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 1907148278   6 QPENLLLASKSKGAAVKLADFGLAIEVQGDQQAWFGFAGTPGYLSPEVLRKDPYGKPVDMWACGVILYILLVGYPPFWDE 85
Cdd:cd14086   127 KPENLLLASKSKGAAVKLADFGLAIEVQGDQQAWFGFAGTPGYLSPEVLRKDPYGKPVDIWACGVILYILLVGYPPFWDE 206

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907148278  86 DQHRLYQQIKAGAYDFPSPEWDTVTPEAKDLINKMLTINPAKRITASEALKHPWICQRSTVASMMHRQETVDCLKKFNAR 165
Cdd:cd14086   207 DQHRLYAQIKAGAYDYPSPEWDTVTPEAKDLINQMLTVNPAKRITAAEALKHPWICQRDRVASMVHRQETVDCLKKFNAR 286

                  ....*.
gi 1907148278 166 RKLKGA 171
Cdd:cd14086   287 RKLKGA 292

Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase Type II; 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. CaMKs contain an N-terminal catalytic domain followed by a regulatory domain that harbors a CaM binding site. In addition, CaMKII contains a C-terminal association domain that facilitates oligomerization. There are four CaMKII proteins (alpha, beta, gamma, delta) encoded by different genes; each gene undergoes alternative splicing to produce more than 30 isoforms. CaMKII-alpha and -beta are enriched in neurons while CaMKII-gamma and -delta are predominant in myocardium. 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. It is a major component of the postsynaptic density and is critical in regulating synaptic plasticity including long-term potentiation. It is critical in regulating ion channels and proteins involved in myocardial excitation-contraction and excitation-transcription coupling. Excessive CaMKII activity promotes processes that contribute to heart failure and arrhythmias. The CaMKII subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907148278   6 QPENLLLASKSKGAAVKLADFGLAIEVQGDQQAWFGFAGTPGYLSPEVLRKDPYGKPVDMWACGVILYILLVGYPPFWDE 85
Cdd:cd14086   127 KPENLLLASKSKGAAVKLADFGLAIEVQGDQQAWFGFAGTPGYLSPEVLRKDPYGKPVDIWACGVILYILLVGYPPFWDE 206

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907148278  86 DQHRLYQQIKAGAYDFPSPEWDTVTPEAKDLINKMLTINPAKRITASEALKHPWICQRSTVASMMHRQETVDCLKKFNAR 165
Cdd:cd14086   207 DQHRLYAQIKAGAYDYPSPEWDTVTPEAKDLINQMLTVNPAKRITAAEALKHPWICQRDRVASMVHRQETVDCLKKFNAR 286

                  ....*.
gi 1907148278 166 RKLKGA 171
Cdd:cd14086   287 RKLKGA 292

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907148278    7 PENLLLASKSKgaaVKLADFGLAIEVQGDQQAWfGFAGTPGYLSPEVLRKDPYGKPVDMWACGVILYILLVGYPPFWDED 86
Cdd:smart00220 125 PENILLDEDGH---VKLADFGLARQLDPGEKLT-TFVGTPEYMAPEVLLGKGYGKAVDIWSLGVILYELLTGKPPFPGDD 200

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1907148278   87 QH-RLYQQIKAGAYDFPSPEWDtVTPEAKDLINKMLTINPAKRITASEALKHPWI 140
Cdd:smart00220 201 QLlELFKKIGKPKPPFPPPEWD-ISPEAKDLIRKLLVKDPEKRLTAEEALQHPFF 254

protein kinase A catalytic subunit; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907148278   6 QPENLLLASKSKgaaVKLADFGLAIEVQgdqQAWFGFAGTPGYLSPEVLRKDPYGKPVDMWACGVILYILLVGYPPFWDE 85
Cdd:PTZ00263  145 KPENLLLDNKGH---VKVTDFGFAKKVP---DRTFTLCGTPEYLAPEVIQSKGHGKAVDWWTMGVLLYEFIAGYPPFFDD 218

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 1907148278  86 DQHRLYQQIKAGAYDFPSpeWdtVTPEAKDLINKMLTINPAKRI 129
Cdd:PTZ00263  219 TPFRIYEKILAGRLKFPN--W--FDGRARDLVKGLLQTDHTKRL 258

