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 908266147 154 TKDKQRLVAKIERSIAEGH----LFAELEAYKHIyktagKHPNLANVHGMavvpYGNRKEEALLMDEVDGWrcsdTLRTL 229
Cdd:cd00180   15 KETGKKVAVKVIPKEKLKKlleeLLREIEILKKL-----NHPNIVKLYDV----FETENFLYLVMEYCEGG----SLKDL 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 908266147 230 ADSWKqGKINSEaywgTIKFIAHRLLDVTNHLAKAGVVHNDIKPGNVVFDRaSGEPVVIDLGL------HSRSGEQPKGF 303
Cdd:cd00180   82 LKENK-GPLSEE----EALSILRQLLSALEYLHSNGIIHRDLKPENILLDS-DGTVKLADFGLakdldsDDSLLKTTGGT 155

                        170       180
                 ....*....|....*....|...
gi 908266147 304 TESFKAPELGVGNLGASEKSDVF 326
Cdd:cd00180  156 TPPYYAPPELLGGRYYGPKVDIW 178

Fic/DOC family; This family consists of the Fic (filamentation induced by cAMP) protein and doc (death on curing). The Fic protein is involved in cell division and is suggested to be involved in the synthesis of PAB or folate, indicating that the Fic protein and cAMP are involved in a regulatory mechanism of cell division via folate metabolism. This family contains a central conserved motif HPFXXGNG in most members. The exact molecular function of these proteins is uncertain. P1 lysogens of Escherichia coli carry the prophage as a stable low copy number plasmid. The frequency with which viable cells cured of prophage are produced is about 10(-5) per cell per generation. A significant part of this remarkable stability can be attributed to a plasmid-encoded mechanism that causes death of cells that have lost P1. In other words, the lysogenic cells appear to be addicted to the presence of the prophage. The plasmid withdrawal response depends on a gene named doc (death on curing) that is represented by this family. Doc induces a reversible growth arrest of E. coli cells by targetting the protein synthesis machinery. Doc hosts the C-terminal domain of its antitoxin partner Phd (prevents host death) through fold complementation, a domain that is intrinsically disordered in solution but that folds into an alpha-helix on binding to Doc.This domain forms complexes with Phd antitoxins containing pfam02604.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 908266147  32 GELNIGGKRYRI--IDNQVLRLNPHSG-FSLFREGVGKIF-SGKmfNFSIARNLTDTLHAAQKTTSQELRS 98
Cdd:PRK14052  25 GKLSIGGKEYHInaDTQQFTRTNPTSSaVARFFEATGKLFrEGS--SQSVAKAITKAVFDNEQGQAQRLQS 93

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 908266147 154 TKDKQRLVAKIERSIAEGH----LFAELEAYKHIyktagKHPNLANVHGMavvpYGNRKEEALLMDEVDGWrcsdTLRTL 229
Cdd:cd00180   15 KETGKKVAVKVIPKEKLKKlleeLLREIEILKKL-----NHPNIVKLYDV----FETENFLYLVMEYCEGG----SLKDL 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 908266147 230 ADSWKqGKINSEaywgTIKFIAHRLLDVTNHLAKAGVVHNDIKPGNVVFDRaSGEPVVIDLGL------HSRSGEQPKGF 303
Cdd:cd00180   82 LKENK-GPLSEE----EALSILRQLLSALEYLHSNGIIHRDLKPENILLDS-DGTVKLADFGLakdldsDDSLLKTTGGT 155

                        170       180
                 ....*....|....*....|...
gi 908266147 304 TESFKAPELGVGNLGASEKSDVF 326
Cdd:cd00180  156 TPPYYAPPELLGGRYYGPKVDIW 178

serine/threonine-protein kinase 1; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 908266147 147 SHISIIETKDKQRL-VAKIersIAEGHlFAELEAYKHIykTAGKHPNLANVHGMavvpYGNRKEEALLMDEVDGWRCSDT 225
Cdd:PHA03390  30 GKVSVLKHKPTQKLfVQKI---IKAKN-FNAIEPMVHQ--LMKDNPNFIKLYYS----VTTLKGHVLIMDYIKDGDLFDL 99

