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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217357499    1 MKTVCGTPGYCAPEILRGCAYGPEVDMWSVGIITYILLCGFEPFYDERGDQFMFRRILNCEYYFISPWWDeVSLNAKDLV 80
Cdd:smart00220 153 LTTFVGTPEYMAPEVLLGKGYGKAVDIWSLGVILYELLTGKPPFPGDDQLLELFKKIGKPKPPFPPPEWD-ISPEAKDLI 231

                           90       100
                   ....*....|....*....|...
gi 2217357499   81 RKLIVLDPKKRLTTFQALQHPWV 103
Cdd:smart00220 232 RKLLVKDPEKRLTAEEALQHPFF 254

protein kinase A catalytic subunit; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217357499   3 TVCGTPGYCAPEILRGCAYGPEVDMWSVGIITYILLCGFEPFYDERGDQfMFRRILNCEYYFisPWWdeVSLNAKDLVRK 82
Cdd:PTZ00263  174 TLCGTPEYLAPEVIQSKGHGKAVDWWTMGVLLYEFIAGYPPFFDDTPFR-IYEKILAGRLKF--PNW--FDGRARDLVKG 248

                          90       100
                  ....*....|....*....|....*...
gi 2217357499  83 LIVLDPKKRLTTFQ-----ALQHPWVTG 105
Cdd:PTZ00263  249 LLQTDHTKRLGTLKggvadVKNHPYFHG 276

The catalytic domain of CAMK family Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CaMKs are multifunctional calcium and calmodulin (CaM) stimulated STKs involved in cell cycle regulation. There are several types of CaMKs including CaMKI, CaMKII, and CaMKIV. CaMKI proteins are monomeric and they play pivotal roles in the nervous system, including long-term potentiation, dendritic arborization, neurite outgrowth, and the formation of spines, synapses, and axons. CaMKII is a signaling molecule that translates upstream calcium and reactive oxygen species (ROS) signals into downstream responses that play important roles in synaptic function and cardiovascular physiology. CAMKIV is implicated in regulating several transcription factors like CREB, MEF2, and retinoid orphan receptors, as well as in T-cell development and signaling. The CAMK family also consists of other related kinases including the Phosphorylase kinase Gamma subunit (PhKG), the C-terminal kinase domains of Ribosomal S6 kinase (RSK) and Mitogen and stress-activated kinase (MSK), Doublecortin-like kinase (DCKL), and the MAPK-activated protein kinases MK2, MK3, and MK5, among others. The CAMK family is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217357499   1 MKTVCGTPGYCAPEILRGCAYGPEVDMWSVGIITYILLCGFEPFYDERgDQFMFRRILNCEYYFISPWWDEVSLNAKDLV 80
Cdd:cd05117   158 LKTVCGTPYYVAPEVLKGKGYGKKCDIWSLGVILYILLCGYPPFYGET-EQELFEKILKGKYSFDSPEWKNVSEEAKDLI 236

                          90       100
                  ....*....|....*....|..
gi 2217357499  81 RKLIVLDPKKRLTTFQALQHPW 102
Cdd:cd05117   237 KRLLVVDPKKRLTAAEALNHPW 258

Catalytic domain of the Serine/Threonine Kinase, Doublecortin-like kinase (also called Doublecortin-like and CAM kinase-like); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. DCKL (or DCAMKL) proteins belong 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, DCKL proteins contain a C-terminal kinase domain with similarity to CAMKs. They are involved in the regulation of cAMP signaling. Vertebrates contain three DCKL proteins (DCKL1-3); DCKL1 and 2 also contain a serine, threonine, and proline rich domain (SP), while DCKL3 contains only a single DCX domain instead of tandem domains. The DCKL 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 2217357499   3 TVCGTPGYCAPEILRGCAYGPEVDMWSVGIITYILLCGFEPFYDERGDQ-FMFRRILNCEYYFISPWWDEVSLNAKDLVR 81
Cdd:cd14095   158 TVCGTPTYVAPEILAETGYGLKVDIWAAGVITYILLCGFPPFRSPDRDQeELFDLILAGEFEFLSPYWDNISDSAKDLIS 237

                          90       100
                  ....*....|....*....|.
gi 2217357499  82 KLIVLDPKKRLTTFQALQHPW 102
Cdd:cd14095   238 RMLVVDPEKRYSAGQVLDHPW 258

