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 664759227    1 MQLQGRNLADLRRSQSRGTFTISTTLRLGRQILESIESIHSVGFLHRDIKPSNFAMGRFPSTCRKCYMLDFGLARQFTNS 80
Cdd:cd14129    75 MQLQGRNLADLRRSQSRGTFTISTTLRLGRQILESIESIHSVGFLHRDIKPSNFAMGRFPSTCRKCYMLDFGLARQFTNS 154

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 664759227   81 CGDVRPPRAVAGFRGTVRYASINAHRNREMGRHDDLWSLFYMLVEFVVGQLPWRKIKDKEQVGSIKERYDHRLMLKHLPP 160
Cdd:cd14129   155 CGDVRPPRAVAGFRGTVRYASINAHRNREMGRHDDLWSLFYMLVEFVVGQLPWRKIKDKEQVGSIKERYEHRLMLKHLPP 234

                         170       180
                  ....*....|....*....|....*...
gi 664759227  161 EFSMFLDHISSLDYFTKPDYQLLTSVFD 188
Cdd:cd14129   235 EFSVFLDHISGLDYFTKPDYQLLVSVFD 262

Catalytic domain of the Serine/Threonine protein kinase, Tau-Tubulin Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TTBK is a neuron-specific kinase that phosphorylates the microtubule-associated protein tau and promotes its aggregation. Higher vertebrates contain two TTBK proteins, TTBK1 and TTBK2, both of which have been implicated in neurodegeneration. Mutations in TTBK2 is associated with the development of spinocerebellar ataxia type 11, belonging to a group of neurodegenerative disorders characterized by progressive incoordination, dysarthria and impairment of eye movements. Brain tissues of SCA11 patients show the presence of neurofibrillary tangles and tau deposition in the brain, similar to Alzheimer's disease (AD) patients. The TTBK2 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 664759227    1 MQLQGRNLADLRRSQSRGTFTISTTLRLGRQILESIESIHSVGFLHRDIKPSNFAMGRFPSTCRKCYMLDFGLARQFTNS 80
Cdd:cd14129    75 MQLQGRNLADLRRSQSRGTFTISTTLRLGRQILESIESIHSVGFLHRDIKPSNFAMGRFPSTCRKCYMLDFGLARQFTNS 154

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 664759227   81 CGDVRPPRAVAGFRGTVRYASINAHRNREMGRHDDLWSLFYMLVEFVVGQLPWRKIKDKEQVGSIKERYDHRLMLKHLPP 160
Cdd:cd14129   155 CGDVRPPRAVAGFRGTVRYASINAHRNREMGRHDDLWSLFYMLVEFVVGQLPWRKIKDKEQVGSIKERYEHRLMLKHLPP 234

                         170       180
                  ....*....|....*....|....*...
gi 664759227  161 EFSMFLDHISSLDYFTKPDYQLLTSVFD 188
Cdd:cd14129   235 EFSVFLDHISGLDYFTKPDYQLLVSVFD 262

putative serine/threonine kinase; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 664759227   32 ILESIESIHSVGFLHRDIKPSNFAMgrfpSTCRKCYMLDFGLARQFTNSCGDVRPPRAVAGF-RGTVRYASINAHRNREM 110
Cdd:PHA02882  135 MLTTLEYIHEHGISHGDIKPENIMV----DGNNRGYIIDYGIASHFIIHGKHIEYSKEQKDLhRGTLYYAGLDAHNGACV 210

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 664759227  111 GRHDDLWSLFYMLVEFVVGQLPWRKIKDKEQV------GSIKERYDHRLMLKHLPPEFSMFLDHISSLDYFTKPDYQLLT 184
Cdd:PHA02882  211 TRRGDLESLGYCMLKWAGIKLPWKGFGHNGNLihaakcDFIKRLHEGKIKIKNANKFIYDFIECVTKLSYEEKPDYDALI 290

                  ....
gi 664759227  185 SVFD 188
Cdd:PHA02882  291 KIFD 294

Stk1 family PASTA domain-containing Ser/Thr kinase;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 664759227    5 GRNLADLRRSqsRGTFTISTTLRLGRQILESIESIHSVGFLHRDIKPSNFamgrfpstcrkcyML---------DFGLAR 75
Cdd:NF033483   91 GRTLKDYIRE--HGPLSPEEAVEIMIQILSALEHAHRNGIVHRDIKPQNI-------------LItkdgrvkvtDFGIAR 155

