The phosphoinositide binding Phox Homology domain of RPK118-like proteins; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions such as cell signaling, vesicular trafficking, protein sorting, and lipid modification, among others. Members of this subfamily bear similarity to human RPK118, which contains an N-terminal PX domain, a Microtubule Interacting and Trafficking (MIT) domain, and a kinase domain. RPK118 binds sphingosine kinase, a key enzyme in the synthesis of sphingosine 1-phosphate (SPP), a lipid messenger involved in many cellular events. RPK118 may be involved in transmitting SPP-mediated signaling. It also binds the antioxidant peroxiredoxin-3 (PRDX3) and may be involved in the transport of PRDX3 from the cytoplasm to its site of function in the mitochondria. Members of this subfamily also show similarity to sorting nexin 15 (SNX15), which contains PX and MIT domains but does not contain a kinase domain. SNXs make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNX15 plays a role in protein trafficking processes in the endocytic pathway and the trans-Golgi network. The PX domain of SNX15 interacts with the PDGF receptor and is responsible for the membrane association of the protein.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622828809   11 LARFYTVTEPQRHPRGYTVYKVTARVVSRRNPEDVQEIIVWKRYSDFKKLHKELWQIHKNLFRHSELFPPFAKGIVFGRF 90
Cdd:cd07287      1 LARFYTVTDPRRHPKGYTVYKVTARIVSRKNPEDVQEIVVWKRYSDFKKLHKDLWQIHKNLCRQSELFPPFAKAKVFGRF 80

                           90       100       110
                   ....*....|....*....|....*....|....*...
gi 1622828809   91 DETVIEERRQCAEDLLQFSANIPALYNSKQLEDFFKGG 128
Cdd:cd07287     81 DESVIEERRQCAEDLLQFSANIPALYNSSQLEDFFKGG 118

MIT: domain contained within Microtubule Interacting and Trafficking molecules. This MIT domain sub-family is found in sorting nexin 15 and related proteins. The molecular function of the MIT domain is unclear.

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622828809  238 DYLEKAGELIKLALKKEEEDDYEAASDFYRKGVDLLLEGVQGESSPTRREAVKRRTAEYLMRAESISGLY 307
Cdd:cd02677      1 DYLEQAAELIRLALEKEEEGDYEAAFEFYRAGVDLLLKGVQGDSSPERREAVKRKIAEYLKRAEEILRLH 70

The phosphoinositide binding Phox Homology domain of RPK118-like proteins; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions such as cell signaling, vesicular trafficking, protein sorting, and lipid modification, among others. Members of this subfamily bear similarity to human RPK118, which contains an N-terminal PX domain, a Microtubule Interacting and Trafficking (MIT) domain, and a kinase domain. RPK118 binds sphingosine kinase, a key enzyme in the synthesis of sphingosine 1-phosphate (SPP), a lipid messenger involved in many cellular events. RPK118 may be involved in transmitting SPP-mediated signaling. It also binds the antioxidant peroxiredoxin-3 (PRDX3) and may be involved in the transport of PRDX3 from the cytoplasm to its site of function in the mitochondria. Members of this subfamily also show similarity to sorting nexin 15 (SNX15), which contains PX and MIT domains but does not contain a kinase domain. SNXs make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNX15 plays a role in protein trafficking processes in the endocytic pathway and the trans-Golgi network. The PX domain of SNX15 interacts with the PDGF receptor and is responsible for the membrane association of the protein.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622828809   11 LARFYTVTEPQRHPRGYTVYKVTARVVSRRNPEDVQEIIVWKRYSDFKKLHKELWQIHKNLFRHSELFPPFAKGIVFGRF 90
Cdd:cd07287      1 LARFYTVTDPRRHPKGYTVYKVTARIVSRKNPEDVQEIVVWKRYSDFKKLHKDLWQIHKNLCRQSELFPPFAKAKVFGRF 80

                           90       100       110
                   ....*....|....*....|....*....|....*...
gi 1622828809   91 DETVIEERRQCAEDLLQFSANIPALYNSKQLEDFFKGG 128
Cdd:cd07287     81 DESVIEERRQCAEDLLQFSANIPALYNSSQLEDFFKGG 118

MIT: domain contained within Microtubule Interacting and Trafficking molecules. This MIT domain sub-family is found in sorting nexin 15 and related proteins. The molecular function of the MIT domain is unclear.

