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 21426781  69 LEREQGNCTYRALHCPTGTEYTCKVYPASEAQAVLAPYARLPTHQHVARPTEVLLGSQLLYTFFTKTHGDLHSLVRSRRG 148
Cdd:cd14024   1 LEPWEGQELYRAEHYQTEKEYTCKVLSLRSYQECLAPYDRLGPHEGVCSVLEVVIGQDRAYAFFSRHYGDMHSHVRRRRR 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21426781 149 IPEPEAAALFRQMASAVAHCHKHGLILRDLKLRRFVFSNCERTKLVLENLEDACVMTGPDDSLWDKHACPAYVGPEILSS 228
Cdd:cd14024  81 LSEDEARGLFTQMARAVAHCHQHGVILRDLKLRRFVFTDELRTKLVLVNLEDSCPLNGDDDSLTDKHGCPAYVGPEILSS 160

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21426781 229 RPSYSGRAADVWSLGVALFTMLAGRYPFQDSEPALLFGKIRRGTFALPEGLSASARCLIRCLLRREPSERLVALGILLHP 308
Cdd:cd14024 161 RRSYSGKAADVWSLGVCLYTMLLGRYPFQDTEPAALFAKIRRGAFSLPAWLSPGARCLVSCMLRRSPAERLKASEILLHP 240

                ..
gi 21426781 309 WL 310
Cdd:cd14024 241 WL 242

Pseudokinase domain of Tribbles Homolog 3; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. TRB3 binds and regulates ATF4, p65/RelA, and PKB (or Akt). It negatively regulates ATF4-mediated gene expression including that of CHOP (C/EBP homologous protein) and HO-1, which are both involved in modulating apoptosis. It also inhibits insulin-mediated phosphorylation of PKB and is a possible determinant of insulin resistance and related disorders. In osteoarthritic chondrocytes where it inhibits insulin-like growth factor 1-mediated cell survival, TRB3 is overexpressed, resulting in increased cell death. TRB3 is one of three Tribbles Homolog (TRB) proteins present in vertebrates that are encoded by three separate genes. TRB proteins interact with many proteins involved in signalling pathways. They play scaffold-like regulatory functions and affect many cellular processes such as mitosis, apoptosis, and gene expression. The TRB3 subfamily is part of a larger superfamily that includes the catalytic domains of serine/threonine kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21426781  69 LEREQGNCTYRALHCPTGTEYTCKVYPASEAQAVLAPYARLPTHQHVARPTEVLLGSQLLYTFFTKTHGDLHSLVRSRRG 148
Cdd:cd14024   1 LEPWEGQELYRAEHYQTEKEYTCKVLSLRSYQECLAPYDRLGPHEGVCSVLEVVIGQDRAYAFFSRHYGDMHSHVRRRRR 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21426781 149 IPEPEAAALFRQMASAVAHCHKHGLILRDLKLRRFVFSNCERTKLVLENLEDACVMTGPDDSLWDKHACPAYVGPEILSS 228
Cdd:cd14024  81 LSEDEARGLFTQMARAVAHCHQHGVILRDLKLRRFVFTDELRTKLVLVNLEDSCPLNGDDDSLTDKHGCPAYVGPEILSS 160

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21426781 229 RPSYSGRAADVWSLGVALFTMLAGRYPFQDSEPALLFGKIRRGTFALPEGLSASARCLIRCLLRREPSERLVALGILLHP 308
Cdd:cd14024 161 RRSYSGKAADVWSLGVCLYTMLLGRYPFQDTEPAALFAKIRRGAFSLPAWLSPGARCLVSCMLRRSPAERLKASEILLHP 240

                ..
gi 21426781 309 WL 310
Cdd:cd14024 241 WL 242

Protein kinase domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21426781    76 CTYRALHCPTGTEYTCKVypaseaqaVLAPYARLPTHQHVARPTEVLLGSQ------LLYTFFTKTH----------GDL 139
Cdd:pfam00069  14 TVYKAKHRDTGKIVAIKK--------IKKEKIKKKKDKNILREIKILKKLNhpnivrLYDAFEDKDNlylvleyvegGSL 85

