3-Phosphoinositide dependent protein kinase 1 (PDK1) pleckstrin homology (PH) domain; PDK1 plays an important role in insulin and growth factor signalling cascades. It phosphorylates and activates many AGC (cAMP-dependent, cGMP-dependent, protein kinase C (PKC)) family of protein kinases members, including protein kinase B (PKB, also known as Akt), p70 ribosomal S6-kinase (S6K), serum and glucocorticoid responsive kinase (SGK), p90 ribosomal S6 kinase (RSK), and PKC. PDK1 contains an N-terminal serine/threonine kinase domain followed by a PH domain. Following binding of the PH domain to PtdIns(3,4,5)P3 and PtdIns(3,4)P2, PDK1 activates these enzymes by phosphorylating a Ser/Thr residue in their activation loop. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 47680169 314 KQAGGNPWHQFVENNLILKMGPVDKRKGLFARRRQLLLTEGPHLYYVDPVNKVLKGEIPWSQELRPEAKNFKTFFVHTPN 393
Cdd:cd01262   1 QQQSENWWHFLVNGELILKMGLVDKRKGLFAKKRQLILTDGPRLYYVDPVKMVLKGEIPWSPELRPEVKNFKTFFIHTPN 80

                        90       100
                ....*....|....*....|....*..
gi 47680169 394 RTYYLMDPSGNAHKWCRKIQEVWRQRY 420
Cdd:cd01262  81 RTYYLEDPEGNAKKWCKAIEEVLKLYK 107

3-Phosphoinositide dependent protein kinase 1 (PDK1) pleckstrin homology (PH) domain; PDK1 plays an important role in insulin and growth factor signalling cascades. It phosphorylates and activates many AGC (cAMP-dependent, cGMP-dependent, protein kinase C (PKC)) family of protein kinases members, including protein kinase B (PKB, also known as Akt), p70 ribosomal S6-kinase (S6K), serum and glucocorticoid responsive kinase (SGK), p90 ribosomal S6 kinase (RSK), and PKC. PDK1 contains an N-terminal serine/threonine kinase domain followed by a PH domain. Following binding of the PH domain to PtdIns(3,4,5)P3 and PtdIns(3,4)P2, PDK1 activates these enzymes by phosphorylating a Ser/Thr residue in their activation loop. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 47680169 314 KQAGGNPWHQFVENNLILKMGPVDKRKGLFARRRQLLLTEGPHLYYVDPVNKVLKGEIPWSQELRPEAKNFKTFFVHTPN 393
Cdd:cd01262   1 QQQSENWWHFLVNGELILKMGLVDKRKGLFAKKRQLILTDGPRLYYVDPVKMVLKGEIPWSPELRPEVKNFKTFFIHTPN 80

                        90       100
                ....*....|....*....|....*..
gi 47680169 394 RTYYLMDPSGNAHKWCRKIQEVWRQRY 420
Cdd:cd01262  81 RTYYLEDPEGNAKKWCKAIEEVLKLYK 107

PH domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 47680169   319 NPWHQFVE-NNLILKMGPVDKRKGLFARRRQLLLTEGPHLYYVDPVNKVLKGEIPWSQELRPEAKNFKTFFVHTPNRTYY 397
Cdd:pfam14593   1 NRWHQFLLpGELILKQGLVKKRKGLFAKKRQLILTDGPRLIYVDPVKMVLKGEIPWSKELKVEAKNFKTFFIHTPNRTYY 80

                          90       100
                  ....*....|....*....|...
gi 47680169   398 LMDPSGNAHKWCRKIQEVWRQRY 420
Cdd:pfam14593  81 LEDPEGDALKWCKAIEDVRKKYY 103

Protein kinase domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 47680169    84 FGKILGEGSFS---TVVLARELATSREYATRANSFVGTAQYVSPELLTEKSACKSSDLWALGCIIYQLVAGLPPFRAGNE 160
Cdd:pfam00069  86 FDLLSEKGAFSereAKFIMKQILEGLESGSSLTTFVGTPWYMAPEVLGGNPYGPKVDVWSLGCILYELLTGKPPFPGING 165

