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 208431817 145 GSGYTKAVYRVRLPGGAAVALKAVDFSGHDlgscvrefgvrrgcyRLAAHKLLKEMVLLERLRH-PNVLQLYGYCYQDSe 223
Cdd:cd14131   10 GKGGSSKVYKVLNPKKKIYALKRVDLEGAD---------------EQTLQSYKNEIELLKKLKGsDRIIQLYDYEVTDE- 73

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 208431817 224 diPDTLTTITELGApVEMIQLLQTSWE----DRFRI-----CLSLGRLLHH--LAHSplgsvtllDFRPRQFVLVDGELK 292
Cdd:cd14131   74 --DDYLYMVMECGE-IDLATILKKKRPkpidPNFIRyywkqMLEAVHTIHEegIVHS--------DLKPANFLLVKGRLK 142

                 ...
gi 208431817 293 VTD 295
Cdd:cd14131  143 LID 145

Catalytic domain of the Dual-specificity Mitotic checkpoint protein kinase, Monopolar spindle 1 (also called TTK); Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine as well as tyrosine residues on protein substrates. TTK/Mps1 is a spindle checkpoint kinase that was first discovered due to its necessity in centrosome duplication in budding yeast. It was later found to function in the spindle assembly checkpoint, which monitors the proper attachment of chromosomes to the mitotic spindle. In yeast, substrates of Mps1 include the spindle pole body components Spc98p, Spc110p, and Spc42p. The TTK/Mps1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein serine/threonine PKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 208431817 145 GSGYTKAVYRVRLPGGAAVALKAVDFSGHDlgscvrefgvrrgcyRLAAHKLLKEMVLLERLRH-PNVLQLYGYCYQDSe 223
Cdd:cd14131   10 GKGGSSKVYKVLNPKKKIYALKRVDLEGAD---------------EQTLQSYKNEIELLKKLKGsDRIIQLYDYEVTDE- 73

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 208431817 224 diPDTLTTITELGApVEMIQLLQTSWE----DRFRI-----CLSLGRLLHH--LAHSplgsvtllDFRPRQFVLVDGELK 292
Cdd:cd14131   74 --DDYLYMVMECGE-IDLATILKKKRPkpidPNFIRyywkqMLEAVHTIHEegIVHS--------DLKPANFLLVKGRLK 142

                 ...
gi 208431817 293 VTD 295
Cdd:cd14131  143 LID 145

Tyrosine kinase, catalytic domain; Phosphotransferases. Tyrosine-specific kinase subfamily.

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 208431817   172 GHDLGSCvrEFG-VRRGCYRLAAHK---------------------LLKEMVLLERLRHPNVLQLYGYCYQD 221
Cdd:smart00219   4 GKKLGEG--AFGeVYKGKLKGKGGKkkvevavktlkedaseqqieeFLREARIMRKLDHPNVVKLLGVCTEE 73

Catalytic domain of the Dual-specificity Mitotic checkpoint protein kinase, Monopolar spindle 1 (also called TTK); Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine as well as tyrosine residues on protein substrates. TTK/Mps1 is a spindle checkpoint kinase that was first discovered due to its necessity in centrosome duplication in budding yeast. It was later found to function in the spindle assembly checkpoint, which monitors the proper attachment of chromosomes to the mitotic spindle. In yeast, substrates of Mps1 include the spindle pole body components Spc98p, Spc110p, and Spc42p. The TTK/Mps1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein serine/threonine PKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 208431817 145 GSGYTKAVYRVRLPGGAAVALKAVDFSGHDlgscvrefgvrrgcyRLAAHKLLKEMVLLERLRH-PNVLQLYGYCYQDSe 223
Cdd:cd14131   10 GKGGSSKVYKVLNPKKKIYALKRVDLEGAD---------------EQTLQSYKNEIELLKKLKGsDRIIQLYDYEVTDE- 73

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 208431817 224 diPDTLTTITELGApVEMIQLLQTSWE----DRFRI-----CLSLGRLLHH--LAHSplgsvtllDFRPRQFVLVDGELK 292
Cdd:cd14131   74 --DDYLYMVMECGE-IDLATILKKKRPkpidPNFIRyywkqMLEAVHTIHEegIVHS--------DLKPANFLLVKGRLK 142

