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 1720389304 225 KQAGGNPWHQFVENNLILKMGPVDKRKGLFARRRQLLLTEGPHLYYVDPVNKVLKGEIPWSQELRPEAKNFKTFFVHTPN 304
Cdd:cd01262     1 QQQSENWWHFLVNGELILKMGLVDKRKGLFAKKRQLILTDGPRLYYVDPVKMVLKGEIPWSPELRPEVKNFKTFFIHTPN 80

                          90       100
                  ....*....|....*....|....*..
gi 1720389304 305 RTYYLMDPSGNAHKWCRKIQEVWRQQY 331
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 1720389304 225 KQAGGNPWHQFVENNLILKMGPVDKRKGLFARRRQLLLTEGPHLYYVDPVNKVLKGEIPWSQELRPEAKNFKTFFVHTPN 304
Cdd:cd01262     1 QQQSENWWHFLVNGELILKMGLVDKRKGLFAKKRQLILTDGPRLYYVDPVKMVLKGEIPWSPELRPEVKNFKTFFIHTPN 80

                          90       100
                  ....*....|....*....|....*..
gi 1720389304 305 RTYYLMDPSGNAHKWCRKIQEVWRQQY 331
Cdd:cd01262    81 RTYYLEDPEGNAKKWCKAIEEVLKLYK 107

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720389304    1 MHIQITDFGTAKVLSPESkqaRANSFVGTAQYVSPELLTEKSACKSSDLWALGCIIYQLVAGLPPFRAGNEYL-IFQKII 79
Cdd:smart00220 134 GHVKLADFGLARQLDPGE---KLTTFVGTPEYMAPEVLLGKGYGKAVDIWSLGVILYELLTGKPPFPGDDQLLeLFKKIG 210

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|
gi 1720389304   80 KLEYHFPEKFF---PKARDLVEKLLVLDATKRLGCEEmegygpLKAHPFF 126
Cdd:smart00220 211 KPKPPFPPPEWdisPEAKDLIRKLLVKDPEKRLTAEE------ALQHPFF 254

Protein kinase domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720389304  23 ANSFVGTAQYVSPELLTEKSACKSSDLWALGCIIYQLVAGLPPFRAGNEYLIFQKIIKLEYHFPEKFF---PKARDLVEK 99
Cdd:pfam00069 117 LTTFVGTPWYMAPEVLGGNPYGPKVDVWSLGCILYELLTGKPPFPGINGNEIYELIIDQPYAFPELPSnlsEEAKDLLKK 196

                          90       100
                  ....*....|....*....|....*..
gi 1720389304 100 LLVLDATKRLGCEEmegygpLKAHPFF 126
Cdd:pfam00069 197 LLKKDPSKRLTATQ------ALQHPWF 217

Stk1 family PASTA domain-containing Ser/Thr kinase;

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1720389304   3 IQITDFGTAKVLSpESKQARANSFVGTAQYVSPELLTEKSACKSSDLWALGCIIYQLVAGLPPF 66
Cdd:NF033483  146 VKVTDFGIARALS-STTMTQTNSVLGTVHYLSPEQARGGTVDARSDIYSLGIVLYEMLTGRPPF 208

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 1720389304 225 KQAGGNPWHQFVENNLILKMGPVDKRKGLFARRRQLLLTEGPHLYYVDPVNKVLKGEIPWSQELRPEAKNFKTFFVHTPN 304
Cdd:cd01262     1 QQQSENWWHFLVNGELILKMGLVDKRKGLFAKKRQLILTDGPRLYYVDPVKMVLKGEIPWSPELRPEVKNFKTFFIHTPN 80

                          90       100
                  ....*....|....*....|....*..
gi 1720389304 305 RTYYLMDPSGNAHKWCRKIQEVWRQQY 331
Cdd:cd01262    81 RTYYLEDPEGNAKKWCKAIEEVLKLYK 107

