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 145340316 401 YTIVEEEGSGGYGIVYKATRKTD-------GTEFAIKCPHVGAQKYYVNNEIRMLERFGGKNCIIKHEGCLKNGDSDCII 473
Cdd:cd14019    3 YRIIEKIGEGTFSSVYKAEDKLHdlydrnkGRLVALKHIYPTSSPSRILNELECLERLGGSNNVSGLITAFRNEDQVVAV 82

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 145340316 474 LEHLEHDRPDSLKREIDVYQLQWYGYCMFKALSSLHKQGVVHRDVKPGNFLFSRKTNKGYLIDFNLAMDLHQKyrradks 553
Cdd:cd14019   83 LPYIEHDDFRDFYRKMSLTDIRIYLRNLFKALKHVHSFGIIHRDVKPGNFLYNRETGKGVLVDFGLAQREEDR------- 155

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 145340316 554 kaasglptaskkhhtlvksldavnrgtnkpsqktlapnsikkaagktrarndmtrwerlnsqgaegsgltsakdvtstrn 633
Cdd:cd14019      --------------------------------------------------------------------------------

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 145340316 634 npsgekrreplpcHGRKAlldflqetmsvpipnhevsskaptsmrkrvaalpgkaekellyltpmplcsngrpeagdvie 713
Cdd:cd14019  156 -------------PEQRA-------------------------------------------------------------- 160

                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 145340316 714 kkdgPCSGTKGFRAPEVCFRSLHQGPKIDVWSAGVTLLYLIMGRTPFTG--DPEQNIKDIAQLRGSEElwevaklhnres 791
Cdd:cd14019  161 ----PRAGTRGFRAPEVLFKCPHQTTAIDIWSAGVILLSILSGRFPFFFssDDIDALAEIATIFGSDE------------ 224

                        410       420       430       440       450       460
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 145340316 792 sfpkelyesrylkgmelrkwcelntkrrefldviplsLLDLVDKCLTVNPRRRISAEDALKHDFF 856
Cdd:cd14019  225 -------------------------------------AYDLLDKLLELDPSKRITAEEALKHPFF 252

Catalytic domain of the Serine/Threonine Kinase, Cell Division Cycle 7 kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Cdc7 kinase (or Hsk1 in fission yeast) is a critical regulator in the initiation of DNA replication. It forms a complex with a Dbf4-related regulatory subunit, a cyclin-like molecule that activates the kinase in late G1 phase, and is also referred to as Dbf4-dependent kinase (DDK). Its main targets are mini-chromosome maintenance (MCM) proteins. Cdc7 kinase may also have additional roles in meiosis, checkpoint responses, the maintenance and repair of chromosome structures, and cancer progression. The Cdc7 kinase 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 145340316 401 YTIVEEEGSGGYGIVYKATRKTD-------GTEFAIKCPHVGAQKYYVNNEIRMLERFGGKNCIIKHEGCLKNGDSDCII 473
Cdd:cd14019    3 YRIIEKIGEGTFSSVYKAEDKLHdlydrnkGRLVALKHIYPTSSPSRILNELECLERLGGSNNVSGLITAFRNEDQVVAV 82

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 145340316 474 LEHLEHDRPDSLKREIDVYQLQWYGYCMFKALSSLHKQGVVHRDVKPGNFLFSRKTNKGYLIDFNLAMDLHQKyrradks 553
Cdd:cd14019   83 LPYIEHDDFRDFYRKMSLTDIRIYLRNLFKALKHVHSFGIIHRDVKPGNFLYNRETGKGVLVDFGLAQREEDR------- 155

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 145340316 554 kaasglptaskkhhtlvksldavnrgtnkpsqktlapnsikkaagktrarndmtrwerlnsqgaegsgltsakdvtstrn 633
Cdd:cd14019      --------------------------------------------------------------------------------

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 145340316 634 npsgekrreplpcHGRKAlldflqetmsvpipnhevsskaptsmrkrvaalpgkaekellyltpmplcsngrpeagdvie 713
Cdd:cd14019  156 -------------PEQRA-------------------------------------------------------------- 160

