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 139472874  88 KRLGRGAFGIIVpisedLC----------VKQFdsRREFFYEAIANDLMQATRE--RYPMHSGGSRLL------GFVQPC 149
Cdd:cd05118    5 RKIGEGAFGTVW-----LArdkvtgekvaIKKI--KNDFRHPKAALREIKLLKHlnDVEGHPNIVKLLdvfehrGGNHLC 77

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 139472874 150 IpcrsiVYPRMKCNLLQL-DWSQ--VNLSVMAAEFTGLMAAVSFLNRyCGMVHCDVSPDNILATGDLtpmnpGRLVLTDF 226
Cdd:cd05118   78 L-----VFELMGMNLYELiKDYPrgLPLDLIKSYLYQLLQALDFLHS-NGIIHRDLKPENILINLEL-----GQLKLADF 146

                        170
                 ....*....|....*..
gi 139472874 227 GSVALHSGSKWTNLVVT 243
Cdd:cd05118  147 GLARSFTSPPYTPYVAT 163

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 139472874  88 KRLGRGAFGIIVpisedLC----------VKQFdsRREFFYEAIANDLMQATRE--RYPMHSGGSRLL------GFVQPC 149
Cdd:cd05118    5 RKIGEGAFGTVW-----LArdkvtgekvaIKKI--KNDFRHPKAALREIKLLKHlnDVEGHPNIVKLLdvfehrGGNHLC 77

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 139472874 150 IpcrsiVYPRMKCNLLQL-DWSQ--VNLSVMAAEFTGLMAAVSFLNRyCGMVHCDVSPDNILATGDLtpmnpGRLVLTDF 226
Cdd:cd05118   78 L-----VFELMGMNLYELiKDYPrgLPLDLIKSYLYQLLQALDFLHS-NGIIHRDLKPENILINLEL-----GQLKLADF 146

                        170
                 ....*....|....*..
gi 139472874 227 GSVALHSGSKWTNLVVT 243
Cdd:cd05118  147 GLARSFTSPPYTPYVAT 163

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

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 139472874   184 LMAAVSFLNRyCGMVHCDVSPDNILatgdLTpmNPGRLVLTDFG-SVALHSGSKWTNLVVT 243
Cdd:smart00220 106 ILSALEYLHS-KGIVHRDLKPENIL----LD--EDGHVKLADFGlARQLDPGEKLTTFVGT 159

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 139472874  88 KRLGRGAFGIIVpisedLC----------VKQFdsRREFFYEAIANDLMQATRE--RYPMHSGGSRLL------GFVQPC 149
Cdd:cd05118    5 RKIGEGAFGTVW-----LArdkvtgekvaIKKI--KNDFRHPKAALREIKLLKHlnDVEGHPNIVKLLdvfehrGGNHLC 77

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 139472874 150 IpcrsiVYPRMKCNLLQL-DWSQ--VNLSVMAAEFTGLMAAVSFLNRyCGMVHCDVSPDNILATGDLtpmnpGRLVLTDF 226
Cdd:cd05118   78 L-----VFELMGMNLYELiKDYPrgLPLDLIKSYLYQLLQALDFLHS-NGIIHRDLKPENILINLEL-----GQLKLADF 146

                        170
                 ....*....|....*..
gi 139472874 227 GSVALHSGSKWTNLVVT 243
Cdd:cd05118  147 GLARSFTSPPYTPYVAT 163

Serine/threonine protein kinase [Signal transduction mechanisms];

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|...
gi 139472874 196 GMVHCDVSPDNILATGDltpmnpGRLVLTDFGSVALHSGSKWT 238
Cdd:COG0515  127 GIVHRDIKPANILLTPD------GRVKLIDFGIARALGGATLT 163