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 2217357499   1 MKTVCGTPGYCAPEILRGCAYGPEVDMWSVGIITYILLCGFEPFYDErGDQFMFRRILNCEYYFISPWWDEVSLNAKDLV 80
Cdd:cd14167   160 MSTACGTPGYVAPEVLAQKPYSKAVDCWSIGVIAYILLCGYPPFYDE-NDAKLFEQILKAEYEFDSPYWDDISDSAKDFI 238

                          90       100
                  ....*....|....*....|....*
gi 2217357499  81 RKLIVLDPKKRLTTFQALQHPWVTG 105
Cdd:cd14167   239 QHLMEKDPEKRFTCEQALQHPWIAG 263

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 2217357499   6 GTPGYCAPEILRGCAYGPEVDMWSVGIITYILLCGFEPFYDErGDQFMFRRILNCEYYFISPWWDEVSLNAKDLVRKLIV 85
Cdd:cd14086   165 GTPGYLSPEVLRKDPYGKPVDIWACGVILYILLVGYPPFWDE-DQHRLYAQIKAGAYDYPSPEWDTVTPEAKDLINQMLT 243

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*....
gi 2217357499  86 LDPKKRLTTFQALQHPWVTGK--AANFVHMDTAQKKLQEFNARRKLKAA 132
Cdd:cd14086   244 VNPAKRITAAEALKHPWICQRdrVASMVHRQETVDCLKKFNARRKLKGA 292

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 2217357499   1 MKTVCGTPGYCAPEILRGCAYGPEVDMWSVGIITYILLCGFEPFYDERGDQfMFRRILNCEYYFISPWWDEVSLNAKDLV 80
Cdd:cd14166   158 MSTACGTPGYVAPEVLAQKPYSKAVDCWSIGVITYILLCGYPPFYEETESR-LFEKIKEGYYEFESPFWDDISESAKDFI 236

                          90       100
                  ....*....|....*....|....*...
gi 2217357499  81 RKLIVLDPKKRLTTFQALQHPWVTGKAA 108
Cdd:cd14166   237 RHLLEKNPSKRYTCEKALSHPWIIGNTA 264

Catalytic domain of the Serine/Threonine Kinase, Phosphorylase kinase Gamma 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). Each subunit has tissue-specific isoforms or splice variants. Vertebrates contain two isoforms of the gamma subunit (gamma 1 and gamma 2). 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 PhKG 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 2217357499   1 MKTVCGTPGYCAPEILRgCA-------YGPEVDMWSVGIITYILLCGFEPFYdERGDQFMFRRILNCEYYFISPWWDEVS 73
Cdd:cd14093   165 LRELCGTPGYLAPEVLK-CSmydnapgYGKEVDMWACGVIMYTLLAGCPPFW-HRKQMVMLRNIMEGKYEFGSPEWDDIS 242

                          90       100
                  ....*....|....*....|....*....
gi 2217357499  74 LNAKDLVRKLIVLDPKKRLTTFQALQHPW 102
Cdd:cd14093   243 DTAKDLISKLLVVDPKKRLTAEEALEHPF 271

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 2217357499   1 MKTVCGTPGYCAPEILR---GCAYGPEVDMWSVGIITYILLCGFEPFYDERGDQFMFRRILNCEYYFISPWWDEVSLNAK 77
Cdd:cd14084   170 MKTLCGTPTYLAPEVLRsfgTEGYTRAVDCWSLGVILFICLSGYPPFSEEYTQMSLKEQILSGKYTFIPKAWKNVSEEAK 249

                          90       100
                  ....*....|....*....|....*.
gi 2217357499  78 DLVRKLIVLDPKKRLTTFQALQHPWV 103
Cdd:cd14084   250 DLVKKMLVVDPSRRPSIEEALEHPWL 275

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 2217357499   1 MKTVCGTPGYCAPEILrgcayGPE-----VDMWSVGIITYILLCGFEPFYDERGDQF---MFRRILNCEYYFISPWWDEV 72
Cdd:cd14089   159 LQTPCYTPYYVAPEVL-----GPEkydksCDMWSLGVIMYILLCGYPPFYSNHGLAIspgMKKRIRNGQYEFPNPEWSNV 233

                          90       100       110
                  ....*....|....*....|....*....|
gi 2217357499  73 SLNAKDLVRKLIVLDPKKRLTTFQALQHPW 102
Cdd:cd14089   234 SEEAKDLIRGLLKTDPSERLTIEEVMNHPW 263