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21426781   140 HSLVRSRRGIPEPEAAALFRQMASAvahchkhglilrdlklrrfvfsncertklvLENLEDACVMTGpddSLWdkhacpa 219
Cdd:pfam00069  86 FDLLSEKGAFSEREAKFIMKQILEG------------------------------LESGSSLTTFVG---TPW------- 125

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21426781   220 YVGPEILSSRPsYsGRAADVWSLGVALFTMLAGRYPFQDSEPALLFGKIRRGTFA---LPEGLSASARCLIRCLLRREPS 296
Cdd:pfam00069 126 YMAPEVLGGNP-Y-GPKVDVWSLGCILYELLTGKPPFPGINGNEIYELIIDQPYAfpeLPSNLSEEAKDLLKKLLKKDPS 203

                         250
                  ....*....|....
gi 21426781   297 ERLVALGILLHPWL 310
Cdd:pfam00069 204 KRLTATQALQHPWF 217

protein kinase A catalytic subunit; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21426781  137 GDLHSLVRSRRGIPEPEAAALFRQMASAVAHCHKHGLILRDLKLRRFVFSNCERTKLVlenleDACVMTGPDDSLWDKHA 216
Cdd:PTZ00263 103 GELFTHLRKAGRFPNDVAKFYHAELVLAFEYLHSKDIIYRDLKPENLLLDNKGHVKVT-----DFGFAKKVPDRTFTLCG 177

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21426781  217 CPAYVGPEILSSRPSysGRAADVWSLGVALFTMLAGRYPFQDSEPALLFGKIRRGTFALPEGLSASARCLIRCLLRREPS 296
Cdd:PTZ00263 178 TPEYLAPEVIQSKGH--GKAVDWWTMGVLLYEFIAGYPPFFDDTPFRIYEKILAGRLKFPNWFDGRARDLVKGLLQTDHT 255

                 ....*.
gi 21426781  297 ERLVAL 302
Cdd:PTZ00263 256 KRLGTL 261

Pseudokinase domain of Tribbles Homolog 3; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. TRB3 binds and regulates ATF4, p65/RelA, and PKB (or Akt). It negatively regulates ATF4-mediated gene expression including that of CHOP (C/EBP homologous protein) and HO-1, which are both involved in modulating apoptosis. It also inhibits insulin-mediated phosphorylation of PKB and is a possible determinant of insulin resistance and related disorders. In osteoarthritic chondrocytes where it inhibits insulin-like growth factor 1-mediated cell survival, TRB3 is overexpressed, resulting in increased cell death. TRB3 is one of three Tribbles Homolog (TRB) proteins present in vertebrates that are encoded by three separate genes. TRB proteins interact with many proteins involved in signalling pathways. They play scaffold-like regulatory functions and affect many cellular processes such as mitosis, apoptosis, and gene expression. The TRB3 subfamily is part of a larger superfamily that includes the catalytic domains of serine/threonine kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21426781  69 LEREQGNCTYRALHCPTGTEYTCKVYPASEAQAVLAPYARLPTHQHVARPTEVLLGSQLLYTFFTKTHGDLHSLVRSRRG 148
Cdd:cd14024   1 LEPWEGQELYRAEHYQTEKEYTCKVLSLRSYQECLAPYDRLGPHEGVCSVLEVVIGQDRAYAFFSRHYGDMHSHVRRRRR 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21426781 149 IPEPEAAALFRQMASAVAHCHKHGLILRDLKLRRFVFSNCERTKLVLENLEDACVMTGPDDSLWDKHACPAYVGPEILSS 228
Cdd:cd14024  81 LSEDEARGLFTQMARAVAHCHQHGVILRDLKLRRFVFTDELRTKLVLVNLEDSCPLNGDDDSLTDKHGCPAYVGPEILSS 160

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21426781 229 RPSYSGRAADVWSLGVALFTMLAGRYPFQDSEPALLFGKIRRGTFALPEGLSASARCLIRCLLRREPSERLVALGILLHP 308
Cdd:cd14024 161 RRSYSGKAADVWSLGVCLYTMLLGRYPFQDTEPAALFAKIRRGAFSLPAWLSPGARCLVSCMLRRSPAERLKASEILLHP 240