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 47680169   161 YLIFQKIIKLEYDFPEKFF---PKARDLVEKLLVLDATKRLGCEEmegygpLKAHPFF 215
Cdd:pfam00069 166 NEIYELIIDQPYAFPELPSnlsEEAKDLLKKLLKKDPSKRLTATQ------ALQHPWF 217

Serine/threonine protein kinase [Signal transduction mechanisms];

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 47680169  98 LARELATSReyATRANSFVGTAQYVSPELLTEKSACKSSDLWALGCIIYQLVAGLPPFRAGNEYLIFQKIIKLEYDFPEK 177
Cdd:COG0515 153 IARALGGAT--LTQTGTVVGTPGYMAPEQARGEPVDPRSDVYSLGVTLYELLTGRPPFDGDSPAELLRAHLREPPPPPSE 230

                        90       100
                ....*....|....*....|....
gi 47680169 178 FFPKA----RDLVEKLLVLDATKR 197
Cdd:COG0515 231 LRPDLppalDAIVLRALAKDPEER 254

3-Phosphoinositide dependent protein kinase 1 (PDK1) pleckstrin homology (PH) domain; PDK1 plays an important role in insulin and growth factor signalling cascades. It phosphorylates and activates many AGC (cAMP-dependent, cGMP-dependent, protein kinase C (PKC)) family of protein kinases members, including protein kinase B (PKB, also known as Akt), p70 ribosomal S6-kinase (S6K), serum and glucocorticoid responsive kinase (SGK), p90 ribosomal S6 kinase (RSK), and PKC. PDK1 contains an N-terminal serine/threonine kinase domain followed by a PH domain. Following binding of the PH domain to PtdIns(3,4,5)P3 and PtdIns(3,4)P2, PDK1 activates these enzymes by phosphorylating a Ser/Thr residue in their activation loop. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 47680169 314 KQAGGNPWHQFVENNLILKMGPVDKRKGLFARRRQLLLTEGPHLYYVDPVNKVLKGEIPWSQELRPEAKNFKTFFVHTPN 393
Cdd:cd01262   1 QQQSENWWHFLVNGELILKMGLVDKRKGLFAKKRQLILTDGPRLYYVDPVKMVLKGEIPWSPELRPEVKNFKTFFIHTPN 80

                        90       100
                ....*....|....*....|....*..
gi 47680169 394 RTYYLMDPSGNAHKWCRKIQEVWRQRY 420
Cdd:cd01262  81 RTYYLEDPEGNAKKWCKAIEEVLKLYK 107

PH domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 47680169   319 NPWHQFVE-NNLILKMGPVDKRKGLFARRRQLLLTEGPHLYYVDPVNKVLKGEIPWSQELRPEAKNFKTFFVHTPNRTYY 397
Cdd:pfam14593   1 NRWHQFLLpGELILKQGLVKKRKGLFAKKRQLILTDGPRLIYVDPVKMVLKGEIPWSKELKVEAKNFKTFFIHTPNRTYY 80

                          90       100
                  ....*....|....*....|...
gi 47680169   398 LMDPSGNAHKWCRKIQEVWRQRY 420
Cdd:pfam14593  81 LEDPEGDALKWCKAIEDVRKKYY 103

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 47680169 110 TRANSFVGTAQYVSPELLTEKSACKSSDLWALGCIIYQLVAGLPPFRAGNEYLIFQKIIKLEYDFPEKFF--PKARDLVE 187
Cdd:cd05579 163 KEDRRIVGTPDYLAPEILLGQGHGKTVDWWSLGVILYEFLVGIPPFHAETPEEIFQNILNGKIEWPEDPEvsDEAKDLIS 242

                        90       100       110
                ....*....|....*....|....*....|...
gi 47680169 188 KLLVLDATKRLGCeemEGYGPLKAHPFFESVTW 220
Cdd:cd05579 243 KLLTPDPEKRLGA---KGIEEIKNHPFFKGIDW 272