                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 145340316 714 kkdgPCSGTKGFRAPEVCFRSLHQGPKIDVWSAGVTLLYLIMGRTPFTG--DPEQNIKDIAQLRGSEElwevaklhnres 791
Cdd:cd14019  161 ----PRAGTRGFRAPEVLFKCPHQTTAIDIWSAGVILLSILSGRFPFFFssDDIDALAEIATIFGSDE------------ 224

                        410       420       430       440       450       460
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 145340316 792 sfpkelyesrylkgmelrkwcelntkrrefldviplsLLDLVDKCLTVNPRRRISAEDALKHDFF 856
Cdd:cd14019  225 -------------------------------------AYDLLDKLLELDPSKRITAEEALKHPFF 252

Protein kinase domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 145340316  721 GTKGFRAPEVcFRSLHQGPKIDVWSAGVTLLYLIMGRTPFTGDPEQNI--KDIAQLRGSEELWevaklhnressfpkely 798
Cdd:pfam00069 122 GTPWYMAPEV-LGGNPYGPKVDVWSLGCILYELLTGKPPFPGINGNEIyeLIIDQPYAFPELP----------------- 183

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 145340316  799 esrylkgmelrkwcelntkrreflDVIPLSLLDLVDKCLTVNPRRRISAEDALKHDFF 856
Cdd:pfam00069 184 ------------------------SNLSEEAKDLLKKLLKKDPSKRLTATQALQHPWF 217

cyclin-dependent protein kinase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 145340316 725 FRAPEVCFRSLHQGPKIDVWSAGVTLLYLIMGRTPFTGDPE-QNIKDIAQLRGSEElwevaklhnrESSFPkelyESRYL 803
Cdd:PTZ00024 199 YRAPELLMGAEKYHFAVDMWSVGCIFAELLTGKPLFPGENEiDQLGRIFELLGTPN----------EDNWP----QAKKL 264

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 145340316 804 KgmelrKWCELN-TKRREFLDVIPL---SLLDLVDKCLTVNPRRRISAEDALKHDFF 856
Cdd:PTZ00024 265 P-----LYTEFTpRKPKDLKTIFPNasdDAIDLLQSLLKLNPLERISAKEALKHEYF 316

Stk1 family PASTA domain-containing Ser/Thr kinase;

                         10        20
                 ....*....|....*....|....
gi 145340316 504 ALSSLHKQGVVHRDVKPGNFLFSR 527
Cdd:NF033483 119 ALEHAHRNGIVHRDIKPQNILITK 142

Catalytic domain of the Serine/Threonine Kinase, Cell Division Cycle 7 kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Cdc7 kinase (or Hsk1 in fission yeast) is a critical regulator in the initiation of DNA replication. It forms a complex with a Dbf4-related regulatory subunit, a cyclin-like molecule that activates the kinase in late G1 phase, and is also referred to as Dbf4-dependent kinase (DDK). Its main targets are mini-chromosome maintenance (MCM) proteins. Cdc7 kinase may also have additional roles in meiosis, checkpoint responses, the maintenance and repair of chromosome structures, and cancer progression. The Cdc7 kinase 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 145340316 401 YTIVEEEGSGGYGIVYKATRKTD-------GTEFAIKCPHVGAQKYYVNNEIRMLERFGGKNCIIKHEGCLKNGDSDCII 473
Cdd:cd14019    3 YRIIEKIGEGTFSSVYKAEDKLHdlydrnkGRLVALKHIYPTSSPSRILNELECLERLGGSNNVSGLITAFRNEDQVVAV 82

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 145340316 474 LEHLEHDRPDSLKREIDVYQLQWYGYCMFKALSSLHKQGVVHRDVKPGNFLFSRKTNKGYLIDFNLAMDLHQKyrradks 553
Cdd:cd14019   83 LPYIEHDDFRDFYRKMSLTDIRIYLRNLFKALKHVHSFGIIHRDVKPGNFLYNRETGKGVLVDFGLAQREEDR------- 155

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 145340316 554 kaasglptaskkhhtlvksldavnrgtnkpsqktlapnsikkaagktrarndmtrwerlnsqgaegsgltsakdvtstrn 633
Cdd:cd14019      --------------------------------------------------------------------------------

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 145340316 634 npsgekrreplpcHGRKAlldflqetmsvpipnhevsskaptsmrkrvaalpgkaekellyltpmplcsngrpeagdvie 713
Cdd:cd14019  156 -------------PEQRA-------------------------------------------------------------- 160