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 1720389304   2 HIQITDFGTAKVLSPESkqARANSFVGTAQYVSPELLTEKSACKSSDLWALGCIIYQLVAGLPPFRAGNEYLIFQKIIKL 81
Cdd:cd05123   131 HIKLTDFGLAKELSSDG--DRTYTFCGTPEYLAPEVLLGKGYGKAVDWWSLGVLLYEMLTGKPPFYAENRKEIYEKILKS 208

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*
gi 1720389304  82 EYHFPEKFFPKARDLVEKLLVLDATKRLGCEEMEgygPLKAHPFF 126
Cdd:cd05123   209 PLKFPEYVSPEAKSLISGLLQKDPTKRLGSGGAE---EIKAHPFF 250

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 1720389304   2 HIQITDFGTAKV-------------LSPESKQARANSFVGTAQYVSPELLTEKSACKSSDLWALGCIIYQLVAGLPPFRA 68
Cdd:cd05579   131 HLKLTDFGLSKVglvrrqiklsiqkKSNGAPEKEDRRIVGTPDYLAPEILLGQGHGKTVDWWSLGVILYEFLVGIPPFHA 210

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1720389304  69 GNEYLIFQKIIKLEYHFPEKFF--PKARDLVEKLLVLDATKRLGCeemEGYGPLKAHPFFETITW 131
Cdd:cd05579   211 ETPEEIFQNILNGKIEWPEDPEvsDEAKDLISKLLTPDPEKRLGA---KGIEEIKNHPFFKGIDW 272

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 1720389304   2 HIQITDFGTAKVLSPESKqarANSFVGTAQYVSPELLTEKSACKSSDLWALGCIIYQLVAGLPPFRAGNEYLIFQKIIKL 81
Cdd:cd05117   140 PIKIIDFGLAKIFEEGEK---LKTVCGTPYYVAPEVLKGKGYGKKCDIWSLGVILYILLCGYPPFYGETEQELFEKILKG 216

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*...
gi 1720389304  82 EYHFPEKFFPK----ARDLVEKLLVLDATKRLGCEEmegygpLKAHPF 125
Cdd:cd05117   217 KYSFDSPEWKNvseeAKDLIKRLLVVDPKKRLTAAE------ALNHPW 258

Catalytic domain of the Serine/Threonine Kinase, Protein Kinase C; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. PKCs undergo three phosphorylations in order to take mature forms. In addition, classical PKCs depend on calcium, DAG (1,2-diacylglycerol), and in most cases, phosphatidylserine (PS) for activation. Novel PKCs are calcium-independent, but require DAG and PS for activity, while atypical PKCs only require PS. PKCs phosphorylate and modify the activities of a wide variety of cellular proteins including receptors, enzymes, cytoskeletal proteins, transcription factors, and other kinases. They play a central role in signal transduction pathways that regulate cell migration and polarity, proliferation, differentiation, and apoptosis. Also included in this subfamily are the PKC-like proteins, called PKNs. The PKC 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 1720389304   2 HIQITDFGTAKvlspE--SKQARANSFVGTAQYVSPELLTEKSACKSSDLWALGCIIYQLVAGLPPFRAGNEYLIFQKII 79
Cdd:cd05570   134 HIKIADFGMCK----EgiWGGNTTSTFCGTPDYIAPEILREQDYGFSVDWWALGVLLYEMLAGQSPFEGDDEDELFEAIL 209

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1720389304  80 KLEYHFPEKFFPKARDLVEKLLVLDATKRLGCEEmEGYGPLKAHPFFETITWENL-HQQTPP 140
Cdd:cd05570   210 NDEVLYPRWLSREAVSILKGLLTKDPARRLGCGP-KGEADIKAHPFFRNIDWDKLeKKEVEP 270

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 1720389304   2 HIQITDFGTAKVLSPESKQ---------------------------ARANSFVGTAQYVSPELLTEKSACKSSDLWALGC 54
Cdd:cd05574   141 HIMLTDFDLSKQSSVTPPPvrkslrkgsrrssvksieketfvaepsARSNSFVGTEEYIAPEVIKGDGHGSAVDWWTLGI 220