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 2217357499   1 MKTVCGTPGYCAPEILRGCAY-GPEVDMWSVGIITYILLCGFEPFyDERGDQFMFRRILNCEYYfISPWwdeVSLNAKDL 79
Cdd:cd14003   155 LKTFCGTPAYAAPEVLLGRKYdGPKADVWSLGVILYAMLTGYLPF-DDDNDSKLFRKILKGKYP-IPSH---LSPDARDL 229

                          90       100
                  ....*....|....*....|...
gi 2217357499  80 VRKLIVLDPKKRLTTFQALQHPW 102
Cdd:cd14003   230 IRRMLVVDPSKRITIEEILNHPW 252

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 2217357499   2 KTVCGTPGYCAPEILRGCAYGPEVDMWSVGIITYILLCGFEPFYDErGDQFMFRRILNCEYYFISPWWDEVSLNAKDLVR 81
Cdd:cd14006   148 KEIFGTPEFVAPEIVNGEPVSLATDMWSIGVLTYVLLSGLSPFLGE-DDQETLANISACRVDFSEEYFSSVSQEAKDFIR 226

                          90       100
                  ....*....|....*....|.
gi 2217357499  82 KLIVLDPKKRLTTFQALQHPW 102
Cdd:cd14006   227 KLLVKEPRKRPTAQEALQHPW 247

Catalytic domain of the Serine/Threonine Kinase, Doublecortin-like kinase 1 (also called Doublecortin-like and CAM kinase-like 1); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. DCKL1 (or DCAMKL1) 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, DCKL1 contains a serine, threonine, and proline rich domain (SP) and a C-terminal kinase domain with similarity to CAMKs. DCKL1 interacts with tubulin, glucocorticoid receptor, dynein, JIP1/2, caspases (3 and 8), and calpain, among others. It plays roles in neurogenesis, neuronal migration, retrograde transport, and neuronal apoptosis. The DCKL1 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 2217357499   3 TVCGTPGYCAPEILRGCAYGPEVDMWSVGIITYILLCGFEPFYDERGDQ-FMFRRILNCEYYFISPWWDEVSLNAKDLVR 81
Cdd:cd14183   164 TVCGTPTYVAPEIIAETGYGLKVDIWAAGVITYILLCGFPPFRGSGDDQeVLFDQILMGQVDFPSPYWDNVSDSAKELIT 243

                          90       100
                  ....*....|....*....|...
gi 2217357499  82 KLIVLDPKKRLTTFQALQHPWVT 104
Cdd:cd14183   244 MMLQVDVDQRYSALQVLEHPWVN 266

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 2217357499   1 MKTVCGTPGYCAPEILRgCA-------YGPEVDMWSVGIITYILLCGFEPFYdERGDQFMFRRILNCEYYFISPWWDEVS 73
Cdd:cd14181   172 LRELCGTPGYLAPEILK-CSmdethpgYGKEVDLWACGVILFTLLAGSPPFW-HRRQMLMLRMIMEGRYQFSSPEWDDRS 249

                          90       100
                  ....*....|....*....|....*....
gi 2217357499  74 LNAKDLVRKLIVLDPKKRLTTFQALQHPW 102
Cdd:cd14181   250 STVKDLISRLLVVDPEIRLTAEQALQHPF 278

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 2217357499   1 MKTVCGTPGYCAPEILRGCAYGPEVDMWSVGIITYILLCGFEPFYDERGDQF---MFRRILNCEYYFISPWWDEVSLNAK 77
Cdd:cd14172   162 LQTPCYTPYYVAPEVLGPEKYDKSCDMWSLGVIMYILLCGFPPFYSNTGQAIspgMKRRIRMGQYGFPNPEWAEVSEEAK 241

                          90       100
                  ....*....|....*....|....*.
gi 2217357499  78 DLVRKLIVLDPKKRLTTFQALQHPWV 103
Cdd:cd14172   242 QLIRHLLKTDPTERMTITQFMNHPWI 267