                 ...
gi 208431817 293 VTD 295
Cdd:cd14131  143 LID 145

Protein-kinase domain of FAM69; This is the C-terminal region of a family of FAM69 proteins from Metazoa and Viridiplantae that are active protein-kinases. The family members have a short transmembrane helix close to the N-terminus, and thereafter are highly enriched with cysteines. FAM69 proteins are localized to the endoplasmic reticulum. Many members also have a short EF-hand, calcium-binding, domain just upstream of the kinase domain. The exact function of the more N-terminal family is uncertain.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 208431817  200 MVLLERLRHpnVLQLYGYC--YQDSEDIPDTLTtiteLGAPVEMIQLLQTSWEDRFRICLSLGRLLHHLAHSPLGSVTLL 277
Cdd:pfam12260  13 LQIFQDREP--FPKYLGSCgrLYVVEYVGAGPL----LGISRRPLDWFSPPWPRRAKIALQLLELVEDLFNGDPGFLYMC 86

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 208431817  278 DFRPRQF-VLVDGELKVTDLD--------DARVEETPCAGSTDCILEFparNFTLPCSAQGWCEGMNEKRNLYNAYRFFF 348
Cdd:pfam12260  87 DVSLENFgVTNDGRLKLVDLDnvfpedklRRKISEQKCEKDEDCDFFD---CLSFCDLEKDRCSSEVVNPNLQKVCQKLL 163

                         170       180
                  ....*....|....*....|..
gi 208431817  349 TYLLpHSAPPSLRPLLDSIVNA 370
Cdd:pfam12260 164 DYLL-RGPPSPLPEELEKLLQE 184

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 208431817 145 GSGYTKAVYRVR-LPGGAAVALKAVDFSGHDLgscvrefgvrrgcyrlAAHKLLKEMVLLERLRHPNVLQLYGYCYQDse 223
Cdd:cd00180    2 GKGSFGKVYKARdKETGKKVAVKVIPKEKLKK----------------LLEELLREIEILKKLNHPNIVKLYDVFETE-- 63

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 208431817 224 dipDTLTTITELGAPVEMIQLLQT-----SWEDRFRICLSLGRLLHHLaHSpLGsVTLLDFRPRQFVLV-DGELKVTDLD 297
Cdd:cd00180   64 ---NFLYLVMEYCEGGSLKDLLKEnkgplSEEEALSILRQLLSALEYL-HS-NG-IIHRDLKPENILLDsDGTVKLADFG 137

                        170       180
                 ....*....|....*....|..
gi 208431817 298 DARVEETPCAGSTDCILEFPAR 319
Cdd:cd00180  138 LAKDLDSDDSLLKTTGGTTPPY 159

Catalytic domain of the Dual-specificity protein kinase, Testicular protein kinase; Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine as well as tyrosine residues on protein substrates. TESK proteins phosphorylate cofilin and induce actin cytoskeletal reorganization. In the Drosphila eye, TESK is required for epithelial cell organization. Mammals contain two TESK proteins, TESK1 and TESK2, which are highly expressed in testis and play roles in spermatogenesis. TESK1 is found in testicular germ cells while TESK2 is expressed mainly in nongerminal Sertoli cells. TESK1 is stimulated by integrin-mediated signaling pathways. It regulates cell spreading and focal adhesion formation. The TESK subfamily is part of a larger superfamily that includes the catalytic domains of other protein serine/threonine PKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 208431817 144 MGSGYTKAVYRVR-LPGGAAVALKAvdfsghdlgscvrefgvrrgcYRLAAHK--LLKEMVLLERLRHPNVLQLYGYCYQ 220
Cdd:cd14155    1 IGSGFFSEVYKVRhRTSGQVMALKM---------------------NTLSSNRanMLREVQLMNRLSHPNILRFMGVCVH 59

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 208431817 221 DSEdipdtLTTITEL--GAPVEmiQLLQT----SWEDRFRICLSLGRLLHHLA-----HSPLGSVTLLDFR-PRQFVLVD 288
Cdd:cd14155   60 QGQ-----LHALTEYinGGNLE--QLLDSneplSWTVRVKLALDIARGLSYLHskgifHRDLTSKNCLIKRdENGYTAVV 132

                        170       180
                 ....*....|....*....|....*
gi 208431817 289 GEL----KVTDLDDaRVEETPCAGS 309
Cdd:cd14155  133 GDFglaeKIPDYSD-GKEKLAVVGS 156

Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 10; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK10, also called PISSLRE, is essential for cell growth and proliferation, and acts through the G2/M phase of the cell cycle. CDK10 has also been identified as an important factor in endocrine therapy resistance in breast cancer. CDK10 silencing increases the transcription of c-RAF and the activation of the p42/p44 MAPK pathway, which leads to antiestrogen resistance. Patients who express low levels of CDK10 relapse early on tamoxifen. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK10 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 208431817 132 CAALRNVSGAQYMGSGYTKAVYRVR-LPGGAAVALKAVDFSGHDLGSCVREfgvrrgcyrlaahklLKEMVLLERLRHPN 210
Cdd:cd07845    3 CRSVTEFEKLNRIGEGTYGIVYRARdTTSGEIVALKKVRMDNERDGIPISS---------------LREITLLLNLRHPN 67

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 208431817 211 VLQL---------------YGYCYQDSEDIPDTLTT-ITELGAPVEMIQLLQTSwedrfriclslgRLLHH--LAHSPLG 272
Cdd:cd07845   68 IVELkevvvgkhldsiflvMEYCEQDLASLLDNMPTpFSESQVKCLMLQLLRGL------------QYLHEnfIIHRDLK 135

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|..
gi 208431817 273 SVTLLdfrprqfvLVD-GELKVTDLDDARVEETPCAGSTDCI 313
Cdd:cd07845  136 VSNLL--------LTDkGCLKIADFGLARTYGLPAKPMTPKV 169

Catalytic domain of the Serine/Threonine kinase, Receptor Interacting Protein; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. RIP kinases serve as essential sensors of cellular stress. They are involved in regulating NF-kappaB and MAPK signaling, and are implicated in mediating cellular processes such as apoptosis, necroptosis, differentiation, and survival. RIP kinases contain a homologous N-terminal kinase domain and varying C-terminal domains. Higher vertebrates contain multiple RIP kinases, with mammals harboring at least five members. RIP1 and RIP2 harbor C-terminal domains from the Death domain (DD) superfamily while RIP4 contains ankyrin (ANK) repeats. RIP3 contain a RIP homotypic interaction motif (RHIM) that facilitates binding to RIP1. RIP1 and RIP3 are important in apoptosis and necroptosis, while RIP2 and RIP4 play roles in keratinocyte differentiation and inflammatory immune responses. The RIP 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 208431817 196 LLKEMVLLERLRHPNVLQLYGYCyqdSEDIPDTLTT-ITELGAPVEMIQLLQTS--WEDRFRICL--SLG-RLLHHLAhS 269
Cdd:cd13978   39 LLKEAEKMERARHSYVLPLLGVC---VERRSLGLVMeYMENGSLKSLLEREIQDvpWSLRFRIIHeiALGmNFLHNMD-P 114

                         90       100       110
                 ....*....|....*....|....*....|....
gi 208431817 270 PLgsvTLLDFRPrQFVLVDGEL--KVTDLDDARV 301
Cdd:cd13978  115 PL---LHHDLKP-ENILLDNHFhvKISDFGLSKL 144

Catalytic domain of Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. They can be classified into receptor and non-receptor tyr kinases. PTKs play important roles in many cellular processes including, lymphocyte activation, epithelium growth and maintenance, metabolism control, organogenesis regulation, survival, proliferation, differentiation, migration, adhesion, motility, and morphogenesis. Receptor tyr kinases (RTKs) are integral membrane proteins which contain an extracellular ligand-binding region, a transmembrane segment, and an intracellular tyr kinase domain. RTKs are usually activated through ligand binding, which causes dimerization and autophosphorylation of the intracellular tyr kinase catalytic domain, leading to intracellular signaling. Some RTKs are orphan receptors with no known ligands. Non-receptor (or cytoplasmic) tyr kinases are distributed in different intracellular compartments and are usually multi-domain proteins containing a catalytic tyr kinase domain as well as various regulatory domains such as SH3 and SH2. PTKs are usually autoinhibited and require a mechanism for activation. In many PTKs, the phosphorylation of tyr residues in the activation loop is essential for optimal activity. Aberrant expression of PTKs is associated with many development abnormalities and cancers.The PTK family is part of a larger superfamily that includes the catalytic domains of serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 208431817 195 KLLKEMVLLERLRHPNVLQLYGYCYQDsedipDTLTTITELGAPVEMIQLLQTSWEDRF---RICLSLGRLLH 264
Cdd:cd00192   42 DFLKEARVMKKLGHPNVVRLLGVCTEE-----EPLYLVMEYMEGGDLLDFLRKSRPVFPspePSTLSLKDLLS 109