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720389304  55 IIYQLVAGLPPFRAGNEYLIFQKIIKLEYHFPEKFF--PKARDLVEKLLVLDATKRLGCEemEGYGPLKAHPFFETITWE 132
Cdd:cd05574   221 LLYEMLYGTTPFKGSNRDETFSNILKKELTFPESPPvsSEAKDLIRKLLVKDPSKRLGSK--RGASEIKRHPFFRGVNWA 298

                         170       180
                  ....*....|....*....|..
gi 1720389304 133 NLHQQTPPkltaYLPAMSEDDE 154
Cdd:cd05574   299 LIRNMTPP----IIPRPDDPID 316

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 1720389304   2 HIQITDFGTAK-----------------VLSPESKQAR----------ANSFVGTAQYVSPELLTEKSACKSSDLWALGC 54
Cdd:cd05573   139 HIKLADFGLCTkmnksgdresylndsvnTLFQDNVLARrrphkqrrvrAYSAVGTPDYIAPEVLRGTGYGPECDWWSLGV 218

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720389304  55 IIYQLVAGLPPFRAGNEYLIFQKII--KLEYHFP--EKFFPKARDLVEKLLVlDATKRLGC-EEmegygpLKAHPFFETI 129
Cdd:cd05573   219 ILYEMLYGFPPFYSDSLVETYSKIMnwKESLVFPddPDVSPEAIDLIRRLLC-DPEDRLGSaEE------IKAHPFFKGI 291

                         170       180
                  ....*....|....*....|....*...
gi 1720389304 130 TWENLHQQTPPkltaYLPAMSEDDEDCY 157
Cdd:cd05573   292 DWENLRESPPP----FVPELSSPTDTSN 315

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 1720389304   2 HIQITDFGTAKVLSpesKQARANSFVGTAQYVSPELLTEKSACKSSDLWALGCIIYQLVAGLPPFRAGNEYLIFQKIIKL 81
Cdd:cd05599   139 HIKLSDFGLCTGLK---KSHLAYSTVGTPDYIAPEVFLQKGYGKECDWWSLGVIMYEMLIGYPPFCSDDPQETCRKIMNW 215

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1720389304  82 EYH--FPE--KFFPKARDLVEKLLVlDATKRLGceeMEGYGPLKAHPFFETITWENLHQQTPPkltaYLPAM-SEDD 153
Cdd:cd05599   216 RETlvFPPevPISPEAKDLIERLLC-DAEHRLG---ANGVEEIKSHPFFKGVDWDHIRERPAP----ILPEVkSILD 284

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 1720389304   2 HIQITDFGtakvLSPESKQ--ARANSFVGTAQYVSPELLTEKSACKSSDLWALGCIIYQLVAGLPPFRAGNEYLIFQKII 79
Cdd:cd05584   138 HVKLTDFG----LCKESIHdgTVTHTFCGTIEYMAPEILTRSGHGKAVDWWSLGALMYDMLTGAPPFTAENRKKTIDKIL 213

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1720389304  80 KLEYHFPEKFFPKARDLVEKLLVLDATKRLGcEEMEGYGPLKAHPFFETITWENLHQQT--PPkltaYLPAMSEDDE 154
Cdd:cd05584   214 KGKLNLPPYLTNEARDLLKKLLKRNVSSRLG-SGPGDAEEIKAHPFFRHINWDDLLAKKvePP----FKPLLQSEED 285

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 1720389304   2 HIQITDFG--TAKVLSPESKQARANSFVGTAQYVSPELLTEKSACKSSDLWALGCIIYQLVAGLPPFRAGNEYLIFQKII 79
Cdd:cd05598   139 HIKLTDFGlcTGFRWTHDSKYYLAHSLVGTPNYIAPEVLLRTGYTQLCDWWSVGVILYEMLVGQPPFLAQTPAETQLKVI 218

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1720389304  80 --KLEYHFPE--KFFPKARDLVEKLLVlDATKRLGCeemEGYGPLKAHPFFETITWENLHQQTPPkltaYLPAMSEDDE 154
Cdd:cd05598   219 nwRTTLKIPHeaNLSPEAKDLILRLCC-DAEDRLGR---NGADEIKAHPFFAGIDWEKLRKQKAP----YIPTIRHPTD 289