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 908266147 226 LRtladswKQGKInSEAywgTIKFIAHRLLDVTNHLAKAGVVHNDIKPGNVVFDRASGEPVVIDLGL 292
Cdd:PHA03390 100 LK------KEGKL-SEA---EVKKIIRQLVEALNDLHKHNIIHNDIKLENVLYDRAKDRIYLCDYGL 156

Catalytic domain of the Serine/Threonine Kinase, p38beta Mitogen-Activated Protein Kinase (also called MAPK11); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. p38beta/MAPK11 is widely expressed in tissues and shows more similarity with p38alpha than with the other isoforms. Both are sensitive to pyridinylimidazoles and share some common substrates such as MAPK activated protein kinase 2 (MK2) and the transcription factors ATF2, c-Fos and, ELK-1. p38beta is involved in regulating the activation of the cyclooxygenase-2 promoter and the expression of TGFbeta-induced alpha-smooth muscle cell actin. p38 kinases are mitogen-activated protein kinases (MAPKs), serving as important mediators of cellular responses to extracellular signals. They are activated by the MAPK kinases MKK3 and MKK6, which in turn are activated by upstream MAPK kinase kinases including TAK1, ASK1, and MLK3, in response to cellular stresses or inflammatory cytokines. The p38beta subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 908266147 247 IKFIAHRLLDVTNHLAKAGVVHNDIKPGNVVFDRASgEPVVIDLGLHSRSGEQPKGF--TESFKAPELGVGNLGASEKSD 324
Cdd:cd07878  120 VQFLIYQLLRGLKYIHSAGIIHRDLKPSNVAVNEDC-ELRILDFGLARQADDEMTGYvaTRWYRAPEIMLNWMHYNQTVD 198

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 908266147 325 VFLVVSTLLHCIEG---FEKNPEI-----------KPN-QGLRFITSEPAHVMDENGYPIHRPGIAGVETAYTRFITDIL 389
Cdd:cd07878  199 IWSVGCIMAELLKGkalFPGNDYIdqlkrimevvgTPSpEVLKKISSEHARKYIQSLPHMPQQDLKKIFRGANPLAIDLL 278

                        170       180
                 ....*....|....*....|....
gi 908266147 390 G----VSADSRPDSNEARLHEFLS 409
Cdd:cd07878  279 EkmlvLDSDKRISASEALAHPYFS 302

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 908266147 154 TKDKQRLVAKIERSIAEGH----LFAELEAYKHIyktagKHPNLANVHGMavvpYGNRKEEALLMDEVDGWrcsdTLRTL 229
Cdd:cd00180   15 KETGKKVAVKVIPKEKLKKlleeLLREIEILKKL-----NHPNIVKLYDV----FETENFLYLVMEYCEGG----SLKDL 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 908266147 230 ADSWKqGKINSEaywgTIKFIAHRLLDVTNHLAKAGVVHNDIKPGNVVFDRaSGEPVVIDLGL------HSRSGEQPKGF 303
Cdd:cd00180   82 LKENK-GPLSEE----EALSILRQLLSALEYLHSNGIIHRDLKPENILLDS-DGTVKLADFGLakdldsDDSLLKTTGGT 155

                        170       180
                 ....*....|....*....|...
gi 908266147 304 TESFKAPELGVGNLGASEKSDVF 326
Cdd:cd00180  156 TPPYYAPPELLGGRYYGPKVDIW 178

Serine/threonine protein kinase [Signal transduction mechanisms];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 908266147 189 KHPNLANVHGMAV---VPYgnrkeeaLLMDEVDGwrcsDTLRTLADSwkQGKINseayWGTIKFIAHRLLDVTNHLAKAG 265
Cdd:COG0515   65 NHPNIVRVYDVGEedgRPY-------LVMEYVEG----ESLADLLRR--RGPLP----PAEALRILAQLAEALAAAHAAG 127

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 908266147 266 VVHNDIKPGNVVFDRaSGEPVVIDLGL--------HSRSGeQPKGfTESFKAPELGVGnLGASEKSDVFLVVSTLLHCIE 337
Cdd:COG0515  128 IVHRDIKPANILLTP-DGRVKLIDFGIaralggatLTQTG-TVVG-TPGYMAPEQARG-EPVDPRSDVYSLGVTLYELLT 203