                ..
gi 21426781 309 WL 310
Cdd:cd14024 241 WL 242

Pseudokinase domain of Tribbles Homolog 2; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. TRB2 binds and negatively regulates the mitogen activated protein kinase (MAPK) kinases, MKK7 and MEK1, which are activators of the MAPKs, ERK and JNK. It controls the activation of inflammatory monocytes, which is essential in innate immune responses and the pathogenesis of inflammatory diseases such as atherosclerosis. TRB2 expression is down-regulated in human acute myeloid leukaemia (AML), which may lead to enhanced cell survival and pathogenesis of the disease. TRB2 is one of three Tribbles Homolog (TRB) proteins present in vertebrates that are encoded by three separate genes. TRB proteins interact with many proteins involved in signalling pathways. They play scaffold-like regulatory functions and affect many cellular processes such as mitosis, apoptosis, and gene expression. The TRB2 subfamily is part of a larger superfamily that includes the catalytic domains of serine/threonine kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21426781  69 LEREQGNCTYRALHCPTGTEYTCKVYPASEAQAVLAPYARLPTHQHVARPTEVLLGSQLLYTFFTKTHGDLHSLVRSRRG 148
Cdd:cd14022   1 LEPLEGDHVFRAVHLHSGEELVCKVFDIGCYQESLAPCFCLPAHSNINQITEIILGETKAYVFFERSYGDMHSFVRTCKK 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21426781 149 IPEPEAAALFRQMASAVAHCHKHGLILRDLKLRRFVFSNCERTKLVLENLEDACVMTGPDDSLWDKHACPAYVGPEILSS 228
Cdd:cd14022  81 LREEEAARLFYQIASAVAHCHDGGLVLRDLKLRKFVFKDEERTRVKLESLEDAYILRGHDDSLSDKHGCPAYVSPEILNT 160

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21426781 229 RPSYSGRAADVWSLGVALFTMLAGRYPFQDSEPALLFGKIRRGTFALPEGLSASARCLIRCLLRREPSERLVALGILLHP 308
Cdd:cd14022 161 SGSYSGKAADVWSLGVMLYTMLVGRYPFHDIEPSSLFSKIRRGQFNIPETLSPKAKCLIRSILRREPSERLTSQEILDHP 240

                ..
gi 21426781 309 WL 310
Cdd:cd14022 241 WF 242

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 21426781  65 PYILLER-EQGNC--TYRALHCPTGTEYTCKVYPASEAQAVLAPYA-------RLPTHQHVARPTEVLLgsqllytffTK 134
Cdd:cd14003   1 NYELGKTlGEGSFgkVKLARHKLTGEKVAIKIIDKSKLKEEIEEKIkreieimKLLNHPNIIKLYEVIE---------TE 71

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21426781 135 TH----------GDLHSLVRSRRGIPEPEAAALFRQMASAVAHCHKHGLILRDLKLRRFVFSNCERTKLVlenleD--AC 202
Cdd:cd14003  72 NKiylvmeyasgGELFDYIVNNGRLSEDEARRFFQQLISAVDYCHSNGIVHRDLKLENILLDKNGNLKII-----DfgLS 146

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21426781 203 VMTGPDDSLwdKHAC--PAYVGPEILSSRPsYSGRAADVWSLGVALFTMLAGRYPFQDSEPALLFGKIRRGTFALPEGLS 280
Cdd:cd14003 147 NEFRGGSLL--KTFCgtPAYAAPEVLLGRK-YDGPKADVWSLGVILYAMLTGYLPFDDDNDSKLFRKILKGKYPIPSHLS 223

                       250       260
                ....*....|....*....|....*....
gi 21426781 281 ASARCLIRCLLRREPSERLVALGILLHPW 309
Cdd:cd14003 224 PDARDLIRRMLVVDPSKRITIEEILNHPW 252

