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 2248185536 339 TRAADLLVNPLDPRNADKIRVKIADLGNACWVHKHFTEDIQTRQYRSIEVLIGAGYSTPADIWSTACMAFELATGDYLFE 418
Cdd:cd14217   186 STAPDLLVNPLDPRNADKIRVKIADLGNACWVHKHFTEDIQTRQYRSIEVLIGAGYSTPADIWSTACMAFELATGDYLFE 265

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2248185536 419 PHSGEDYSRDEDHIAHIIELLGSIPRHFALSGKYSREFFNRRGELRHITKLKPWSLFDVLVEKYGWPHEDAAQFTDFLIP 498
Cdd:cd14217   266 PHSGEDYSRDEDHIAHIIELLGCIPRHFALSGKYSREFFNRRGELRHITKLKPWSLFDVLVEKYGWPHEDAAQFTDFLIP 345

                         170       180
                  ....*....|....*....|.
gi 2248185536 499 MLEMVPEKRASAGECLRHPWL 519
Cdd:cd14217   346 MLEMVPEKRASAGECLRHPWL 366

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2248185536  140 EENITSAEASGEQQDGEYQPEVTLKAADLEDTTEEETAKDNGEVEDQEEKEDAEKENAEKDEDDVEQELANLDPTWVESP 219
Cdd:TIGR00927  820 ETQADDTEVKDETGEQELNAENQGEAKQDEKGVDGGGGSDGGDSEEEEEEEEEEEEEEEEEEEEEEEEEENEEPLSLEWP 899

                   .
gi 2248185536  220 K 220
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 2248185536 339 TRAADLLVNPLDPRNADKIRVKIADLGNACWVHKHFTEDIQTRQYRSIEVLIGAGYSTPADIWSTACMAFELATGDYLFE 418
Cdd:cd14217   186 STAPDLLVNPLDPRNADKIRVKIADLGNACWVHKHFTEDIQTRQYRSIEVLIGAGYSTPADIWSTACMAFELATGDYLFE 265

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2248185536 419 PHSGEDYSRDEDHIAHIIELLGSIPRHFALSGKYSREFFNRRGELRHITKLKPWSLFDVLVEKYGWPHEDAAQFTDFLIP 498
Cdd:cd14217   266 PHSGEDYSRDEDHIAHIIELLGCIPRHFALSGKYSREFFNRRGELRHITKLKPWSLFDVLVEKYGWPHEDAAQFTDFLIP 345

                         170       180
                  ....*....|....*....|.
gi 2248185536 499 MLEMVPEKRASAGECLRHPWL 519
Cdd:cd14217   346 MLEMVPEKRASAGECLRHPWL 366

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2248185536  358 RVKIADLGNACWVH--KHFTEDIQTRQYRSIEVLIGAGYSTPADIWSTACMAFELATGDYLFEphsgedysrDEDHIAHI 435
Cdd:smart00220 135 HVKLADFGLARQLDpgEKLTTFVGTPEYMAPEVLLGKGYGKAVDIWSLGVILYELLTGKPPFP---------GDDQLLEL 205

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2248185536  436 IELLGSIPRHFAL-SGKYSREFFNrrgelrhitklkpwslfdvLVEKygwphedaaqftdflipMLEMVPEKRASAGECL 514
Cdd:smart00220 206 FKKIGKPKPPFPPpEWDISPEAKD-------------------LIRK-----------------LLVKDPEKRLTAEEAL 249

                   ....*
gi 2248185536  515 RHPWL 519
Cdd:smart00220 250 QHPFF 254

protein kinase; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2248185536 342 ADLLVNPLDPRN--ADKIRVKIADLGNACWVHKHFTEDIQTRQYRSIEVLIGAGYSTPADIWSTACMAFELATGDYLFEP 419
Cdd:PTZ00284  268 SDTVVDPVTNRAlpPDPCRVRICDLGGCCDERHSRTAIVSTRHYRSPEVVLGLGWMYSTDMWSMGCIIYELYTGKLLYDT 347

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2248185536 420 HSgedysrDEDHIaHIIE-LLGSIPRHFAL--SGKYSREFFNRRGELR------HITKL-KPWSLFDVLVEKYgwpheda 489
Cdd:PTZ00284  348 HD------NLEHL-HLMEkTLGRLPSEWAGrcGTEEARLLYNSAGQLRpctdpkHLARIaRARPVREVIRDDL------- 413

