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 1159261240   1 MIIEMATGNPYLPSSSDLDLLHKIVLKVGNLSPHLQNIFSKSPIFAGVVLPQVQHPKNARKKYPKLNGLLADIVHACLQI 80
Cdd:cd07846   190 LVTEMLTGEPLFPGDSDIDQLYHIIKCLGNLIPRHQELFQKNPLFAGVRLPEVKEVEPLERRYPKLSGVVIDLAKKCLHI 269

                          90
                  ....*....|....*..
gi 1159261240  81 DPADRISSSDLLHHEYF 97
Cdd:cd07846   270 DPDKRPSCSELLHHEFF 286

Catalytic domain of the Serine/Threonine Kinases, Cyclin-Dependent protein Kinase Like 2 and 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDKL2, also called p56 KKIAMRE, is expressed in testis, kidney, lung, and brain. It functions mainly in mature neurons and plays an important role in learning and memory. Inactivation of CDKL3, also called NKIAMRE (NKIATRE in rat), by translocation is associated with mild mental retardation. It has been reported that CDKL3 is lost in leukemic cells having a chromosome arm 5q deletion, and may contribute to the transformed phenotype. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDKL2/3 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 1159261240   1 MIIEMATGNPYLPSSSDLDLLHKIVLKVGNLSPHLQNIFSKSPIFAGVVLPQVQHPKNARKKYPKLNGLLADIVHACLQI 80
Cdd:cd07846   190 LVTEMLTGEPLFPGDSDIDQLYHIIKCLGNLIPRHQELFQKNPLFAGVRLPEVKEVEPLERRYPKLSGVVIDLAKKCLHI 269

                          90
                  ....*....|....*..
gi 1159261240  81 DPADRISSSDLLHHEYF 97
Cdd:cd07846   270 DPDKRPSCSELLHHEFF 286

cyclin-dependent protein kinase; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1159261240   4 EMATGNPYLPSSSDLDLLHKIVLKVGNLSPHLQNIFSKSPIFAGVVLPQvqhPKNARKKYPKLNGLLADIVHACLQIDPA 83
Cdd:PTZ00024  226 ELLTGKPLFPGENEIDQLGRIFELLGTPNEDNWPQAKKLPLYTEFTPRK---PKDLKTIFPNASDDAIDLLQSLLKLNPL 302

                          90
                  ....*....|....*..
gi 1159261240  84 DRISSSDLLHHEYFTRD 100
Cdd:PTZ00024  303 ERISAKEALKHEYFKSD 319

Catalytic domain of the Serine/Threonine Kinases, Cyclin-Dependent protein Kinase Like 2 and 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDKL2, also called p56 KKIAMRE, is expressed in testis, kidney, lung, and brain. It functions mainly in mature neurons and plays an important role in learning and memory. Inactivation of CDKL3, also called NKIAMRE (NKIATRE in rat), by translocation is associated with mild mental retardation. It has been reported that CDKL3 is lost in leukemic cells having a chromosome arm 5q deletion, and may contribute to the transformed phenotype. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDKL2/3 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 1159261240   1 MIIEMATGNPYLPSSSDLDLLHKIVLKVGNLSPHLQNIFSKSPIFAGVVLPQVQHPKNARKKYPKLNGLLADIVHACLQI 80
Cdd:cd07846   190 LVTEMLTGEPLFPGDSDIDQLYHIIKCLGNLIPRHQELFQKNPLFAGVRLPEVKEVEPLERRYPKLSGVVIDLAKKCLHI 269

                          90
                  ....*....|....*..
gi 1159261240  81 DPADRISSSDLLHHEYF 97
Cdd:cd07846   270 DPDKRPSCSELLHHEFF 286

Catalytic domain of Cyclin-Dependent protein Kinase Like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of CDKL1-5 and similar proteins. Some CDKLs, like CDKL1 and CDKL3, may be implicated in transformation and others, like CDKL3 and CDKL5, are associated with mental retardation when impaired. CDKL2 plays a role in learning and memory. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDKL subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1159261240   4 EMATGNPYLPSSSDLDLLHKIVLKVGNLSPHLQNIFSKSPIFAGVVLPQVQHPKNARKKYP-KLNGLLADIVHACLQIDP 82
Cdd:cd07833   194 ELLDGEPLFPGDSDIDQLYLIQKCLGPLPPSHQELFSSNPRFAGVAFPEPSQPESLERRYPgKVSSPALDFLKACLRMDP 273