                 .
gi 908266147 338 G 338
Cdd:COG0515  204 G 204

serine/threonine-protein kinase 1; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 908266147 147 SHISIIETKDKQRL-VAKIersIAEGHlFAELEAYKHIykTAGKHPNLANVHGMavvpYGNRKEEALLMDEVDGWRCSDT 225
Cdd:PHA03390  30 GKVSVLKHKPTQKLfVQKI---IKAKN-FNAIEPMVHQ--LMKDNPNFIKLYYS----VTTLKGHVLIMDYIKDGDLFDL 99

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 908266147 226 LRtladswKQGKInSEAywgTIKFIAHRLLDVTNHLAKAGVVHNDIKPGNVVFDRASGEPVVIDLGL 292
Cdd:PHA03390 100 LK------KEGKL-SEA---EVKKIIRQLVEALNDLHKHNIIHNDIKLENVLYDRAKDRIYLCDYGL 156

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 908266147 254 LLDVTNHLAKAGVVHNDIKPGNVVFDRASGEPVVIDLGL----HSRSGEQ-PKGFTESFKAPE 311
Cdd:cd14019  110 LFKALKHVHSFGIIHRDVKPGNFLYNRETGKGVLVDFGLaqreEDRPEQRaPRAGTRGFRAPE 172

Catalytic domain of fungal Rim15-like Protein Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Members of this group include Saccharomyces cerevisiae Rim15, Schizosaccharomyces pombe cek1, and similar fungal proteins. They contain a central catalytic domain, which contains an insert relative to MAST kinases. In addition, Rim15 contains a C-terminal signal receiver (REC) domain while cek1 contains an N-terminal PAS domain. Rim15 (or Rim15p) functions as a regulator of meiosis. It acts as a downstream effector of PKA and regulates entry into stationary phase (G0). Thus, it plays a crucial role in regulating yeast proliferation, differentiation, and aging. Cek1 may facilitate progression of mitotic anaphase. The Rim15-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 908266147 212 LLMDEVDGWRCSDTLRT---LADSWKQgkinseaywgtiKFIAHRLLDVtNHLAKAGVVHNDIKPGNVVFDrASGEPVVI 288
Cdd:cd05611   74 LVMEYLNGGDCASLIKTlggLPEDWAK------------QYIAEVVLGV-EDLHQRGIIHRDIKPENLLID-QTGHLKLT 139

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|
gi 908266147 289 DLGLhSRSGE---QPKGF--TESFKAPE--LGVGNLGASE 321
Cdd:cd05611  140 DFGL-SRNGLekrHNKKFvgTPDYLAPEtiLGVGDDKMSD 178

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 908266147 189 KHPNLANVHGMAVvpygNRKEEALLMDEVDGwrcsdtlRTLADSWKQGKINSEAYwgtIKFIAHRLLDVTNHLAKAGVVH 268
Cdd:cd06626   57 DHPNLVRYYGVEV----HREEVYIFMEYCQE-------GTLEELLRHGRILDEAV---IRVYTLQLLEGLAYLHENGIVH 122

                         90
                 ....*....|..
gi 908266147 269 NDIKPGNVVFDR 280
Cdd:cd06626  123 RDIKPANIFLDS 134

Catalytic domain of the Serine/Threonine Kinase, p38beta Mitogen-Activated Protein Kinase (also called MAPK11); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. p38beta/MAPK11 is widely expressed in tissues and shows more similarity with p38alpha than with the other isoforms. Both are sensitive to pyridinylimidazoles and share some common substrates such as MAPK activated protein kinase 2 (MK2) and the transcription factors ATF2, c-Fos and, ELK-1. p38beta is involved in regulating the activation of the cyclooxygenase-2 promoter and the expression of TGFbeta-induced alpha-smooth muscle cell actin. p38 kinases are mitogen-activated protein kinases (MAPKs), serving as important mediators of cellular responses to extracellular signals. They are activated by the MAPK kinases MKK3 and MKK6, which in turn are activated by upstream MAPK kinase kinases including TAK1, ASK1, and MLK3, in response to cellular stresses or inflammatory cytokines. The p38beta subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 908266147 247 IKFIAHRLLDVTNHLAKAGVVHNDIKPGNVVFDRASgEPVVIDLGLHSRSGEQPKGF--TESFKAPELGVGNLGASEKSD 324
Cdd:cd07878  120 VQFLIYQLLRGLKYIHSAGIIHRDLKPSNVAVNEDC-ELRILDFGLARQADDEMTGYvaTRWYRAPEIMLNWMHYNQTVD 198