                         170       180       190
                  ....*....|....*....|....*....|
gi 2248185536 490 aqFTDFLIPMLEMVPEKRASAGECLRHPWL 519
Cdd:PTZ00284  414 --LCDLIYGLLHYDRQKRLNARQMTTHPYV 441

Serine/threonine protein kinase [Signal transduction mechanisms];

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 2248185536   1 MVFE-VLGHHLLKWIikSNYQGLPVRCVKSIIRQVLQGLDYLHSKcKIIHTDIKPENILMCVD 62
Cdd:COG0515    84 LVMEyVEGESLADLL--RRRGPLPPAEALRILAQLAEALAAAHAA-GIVHRDIKPANILLTPD 143

protein kinase; Provisional

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 2248185536  10 LLKWIIKsnYQGLPVRCVKSIIRQVLQGLDYLHSKCKIIHTDIKPENILMCVDDAYVRRMAAEAT 74
Cdd:PTZ00284  218 LLDWIMK--HGPFSHRHLAQIIFQTGVALDYFHTELHLMHTDLKPENILMETSDTVVDPVTNRAL 280

Serine/threonine protein kinase [Signal transduction mechanisms];

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 2248185536 358 RVKIADLGNACWVHK-HFTED---IQTRQYRSIEVLIGAGYSTPADIWSTACMAFELATGDYLFEPHSGED 424
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 2248185536 339 TRAADLLVNPLDPRNADKIRVKIADLGNACWVHKHFTEDIQTRQYRSIEVLIGAGYSTPADIWSTACMAFELATGDYLFE 418
Cdd:cd14217   186 STAPDLLVNPLDPRNADKIRVKIADLGNACWVHKHFTEDIQTRQYRSIEVLIGAGYSTPADIWSTACMAFELATGDYLFE 265

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2248185536 419 PHSGEDYSRDEDHIAHIIELLGSIPRHFALSGKYSREFFNRRGELRHITKLKPWSLFDVLVEKYGWPHEDAAQFTDFLIP 498
Cdd:cd14217   266 PHSGEDYSRDEDHIAHIIELLGCIPRHFALSGKYSREFFNRRGELRHITKLKPWSLFDVLVEKYGWPHEDAAQFTDFLIP 345

                         170       180
                  ....*....|....*....|.
gi 2248185536 499 MLEMVPEKRASAGECLRHPWL 519
Cdd:cd14217   346 MLEMVPEKRASAGECLRHPWL 366

Catalytic domain of the Serine/Threonine Kinase, Serine-aRginine Protein Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SRPKs phosphorylate and regulate splicing factors from the SR protein family by specifically phosphorylating multiple serine residues residing in SR/RS dipeptide motifs (also known as RS domains). Phosphorylation of the RS domains enhances interaction with transportin SR and facilitates entry of the SR proteins into the nucleus. SRPKs contain a nonconserved insert domain, within the well-conserved catalytic kinase domain, that regulates their subcellular localization. They play important roles in mediating pre-mRNA processing and mRNA maturation, as well as other cellular functions such as chromatin reorganization, cell cycle and p53 regulation, and metabolic signaling. Vertebrates contain three distinct SRPKs, called SRPK1-3. The SRPK homolog in budding yeast, Sky1p, recognizes and phosphorylates its substrate Npl3p, which lacks a classic RS domain but contains a single RS dipeptide at the C-terminus of its RGG domain. Npl3p is a shuttling heterogeneous nuclear ribonucleoprotein (hnRNP) that exports a distinct class of mRNA from the nucleus to the cytoplasm. The SRPK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2248185536 349 LDPRN----ADKIRVKIADLGNACWVHKHFTEDIQTRQYRSIEVLIGAGYSTPADIWSTACMAFELATGDYLFEPHSGED 424
Cdd:cd14136   146 IKPENvllcISKIEVKIADLGNACWTDKHFTEDIQTRQYRSPEVILGAGYGTPADIWSTACMAFELATGDYLFDPHSGED 225

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2248185536 425 YSRDEDHIAHIIELLGSIPRHFALSGKYSREFFNRRGELRHITKLKPWSLFDVLVEKYGWPHEDAAQFTDFLIPMLEMVP 504
Cdd:cd14136   226 YSRDEDHLALIIELLGRIPRSIILSGKYSREFFNRKGELRHISKLKPWPLEDVLVEKYKWSKEEAKEFASFLLPMLEYDP 305