Catalytic domain of Brain-specific serine/threonine-protein kinases 1 and 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. BRSK1, also called SAD-B or SAD1 (Synapses of Amphids Defective homolog 1), and BRSK2, also called SAD-A, are highly expressed in mammalian forebrain. They play important roles in establishing neuronal polarity. BRSK1/2 double knock-out mice die soon after birth, showing thin cerebral cortices due to disordered subplate layers and neurons that lack distinct axons and dendrites. BRSK1 regulates presynaptic neurotransmitter release. Its activity fluctuates during cell cysle progression and it acts as a regulator of centrosome duplication. BRSK2 is also abundant in pancreatic islets, where it is involved in the regulation of glucose-stimulated insulin secretion. The BRSK1/2 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 21426781  64 GPYIL---LEREQGNCTYRALHCPTGTEYTCKVYPASEAQAVLAPYA--------RLPTHQHVARPTEVLLGSQLLYTFF 132
Cdd:cd14081   1 GPYRLgktLGKGQTGLVKLAKHCVTGQKVAIKIVNKEKLSKESVLMKvereiaimKLIEHPNVLKLYDVYENKKYLYLVL 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21426781 133 TKTH-GDLHSLVRSRRGIPEPEAAALFRQMASAVAHCHKHGLILRDLKLRRFVFSNCERTK--------LVLEN--LEDA 201
Cdd:cd14081  81 EYVSgGELFDYLVKKGRLTEKEARKFFRQIISALDYCHSHSICHRDLKPENLLLDEKNNIKiadfgmasLQPEGslLETS 160

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21426781 202 CvmtgpddslwdkhACPAYVGPEILSSRPsYSGRAADVWSLGVALFTMLAGRYPFQDSEPALLFGKIRRGTFALPEGLSA 281
Cdd:cd14081 161 C-------------GSPHYACPEVIKGEK-YDGRKADIWSCGVILYALLVGALPFDDDNLRQLLEKVKRGVFHIPHFISP 226

                       250       260
                ....*....|....*....|....*....
gi 21426781 282 SARCLIRCLLRREPSERLVALGILLHPWL 310
Cdd:cd14081 227 DAQDLLRRMLEVNPEKRITIEEIKKHPWF 255

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 21426781 137 GDLHSLVRSRRGIPEPEAAALFRQMASAVAHCHKHGLILRDLKLRRFVFSNCErtklvlenlEDACVM---------TGP 207
Cdd:cd05117  84 GELFDRIVKKGSFSEREAAKIMKQILSAVAYLHSQGIVHRDLKPENILLASKD---------PDSPIKiidfglakiFEE 154

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21426781 208 DDSLWDKHACPAYVGPEILSSRPsYsGRAADVWSLGVALFTMLAGRYPFQDSEPALLFGKIRRGTFALPE----GLSASA 283
Cdd:cd05117 155 GEKLKTVCGTPYYVAPEVLKGKG-Y-GKKCDIWSLGVILYILLCGYPPFYGETEQELFEKILKGKYSFDSpewkNVSEEA 232

                       170       180
                ....*....|....*....|....*.
gi 21426781 284 RCLIRCLLRREPSERLVALGILLHPW 309
Cdd:cd05117 233 KDLIKRLLVVDPKKRLTAAEALNHPW 258

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 21426781 126 QLLYTFFTKTH----------GDLHSLVRSRRGIPEPEAAALFRQMASAVAHCHKHGLILRDLKlrrfvfsncertklvL 195
Cdd:cd05123  57 KLHYAFQTEEKlylvldyvpgGELFSHLSKEGRFPEERARFYAAEIVLALEYLHSLGIIYRDLK---------------P 121

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21426781 196 EN-LEDA---CVMTgpDDSLW-----DKHAC------PAYVGPEILSSRPsYsGRAADVWSLGVALFTMLAGRYPFQDSE 260
Cdd:cd05123 122 ENiLLDSdghIKLT--DFGLAkelssDGDRTytfcgtPEYLAPEVLLGKG-Y-GKAVDWWSLGVLLYEMLTGKPPFYAEN 197

                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|..
gi 21426781 261 PALLFGKIRRGTFALPEGLSASARCLIRCLLRREPSERLVALG---ILLHPW 309
Cdd:cd05123 198 RKEIYEKILKSPLKFPEYVSPEAKSLISGLLQKDPTKRLGSGGaeeIKAHPF 249