                          90
                  ....*....|....*
gi 1159261240  83 ADRISSSDLLHHEYF 97
Cdd:cd07833   274 KERLTCDELLQHPYF 288

Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase Like 5; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Mutations in the gene encoding CDKL5, previously called STK9, are associated with early onset epilepsy and severe mental retardation [X-linked infantile spasm syndrome (ISSX) or West syndrome]. In addition, CDKL5 mutations also sometimes cause a phenotype similar to Rett syndrome (RTT), a progressive neurodevelopmental disorder. These pathogenic mutations are located in the N-terminal portion of the protein within the kinase domain. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDKL5 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 1159261240   4 EMATGNPYLPSSSDLDLLHKIVLKVGNLSPHLQNIFSKSPIFAGVVLPQVQHPKNARKKYPK-LNGLLADIVHACLQIDP 82
Cdd:cd07848   193 ELSDGQPLFPGESEIDQLFTIQKVLGPLPAEQMKLFYSNPRFHGLRFPAVNHPQSLERRYLGiLSGVLLDLMKNLLKLNP 272

                          90
                  ....*....|....*
gi 1159261240  83 ADRISSSDLLHHEYF 97
Cdd:cd07848   273 TDRYLTEQCLNHPAF 287

Catalytic domain of the Serine/Threonine Kinase, Fungal Cyclin-Dependent protein Kinase Pho85; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Pho85 is a multifunctional CDK in yeast. It is regulated by 10 different cyclins (Pcls) and plays a role in G1 progression, cell polarity, phosphate and glycogen metabolism, gene expression, and in signaling changes in the environment. It is not essential for yeast viability and is the functional homolog of mammalian CDK5, which plays a role in central nervous system development. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The Pho85 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1159261240   4 EMATGNPYLPSSSDLDLLHKIVLKVGNLSPHLQNIFSKSPIFAgVVLPQVQhPKNARKKYPKLNGLLADIVHACLQIDPA 83
Cdd:cd07836   193 EMITGRPLFPGTNNEDQLLKIFRIMGTPTESTWPGISQLPEYK-PTFPRYP-PQDLQQLFPHADPLGIDLLHRLLQLNPE 270

                          90
                  ....*....|....
gi 1159261240  84 DRISSSDLLHHEYF 97
Cdd:cd07836   271 LRISAHDALQHPWF 284

Catalytic domain of PCTAIRE-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PCTAIRE-like proteins show unusual expression patterns with high levels in post-mitotic tissues, suggesting that they may be involved in regulating post-mitotic cellular events. They share sequence similarity with Cyclin-Dependent Kinases (CDKs), which belong to a large family of STKs that are regulated by their cognate cyclins. Together, CDKs and cyclins are involved in the control of cell-cycle progression, transcription, and neuronal function. The association of PCTAIRE-like proteins with cyclins has not been widely studied, although PFTAIRE-1 has been shown to function as a CDK which is regulated by cyclin D3 as well as the membrane-associated cyclin Y. The PCTAIRE-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 1159261240   3 IEMATGNPYLPSSSD-LDLLHKIVLKVGNLSPHLQNIFSKSPIFAGVVLPQVQhPKNARKKYPKLNGLL--ADIVHACLQ 79
Cdd:cd07844   190 YEMATGRPLFPGSTDvEDQLHKIFRVLGTPTEETWPGVSSNPEFKPYSFPFYP-PRPLINHAPRLDRIPhgEELALKFLQ 268

