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 2462598081  60 SFGLSGGIQREAPEVFQVYmdrgpGYSYPVDWWSLGITAYELLRGWRPYEIHSVTPIDEILNMFKVERVHYSSTWCKGMV 139
Cdd:cd05578   156 ATSTSGTKPYMAPEVFMRA-----GYSFAVDWWSLGVTAYEMLRGKRPYEIHSRTSIEEIRAKFETASVLYPAGWSEEAI 230

                          90       100
                  ....*....|....*....|....*..
gi 2462598081 140 ALLRKLLTKDPESRVSSLHDIQSVPYL 166
Cdd:cd05578   231 DLINKLLERDPQKRLGDLSDLKNHPYF 257

Catalytic domain of the Serine/Threonine Kinase, Yank1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily contains uncharacterized STKs with similarity to the human protein designated as Yank1 or STK32A. The Yank1 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 2462598081  60 SFGLSGGIQREAPEVFQVYmdrgpGYSYPVDWWSLGITAYELLRGWRPYEIHSVTPIDEILNMFKVERVHYSSTWCKGMV 139
Cdd:cd05578   156 ATSTSGTKPYMAPEVFMRA-----GYSFAVDWWSLGVTAYEMLRGKRPYEIHSRTSIEEIRAKFETASVLYPAGWSEEAI 230

                          90       100
                  ....*....|....*....|....*..
gi 2462598081 140 ALLRKLLTKDPESRVSSLHDIQSVPYL 166
Cdd:cd05578   231 DLINKLLERDPQKRLGDLSDLKNHPYF 257

Protein kinase domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462598081  71 APEVFqvymdRGPGYSYPVDWWSLGITAYELLRGWRPYEIHSVTPIDEILNMFKVERVHYSSTWCKGMVALLRKLLTKDP 150
Cdd:pfam00069 128 APEVL-----GGNPYGPKVDVWSLGCILYELLTGKPPFPGINGNEIYELIIDQPYAFPELPSNLSEEAKDLLKKLLKKDP 202

                          90
                  ....*....|....*.
gi 2462598081 151 ESRvSSLHDIQSVPYL 166
Cdd:pfam00069 203 SKR-LTATQALQHPWF 217

Serine/threonine protein kinase [Signal transduction mechanisms];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462598081  71 APEVFqvymdRGPGYSYPVDWWSLGITAYELLRGWRPYEihSVTPIDEILNMFKVERVHYSSTWCK---GMVALLRKLLT 147
Cdd:COG0515   176 APEQA-----RGEPVDPRSDVYSLGVTLYELLTGRPPFD--GDSPAELLRAHLREPPPPPSELRPDlppALDAIVLRALA 248

                  ....*.
gi 2462598081 148 KDPESR 153
Cdd:COG0515   249 KDPEER 254

Catalytic domain of the Serine/Threonine Kinase, Yank1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily contains uncharacterized STKs with similarity to the human protein designated as Yank1 or STK32A. The Yank1 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 2462598081  60 SFGLSGGIQREAPEVFQVYmdrgpGYSYPVDWWSLGITAYELLRGWRPYEIHSVTPIDEILNMFKVERVHYSSTWCKGMV 139
Cdd:cd05578   156 ATSTSGTKPYMAPEVFMRA-----GYSFAVDWWSLGVTAYEMLRGKRPYEIHSRTSIEEIRAKFETASVLYPAGWSEEAI 230

                          90       100
                  ....*....|....*....|....*..
gi 2462598081 140 ALLRKLLTKDPESRVSSLHDIQSVPYL 166
Cdd:cd05578   231 DLINKLLERDPQKRLGDLSDLKNHPYF 257

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 2462598081  71 APEVFQvymdrGPGYSYPVDWWSLGITAYELLRGWRPYEIHSVtpiDEILNMFKVERVHYSSTWCKGMVALLRKLLTKDP 150
Cdd:cd05123   161 APEVLL-----GKGYGKAVDWWSLGVLLYEMLTGKPPFYAENR---KEIYEKILKSPLKFPEYVSPEAKSLISGLLQKDP 232