                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 145340316 714 kkdgPCSGTKGFRAPEVCFRSLHQGPKIDVWSAGVTLLYLIMGRTPFTG--DPEQNIKDIAQLRGSEElwevaklhnres 791
Cdd:cd14019  161 ----PRAGTRGFRAPEVLFKCPHQTTAIDIWSAGVILLSILSGRFPFFFssDDIDALAEIATIFGSDE------------ 224

                        410       420       430       440       450       460
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 145340316 792 sfpkelyesrylkgmelrkwcelntkrrefldviplsLLDLVDKCLTVNPRRRISAEDALKHDFF 856
Cdd:cd14019  225 -------------------------------------AYDLLDKLLELDPSKRITAEEALKHPFF 252

Catalytic domain of Protein Kinases; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine or tyrosine residues on protein substrates. PKs make up a large family of serine/threonine kinases (STKs), protein tyrosine kinases (PTKs), and dual-specificity PKs that phosphorylate both serine/threonine and tyrosine residues of target proteins. Majority of protein phosphorylation occurs on serine residues while only 1% occurs on tyrosine residues. Protein phosphorylation is a mechanism by which a wide variety of cellular proteins, such as enzymes and membrane channels, are reversibly regulated in response to certain stimuli. PKs often function as components of signal transduction pathways in which one kinase activates a second kinase, which in turn, may act on other kinases; this sequential action transmits a signal from the cell surface to target proteins, which results in cellular responses. The PK family is one of the largest known protein families with more than 100 homologous yeast enzymes and more than 500 human proteins. A fraction of PK family members are pseudokinases that lack crucial residues for catalytic activity. The mutiplicity of kinases allows for specific regulation according to substrate, tissue distribution, and cellular localization. PKs regulate many cellular processes including proliferation, division, differentiation, motility, survival, metabolism, cell-cycle progression, cytoskeletal rearrangement, immunity, and neuronal functions. Many kinases are implicated in the development of various human diseases including different types of cancer. The PK family is part of a larger superfamily that includes the catalytic domains of RIO kinases, aminoglycoside phosphotransferase, choline kinase, phosphoinositide 3-kinase (PI3K), and actin-fragmin kinase.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 145340316 408 GSGGYGIVYKATRKTDGTEFAIKC---PHVGAQKYYVNNEIRMLERFGGKNcIIKHEGCLKNGDSDCIILEHLE----HD 480
Cdd:cd00180    2 GKGSFGKVYKARDKETGKKVAVKVipkEKLKKLLEELLREIEILKKLNHPN-IVKLYDVFETENFLYLVMEYCEggslKD 80

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 145340316 481 RPDSLKREIDVYQLQWYGYCMFKALSSLHKQGVVHRDVKPGNFLFSRKtNKGYLIDFNLA 540
Cdd:cd00180   81 LLKENKGPLSEEEALSILRQLLSALEYLHSNGIIHRDLKPENILLDSD-GTVKLADFGLA 139

Catalytic domain of the Serine/Threonine protein kinase, Casein Kinase 1; 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. Some isoforms have several splice variants such as the long (L) and short (S) variants of CK1alpha. CK1 proteins are involved in the regulation of many cellular processes including membrane transport processes, circadian rhythm, cell division, apoptosis, and the development of cancer and neurodegenerative diseases. The CK1 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 145340316 401 YTIVEEEGSGGYGIVYKATRKTDGTEFAIKCPHVGAQKYYVNNEIRMLERFGGKNCI--IKHEGclKNGDSDCII----- 473
Cdd:cd14016    2 YKLVKKIGSGSFGEVYLGIDLKTGEEVAIKIEKKDSKHPQLEYEAKVYKLLQGGPGIprLYWFG--QEGDYNVMVmdllg 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 145340316 474 --LEHL--EHDRPDSLKReidVYQLqwyGYCMFKALSSLHKQGVVHRDVKPGNFLF--SRKTNKGYLIDFNLAMdlhqKY 547
Cdd:cd14016   80 psLEDLfnKCGRKFSLKT---VLML---ADQMISRLEYLHSKGYIHRDIKPENFLMglGKNSNKVYLIDFGLAK----KY 149