                          90
                  ....*....|....*...
gi 1159261240  80 IDPADRISSSDLLHHEYF 97
Cdd:cd07844   269 YEPKKRISAAEAMKHPYF 286

The catalytic domain of the Serine/Threonine Kinase, Glycogen Synthase Kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. GSK3 is a mutifunctional kinase involved in many cellular processes including cell division, proliferation, differentiation, adhesion, and apoptosis. In plants, GSK3 plays a role in the response to osmotic stress. In Caenorhabditis elegans, it plays a role in regulating normal oocyte-to-embryo transition and response to oxidative stress. In Chlamydomonas reinhardtii, GSK3 regulates flagellar length and assembly. In mammals, there are two isoforms, GSK3alpha and GSK3beta, which show both distinct and redundant functions. The two isoforms differ mainly in their N-termini. They are both involved in axon formation and in Wnt signaling.They play distinct roles in cardiogenesis, with GSKalpha being essential in cardiomyocyte survival, and GSKbeta regulating heart positioning and left-right symmetry. GSK3beta was first identified as a regulator of glycogen synthesis, but has since been determined to play other roles. It regulates the degradation of beta-catenin and IkB. Beta-catenin is the main effector of Wnt, which is involved in normal haematopoiesis and stem cell function. IkB is a central inhibitor of NF-kB, which is critical in maintaining leukemic cell growth. GSK3beta is enriched in the brain and is involved in regulating neuronal signaling pathways. It is implicated in the pathogenesis of many diseases including Type II diabetes, obesity, mood disorders, Alzheimer's disease, osteoporosis, and some types of cancer, among others. The GSK3 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 1159261240   4 EMATGNPYLPSSSDLDLLHKIVlKV-GnlSPHLQNIFSKSPIFAGVVLPQVQhPKNARKKYPK-LNGLLADIVHACLQID 81
Cdd:cd14137   199 ELLLGQPLFPGESSVDQLVEII-KVlG--TPTREQIKAMNPNYTEFKFPQIK-PHPWEKVFPKrTPPDAIDLLSKILVYN 274

                          90
                  ....*....|....*.
gi 1159261240  82 PADRISSSDLLHHEYF 97
Cdd:cd14137   275 PSKRLTALEALAHPFF 290

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1159261240    1 MIIEMATGNPYLPSSSDLDLLHKIVLKVGNLSPHLQNIFSKSpifagvvlpqvqhpknarkkypklnglLADIVHACLQI 80
Cdd:smart00220 185 ILYELLTGKPPFPGDDQLLELFKKIGKPKPPFPPPEWDISPE---------------------------AKDLIRKLLVK 237

                           90
                   ....*....|....*..
gi 1159261240   81 DPADRISSSDLLHHEYF 97
Cdd:smart00220 238 DPEKRLTAEEALQHPFF 254

Catalytic domain of Cyclin-Dependent protein Kinase 1-like Serine/Threonine Kinases and of Plant B-type Cyclin-Dependent protein Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of CDK, CDK2, and CDK3. CDK1 is also called Cell division control protein 2 (Cdc2) or p34 protein kinase, and is regulated by cyclins A, B, and E. The CDK1/cyclin A complex controls G2 phase entry and progression while the CDK1/cyclin B complex is critical for G2 to M phase transition. CDK2 is regulated by cyclin E or cyclin A. Upon activation by cyclin E, it phosphorylates the retinoblastoma (pRb) protein which activates E2F mediated transcription and allows cells to move into S phase. The CDK2/cyclin A complex plays a role in regulating DNA replication. Studies in knockout mice revealed that CDK1 can compensate for the loss of the cdk2 gene as it can also bind cyclin E and drive G1 to S phase transition. CDK3 is regulated by cyclin C and it phosphorylates pRB specifically during the G0/G1 transition. This phosphorylation is required for cells to exit G0 efficiently and enter the G1 phase. The plant-specific B-type CDKs are expressed from the late S to the M phase of the cell cycle. They are characterized by the cyclin binding motif PPT[A/T]LRE. They play a role in controlling mitosis and integrating developmental pathways, such as stomata and leaf development. CdkB has been shown to associate with both cyclin B, which controls G2/M transition, and cyclin D, which acts as a mediator in linking extracellular signals to the cell cycle. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK1 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 1159261240   4 EMATGNPYLPSSSDLDLLHKIVLKVGnlSPhlqnifsKSPIFAGVV-LPQVQH------PKNARKKYPKLNGLLADIVHA 76
Cdd:cd07835   192 EMVTRRPLFPGDSEIDQLFRIFRTLG--TP-------DEDVWPGVTsLPDYKPtfpkwaRQDLSKVVPSLDEDGLDLLSQ 262

                          90       100
                  ....*....|....*....|.
gi 1159261240  77 CLQIDPADRISSSDLLHHEYF 97
Cdd:cd07835   263 MLVYDPAKRISAKAALQHPYF 283

Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 7; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK7 plays essential roles in the cell cycle and in transcription. It associates with cyclin H and MAT1 and acts as a CDK-Activating Kinase (CAK) by phosphorylating and activating cell cycle CDKs (CDK1/2/4/6). In the brain, it activates CDK5. CDK7 is also a component of the general transcription factor TFIIH, which phosphorylates the C-terminal domain (CTD) of RNA polymerase II when it is bound with unphosphorylated DNA, as present in the pre-initiation complex. Following phosphorylation, the CTD dissociates from the DNA which allows transcription initiation. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK7 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1159261240   4 EMATGNPYLPSSSDLDLLHKIVLKVG---------NLSPHLQNIFSKSPifagvvlpqvqhPKNARKKYPKLNGLLADIV 74
Cdd:cd07841   195 ELLLRVPFLPGDSDIDQLGKIFEALGtpteenwpgVTSLPDYVEFKPFP------------PTPLKQIFPAASDDALDLL 262