                         170
                  ....*....|....*
gi 2248185536 505 EKRASAGECLRHPWL 519
Cdd:cd14136   306 EKRATAAQCLQHPWL 320

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 2248185536   1 MVFEVLGHHLLKWIIKSNYQGLPVRCVKSIIRQVLQGLDYLHSKCKIIHTDIKPENILMCVDDAYVRRMAAEATEWQKAG 80
Cdd:cd14217    97 MVFEVLGHHLLKWIIKSNYQGLPIRCVKSIIRQVLQGLDYLHSKCKIIHTDIKPENILMCVDDAYVRRMAAEATEWQKAG 176

                          90
                  ....*....|...
gi 2248185536  81 APPPSGSAVSTAP 93
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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 2248185536   1 MVFEVLGHHLLKWIIKSNYQGLPVRCVKSIIRQVLQGLDYLHSKCKIIHTDIKPENILMCVDDAYVRRMAAEATEWQK 78
Cdd:cd14216    95 MVFEVLGHHLLKWIIKSNYQGLPLPCVKKIIRQVLQGLDYLHTKCRIIHTDIKPENILLSVNEQYIRRLAAEATEWQR 172

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 2248185536 344 LLVNPldprnaDKIRVKIADLGNACWVHKHFTEDIQTRQYRSIEVLIGAGYSTPADIWSTACMAFELATGDYLFephSGE 423
Cdd:cd14210   148 LLKQP------SKSSIKVIDFGSSCFEGEKVYTYIQSRFYRAPEVILGLPYDTAIDMWSLGCILAELYTGYPLF---PGE 218

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2248185536 424 DysrDEDHIAHIIELLGSIPRHFALSGKYSREFFNRRGELRHITklkpwslfdVLVEKYGWP---------HEDAAQFTD 494
Cdd:cd14210   219 N---EEEQLACIMEVLGVPPKSLIDKASRRKKFFDSNGKPRPTT---------NSKGKKRRPgskslaqvlKCDDPSFLD 286

                         170       180
                  ....*....|....*....|....*
gi 2248185536 495 FLIPMLEMVPEKRASAGECLRHPWL 519
Cdd:cd14210   287 FLKKCLRWDPSERMTPEEALQHPWI 311

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 2248185536 353 NADKIRVKIADLGNACWVHKHF-TEDIQTRQYRSIEVLIGA-GYSTPADIWSTACMAFELATGDYLFEPHSgedysrDED 430
Cdd:cd05118   135 NLELGQLKLADFGLARSFTSPPyTPYVATRWYRAPEVLLGAkPYGSSIDIWSLGCILAELLTGRPLFPGDS------EVD 208

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2248185536 431 HIAHIIELLGsiprhfalsgkysreffnrrgelrhitklkpwslfdvlvekygwphedAAQFTDFLIPMLEMVPEKRASA 510
Cdd:cd05118   209 QLAKIVRLLG------------------------------------------------TPEALDLLSKMLKYDPAKRITA 240

                  ....*....
gi 2248185536 511 GECLRHPWL 519
Cdd:cd05118   241 SQALAHPYF 249

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 2248185536 344 LLVNPldPRNAdkirVKIADLGNACWVHKHFTEDIQTRQYRSIEVLIGAGYSTPADIWSTACMAFELATGDYLFephSGe 423
Cdd:cd14226   150 LLCNP--KRSA----IKIIDFGSSCQLGQRIYQYIQSRFYRSPEVLLGLPYDLAIDMWSLGCILVEMHTGEPLF---SG- 219

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2248185536 424 dySRDEDHIAHIIELLGSIPRHFALSGKYSREFFNRRGE-----LRHITKLKPW-----SLFDVLVEKYGWP-------- 485
Cdd:cd14226   220 --ANEVDQMNKIVEVLGMPPVHMLDQAPKARKFFEKLPDgtyylKKTKDGKKYKppgsrKLHEILGVETGGPggrragep 297

                         170       180       190
                  ....*....|....*....|....*....|....*....
gi 2248185536 486 -H--EDAAQFTDFLIPMLEMVPEKRASAGECLRHPWLNS 521
Cdd:cd14226   298 gHtvEDYLKFKDLILRMLDYDPKTRITPAEALQHSFFKR 336

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 2248185536 359 VKIADLGNACWVHKHFTEDIQTRQYRSIEVLIGAGYSTPADIWSTACMAFELATGDYLFephSGEDysrDEDHIAHIIEL 438
Cdd:cd14225   187 IKVIDFGSSCYEHQRVYTYIQSRFYRSPEVILGLPYSMAIDMWSLGCILAELYTGYPLF---PGEN---EVEQLACIMEV 260