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 908266147 325 VFLVVSTLLHCIEG---FEKNPEI-----------KPN-QGLRFITSEPAHVMDENGYPIHRPGIAGVETAYTRFITDIL 389
Cdd:cd07878  199 IWSVGCIMAELLKGkalFPGNDYIdqlkrimevvgTPSpEVLKKISSEHARKYIQSLPHMPQQDLKKIFRGANPLAIDLL 278

                        170       180
                 ....*....|....*....|....
gi 908266147 390 G----VSADSRPDSNEARLHEFLS 409
Cdd:cd07878  279 EkmlvLDSDKRISASEALAHPYFS 302

C-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MSK2 and MSK1 play nonredundant roles in activating histone H3 kinases, which play pivotal roles in compaction of the chromatin fiber. MSK2 is the required H3 kinase in response to stress stimuli and activation of the p38 MAPK pathway. MSK2 also plays a role in the pathogenesis of psoriasis. MSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family, similar to 90 kDa ribosomal protein S6 kinases (RSKs). 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 MSK2 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 908266147 190 HPNLANVHGMavvpYGNRKEEALLMDEVDGWRCSDTLRTladswKQGKINSEAywgtiKFIAHRLLDVTNHLAKAGVVHN 269
Cdd:cd14180   60 HPNIVALHEV----LHDQYHTYLVMELLRGGELLDRIKK-----KARFSESEA-----SQLMRSLVSAVSFMHEAGVVHR 125

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 908266147 270 DIKPGNVVF-DRASGEPV-VIDLGLhSR---SGEQP---KGFTESFKAPELgVGNLGASEKSDVF 326
Cdd:cd14180  126 DLKPENILYaDESDGAVLkVIDFGF-ARlrpQGSRPlqtPCFTLQYAAPEL-FSNQGYDESCDLW 188

Catalytic domain of the Serine/Threonine Kinase, c-Jun N-terminal Kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. JNK3 is expressed primarily in the brain, and to a lesser extent in the heart and testis. Mice deficient in JNK3 are protected against kainic acid-induced seizures, stroke, sciatic axotomy neural death, and neuronal death due to NGF deprivation, oxidative stress, or exposure to beta-amyloid peptide. This suggests that JNK3 may play roles in the pathogenesis of these diseases. JNKs are mitogen-activated protein kinases (MAPKs) that are involved in many stress-activated responses including those during inflammation, neurodegeneration, apoptosis, and persistent pain sensitization, among others. The JNK3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 908266147 247 IKFIAHRLLDVTNHLAKAGVVHNDIKPGNVVFdRASGEPVVIDLGLHSRSGEQ----PKGFTESFKAPELGVGnLGASEK 322
Cdd:cd07874  121 MSYLLYQMLCGIKHLHSAGIIHRDLKPSNIVV-KSDCTLKILDFGLARTAGTSfmmtPYVVTRYYRAPEVILG-MGYKEN 198

                 ....*.
gi 908266147 323 SDVFLV 328
Cdd:cd07874  199 VDIWSV 204

adenosine monophosphate-protein transferase vopS;

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 908266147  32 GELNIGGKRYRI--IDNQVLRLNPHSG-FSLFREGVGKIF-SGKmfNFSIARNLTDTLHAAQKTTSQELRS 98
Cdd:PRK14052  25 GKLSIGGKEYHInaDTQQFTRTNPTSSaVARFFEATGKLFrEGS--SQSVAKAITKAVFDNEQGQAQRLQS 93

