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 1907161723 330 TRAADLLVNPLDPRNADKIRVKIADLGNACWVHKHFTEDIQTRQYRSIEVLIGAGYSTPADIWSTACMAFELATGDYLFE 409
Cdd:cd14217   186 STAPDLLVNPLDPRNADKIRVKIADLGNACWVHKHFTEDIQTRQYRSIEVLIGAGYSTPADIWSTACMAFELATGDYLFE 265

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161723 410 PHSGEDYSRDEDHIAHIIELLGSIPRHFALSGKYSREFFNRRdhialiiellgkvprkyamlgkyskefftrkGELRHIT 489
Cdd:cd14217   266 PHSGEDYSRDEDHIAHIIELLGCIPRHFALSGKYSREFFNRR-------------------------------GELRHIT 314

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1907161723 490 KLKPWSLFDVLVEKYGWPHEDAAQFTDFLIPMLEMVPEKRASAGECLRHPWL 541
Cdd:cd14217   315 KLKPWSLFDVLVEKYGWPHEDAAQFTDFLIPMLEMVPEKRASAGECLRHPWL 366

K+-dependent Na+/Ca+ exchanger; [Transport and binding proteins, Cations and iron carrying compounds]

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161723  131 EENITSAEASGEQQDGEYQPEVTLKAADLEDTTEEETAKDNGEVEDQEEKEDAEKENAEKDEDDVEQELANLDPTWVESP 210
Cdd:TIGR00927  820 ETQADDTEVKDETGEQELNAENQGEAKQDEKGVDGGGGSDGGDSEEEEEEEEEEEEEEEEEEEEEEEEEENEEPLSLEWP 899

                   .
gi 1907161723  211 K 211
Cdd:TIGR00927  900 E 900

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 1907161723 330 TRAADLLVNPLDPRNADKIRVKIADLGNACWVHKHFTEDIQTRQYRSIEVLIGAGYSTPADIWSTACMAFELATGDYLFE 409
Cdd:cd14217   186 STAPDLLVNPLDPRNADKIRVKIADLGNACWVHKHFTEDIQTRQYRSIEVLIGAGYSTPADIWSTACMAFELATGDYLFE 265

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161723 410 PHSGEDYSRDEDHIAHIIELLGSIPRHFALSGKYSREFFNRRdhialiiellgkvprkyamlgkyskefftrkGELRHIT 489
Cdd:cd14217   266 PHSGEDYSRDEDHIAHIIELLGCIPRHFALSGKYSREFFNRR-------------------------------GELRHIT 314

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1907161723 490 KLKPWSLFDVLVEKYGWPHEDAAQFTDFLIPMLEMVPEKRASAGECLRHPWL 541
Cdd:cd14217   315 KLKPWSLFDVLVEKYGWPHEDAAQFTDFLIPMLEMVPEKRASAGECLRHPWL 366

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161723  349 RVKIADLGNACWVH--KHFTEDIQTRQYRSIEVLIGAGYSTPADIWSTACMAFELATGDYLFEphsgedysrDEDHIAHI 426
Cdd:smart00220 135 HVKLADFGLARQLDpgEKLTTFVGTPEYMAPEVLLGKGYGKAVDIWSLGVILYELLTGKPPFP---------GDDQLLEL 205

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161723  427 IELLGSIPRHFAL-SGKYSREFFNrrdhialiiellgkvprkyamlgkyskefftrkgelrhitklkpwslfdvLVEKyg 505
Cdd:smart00220 206 FKKIGKPKPPFPPpEWDISPEAKD--------------------------------------------------LIRK-- 233