                          90       100
                  ....*....|....*....|....
gi 1159261240  75 HACLQIDPADRISSSDLLHHEYFT 98
Cdd:cd07841   263 QRLLTLNPNKRITARQALEHPYFS 286

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 1159261240   4 EMATGNPYLPSSSDLDLLHKIVLKVGNLSPHLQNifskspifagvvlpqvqhpkNARKKYPklngLLADIVHACLQIDPA 83
Cdd:cd14133   193 ELYTGEPLFPGASEVDQLARIIGTIGIPPAHMLD--------------------QGKADDE----LFVDFLKKLLEIDPK 248

                          90
                  ....*....|....
gi 1159261240  84 DRISSSDLLHHEYF 97
Cdd:cd14133   249 ERPTASQALSHPWL 262

Catalytic domain of the Serine/Threonine Kinase, PCTAIRE-3 kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PCTAIRE-3 shows a restricted pattern of expression and is present in brain, kidney, and intestine. It is elevated in Alzheimer's disease (AD) and has been shown to associate with paired helical filaments (PHFs) and stimulate Tau phosphorylation. As AD progresses, phosphorylated Tau aggregates and forms PHFs, which leads to the formation of neurofibrillary tangles. In human glioma cells, PCTAIRE-3 induces cell cycle arrest and cell death. PCTAIRE-3 shares sequence similarity with Cyclin-Dependent Kinases (CDKs), which belong to a large family of STKs that are regulated by their cognate cyclins. Together, CDKs and cyclins are involved in the control of cell-cycle progression, transcription, and neuronal function. The PCTAIRE-3 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 1159261240   4 EMATGNPYLPSSSDLDLLHKIVLKVGNLSPHLQNIFSKSPIFAGVVLPQVQhPKNARKKYPKLNGLLADIVHACLQIDPA 83
Cdd:cd07871   196 EMATGRPMFPGSTVKEELHLIFRLLGTPTEETWPGVTSNEEFRSYLFPQYR-AQPLINHAPRLDTDGIDLLSSLLLYETK 274

                          90
                  ....*....|....
gi 1159261240  84 DRISSSDLLHHEYF 97
Cdd:cd07871   275 SRISAEAALRHSYF 288

Catalytic domain of Mammalian Ste20-like protein kinase 3-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of MST3, MST4, STK25, Schizosaccharomyces pombe Nak1 and Sid1, Saccharomyces cerevisiae sporulation-specific protein 1 (SPS1), and related proteins. Nak1 is required by fission yeast for polarizing the tips of actin cytoskeleton and is involved in cell growth, cell separation, cell morphology and cell-cycle progression. Sid1 is a component in the septation initiation network (SIN) signaling pathway, and plays a role in cytokinesis. SPS1 plays a role in regulating proteins required for spore wall formation. MST4 plays a role in mitogen-activated protein kinase (MAPK) signaling during cytoskeletal rearrangement, morphogenesis, and apoptosis. MST3 phosphorylates the STK NDR and may play a role in cell cycle progression and cell morphology. STK25 may play a role in the regulation of cell migration and polarization. The MST3-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1159261240   3 IEMATGNPYLpssSDLDllhkiVLKVgnlsphLQNIfSKSPIfagvvlPQVQHPKNARkkypklngLLADIVHACLQIDP 82
Cdd:cd06609   189 IELAKGEPPL---SDLH-----PMRV------LFLI-PKNNP------PSLEGNKFSK--------PFKDFVELCLNKDP 239

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 1159261240  83 ADRISSSDLLHHEyftrdgFIEKFMPELKAKLLQE 117
Cdd:cd06609   240 KERPSAKELLKHK------FIKKAKKTSYLTLLIE 268

Catalytic domain of Fungal Nak1-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of Schizosaccharomyces pombe Nak1, Saccharomyces cerevisiae Kic1p (kinase that interacts with Cdc31p) and related proteins. Nak1 (also called N-rich kinase 1), is required by fission yeast for polarizing the tips of actin cytoskeleton and is involved in cell growth, cell separation, cell morphology and cell-cycle progression. Kic1p is required by budding yeast for cell integrity and morphogenesis. Kic1p interacts with Cdc31p, the yeast homologue of centrin, and phosphorylates substrates in a Cdc31p-dependent manner. The Nak1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1159261240   2 IIEMATGNPYLpssSDLDLLHKIVLKVGNLSPHLQ-NIFSKspifagvvlpqvqhpknarkkypklngLLADIVHACLQI 80
Cdd:cd06917   192 TYEMATGNPPY---SDVDALRAVMLIPKSKPPRLEgNGYSP---------------------------LLKEFVAACLDE 241