                  ....*
gi 664759227   76 QFTNS 80
Cdd:NF033483  156 ALSST 160

Catalytic domain of the Serine/Threonine protein kinase, Tau-Tubulin Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TTBK is a neuron-specific kinase that phosphorylates the microtubule-associated protein tau and promotes its aggregation. Higher vertebrates contain two TTBK proteins, TTBK1 and TTBK2, both of which have been implicated in neurodegeneration. Mutations in TTBK2 is associated with the development of spinocerebellar ataxia type 11, belonging to a group of neurodegenerative disorders characterized by progressive incoordination, dysarthria and impairment of eye movements. Brain tissues of SCA11 patients show the presence of neurofibrillary tangles and tau deposition in the brain, similar to Alzheimer's disease (AD) patients. The TTBK2 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 664759227    1 MQLQGRNLADLRRSQSRGTFTISTTLRLGRQILESIESIHSVGFLHRDIKPSNFAMGRFPSTCRKCYMLDFGLARQFTNS 80
Cdd:cd14129    75 MQLQGRNLADLRRSQSRGTFTISTTLRLGRQILESIESIHSVGFLHRDIKPSNFAMGRFPSTCRKCYMLDFGLARQFTNS 154

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 664759227   81 CGDVRPPRAVAGFRGTVRYASINAHRNREMGRHDDLWSLFYMLVEFVVGQLPWRKIKDKEQVGSIKERYDHRLMLKHLPP 160
Cdd:cd14129   155 CGDVRPPRAVAGFRGTVRYASINAHRNREMGRHDDLWSLFYMLVEFVVGQLPWRKIKDKEQVGSIKERYEHRLMLKHLPP 234

                         170       180
                  ....*....|....*....|....*...
gi 664759227  161 EFSMFLDHISSLDYFTKPDYQLLTSVFD 188
Cdd:cd14129   235 EFSVFLDHISGLDYFTKPDYQLLVSVFD 262

Catalytic domain of the Serine/Threonine protein kinase, Tau-Tubulin Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TTBK is a neuron-specific kinase that phosphorylates the microtubule-associated protein tau and promotes its aggregation. Higher vertebrates contain two TTBK proteins, TTBK1 and TTBK2, both of which have been implicated in neurodegeneration. TTBK1 has been linked to Alzheimer's disease (AD) while TTBK2 is associated with spinocerebellar ataxia type 11 (SCA11). Both AD and SCA11 patients show the presence of neurofibrillary tangles in the brain. The Drosophila TTBK homolog, Asator, is an essential protein that localizes to the mitotic spindle during mitosis and may be involved in regulating microtubule dynamics and function. The TTBK 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 664759227    1 MQLQGRNLADLRRSQSRGTFTISTTLRLGRQILESIESIHSVGFLHRDIKPSNFAMGRFPSTCRKCYMLDFGLARQFTNS 80
Cdd:cd14017    75 MTLLGPNLAELRRSQPRGKFSVSTTLRLGIQILKAIEDIHEVGFLHRDVKPSNFAIGRGPSDERTVYILDFGLARQYTNK 154

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 664759227   81 CGDV-RPPRAVAGFRGTVRYASINAHRNREMGRHDDLWSLFYMLVEFVVGQLPWRKIKDKEQVGSIKERYDHRLMLKHLP 159
Cdd:cd14017   155 DGEVeRPPRNAAGFRGTVRYASVNAHRNKEQGRRDDLWSWFYMLIEFVTGQLPWRKLKDKEEVGKMKEKIDHEELLKGLP 234

                         170       180
                  ....*....|....*....|....*....
gi 664759227  160 PEFSMFLDHISSLDYFTKPDYQLLTSVFD 188
Cdd:cd14017   235 KEFFQILKHIRSLSYFDTPDYKKLHSLLE 263

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 664759227    1 MQLQGRNLADLRRSQSRgTFTISTTLRLGRQILESIESIHSVGFLHRDIKPSNFAMGrFPSTCRKCYMLDFGLARQFTNS 80
Cdd:cd14128    75 MDLLGPSLEDLFNFCSR-RFTMKTVLMLADQMIGRIEYVHNKNFIHRDIKPDNFLMG-IGRHCNKLFLIDFGLAKKYRDS 152

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 664759227   81 -CGDVRPPRAVAGFRGTVRYASINAHRNREMGRHDDLWSLFYMLVEFVVGQLPWRKIKDK------EQVGSIKERYDHRL 153
Cdd:cd14128   153 rTRQHIPYREDKNLTGTARYASINAHLGIEQSRRDDMESLGYVLMYFNRGSLPWQGLKAAtkkqkyEKISEKKMSTPVEV 232

                         170       180       190
                  ....*....|....*....|....*....|....
gi 664759227  154 MLKHLPPEFSMFLDHISSLDYFTKPDYQLLTSVF 187
Cdd:cd14128   233 LCKGFPAEFAMYLNYCRGLRFEEAPDYMYLRQLF 266