Catalytic domain of the Serine/Threonine Kinases, Sucrose nonfermenting 1-related protein kinase subfamily 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The SnRKs form three different subfamilies designated SnRK1-3. SnRK3 is represented in this cd. The SnRK3 group contains members also known as CBL-interacting protein kinase, salt overly sensitive 2, SOS3-interacting proteins and protein kinase S. These kinases interact with calcium-binding proteins such as SOS3, SCaBPs, and CBL proteins, and are involved in responses to salt stress and in sugar and ABA signaling. The SnRKs belong to 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 21426781 108 RLPTHQHVARPTEVLLGSQLLYTFFT-KTHGDLHSLVRSRRGIPEPEAAALFRQMASAVAHCHKHGLILRDLKLRRFVFS 186
Cdd:cd14663  55 KLLRHPNIVELHEVMATKTKIFFVMElVTGGELFSKIAKNGRLKEDKARKYFQQLIDAVDYCHSRGVFHRDLKPENLLLD 134

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21426781 187 NCERTKLV---LENLEDAcvmTGPDDSLWDKHACPAYVGPEILSSRpSYSGRAADVWSLGVALFTMLAGRYPFQDSEPAL 263
Cdd:cd14663 135 EDGNLKISdfgLSALSEQ---FRQDGLLHTTCGTPNYVAPEVLARR-GYDGAKADIWSCGVILFVLLAGYLPFDDENLMA 210

                       170       180       190       200
                ....*....|....*....|....*....|....*....|....*.
gi 21426781 264 LFGKIRRGTFALPEGLSASARCLIRCLLRREPSERLVALGILLHPW 309
Cdd:cd14663 211 LYRKIMKGEFEYPRWFSPGAKSLIKRILDPNPSTRITVEQIMASPW 256

Catalytic domain of the Serine/Threonine Kinase, Maternal Embryonic Leucine zipper Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MELK is a cell cycle dependent protein which functions in cytokinesis, cell cycle, apoptosis, cell proliferation, and mRNA processing. It is found upregulated in many types of cancer cells, playing an indispensable role in cancer cell survival. It makes an attractive target in the design of inhibitors for use in the treatment of a wide range of human cancer. The MELK 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 21426781 111 THQHVARPTEVLLGSQLLYTFFTK-THGDLHSLVRSRRGIPEPEAAALFRQMASAVAHCHKHGLILRDLKLRRFVFSNCE 189
Cdd:cd14078  59 SHQHICRLYHVIETDNKIFMVLEYcPGGELFDYIVAKDRLSEDEARVFFRQIVSAVAYVHSQGYAHRDLKPENLLLDEDQ 138

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21426781 190 RTKLVLENLedaCVMT--GPDDSLWDKHACPAYVGPEILSSRPsYSGRAADVWSLGVALFTMLAGRYPFQDSEPALLFGK 267
Cdd:cd14078 139 NLKLIDFGL---CAKPkgGMDHHLETCCGSPAYAAPELIQGKP-YIGSEADVWSMGVLLYALLCGFLPFDDDNVMALYRK 214

                       170       180       190       200
                ....*....|....*....|....*....|....*....|...
gi 21426781 268 IRRGTFALPEGLSASARCLIRCLLRREPSERLVALGILLHPWL 310
Cdd:cd14078 215 IQSGKYEEPEWLSPSSKLLLDQMLQVDPKKRITVKELLNHPWV 257

C-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family. MSKs are activated by two major signaling cascades, the Ras-MAPK and p38 stress kinase pathways, in response to various stimuli such as growth factors, hormones, neurotransmitters, cellular stress, and pro-inflammatory cytokines. This triggers phosphorylation in the activation loop (A-loop) of the CTD of MSK. The active CTD phosphorylates the hydrophobic motif (HM) in the C-terminal extension of NTD, which facilitates the phosphorylation of the A-loop and activates the NTD, which in turn phosphorylates downstream targets. MSKs are predominantly nuclear proteins. They are widely expressed in many tissues including heart, brain, lung, liver, kidney, and pancreas. There are two isoforms of MSK, called MSK1 and MSK2. The MSK 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 21426781 137 GDLHSLVRSRRGIPEPEAAALFRQMASAVAHCHKHGLILRDLKLRRFVFSNCERT---KLV----LENLEDACVMTGPDD 209
Cdd:cd14092  84 GELLERIRKKKRFTESEASRIMRQLVSAVSFMHSKGVVHRDLKPENLLFTDEDDDaeiKIVdfgfARLKPENQPLKTPCF 163