                          170       180       190
                   ....*....|....*....|....*....|....*.
gi 1907161723  506 wphedaaqftdflipMLEMVPEKRASAGECLRHPWL 541
Cdd:smart00220 234 ---------------LLVKDPEKRLTAEEALQHPFF 254

protein kinase; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161723 333 ADLLVNPLDPRN--ADKIRVKIADLGNACWVHKHFTEDIQTRQYRSIEVLIGAGYSTPADIWSTACMAFELATGDYLFEP 410
Cdd:PTZ00284  268 SDTVVDPVTNRAlpPDPCRVRICDLGGCCDERHSRTAIVSTRHYRSPEVVLGLGWMYSTDMWSMGCIIYELYTGKLLYDT 347

                          90       100
                  ....*....|....*....|....*....
gi 1907161723 411 HSgedysrDEDHIaHIIE-LLGSIPRHFA 438
Cdd:PTZ00284  348 HD------NLEHL-HLMEkTLGRLPSEWA 369

Serine/threonine protein kinase [Signal transduction mechanisms];

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1907161723   1 MVFE-VLGHHLLKWIikSNYQGLPVRCVKSIIRQVLQGLDYLHSKcKIIHTDIKPENILMCVD 62
Cdd:COG0515    84 LVMEyVEGESLADLL--RRRGPLPPAEALRILAQLAEALAAAHAA-GIVHRDIKPANILLTPD 143

protein kinase; Provisional

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1907161723   7 GHHLLKWIIKsnYQGLPVRCVKSIIRQVLQGLDYLHSKCKIIHTDIKPENILMCVDDAYVRRMAAEAT 74
Cdd:PTZ00284  215 GPCLLDWIMK--HGPFSHRHLAQIIFQTGVALDYFHTELHLMHTDLKPENILMETSDTVVDPVTNRAL 280

Serine/threonine protein kinase [Signal transduction mechanisms];

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1907161723 349 RVKIADLGNACWVHK-HFTED---IQTRQYRSIEVLIGAGYSTPADIWSTACMAFELATGDYLFEPHSGED 415
Cdd:COG0515   145 RVKLIDFGIARALGGaTLTQTgtvVGTPGYMAPEQARGEPVDPRSDVYSLGVTLYELLTGRPPFDGDSPAE 215

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 1907161723 330 TRAADLLVNPLDPRNADKIRVKIADLGNACWVHKHFTEDIQTRQYRSIEVLIGAGYSTPADIWSTACMAFELATGDYLFE 409
Cdd:cd14217   186 STAPDLLVNPLDPRNADKIRVKIADLGNACWVHKHFTEDIQTRQYRSIEVLIGAGYSTPADIWSTACMAFELATGDYLFE 265

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161723 410 PHSGEDYSRDEDHIAHIIELLGSIPRHFALSGKYSREFFNRRdhialiiellgkvprkyamlgkyskefftrkGELRHIT 489
Cdd:cd14217   266 PHSGEDYSRDEDHIAHIIELLGCIPRHFALSGKYSREFFNRR-------------------------------GELRHIT 314

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1907161723 490 KLKPWSLFDVLVEKYGWPHEDAAQFTDFLIPMLEMVPEKRASAGECLRHPWL 541
Cdd:cd14217   315 KLKPWSLFDVLVEKYGWPHEDAAQFTDFLIPMLEMVPEKRASAGECLRHPWL 366

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 1907161723 334 DLLVNPLDPRNADKIRVKIADLGNACWVHKHFTEDIQTRQYRSIEVLIGAGYSTPADIWSTACMAFELATGDYLFEPHSG 413
Cdd:cd14216   173 NFLVNPLEPKNAEKLKVKIADLGNACWVHKHFTEDIQTRQYRSLEVLIGSGYNTPADIWSTACMAFELATGDYLFEPHSG 252

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161723 414 EDYSRDEDHIAhiiellgsiprhfalsgkysreffnrrdhiaLIIELLGKVPRKYAMLGKYSKEFFTRKGELRHITKLKP 493
Cdd:cd14216   253 EDYSRDEDHIA-------------------------------LIIELLGKVPRKLIVAGKYSKEFFTKKGDLKHITKLKP 301