Catalytic domain of the Serine/Threonine Kinase, Myosin Light Chain Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MLCK phosphorylates myosin regulatory light chain and controls the contraction of all muscle types. In vertebrates, different MLCKs function in smooth (MLCK1), skeletal (MLCK2), and cardiac (MLCK3) muscles. A fourth protein, MLCK4, has also been identified through comprehensive genome analysis although it has not been biochemically characterized. The MLCK1 gene expresses three transcripts in a cell-specific manner: a short MLCK1 which contains three immunoglobulin (Ig)-like and one fibronectin type III (FN3) domains, PEVK and actin-binding regions, and a kinase domain near the C-terminus; a long MLCK1 containing six additional Ig-like domains at the N-terminus compared to the short MLCK1; and the C-terminal Ig module. MLCK2, MLCK3, and MLCK4 share a simpler domain architecture of a single kinase domain near the C-terminus and the absence of Ig-like or FN3 domains. The MLCK 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 2217357499   2 KTVCGTPGYCAPEILRGCAYGPEVDMWSVGIITYILLCGFEPFYDErGDQFMFRRILNCEYYFISPWWDEVSLNAKDLVR 81
Cdd:cd14103   150 KVLFGTPEFVAPEVVNYEPISYATDMWSVGVICYVLLSGLSPFMGD-NDAETLANVTRAKWDFDDEAFDDISDEAKDFIS 228

                          90       100
                  ....*....|....*....|.
gi 2217357499  82 KLIVLDPKKRLTTFQALQHPW 102
Cdd:cd14103   229 KLLVKDPRKRMSAAQCLQHPW 249

Catalytic domain of the Serine/Threonine Kinases, Polo-like kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PLKs play important roles in cell cycle progression and in DNA damage responses. They regulate mitotic entry, mitotic exit, and cytokinesis. In general PLKs contain an N-terminal catalytic kinase domain and a C-terminal regulatory polo box domain (PBD), which is comprised by two bipartite polo-box motifs (or polo boxes) and is involved in protein interactions. PLKs derive their names from homology to polo, a kinase first identified in Drosophila. There are five mammalian PLKs (PLK1-5) from distinct genes. There is good evidence that PLK1 may function as an oncogene while PLK2-5 have tumor suppressive properties. PLK1 functions as a positive regulator of mitosis, meiosis, and cytokinesis. PLK2 functions in G1 progression, S-phase arrest, and centriole duplication. PLK3 regulates angiogenesis and responses to DNA damage. PLK4 is required for late mitotic progression, cell survival, and embryonic development. PLK5 was first identified as a pseudogene containing a stop codon within the kinase domain, however, both murine and human genes encode expressed proteins. PLK5 functions in cell cycle arrest.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217357499   2 KTVCGTPGYCAPEILRGC-AYGPEVDMWSVGIITYILLCGFEPFydERGDQ-FMFRRILNCEYYFisPWWDEVSLNAKDL 79
Cdd:cd14099   159 KTLCGTPNYIAPEVLEKKkGHSFEVDIWSLGVILYTLLVGKPPF--ETSDVkETYKRIKKNEYSF--PSHLSISDEAKDL 234

                          90       100
                  ....*....|....*....|...
gi 2217357499  80 VRKLIVLDPKKRLTTFQALQHPW 102
Cdd:cd14099   235 IRSMLQPDPTKRPSLDEILSHPF 257

Catalytic domain of the Alpha subunit of the Serine/Threonine Kinase, AMP-activated protein kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. 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. In response to decreased ATP levels, it enhances energy-producing processes and inhibits energy-consuming pathways. Once activated, AMPK phosphorylates a broad range of downstream targets, with effects in carbohydrate metabolism and uptake, lipid and fatty acid biosynthesis, carbon energy storage, and inflammation, among others. Defects in energy homeostasis underlie many human diseases including Type 2 diabetes, obesity, heart disease, and cancer. As a result, AMPK has emerged as a therapeutic target in the treatment of these diseases. The AMPK 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 2217357499   1 MKTVCGTPGYCAPEILRGCAY-GPEVDMWSVGIITYILLCGFEPFYDERgDQFMFRRILNCEYYFisPwwDEVSLNAKDL 79
Cdd:cd14079   158 LKTSCGSPNYAAPEVISGKLYaGPEVDVWSCGVILYALLCGSLPFDDEH-IPNLFKKIKSGIYTI--P--SHLSPGARDL 232

                          90       100
                  ....*....|....*....|...
gi 2217357499  80 VRKLIVLDPKKRLTTFQALQHPW 102
Cdd:cd14079   233 IKRMLVVDPLKRITIPEIRQHPW 255