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21426781 210 SLwdkhacpAYVGPEILSSRPSYSG--RAADVWSLGVALFTMLAGRYPFQ----DSEPALLFGKIRRGTFALP----EGL 279
Cdd:cd14092 164 TL-------PYAAPEVLKQALSTQGydESCDLWSLGVILYTMLSGQVPFQspsrNESAAEIMKRIKSGDFSFDgeewKNV 236

                       170       180       190       200
                ....*....|....*....|....*....|....*....|.
gi 21426781 280 SASARCLIRCLLRREPSERLVALGILLHPWLREDCSQVSPP 320
Cdd:cd14092 237 SSEAKSLIQGLLTVDPSKRLTMSELRNHPWLQGSSSPSSTP 277

Catalytic domain of the Serine/Threonine kinase, Aurora kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Aurora kinases are key regulators of mitosis and are essential for the accurate and equal division of genomic material from parent to daughter cells. Yeast contains only one Aurora kinase while most higher eukaryotes have two. Vertebrates contain at least 2 Aurora kinases (A and B); mammals contains a third Aurora kinase gene (C). Aurora-A regulates cell cycle events from the late S-phase through the M-phase including centrosome maturation, mitotic entry, centrosome separation, spindle assembly, chromosome alignment, cytokinesis, and mitotic exit. Aurora-A activation depends on its autophosphorylation and binding to the microtubule-associated protein TPX2. Aurora-B is most active at the transition during metaphase to the end of mitosis. It is critical for accurate chromosomal segregation, cytokinesis, protein localization to the centrosome and kinetochore, correct microtubule-kinetochore attachments, and regulation of the mitotic checkpoint. Aurora-C is mainly expressed in meiotically dividing cells; it was originally discovered in mice as a testis-specific STK called Aie1. Both Aurora-B and -C are chromosomal passenger proteins that can form complexes with INCENP and survivin, and they may have redundant cellular functions. The Aurora 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 21426781 128 LYTFF-TKT----------HGDLHSLVRSRRGIPEPEAAALFRQMASAVAHCHKHGLILRDLKLRRFVFSNCERTKLVle 196
Cdd:cd14007  65 LYGYFeDKKriylileyapNGELYKELKKQKRFDEKEAAKYIYQLALALDYLHSKNIIHRDIKPENILLGSNGELKLA-- 142

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21426781 197 nledacvmtgpdDSLWDKHACPA----------YVGPEILSSRPsYsGRAADVWSLGVALFTMLAGRYPFQDSEPALLFG 266
Cdd:cd14007 143 ------------DFGWSVHAPSNrrktfcgtldYLPPEMVEGKE-Y-DYKVDIWSLGVLCYELLVGKPPFESKSHQETYK 208

                       170       180       190       200
                ....*....|....*....|....*....|....*....|....*
gi 21426781 267 KIRRGTFALPEGLSASARCLIRCLLRREPSERLVALGILLHPWLR 311
Cdd:cd14007 209 RIQNVDIKFPSSVSPEAKDLISKLLQKDPSKRLSLEQVLNHPWIK 253

Catalytic domain of the Serine/Threonine Kinase, SNF1-related kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SNRK is a kinase highly expressed in testis and brain that is found inactive in cells that lack the LKB1 tumour suppressor protein kinase. The regulatory subunits STRAD and MO25 are required for LKB1 to activate SNRK. The SNRK mRNA is increased 3-fold when granule neurons are cultured in low potassium, and may thus play a role in the survival responses in these cells. In some vertebrates, a second SNRK gene (snrkb or snrk-1) has been sequenced and/or identified. Snrk-1 is expressed specifically in embryonic zebrafish vasculature; it plays an essential role in angioblast differentiation, maintenance, and migration. The SNRK 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 21426781 108 RLPTHQHVARPTEVLLGSQLLYTFFT-KTHGDLHS-LVRSRRGIPEPEAAALFRQMASAVAHCHKHGLILRDLK------ 179
Cdd:cd14074  57 KLVQHPNVVRLYEVIDTQTKLYLILElGDGGDMYDyIMKHENGLNEDLARKYFRQIVSAISYCHKLHVVHRDLKpenvvf 136