Ketosteroid isomerase homolog YybH [General function prediction only];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907148278 210 DVKARKQEIIKVTEQLIEAINNGDFEAYTKICDPGLTAFEPEalGNLVEGMDFHRFYFENALSKSNKPIHTIIlNPHVHL 289
Cdd:COG4319     3 RSAEDEAAIRALLAAFAEAFNAGDADALAALYAEDAVFFDPG--GPPVRGREAIRAAWAAAFAAGPRVTFEVE-DVRVLV 79

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1907148278 290 VGDDAACIAYIRLTqYMDGSGMPKTMQSEETRVWHRR-DGKWQNVHFHRSGSP 341
Cdd:COG4319    80 SGDVAVVTGRWRLT-GTDPDGEPVELAGRYTLVFRKQaDGRWKIVHDHASGVP 131

Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase Type II; 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. CaMKs contain an N-terminal catalytic domain followed by a regulatory domain that harbors a CaM binding site. In addition, CaMKII contains a C-terminal association domain that facilitates oligomerization. There are four CaMKII proteins (alpha, beta, gamma, delta) encoded by different genes; each gene undergoes alternative splicing to produce more than 30 isoforms. CaMKII-alpha and -beta are enriched in neurons while CaMKII-gamma and -delta are predominant in myocardium. 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. It is a major component of the postsynaptic density and is critical in regulating synaptic plasticity including long-term potentiation. It is critical in regulating ion channels and proteins involved in myocardial excitation-contraction and excitation-transcription coupling. Excessive CaMKII activity promotes processes that contribute to heart failure and arrhythmias. The CaMKII subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907148278   6 QPENLLLASKSKGAAVKLADFGLAIEVQGDQQAWFGFAGTPGYLSPEVLRKDPYGKPVDMWACGVILYILLVGYPPFWDE 85
Cdd:cd14086   127 KPENLLLASKSKGAAVKLADFGLAIEVQGDQQAWFGFAGTPGYLSPEVLRKDPYGKPVDIWACGVILYILLVGYPPFWDE 206

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907148278  86 DQHRLYQQIKAGAYDFPSPEWDTVTPEAKDLINKMLTINPAKRITASEALKHPWICQRSTVASMMHRQETVDCLKKFNAR 165
Cdd:cd14086   207 DQHRLYAQIKAGAYDYPSPEWDTVTPEAKDLINQMLTVNPAKRITAAEALKHPWICQRDRVASMVHRQETVDCLKKFNAR 286

                  ....*.
gi 1907148278 166 RKLKGA 171
Cdd:cd14086   287 RKLKGA 292

Calcium/calmodulin dependent protein kinase II association domain; This domain is found at the C-terminus of the Calcium/calmodulin dependent protein kinases II (CaMKII). These proteins also have a Ser/Thr protein kinase domain (pfam00069) at their N-terminus. The function of the CaMKII association domain is the assembly of the single proteins into large (8 to 14 subunits) multimers.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907148278 214 RKQEIIKVTEQLIEAINNGDFEAYTKICDPGLTAFEPEALGNLVEGMDFHRFYFENALSKSNKPIHTIILNPHVHLVGDD 293
Cdd:pfam08332   1 RKQEIIKVTETLLEAISTGDFETYTKLCDPDLTAFEPEVLGNLVEGLEFHRFYFENFLGKRPKAVHTTILNPHVHLLGDD 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*...
gi 1907148278 294 AACIAYIRLTQYMDGSGMPKTMQSEETRVWHRRDGKWQNVHFHRSGSP 341
Cdd:pfam08332  81 SACIAYVRLTTYLDKNGKAHTRQSEETRVWHKRDGKWQIVHVHRSAAP 128

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907148278    7 PENLLLASKSKgaaVKLADFGLAIEVQGDQQAWfGFAGTPGYLSPEVLRKDPYGKPVDMWACGVILYILLVGYPPFWDED 86
Cdd:smart00220 125 PENILLDEDGH---VKLADFGLARQLDPGEKLT-TFVGTPEYMAPEVLLGKGYGKAVDIWSLGVILYELLTGKPPFPGDD 200

