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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462602829   75 TVPVDIWALGCMIIEMATGNPYLPSSSDLDLLHKIVLKVGNLSPHLQNIFSKSpifagvvlpqvqhpknarkkypklngl 154
Cdd:smart00220 174 GKAVDIWSLGVILYELLTGKPPFPGDDQLLELFKKIGKPKPPFPPPEWDISPE--------------------------- 226

                           90       100
                   ....*....|....*....|....*...
gi 2462602829  155 LADIVHACLQIDPADRISSSDLLHHEYF 182
Cdd:smart00220 227 AKDLIRKLLVKDPEKRLTAEEALQHPFF 254

cyclin-dependent kinase A; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462602829  75 TVPVDIWALGCMIIEMATGNPYLPSSSDLDLLHKIVLKVGNLS----------PHLQNIFSKSPifagvvlpqvqhPKNA 144
Cdd:PLN00009  182 STPVDIWSVGCIFAEMVNQKPLFPGDSEIDELFKIFRILGTPNeetwpgvtslPDYKSAFPKWP------------PKDL 249

                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 2462602829 145 RKKYPKLNGLLADIVHACLQIDPADRISSSDLLHHEYF 182
Cdd:PLN00009  250 ATVVPTLEPAGVDLLSKMLRLDPSKRITARAALEHEYF 287

Catalytic domain of the Serine/Threonine Kinases, Cyclin-Dependent protein Kinase Like 1 and 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDKL1, also called p42 KKIALRE, is a glial protein that is upregulated in gliosis. It is present in neuroblastoma and A431 human carcinoma cells, and may be implicated in neoplastic transformation. The function of CDKL4 is unknown. 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 CDKL1/4 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 2462602829  77 PVDIWALGCMIIEMATGNPYLPSSSDLDLLHKIVLKVGNLSPHLQNIFSKSPIFAGVVLPQVQHPKNARKKYPKLNGLLA 156
Cdd:cd07847   181 PVDVWAIGCVFAELLTGQPLWPGKSDVDQLYLIRKTLGDLIPRHQQIFSTNQFFKGLSIPEPETREPLESKFPNISSPAL 260

                          90       100
                  ....*....|....*....|....*.
gi 2462602829 157 DIVHACLQIDPADRISSSDLLHHEYF 182
Cdd:cd07847   261 SFLKGCLQMDPTERLSCEELLEHPYF 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. 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 2462602829  75 TVPVDIWALGCMIIEMATGNPYLPSSSDLDLLHKIVLKVGNLSPHLQNIFSKSPIFAgVVLPQvQHPKNARKKYPKLNGL 154
Cdd:cd07829   177 STAVDIWSVGCIFAELITGKPLFPGDSEIDQLFKIFQILGTPTEESWPGVTKLPDYK-PTFPK-WPKNDLEKVLPRLDPE 254

                          90       100
                  ....*....|....*....|....*...
gi 2462602829 155 LADIVHACLQIDPADRISSSDLLHHEYF 182
Cdd:cd07829   255 GIDLLSKMLQYNPAKRISAKEALKHPYF 282

Catalytic domain of the Serine/Threonine Kinase, Fungal Cyclin-Dependent protein Kinase (CDK), Bypass UAS Requirement 1, and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. BUR1, also called SGV1, is a yeast CDK that is functionally equivalent to mammalian CDK9. It associates with the cyclin BUR2. BUR genes were orginally identified in a genetic screen as factors involved in general transcription. The BUR1/BUR2 complex phosphorylates the C-terminal domain of RNA polymerase II. In addition, this complex regulates histone modification by phosporylating Rad6 and mediating the association of the Paf1 complex with chromatin. 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 BUR1 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 2462602829  75 TVPVDIWALGCMIIEMATGNPYLPSSSDLDLLHKIVLKVGNLSPHLQNIFSKSPIFAGvVLPQVQHPKNARKKYPKLNGL 154
Cdd:cd07866   205 TTAVDIWGIGCVFAEMFTRRPILQGKSDIDQLHLIFKLCGTPTEETWPGWRSLPGCEG-VHSFTNYPRTLEERFGKLGPE 283