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*...
gi 1907161723 494 WSLFDVLVEKYGWPHEDAAQFTDFLIPMLEMVPEKRASAGECLRHPWL 541
Cdd:cd14216   302 WGLFEVLVEKYEWSQEEAAGFTDFLLPMLELIPEKRATAAECLRHPWL 349

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 1907161723   1 MVFEVLGHHLLKWIIKSNYQGLPVRCVKSIIRQVLQGLDYLHSKCKIIHTDIKPENILMCVDDAYVRRMAAEATEWQK-- 78
Cdd:cd14217    97 MVFEVLGHHLLKWIIKSNYQGLPIRCVKSIIRQVLQGLDYLHSKCKIIHTDIKPENILMCVDDAYVRRMAAEATEWQKag 176

                          90
                  ....*....|...
gi 1907161723  79 -------AVSTAP 84
Cdd:cd14217   177 apppsgsAVSTAP 189

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 1907161723   1 MVFEVLGHHLLKWIIKSNYQGLPVRCVKSIIRQVLQGLDYLHSKCKIIHTDIKPENILMCVDDAYVRRMAAEATEWQKAV 80
Cdd:cd14216    95 MVFEVLGHHLLKWIIKSNYQGLPLPCVKKIIRQVLQGLDYLHTKCRIIHTDIKPENILLSVNEQYIRRLAAEATEWQRNF 174

                  ....
gi 1907161723  81 STAP 84
Cdd:cd14216   175 LVNP 178

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 1907161723 335 LLVNPldprnaDKIRVKIADLGNACWVHKHFTEDIQTRQYRSIEVLIGAGYSTPADIWSTACMAFELATGDYLFephSGE 414
Cdd:cd14210   148 LLKQP------SKSSIKVIDFGSSCFEGEKVYTYIQSRFYRAPEVILGLPYDTAIDMWSLGCILAELYTGYPLF---PGE 218

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161723 415 DysrDEDHIAHIIELLGSIPRHFALSGKYSREFFNRRDHIaliiellgkvprkyamlgkysKEFFTRKGELRhitKLKPW 494
Cdd:cd14210   219 N---EEEQLACIMEVLGVPPKSLIDKASRRKKFFDSNGKP---------------------RPTTNSKGKKR---RPGSK 271

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*..
gi 1907161723 495 SLFDVLvekygwpHEDAAQFTDFLIPMLEMVPEKRASAGECLRHPWL 541
Cdd:cd14210   272 SLAQVL-------KCDDPSFLDFLKKCLRWDPSERMTPEEALQHPWI 311

Catalytic domain of the protein kinase, Dual-specificity tYrosine-phosphorylated and -Regulated Kinase 1; 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. Mammals contain two types of DYRK1 proteins, DYRK1A and DYRK1B. DYRK1A was previously called minibrain kinase homolog (MNBH) or dual-specificity YAK1-related kinase. It phosphorylates various substrates and is involved in many cellular events. It phosphorylates and inhibits the transcription factors, nuclear factor of activated T cells (NFAT) and forkhead in rhabdomyosarcoma (FKHR). It regulates neuronal differentiation by targetting CREB (cAMP response element-binding protein). It also targets many endocytic proteins including dynamin and amphiphysin and may play a role in the endocytic pathway. The gene encoding DYRK1A is located in the DSCR (Down syndrome critical region) of human chromosome 21 and DYRK1A has been implicated in the pathogenesis of DS. DYRK1B, also called minibrain-related kinase (MIRK), is highly expressed in muscle and 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. DYRKs autophosphorylate themselves on tyrosine residues and phosphorylate their substrates exclusively on S/T residues. The DYRK1 subfamily is part of 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 1907161723 335 LLVNPldPRNAdkirVKIADLGNACWVHKHFTEDIQTRQYRSIEVLIGAGYSTPADIWSTACMAFELATGDYLFephSGe 414
Cdd:cd14226   150 LLCNP--KRSA----IKIIDFGSSCQLGQRIYQYIQSRFYRSPEVLLGLPYDLAIDMWSLGCILVEMHTGEPLF---SG- 219