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1907148278   87 QH-RLYQQIKAGAYDFPSPEWDtVTPEAKDLINKMLTINPAKRITASEALKHPWI 140
Cdd:smart00220 201 QLlELFKKIGKPKPPFPPPEWD-ISPEAKDLIRKLLVKDPEKRLTAEEALQHPFF 254

Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase Type IV; 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. CaMKs contain an N-terminal catalytic domain and a C-terminal regulatory domain that harbors a CaM binding site. CaMKIV is found predominantly in neurons and immune cells. It is activated by the binding of calcium/CaM and phosphorylation by CaMKK (alpha or beta). The CaMKK-CaMKIV cascade participates in regulating several transcription factors like CREB, MEF2, and retinoid orphan receptors. It also is implicated in T-cell development and signaling, cytokine secretion, and signaling through Toll-like receptors, and is thus, pivotal in immune response and inflammation. The CaMKIV subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907148278   6 QPENLLLASKSKGAAVKLADFGLAiEVQGDQQAWFGFAGTPGYLSPEVLRKDPYGKPVDMWACGVILYILLVGYPPFWDE 85
Cdd:cd14085   125 KPENLLYATPAPDAPLKIADFGLS-KIVDQQVTMKTVCGTPGYCAPEILRGCAYGPEVDMWSVGVITYILLCGFEPFYDE 203

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907148278  86 --DQHrLYQQIKAGAYDFPSPEWDTVTPEAKDLINKMLTINPAKRITASEALKHPWIcqRSTVASMMHRQETVDCLKKFN 163
Cdd:cd14085   204 rgDQY-MFKRILNCDYDFVSPWWDDVSLNAKDLVKKLIVLDPKKRLTTQQALQHPWV--TGKAANFAHMDTAQKKLQEFN 280

                         170
                  ....*....|...
gi 1907148278 164 ARRKLKGAILTTM 176
Cdd:cd14085   281 ARRKLKAAVKAVV 293

Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase Type I; 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. In vertebrates, there are four CaMKI proteins encoded by different genes (alpha, beta, gamma, and delta), each producing at least one variant. CaMKs contain an N-terminal catalytic domain and a C-terminal regulatory domain that harbors a CaM binding site. 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. In addition, they may be involved in osteoclast differentiation and bone resorption. The CaMKI subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907148278   6 QPENLLLASKSKGAAVKLADFGLA-IEVQGDqqawFGFA-GTPGYLSPEVLRKDPYGKPVDMWACGVILYILLVGYPPFW 83
Cdd:cd14083   128 KPENLLYYSPDEDSKIMISDFGLSkMEDSGV----MSTAcGTPGYVAPEVLAQKPYGKAVDCWSIGVISYILLCGYPPFY 203

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1907148278  84 DEDQHRLYQQIKAGAYDFPSPEWDTVTPEAKDLINKMLTINPAKRITASEALKHPW 139
Cdd:cd14083   204 DENDSKLFAQILKAEYEFDSPYWDDISDSAKDFIRHLMEKDPNKRYTCEQALEHPW 259

Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase Type I gamma; 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. The CaMK family includes CaMKI, CaMKII, CaMKIV, and CaMK kinase (CaMKK). In vertebrates, there are four CaMKI proteins encoded by different genes (alpha, beta, gamma, and delta), each producing at least one variant. CaMKs contain an N-terminal catalytic domain and a C-terminal regulatory domain that harbors a CaM binding site. 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. In addition, they may be involved in osteoclast differentiation and bone resorption. The CaMKI-gamma subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907148278   6 QPENLLLASKSKGAAVKLADFGLAievQGDQQAWFGFA-GTPGYLSPEVLRKDPYGKPVDMWACGVILYILLVGYPPFWD 84
Cdd:cd14166   127 KPENLLYLTPDENSKIMITDFGLS---KMEQNGIMSTAcGTPGYVAPEVLAQKPYSKAVDCWSIGVITYILLCGYPPFYE 203

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1907148278  85 EDQHRLYQQIKAGAYDFPSPEWDTVTPEAKDLINKMLTINPAKRITASEALKHPWI 140
Cdd:cd14166   204 ETESRLFEKIKEGYYEFESPFWDDISESAKDFIRHLLEKNPSKRYTCEKALSHPWI 259

Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase Type I alpha; 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. The CaMK family includes CaMKI, CaMKII, CaMKIV, and CaMK kinase (CaMKK). In vertebrates, there are four CaMKI proteins encoded by different genes (alpha, beta, gamma, and delta), each producing at least one variant. CaMKs contain an N-terminal catalytic domain and a C-terminal regulatory domain that harbors a CaM binding site. 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. In addition, they may be involved in osteoclast differentiation and bone resorption. The CaMKI-alpha subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907148278   6 QPENLLLASKSKGAAVKLADFGLAiEVQGDQQAWFGFAGTPGYLSPEVLRKDPYGKPVDMWACGVILYILLVGYPPFWDE 85
Cdd:cd14167   128 KPENLLYYSLDEDSKIMISDFGLS-KIEGSGSVMSTACGTPGYVAPEVLAQKPYSKAVDCWSIGVIAYILLCGYPPFYDE 206

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1907148278  86 DQHRLYQQIKAGAYDFPSPEWDTVTPEAKDLINKMLTINPAKRITASEALKHPWI 140
Cdd:cd14167   207 NDAKLFEQILKAEYEFDSPYWDDISDSAKDFIQHLMEKDPEKRFTCEQALQHPWI 261

Catalytic domain of the Serine/Threonine kinases, Mitogen-activated protein kinase-activated protein kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of the MAPK-activated protein kinases MK2, MK3, MK5 (also called PRAK for p38-regulated/activated protein kinase), and related proteins. These proteins contain a catalytic kinase domain followed by a C-terminal autoinhibitory region that contains nuclear localization (NLS) and nuclear export (NES) signals with a p38 MAPK docking motif that overlaps the NLS. In addition, MK2 and MK3 contain an N-terminal proline-rich region that can bind to SH3 domains. MK2 and MK3 are bonafide substrates for the MAPK p38, while MK5 plays a functional role in the p38 MAPK pathway although their direct interaction has been difficult to detect. MK2 and MK3 are closely related and show, thus far, indistinguishable substrate specificity, while MK5 shows a distinct spectrum of substrates. MK2 and MK3 are mainly involved in the regulation of gene expression and they participate in diverse cellular processes such as endocytosis, cytokine production, cytoskeletal reorganization, cell migration, cell cycle control and chromatin remodeling. They are implicated in inflammation and cance and their substrates include mRNA-AU-rich-element (ARE)-binding proteins (TTP and hnRNP A0), Hsp proteins (Hsp27 and Hsp25) and RSK, among others. MK2/3 are both expressed ubiquitously but MK2 is expressed at significantly higher levels. MK5 is a ubiquitous protein that is implicated in neuronal morphogenesis, cell migration, and tumor angiogenesis. It interacts with PKA, which induces cytoplasmic translocation of MK5. Its substrates includes p53, ERK3/4, Hsp27, and cytosolic phospholipase A2 (cPLA2). The MAPKAPK 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 1907148278   7 PENLLLASKSKGAAVKLADFGLAIEVQGD---QQAWFgfagTPGYLSPEVLRKDPYGKPVDMWACGVILYILLVGYPPFW 83
Cdd:cd14089   128 PENLLYSSKGPNAILKLTDFGFAKETTTKkslQTPCY----TPYYVAPEVLGPEKYDKSCDMWSLGVIMYILLCGYPPFY 203

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1907148278  84 DedQHRL------YQQIKAGAYDFPSPEWDTVTPEAKDLINKMLTINPAKRITASEALKHPW 139
Cdd:cd14089   204 S--NHGLaispgmKKRIRNGQYEFPNPEWSNVSEEAKDLIRGLLKTDPSERLTIEEVMNHPW 263