                          90
                  ....*....|..
gi 1159261240  81 DPADRISSSDLL 92
Cdd:cd06917   242 EPKDRLSADELL 253

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1159261240   2 IIEMATGNPYLPSSSDLDLLHKIVLKVGnlSPhlqnifSKSPIFAGVVLPQVQHPKNARKKY----PKLNGLLADIVHAC 77
Cdd:cd07838   196 FAELFNRRPLFRGSSEADQLGKIFDVIG--LP------SEEEWPRNSALPRSSFPSYTPRPFksfvPEIDEEGLDLLKKM 267

                          90       100
                  ....*....|....*....|
gi 1159261240  78 LQIDPADRISSSDLLHHEYF 97
Cdd:cd07838   268 LTFNPHKRISAFEALQHPYF 287

Catalytic domain of the Serine/Threonine Kinase, c-Jun N-terminal Kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. JNK3 is expressed primarily in the brain, and to a lesser extent in the heart and testis. Mice deficient in JNK3 are protected against kainic acid-induced seizures, stroke, sciatic axotomy neural death, and neuronal death due to NGF deprivation, oxidative stress, or exposure to beta-amyloid peptide. This suggests that JNK3 may play roles in the pathogenesis of these diseases. JNKs are mitogen-activated protein kinases (MAPKs) that are involved in many stress-activated responses including those during inflammation, neurodegeneration, apoptosis, and persistent pain sensitization, among others. The JNK3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1159261240   4 EMATGNPYLPSSSDLDLLHKIVLKVGN--------LSPHLQNIFSKSPIFAGVVLPQVqHPKN---ARKKYPKLNGLLA- 71
Cdd:cd07874   210 EMVRHKILFPGRDYIDQWNKVIEQLGTpcpefmkkLQPTVRNYVENRPKYAGLTFPKL-FPDSlfpADSEHNKLKASQAr 288

                          90       100
                  ....*....|....*....|....*
gi 1159261240  72 DIVHACLQIDPADRISSSDLLHHEY 96
Cdd:cd07874   289 DLLSKMLVIDPAKRISVDEALQHPY 313

Catalytic domain of the Serine/Threonine Kinase, Plant B-type Cyclin-Dependent protein Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The plant-specific B-type CDKs are expressed from the late S to the M phase of the cell cycle. They are characterized by the cyclin binding motif PPT[A/T]LRE. They play a role in controlling mitosis and integrating developmental pathways, such as stomata and leaf development. CdkB has been shown to associate with both cyclin B, which controls G2/M transition, and cyclin D, which acts as a mediator in linking extracellular signals to the cell cycle. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CdkB subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1159261240   1 MIIEMATGNPYLPSSSDLDLLHKIVLKVGnlSPHLQnifskspIFAGV-------VLPQvQHPKNARKKYPKLNGLLADI 73
Cdd:cd07837   200 IFAEMSRKQPLFPGDSELQQLLHIFRLLG--TPNEE-------VWPGVsklrdwhEYPQ-WKPQDLSRAVPDLEPEGVDL 269

                          90       100
                  ....*....|....*....|....
gi 1159261240  74 VHACLQIDPADRISSSDLLHHEYF 97
Cdd:cd07837   270 LTKMLAYDPAKRISAKAALQHPYF 293

Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. PAKs are implicated in the regulation of many cellular processes including growth factor receptor-mediated proliferation, cell polarity, cell motility, cell death and survival, and actin cytoskeleton organization. PAK deregulation is associated with tumor development. PAKs from higher eukaryotes are classified into two groups (I and II), according to their biochemical and structural features. Group I PAKs contain a PBD (p21-binding domain) overlapping with an AID (autoinhibitory domain), a C-terminal catalytic domain, SH3 binding sites and a non-classical SH3 binding site for PIX (PAK-interacting exchange factor). Group II PAKs contain a PBD and a catalytic domain, but lack other motifs found in group I PAKs. Since group II PAKs do not contain an obvious AID, they may be regulated differently from group I PAKs. Group I PAKs interact with the SH3 containing proteins Nck, Grb2 and PIX; no such binding has been demonstrated for group II PAKs. The PAK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1159261240   1 MIIEMATGNP-YLpsssDLDLLHKIVLKVGNLSPHLQNIFSKSPIFAgvvlpqvqhpknarkkypklngllaDIVHACLQ 79
Cdd:cd06614   186 MCIEMAEGEPpYL----EEPPLRALFLITTKGIPPLKNPEKWSPEFK-------------------------DFLNKCLV 236