                          90
                  ....*....|....*..
gi 2462598081 151 ESRVSSLH--DIQSVPY 165
Cdd:cd05123   233 TKRLGSGGaeEIKAHPF 249

Catalytic domain of the Serine/Threonine Kinase, Novel Protein Kinase C eta; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKC-eta is predominantly expressed in squamous epithelia, where it plays a crucial role in the signaling of cell-type specific differentiation. It is also expressed in pro-B cells and early-stage thymocytes, and acts as a key regulator in early B-cell development. PKC-eta increases glioblastoma multiforme (GBM) proliferation and resistance to radiation, and is being developed as a therapeutic target for the management of GBM. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. nPKCs are calcium-independent, but require DAG (1,2-diacylglycerol) and phosphatidylserine (PS) for activity. The nPKC-eta 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 2462598081  71 APEVFQvYMDRGPGysypVDWWSLGITAYELLRGWRPYEIHSVTPIDE-ILNmfkvERVHYSSTWCKGMVALLRKLLTKD 149
Cdd:cd05590   164 APEILQ-EMLYGPS----VDWWAMGVLLYEMLCGHAPFEAENEDDLFEaILN----DEVVYPTWLSQDAVDILKAFMTKN 234

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 2462598081 150 PESRVSSL-----HDIQSVPYLADMNWDAVFKKALMPGFVPN-KGR---LNCDPTFELEEMIL 203
Cdd:cd05590   235 PTMRLGSLtlggeEAILRHPFFKELDWEKLNRRQIEPPFRPRiKSRedvSNFDPDFIKEDPVL 297

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462598081  58 KPSFGLSGGIQREAPEVFQvymdRGPGYSYPVDWWSLGITAYELLRGWRPYEIHSvTPID--EILNMFKVERVHYSSTWC 135
Cdd:cd05577   149 KKIKGRVGTHGYMAPEVLQ----KEVAYDFSVDWFALGCMLYEMIAGRSPFRQRK-EKVDkeELKRRTLEMAVEYPDSFS 223

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 2462598081 136 KGMVALLRKLLTKDPESRVSSL----HDIQSVPYLADMNWDAVFKKALMPGFVPN 186
Cdd:cd05577   224 PEARSLCEGLLQKDPERRLGCRggsaDEVKEHPFFRSLNWQRLEAGMLEPPFVPD 278

Catalytic domain of the Serine/Threonine Kinase, Novel Protein Kinase C delta; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKC-delta plays a role in cell cycle regulation and programmed cell death in many cell types. It slows down cell proliferation, inducing cell cycle arrest and enhancing cell differentiation. PKC-delta is also involved in the regulation of transcription as well as immune and inflammatory responses. It plays a central role in the genotoxic stress response that leads to DNA damaged-induced apoptosis. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. nPKCs are calcium-independent, but require DAG (1,2-diacylglycerol) and phosphatidylserine (PS) for activity. The nPKC-delta 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 2462598081  71 APEVFQvymdrGPGYSYPVDWWSLGITAYELLRGWRPYeiHSVTPiDEILNMFKVERVHYSSTWCKGMVALLRKLLTKDP 150
Cdd:cd05620   164 APEILQ-----GLKYTFSVDWWSFGVLLYEMLIGQSPF--HGDDE-DELFESIRVDTPHYPRWITKESKDILEKLFERDP 235

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 2462598081 151 ESRVSSLHDIQSVPYLADMNWDAVFKKALMPGFVPNKGRLNCDPTFELEemILESKP 207
Cdd:cd05620   236 TRRLGVVGNIRGHPFFKTINWTALEKRELDPPFKPKVKSPSDYSNFDRE--FLSEKP 290

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462598081   61 FGLSGGIQRE-------------APEVFqvymdRGPGYSYPVDWWSLGITAYELLRGWRPYEIHSvtPIDEILNMFKVER 127
Cdd:smart00220 141 FGLARQLDPGeklttfvgtpeymAPEVL-----LGKGYGKAVDIWSLGVILYELLTGKPPFPGDD--QLLELFKKIGKPK 213