Catalytic domain of the Serine/Threonine Kinase, BRI1 associated kinase 1 and related STKs; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily includes three leucine-rich repeat receptor-like kinases (LRR-RLKs): Arabidopsis thaliana BAK1 and CLAVATA1 (CLV1), and Physcomitrella patens CLL1B clavata1-like receptor S/T protein kinase. BAK1 functions in various signaling pathways. It plays a role in BR (brassinosteroid)-regulated plant development as a co-receptor of BRASSINOSTEROID (BR) INSENSITIVE 1 (BRI1), the receptor for BRs, and is required for full activation of BR signaling. It also modulates pathways involved in plant resistance to pathogen infection (pattern-triggered immunity, PTI) and herbivore attack (wound- or herbivore feeding-induced accumulation of jasmonic acid (JA) and JA-isoleucine. CLV1, directly binds small signaling peptides, CLAVATA3 (CLV3) and CLAVATA3/EMBRYO SURROUNDING REGI0N (CLE), to restrict stem cell proliferation: the CLV3-CLV1-WUS (WUSCHEL) module influences stem cell maintenance in the shoot apical meristem, and the CLE40 (CLAVATA3/EMBRYO SURROUNDING REGION40) -ACR4 (CRINKLY4) -CLV1- WOX5 (WUSCHEL-RELATED HOMEOBOX5) module at the root apical meristem. The STK_BAK1-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 208431817 144 MGSGYTKAVYRVRLPGGAAVALKAVdfsghdlgscvrefgVRRGCYRlAAHKLLKEMVLLERLRHPNVLQLYGYCYQdse 223
Cdd:cd14664    1 IGRGGAGTVYKGVMPNGTLVAVKRL---------------KGEGTQG-GDHGFQAEIQTLGMIRHRNIVRLRGYCSN--- 61

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 208431817 224 diPDTLTTITELGAPVEMIQLLQTS--------WEDRFRICLSLGRLLHHLAH--SPL 271
Cdd:cd14664   62 --PTTNLLVYEYMPNGSLGELLHSRpesqppldWETRQRIALGSARGLAYLHHdcSPL 117

Catalytic domain of C-terminal Src kinase-like Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. This subfamily is composed of Csk, Chk, and similar proteins. They are cytoplasmic (or nonreceptor) PTKs containing the Src homology domains, SH3 and SH2, N-terminal to the catalytic tyr kinase domain. They negatively regulate the activity of Src kinases that are anchored to the plasma membrane. To inhibit Src kinases, Csk and Chk are translocated to the membrane via binding to specific transmembrane proteins, G-proteins, or adaptor proteins near the membrane. Csk catalyzes the tyr phosphorylation of the regulatory C-terminal tail of Src kinases, resulting in their inactivation. Chk inhibit Src kinases using a noncatalytic mechanism by simply binding to them. As negative regulators of Src kinases, Csk and Chk play important roles in cell proliferation, survival, and differentiation, and consequently, in cancer development and progression. The Csk-like subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 208431817 181 EFG-VRRGCYR-------------LAAHKLLKEMVLLERLRHPNVLQLYGYCYQDsedipDTLTTITELGAPVEMIQLLQ 246
Cdd:cd05039   18 EFGdVMLGDYRgqkvavkclkddsTAAQAFLAEASVMTTLRHPNLVQLLGVVLEG-----NGLYIVTEYMAKGSLVDYLR 92

                 .
gi 208431817 247 T 247
Cdd:cd05039   93 S 93

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

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 208431817   152 VYRVR-LPGGAAVALKAVDFSgHDLGSCVRefgvrrgcyrlaahkLLKEMVLLERLRHPNVLQLYGyCYQDSEDI 225
Cdd:smart00220  15 VYLARdKKTGKLVAIKVIKKK-KIKKDRER---------------ILREIKILKKLKHPNIVRLYD-VFEDEDKL 72