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 1720389304   2 HIQITDFGTAKVLSPESKqaRANSFVGTAQYVSPELLTEKSACKSSDLWALGCIIYQLVAGLPPFRAGNEYLIFQKIIKL 81
Cdd:cd05585   132 HIALCDFGLCKLNMKDDD--KTNTFCGTPEYLAPELLLGHGYTKAVDWWTLGVLLYEMLTGLPPFYDENTNEMYRKILQE 209

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1720389304  82 EYHFPEKFFPKARDLVEKLLVLDATKRLGceeMEGYGPLKAHPFFETITWENLHQQ--TPPkltaYLPAMS 150
Cdd:cd05585   210 PLRFPDGFDRDAKDLLIGLLNRDPTKRLG---YNGAQEIKNHPFFDQIDWKRLLMKkiQPP----FKPAVE 273

Protein kinase domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720389304  23 ANSFVGTAQYVSPELLTEKSACKSSDLWALGCIIYQLVAGLPPFRAGNEYLIFQKIIKLEYHFPEKFF---PKARDLVEK 99
Cdd:pfam00069 117 LTTFVGTPWYMAPEVLGGNPYGPKVDVWSLGCILYELLTGKPPFPGINGNEIYELIIDQPYAFPELPSnlsEEAKDLLKK 196

                          90       100
                  ....*....|....*....|....*..
gi 1720389304 100 LLVLDATKRLGCEEmegygpLKAHPFF 126
Cdd:pfam00069 197 LLKKDPSKRLTATQ------ALQHPWF 217

N-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 1720389304   2 HIQITDFGTAKVLSPESKQaRANSFVGTAQYVSPELLTEKSAC--KSSDLWALGCIIYQLVAGLPPF----RAGNEYLIF 75
Cdd:cd05583   137 HVVLTDFGLSKEFLPGEND-RAYSFCGTIEYMAPEVVRGGSDGhdKAVDWWSLGVLTYELLTGASPFtvdgERNSQSEIS 215

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1720389304  76 QKIIKLEYHFPEKFFPKARDLVEKLLVLDATKRLGCEEmEGYGPLKAHPFFETI 129
Cdd:cd05583   216 KRILKSHPPIPKTFSAEAKDFILKLLEKDPKKRLGAGP-RGAHEIKEHPFFKGL 268

N-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MSK1 plays a role in the regulation of translational control and transcriptional activation. It phosphorylates the transcription factors, CREB and NFkB. It also phosphorylates the nucleosomal proteins H3 and HMG-14. Increased phosphorylation of MSK1 is associated with the development of cerebral ischemic/hypoxic preconditioning. 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, which trigger phosphorylation in the activation loop (A-loop) of the CTD of MSK. The active CTD phosphorylates the hydrophobic motif (HM) of NTD, which facilitates the phosphorylation of the A-loop and activates the NTD, which in turn phosphorylates downstream targets. The MSK1 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 1720389304   2 HIQITDFGTAKVLSPESKQaRANSFVGTAQYVSPELLT--EKSACKSSDLWALGCIIYQLVAGLPPFRAGNE----YLIF 75
Cdd:cd05613   143 HVVLTDFGLSKEFLLDENE-RAYSFCGTIEYMAPEIVRggDSGHDKAVDWWSLGVLMYELLTGASPFTVDGEknsqAEIS 221

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1720389304  76 QKIIKLEYHFPEKFFPKARDLVEKLLVLDATKRLGCEEmEGYGPLKAHPFFETITWENLHQQTPP 140
Cdd:cd05613   222 RRILKSEPPYPQEMSALAKDIIQRLLMKDPKKRLGCGP-NGADEIKKHPFFQKINWDDLAAKKVP 285