Catalytic domain of the Serine/Threonine protein kinase, Casein Kinase 1 gamma; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CK1 phosphorylates a variety of substrates including enzymes, transcription and splice factors, cytoskeletal proteins, viral oncogenes, receptors, and membrane-associated proteins. There are mutliple isoforms of CK1 and in mammals, seven isoforms (alpha, beta, gamma1-3, delta, and epsilon) have been characterized. These isoforms differ mainly in the length and structure of their C-terminal non-catalytic region. CK1gamma proteins are unique within the CK1 subfamily in that they are palmitoylated at the C-termini and are anchored to the plasma membrane. CK1gamma is involved in transducing the signaling of LDL-receptor-related protein 6 (LRP6) through direct phosphorylation following Wnt stimulation, resulting in the recruitment of the scaffold protein Axin. In Xenopus embryos, CK1gamma is required during anterio-posterior patterning. In higher vertebrates, three CK1gamma (gamma1-3) isoforms exist. In mammalian cells, CK1gamma2 has been implicated in regulating the synthesis of sphingomyelin, a phospholipid that is found in the outer leaflet of the plasma membrane, by hyperphosphorylating and inactivating the ceramide transfer protein CERT. CK1gamma2 also phosphorylates the transcription factor Smad-3 resulting in its ubiquitination and degradation. It inhibits Smad-3 mediated responses of Transforming Growth Factor-beta (TGF-beta) including cell growth arrest. The CK1 gamma 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 664759227    1 MQLQGRNLADLRRSQSRgTFTISTTLRLGRQILESIESIHSVGFLHRDIKPSNFAMGRfPSTCRK--CYMLDFGLARQFT 78
Cdd:cd14126    75 LELLGPSLEDLFDLCDR-TFSLKTVLMIAIQLISRIEYVHSKHLIYRDVKPENFLIGR-QSTKKQhvIHIIDFGLAKEYI 152

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 664759227   79 NS-CGDVRPPRAVAGFRGTVRYASINAHRNREMGRHDDLWSLFYMLVEFVVGQLPWRKIKdkeqVGSIKERYDH------ 151
Cdd:cd14126   153 DPeTNKHIPYREHKSLTGTARYMSINTHLGKEQSRRDDLEALGHMFMYFLRGSLPWQGLK----ADTLKERYQKigdtkr 228

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 664759227  152 ----RLMLKHLPPEFSMFLDHISSLDYFTKPDYQLLTSVFDNSIKTFGVIESDPFDW 204
Cdd:cd14126   229 atpiEVLCENFPEEMATYLRYVRRLDFFETPDYDYLRKLFTDLFDRKGYTDDYEFDW 285

Catalytic domain of the Serine/Threonine protein kinase, Vaccinia Related Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. VRKs were initially discovered due to its similarity to vaccinia virus B1R STK, which is important for viral replication. They play important roles in cell signaling, nuclear envelope dynamics, apoptosis, and stress responses. Vertebrates contain three VRK proteins (VRK1, VRK2, and VRK3) while invertebrates, specifically fruit flies and nematodes, seem to carry only a single ortholog. Mutations of VRK in Drosophila and Caenorhabditis elegans showed varying phenotypes ranging from embryonic lethality to mitotic and meiotic defects resulting in sterility. In vertebrates, VRK1 is implicated in cell cycle progression and proliferation, nuclear envelope assembly, and chromatin condensation. VRK2 is involved in modulating JNK signaling. VRK3 is an inactive pseudokinase that inhibits ERK signaling. The VRK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 664759227   15 QSRGTFTISTTLRLGRQILESIESIHSVGFLHRDIKPSNFAMGrFPSTCRKCYMLDFGLARQFTNSCGDVR----PPRAv 90
Cdd:cd14015   119 KNGKRFPEKTVLQLALRILDVLEYIHENGYVHADIKASNLLLG-FGKNKDQVYLVDYGLASRYCPNGKHKEykedPRKA- 196

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 664759227   91 agFRGTVRYASINAHRNREMGRHDDLWSLFYMLVEFVVGQLPWR-KIKDKEQVGSIKERY--DHRLMLKHL------PPE 161
Cdd:cd14015   197 --HNGTIEFTSRDAHKGVAPSRRGDLEILGYNMLQWLCGKLPWEdNLKNPEYVQKQKEKYmdDIPLLLKKCfpgkdvPEE 274

                         170       180
                  ....*....|....*....|....*.
gi 664759227  162 FSMFLDHISSLDYFTKPDYQLLTSVF 187
Cdd:cd14015   275 LQKYLKYVASLEYEEKPDYEKLRKIL 300