Catalytic domain of the Serine/Threonine kinase, Plant SNT7; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SNT7 is a plant thylakoid-associated kinase that is essential in short- and long-term acclimation responses to cope with various light conditions in order to maintain photosynthetic redox poise for optimal photosynthetic performance. Short-term response involves state transitions over periods of minutes while the long-term response (LTR) occurs over hours to days and involves changing the relative amounts of photosystems I and II. SNT7 acts as a redox sensor and a signal transducer for both responses, which are triggered by the redox state of the plastoquinone (PQ) pool. It is positioned at the top of a phosphorylation cascade that induces state transitions by phosphorylating light-harvesting complex II (LHCII), and triggers the LTR through the phosphorylation of chloroplast proteins. The SNT7 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 908266147 244 WGTIKFIAHRLLDVTNHLAKAGVVHNDIKPGNVVFDRASGEPVVIDLG 291
Cdd:cd14013  119 NVIIKSIMRQILVALRKLHSTGIVHRDVKPQNIIVSEGDGQFKIIDLG 166

Catalytic domain of Serine/Threonine Kinase 16; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. STK16 is associated with many names including Myristylated and Palmitylated Serine/threonine Kinase 1 (MPSK1), Kinase related to cerevisiae and thaliana (Krct), and Protein Kinase expressed in day 12 fetal liver (PKL12). It is widely expressed in mammals with highest levels found in liver, testis, and kidney. It is localized in the Golgi but is translocated to the nucleus upon disorganization of the Golgi. STK16 is constitutively active and is capable of phosphorylating itself and other substrates. It may be involved in regulating stromal-epithelial interactions during mammary gland ductal morphogenesis. It may also function as a transcriptional co-activator of type-C natriuretic peptide and VEGF. The STK16 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 908266147 176 ELEAYKHIyktagKHPNLANVHGMAVVPYGNRKEEALLMDEV--DGwrcsdtlrTLADSWKQGKIN----SEAywgTIKF 249
Cdd:cd13986   47 EIENYRLF-----NHPNILRLLDSQIVKEAGGKKEVYLLLPYykRG--------SLQDEIERRLVKgtffPED---RILH 110

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 908266147 250 IAHRLLDVTNHLAKA---GVVHNDIKPGNVVFDRaSGEPVVIDLGLHSRSGEQPKGFTE--------------SFKAPEL 312
Cdd:cd13986  111 IFLGICRGLKAMHEPelvPYAHRDIKPGNVLLSE-DDEPILMDLGSMNPARIEIEGRREalalqdwaaehctmPYRAPEL 189

Catalytic domain of the Serine/Threonine Kinase, 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. 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 CdkB 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 908266147 246 TIKFIAHRLLDVTNHLAKAGVVHNDIKPGNVVFDRASGEPVVIDLGLhSRSGEQP-KGFTES-----FKAPELGVGNLGA 319
Cdd:cd07837  110 TIQSFMYQLCKGVAHCHSHGVMHRDLKPQNLLVDKQKGLLKIADLGL-GRAFTIPiKSYTHEivtlwYRAPEVLLGSTHY 188

                 ....*....
gi 908266147 320 SEKSDVFLV 328
Cdd:cd07837  189 STPVDMWSV 197

Catalytic kinase domain of Myosin Light Chain Kinase-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This family is composed of MLCKs and related MLCK-like kinase domains from giant STKs such as titin, obscurin, SPEG, Unc-89, Trio, kalirin, and Twitchin. Also included in this family are Death-Associated Protein Kinases (DAPKs) and Death-associated protein kinase-Related Apoptosis-inducing protein Kinase (DRAKs). MLCK phosphorylates myosin regulatory light chain and controls the contraction of all muscle types. Titin, obscurin, Twitchin, and SPEG are muscle proteins involved in the contractile apparatus. The giant STKs are multidomain proteins containing immunoglobulin (Ig), fibronectin type III (FN3), SH3, RhoGEF, PH and kinase domains. Titin, obscurin, Twitchin, and SPEG contain many Ig domain repeats at the N-terminus, while Trio and Kalirin contain spectrin-like repeats. The MLCK-like 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 908266147 151 IIETKDKQRLVAKI--ERSIAEGHLFAELEAYKHIyktagKHPNLANVHGMavvpYGNRKEEALLMDEVDGwrcSDTLRT 228
Cdd:cd14006   12 CIEKATGREFAAKFipKRDKKKEAVLREISILNQL-----QHPRIIQLHEA----YESPTELVLILELCSG---GELLDR 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 908266147 229 LADSWKqgkiNSEAywgTIKFIAHRLLDVTNHLAKAGVVHNDIKPGNVVF-DRASGEPVVIDLGLHSR--SGE---QPKG 302
Cdd:cd14006   80 LAERGS----LSEE---EVRTYMRQLLEGLQYLHNHHILHLDLKPENILLaDRPSPQIKIIDFGLARKlnPGEelkEIFG 152