Catalytic subunit of the Serine/Threonine Kinases, cAMP-dependent protein kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of the cAMP-dependent protein kinases, PKA and PRKX, and similar proteins. 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. PRKX is also reulated by the R subunit and is is present in many tissues including fetal and adult brain, kidney, and lung. It is implicated in granulocyte/macrophage lineage differentiation, renal cell epithelial migration, and tubular morphogenesis in the developing kidney. The PKA-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 47680169 109 ATRANSFVGTAQYVSPELLTEKSACKSSDLWALGCIIYQLVAGLPPFRAGNEYLIFQKIIKLEYDFPEKFFPKARDLVEK 188
Cdd:cd05580 152 KDRTYTLCGTPEYLAPEIILSKGHGKAVDWWALGILIYEMLAGYPPFFDENPMKIYEKILEGKIRFPSFFDPDAKDLIKR 231

                        90       100       110
                ....*....|....*....|....*....|....*..
gi 47680169 189 LLVLDATKRLGCEEmEGYGPLKAHPFFESVTWENLHQ 225
Cdd:cd05580 232 LLVVDLTKRLGNLK-NGVEDIKNHPWFAGIDWDALLQ 267

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 47680169  81 DFKFGKILGEGSFstvvlarelatsreyatrANSFVGTAQYVSPELLTEKSACKSSDLWALGCIIYQLVAGLPPFRAGNE 160
Cdd:cd05117 145 DFGLAKIFEEGEK------------------LKTVCGTPYYVAPEVLKGKGYGKKCDIWSLGVILYILLCGYPPFYGETE 206

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*...
gi 47680169 161 YLIFQKIIKLEYDFPEKFFPK----ARDLVEKLLVLDATKRLGCEEmegygpLKAHPF 214
Cdd:cd05117 207 QELFEKILKGKYSFDSPEWKNvseeAKDLIKRLLVVDPKKRLTAAE------ALNHPW 258

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 47680169 115 FVGTAQYVSPELLTEKSACKSSDLWALGCIIYQLVAGLPPFRAGNEYLIFQKIIKLEYDFPEKFF----PKARDLVEKLL 190
Cdd:cd05611 156 FVGTPDYLAPETILGVGDDKMSDWWSLGCVIFEFLFGYPPFHAETPDAVFDNILSRRINWPEEVKefcsPEAVDLINRLL 235

                        90       100       110
                ....*....|....*....|....*....|.
gi 47680169 191 VLDATKRLGCeemEGYGPLKAHPFFESVTWE 221
Cdd:cd05611 236 CMDPAKRLGA---NGYQEIKSHPFFKSINWD 263

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 47680169  92 SFSTVVLARELATSREYAtRANSFVGTAQYVSPELLTEKSACKSSDLWALGCIIYQLVAGLPPFRAGNEYLIFQKII--K 169
Cdd:cd05573 168 LFQDNVLARRRPHKQRRV-RAYSAVGTPDYIAPEVLRGTGYGPECDWWSLGVILYEMLYGFPPFYSDSLVETYSKIMnwK 246

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 47680169 170 LEYDFP--EKFFPKARDLVEKLLVlDATKRLGC-EEmegygpLKAHPFFESVTWENLHQQTPPkltaYLPAMSEDDEDCY 246
Cdd:cd05573 247 ESLVFPddPDVSPEAIDLIRRLLC-DPEDRLGSaEE------IKAHPFFKGIDWENLRESPPP----FVPELSSPTDTSN 315

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 47680169 110 TRANSFVGTAQYVSPELLTEKSACKSSDLWALGCIIYQLVAGLPPFRAGNEYLIFQKIIKLEYDFPEKFFPKARDLVEKL 189
Cdd:cd14209 153 GRTWTLCGTPEYLAPEIILSKGYNKAVDWWALGVLIYEMAAGYPPFFADQPIQIYEKIVSGKVRFPSHFSSDLKDLLRNL 232

                        90       100       110
                ....*....|....*....|....*....|....*...
gi 47680169 190 LVLDATKRLGcEEMEGYGPLKAHPFFESVTWENLHQQT 227
Cdd:cd14209 233 LQVDLTKRFG-NLKNGVNDIKNHKWFATTDWIAIYQRK 269