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21426781 180 --------LRRFVFSNCERTKlvlENLEDACvmtgpdDSLwdkhacpAYVGPEILSSRpSYSGRAADVWSLGVALFTMLA 251
Cdd:cd14074 137 fekqglvkLTDFGFSNKFQPG---EKLETSC------GSL-------AYSAPEILLGD-EYDAPAVDIWSLGVILYMLVC 199

                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|....*....
gi 21426781 252 GRYPFQDSEPALLFGKIRRGTFALPEGLSASARCLIRCLLRREPSERLVALGILLHPWL 310
Cdd:cd14074 200 GQPPFQEANDSETLTMIMDCKYTVPAHVSPECKDLIRRMLIRDPKKRASLEEIENHPWL 258

Catalytic domain of the Serine/Threonine kinases, Liver Kinase B1, Calmodulin Dependent Protein Kinase Kinase, and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Both LKB1 and CaMKKs can phosphorylate and activate AMP-activated protein kinase (AMPK). LKB1, also called STK11, serves as a master upstream kinase that activates AMPK and most AMPK-like kinases. LKB1 and AMPK are part of an energy-sensing pathway that links cell energy to metabolism and cell growth. They play critical roles in the establishment and maintenance of cell polarity, cell proliferation, cytoskeletal organization, as well as T-cell metabolism, including T-cell development, homeostasis, and effector function. CaMKKs are upstream kinases of the CaM kinase cascade that phosphorylate and activate CaMKI and CamKIV. They may also phosphorylate other substrates including PKB and AMPK. Vertebrates contain two CaMKKs, CaMKK1 (or alpha) and CaMKK2 (or beta). CaMKK1 is involved in the regulation of glucose uptake in skeletal muscles. CaMKK2 is involved in regulating energy balance, glucose metabolism, adiposity, hematopoiesis, inflammation, and cancer. The LKB1/CaMKK 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 21426781 146 RRGIPEPEAAALFRQMASAVAHCHKHGLILRDLKLrrfvfsncertklvlENL---EDACV----------MTGPDDSLW 212
Cdd:cd14008 102 VPPLPEETARKYFRDLVLGLEYLHENGIVHRDIKP---------------ENLlltADGTVkisdfgvsemFEDGNDTLQ 166

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21426781 213 DKHACPAYVGPEILS-SRPSYSGRAADVWSLGVALFTMLAGRYPFQDSEPALLFGKIRRGT--FALPEGLSASARCLIRC 289
Cdd:cd14008 167 KTAGTPAFLAPELCDgDSKTYSGKAADIWALGVTLYCLVFGRLPFNGDNILELYEAIQNQNdeFPIPPELSPELKDLLRR 246

                       170       180
                ....*....|....*....|.
gi 21426781 290 LLRREPSERLVALGILLHPWL 310
Cdd:cd14008 247 MLEKDPEKRITLKEIKEHPWV 267

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 21426781 137 GDLHSLVRSRRGIPEPEAAALFRQMASAVAHCHKHGLILRDLKLRRFVF-SNCERTKLV-----LENLEDACVMTGpdds 210
Cdd:cd14166  85 GELFDRILERGVYTEKDASRVINQVLSAVKYLHENGIVHRDLKPENLLYlTPDENSKIMitdfgLSKMEQNGIMST---- 160

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21426781 211 lwdkhAC--PAYVGPEILSSRPsYSgRAADVWSLGVALFTMLAGRYPFQDSEPALLFGKIRRGTFALP----EGLSASAR 284
Cdd:cd14166 161 -----ACgtPGYVAPEVLAQKP-YS-KAVDCWSIGVITYILLCGYPPFYEETESRLFEKIKEGYYEFEspfwDDISESAK 233

                       170       180
                ....*....|....*....|....*.
gi 21426781 285 CLIRCLLRREPSERLVALGILLHPWL 310
Cdd:cd14166 234 DFIRHLLEKNPSKRYTCEKALSHPWI 259