Catalytic domain of Microtubule-associated serine/threonine (MAST) kinase-like proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily includes MAST kinases, MAST-like (MASTL) kinases (also called greatwall kinase or Gwl), and fungal kinases with similarity to Saccharomyces cerevisiae Rim15 and Schizosaccharomyces pombe cek1. MAST kinases contain an N-terminal domain of unknown function, a central catalytic domain, and a C-terminal PDZ domain that mediates protein-protein interactions. MASTL kinases carry only a catalytic domain which contains a long insert relative to other kinases. The fungal kinases in this subfamily harbor other domains in addition to a central catalytic domain, which like in MASTL, also contains an insert relative to MAST kinases. Rim15 contains a C-terminal signal receiver (REC) domain while cek1 contains an N-terminal PAS domain. MAST kinases are cytoskeletal associated kinases of unknown function that are also expressed at neuromuscular junctions and postsynaptic densities. MASTL/Gwl is involved in the regulation of mitotic entry, mRNA stabilization, and DNA checkpoint recovery. The fungal proteins Rim15 and cek1 are involved in the regulation of meiosis and mitosis, respectively. The MAST-like 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
                 ....*....|....*....|....*....|...
gi 139472874 195 CGMVHCDVSPDNILATGDltpmnpGRLVLTDFG 227
Cdd:cd05579  112 HGIIHRDLKPDNILIDAN------GHLKLTDFG 138

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 139472874  90 LGRGAFGII-----VPISEDLCVKQFDSRREffyeaiANDLMQATRERYPM----HSGGSRLLGFVQpCIPCRSIVYPRM 160
Cdd:cd00180    1 LGKGSFGKVykardKETGKKVAVKVIPKEKL------KKLLEELLREIEILkklnHPNIVKLYDVFE-TENFLYLVMEYC 73

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 139472874 161 K-CNLLQ--------LDWSQVnLSVmaaeFTGLMAAVSFLNRyCGMVHCDVSPDNILatgdLTpmNPGRLVLTDFG 227
Cdd:cd00180   74 EgGSLKDllkenkgpLSEEEA-LSI----LRQLLSALEYLHS-NGIIHRDLKPENIL----LD--SDGTVKLADFG 137

Catalytic domain of the Dual-specificity protein kinase, YAK1; Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (S/T) as well as tyrosine residues on protein substrates. This subfamily is composed of proteins with similarity to Saccharomyces cerevisiae YAK1 (or Yak1p), a dual-specificity kinase that autophosphorylates at tyrosine residues and phosphorylates substrates on S/T residues. YAK1 phosphorylates and activates the transcription factors Hsf1 and Msn2, which play important roles in cellular homeostasis during stress conditions including heat shock, oxidative stress, and nutrient deficiency. It also phosphorylates the protein POP2, a component of a complex that regulates transcription, under glucose-deprived conditions. It functions as a part of a glucose-sensing system that is involved in controlling growth in yeast. The YAK1 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
                 ....*....|....*....|....*....|....*....|....*
gi 139472874 184 LMAAVSFLNRyCGMVHCDVSPDNILatgdLTPMNPGRLVLTDFGS 228
Cdd:cd14212  112 LLDALSVLKD-ARIIHCDLKPENIL----LVNLDSPEIKLIDFGS 151

Catalytic domain of cyclin G-Associated Kinase-like proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily includes cyclin G-Associated Kinase (GAK), Drosophila melanogaster Numb-Associated Kinase (NAK)-like proteins, and similar protein kinases. GAK plays regulatory roles in clathrin-mediated membrane trafficking, the maintenance of centrosome integrity and chromosome congression, neural patterning, survival of neurons, and immune responses. NAK plays a role in asymmetric cell division through its association with Numb. It also regulates the localization of Dlg, a protein essential for septate junction formation. The GAK-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
                 ....*....|....*....|....*....|....*....|....
gi 139472874 187 AVSFLNRYC-GMVHCDVSPDNILATgdltpmNPGRLVLTDFGSV 229
Cdd:cd13985  115 AVGHLHSQSpPIIHRDIKIENILFS------NTGRFKLCDFGSA 152