Catalytic domain of AGC family Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. AGC kinases regulate many cellular processes including division, growth, survival, metabolism, motility, and differentiation. Many are implicated in the development of various human diseases. Members of this family include cAMP-dependent Protein Kinase (PKA), cGMP-dependent Protein Kinase (PKG), Protein Kinase C (PKC), Protein Kinase B (PKB), G protein-coupled Receptor Kinase (GRK), Serum- and Glucocorticoid-induced Kinase (SGK), and 70 kDa ribosomal Protein S6 Kinase (p70S6K or S6K), among others. AGC kinases share an activation mechanism based on the phosphorylation of up to three sites: the activation loop (A-loop), the hydrophobic motif (HM) and the turn motif. Phosphorylation at the A-loop is required of most AGC kinases, which results in a disorder-to-order transition of the A-loop. The ordered conformation results in the access of substrates and ATP to the active site. A subset of AGC kinases with C-terminal extensions containing the HM also requires phosphorylation at this site. Phosphorylation at the HM allows the C-terminal extension to form an ordered structure that packs into the hydrophobic pocket of the catalytic domain, which then reconfigures the kinase into an active bi-lobed state. In addition, growth factor-activated AGC kinases such as PKB, p70S6K, RSK, MSK, PKC, and SGK, require phosphorylation at the turn motif (also called tail or zipper site), located N-terminal to the HM at the C-terminal extension. The AGC 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 1907148278   7 PENLLLasKSKGAaVKLADFGLAIEVQGDQQAWFGFAGTPGYLSPEVLRKDPYGKPVDMWACGVILYILLVGYPPFWDED 86
Cdd:cd05123   121 PENILL--DSDGH-IKLTDFGLAKELSSDGDRTYTFCGTPEYLAPEVLLGKGYGKAVDWWSLGVLLYEMLTGKPPFYAEN 197

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1907148278  87 QHRLYQQIKAGAYDFPspewDTVTPEAKDLINKMLTINPAKRITA--SEALK-HPW 139
Cdd:cd05123   198 RKEIYEKILKSPLKFP----EYVSPEAKSLISGLLQKDPTKRLGSggAEEIKaHPF 249

Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase Type I delta; 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. The CaMK family includes CaMKI, CaMKII, CaMKIV, and CaMK kinase (CaMKK). In vertebrates, there are four CaMKI proteins encoded by different genes (alpha, beta, gamma, and delta), each producing at least one variant. CaMKs contain an N-terminal catalytic domain and a C-terminal regulatory domain that harbors a CaM binding site. 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. In addition, they may be involved in osteoclast differentiation and bone resorption. The CaMKI-delta subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907148278   6 QPENLLLASKSKGAAVKLADFGLAiEVQGDQQAWFGFAGTPGYLSPEVLRKDPYGKPVDMWACGVILYILLVGYPPFWDE 85
Cdd:cd14168   135 KPENLLYFSQDEESKIMISDFGLS-KMEGKGDVMSTACGTPGYVAPEVLAQKPYSKAVDCWSIGVIAYILLCGYPPFYDE 213

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907148278  86 DQHRLYQQIKAGAYDFPSPEWDTVTPEAKDLINKMLTINPAKRITASEALKHPWICQRSTVASMMHRQETVDCLKKFnAR 165
Cdd:cd14168   214 NDSKLFEQILKADYEFDSPYWDDISDSAKDFIRNLMEKDPNKRYTCEQALRHPWIAGDTALCKNIHESVSAQIRKNF-AK 292

                  ....*.
gi 1907148278 166 RKLKGA 171
Cdd:cd14168   293 SKWRQA 298

Catalytic domain of the Serine/Threonine Kinase, Doublecortin-like kinase 2 (also called Doublecortin-like and CAM kinase-like 2); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. DCKL2 (or DCAMKL2) belongs to the doublecortin (DCX) family of proteins which are involved in neuronal migration, neurogenesis, and eye receptor development, among others. Family members typically contain tandem doublecortin (DCX) domains at the N-terminus; DCX domains can bind microtubules and serve as protein-interaction platforms. In addition, DCKL2 contains a serine, threonine, and proline rich domain (SP) and a C-terminal kinase domain with similarity to CAMKs. DCKL2 has been shown to interact with tubulin, JIP1/2, JNK, neurabin 2, and actin. It is associated with the terminal segments of axons and dendrites, and may function as a phosphorylation-dependent switch to control microtubule dynamics in neuronal growth cones. The DCKL2 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 1907148278   6 QPENLLLASKSKGA-AVKLADFGLAIEVQGdqqAWFGFAGTPGYLSPEVLRKDPYGKPVDMWACGVILYILLVGYPPFWD 84
Cdd:cd14184   126 KPENLLVCEYPDGTkSLKLGDFGLATVVEG---PLYTVCGTPTYVAPEIIAETGYGLKVDIWAAGVITYILLCGFPPFRS 202