                 .
gi 145340316 548 R 548
Cdd:cd14016  150 R 150

Catalytic domain of Cyclin-Dependent protein Kinase 9-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 CDK9 and CDK12 from higher eukaryotes, yeast BUR1, C-type plant CDKs (CdkC), and similar proteins. CDK9, BUR1, and CdkC are functionally equivalent. They act as a kinase for the C-terminal domain of RNA polymerase II and participate in regulating mutliple steps of gene expression including transcription elongation and RNA processing. CDK9 and CdkC associate with T-type cyclins while BUR1 associates with the cyclin BUR2. CDK12 is a unique CDK that contains an arginine/serine-rich (RS) domain, which is predominantly found in splicing factors. CDK12 interacts with cyclins L1 and L2, and participates in regulating transcription and alternative splicing. 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-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 145340316 725 FRAPEVCFRSLHQGPKIDVWSAGVTLLYLIMGRTPFTGDPEQN-IKDIAQLRGS--EELW-EVAKLHNRESSFPKELYES 800
Cdd:cd07840  171 YRPPELLLGATRYGPEVDMWSVGCILAELFTGKPIFQGKTELEqLEKIFELCGSptEENWpGVSDLPWFENLKPKKPYKR 250

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 145340316 801 RylkgmelrkwcelntKRREFLDVIPLSLLDLVDKCLTVNPRRRISAEDALKHDFF 856
Cdd:cd07840  251 R---------------LREVFKNVIDPSALDLLDKLLTLDPKKRISADQALQHEYF 291

The catalytic domain of CAMK family Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CaMKs are multifunctional calcium and calmodulin (CaM) stimulated STKs involved in cell cycle regulation. There are several types of CaMKs including CaMKI, CaMKII, and CaMKIV. CaMKI proteins are monomeric and they play pivotal roles in the nervous system, including long-term potentiation, dendritic arborization, neurite outgrowth, and the formation of spines, synapses, and axons. CaMKII is a signaling molecule that translates upstream calcium and reactive oxygen species (ROS) signals into downstream responses that play important roles in synaptic function and cardiovascular physiology. CAMKIV is implicated in regulating several transcription factors like CREB, MEF2, and retinoid orphan receptors, as well as in T-cell development and signaling. The CAMK family also consists of other related kinases including the Phosphorylase kinase Gamma subunit (PhKG), the C-terminal kinase domains of Ribosomal S6 kinase (RSK) and Mitogen and stress-activated kinase (MSK), Doublecortin-like kinase (DCKL), and the MAPK-activated protein kinases MK2, MK3, and MK5, among others. The CAMK family 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 145340316 401 YTIVEEEGSGGYGIVYKATRKTDGTEFAIKC----PHVGAQKYYVNNEIRMLERFGGKNcIIKHEGCLKNGDSDCIILEH 476
Cdd:cd05117    2 YELGKVLGRGSFGVVRLAVHKKTGEEYAVKIidkkKLKSEDEEMLRREIEILKRLDHPN-IVKLYEVFEDDKNLYLVMEL 80

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 145340316 477 LE----HDRPDSLKR--EIDVyqlQWYGYCMFKALSSLHKQGVVHRDVKPGNFLFSRKTNKG--YLIDFNLAMDLHQKY 547
Cdd:cd05117   81 CTggelFDRIVKKGSfsEREA---AKIMKQILSAVAYLHSQGIVHRDLKPENILLASKDPDSpiKIIDFGLAKIFEEGE 156

Catalytic domain of CMGC family Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The CMGC family consists of Cyclin-Dependent protein Kinases (CDKs), Mitogen-activated protein kinases (MAPKs) such as Extracellular signal-regulated kinase (ERKs), c-Jun N-terminal kinases (JNKs), and p38, and other kinases. CDKs belong to a large subfamily of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. MAPKs serve as important mediators of cellular responses to extracellular signals. They control critical cellular functions including differentiation, proliferation, migration, and apoptosis. They are also implicated in the pathogenesis of many diseases including multiple types of cancer, stroke, diabetes, and chronic inflammation. Other members of the CMGC family include casein kinase 2 (CK2), Dual-specificity tYrosine-phosphorylated and -Regulated Kinase (DYRK), Glycogen Synthase Kinase 3 (GSK3), among many others. The CMGC family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 145340316 401 YTIVEEEGSGGYGIVYKATRKTDGTEFAIKcpHVGAQKYYVNN---EIRMLERF----GGKNCI-----IKHEGclknGD 468
Cdd:cd05118    1 YEVLRKIGEGAFGTVWLARDKVTGEKVAIK--KIKNDFRHPKAalrEIKLLKHLndveGHPNIVklldvFEHRG----GN 74