                          90       100
                  ....*....|....*....|....*...
gi 2462602829 155 LADIVHACLQIDPADRISSSDLLHHEYF 182
Cdd:cd07866   284 GLDLLSKLLSLDPYKRLTASDALEHPYF 311

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 2462602829  77 PVDIWALGCMIIEMATGNPYLPSSSDLDLLHKIVLKVGNLSPhlqNIFSKSPIFA---GVVLPQVQhPKNARKKYPKLNG 153
Cdd:cd07830   179 PVDIWALGCIMAELYTLRPLFPGSSEIDQLYKICSVLGTPTK---QDWPEGYKLAsklGFRFPQFA-PTSLHQLIPNASP 254

                          90       100
                  ....*....|....*....|....*....
gi 2462602829 154 LLADIVHACLQIDPADRISSSDLLHHEYF 182
Cdd:cd07830   255 EAIDLIKDMLRWDPKKRPTASQALQHPYF 283

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 2462602829  71 SAATTVPVDIWALGCMIIEMATGNPYLPSSSDLDLLHKIVLKVGNLSPHLQNIFSKSPIFAgVVLPQVQhPKNARKKYPK 150
Cdd:cd07836   175 SRTYSTSIDIWSVGCIMAEMITGRPLFPGTNNEDQLLKIFRIMGTPTESTWPGISQLPEYK-PTFPRYP-PQDLQQLFPH 252

                          90       100       110
                  ....*....|....*....|....*....|..
gi 2462602829 151 LNGLLADIVHACLQIDPADRISSSDLLHHEYF 182
Cdd:cd07836   253 ADPLGIDLLHRLLQLNPELRISAHDALQHPWF 284

Protein kinase domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462602829  75 TVPVDIWALGCMIIEMATGNPYLPSSSDLDLLHKIVLKvGNLSPHLQNIFSKSpifagvvlpqvqhpknarkkypklngl 154
Cdd:pfam00069 138 GPKVDVWSLGCILYELLTGKPPFPGINGNEIYELIIDQ-PYAFPELPSNLSEE--------------------------- 189

                          90       100
                  ....*....|....*....|....*...
gi 2462602829 155 LADIVHACLQIDPADRISSSDLLHHEYF 182
Cdd:pfam00069 190 AKDLLKKLLKKDPSKRLTATQALQHPWF 217

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 2462602829  69 PP-----SAATTVPVDIWALGCMIIEMATGNPYLPSSSD-LDLLHKIVLKVGNLSPHLQNIFSKSPIFAGVVLPQVQhPK 142
Cdd:cd07844   166 PPdvllgSTEYSTSLDMWGVGCIFYEMATGRPLFPGSTDvEDQLHKIFRVLGTPTEETWPGVSSNPEFKPYSFPFYP-PR 244

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|..
gi 2462602829 143 NARKKYPKLNGLL--ADIVHACLQIDPADRISSSDLLHHEYF 182
Cdd:cd07844   245 PLINHAPRLDRIPhgEELALKFLQYEPKKRISAAEAMKHPYF 286

Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 10; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK10, also called PISSLRE, is essential for cell growth and proliferation, and acts through the G2/M phase of the cell cycle. CDK10 has also been identified as an important factor in endocrine therapy resistance in breast cancer. CDK10 silencing increases the transcription of c-RAF and the activation of the p42/p44 MAPK pathway, which leads to antiestrogen resistance. Patients who express low levels of CDK10 relapse early on tamoxifen. 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 CDK10 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 2462602829  75 TVPVDIWALGCMIIEMATGNPYLPSSSDLDLLHKIVLKVGNLSPHLQNIFSKSPIFAGVVLPQvQHPKNARKKYPKLNGL 154
Cdd:cd07845   187 TTAIDMWAVGCILAELLAHKPLLPGKSEIEQLDLIIQLLGTPNESIWPGFSDLPLVGKFTLPK-QPYNNLKHKFPWLSEA 265

                          90       100
                  ....*....|....*....|....*...
gi 2462602829 155 LADIVHACLQIDPADRISSSDLLHHEYF 182
Cdd:cd07845   266 GLRLLNFLLMYDPKKRATAEEALESSYF 293