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1907148278  85 ED--QHRLYQQIKAGAYDFPSPEWDTVTPEAKDLINKMLTINPAKRITASEALKHPW 139
Cdd:cd14184   203 ENnlQEDLFDQILLGKLEFPSPYWDNITDSAKELISHMLQVNVEARYTAEQILSHPW 259

Catalytic domain of the Serine/Threonine kinase, Cell cycle Checkpoint Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Checkpoint Kinase 2 (Chk2) plays an important role in cellular responses to DNA double-strand breaks and related lesions. It is phosphorylated and activated by ATM kinase, resulting in its dissociation from sites of damage to phosphorylate downstream targets such as BRCA1, p53, cell cycle transcription factor E2F1, the promyelocytic leukemia protein (PML) involved in apoptosis, and CDC25 phosphatases, among others. Mutations in Chk2 is linked to a variety of cancers including familial breast cancer, myelodysplastic syndromes, prostate cancer, lung cancer, and osteosarcomas. Chk2 contains an N-terminal SQ/TQ cluster domain (SCD), a central forkhead-associated (FHA) domain, and a C-terminal catalytic kinase domain. The Chk2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907148278   6 QPENLLLASKSKGAAVKLADFGLAiEVQGDQQAWFGFAGTPGYLSPEVLR---KDPYGKPVDMWACGVILYILLVGYPPF 82
Cdd:cd14084   138 KPENVLLSSQEEECLIKITDFGLS-KILGETSLMKTLCGTPTYLAPEVLRsfgTEGYTRAVDCWSLGVILFICLSGYPPF 216

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 1907148278  83 WDE-DQHRLYQQIKAGAYDFPSPEWDTVTPEAKDLINKMLTINPAKRITASEALKHPWI 140
Cdd:cd14084   217 SEEyTQMSLKEQILSGKYTFIPKAWKNVSEEAKDLVKKMLVVDPSRRPSIEEALEHPWL 275

Catalytic domain of the Serine/Threonine Kinase, Phosphorylase kinase Gamma 2 subunit; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Phosphorylase kinase (PhK) catalyzes the phosphorylation of inactive phosphorylase b to form the active phosphorylase a. It coordinates hormonal, metabolic, and neuronal signals to initiate the breakdown of glycogen stores, which enables the maintenance of blood-glucose homeostasis during fasting, and is also used as a source of energy for muscle contraction. PhK is one of the largest and most complex protein kinases, composed of a heterotetramer containing four molecules each of four subunit types: one catalytic (gamma) and three regulatory (alpha, beta, and delta). The gamma 2 subunit (PhKG2) is also referred to as the testis/liver gamma isoform. Mutations in its gene cause autosomal-recessive glycogenosis of the liver. The gamma subunit, when isolated, is constitutively active and does not require phosphorylation of the A-loop for activity. The regulatory subunits restrain this kinase activity until signals are received to relieve this inhibition. For example, the kinase is activated in response to hormonal stimulation, after autophosphorylation or phosphorylation by cAMP-dependent kinase of the alpha and beta subunits. The high-affinity binding of ADP to the beta subunit also stimulates kinase activity, whereas calcium relieves inhibition by binding to the delta (calmodulin) subunit. The PhKG2 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 1907148278   6 QPENLLLASKSKgaaVKLADFGLAIEVQGDQQAWfGFAGTPGYLSPEVLR------KDPYGKPVDMWACGVILYILLVGY 79
Cdd:cd14181   143 KPENILLDDQLH---IKLSDFGFSCHLEPGEKLR-ELCGTPGYLAPEILKcsmdetHPGYGKEVDLWACGVILFTLLAGS 218

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907148278  80 PPFWDEDQHRLYQQIKAGAYDFPSPEWDTVTPEAKDLINKMLTINPAKRITASEALKHPW 139
Cdd:cd14181   219 PPFWHRRQMLMLRMIMEGRYQFSSPEWDDRSSTVKDLISRLLVVDPEIRLTAEQALQHPF 278

Protein kinase domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907148278  42 FAGTPGYLSPEVLRKDPYGKPVDMWACGVILYILLVGYPPFWDEDQHRLYQQIKAGAYDFPSPeWDTVTPEAKDLINKML 121
Cdd:pfam00069 120 FVGTPWYMAPEVLGGNPYGPKVDVWSLGCILYELLTGKPPFPGINGNEIYELIIDQPYAFPEL-PSNLSEEAKDLLKKLL 198