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        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217357499   2 KTVCGTPGYCAPEILRGCAYGPEVDMWSVGIITYILLCGFEPFYDERGDQfMFRRILNCEYYFISPwwDEVSLNAKDLVR 81
Cdd:cd05579   166 RRIVGTPDYLAPEILLGQGHGKTVDWWSLGVILYEFLVGIPPFHAETPEE-IFQNILNGKIEWPED--PEVSDEAKDLIS 242

                          90       100
                  ....*....|....*....|....*..
gi 2217357499  82 KLIVLDPKKRL--TTFQAL-QHPWVTG 105
Cdd:cd05579   243 KLLTPDPEKRLgaKGIEEIkNHPFFKG 269

Catalytic domain of Rho-associated coiled-coil containing protein kinase (ROCK)- and Nuclear Dbf2-Related (NDR)-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Members of this subfamily include ROCK and ROCK-like proteins such as DMPK, MRCK, and CRIK, as well as NDR and NDR-like proteins such as LATS, CBK1 and Sid2p. ROCK and CRIK are effectors of the small GTPase Rho, while MRCK is an effector of the small GTPase Cdc42. NDR and NDR-like kinases contain an N-terminal regulatory (NTR) domain and an insert within the catalytic domain that contains an auto-inhibitory sequence. Proteins in this subfamily are involved in regulating many cellular functions including contraction, motility, division, proliferation, apoptosis, morphogenesis, and cytokinesis. The ROCK/NDR-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 2217357499   3 TVCGTPGYCAPEILRGCAYGPEVDMWSVGIITYILLCGFEPFYDErGDQFMFRRILNCEYYFISPWWDEVSLNAKDLVRK 82
Cdd:cd05573   189 SAVGTPDYIAPEVLRGTGYGPECDWWSLGVILYEMLYGFPPFYSD-SLVETYSKIMNWKESLVFPDDPDVSPEAIDLIRR 267

                          90       100
                  ....*....|....*....|.
gi 2217357499  83 LIVlDPKKRLTTF-QALQHPW 102
Cdd:cd05573   268 LLC-DPEDRLGSAeEIKAHPF 287

Catalytic domain of the Serine/Threonine kinases, Mitogen-activated protein kinase signal-integrating kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAPK signal-integrating kinases (Mnks) are MAPK-activated protein kinases and is comprised by a group of four proteins, produced by alternative splicing from two genes (Mnk1 and Mnk2). The isoforms of Mnk1 (1a/1b) and Mnk2 (2a/2b) differ at their C-termini, with the a-form having a longer C-terminus containing a MAPK-binding region. All Mnks contain a catalytic kinase domain and a polybasic region at the N-terminus which binds importin and the eukaryotic initiation factor eIF4G. The best characterized Mnk substrate is eIF4G, whose phosphorylation may promote the export of certain mRNAs from the nucleus. Mnk also phosphorylate substrates that bind to AU-rich elements that regulate mRNA stability and translation. Mnks have also been implicated in tyrosine kinase receptor signaling, inflammation, and cell prolieration or survival. The Mnk 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 2217357499   3 TVCGTPGYCAPEIL-----RGCAYGPEVDMWSVGIITYILLCGFEPFYD--------ERGD------QFMFRRILNCEYY 63
Cdd:cd14090   170 TPVGSAEYMAPEVVdafvgEALSYDKRCDLWSLGVILYIMLCGYPPFYGrcgedcgwDRGEacqdcqELLFHSIQEGEYE 249

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|
gi 2217357499  64 FISPWWDEVSLNAKDLVRKLIVLDPKKRLTTFQALQHPWV 103
Cdd:cd14090   250 FPEKEWSHISAEAKDLISHLLVRDASQRYTAEQVLQHPWV 289

Catalytic domain of the Serine/Threonine Kinase, Death-associated protein kinase-Related Apoptosis-inducing protein Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. DRAKs, also called STK17, were named based on their similarity (around 50% identity) to the kinase domain of DAPKs. They contain an N-terminal kinase domain and a C-terminal regulatory domain. Vertebrates contain two subfamily members, DRAK1 and DRAK2. Both DRAKs are localized to the nucleus, autophosphorylate themselves, and phosphorylate myosin light chain as a substrate. They may play a role in apoptotic signaling. The DRAK 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 2217357499   6 GTPGYCAPEILrgcAYGP---EVDMWSVGIITYILLCGFEPFydeRGD--QFMFRRILNCEYYFISPWWDEVSLNAKDLV 80
Cdd:cd14106   172 GTPDYVAPEIL---SYEPislATDMWSIGVLTYVLLTGHSPF---GGDdkQETFLNISQCNLDFPEELFKDVSPLAIDFI 245