Catalytic domain of the Serine/Threonine protein kinase, Vaccinia Related Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. VRKs were initially discovered due to its similarity to vaccinia virus B1R STK, which is important for viral replication. They play important roles in cell signaling, nuclear envelope dynamics, apoptosis, and stress responses. Vertebrates contain three VRK proteins. VRK2 exists as two alternative splice forms, A and B, which differ in their C-terminal regions. VRK2A, the predominant isoform, contains a hydrophobic tail and is anchored to the ER and mitochondria. It is expressed in all cell types. VRK2B lacks a membrane-anchor tail and is detected in the cytosol and the nucleus. Like VRK1, it can stabilize p53. VRK2B functionally replaces VRK1 in the nucleus of cell types where VRK1 is absent. VRK2 modulates hypoxia-induced stress responses by interacting with TAK1, an atypical MAPK kinase kinase which triggers cascades that activate JNK following oxidative stress. VRK2 also interacts with JIP1, a scaffold protein that assembles three consecutive members of a MAPK pathway. This interaction prevents the association of JNK with the signaling complex, leading to reduced phosphorylation and AP1-dependent transcription. The VRK2 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 664759227   10 DLRR--SQSRGTFTISTTLRLGRQILESIESIHSVGFLHRDIKPSNFAMGRfpSTCRKCYMLDFGLARQFT---NSCGDV 84
Cdd:cd14123   114 DLQKilIDNGGQFKKTTVLQLGIRMLDVLEYIHENEYVHGDIKAANLLLGY--RNPNEVYLADYGLSYRYCpngNHKEYK 191

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 664759227   85 RPPRAvaGFRGTVRYASINAHRNREMGRHDDLWSLFYMLVEFVVGQLPW-RKIKDKEQVGSIKERYDHRL---MLKHLPP 160
Cdd:cd14123   192 ENPRK--GHNGTIEFTSLDAHKGVAPSRRGDLEILGYCMLHWLCGKLPWeQNLKNPVAVQEAKAKLLSNLpdsVLKWSTG 269

                         170       180       190
                  ....*....|....*....|....*....|.
gi 664759227  161 -----EFSMFLDHISSLDYFTKPDYQLLTSV 186
Cdd:cd14123   270 gsssmEIAQFLSRVKDLAYDEKPDYQALKKI 300

Catalytic domain of the Serine/Threonine protein kinase, Vaccinia Related Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. VRKs were initially discovered due to its similarity to vaccinia virus B1R STK, which is important for viral replication. Vertebrates contain three VRK proteins. Human VRK1 is implicated in the regulation of many cellular processes including cell cycle progression and proliferation, stress responses, nuclear envelope assembly and chromatin condensation. It regulates cell cycle progression during the DNA replication period by inducing cyclin D1 expression. VRK1 also phosphorylates and regulates some transcription factors including p53, c-Jun, ATF2, and nuclear factor BAF. VRK1 stabilizes p53 by interfering with its mdm2-mediated degradation. Accumulation of p53, which blocks cell growth and division, is modulated by an autoregulatory loop between p53 and VRK1 (accumulated p53 downregulates VRK1). This autoregulatory loop has been found to be nonfunctional in some lung carcinomas. The VRK1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 664759227    1 MQLQGRNLADLRRSQSRgTFTISTTLRLGRQILESIESIHSVGFLHRDIKPSNFAMGRfpSTCRKCYMLDFGLARQFtns 80
Cdd:cd14122   106 MDRFGSDLQKIYEANAK-RFSRKTVLQLGLRILDILEYIHEHEYVHGDIKASNLLLSY--KNPDQVYLVDYGLAYRY--- 179

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 664759227   81 CGDVRPPRAVAGFR----GTVRYASINAHRNREMGRHDDLWSLFYMLVEFVVGQLPWR-KIKDKEQVGSIKERYDH---R 152
Cdd:cd14122   180 CPEGVHKEYKEDPKrchdGTIEFTSIDAHKGVAPSRRGDLEILGYCMIQWLCGHLPWEdNLKDPNYVRDSKIRYRDnisE 259

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|
gi 664759227  153 LM-----LKHLPPEFSMFLDHISSLDYFTKPDYQLLTSVF 187
Cdd:cd14122   260 LMekcfpGKNKPGEIRKYMETVKLLGYTEKPLYPHLREIL 299