                          90
                  ....*....|....*....
gi 1907148278 122 TINPAKRITASEALKHPWI 140
Cdd:pfam00069 199 KKDPSKRLTATQALQHPWF 217

Catalytic domain of the Serine/Threonine kinase, Mitogen-activated protein kinase-activated protein kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAPK-activated protein kinase 3 (MAPKAP3 or MK3) contains an N-terminal proline-rich region that can bind to SH3 domains, a catalytic kinase domain followed by a C-terminal autoinhibitory region that contains nuclear localization (NLS) and nuclear export (NES) signals with a p38 MAPK docking motif that overlaps the NLS. MK3 is a bonafide substrate for the MAPK p38. It is closely related to MK2 and thus far, MK2/3 show indistinguishable substrate specificity. They are mainly involved in the regulation of gene expression and they participate in diverse cellular processes such as endocytosis, cytokine production, cytoskeletal reorganization, cell migration, cell cycle control and chromatin remodeling. They are implicated in inflammation and cance and their substrates include mRNA-AU-rich-element (ARE)-binding proteins (TTP and hnRNP A0), Hsp proteins (Hsp27 and Hsp25) and RSK, among others. MK2/3 are both expressed ubiquitously but MK2 is expressed at significantly higher levels. MK3 activity is only significant when MK2 is absent. The MK3 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 1907148278   6 QPENLLLASKSKGAAVKLADFGLAIEVQgDQQAWFGFAGTPGYLSPEVLRKDPYGKPVDMWACGVILYILLVGYPPFWDE 85
Cdd:cd14172   130 KPENLLYTSKEKDAVLKLTDFGFAKETT-VQNALQTPCYTPYYVAPEVLGPEKYDKSCDMWSLGVIMYILLCGFPPFYSN 208

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 1907148278  86 DQHR----LYQQIKAGAYDFPSPEWDTVTPEAKDLINKMLTINPAKRITASEALKHPWI 140
Cdd:cd14172   209 TGQAispgMKRRIRMGQYGFPNPEWAEVSEEAKQLIRHLLKTDPTERMTITQFMNHPWI 267

Catalytic domain of an Uncharacterized group of Serine/Threonine kinases with similarity to Calcium/calmodulin-dependent protein kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of uncharacterized STKs with similarity to CaMKs, which are multifunctional calcium and calmodulin (CaM) stimulated STKs involved in cell cycle regulation. The CaMK family includes CaMKI, CaMKII, CaMKIV, and CaMK kinase (CaMKK). CaMKs contain an N-terminal catalytic domain followed by a regulatory domain that harbors a CaM binding site. This uncharacterized subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907148278   8 ENLLLASKSKGAAVKLADFGLA-IEVQGDQQAwfgfAGTPGYLSPEVLRKDPYGKPVDMWACGVILYILLVGYPPFWDE- 85
Cdd:cd14088   128 ENLVYYNRLKNSKIVISDFHLAkLENGLIKEP----CGTPEYLAPEVVGRQRYGRPVDCWAIGVIMYILLSGNPPFYDEa 203

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1907148278  86 -----DQH--RLYQQIKAGAYDFPSPEWDTVTPEAKDLINKMLTINPAKRITASEALKHPWI 140
Cdd:cd14088   204 eeddyENHdkNLFRKILAGDYEFDSPYWDDISQAAKDLVTRLMEVEQDQRITAEEAISHEWI 265

C-terminal catalytic domain of the Serine/Threonine Kinases, Ribosomal S6 kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. RSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family. They are activated by signaling inputs from extracellular regulated kinase (ERK) and phosphoinositide dependent kinase 1 (PDK1). ERK phosphorylates and activates the CTD of RSK, serving as a docking site for PDK1, which phosphorylates and activates the NTD, which in turn phosphorylates all known RSK substrates. RSKs act as downstream effectors of mitogen-activated protein kinase (MAPK) and play key roles in mitogen-activated cell growth, differentiation, and survival. Mammals possess four RSK isoforms (RSK1-4) from distinct genes. RSK proteins are also referred to as MAP kinase-activated protein kinases (MAPKAPKs), 90 kDa ribosomal protein S6 kinases (p90-RSKs), or p90S6Ks. The RSK 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 1907148278   6 QPENLLLASKSKGA-AVKLADFGLAIEVQGDQqawfGFAGTPGY----LSPEVLRKDPYGKPVDMWACGVILYILLVGYP 80
Cdd:cd14091   121 KPSNILYADESGDPeSLRICDFGFAKQLRAEN----GLLMTPCYtanfVAPEVLKKQGYDAACDIWSLGVLLYTMLAGYT 196