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 145340316 469 SDCIILEHLEHDRPDSLK---REIDVYQLQWYGYCMFKALSSLHKQGVVHRDVKPGNFLFSRKTNKGYLIDFNLAMDLHQ 545
Cdd:cd05118   75 HLCLVFELMGMNLYELIKdypRGLPLDLIKSYLYQLLQALDFLHSNGIIHRDLKPENILINLELGQLKLADFGLARSFTS 154

                 ..
gi 145340316 546 KY 547
Cdd:cd05118  155 PP 156

Serine/threonine protein kinase [Signal transduction mechanisms];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 145340316 398 FDSYTIVEEEGSGGYGIVYKATRKTDGTEFAIKC--PHVGAQKYYVN---NEIRMLERFGGKNcIIKHEGCLKNGDSDCI 472
Cdd:COG0515    6 LGRYRILRLLGRGGMGVVYLARDLRLGRPVALKVlrPELAADPEARErfrREARALARLNHPN-IVRVYDVGEEDGRPYL 84

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 145340316 473 ILEHLEHDrpdSLKREI------DVYQLQWYGYCMFKALSSLHKQGVVHRDVKPGNFLFSRkTNKGYLIDFNLA 540
Cdd:COG0515   85 VMEYVEGE---SLADLLrrrgplPPAEALRILAQLAEALAAAHAAGIVHRDIKPANILLTP-DGRVKLIDFGIA 154

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 145340316 725 FRAPEVCFRSLHQGPKIDVWSAGVtllylIMG----RTP-FTGDPEQN-IKDIAQLRGS--EELW-EVAKLhnressfpk 795
Cdd:cd07865  189 YRPPELLLGERDYGPPIDMWGAGC-----IMAemwtRSPiMQGNTEQHqLTLISQLCGSitPEVWpGVDKL--------- 254

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 145340316 796 ELYESrylkgMELRKwcelNTKRREFLDVIP----LSLLDLVDKCLTVNPRRRISAEDALKHDFF 856
Cdd:cd07865  255 ELFKK-----MELPQ----GQKRKVKERLKPyvkdPYALDLIDKLLVLDPAKRIDADTALNHDFF 310

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 145340316 401 YTIVEEEGSGGYGIVYKATRKTDGTEFAIKC--PHVGAQKYYVN---NEIRMLERFGGKNcIIK------HEGCLkngds 469
Cdd:cd14014    2 YRLVRLLGRGGMGEVYRARDTLLGRPVAIKVlrPELAEDEEFRErflREARALARLSHPN-IVRvydvgeDDGRP----- 75

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 145340316 470 dCIILEHLEHDrpdSLKREIDVYQLQWYGYC------MFKALSSLHKQGVVHRDVKPGNFLFSrKTNKGYLIDFNLA 540
Cdd:cd14014   76 -YIVMEYVEGG---SLADLLRERGPLPPREAlrilaqIADALAAAHRAGIVHRDIKPANILLT-EDGRVKLTDFGIA 147

Catalytic domain of Cell division control protein 7-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Members of this subfamily include Schizosaccharomyces pombe Cdc7, Saccharomyces cerevisiae Cdc15, Arabidopsis thaliana mitogen-activated protein kinase kinase kinase (MAPKKK) epsilon, and related proteins. MAPKKKs phosphorylate and activate MAPK kinases, which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. Fission yeast Cdc7 is essential for cell division by playing a key role in the initiation of septum formation and cytokinesis. Budding yeast Cdc15 functions to coordinate mitotic exit with cytokinesis. Arabidopsis MAPKKK epsilon is required for pollen development in the plasma membrane. The Cdc7-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 145340316 401 YTIVEEEGSGGYGIVYKATRKTDGTEFAIKCPHV----GAQKYYVNNEIRMLERFGGKNcIIKHEGCLKNGDSDCIILEH 476
Cdd:cd06627    2 YQLGDLIGRGAFGSVYKGLNLNTGEFVAIKQISLekipKSDLKSVMGEIDLLKKLNHPN-IVKYIGSVKTKDSLYIILEY 80