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2248185536 439 LGSIPRHFALSGKYSREFFNRRGELRHIT-----KLKPWS--LFDVLvekygwpHEDAAQFTDFLIPMLEMVPEKRASAG 511
Cdd:cd14225   261 LGLPPPELIENAQRRRLFFDSKGNPRCITnskgkKRRPNSkdLASAL-------KTSDPLFLDFIRRCLEWDPSKRMTPD 333

                  ....*...
gi 2248185536 512 ECLRHPWL 519
Cdd:cd14225   334 EALQHEWI 341

Catalytic domain of the Dual-specificity protein kinase, CDC-like kinase 3; Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine as well as tyrosine residues on protein substrates. CLK3 is predominantly expressed in mature spermatozoa, and might play a role in the fertilization process. 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 CLK3 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 2248185536 359 VKIADLGNACWVHKHFTEDIQTRQYRSIEVLIGAGYSTPADIWSTACMAFELATGDYLFEPHSgedysrDEDHIAHIIEL 438
Cdd:cd14214   175 IRVADFGSATFDHEHHTTIVATRHYRPPEVILELGWAQPCDVWSLGCILFEYYRGFTLFQTHE------NREHLVMMEKI 248

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2248185536 439 LGSIPRHFALSGKYSREFFNrrGEL---------RHITK----LKPWSLFDVLvekygwpheDAAQFTDFLIPMLEMVPE 505
Cdd:cd14214   249 LGPIPSHMIHRTRKQKYFYK--GSLvwdenssdgRYVSEnckpLMSYMLGDSL---------EHTQLFDLLRRMLEFDPA 317

                         170
                  ....*....|....
gi 2248185536 506 KRASAGECLRHPWL 519
Cdd:cd14214   318 LRITLKEALLHPFF 331

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 2248185536 350 DPRNADKIRVKIADLGNACWVHKHFTEDIQTRQYRSIEVLIGAGYSTPADIWSTACMAFELATGDYLFEPHSgedysrDE 429
Cdd:cd14215   165 DERSVKSTAIRVVDFGSATFDHEHHSTIVSTRHYRAPEVILELGWSQPCDVWSIGCIIFEYYVGFTLFQTHD------NR 238

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2248185536 430 DHIAHIIELLGSIPRHFALSGKYSREFFnrRGEL---------RHITK-LKPWSLFdVLVEKygwphEDAAQFTDFLIPM 499
Cdd:cd14215   239 EHLAMMERILGPIPSRMIRKTRKQKYFY--HGRLdwdentsagRYVREnCKPLRRY-LTSEA-----EEHHQLFDLIESM 310

                         170       180
                  ....*....|....*....|
gi 2248185536 500 LEMVPEKRASAGECLRHPWL 519
Cdd:cd14215   311 LEYEPSKRLTLAAALKHPFF 330

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 2248185536 344 LLVNPLDprnadkiRVKIADLGNAcwvhKH------FTEDIQTRQYRSIEVLIGAG-YSTPADIWSTACMAFELATGDYL 416
Cdd:cd07830   130 LLVSGPE-------VVKIADFGLA----REirsrppYTDYVSTRWYRAPEILLRSTsYSSPVDIWALGCIMAELYTLRPL 198

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2248185536 417 FEPHSgedysrDEDHIAHIIELLGSI-----PRHFALSGKYSREFfnrrgelrhiTKLKPWSLFDVLVEkygwPHEDAAq 491
Cdd:cd07830   199 FPGSS------EIDQLYKICSVLGTPtkqdwPEGYKLASKLGFRF----------PQFAPTSLHQLIPN----ASPEAI- 257

                         170       180
                  ....*....|....*....|....*...
gi 2248185536 492 ftDFLIPMLEMVPEKRASAGECLRHPWL 519
Cdd:cd07830   258 --DLIKDMLRWDPKKRPTASQALQHPYF 283

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 2248185536 355 DKIRVKIADLGNACWVHKH--FTEDIQTRQYRSIEVLIGAGYSTPA-DIWSTACMAFELATGDYLFEphsGEDysrDEDH 431
Cdd:cd07831   134 KDDILKLADFGSCRGIYSKppYTEYISTRWYRAPECLLTDGYYGPKmDIWAVGCVFFEILSLFPLFP---GTN---ELDQ 207