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 2462602829  75 TVPVDIWALGCMIIEMATGNPYLPSSSDLDLLHKIVLKVG---------NLSPHLQNIFSKSPifagvvlpqvqhPKNAR 145
Cdd:cd07841   181 GVGVDMWSVGCIFAELLLRVPFLPGDSDIDQLGKIFEALGtpteenwpgVTSLPDYVEFKPFP------------PTPLK 248

                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 2462602829 146 KKYPKLNGLLADIVHACLQIDPADRISSSDLLHHEYFT 183
Cdd:cd07841   249 QIFPAASDDALDLLQRLLTLNPNKRITARQALEHPYFS 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 2462602829  77 PVDIWALGCMIIEMATGNPYLPSSSDLDLLHKIVLKVGNLSPHLQNifskspifagvvlpqvqhpkNARKKYPklngLLA 156
Cdd:cd14133   181 KIDMWSLGCILAELYTGEPLFPGASEVDQLARIIGTIGIPPAHMLD--------------------QGKADDE----LFV 236

                          90       100
                  ....*....|....*....|....*.
gi 2462602829 157 DIVHACLQIDPADRISSSDLLHHEYF 182
Cdd:cd14133   237 DFLKKLLEIDPKERPTASQALSHPWL 262

Catalytic domain of STE family Protein Kinases; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. This family is composed of STKs, and some dual-specificity PKs that phosphorylate both threonine and tyrosine residues of target proteins. Most members are kinases involved in mitogen-activated protein kinase (MAPK) signaling cascades, acting as MAPK kinases (MAPKKs), MAPKK kinases (MAPKKKs), or MAPKKK kinases (MAP4Ks). The MAPK signaling pathways are important mediators of cellular responses to extracellular signals. The pathways involve a triple kinase core cascade comprising of the MAPK, which is phosphorylated and activated by a MAPKK, which itself is phosphorylated and activated by a MAPKKK. Each MAPK cascade is activated either by a small GTP-binding protein or by an adaptor protein, which transmits the signal either directly to a MAPKKK to start the triple kinase core cascade or indirectly through a mediator kinase, a MAP4K. Other STE family members include p21-activated kinases (PAKs) and class III myosins, among others. PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. Class III myosins are motor proteins containing an N-terminal kinase catalytic domain and a C-terminal actin-binding domain, which can phosphorylate several cytoskeletal proteins, conventional myosin regulatory light chains, as well as autophosphorylate the C-terminal motor domain. They play an important role in maintaining the structural integrity of photoreceptor cell microvilli. The STE family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462602829  75 TVPVDIWALGCMIIEMATGN-PYLPSSSdldllHKIVLKVG-NLSPHLQNIFSKSPIFagvvlpqvqhpknarkkypkln 152
Cdd:cd05122   175 GFKADIWSLGITAIEMAEGKpPYSELPP-----MKALFLIAtNGPPGLRNPKKWSKEF---------------------- 227

                          90       100       110
                  ....*....|....*....|....*....|
gi 2462602829 153 gllADIVHACLQIDPADRISSSDLLHHEYF 182
Cdd:cd05122   228 ---KDFLKKCLQKDPEKRPTAEQLLKHPFI 254

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 2462602829  78 VDIWALGCMIIEMATGNPYLPSSSDLDLLHKIVLKVGNLSPHLQNIFSKSPIfAGVVLPQvQHPKNARKKYPKLNGLLAD 157
Cdd:cd07831   180 MDIWAVGCVFFEILSLFPLFPGTNELDQIAKIHDVLGTPDAEVLKKFRKSRH-MNYNFPS-KKGTGLRKLLPNASAEGLD 257

                          90       100
                  ....*....|....*....|....*
gi 2462602829 158 IVHACLQIDPADRISSSDLLHHEYF 182
Cdd:cd07831   258 LLKKLLAYDPDERITAKQALRHPYF 282