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 145340316 477 LEHDrpdSLKREIDVY------QLQWYGYCMFKALSSLHKQGVVHRDVKPGNFLfsrkTNKGYLI---DFNLA 540
Cdd:cd06627   81 VENG---SLASIIKKFgkfpesLVAVYIYQVLEGLAYLHEQGVIHRDIKGANIL----TTKDGLVklaDFGVA 146

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 145340316 721 GTKGFRAPEVCFRSLHQGPKIDVWSAGVTLLYLIMGRTPFTG-DPEQNIKDIAQLRG--SEELweVAKLhnrESSFPKEl 797
Cdd:cd07851  177 ATRWYRAPEIMLNWMHYNQTVDIWSVGCIMAELLTGKTLFPGsDHIDQLKRIMNLVGtpDEEL--LKKI---SSESARN- 250

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 145340316 798 yesrYLKGMELRkwcelntKRREFLDVIPLS---LLDLVDKCLTVNPRRRISAEDALKHDFFHPVH 860
Cdd:cd07851  251 ----YIQSLPQM-------PKKDFKEVFSGAnplAIDLLEKMLVLDPDKRITAAEALAHPYLAEYH 305

Catalytic domain of Cyclin-Dependent protein Kinase 1-like Serine/Threonine Kinases and of Plant B-type Cyclin-Dependent protein Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of CDK, CDK2, and CDK3. CDK1 is also called Cell division control protein 2 (Cdc2) or p34 protein kinase, and is regulated by cyclins A, B, and E. The CDK1/cyclin A complex controls G2 phase entry and progression while the CDK1/cyclin B complex is critical for G2 to M phase transition. CDK2 is regulated by cyclin E or cyclin A. Upon activation by cyclin E, it phosphorylates the retinoblastoma (pRb) protein which activates E2F mediated transcription and allows cells to move into S phase. The CDK2/cyclin A complex plays a role in regulating DNA replication. Studies in knockout mice revealed that CDK1 can compensate for the loss of the cdk2 gene as it can also bind cyclin E and drive G1 to S phase transition. CDK3 is regulated by cyclin C and it phosphorylates pRB specifically during the G0/G1 transition. This phosphorylation is required for cells to exit G0 efficiently and enter the G1 phase. The plant-specific B-type CDKs are expressed from the late S to the M phase of the cell cycle. They are characterized by the cyclin binding motif PPT[A/T]LRE. They play a role in controlling mitosis and integrating developmental pathways, such as stomata and leaf development. CdkB has been shown to associate with both cyclin B, which controls G2/M transition, and cyclin D, which acts as a mediator in linking extracellular signals to the cell cycle. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 145340316 725 FRAPEVCFRSLHQGPKIDVWSAGVTLLYLIMGRTPFTGDPE-QNIKDIAQLRGS--EELW-EVAKLHNRESSFPKelyes 800
Cdd:cd07835  165 YRAPEILLGSKHYSTPVDIWSVGCIFAEMVTRRPLFPGDSEiDQLFRIFRTLGTpdEDVWpGVTSLPDYKPTFPK----- 239

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 145340316 801 rylkgmelrkWcelntKRREFLDVIPlSL----LDLVDKCLTVNPRRRISAEDALKHDFF 856
Cdd:cd07835  240 ----------W-----ARQDLSKVVP-SLdedgLDLLSQMLVYDPAKRISAKAALQHPYF 283