                           90       100
                   ....*....|....*....|....*....
gi 2462598081  128 VH---YSSTWCKGMVALLRKLLTKDPESR 153
Cdd:smart00220 214 PPfppPEWDISPEAKDLIRKLLVKDPEKR 242

Catalytic domain of the Serine/Threonine Kinase, Protein Kinase B; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. There are three PKB isoforms from different genes, PKB-alpha (or Akt1), PKB-beta (or Akt2), and PKB-gamma (or Akt3). PKB contains an N-terminal pleckstrin homology (PH) domain and a C-terminal catalytic domain. It is activated downstream of phosphoinositide 3-kinase (PI3K) and plays important roles in diverse cellular functions including cell survival, growth, proliferation, angiogenesis, motility, and migration. PKB also has a central role in a variety of human cancers, having been implicated in tumor initiation, progression, and metastasis. The PKB 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 PI3K.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462598081  71 APEVFQvymDRGpgYSYPVDWWSLGITAYELLRGWRPYEIHSVtpiDEILNMFKVERVHYSSTWCKGMVALLRKLLTKDP 150
Cdd:cd05571   163 APEVLE---DND--YGRAVDWWGLGVVMYEMMCGRLPFYNRDH---EVLFELILMEEVRFPSTLSPEAKSLLAGLLKKDP 234

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|
gi 2462598081 151 ESR----VSSLHDIQSVPYLADMNWDAVFKKALMPGFVPN 186
Cdd:cd05571   235 KKRlgggPRDAKEIMEHPFFASINWDDLYQKKIPPPFKPQ 274

Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. GRK2, also called beta-adrenergic receptor kinase (beta-ARK) or beta-ARK1, is important in regulating several cardiac receptor responses. It plays a role in cardiac development and in hypertension. Deletion of GRK2 in mice results in embryonic lethality, caused by hypoplasia of the ventricular myocardium. GRK2 also plays important roles in the liver (as a regulator of portal blood pressure), in immune cells, and in the nervous system. Altered GRK2 expression has been reported in several disorders including major depression, schizophrenia, bipolar disorder, and Parkinsonism. GRK2 contains an N-terminal RGS homology (RH) domain, a central catalytic domain, and C-terminal pleckstrin homology (PH) domain that mediates PIP2 and G protein betagamma-subunit translocation to the membrane. GRKs phosphorylate and regulate G protein-coupled receptors (GPCRs), the largest superfamily of cell surface receptors which regulate some part of nearly all physiological functions. Phosphorylated GPCRs bind to arrestins, which prevents further G protein signaling despite the presence of activating ligand. TheGRK2 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 2462598081  71 APEVFQvymdRGPGYSYPVDWWSLGITAYELLRGWRPYEIHSVTPIDEILNMFKVERVHYSSTWCKGMVALLRKLLTKDP 150
Cdd:cd14223   169 APEVLQ----KGVAYDSSADWFSLGCMLFKLLRGHSPFRQHKTKDKHEIDRMTLTMAVELPDSFSPELRSLLEGLLQRDV 244

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|..
gi 2462598081 151 ESRVSSL----HDIQSVPYLADMNWDAVFKKALMPGFVPNKGRLNCDPTFEL 198
Cdd:cd14223   245 NRRLGCMgrgaQEVKEEPFFRGLDWQMVFLQKYPPPLIPPRGEVNAADAFDI 296

Catalytic domain of the Serine/Threonine Kinase, Citron Rho-interacting kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CRIK (also called citron kinase) is an effector of the small GTPase Rho. It plays an important function during cytokinesis and affects its contractile process. CRIK-deficient mice show severe ataxia and epilepsy as a result of abnormal cytokinesis and massive apoptosis in neuronal precursors. A Down syndrome critical region protein TTC3 interacts with CRIK and inhibits CRIK-dependent neuronal differentiation and neurite extension. CRIK contains a catalytic domain, a central coiled-coil domain, and a C-terminal region containing a Rho-binding domain (RBD), a zinc finger, and a pleckstrin homology (PH) domain, in addition to other motifs. The CRIK 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 2462598081  71 APEVFQVyMDRGPGYSYPV--DWWSLGITAYELLRGWRPY-EIHSVTPIDEILNMFKVERVHYSSTWCKGMVALLRKLLT 147
Cdd:cd05601   171 APEVLTS-MNGGSKGTYGVecDWWSLGIVAYEMLYGKTPFtEDTVIKTYSNIMNFKKFLKFPEDPKVSESAVDLIKGLLT 249