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907148278  81 PFW---DEDQHRLYQQIKAGAYDFPSPEWDTVTPEAKDLINKMLTINPAKRITASEALKHPWICQRSTVASmmhRQetvd 157
Cdd:cd14091   197 PFAsgpNDTPEVILARIGSGKIDLSGGNWDHVSDSAKDLVRKMLHVDPSQRPTAAQVLQHPWIRNRDSLPQ---RQ---- 269

                         170       180
                  ....*....|....*....|.
gi 1907148278 158 cLKKFNARRKLKGAILTTMLA 178
Cdd:cd14091   270 -LTDPQDAALVKGAVAATFRA 289

Catalytic domain of the Serine/Threonine kinase, Mitogen-activated protein kinase-activated protein kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAPK-activated protein kinase 2 (MAPKAP2 or MK2) contains an N-terminal proline-rich region that can bind to SH3 domains, a catalytic kinase domain followed by a C-terminal autoinhibitory region that contains nuclear localization (NLS) and nuclear export (NES) signals with a p38 MAPK docking motif that overlaps the NLS. MK2 is a bonafide substrate for the MAPK p38. It is closely related to MK3 and thus far, MK2/3 show indistinguishable substrate specificity. They are mainly involved in the regulation of gene expression and they participate in diverse cellular processes such as endocytosis, cytokine production, cytoskeletal reorganization, cell migration, cell cycle control and chromatin remodeling. They are implicated in inflammation and cance and their substrates include mRNA-AU-rich-element (ARE)-binding proteins (TTP and hnRNP A0), Hsp proteins (Hsp27 and Hsp25) and RSK, among others. MK2/3 are both expressed ubiquitously but MK2 is expressed at significantly higher levels. The MK2 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 1907148278   6 QPENLLLASKSKGAAVKLADFGLAIEVQgDQQAWFGFAGTPGYLSPEVLRKDPYGKPVDMWACGVILYILLVGYPPFWDE 85
Cdd:cd14170   128 KPENLLYTSKRPNAILKLTDFGFAKETT-SHNSLTTPCYTPYYVAPEVLGPEKYDKSCDMWSLGVIMYILLCGYPPFYSN 206

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1907148278  86 D----QHRLYQQIKAGAYDFPSPEWDTVTPEAKDLINKMLTINPAKRITASEALKHPWICQRSTV 146
Cdd:cd14170   207 HglaiSPGMKTRIRMGQYEFPNPEWSEVSEEVKMLIRNLLKTEPTQRMTITEFMNHPWIMQSTKV 271

Catalytic domain of the yeast Serine/Threonine Kinases, Rad53 and Cds1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Rad53 and Cds1 are the checkpoint kinase 2 (Chk2) homologs found in budding and fission yeast, respectively. They play a central role in the cell's response to DNA lesions to prevent genome rearrangements and maintain genome integrity. They are phosphorylated in response to DNA damage and incomplete replication, and are essential for checkpoint control. They help promote DNA repair by stalling the cell cycle prior to mitosis in the presence of DNA damage. The Rad53/Cds1 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 1907148278   6 QPENLLLaSKSKGAAVKLADFGLAiEVQGDQQAWFGFAGTPGYLSPEVLR----KDP--YGKPVDMWACGVILYILLVGY 79
Cdd:cd14098   128 KPENILI-TQDDPVIVKISDFGLA-KVIHTGTFLVTFCGTMAYLAPEILMskeqNLQggYSNLVDMWSVGCLVYVMLTGA 205

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907148278  80 PPFWDEDQHRLYQQIKAGAYDFPSPEWDTVTPEAKDLINKMLTINPAKRITASEALKHPW 139
Cdd:cd14098   206 LPFDGSSQLPVEKRIRKGRYTQPPLVDFNISEEAIDFILRLLDVDPEKRMTAAQALDHPW 265