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161723 415 dySRDEDHIAHIIELLGSIPRHFALSGKYSREFFNRrdhialiIELLGKVPRKYAMLGKYsKEFFTRKgelrhitklkpw 494
Cdd:cd14226   220 --ANEVDQMNKIVEVLGMPPVHMLDQAPKARKFFEK-------LPDGTYYLKKTKDGKKY-KPPGSRK------------ 277

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161723 495 sLFDVLVEKYGWP---------H--EDAAQFTDFLIPMLEMVPEKRASAGECLRHPWLNS 543
Cdd:cd14226   278 -LHEILGVETGGPggrragepgHtvEDYLKFKDLILRMLDYDPKTRITPAEALQHSFFKR 336

Catalytic domain of Dual-specificity tYrosine-phosphorylated and -Regulated Kinase-like protein kinases; Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (S/T) as well as tyrosine residues on protein substrates. This subfamily is composed of the dual-specificity DYRKs and YAK1, as well as the S/T kinases (STKs), HIPKs. DYRKs and YAK1 autophosphorylate themselves on tyrosine residues and phosphorylate their substrates exclusively on S/T residues. Proteins in this subfamily play important roles in cell proliferation, differentiation, survival, growth, and development. The DYRK-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161723 335 LLVNPldprnaDKIRVKIADLGNACWVHKHFTEDIQTRQYRSIEVLIGAGYSTPADIWSTACMAFELATGDYLFePHSGE 414
Cdd:cd14133   134 LLASY------SRCQIKIIDFGSSCFLTQRLYSYIQSRYYRAPEVILGLPYDEKIDMWSLGCILAELYTGEPLF-PGASE 206

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161723 415 dysrdEDHIAHIIELLGSIPRHFALSGKysreffnrrdhialiiellgkvprkyamlgkyskefftrkgelrhitklkpw 494
Cdd:cd14133   207 -----VDQLARIIGTIGIPPAHMLDQGK---------------------------------------------------- 229

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*..
gi 1907161723 495 slfdvlvekygwphEDAAQFTDFLIPMLEMVPEKRASAGECLRHPWL 541
Cdd:cd14133   230 --------------ADDELFVDFLKKLLEIDPKERPTASQALSHPWL 262

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 1907161723 350 VKIADLGNACWVHKHFTEDIQTRQYRSIEVLIGAGYSTPADIWSTACMAFELATGDYLFephSGEDysrDEDHIAHIIEL 429
Cdd:cd14224   209 IKVIDFGSSCYEHQRIYTYIQSRFYRAPEVILGARYGMPIDMWSFGCILAELLTGYPLF---PGED---EGDQLACMIEL 282

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161723 430 LGSIPRHFALSGKYSREFFNRRDHialiiellgkvPRkYAMLGKYSKEFF------TRKGELRHITKLKPWSLfdvlvek 503
Cdd:cd14224   283 LGMPPQKLLETSKRAKNFISSKGY-----------PR-YCTVTTLPDGSVvlnggrSRRGKMRGPPGSKDWVT------- 343

                         170       180       190
                  ....*....|....*....|....*....|....*...
gi 1907161723 504 yGWPHEDAAQFTDFLIPMLEMVPEKRASAGECLRHPWL 541
Cdd:cd14224   344 -ALKGCDDPLFLDFLKRCLEWDPAARMTPSQALRHPWL 380