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2248185536 432 IAHIIELLGS----IPRHFALSGKYSREFFNRRGelRHITKLKPwslfdvlvekygwphEDAAQFTDFLIPMLEMVPEKR 507
Cdd:cd07831   208 IAKIHDVLGTpdaeVLKKFRKSRHMNYNFPSKKG--TGLRKLLP---------------NASAEGLDLLKKLLAYDPDER 270

                         170
                  ....*....|.
gi 2248185536 508 ASAGECLRHPW 518
Cdd:cd07831   271 ITAKQALRHPY 281

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 2248185536   1 MVFEVLGHHLLKwIIKSNYQGLPVRCVKSIIRQVLQGLDYLHSkCKIIHTDIKPENILMC 60
Cdd:cd05118    78 LVFELMGMNLYE-LIKDYPRGLPLDLIKSYLYQLLQALDFLHS-NGIIHRDLKPENILIN 135

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 2248185536 360 KIADLGNACWVHKHF--TEDIQTRQYRSIEVLIGAGYSTPADIWSTACMAFELATGDYLFephSGEDYSrdeDHIAHIIE 437
Cdd:cd07850   142 KILDFGLARTAGTSFmmTPYVVTRYYRAPEVILGMGYKENVDIWSVGCIMGEMIRGTVLF---PGTDHI---DQWNKIIE 215

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2248185536 438 LLGSIPRHFALSGKYSREFF--NR-RGELRHITKLKPWSLFDVLVEKYGwpHEDAAQFTDFLIPMLEMVPEKRASAGECL 514
Cdd:cd07850   216 QLGTPSDEFMSRLQPTVRNYveNRpKYAGYSFEELFPDVLFPPDSEEHN--KLKASQARDLLSKMLVIDPEKRISVDDAL 293

                  ....*.
gi 2248185536 515 RHPWLN 520
Cdd:cd07850   294 QHPYIN 299

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 2248185536   1 MVFEVLGHHLLKWIIKSNYQGLPVRCVKSIIRQVLQGLDYLHSKcKIIHTDIKPENILMC 60
Cdd:cd14210    92 IVFELLSINLYELLKSNNFQGLSLSLIRKFAKQILQALQFLHKL-NIIHCDLKPENILLK 150

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

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 2248185536    1 MVFEVLGHHLLKWIIKSNyQGLPVRCVKSIIRQVLQGLDYLHSKcKIIHTDIKPENILMCVD 62
Cdd:smart00220  74 LVMEYCEGGDLFDLLKKR-GRLSEDEARFYLRQILSALEYLHSK-GIVHRDLKPENILLDED 133

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 2248185536 359 VKIADLGNACWVHKHFTEDIQTRQYRSIEVLIGAG-YSTPADIWSTACMAFELATGDYLFEphsGEDYSrdeDHIAHIIE 437
Cdd:cd07851   157 LKILDFGLARHTDDEMTGYVATRWYRAPEIMLNWMhYNQTVDIWSVGCIMAELLTGKTLFP---GSDHI---DQLKRIMN 230

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2248185536 438 LLGSIPRHF--ALSGKYSREFfnrrgeLRHITKLKPWSLFDVlvekYGWPHEDAaqfTDFLIPMLEMVPEKRASAGECLR 515
Cdd:cd07851   231 LVGTPDEELlkKISSESARNY------IQSLPQMPKKDFKEV----FSGANPLA---IDLLEKMLVLDPDKRITAAEALA 297

                  ....
gi 2248185536 516 HPWL 519
Cdd:cd07851   298 HPYL 301

protein kinase; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2248185536 342 ADLLVNPLDPRN--ADKIRVKIADLGNACWVHKHFTEDIQTRQYRSIEVLIGAGYSTPADIWSTACMAFELATGDYLFEP 419
Cdd:PTZ00284  268 SDTVVDPVTNRAlpPDPCRVRICDLGGCCDERHSRTAIVSTRHYRSPEVVLGLGWMYSTDMWSMGCIIYELYTGKLLYDT 347

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2248185536 420 HSgedysrDEDHIaHIIE-LLGSIPRHFAL--SGKYSREFFNRRGELR------HITKL-KPWSLFDVLVEKYgwpheda 489
Cdd:PTZ00284  348 HD------NLEHL-HLMEkTLGRLPSEWAGrcGTEEARLLYNSAGQLRpctdpkHLARIaRARPVREVIRDDL------- 413

                         170       180       190
                  ....*....|....*....|....*....|
gi 2248185536 490 aqFTDFLIPMLEMVPEKRASAGECLRHPWL 519
Cdd:PTZ00284  414 --LCDLIYGLLHYDRQKRLNARQMTTHPYV 441