Catalytic domain of bacterial Serine/Threonine kinases, PknB and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily includes many bacterial eukaryotic-type STKs including Staphylococcus aureus PknB (also called PrkC or Stk1), Bacillus subtilis PrkC, and Mycobacterium tuberculosis Pkn proteins (PknB, PknD, PknE, PknF, PknL, and PknH), among others. S. aureus PknB is the only eukaryotic-type STK present in this species, although many microorganisms encode for several such proteins. It is important for the survival and pathogenesis of S. aureus as it is involved in the regulation of purine and pyrimidine biosynthesis, cell wall metabolism, autolysis, virulence, and antibiotic resistance. M. tuberculosis PknB is essential for growth and it acts on diverse substrates including proteins involved in peptidoglycan synthesis, cell division, transcription, stress responses, and metabolic regulation. B. subtilis PrkC is located at the inner membrane of endospores and functions to trigger spore germination. Bacterial STKs in this subfamily show varied domain architectures. The well-characterized members such as S. aureus and M. tuberculosis PknB, and B. subtilis PrkC, contain an N-terminal cytosolic kinase domain, a transmembrane (TM) segment, and mutliple C-terminal extracellular PASTA domains. The PknB 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 664759227    3 LQGRNLAD-LRRsqsRGTFTISTTLRLGRQILESIESIHSVGFLHRDIKPSNFAMGRFPstcrKCYMLDFGLARQFtnsc 81
Cdd:cd14014    82 VEGGSLADlLRE---RGPLPPREALRILAQIADALAAAHRAGIVHRDIKPANILLTEDG----RVKLTDFGIARAL---- 150

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|...
gi 664759227   82 gDVRPPRAVAGFRGTVRYASINAHRNREMGRHDDLWSLFYMLVEFVVGQLPWR 134
Cdd:cd14014   151 -GDSGLTQTGSVLGTPAYMAPEQARGGPVDPRSDIYSLGVVLYELLTGRPPFD 202

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 664759227    5 GRNLADLRRSqsRGTFTISTTLRLGRQILESIESIHSVGFLHRDIKPSN---FAMGRfpstcrkCYMLDFGLARQFtnsc 81
Cdd:cd06606    83 GGSLASLLKK--FGKLPEPVVRKYTRQILEGLEYLHSNGIVHRDIKGANilvDSDGV-------VKLADFGCAKRL---- 149

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 664759227   82 GDVRPPRAVAGFRGTVRYASINAHRNREMGRHDDLWSLFYMLVEFVVGQLPWRKIKDKEQV----GSIKErydHRLMLKH 157
Cdd:cd06606   150 AEIATGEGTKSLRGTPYWMAPEVIRGEGYGRAADIWSLGCTVIEMATGKPPWSELGNPVAAlfkiGSSGE---PPPIPEH 226

                         170
                  ....*....|.
gi 664759227  158 LPPEFSMFLDH 168
Cdd:cd06606   227 LSEEAKDFLRK 237

Catalytic domain of the Protein Serine/Threonine Kinase, Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase Kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MEKK4 is a MAPK kinase kinase that phosphorylates and activates the c-Jun N-terminal kinase (JNK) and p38 MAPK signaling pathways by directly activating their respective MAPKKs, MKK4/MKK7 and MKK3/MKK6. JNK and p38 are collectively known as stress-activated MAPKs, as they are activated in response to a variety of environmental stresses and pro-inflammatory cytokines. MEKK4 also plays roles in the re-polarization of the actin cytoskeleton in response to osmotic stress, in the proper closure of the neural tube, in cardiovascular development, and in immune responses. The MEKK4 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 664759227   21 TISTTLRLGR------------QILESIESIHSVGFLHRDIKPSNFAMGRfpSTCRKcyMLDFGLARQFTNScGDVRPPR 88
Cdd:cd06626    85 TLEELLRHGRildeavirvytlQLLEGLAYLHENGIVHRDIKPANIFLDS--NGLIK--LGDFGSAVKLKNN-TTTMAPG 159

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*...
gi 664759227   89 AVAGFRGTVRYAS---INAHRNREMGRHDDLWSLFYMLVEFVVGQLPW 133
Cdd:cd06626   160 EVNSLVGTPAYMApevITGNKGEGHGRAADIWSLGCVVLEMATGKRPW 207

Catalytic domain of the Serine/Threonine kinase, eukaryotic translation Initiation Factor 2-Alpha Kinase 2 or Protein Kinase regulated by RNA; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKR (or EIF2AK2) contains an N-terminal double-stranded RNA (dsRNA) binding domain and a C-terminal catalytic kinase domain. It is activated by dsRNA, which is produced as a replication intermediate in virally infected cells. It plays a key role in mediating innate immune responses to viral infection. PKR is also directly activated by PACT (protein activator of PKR) and heparin, and is inhibited by viral proteins and RNAs. PKR also regulates transcription and signal transduction in diseased cells, playing roles in tumorigenesis and neurodegenerative diseases. EIF2AKs phosphorylate the alpha subunit of eIF-2, resulting in the downregulation of protein synthesis. The PKR 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 664759227   26 LRLGRQILESIESIHSVGFLHRDIKPSNFamgrFPSTCRKCYMLDFGLARQFTNscgdvrpPRAVAGFRGTVRYASINAH 105
Cdd:cd14047   120 LEIFEQITKGVEYIHSKKLIHRDLKPSNI----FLVDTGKVKIGDFGLVTSLKN-------DGKRTKSKGTLSYMSPEQI 188