                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 2462598081 148 kDPESRVsSLHDIQSVPYLADMNWDAVfkKALMPGFVP 185
Cdd:cd05601   250 -DAKERL-GYEGLCCHPFFSGIDWNNL--RQTVPPFVP 283

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 2462598081  71 APEVFqvymdRGPGYSYPVDWWSLGITAYELLRGWRPYeiHSVTP---IDEILNmFKVErvhysstWCKGMVA------L 141
Cdd:cd05579   176 APEIL-----LGQGHGKTVDWWSLGVILYEFLVGIPPF--HAETPeeiFQNILN-GKIE-------WPEDPEVsdeakdL 240

                          90       100       110
                  ....*....|....*....|....*....|..
gi 2462598081 142 LRKLLTKDPESRV--SSLHDIQSVPYLADMNW 171
Cdd:cd05579   241 ISKLLTPDPEKRLgaKGIEEIKNHPFFKGIDW 272

Catalytic domain of the Serine/Threonine Kinase, Protein Kinase B beta (also called Akt2); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKB-beta is the predominant PKB isoform expressed in insulin-responsive tissues. It plays a critical role in the regulation of glucose homeostasis. It is also implicated in muscle cell differentiation. Mice deficient in PKB-beta display normal growth weights but exhibit severe insulin resistance and diabetes, accompanied by lipoatrophy and B-cell failure. PKB contains an N-terminal pleckstrin homology (PH) domain and a C-terminal catalytic domain.The PKB-beta 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 2462598081  71 APEVFQvymdrGPGYSYPVDWWSLGITAYELLRGWRPYEIHSVTPIDEILNMfkvERVHYSSTWCKGMVALLRKLLTKDP 150
Cdd:cd05595   163 APEVLE-----DNDYGRAVDWWGLGVVMYEMMCGRLPFYNQDHERLFELILM---EEIRFPRTLSPEAKSLLAGLLKKDP 234

                          90       100       110
                  ....*....|....*....|....*....|....*....
gi 2462598081 151 ESRV----SSLHDIQSVPYLADMNWDAVFKKALMPGFVP 185
Cdd:cd05595   235 KQRLgggpSDAKEVMEHRFFLSINWQDVVQKKLLPPFKP 273

Catalytic domain of the Serine/Threonine Kinase, Atypical Protein Kinase C iota; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKC-iota is directly implicated in carcinogenesis. It is critical to oncogenic signaling mediated by Ras and Bcr-Abl. The PKC-iota gene is the target of tumor-specific gene amplification in many human cancers, and has been identified as a human oncogene. In addition to its role in transformed growth, PKC-iota also promotes invasion, chemoresistance, and tumor cell survival. Expression profiling of PKC-iota is a prognostic marker of poor clinical outcome in several human cancers. PKC-iota also plays a role in establishing cell polarity, and has critical embryonic functions. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. aPKCs only require phosphatidylserine (PS) for activation. The aPKC 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 2462598081  71 APEVFqvymdRGPGYSYPVDWWSLGITAYELLRGWRPYEI--HSVTPI----DEILNMFKVERVHYSSTWCKGMVALLRK 144
Cdd:cd05618   189 APEIL-----RGEDYGFSVDWWALGVLMFEMMAGRSPFDIvgSSDNPDqnteDYLFQVILEKQIRIPRSLSVKAASVLKS 263

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*..
gi 2462598081 145 LLTKDPESRV-----SSLHDIQSVPYLADMNWDAVFKKALMPGFVPN 186
Cdd:cd05618   264 FLNKDPKERLgchpqTGFADIQGHPFFRNVDWDLMEQKQVVPPFKPN 310