Catalytic domain of the Serine/Threonine Kinase, Serum- and Glucocorticoid-induced Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SGKs are activated by insulin and growth factors via phosphoinositide 3-kinase and PDK1. They activate ion channels, ion carriers, and the Na-K-ATPase, as well as regulate the activity of enzymes and transcription factors. SGKs play important roles in transport, hormone release, neuroexcitability, cell proliferation, and apoptosis. There are three isoforms of SGK, named SGK1, SGK2, and SGK3 (also called cytokine-independent survival kinase CISK). The SGK 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 1720389304   2 HIQITDFGTAKVLSPESKQAraNSFVGTAQYVSPELLTEKSACKSSDLWALGCIIYQLVAGLPPFRAGNEYLIFQKIIKL 81
Cdd:cd05575   134 HVVLTDFGLCKEGIEPSDTT--STFCGTPEYLAPEVLRKQPYDRTVDWWCLGAVLYEMLYGLPPFYSRDTAEMYDNILHK 211

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1720389304  82 EYHFPEKFFPKARDLVEKLLVLDATKRLGCEemEGYGPLKAHPFFETITWENLHQQ--TPP 140
Cdd:cd05575   212 PLRLRTNVSPSARDLLEGLLQKDRTKRLGSG--NDFLEIKNHSFFRPINWDDLEAKkiPPP 270

Catalytic domain of the Serine/Threonine Kinases, Novel Protein Kinase C theta, delta, and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKC-theta is selectively expressed in T-cells and plays an important and non-redundant role in several aspects of T-cell biology. PKC-delta plays a role in cell cycle regulation and programmed cell death in many cell types. 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. There are four nPKC isoforms, delta, epsilon, eta, and theta. The nPKC-theta-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 1720389304   2 HIQITDFGTAKV-LSPESKqarANSFVGTAQYVSPELLTEKSACKSSDLWALGCIIYQLVAGLPPFRAGNEYLIFQKIIK 80
Cdd:cd05592   134 HIKIADFGMCKEnIYGENK---ASTFCGTPDYIAPEILKGQKYNQSVDWWSFGVLLYEMLIGQSPFHGEDEDELFWSICN 210

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1720389304  81 LEYHFPEKFFPKARDLVEKLLVLDATKRLGCEEmEGYGPLKAHPFFETITWENLH--QQTPP 140
Cdd:cd05592   211 DTPHYPRWLTKEAASCLSLLLERNPEKRLGVPE-CPAGDIRDHPFFKTIDWDKLErrEIDPP 271

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 1720389304   2 HIQITDFGTAKvlSPESKQARANSFVGTAQYVSPELLTEKSACKSSDLWALGCIIYQLVAGLPPFRAGNEYLIFQKIIKL 81
Cdd:cd05620   134 HIKIADFGMCK--ENVFGDNRASTFCGTPDYIAPEILQGLKYTFSVDWWSFGVLLYEMLIGQSPFHGDDEDELFESIRVD 211

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720389304  82 EYHFPEKFFPKARDLVEKLLVLDATKRLGCeemegYGPLKAHPFFETITWENLHQQT--PPkltaYLPAMSEDDEdcYGN 159
Cdd:cd05620   212 TPHYPRWITKESKDILEKLFERDPTRRLGV-----VGNIRGHPFFKTINWTALEKREldPP----FKPKVKSPSD--YSN 280

                  ..
gi 1720389304 160 YD 161
Cdd:cd05620   281 FD 282

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 1720389304   1 MHIQITDFGTAKVLSPESKqarANSFVGTAQYVSPELLT-EKSACKSSDLWALGCIIYQLVAGLPPFRAGNEYLIFQKII 79
Cdd:cd14003   136 GNLKIIDFGLSNEFRGGSL---LKTFCGTPAYAAPEVLLgRKYDGPKADVWSLGVILYAMLTGYLPFDDDNDSKLFRKIL 212

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*.
gi 1720389304  80 KLEYHFPEKFFPKARDLVEKLLVLDATKRLGCEEmegygpLKAHPF 125
Cdd:cd14003   213 KGKYPIPSHLSPDARDLIRRMLVVDPSKRITIEE------ILNHPW 252