                          90       100
                  ....*....|....*....|...
gi 2217357499  81 RKLIVLDPKKRLTTFQALQHPWV 103
Cdd:cd14106   246 KRLLVKDPEKRLTAKECLEHPWL 268

Catalytic domain of the Serine/Threonine kinase, Mitogen-activated protein kinase-activated protein kinase 5; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAPK-activated protein kinase 5 (MAPKAP5 or MK5) is also called PRAK (p38-regulated/activated protein kinase). It contains 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. 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 2217357499   7 TPGYCAPEIL----------RGC-------AYGPEVDMWSVGIITYILLCGFEPFYDE----RGDQFMFRRILNCEYYFI 65
Cdd:cd14171   172 TPYYVAPQVLeaqrrhrkerSGIptsptpyTYDKSCDMWSLGVIIYIMLCGYPPFYSEhpsrTITKDMKRKIMTGSYEFP 251

                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 2217357499  66 SPWWDEVSLNAKDLVRKLIVLDPKKRLTTFQALQHPWV 103
Cdd:cd14171   252 EEEWSQISEMAKDIVRKLLCVDPEERMTIEEVLHHPWL 289

Catalytic domain of the Serine/Threonine Kinase, Death-Associated Protein Kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. DAPKs mediate cell death and act as tumor suppressors. They are necessary to induce cell death and their overexpression leads to death-associated changes including membrane blebbing, cell rounding, and formation of autophagic vesicles. Vertebrates contain three subfamily members with different domain architecture, localization, and function. DAPK3, also called DAP-like kinase (DLK) and zipper-interacting protein kinase (ZIPk), contains an N-terminal kinase domain and a C-terminal region with nuclear localization signals (NLS) and a leucine zipper motif that mediates homodimerization and interaction with other leucine zipper proteins. It interacts with Par-4, a protein that contains a death domain and interacts with actin filaments. DAPK3 is present in both the cytoplasm and nucleus. Its co-expression with Par-4 results in the co-localization of the two proteins to actin filaments. In addition to cell death, DAPK3 is also implicated in mediating cell motility and the contraction of smooth muscles. The DAPK3 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 2217357499   2 KTVCGTPGYCAPEILRGCAYGPEVDMWSVGIITYILLCGFEPFYDERgDQFMFRRILNCEYYFISPWWDEVSLNAKDLVR 81
Cdd:cd14195   169 KNIFGTPEFVAPEIVNYEPLGLEADMWSIGVITYILLSGASPFLGET-KQETLTNISAVNYDFDEEYFSNTSELAKDFIR 247

                          90       100
                  ....*....|....*....|..
gi 2217357499  82 KLIVLDPKKRLTTFQALQHPWV 103
Cdd:cd14195   248 RLLVKDPKKRMTIAQSLEHSWI 269

C-terminal catalytic domain of the Serine/Threonine Kinase, Ribosomal S6 kinase 1 (also called Ribosomal protein S6 kinase alpha-1 or 90kDa ribosomal protein S6 kinase 1); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. RSK1 is also called S6K-alpha-1, RPS6KA1, p90RSK1 or MAPK-activated protein kinase 1a (MAPKAPK-1a). It is a component of the insulin transduction pathway, regulating the function of IRS1. It also interacts with PKA and promotes its inactivation. RSK1 is one of four RSK isoforms (RSK1-4) from distinct genes present in vertebrates. 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. The RSK1 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 2217357499   1 MKTVCGTPGYCAPEILRGCAYGPEVDMWSVGIITYILLCGFEPFYDERGD--QFMFRRILNCEYYFISPWWDEVSLNAKD 78
Cdd:cd14175   156 LMTPCYTANFVAPEVLKRQGYDEGCDIWSLGILLYTMLAGYTPFANGPSDtpEEILTRIGSGKFTLSGGNWNTVSDAAKD 235

                          90       100
                  ....*....|....*....|....*...
gi 2217357499  79 LVRKLIVLDPKKRLTTFQALQHPWVTGK 106
Cdd:cd14175   236 LVSKMLHVDPHQRLTAKQVLQHPWITQK 263