Catalytic domain of the Serine/Threonine Kinase, Serum- and Glucocorticoid-induced Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SGK2 shows a more restricted distribution than SGK1 and is most abundantly expressed in epithelial tissues including kidney, liver, pancreas, and the choroid plexus of the brain. In vitro cellular assays show that SGK2 can stimulate the activity of ion channels, the glutamate transporter EEAT4, and the glutamate receptors, GluR6 and GLUR1. The SGK2 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 2462598081  49 CREG-SPCRLKPSFglSGGIQREAPEVFqvymdRGPGYSYPVDWWSLGITAYELLRGWRPYEIHSVTPI-DEILNmfkvE 126
Cdd:cd05603   143 CKEGmEPEETTSTF--CGTPEYLAPEVL-----RKEPYDRTVDWWCLGAVLYEMLYGLPPFYSRDVSQMyDNILH----K 211

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462598081 127 RVHYSSTWCKGMVALLRKLLTKDPESRVSSLHDIQSVP---YLADMNWDAVFKKALMPGFVPN---KGRL-NCDPTFElE 199
Cdd:cd05603   212 PLHLPGGKTVAACDLLQGLLHKDQRRRLGAKADFLEIKnhvFFSPINWDDLYHKRITPPYNPNvagPADLrHFDPEFT-Q 290

                  ....*.
gi 2462598081 200 EMILES 205
Cdd:cd05603   291 EAVPHS 296

Catalytic domain of the Serine/Threonine Kinase, Atypical Protein Kinase C; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. aPKCs only require phosphatidylserine (PS) for activation. They contain a C2-like region, instead of a calcium-binding (C2) region found in classical PKCs, in their regulatory domain. There are two aPKC isoforms, zeta and iota. aPKCs are involved in many cellular functions including proliferation, migration, apoptosis, polarity maintenance and cytoskeletal regulation. They also play a critical role in the regulation of glucose metabolism and in the pathogenesis of type 2 diabetes. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. The aPKC 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 2462598081  71 APEVFqvymdRGPGYSYPVDWWSLGITAYELLRGWRPYEIHSVTPIDE----------ILNmfKVERVHYSSTWCKGMVa 140
Cdd:cd05588   164 APEIL-----RGEDYGFSVDWWALGVLMFEMLAGRSPFDIVGSSDNPDqntedylfqvILE--KPIRIPRSLSVKAASV- 235

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 2462598081 141 lLRKLLTKDPESRV-----SSLHDIQSVPYLADMNWDAVFKKALMPGFVPN----KGRLNCDPTFELE 199
Cdd:cd05588   236 -LKGFLNKNPAERLgchpqTGFADIQSHPFFRTIDWEQLEQKQVTPPYKPRieseRDLENFDPQFTNE 302

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 2462598081  71 APEvfqvyMDRGPGYSYPVDWWSLGITAYELLRGWRPYEIHSVtpiDEILNMFKVERVHYSSTWCKGMVALLRKLLTKDP 150
Cdd:cd14007   166 PPE-----MVEGKEYDYKVDIWSLGVLCYELLVGKPPFESKSH---QETYKRIQNVDIKFPSSVSPEAKDLISKLLQKDP 237

                          90
                  ....*....|
gi 2462598081 151 ESRVsSLHDI 160
Cdd:cd14007   238 SKRL-SLEQV 246

N-terminal catalytic domain of the Serine/Threonine Kinase, 90 kDa ribosomal protein S6 kinase; 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), 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 2462598081  58 KPSFGLSGGIQREAPEVfqvyMDRgPGYSYPVDWWSLGITAYELLRGWRPYEIHSVtpiDEILNMF---KVERVHYSSTW 134
Cdd:cd05582   152 KKAYSFCGTVEYMAPEV----VNR-RGHTQSADWWSFGVLMFEMLTGSLPFQGKDR---KETMTMIlkaKLGMPQFLSPE 223

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 2462598081 135 CKgmvALLRKLLTKDPESRVSS----LHDIQSVPYLADMNWDAVFKKALMPGFVPNKGRLncDPTF 196
Cdd:cd05582   224 AQ---SLLRALFKRNPANRLGAgpdgVEEIKRHPFFATIDWNKLYRKEIKPPFKPAVSRP--DDTF 284