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 47680169 112 ANSFVGTAQYVSPELLTEKSACKSSDLWALGCIIYQLVAGLPPFRAGNEYLIFQKII--KLEYDFPE--KFFPKARDLVE 187
Cdd:cd05599 157 AYSTVGTPDYIAPEVFLQKGYGKECDWWSLGVIMYEMLIGYPPFCSDDPQETCRKIMnwRETLVFPPevPISPEAKDLIE 236

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 47680169 188 KLLVlDATKRLGceeMEGYGPLKAHPFFESVTWENLHQQTPPkltaYLPAM-SEDD 242
Cdd:cd05599 237 RLLC-DAEHRLG---ANGVEEIKSHPFFKGVDWDHIRERPAP----ILPEVkSILD 284

Catalytic domain of Yeast Protein Kinase 1-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of fungal proteins with similarity to the AGC STKs, Saccharomyces cerevisiae YPK1 and Schizosaccharomyces pombe Gad8p. YPK1 is required for cell growth and acts as a downstream kinase in the sphingolipid-mediated signaling pathway of yeast. It also plays a role in efficient endocytosis and in the maintenance of cell wall integrity. Gad8p is a downstream target of Tor1p, the fission yeast homolog of mTOR. It plays a role in cell growth and sexual development. The YPK1-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 47680169 111 RANSFVGTAQYVSPELLTEKSACKSSDLWALGCIIYQLVAGLPPFRAGNEYLIFQKIIKLEYDFPEKFFPKARDLVEKLL 190
Cdd:cd05585 150 KTNTFCGTPEYLAPELLLGHGYTKAVDWWTLGVLLYEMLTGLPPFYDENTNEMYRKILQEPLRFPDGFDRDAKDLLIGLL 229

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|.
gi 47680169 191 VLDATKRLGceeMEGYGPLKAHPFFESVTWENLHQQ--TPPkltaYLPAMS 239
Cdd:cd05585 230 NRDPTKRLG---YNGAQEIKNHPFFDQIDWKRLLMKkiQPP----FKPAVE 273

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 47680169 111 RANSFVGTAQYVSPELLTEKSACKSSDLWALGCIIYQLVAGLPPFRAGNEYLIFQKIIKLEYDFPEKFFPKARDLVEKLL 190
Cdd:cd14007 154 RRKTFCGTLDYLPPEMVEGKEYDYKVDIWSLGVLCYELLVGKPPFESKSHQETYKRIQNVDIKFPSSVSPEAKDLISKLL 233

                        90       100
                ....*....|....*....|....
gi 47680169 191 VLDATKRLGCEEMegygplKAHPF 214
Cdd:cd14007 234 QKDPSKRLSLEQV------LNHPW 251

Catalytic domain of the Serine/Threonine Kinase, Large Tumor Suppressor; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. LATS was originally identified in Drosophila using a screen for genes whose inactivation led to overproliferation of cells. In tetrapods, there are two LATS isoforms, LATS1 and LATS2. Inactivation of LATS1 in mice results in the development of various tumors, including sarcomas and ovarian cancer. LATS functions as a tumor suppressor and is implicated in cell cycle regulation. The LATS 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 47680169 112 ANSFVGTAQYVSPELLTEKSACKSSDLWALGCIIYQLVAGLPPFRAGNEYLIFQKII--KLEYDFPE--KFFPKARDLVE 187
Cdd:cd05598 162 AHSLVGTPNYIAPEVLLRTGYTQLCDWWSVGVILYEMLVGQPPFLAQTPAETQLKVInwRTTLKIPHeaNLSPEAKDLIL 241

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 47680169 188 KLLVlDATKRLGCeemEGYGPLKAHPFFESVTWENLHQQTPPkltaYLPAMSeDDEDCyGNYD 250
Cdd:cd05598 242 RLCC-DAEDRLGR---NGADEIKAHPFFAGIDWEKLRKQKAP----YIPTIR-HPTDT-SNFD 294