Catalytic domain of the protein kinase, Dual-specificity tYrosine-phosphorylated and -Regulated Kinase 4; 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. DYRK4 is a testis-specific kinase with restricted expression to postmeiotic spermatids. It may function during spermiogenesis, however, it is not required for male fertility. DYRK4 has also been detected in a human teratocarcinoma cell line induced to produce postmitotic neurons. It may have a role in neuronal differentiation. 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. The DYRK4 subfamily is part of 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 1907161723 350 VKIADLGNACWVHKHFTEDIQTRQYRSIEVLIGAGYSTPADIWSTACMAFELATGDYLFephSGEDysrDEDHIAHIIEL 429
Cdd:cd14225   187 IKVIDFGSSCYEHQRVYTYIQSRFYRSPEVILGLPYSMAIDMWSLGCILAELYTGYPLF---PGEN---EVEQLACIMEV 260

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161723 430 LGSIPRHfalsgkysreffnrrdhialiieLLGKVPRKyamlgkysKEFFTRKGELRHIT-----KLKPWS--LFDVLve 502
Cdd:cd14225   261 LGLPPPE-----------------------LIENAQRR--------RLFFDSKGNPRCITnskgkKRRPNSkdLASAL-- 307

                         170       180       190
                  ....*....|....*....|....*....|....*....
gi 1907161723 503 kygwpHEDAAQFTDFLIPMLEMVPEKRASAGECLRHPWL 541
Cdd:cd14225   308 -----KTSDPLFLDFIRRCLEWDPSKRMTPDEALQHEWI 341

Catalytic domain of the Dual-specificity protein kinase, CDC-like kinase 2; Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine as well as tyrosine residues on protein substrates. CLK2 plays a role in hepatic insulin signaling and glucose metabolism. It is induced by the insulin/Akt pathway as part of the hepatic refeeding reponse, and it directly phosphorylates the SR domain of PGC-1alpha, which results in decreased gluconeogenic gene expression and glucose output. CLKs are involved in the phosphorylation and regulation of serine/arginine-rich (SR) proteins, which play a crucial role in pre-mRNA splicing by directing splice site selection. SR proteins are phosphorylated first by SR protein kinases (SRPKs) at the N-terminus, which leads to its assembly into nuclear speckles where splicing factors are stored. CLKs phosphorylate the C-terminal part of SR proteins, causing the nuclear speckles to dissolve and splicing factors to be recruited at sites of active transcription. Based on a conserved "EHLAMMERILG" signature motif which may be crucial for substrate specificity, CLKs are also referred to as LAMMER kinases. CLKs autophosphorylate at tyrosine residues and phosphorylate their substrates exclusively on serine/threonine residues. The CLK2 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 1907161723 341 DPRNADKIRVKIADLGNACWVHKHFTEDIQTRQYRSIEVLIGAGYSTPADIWSTACMAFELATGDYLFEPHSgedysrDE 420
Cdd:cd14215   165 DERSVKSTAIRVVDFGSATFDHEHHSTIVSTRHYRAPEVILELGWSQPCDVWSIGCIIFEYYVGFTLFQTHD------NR 238

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161723 421 DHIAHIIELLGSIPRHFALSGKYSREFFNRRdhialiielLGKVPRKYAmlGKYSKEfftrkgelrhitKLKPWSLFdVL 500
Cdd:cd14215   239 EHLAMMERILGPIPSRMIRKTRKQKYFYHGR---------LDWDENTSA--GRYVRE------------NCKPLRRY-LT 294

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|.
gi 1907161723 501 VEKygwphEDAAQFTDFLIPMLEMVPEKRASAGECLRHPWL 541
Cdd:cd14215   295 SEA-----EEHHQLFDLIESMLEYEPSKRLTLAAALKHPFF 330

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1907161723   1 MVFEVLGHHLLKWIIKSNYQGLPVRCVKSIIRQVLQGLDYLHsKCKIIHTDIKPENILMcVDDAYVR 67
Cdd:cd14134    91 IVFELLGPSLYDFLKKNNYGPFPLEHVQHIAKQLLEAVAFLH-DLKLTHTDLKPENILL-VDSDYVK 155