                          90       100
                  ....*....|....*....|
gi 664759227  106 RNREMGRHDDLWSLFYMLVE 125
Cdd:cd14047   189 SSQDYGKEVDIYALGLILFE 208

Catalytic domain of Mitogen-Activated Protein Kinase (MAPK) Kinase Kinase-like Serine/Threonine kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed mainly of MAP3Ks and similar proteins, including TGF-beta Activated Kinase-1 (TAK1, also called MAP3K7), MAP3K12, MAP3K13, Mixed lineage kinase (MLK), MLK-Like mitogen-activated protein Triple Kinase (MLTK), and Raf (Rapidly Accelerated Fibrosarcoma) kinases. MAP3Ks (MKKKs or MAPKKKs) phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. Also included in this subfamily is the pseudokinase Kinase Suppressor of Ras (KSR), which is a scaffold protein that functions downstream of Ras and upstream of Raf in the Extracellular signal-Regulated Kinase (ERK) pathway.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 664759227    3 LQGRNLADLRRSQSRgTFTISTTLRLGRQILESIESIHSVGFLHRDIKPSNFAMGRFPsTCRKCymlDFGLARqFTNSCG 82
Cdd:cd13999    72 MPGGSLYDLLHKKKI-PLSWSLRLKIALDIARGMNYLHSPPIIHRDLKSLNILLDENF-TVKIA---DFGLSR-IKNSTT 145

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 664759227   83 DVRppravAGFRGTVRYASINAHRNREMGRHDDLWSLFYMLVEFVVGQLPWRKIKDKEQVGSIKERYDHRLMLKHLPPEF 162
Cdd:cd13999   146 EKM-----TGVVGTPRWMAPEVLRGEPYTEKADVYSFGIVLWELLTGEVPFKELSPIQIAAAVVQKGLRPPIPPDCPPEL 220

                  .
gi 664759227  163 S 163
Cdd:cd13999   221 S 221

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 664759227   31 QILESIESIHSVGFLHRDIKPSNFAMGRFPSTCrkcyMLDFGLARQFTN------------SCGDVRPPRAvAGFRGTVR 98
Cdd:cd05581   109 EIVLALEYLHSKGIIHRDLKPENILLDEDMHIK----ITDFGTAKVLGPdsspestkgdadSQIAYNQARA-ASFVGTAE 183

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 664759227   99 YASINAHRNREMGRHDDLWSLFYMLVEFVVGQLPWR 134
Cdd:cd05581   184 YVSPELLNEKPAGKSSDLWALGCIIYQMLTGKPPFR 219

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 664759227   30 RQILESIESIHSVGFLHRDIKPSNFAMgrfpSTCRKCYMLDFGLARQFTNSCGDVRppravagFRGTVRYAS---INAhr 106
Cdd:cd05122   105 KEVLKGLEYLHSHGIIHRDIKAANILL----TSDGEVKLIDFGLSAQLSDGKTRNT-------FVGTPYWMApevIQG-- 171

                          90       100       110
                  ....*....|....*....|....*....|...
gi 664759227  107 nremGRHD---DLWSLFYMLVEFVVGQLPWRKI 136
Cdd:cd05122   172 ----KPYGfkaDIWSLGITAIEMAEGKPPYSEL 200

Catalytic domain of the Serine/Threonine kinase, Mitogen-Activated Protein Kinase (MAPK) Kinase Kinase 8; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAP3K8 is also called Tumor progression locus 2 (Tpl2) or Cancer Osaka thyroid (Cot), and was first identified as a proto-oncogene in T-cell lymphoma induced by MoMuL virus and in breast carcinoma induced by MMTV. Activated MAP3K8 induces various MAPK pathways including Extracellular Regulated Kinase (ERK) 1/2, c-Jun N-terminal kinase (JNK), and p38. It plays a pivotal role in innate immunity, linking Toll-like receptors to the production of TNF and the activation of ERK in macrophages. It is also required in interleukin-1beta production and is critical in host defense against Gram-positive bacteria. MAP3Ks (MKKKs or MAPKKKs) phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. The MAP3K8 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 664759227   30 RQILESIESIHSVGFLHRDIKPSNFAmgrFPSTcrKCYMLDFGLARQFTNscgDVRPPRavaGFRGTVRYASINAHRNRE 109
Cdd:cd13995   103 KHVLKGLDFLHSKNIIHHDIKPSNIV---FMST--KAVLVDFGLSVQMTE---DVYVPK---DLRGTEIYMSPEVILCRG 171