Catalytic domain of the Serine/Threonine Kinase, 70 kDa ribosomal protein S6 kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. p70S6K (or S6K) contains only one catalytic kinase domain, unlike p90 ribosomal S6 kinases (RSKs). It acts as a downstream effector of the STK mTOR (mammalian Target of Rapamycin) and plays a role in the regulation of the translation machinery during protein synthesis. p70S6K also plays a pivotal role in regulating cell size and glucose homeostasis. Its targets include S6, the translation initiation factor eIF3, and the insulin receptor substrate IRS-1, among others. Mammals contain two isoforms of p70S6K, named S6K1 and S6K2 (or S6K-beta). The p70S6K 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 47680169 113 NSFVGTAQYVSPELLTEKSACKSSDLWALGCIIYQLVAGLPPFRAGNEYLIFQKIIKLEYDFPEKFFPKARDLVEKLLVL 192
Cdd:cd05584 158 HTFCGTIEYMAPEILTRSGHGKAVDWWSLGALMYDMLTGAPPFTAENRKKTIDKILKGKLNLPPYLTNEARDLLKKLLKR 237

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|...
gi 47680169 193 DATKRLGcEEMEGYGPLKAHPFFESVTWENLHQQT--PPkltaYLPAMSEDDE 243
Cdd:cd05584 238 NVSSRLG-SGPGDAEEIKAHPFFRHINWDDLLAKKvePP----FKPLLQSEED 285

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 47680169 116 VGTAQYVSPELLT---EKSACK---SSDLWALGCIIYQLVAGLPPFRAGNEYLIFQKII--KLEYDFPE--KFFPKARDL 185
Cdd:cd05601 164 VGTPDYIAPEVLTsmnGGSKGTygvECDWWSLGIVAYEMLYGKTPFTEDTVIKTYSNIMnfKKFLKFPEdpKVSESAVDL 243

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*...
gi 47680169 186 VEKLLVlDATKRLGceemegYGPLKAHPFFESVTWENLHQQTPPkltaYLPAMSEDDE 243
Cdd:cd05601 244 IKGLLT-DAKERLG------YEGLCCHPFFSGIDWNNLRQTVPP----FVPTLTSDDD 290

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 47680169 114 SFVGTAQYVSPELLTEKSACKSSDLWALGCIIYQLVAGLPPFRAGNEYLIFQKIIKLEYDFPEKFFPKARDLVEKLLVLD 193
Cdd:cd05590 155 TFCGTPDYIAPEILQEMLYGPSVDWWAMGVLLYEMLCGHAPFEAENEDDLFEAILNDEVVYPTWLSQDAVDILKAFMTKN 234

                        90       100       110
                ....*....|....*....|....*....|....*...
gi 47680169 194 ATKRLGCEEMEGYGPLKAHPFFESVTWENLHQQ--TPP 229
Cdd:cd05590 235 PTMRLGSLTLGGEEAILRHPFFKELDWEKLNRRqiEPP 272

Catalytic domain of G protein-coupled Receptor Kinase 4-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Members of the GRK4-like group include GRK4, GRK5, GRK6, and similar GRKs. They contain an N-terminal RGS homology (RH) domain and a catalytic domain, but lack a G protein betagamma-subunit binding domain. They are localized to the plasma membrane through post-translational lipid modification or direct binding to PIP2. 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 GRK4-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 47680169 116 VGTAQYVSPELLTEKSACKSSDLWALGCIIYQLVAGLPPFRAGNEylifqKIIKLEYD---------FPEKFFPKARDLV 186
Cdd:cd05605 162 VGTVGYMAPEVVKNERYTFSPDWWGLGCLIYEMIEGQAPFRARKE-----KVKREEVDrrvkedqeeYSEKFSEEAKSIC 236

                        90       100       110
                ....*....|....*....|....*....|....*..
gi 47680169 187 EKLLVLDATKRLGCEEmEGYGPLKAHPFFESVTWENL 223
Cdd:cd05605 237 SQLLQKDPKTRLGCRG-EGAEDVKSHPFFKSINFKRL 272

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 47680169 108 YATRANSFVGTAQYVSPELLTEKSACKSSDLWALGCIIYQLVAGLPPFRAGNEYLIFQKIIKLEYDFPEKFFPKARDLVE 187
Cdd:cd05571 148 YGATTKTFCGTPEYLAPEVLEDNDYGRAVDWWGLGVVMYEMMCGRLPFYNRDHEVLFELILMEEVRFPSTLSPEAKSLLA 227