Catalytic subunit of the Serine/Threonine Kinase, cAMP-dependent protein kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The inactive PKA holoenzyme is a heterotetramer composed of two phosphorylated and active catalytic subunits with a dimer of regulatory (R) subunits. Activation is achieved through the binding of the important second messenger cAMP to the R subunits, which leads to the dissociation of PKA into the R dimer and two active subunits. PKA is present ubiquitously in cells and interacts with many different downstream targets. It plays a role in the regulation of diverse processes such as growth, development, memory, metabolism, gene expression, immunity, and lipolysis. The PKA 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 2462598081  63 LSGGIQREAPEVFQvymdrGPGYSYPVDWWSLGITAYELLRGWRPYEIHSVTPIDEILNMFKVE-RVHYSSTwckgMVAL 141
Cdd:cd14209   158 LCGTPEYLAPEIIL-----SKGYNKAVDWWALGVLIYEMAAGYPPFFADQPIQIYEKIVSGKVRfPSHFSSD----LKDL 228

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*....
gi 2462598081 142 LRKLLTKDPESRVSSL----HDIQSVPYLADMNWDAVFKKALMPGFVPN 186
Cdd:cd14209   229 LRNLLQVDLTKRFGNLkngvNDIKNHKWFATTDWIAIYQRKVEAPFIPK 277

Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. GRK3, also called beta-adrenergic receptor kinase 2 (beta-ARK2), is widely expressed in many tissues. It is involved in modulating the cholinergic response of airway smooth muscles, and also plays a role in dopamine receptor regulation. GRK3-deficient mice show a lack of olfactory receptor desensitization and altered regulation of the M2 muscarinic airway. GRK3 promoter polymorphisms may also be associated with bipolar disorder. GRK3 contains an N-terminal RGS homology (RH) domain, a central catalytic domain, and C-terminal pleckstrin homology (PH) domain that mediates PIP2 and G protein betagamma-subunit translocation to the membrane. GRKs phosphorylate and regulate G protein-coupled receptors (GPCRs), the largest superfamily of cell surface receptors which regulate some part of nearly all physiological functions. Phosphorylated GPCRs bind to arrestins, which prevents further G protein signaling despite the presence of activating ligand. The GRK3 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 2462598081  71 APEVFQvymdRGPGYSYPVDWWSLGITAYELLRGWRPYEIHSVTPIDEILNMFKVERVHYSSTWCKGMVALLRKLLTKDP 150
Cdd:cd05633   174 APEVLQ----KGTAYDSSADWFSLGCMLFKLLRGHSPFRQHKTKDKHEIDRMTLTVNVELPDSFSPELKSLLEGLLQRDV 249

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|..
gi 2462598081 151 ESRV----SSLHDIQSVPYLADMNWDAVFKKALMPGFVPNKGRLNCDPTFEL 198
Cdd:cd05633   250 SKRLgchgRGAQEVKEHSFFKGIDWQQVYLQKYPPPLIPPRGEVNAADAFDI 301

Catalytic domain of Nuclear Dbf2-Related kinase-like Protein Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. NDR kinases regulate mitosis, cell growth, embryonic development, and neurological processes. They are also required for proper centrosome duplication. Higher eukaryotes contain two NDR isoforms, NDR1 and NDR2. This subfamily also contains fungal NDR-like kinases. NDR kinase contains an N-terminal regulatory (NTR) domain and an insert within the catalytic domain that contains an auto-inhibitory sequence. Like many other AGC kinases, NDR kinase requires phosphorylation at two sites, the activation loop (A-loop) and the hydrophobic motif (HM), for activity. The NDR 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 2462598081  71 APEVFqvyMDRGpgYSYPVDWWSLGITAYELLRGWRPYeiHSVTPID---EILN-----MFKVErVHYSSTwCKgmvALL 142
Cdd:cd05599   168 APEVF---LQKG--YGKECDWWSLGVIMYEMLIGYPPF--CSDDPQEtcrKIMNwretlVFPPE-VPISPE-AK---DLI 235