Catalytic domain of the Serine/Threonine Kinase, Homeodomain-Interacting Protein Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. HIPKs, originally identified by their ability to bind homeobox factors, are nuclear proteins containing catalytic kinase and homeobox-interacting domains as well as a PEST region overlapping with the speckle-retention signal (SRS). They show speckled localization in the nucleus, apart from the nucleoles. They play roles in the regulation of many nuclear pathways including gene transcription, cell survival, proliferation, differentiation, development, and DNA damage response. Vertebrates contain three HIPKs (HIPK1-3) and mammals harbor an additional family member HIPK4, which does not contain a homeobox-interacting domain and is localized in the cytoplasm. HIPK2, the most studied HIPK, is a coregulator of many transcription factors and cofactors and it regulates gene transcription during development and in DNA damage response. The HIPK subfamily is part of 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 1907161723 335 LLVNPLDPRnadkIRVKIADLGNACWVHKHFTED-IQTRQYRSIEVLIGAGYSTPADIWSTACMAFELATGDYLFePHSG 413
Cdd:cd14211   133 MLVDPVRQP----YRVKVIDFGSASHVSKAVCSTyLQSRYYRAPEIILGLPFCEAIDMWSLGCVIAELFLGWPLY-PGSS 207

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161723 414 EdysrdEDHIAHIIELLGSIPRHFALSGKYSREFFNRRDHIALIIELLgKVPRKY-AMLGKYSKE----FFTRKGELRHI 488
Cdd:cd14211   208 E-----YDQIRYISQTQGLPAEHLLNAATKTSRFFNRDPDSPYPLWRL-KTPEEHeAETGIKSKEarkyIFNCLDDMAQV 281

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1907161723 489 TKLKPWSLFDVLVEKYgwpheDAAQFTDFLIPMLEMVPEKRASAGECLRHPWL 541
Cdd:cd14211   282 NGPSDLEGSELLAEKA-----DRREFIDLLKRMLTIDQERRITPGEALNHPFV 329

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161723  349 RVKIADLGNACWVH--KHFTEDIQTRQYRSIEVLIGAGYSTPADIWSTACMAFELATGDYLFEphsgedysrDEDHIAHI 426
Cdd:smart00220 135 HVKLADFGLARQLDpgEKLTTFVGTPEYMAPEVLLGKGYGKAVDIWSLGVILYELLTGKPPFP---------GDDQLLEL 205

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161723  427 IELLGSIPRHFAL-SGKYSREFFNrrdhialiiellgkvprkyamlgkyskefftrkgelrhitklkpwslfdvLVEKyg 505
Cdd:smart00220 206 FKKIGKPKPPFPPpEWDISPEAKD--------------------------------------------------LIRK-- 233

                          170       180       190
                   ....*....|....*....|....*....|....*.
gi 1907161723  506 wphedaaqftdflipMLEMVPEKRASAGECLRHPWL 541
Cdd:smart00220 234 ---------------LLVKDPEKRLTAEEALQHPFF 254

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161723 351 KIADLGNACWVHKHF--TEDIQTRQYRSIEVLIGAGYSTPADIWSTACMAFELATGDYLFephSGEDYSrdeDHIAHIIE 428
Cdd:cd07850   142 KILDFGLARTAGTSFmmTPYVVTRYYRAPEVILGMGYKENVDIWSVGCIMGEMIRGTVLF---PGTDHI---DQWNKIIE 215

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161723 429 LLGSIPRHFalsgkysreffnrrdhialiIELLGKVPRKYAM-LGKYSKefftrkgelRHITKLKPWSLFDVLVEKYGwp 507
Cdd:cd07850   216 QLGTPSDEF--------------------MSRLQPTVRNYVEnRPKYAG---------YSFEELFPDVLFPPDSEEHN-- 264

                         170       180       190
                  ....*....|....*....|....*....|....*
gi 1907161723 508 HEDAAQFTDFLIPMLEMVPEKRASAGECLRHPWLN 542
Cdd:cd07850   265 KLKASQARDLLSKMLVIDPEKRISVDDALQHPYIN 299