Catalytic domain of the Serine/Threonine Kinase, Cell Division Cycle 2-like 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDC2L1, also called PITSLRE, exists in different isoforms which are named using the alias CDK11(p). The CDC2L1 gene produces two protein products, CDK11(p110) and CDK11(p58). CDC2L1 is also represented by the caspase-processed CDK11(p46). CDK11(p110), the major isoform, associates with cyclin L and is expressed throughout the cell cycle. It is involved in RNA processing and the regulation of transcription. CDK11(p58) associates with cyclin D3 and is expressed during the G2/M phase of the cell cycle. It plays roles in spindle morphogenesis, centrosome maturation, sister chromatid cohesion, and the completion of mitosis. CDK11(p46) is formed from the larger isoforms by caspases during TNFalpha- and Fas-induced apoptosis. It functions as a downstream effector kinase in apoptotic signaling pathways and interacts with eukaryotic initiation factor 3f (eIF3f), p21-activated kinase (PAK1), and Ran-binding protein (RanBPM). 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 CDC2L1 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 2462602829  75 TVPVDIWALGCMIIEMATGNPYLPSSSDLDLLHKIVLKVGnlSPHLQNI--FSKSPiFAGVVLPQVQHPKNARKKYPKL- 151
Cdd:cd07843   185 STAIDMWSVGCIFAELLTKKPLFPGKSEIDQLNKIFKLLG--TPTEKIWpgFSELP-GAKKKTFTKYPYNQLRKKFPALs 261

                          90       100       110
                  ....*....|....*....|....*....|....
gi 2462602829 152 ---NGLlaDIVHACLQIDPADRISSSDLLHHEYF 182
Cdd:cd07843   262 lsdNGF--DLLNRLLTYDPAKRISAEDALKHPYF 293

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 2462602829  77 PVDIWALGCMIIEMATGNPYLPSSSDLDLLHKIV-------LKVGNLSPHLQNIFSKSPIfagvvlPQVQHPKNARKKYP 149
Cdd:cd14210   195 AIDMWSLGCILAELYTGYPLFPGENEEEQLACIMevlgvppKSLIDKASRRKKFFDSNGK------PRPTTNSKGKKRRP 268

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|...
gi 2462602829 150 K---LNGLLA-------DIVHACLQIDPADRISSSDLLHHEYF 182
Cdd:cd14210   269 GsksLAQVLKcddpsflDFLKKCLRWDPSERMTPEEALQHPWI 311

Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 9; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK9, together with a cyclin partner (cyclin T1, T2a, T2b, or K), is the main component of distinct positive transcription elongation factors (P-TEFb), which function as Ser2 C-terminal domain kinases of RNA polymerase II. P-TEFb participates in multiple steps of gene expression including transcription elongation, mRNA synthesis, processing, export, and translation. It also plays a role in mediating cytokine induced transcription networks such as IL6-induced STAT3 signaling. In addition, the CDK9/cyclin T2a complex promotes muscle differentiation and enhances the function of some myogenic regulatory factors. 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 CDK9 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 2462602829  77 PVDIWALGCMIIEMATGNPYLPSSSDLDLLHKIVLKVGNLSPHLQNIFSKSPIFAGVVLPQVQHPKNARKKYPKLNGLLA 156
Cdd:cd07865   204 PIDMWGAGCIMAEMWTRSPIMQGNTEQHQLTLISQLCGSITPEVWPGVDKLELFKKMELPQGQKRKVKERLKPYVKDPYA 283

                          90       100
                  ....*....|....*....|....*..
gi 2462602829 157 -DIVHACLQIDPADRISSSDLLHHEYF 182
Cdd:cd07865   284 lDLIDKLLVLDPAKRIDADTALNHDFF 310

Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein Kinase Kinase Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAPKKKs (MKKKs or MAP3Ks) are also called MAP/ERK kinase kinases (MEKKs) in some cases. They phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. This subfamily is composed of the Apoptosis Signal-regulating Kinases ASK1 (or MAPKKK5) and ASK2 (or MAPKKK6), MEKK1, MEKK2, MEKK3, MEKK4, as well as plant and fungal MAPKKKs. Also included in this subfamily are the cell division control proteins Schizosaccharomyces pombe Cdc7 and Saccharomyces cerevisiae Cdc15. The MAPKKK 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 2462602829  77 PVDIWALGCMIIEMATGNPYLPSSSD-LDLLHKIVLKVG------NLSPHLQNIFSKspifagvvlpqvqhpknarkkyp 149
Cdd:cd06606   181 AADIWSLGCTVIEMATGKPPWSELGNpVAALFKIGSSGEpppipeHLSEEAKDFLRK----------------------- 237