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462598081 143 RKLLTkDPESRV--SSLHDIQSVPYLADMNWDAVFKKAlmPGFVPNKGRL----NCDpTFELEEMILESKPLHKKKKRLA 216
Cdd:cd05599   236 ERLLC-DAEHRLgaNGVEEIKSHPFFKGVDWDHIRERP--APILPEVKSIldtsNFD-EFEEVDLQIPSSPEAGKDSKEL 311

                  ...
gi 2462598081 217 KNR 219
Cdd:cd05599   312 KSK 314

Catalytic domain of fungal Rim15-like Protein Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Members of this group include Saccharomyces cerevisiae Rim15, Schizosaccharomyces pombe cek1, and similar fungal proteins. They contain a central catalytic domain, which contains an insert relative to MAST kinases. In addition, Rim15 contains a C-terminal signal receiver (REC) domain while cek1 contains an N-terminal PAS domain. Rim15 (or Rim15p) functions as a regulator of meiosis. It acts as a downstream effector of PKA and regulates entry into stationary phase (G0). Thus, it plays a crucial role in regulating yeast proliferation, differentiation, and aging. Cek1 may facilitate progression of mitotic anaphase. The Rim15-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462598081  61 FGLS--GGIQRE-----------APEVFQvymdrGPGYSYPVDWWSLGITAYELLRGWRPYeiHSVTPiDEILNMFKVER 127
Cdd:cd05611   141 FGLSrnGLEKRHnkkfvgtpdylAPETIL-----GVGDDKMSDWWSLGCVIFEFLFGYPPF--HAETP-DAVFDNILSRR 212

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|.
gi 2462598081 128 VHYSS---TWC-KGMVALLRKLLTKDPESRVSS--LHDIQSVPYLADMNWD 172
Cdd:cd05611   213 INWPEevkEFCsPEAVDLINRLLCMDPAKRLGAngYQEIKSHPFFKSINWD 263

Catalytic domain of Phototropin-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Phototropins are blue-light receptors that control responses such as phototropism, stromatal opening, and chloroplast movement in order to optimize the photosynthetic efficiency of plants. They are light-activated STKs that contain an N-terminal photosensory domain and a C-terminal catalytic domain. The N-terminal domain contains two LOV (Light, Oxygen or Voltage) domains that binds FMN. Photoexcitation of the LOV domains results in autophosphorylation at multiple sites and activation of the catalytic domain. In addition to plant phototropins, included in this subfamily are predominantly uncharacterized fungal STKs whose catalytic domains resemble the phototropin kinase domain. One protein from Neurospora crassa is called nrc-2, which plays a role in growth and development by controlling entry into the conidiation program. The phototropin-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 2462598081  71 APEVFqvymdRGPGYSYPVDWWSLGITAYELLRGWRPYEIHSvtpIDEILNMFKVERVHYSSTW-----CKgmvALLRKL 145
Cdd:cd05574   200 APEVI-----KGDGHGSAVDWWTLGILLYEMLYGTTPFKGSN---RDETFSNILKKELTFPESPpvsseAK---DLIRKL 268

                          90       100       110
                  ....*....|....*....|....*....|
gi 2462598081 146 LTKDPESRVSSLH---DIQSVPYLADMNWD 172
Cdd:cd05574   269 LVKDPSKRLGSKRgasEIKRHPFFRGVNWA 298

protein kinase A catalytic subunit; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462598081  60 SFGLSGGIQREAPEVFQvymdrGPGYSYPVDWWSLGITAYELLRGWRPYeiHSVTPI---DEILnmfkVERVHYSStWCK 136
Cdd:PTZ00263  172 TFTLCGTPEYLAPEVIQ-----SKGHGKAVDWWTMGVLLYEFIAGYPPF--FDDTPFriyEKIL----AGRLKFPN-WFD 239

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*.
gi 2462598081 137 GMVA-LLRKLLTKDPESRVSSL----HDIQSVPYLADMNWDAVFKK 177
Cdd:PTZ00263  240 GRARdLVKGLLQTDHTKRLGTLkggvADVKNHPYFHGANWDKLYAR 285