Catalytic domain of the Serine/Threonine kinases, Liver Kinase B1, Calmodulin Dependent Protein Kinase Kinase, and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Both LKB1 and CaMKKs can phosphorylate and activate AMP-activated protein kinase (AMPK). LKB1, also called STK11, serves as a master upstream kinase that activates AMPK and most AMPK-like kinases. LKB1 and AMPK are part of an energy-sensing pathway that links cell energy to metabolism and cell growth. They play critical roles in the establishment and maintenance of cell polarity, cell proliferation, cytoskeletal organization, as well as T-cell metabolism, including T-cell development, homeostasis, and effector function. CaMKKs are upstream kinases of the CaM kinase cascade that phosphorylate and activate CaMKI and CamKIV. They may also phosphorylate other substrates including PKB and AMPK. Vertebrates contain two CaMKKs, CaMKK1 (or alpha) and CaMKK2 (or beta). CaMKK1 is involved in the regulation of glucose uptake in skeletal muscles. CaMKK2 is involved in regulating energy balance, glucose metabolism, adiposity, hematopoiesis, inflammation, and cancer. The LKB1/CaMKK 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 145340316 711 VIEKKDGPCSGTKG---FRAPEVCF--RSLHQGPKIDVWSAGVTLLYLIMGRTPFTGDPEQnikdiaqlrgseELWEVAK 785
Cdd:cd14008  157 MFEDGNDTLQKTAGtpaFLAPELCDgdSKTYSGKAADIWALGVTLYCLVFGRLPFNGDNIL------------ELYEAIQ 224

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 145340316 786 LHNRESSFPKELYEsrylkgmELRkwcelntkrrefldviplsllDLVDKCLTVNPRRRISAEDALKHDFF 856
Cdd:cd14008  225 NQNDEFPIPPELSP-------ELK---------------------DLLRRMLEKDPEKRITLKEIKEHPWV 267

Catalytic domain of the Serine/Threonine Kinases, Chlamydomonas reinhardtii CNK2 and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Chlamydomonas reinhardtii CNK2 has both cilliary and cell cycle functions. It influences flagellar length through promoting flagellar disassembly, and it regulates cell size, through influencing the size threshold at which cells commit to mitosis. This subfamily belongs to the (NIMA)-related kinase (Nek) family, which includes seven different Chlamydomonas Neks (CNKs 1-6 and Fa2). This subfamily includes CNK1, and -2. The Nek 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 145340316 401 YTIVEEEGSGGYGIVYKATRKTDGTEFAIKCPHVG----AQKYYVNNEIRMLERFGGKNCIIKHEGCLkNGDSDCIILEH 476
Cdd:cd08530    2 FKVLKKLGKGSYGSVYKVKRLSDNQVYALKEVNLGslsqKEREDSVNEIRLLASVNHPNIIRYKEAFL-DGNRLCIVMEY 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 145340316 477 lehdRPDS-LKREIDVYQLQ---------W-YGYCMFKALSSLHKQGVVHRDVKPGNFLFSRktnkGYLI---DFNLAMD 542
Cdd:cd08530   81 ----APFGdLSKLISKRKKKrrlfpeddiWrIFIQMLRGLKALHDQKILHRDLKSANILLSA----GDLVkigDLGISKV 152

                 ...
gi 145340316 543 LHQ 545
Cdd:cd08530  153 LKK 155

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 145340316 408 GSGGYGIVYKATRKTDGTEFAIKCPHVG--AQKYY--VNNEIRMLERFGGKNcIIKHEGCLKNGDSDCIILEHLehdrP- 482
Cdd:cd06606    9 GKGSFGSVYLALNLDTGELMAVKEVELSgdSEEELeaLEREIRILSSLKHPN-IVRYLGTERTENTLNIFLEYV----Pg 83

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 145340316 483 ----DSLKR-------EIDVYQLQwygycMFKALSSLHKQGVVHRDVKPGN-FLFSRKTNKgyLIDFNLAMDLHQ 545
Cdd:cd06606   84 gslaSLLKKfgklpepVVRKYTRQ-----ILEGLEYLHSNGIVHRDIKGANiLVDSDGVVK--LADFGCAKRLAE 151

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 145340316 725 FRAPEVCFRSLHQGPKIDVWSAGVTLLYLIMGRTPFTGDPEQN-IKDIAQLRG--SEELW-EVAKL-HNRESSFPKELYe 799
Cdd:cd07843  172 YRAPELLLGAKEYSTAIDMWSVGCIFAELLTKKPLFPGKSEIDqLNKIFKLLGtpTEKIWpGFSELpGAKKKTFTKYPY- 250

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 145340316 800 srylkgmelrkwcelNTKRREFLdviPLSL----LDLVDKCLTVNPRRRISAEDALKHDFF 856
Cdd:cd07843  251 ---------------NQLRKKFP---ALSLsdngFDLLNRLLTYDPAKRISAEDALKHPYF 293