                          90       100
                  ....*....|....*....|....*.
gi 664759227  110 MGRHDDLWSLFYMLVEFVVGQLPWRK 135
Cdd:cd13995   172 HNTKADIYSLGATIIHMQTGSPPWVR 197

Catalytic domain of Fungal Pat1-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 Pat1 (also called Ran1), Saccharomyces cerevisiae VHS1 and KSP1, and similar fungal STKs. Pat1 blocks Mei2, an RNA-binding protein which is indispensable in the initiation of meiosis. Pat1 is inactivated and Mei2 activated, which initiates meiosis, under nutrient-deprived conditions through a signaling cascade involving Ste11. Meiosis induced by Pat1 inactivation may show different characteristics than normal meiosis including aberrant positioning of centromeres. VHS1 was identified in a screen for suppressors of cell cycle arrest at the G1/S transition, while KSP1 may be involved in regulating PRP20, which is required for mRNA export and maintenance of nuclear structure. The Pat1-like 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 664759227   31 QILESIESIHSVGFLHRDIKPSNFAMGRFPSTCRKCymlDFGLARQFTNSCgDVRppravagfRGTVRYAS----INAHR 106
Cdd:cd13993   115 QLIDAVKHCHSLGIYHRDIKPENILLSQDEGTVKLC---DFGLATTEKISM-DFG--------VGSEFYMApecfDEVGR 182

                          90       100       110
                  ....*....|....*....|....*....|.
gi 664759227  107 NREM--GRHDDLWSLFYMLVEFVVGQLPWRK 135
Cdd:cd13993   183 SLKGypCAAGDIWSLGIILLNLTFGRNPWKI 213

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 664759227   10 DLRR--SQSRGTFTISTTLRLGRQILESIESIHSVGFLHRDIKPSNFAMGRfpSTCRKcyMLDFGLARQFT 78
Cdd:cd07829    83 DLKKylDKRPGPLPPNLIKSIMYQLLRGLAYCHSHRILHRDLKPQNLLINR--DGVLK--LADFGLARAFG 149

Catalytic domain of the Serine/Threonine kinase, Aurora kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Aurora kinases are key regulators of mitosis and are essential for the accurate and equal division of genomic material from parent to daughter cells. Yeast contains only one Aurora kinase while most higher eukaryotes have two. Vertebrates contain at least 2 Aurora kinases (A and B); mammals contains a third Aurora kinase gene (C). Aurora-A regulates cell cycle events from the late S-phase through the M-phase including centrosome maturation, mitotic entry, centrosome separation, spindle assembly, chromosome alignment, cytokinesis, and mitotic exit. Aurora-A activation depends on its autophosphorylation and binding to the microtubule-associated protein TPX2. Aurora-B is most active at the transition during metaphase to the end of mitosis. It is critical for accurate chromosomal segregation, cytokinesis, protein localization to the centrosome and kinetochore, correct microtubule-kinetochore attachments, and regulation of the mitotic checkpoint. Aurora-C is mainly expressed in meiotically dividing cells; it was originally discovered in mice as a testis-specific STK called Aie1. Both Aurora-B and -C are chromosomal passenger proteins that can form complexes with INCENP and survivin, and they may have redundant cellular functions. The Aurora subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 664759227   15 QSRGTFTISTTLRLGRQILESIESIHSVGFLHRDIKPSNFAMGrFPSTCRKCymlDFGLARQFTNScgdvrpPRAVagFR 94
Cdd:cd14007    92 KKQKRFDEKEAAKYIYQLALALDYLHSKNIIHRDIKPENILLG-SNGELKLA---DFGWSVHAPSN------RRKT--FC 159

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 664759227   95 GTVRYASinahrnREM---GRHD---DLWSLFYMLVEFVVGQLPWRKIKDKEQVGSIKE-RYDhrlMLKHLPPEFSmflD 167
Cdd:cd14007   160 GTLDYLP------PEMvegKEYDykvDIWSLGVLCYELLVGKPPFESKSHQETYKRIQNvDIK---FPSSVSPEAK---D 227

                  ....*
gi 664759227  168 HISSL 172
Cdd:cd14007   228 LISKL 232

mitogen-activated protein kinase kinase; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 664759227   28 LGRQILESIESIHSVGFLHRDIKPSNFAMgrfpSTCRKCYMLDFGLAR---QFTNSCGDvrpprAVagfrGTVRYAS--- 101
Cdd:PLN00034  173 VARQILSGIAYLHRRHIVHRDIKPSNLLI----NSAKNVKIADFGVSRilaQTMDPCNS-----SV----GTIAYMSper 239