                        170
                 ....*....|
gi 908266147 303 FTEsFKAPEL 312
Cdd:cd14006  153 TPE-FVAPEI 161

Catalytic domain of AMP-activated protein kinase-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The AMPK-like subfamily is composed of AMPK, MARK, BRSK, NUAK, MELK, SNRK, TSSK, and SIK, among others. LKB1 serves as a master upstream kinase that activates AMPK and most AMPK-like kinases. AMPK, also called SNF1 (sucrose non-fermenting1) in yeasts and SnRK1 (SNF1-related kinase1) in plants, is a heterotrimeric enzyme composed of a catalytic alpha subunit and two regulatory subunits, beta and gamma. It is a stress-activated kinase that serves as master regulator of glucose and lipid metabolism by monitoring carbon and energy supplies, via sensing the cell's AMP:ATP ratio. MARKs phosphorylate tau and related microtubule-associated proteins (MAPs), and regulates microtubule-based intracellular transport. They are involved in embryogenesis, epithelial cell polarization, cell signaling, and neuronal differentiation. BRSKs play important roles in establishing neuronal polarity. TSSK proteins are almost exclusively expressed postmeiotically in the testis and play important roles in spermatogenesis and/or spermiogenesis. The AMPK-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 908266147 248 KFIAHRLLDVTNHLAKAGVVHNDIKPGNVVFDRAsGEPVVIDLGL--HSRSGEQPKGF--TESFKAPELGVGNLGASEKS 323
Cdd:cd14003  102 RRFFQQLISAVDYCHSNGIVHRDLKLENILLDKN-GNLKIIDFGLsnEFRGGSLLKTFcgTPAYAAPEVLLGRKYDGPKA 180

                 ..
gi 908266147 324 DV 325
Cdd:cd14003  181 DV 182

Catalytic domain of the Serine/Threonine Kinase, p38gamma Mitogen-Activated Protein Kinase (also called MAPK12); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. p38gamma/MAPK12 is predominantly expressed in skeletal muscle. Unlike p38alpha and p38beta, p38gamma is insensitive to pyridinylimidazoles. It displays an antagonizing function compared to p38alpha. p38gamma inhibits, while p38alpha stimulates, c-Jun phosphorylation and AP-1 mediated transcription. p38gamma also plays a role in the signaling between Ras and the estrogen receptor and has been implicated to increase cell invasion and breast cancer progression. In Xenopus, p38gamma is critical in the meiotic maturation of oocytes. p38 kinases are MAPKs, serving as important mediators of cellular responses to extracellular signals. They are activated by the MAPK kinases MKK3 and MKK6, which in turn are activated by upstream MAPK kinase kinases including TAK1, ASK1, and MLK3, in response to cellular stresses or inflammatory cytokines. The p38gamma subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 908266147 247 IKFIAHRLLDVTNHLAKAGVVHNDIKPGNVVFDRASgEPVVIDLGLHSRSGEQPKGF--TESFKAPEL 312
Cdd:cd07880  120 IQFLVYQMLKGLKYIHAAGIIHRDLKPGNLAVNEDC-ELKILDFGLARQTDSEMTGYvvTRWYRAPEV 186

Catalytic domain of the Serine/Threonine Kinase, p38alpha Mitogen-Activated Protein Kinase (also called MAPK14); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. p38alpha/MAPK14 is expressed in most tissues and is the major isoform involved in the immune and inflammatory response. It is the central p38 MAPK involved in myogenesis. It plays a role in regulating cell cycle check-point transition and promoting cell differentiation. p38alpha also regulates cell proliferation and death through crosstalk with the JNK pathway. Its substrates include MAPK activated protein kinase 2 (MK2), MK5, and the transcription factors ATF2 and Mitf. p38 kinases MAPKs, serving as important mediators of cellular responses to extracellular signals. They are activated by the MAPK kinases MKK3 and MKK6, which in turn are activated by upstream MAPK kinase kinases including TAK1, ASK1, and MLK3, in response to cellular stresses or inflammatory cytokines. The p38alpha subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 908266147 247 IKFIAHRLLDVTNHLAKAGVVHNDIKPGNVVFDRASgEPVVIDLGLHSRSGEQPKGF--TESFKAPELGVGNLGASEKSD 324
Cdd:cd07877  122 VQFLIYQILRGLKYIHSADIIHRDLKPSNLAVNEDC-ELKILDFGLARHTDDEMTGYvaTRWYRAPEIMLNWMHYNQTVD 200