                          90       100       110
                  ....*....|....*....|....*....|...
gi 2462602829 150 klnglladivhaCLQIDPADRISSSDLLHHEYF 182
Cdd:cd06606   238 ------------CLQRDPKKRPTADELLQHPFL 258

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 2462602829  78 VDIWALGCMIIEMATGNPYLpssSDLDllhkiVLKVgnlsphLQNIfSKSPIfagvvlPQVQHPKNARkkypklngLLAD 157
Cdd:cd06609   179 ADIWSLGITAIELAKGEPPL---SDLH-----PMRV------LFLI-PKNNP------PSLEGNKFSK--------PFKD 229

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*
gi 2462602829 158 IVHACLQIDPADRISSSDLLHHEyftrdgFIEKFMPELKAKLLQE 202
Cdd:cd06609   230 FVELCLNKDPKERPSAKELLKHK------FIKKAKKTSYLTLLIE 268

Catalytic domain of the Serine/Threonine Kinase, p38gamma Mitogen-Activated Protein Kinase (also called MAPK12); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. p38gamma/MAPK12 is predominantly expressed in skeletal muscle. Unlike p38alpha and p38beta, p38gamma is insensitive to pyridinylimidazoles. It displays an antagonizing function compared to p38alpha. p38gamma inhibits, while p38alpha stimulates, c-Jun phosphorylation and AP-1 mediated transcription. p38gamma also plays a role in the signaling between Ras and the estrogen receptor and has been implicated to increase cell invasion and breast cancer progression. In Xenopus, p38gamma is critical in the meiotic maturation of oocytes. p38 kinases are MAPKs, serving as important mediators of cellular responses to extracellular signals. They 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. The p38gamma 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 2462602829  75 TVPVDIWALGCMIIEMATGNPYLPSSSDLDLLHKIVLKVG----NLSPHLQNIFSKSPIFAgvvLPQVQHpKNARKKYPK 150
Cdd:cd07880   194 TQTVDIWSVGCIMAEMLTGKPLFKGHDHLDQLMEIMKVTGtpskEFVQKLQSEDAKNYVKK---LPRFRK-KDFRSLLPN 269

                          90       100       110
                  ....*....|....*....|....*....|..
gi 2462602829 151 LNGLLADIVHACLQIDPADRISSSDLLHHEYF 182
Cdd:cd07880   270 ANPLAVNVLEKMLVLDAESRITAAEALAHPYF 301

Catalytic domain of the Serine/Threonine Kinase, p38beta Mitogen-Activated Protein Kinase (also called MAPK11); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. p38beta/MAPK11 is widely expressed in tissues and shows more similarity with p38alpha than with the other isoforms. Both are sensitive to pyridinylimidazoles and share some common substrates such as MAPK activated protein kinase 2 (MK2) and the transcription factors ATF2, c-Fos and, ELK-1. p38beta is involved in regulating the activation of the cyclooxygenase-2 promoter and the expression of TGFbeta-induced alpha-smooth muscle cell actin. p38 kinases are mitogen-activated protein kinases (MAPKs), serving as important mediators of cellular responses to extracellular signals. They 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. The p38beta 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 2462602829  78 VDIWALGCMIIEMATGNPYLPSSSDLDLLHKIVLKVGNLSPH-LQNIFSKSPIFAGVVLPQVQHpKNARKKYPKLNGLLA 156
Cdd:cd07878   197 VDIWSVGCIMAELLKGKALFPGNDYIDQLKRIMEVVGTPSPEvLKKISSEHARKYIQSLPHMPQ-QDLKKIFRGANPLAI 275

                          90       100
                  ....*....|....*....|....*...
gi 2462602829 157 DIVHACLQIDPADRISSSDLLHHEYFTR 184
Cdd:cd07878   276 DLLEKMLVLDSDKRISASEALAHPYFSQ 303

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 2462602829  78 VDIWALGCMIIEMATGNPYLPSSSDLDLLHKIVLKVGN--------LSPHLQNIFSKSPIFAGVVLPQVqHPKN---ARK 146
Cdd:cd07874   199 VDIWSVGCIMGEMVRHKILFPGRDYIDQWNKVIEQLGTpcpefmkkLQPTVRNYVENRPKYAGLTFPKL-FPDSlfpADS 277