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....
gi 47680169 188 KLLVLDATKRLGCEEmEGYGPLKAHPFFESVTWENLHQQ--TPP 229
Cdd:cd05571 228 GLLKKDPKKRLGGGP-RDAKEIMEHPFFASINWDDLYQKkiPPP 270

Catalytic domain of the Serine/Threonine Kinase, beta-adrenergic receptor kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The beta-ARK group is composed of GRK2, GRK3, and similar proteins. GRK2 and GRK3 are both widely expressed in many tissues, although GRK2 is present at higher levels. They contain 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. GRK2 (also called 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. 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 beta-ARK 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 47680169 116 VGTAQYVSPELLTEKSACKSS-DLWALGCIIYQLVAGLPPFR---AGNEYLIFQKIIKLEYDFPEKFFPKARDLVEKLLV 191
Cdd:cd05606 157 VGTHGYMAPEVLQKGVAYDSSaDWFSLGCMLYKLLKGHSPFRqhkTKDKHEIDRMTLTMNVELPDSFSPELKSLLEGLLQ 236

                        90       100       110       120
                ....*....|....*....|....*....|....*....|
gi 47680169 192 LDATKRLGCEEmEGYGPLKAHPFFESVTWENLHQQ--TPP 229
Cdd:cd05606 237 RDVSKRLGCLG-RGATEVKEHPFFKGVDWQQVYLQkyPPP 275

Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. GRK4 has a limited tissue distribution. It is mainly found in the testis, but is also present in the cerebellum and kidney. It is expressed as multiple splice variants with different domain architectures and is post-translationally palmitoylated and localized in the membrane. GRK4 polymorphisms are associated with hypertension and salt sensitivity, as they cause hyperphosphorylation, desensitization, and internalization of the dopamine 1 (D1) receptor while increasing the expression of the angiotensin II type 1 receptor. GRK4 plays a crucial role in the D1 receptor regulation of sodium excretion and blood pressure. 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 GRK4 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 47680169 102 LATSREYATRANSFVGTAQYVSPELLTEKSACKSSDLWALGCIIYQLVAGLPPFRAGNEYL----IFQKIIKLEYDFPEK 177
Cdd:cd05631 148 LAVQIPEGETVRGRVGTVGYMAPEVINNEKYTFSPDWWGLGCLIYEMIQGQSPFRKRKERVkreeVDRRVKEDQEEYSEK 227

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....
gi 47680169 178 FFPKARDLVEKLLVLDATKRLGCEEmEGYGPLKAHPFFESVTWENLHQQT--PP 229
Cdd:cd05631 228 FSEDAKSICRMLLTKNPKERLGCRG-NGAAGVKQHPIFKNINFKRLEANMlePP 280

Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase 5; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. GRK5 is widely expressed in many tissues. It associates with the membrane though an N-terminal PIP2 binding domain and also binds phospholipids via its C-terminus. GRK5 deficiency is associated with early Alzheimer's disease in humans and mouse models. GRK5 also plays a crucial role in the pathogenesis of sporadic Parkinson's disease. It participates in the regulation and desensitization of PDGFRbeta, a receptor tyrosine kinase involved in a variety of downstream cellular effects including cell growth, chemotaxis, apoptosis, and angiogenesis. GRK5 also regulates Toll-like receptor 4, which is involved in innate and adaptive immunity. 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 GRK5 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 47680169 116 VGTAQYVSPELLTEKSACKSSDLWALGCIIYQLVAGLPPFRAGNEYL----IFQKIIKLEYDFPEKFFPKARDLVEKLLV 191
Cdd:cd05632 164 VGTVGYMAPEVLNNQRYTLSPDYWGLGCLIYEMIEGQSPFRGRKEKVkreeVDRRVLETEEVYSAKFSEEAKSICKMLLT 243

                        90       100       110
                ....*....|....*....|....*....|..
gi 47680169 192 LDATKRLGCEEmEGYGPLKAHPFFESVTWENL 223
Cdd:cd05632 244 KDPKQRLGCQE-EGAGEVKRHPFFRNMNFKRL 274