                          90
                  ....*....|....*....
gi 1159261240  80 IDPADRISSSDLLHHEYFT 98
Cdd:cd06614   237 KDPEKRPSAEELLQHPFLK 255

Catalytic domain of the Serine/Threonine Kinase, PCTAIRE-2 kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PCTAIRE-2 is specifically expressed in neurons in the central nervous system, mainly in terminally differentiated neurons. It associates with Trap (Tudor repeat associator with PCTAIRE-2) and could play a role in regulating mitochondrial function in neurons. PCTAIRE-2 shares sequence similarity with Cyclin-Dependent Kinases (CDKs), which belong to a large family of STKs that are regulated by their cognate cyclins. Together, CDKs and cyclins are involved in the control of cell-cycle progression, transcription, and neuronal function. The PCTAIRE-2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1159261240   1 MIIEMATGNPYLPSSSDLDLLHKIVLKVGNLSPHLQNIFSKSPIFAGVVLPQVQhPKNARKKYPKLNGLLADIVHACLQI 80
Cdd:cd07872   194 IFFEMASGRPLFPGSTVEDELHLIFRLLGTPTEETWPGISSNDEFKNYNFPKYK-PQPLINHAPRLDTEGIELLTKFLQY 272

                          90       100
                  ....*....|....*....|....*....
gi 1159261240  81 DPADRISSSDLLHHEYFTRDGFIEKFMPE 109
Cdd:cd07872   273 ESKKRISAEEAMKHAYFRSLGTRIHSLPE 301

Catalytic domain of the Serine/Threonine Kinases, Fungal Mitogen-Activated Protein Kinases Sty1 and Hog1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of the MAPKs Sty1 from Schizosaccharomyces pombe, Hog1 from Saccharomyces cerevisiae, and similar proteins. Sty1 and Hog1 are stress-activated MAPKs that partipate in transcriptional regulation in response to stress. Sty1 is activated in response to oxidative stress, osmotic stress, and UV radiation. It is regulated by the MAP2K Wis1, which is activated by the MAP3Ks Wis4 and Win1, which receive signals of the stress condition from membrane-spanning histidine kinases Mak1-3. Activated Sty1 stabilizes the Atf1 transcription factor and induces transcription of Atf1-dependent genes of the core environmetal stress response. Hog1 is the key element in the high osmolarity glycerol (HOG) pathway and is activated upon hyperosmotic stress. Activated Hog1 accumulates in the nucleus and regulates stress-induced transcription. The HOG pathway is mediated by two transmembrane osmosensors, Sln1 and Sho1. MAPKs are important mediators of cellular responses to extracellular signals. The Sty1/Hog1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1159261240   4 EMATGNPYLPSSSDLDLLHKIVLKVGNlSPH--LQNIFSKSPIFAGVVLPQvQHPKNARKKYPKLNGLLADIVHACLQID 81
Cdd:cd07856   198 EMLEGKPLFPGKDHVNQFSIITELLGT-PPDdvINTICSENTLRFVQSLPK-RERVPFSEKFKNADPDAIDLLEKMLVFD 275

                          90
                  ....*....|....*
gi 1159261240  82 PADRISSSDLLHHEY 96
Cdd:cd07856   276 PKKRISAAEALAHPY 290

Catalytic domain of the Serine/Threonine Kinases, Thousand-and-One Amino acids proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TAO proteins possess mitogen-activated protein kinase (MAPK) kinase kinase activity. They activate the MAPKs, p38 and c-Jun N-terminal kinase (JNK), by phosphorylating and activating the respective MAP/ERK kinases (MEKs, also known as MKKs or MAPKKs), MEK3/MEK6 and MKK4/MKK7. MAPK signaling cascades are important in mediating cellular responses to extracellular signals. Vertebrates contain three TAO subfamily members, named TAO1, TAO2, and TAO3. The TAO 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
                  ....*....|....*....|....*.
gi 1159261240  74 VHACLQIDPADRISSSDLLHHEYFTR 99
Cdd:cd06607   233 VDSCLQKIPQDRPSAEDLLKHPFVTR 258