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 664759227  102 INAHRNRemGRHD----DLWSLFYMLVEFVVGQLP 132
Cdd:PLN00034  240 INTDLNH--GAYDgyagDIWSLGVSILEFYLGRFP 272

Catalytic domain of the Serine/Threonine kinase, Checkpoint kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Chk1 is implicated in many major checkpoints of the cell cycle, providing a link between upstream sensors and the cell cycle engine. It plays an important role in DNA damage response and maintaining genomic stability. Chk1 acts as an effector of the sensor kinase, ATR (ATM and Rad3-related), a member of the PI3K family, which is activated upon DNA replication stress. Chk1 delays mitotic entry in response to replication blocks by inhibiting cyclin dependent kinase (Cdk) activity. In addition, Chk1 contributes to the function of centrosome and spindle-based checkpoints, inhibits firing of origins of DNA replication (Ori), and represses transcription of cell cycle proteins including cyclin B and Cdk1. The Chk1 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 664759227   31 QILESIESIHSVGFLHRDIKPSNfamgrfpstcrkcyML----------DFGLARQFTNSCGDvrppRAVAGFRGTVRYA 100
Cdd:cd14069   108 QLMAGLKYLHSCGITHRDIKPEN--------------LLldendnlkisDFGLATVFRYKGKE----RLLNKMCGTLPYV 169

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|..
gi 664759227  101 SINAHRNREM-GRHDDLWSLFYMLVEFVVGQLPWRKIKDKEQ 141
Cdd:cd14069   170 APELLAKKKYrAEPVDVWSCGIVLFAMLAGELPWDQPSDSCQ 211

C-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MSK1 plays a role in the regulation of translational control and transcriptional activation. It phosphorylates the transcription factors, CREB and NFkB. It also phosphorylates the nucleosomal proteins H3 and HMG-14. Increased phosphorylation of MSK1 is associated with the development of cerebral ischemic/hypoxic preconditioning. MSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family. MSKs are activated by two major signaling cascades, the Ras-MAPK and p38 stress kinase pathways, which trigger phosphorylation in the activation loop (A-loop) of the CTD of MSK. The active CTD phosphorylates the hydrophobic motif (HM) of NTD, which facilitates the phosphorylation of the A-loop and activates the NTD, which in turn phosphorylates downstream targets. The MSK1 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 664759227   11 LRRSQSRGTFTISTTLRLGRQILESIESIHSVGFLHRDIKPSNFAMGRfPSTCRKCYMLDFGLARqftnscgdVRPP--R 88
Cdd:cd14179    90 LERIKKKQHFSETEASHIMRKLVSAVSHMHDVGVVHRDLKPENLLFTD-ESDNSEIKIIDFGFAR--------LKPPdnQ 160

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*.
gi 664759227   89 AVAGFRGTVRYASINAHRNREMGRHDDLWSLFYMLVEFVVGQLPWR 134
Cdd:cd14179   161 PLKTPCFTLHYAAPELLNYNGYDESCDLWSLGVILYTMLSGQVPFQ 206

Catalytic domain of an Uncharacterized subfamily of Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase 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 uncharacterized proteins with similarity to MEKK3, MEKK2, and related proteins; they contain an N-terminal PB1 domain, which mediates oligomerization, and a C-terminal catalytic domain. MEKK2 and MEKK3 are MAPK kinase kinases (MAPKKKs or MKKKs), proteins that phosphorylate and activate MAPK kinases (MAPKKs or MKKs), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. MEKK2 and MEKK3 activate MEK5 (also called MKK5), which activates ERK5. The ERK5 cascade plays roles in promoting cell proliferation, differentiation, neuronal survival, and neuroprotection. MEKK3 plays an essential role in embryonic angiogenesis and early heart development. MEKK2 and MEKK3 can also activate the MAPKs, c-Jun N-terminal kinase (JNK) and p38, through their respective MAPKKs. The MEKK3-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 664759227   15 QSRGTFTISTTLRLGRQILESIESIHSVGFLHRDIKPSNFamgrFPSTCRKCYMLDFGLARQFTNSCgdvRPPRAVAGFR 94
Cdd:cd06653    98 KAYGALTENVTRRYTRQILQGVSYLHSNMIVHRDIKGANI----LRDSAGNVKLGDFGASKRIQTIC---MSGTGIKSVT 170

                          90       100       110
                  ....*....|....*....|....*....|....*....
gi 664759227   95 GTVRYASINAHRNREMGRHDDLWSLFYMLVEFVVGQLPW 133
Cdd:cd06653   171 GTPYWMSPEVISGEGYGRKADVWSVACTVVEMLTEKPPW 209