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 2462602829 147 KYPKLNGLLA-DIVHACLQIDPADRISSSDLLHHEY 181
Cdd:cd07874   278 EHNKLKASQArDLLSKMLVIDPAKRISVDEALQHPY 313

Catalytic domain of the Serine/Threonine Kinase, p38alpha Mitogen-Activated Protein Kinase (also called MAPK14); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. p38alpha/MAPK14 is expressed in most tissues and is the major isoform involved in the immune and inflammatory response. It is the central p38 MAPK involved in myogenesis. It plays a role in regulating cell cycle check-point transition and promoting cell differentiation. p38alpha also regulates cell proliferation and death through crosstalk with the JNK pathway. Its substrates include MAPK activated protein kinase 2 (MK2), MK5, and the transcription factors ATF2 and Mitf. p38 kinases MAPKs, serving as important mediators of cellular responses to extracellular signals. They 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. The p38alpha 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 2462602829  76 VPVDIWALGCMIIEMATGNPYLPSSSDLDLLHKIVLKVGNLSPHL-QNIFSKSPIFAGVVLPQVqhPK-NARKKYPKLNG 153
Cdd:cd07877   197 QTVDIWSVGCIMAELLTGRTLFPGTDHIDQLKLILRLVGTPGAELlKKISSESARNYIQSLTQM--PKmNFANVFIGANP 274

                          90       100       110
                  ....*....|....*....|....*....|.
gi 2462602829 154 LLADIVHACLQIDPADRISSSDLLHHEYFTR 184
Cdd:cd07877   275 LAVDLLEKMLVLDSDKRITAAQALAHAYFAQ 305

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 2462602829  78 VDIWALGCMIIEMATGN-PYLpsssDLDLLHKIVLKVGNLSPHLQNIFSKSPIFagvvlpqvqhpknarkkypklngllA 156
Cdd:cd06614   178 VDIWSLGIMCIEMAEGEpPYL----EEPPLRALFLITTKGIPPLKNPEKWSPEF-------------------------K 228

                          90       100
                  ....*....|....*....|....*..
gi 2462602829 157 DIVHACLQIDPADRISSSDLLHHEYFT 183
Cdd:cd06614   229 DFLNKCLVKDPEKRPSAEELLQHPFLK 255

Catalytic domain of the Serine/Threonine Kinase, PCTAIRE-1 kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PCTAIRE-1 is expressed ubiquitously and is localized in the cytoplasm. Its kinase activity is cell cycle dependent and peaks at the S and G2 phases. PCTAIRE-1 is highly expressed in the brain and may play a role in regulating neurite outgrowth. It can also associate with Trap (Tudor repeat associator with PCTAIRE-2), a physiological partner of PCTAIRE-2; with p11, a small dimeric protein with similarity to S100; and with 14-3-3 proteins, mediators of phosphorylation-dependent interactions in many different proteins. PCTAIRE-1 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-1 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 2462602829  69 PP-----SAATTVPVDIWALGCMIIEMATGNPYLPSSSDLDLLHKIVLKVGNLSPHLQNIFSKSPIFAGVVLPQVQhPKN 143
Cdd:cd07873   168 PPdillgSTDYSTQIDMWGVGCIFYEMSTGRPLFPGSTVEEQLHFIFRILGTPTEETWPGILSNEEFKSYNYPKYR-ADA 246

                          90       100       110
                  ....*....|....*....|....*....|....*....
gi 2462602829 144 ARKKYPKLNGLLADIVHACLQIDPADRISSSDLLHHEYF 182
Cdd:cd07873   247 LHNHAPRLDSDGADLLSKLLQFEGRKRISAEEAMKHPYF 285

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 2462602829  78 VDIWALGCMIIEMATGNPYLPSSSDLDLLHKIVLKVGNLSPHL-QNIFSKSPIFAGVVLPQVQHpKNARKKYPKLNGLLA 156
Cdd:cd07851   197 VDIWSVGCIMAELLTGKTLFPGSDHIDQLKRIMNLVGTPDEELlKKISSESARNYIQSLPQMPK-KDFKEVFSGANPLAI 275

                          90       100
                  ....*....|....*....|....*.
gi 2462602829 157 DIVHACLQIDPADRISSSDLLHHEYF 182
Cdd:cd07851   276 DLLEKMLVLDPDKRITAAEALAHPYL 301