                 ....
gi 908266147 325 VFLV 328
Cdd:cd07877  201 IWSV 204

Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. GRKs phosphorylate and regulate G protein-coupled receptors (GPCRs), the largest superfamily of cell surface receptors, which regulate some part of nearly all physiological functions. Phosphorylated GPCRs bind to arrestins, which prevents further G protein signaling despite the presence of activating ligand. GRKs play important roles in the cardiovascular, immune, respiratory, skeletal, and nervous systems. They contain a central catalytic domain, flanked by N- and C-terminal extensions. The N-terminus contains an RGS (regulator of G protein signaling) homology (RH) domain and several motifs. The C-terminus diverges among different groups of GRKs. There are seven types of GRKs, named GRK1 to GRK7, which are subdivided into three main groups: visual (GRK1/7); beta-adrenergic receptor kinases (GRK2/3); and GRK4-like (GRK4/5/6). Expression of GRK2/3/5/6 is widespread while GRK1/4/7 show a limited tissue distribution. The substrate spectrum of the widely expressed GRKs partially overlaps. The GRK 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 908266147 260 HLAKAGVVHNDIKPGNVVFDRaSGEPVVIDLGL--HSRSGEQPKGF--TESFKAPELGVGNLGASEKSDVFLVVSTLLHC 335
Cdd:cd05577  110 HLHNRFIVYRDLKPENILLDD-HGHVRISDLGLavEFKGGKKIKGRvgTHGYMAPEVLQKEVAYDFSVDWFALGCMLYEM 188

                         90       100
                 ....*....|....*....|....*..
gi 908266147 336 IEG---FEKNPEIKPNQGLRFITSEPA 359
Cdd:cd05577  189 IAGrspFRQRKEKVDKEELKRRTLEMA 215

Catalytic domain of the Serine/Threonine kinase, Per-ARNT-Sim (PAS) domain Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PASK (or PASKIN) is a nutrient and energy sensor and thus, plays an important role in maintaining cellular energy homeostasis. It coordinates the utilization of glucose in response to metabolic demand. It contains an N-terminal PAS domain which directly interacts and inhibits a C-terminal catalytic kinase domain. The PAS domain serves as a sensory module for different environmental signals such as light, redox state, and various metabolites. Binding of ligands to the PAS domain causes structural changes which leads to kinase activation and the phosphorylation of substrates to trigger the appropriate cellular response. The PASK 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 908266147 248 KFIAHRLLDVTNHLAKAGVVHNDIKPGNVVFDrASGEPVVIDLG--LHSRSGEqpkgF-----TESFKAPELGVGNLGAS 320
Cdd:cd14004  112 KYIFRQVADAVKHLHDQGIVHRDIKDENVILD-GNGTIKLIDFGsaAYIKSGP----FdtfvgTIDYAAPEVLRGNPYGG 186

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*
gi 908266147 321 EKSDVFLVVSTLLHCIegFEKNPEIKPNQGLRFITSEPAHVMDEN 365
Cdd:cd14004  187 KEQDIWALGVLLYTLV--FKENPFYNIEEILEADLRIPYAVSEDL 229

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 908266147 245 GTIKFIAHRLLDVTNHLAKAGVVHNDIKPGNVVFDRA-SGEPVVIDLG 291
Cdd:cd14212  103 QLIRKFLQQLLDALSVLKDARIIHCDLKPENILLVNLdSPEIKLIDFG 150

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
                 ....*....|....*....|....*....|....*
gi 908266147 246 TIKFIAHRLLDVTNHLAKAGVVHNDIKPGNVVFDR 280
Cdd:cd05581  102 CTRFYTAEIVLALEYLHSKGIIHRDLKPENILLDE 136