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161723 346 DKIRVKIADLGNACWVHKH--FTEDIQTRQYRSIEVLIGAGYSTPA-DIWSTACMAFELATGDYLFEphsGEDysrDEDH 422
Cdd:cd07831   134 KDDILKLADFGSCRGIYSKppYTEYISTRWYRAPECLLTDGYYGPKmDIWAVGCVFFEILSLFPLFP---GTN---ELDQ 207

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161723 423 IAHIIELLGSIPRHFAlsgkysrEFFNRRDHIaliiellgkvprkyamlgkySKEFFTRKGelRHITKLKPwslfdvlve 502
Cdd:cd07831   208 IAKIHDVLGTPDAEVL-------KKFRKSRHM--------------------NYNFPSKKG--TGLRKLLP--------- 249

                         170       180       190
                  ....*....|....*....|....*....|....*...
gi 1907161723 503 kygwphEDAAQFTDFLIPMLEMVPEKRASAGECLRHPW 540
Cdd:cd07831   250 ------NASAEGLDLLKKLLAYDPDERITAKQALRHPY 281

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 1907161723 335 LLVNPLDprnadkiRVKIADLGNAcwvhKH------FTEDIQTRQYRSIEVLIGAG-YSTPADIWSTACMAFELATGDYL 407
Cdd:cd07830   130 LLVSGPE-------VVKIADFGLA----REirsrppYTDYVSTRWYRAPEILLRSTsYSSPVDIWALGCIMAELYTLRPL 198

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161723 408 FEPHSgedysrDEDHIAHIIELLGSI-----PRHFALSGKYSREFfnrrdhialiiellgkvprkyamlgkyskefftrk 482
Cdd:cd07830   199 FPGSS------EIDQLYKICSVLGTPtkqdwPEGYKLASKLGFRF----------------------------------- 237

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 1907161723 483 gelrhiTKLKPWSLFDVLVEkygwPHEDAAqftDFLIPMLEMVPEKRASAGECLRHPWL 541
Cdd:cd07830   238 ------PQFAPTSLHQLIPN----ASPEAI---DLIKDMLRWDPKKRPTASQALQHPYF 283

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        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161723 350 VKIADLGNACWVH---KHFTEDIQTRQYRSIEVLIGA-GYSTPADIWSTACMAFELATGDYLFephsgedysRDEDHIah 425
Cdd:cd07829   137 LKLADFGLARAFGiplRTYTHEVVTLWYRAPEILLGSkHYSTAVDIWSVGCIFAELITGKPLF---------PGDSEI-- 205

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161723 426 iiellgsiprhfalsgkysreffnrrDHIALIIELLG----KVPRKYAMLGKYSKEFFTRKGElrhitklkpwSLFDVLv 501
Cdd:cd07829   206 --------------------------DQLFKIFQILGtpteESWPGVTKLPDYKPTFPKWPKN----------DLEKVL- 248

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|
gi 1907161723 502 ekygwPHEDaAQFTDFLIPMLEMVPEKRASAGECLRHPWL 541
Cdd:cd07829   249 -----PRLD-PEGIDLLSKMLQYNPAKRISAKEALKHPYF 282

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161723 350 VKIADLGNACWVHKHFTEDIQTRQYRSIEVLIGAG-YSTPADIWSTACMAFELATGDYLFEphsGEDYSrdeDHIAHIIE 428
Cdd:cd07851   157 LKILDFGLARHTDDEMTGYVATRWYRAPEIMLNWMhYNQTVDIWSVGCIMAELLTGKTLFP---GSDHI---DQLKRIMN 230

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907161723 429 LLGSIPRHF--ALSGKYSREFfnrrdhialiIELLGKVPRKyamlgkyskefftrkgELRHItklkpwslfdvlvekYGW 506
Cdd:cd07851   231 LVGTPDEELlkKISSESARNY----------IQSLPQMPKK----------------DFKEV---------------FSG 269