED-LFNFCSRRFTMKTVLMLADQMISRIEYVHTKNFIHRDIKPDNFLMgigrHCNKCLESPVGKRKRSMTVS 79
Cdd:cd14134   93 FELLGPSLYDfLKKNNYGPFPLEHVQHIAKQLLEAVAFLHDLKLTHTDLKPENILL----VDSDYVKVYNPKKKRQIRVP 168

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|.
gi 414144880  80 TSQDpsfsglnqLFLIDFGLAKKYRDNR-----TRQhipYR 115
Cdd:cd14134  169 KSTD--------IKLIDFGSATFDDEYHssivsTRH---YR 198

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 414144880   5 GPSLEDLFNFCSRRFTMKTVLMLADQMISRIEYVHTKNFIHRDIKPDNFLMGIGrhcnkclespvGKRKrsmtvstsqdp 84
Cdd:cd05122   81 GGSLKDLLKNTNKTLTEQQIAYVCKEVLKGLEYLHSHGIIHRDIKAANILLTSD-----------GEVK----------- 138

                         90       100       110
                 ....*....|....*....|....*....|...
gi 414144880  85 sfsglnqlfLIDFGLAKKYRDNRTRQHI---PY 114
Cdd:cd05122  139 ---------LIDFGLSAQLSDGKTRNTFvgtPY 162

Catalytic domain of Rho-associated coiled-coil containing protein kinase (ROCK)- and Nuclear Dbf2-Related (NDR)-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 ROCK and ROCK-like proteins such as DMPK, MRCK, and CRIK, as well as NDR and NDR-like proteins such as LATS, CBK1 and Sid2p. ROCK and CRIK are effectors of the small GTPase Rho, while MRCK is an effector of the small GTPase Cdc42. NDR and NDR-like kinases contain an N-terminal regulatory (NTR) domain and an insert within the catalytic domain that contains an auto-inhibitory sequence. Proteins in this subfamily are involved in regulating many cellular functions including contraction, motility, division, proliferation, apoptosis, morphogenesis, and cytokinesis. The ROCK/NDR-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 414144880  10 DLFNFCSR--RFTMKTVLMLADQMISRIEYVHTKNFIHRDIKPDNFLMGIGRHcnkclespvgkrkrsmtvstsqdpsfs 87
Cdd:cd05573   87 DLMNLLIKydVFPEETARFYIAELVLALDSLHKLGFIHRDIKPDNILLDADGH--------------------------- 139

                         90       100
                 ....*....|....*....|..
gi 414144880  88 glnqLFLIDFGLAKKYRDNRTR 109
Cdd:cd05573  140 ----IKLADFGLCTKMNKSGDR 157

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 414144880  30 QMISRIEYVHTKNFIHRDIKPDNFLMGigrhcnkclespvgkrkrsmtvstsqdpsFSGLnqLFLIDFGLAKKYRDNRTR 109
Cdd:cd06626  107 QLLEGLAYLHENGIVHRDIKPANIFLD-----------------------------SNGL--IKLGDFGSAVKLKNNTTT 155

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....
gi 414144880 110 qhIPYREDKNLTGTARYAS---INAHLGIEQSRRDDMESLGYVLMYFNRTSLPW 160
Cdd:cd06626  156 --MAPGEVNSLVGTPAYMApevITGNKGEGHGRAADIWSLGCVVLEMATGKRPW 207

Catalytic domain of RCK1-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of fungal STKs including Saccharomyces cerevisiae RCK1 and RCK2, Schizosaccharomyces pombe Sty1-regulated kinase 1 (Srk1), and similar proteins. RCK1, RCK2 (or Rck2p), and Srk1 are MAPK-activated protein kinases. RCK1 and RCK2 are involved in oxidative and metal stress resistance in budding yeast. RCK2 also regulates rapamycin sensitivity in both S. cerevisiae and Candida albicans. Srk1 is activated by Sty1/Spc1 and is involved in negatively regulating cell cycle progression by inhibiting Cdc25. The RCK1-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 414144880  30 QMISRIEYVHTKNFIHRDIKPDNFLMgigrhcnkcleSPVGKRKRSMTVSTSQDP-------SF------SGLNQLFLID 96
Cdd:cd14096  114 QVASAVKYLHEIGVVHRDIKPENLLF-----------EPIPFIPSIVKLRKADDDetkvdegEFipgvggGGIGIVKLAD 182

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....
gi 414144880  97 FGLAKKYRDNRTrqhipyredKNLTGTARYASINAHLGIEQSRRDDMESLGYVL 150
Cdd:cd14096  183 FGLSKQVWDSNT---------KTPCGTVGYTAPEVVKDERYSKKVDMWALGCVL 227

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 414144880  10 DLFNFCSR--RFTMKTVLMLADQMISRIEYVHTKNFIHRDIKPDNFLMgigrhcnkclespvgkrkrsmtvstSQDpsfs 87
Cdd:cd05581   87 DLLEYIRKygSLDEKCTRFYTAEIVLALEYLHSKGIIHRDLKPENILL-------------------------DED---- 137

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|.
gi 414144880  88 glNQLFLIDFGLAKKY----------RDNRTRQHIPYREDKNLTGTARYAS 128
Cdd:cd05581  138 --MHIKITDFGTAKVLgpdsspestkGDADSQIAYNQARAASFVGTAEYVS 186

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.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*....
gi 414144880  10 DLFNF--CSRRFTMKTVLMLADQMISRIEYVHTKNFIHRDIKPDNFLMG 56
Cdd:cd14007   86 ELYKElkKQKRFDEKEAAKYIYQLALALDYLHSKNIIHRDIKPENILLG 134

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 414144880   1 MDLLGPSLEDLFNFCSRRFTMKTVLMLADQMISRIEYVHTKNFIHRDIKPDNFLMgigrhcnkclespvgkrkrsmtvst 80
Cdd:cd05118   80 FELMGMNLYELIKDYPRGLPLDLIKSYLYQLLQALDFLHSNGIIHRDLKPENILI------------------------- 134

                         90       100
                 ....*....|....*....|....*.
gi 414144880  81 SQDPSfsglnQLFLIDFGLAKKYRDN 106
Cdd:cd05118  135 NLELG-----QLKLADFGLARSFTSP 155

Signaling protein combining a Ser/Thr protein kinase domain and the GUN4/Ycf53 porphyrin-binding domain [Signal transduction mechanisms];

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 414144880  36 EYVHTKNFIHRDIKPDNflmgIGRHCNKclespvgkrkrsmtvstsqdpsfsglNQLFLIDFGLAK 101
Cdd:COG5752  152 QFIHSRNVIHRDIKPAN----IIRRRSD--------------------------GKLVLIDFGVAK 187

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.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 414144880  10 DLFNFCSRR---FTMKTVLMLADQMISRIEYVHTKNFIHRDIKPDNFLMG 56
Cdd:cd07829   83 DLKKYLDKRpgpLPPNLIKSIMYQLLRGLAYCHSHRILHRDLKPQNLLIN 132

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
                 ....*....|....*....|....*....|....*....|....*..
gi 414144880  15 CSRRFTMKTVLMLADQMISRIEYVHTKNFIHRDIKPDNFLMGIGRHC 61
Cdd:cd14008  101 RVPPLPEETARKYFRDLVLGLEYLHENGIVHRDIKPENLLLTADGTV 147

Catalytic domain of the Dual-specificity Mitotic checkpoint protein kinase, Monopolar spindle 1 (also called TTK); Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine as well as tyrosine residues on protein substrates. TTK/Mps1 is a spindle checkpoint kinase that was first discovered due to its necessity in centrosome duplication in budding yeast. It was later found to function in the spindle assembly checkpoint, which monitors the proper attachment of chromosomes to the mitotic spindle. In yeast, substrates of Mps1 include the spindle pole body components Spc98p, Spc110p, and Spc42p. The TTK/Mps1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein serine/threonine PKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 414144880  30 QMISRIEYVHTKNFIHRDIKPDNFLMGIGRhcnkclespvgkrkrsmtvstsqdpsfsglnqLFLIDFGLAKKYRDNRTr 109
Cdd:cd14131  111 QMLEAVHTIHEEGIVHSDLKPANFLLVKGR--------------------------------LKLIDFGIAKAIQNDTT- 157

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 414144880 110 qHIpYREDKnlTGTARYASINAHLGIEQ----------SRRDDMESLG---YVLMY----FNRTSLPWQGLKAATKKQ-- 170
Cdd:cd14131  158 -SI-VRDSQ--VGTLNYMSPEAIKDTSAsgegkpkskiGRPSDVWSLGcilYQMVYgktpFQHITNPIAKLQAIIDPNhe 233

                 ....*....
gi 414144880 171 -KYEKISEK 178
Cdd:cd14131  234 iEFPDIPNP 242

Catalytic domain of PRKX-like Protein Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Members of this group include human PRKX (X chromosome-encoded protein kinase), Drosophila DC2, and similar proteins. PRKX is present in many tissues including fetal and adult brain, kidney, and lung. The PRKX gene is located in the Xp22.3 subregion and has a homolog called PRKY on the Y chromosome. An abnormal interchange between PRKX aand PRKY leads to the sex reversal disorder of XX males and XY females. PRKX is implicated in granulocyte/macrophage lineage differentiation, renal cell epithelial migration, and tubular morphogenesis in the developing kidney. The PRKX-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 414144880  10 DLFNF--CSRRFTMKTVLMLADQMISRIEYVHTKNFIHRDIKPDNFLMGIGRHcnkclespvgkrkrsmtvstsqdpsfs 87
Cdd:cd05612   87 ELFSYlrNSGRFSNSTGLFYASEIVCALEYLHSKEIVYRDLKPENILLDKEGH--------------------------- 139

                         90       100
                 ....*....|....*....|.
gi 414144880  88 glnqLFLIDFGLAKKYRDnRT 108
Cdd:cd05612  140 ----IKLTDFGFAKKLRD-RT 155

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 414144880  10 DLFNFCSRR--FTMKTVLMLADQMISRIEYVHTKNFIHRDIKPDNFLMgigrhCNKCLESPVGKrkrsmtvstsqdpsfs 87
Cdd:cd14105   94 ELFDFLAEKesLSEEEATEFLKQILDGVNYLHTKNIAHFDLKPENIML-----LDKNVPIPRIK---------------- 152

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 414144880  88 glnqlfLIDFGLAKKYRDNrtrqhipyREDKNLTGTARYAS---INAH-LGIEQsrrdDMESLGYVLMYFNRTSLPWQGl 163
Cdd:cd14105  153 ------LIDFGLAHKIEDG--------NEFKNIFGTPEFVApeiVNYEpLGLEA----DMWSIGVITYILLSGASPFLG- 213

                        170
                 ....*....|...
gi 414144880 164 kaATKKQKYEKIS 176
Cdd:cd14105  214 --DTKQETLANIT 224

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.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 414144880   7 SLEDLFNFCSRRFTMKTVLMLADQmISR-IEYVHTKNFIHRDIKPDNFLM 55
Cdd:cd13999   76 SLYDLLHKKKIPLSWSLRLKIALD-IARgMNYLHSPPIIHRDLKSLNILL 124