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622828809  238 DYLEKAGELIKLALKKEEEDDYEAASDFYRKGVDLLLEGVQGESSPTRREAVKRRTAEYLMRAESISGLY 307
Cdd:cd02677      1 DYLEQAAELIRLALEKEEEGDYEAAFEFYRAGVDLLLKGVQGDSSPERREAVKRKIAEYLKRAEEILRLH 70

Microtubule Interacting and Trafficking molecule domain;

                            10        20        30        40        50        60
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1622828809   236 KRDYLEKAGELIKLALKKEEEDDYEAASDFYRKGVDLLLEGVQGESSPTRREAVKRRTAEYLMRAESI 303
Cdd:smart00745    1 TRDYLSKAKELISKALKADEAGNYEEALELYKKAIEYLLEGIKVESDSKRREALKAKAAEYLDRAEEI 68

MIT (microtubule interacting and transport) domain; The MIT domain forms an asymmetric three-helix bundle and binds ESCRT-III (endosomal sorting complexes required for transport) substrates.

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1622828809  240 LEKAGELIKLALKKEEEDDYEAASDFYRKGVDLLLEGVQGESSPTRREAVKRRTAEYLMRAESI 303
Cdd:pfam04212    1 LSKALELVKKAVEEDNAGNYEEALELYKEALDYLLLALKETKNEERRELLRAKIAEYLERAEEL 64

PX domain; PX domains bind to phosphoinositides.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622828809   40 RNPEDVQEIIVWKRYSDFKKLHKELWQIHKNLFrhselFPPFAKGIVFGRFDETVIEERRQCAEDLLQFSANIPALYNSK 119
Cdd:pfam00787    1 LPTFSLEEWSVRRRYSDFVELHKKLLRKFPSVI-----IPPLPPKRWLGRYNEEFIEKRRKGLEQYLQRLLQHPELRNSE 75

                   ....*.
gi 1622828809  120 QLEDFF 125
Cdd:pfam00787   76 VLLEFL 81

PhoX homologous domain, present in p47phox and p40phox; Eukaryotic domain of unknown function present in phox proteins, PLD isoforms, a PI3K isoform.

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622828809    17 VTEPQRHPRG---YTVYKVTarvvsRRNPEdvQEIIVWKRYSDFKKLHKELwqihKNLFRHSELFPPFAKGIV--FGRFD 91
Cdd:smart00312    1 VVEPEKIGDGkhyYYVIEIE-----TKTGL--EEWTVSRRYSDFLELHSKL----KKHFPRSILPPLPGKKLFgrLNNFS 69

                            90       100       110
                    ....*....|....*....|....*....|....*
gi 1622828809    92 ETVIEERRQCAEDLLQFSANIPALYN-SKQLEDFF 125
Cdd:smart00312   70 EEFIEKRRRGLEKYLQSLLNHPELINhSEVVLEFL 104

The phosphoinositide binding Phox Homology domain of RPK118-like proteins; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions such as cell signaling, vesicular trafficking, protein sorting, and lipid modification, among others. Members of this subfamily bear similarity to human RPK118, which contains an N-terminal PX domain, a Microtubule Interacting and Trafficking (MIT) domain, and a kinase domain. RPK118 binds sphingosine kinase, a key enzyme in the synthesis of sphingosine 1-phosphate (SPP), a lipid messenger involved in many cellular events. RPK118 may be involved in transmitting SPP-mediated signaling. It also binds the antioxidant peroxiredoxin-3 (PRDX3) and may be involved in the transport of PRDX3 from the cytoplasm to its site of function in the mitochondria. Members of this subfamily also show similarity to sorting nexin 15 (SNX15), which contains PX and MIT domains but does not contain a kinase domain. SNXs make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNX15 plays a role in protein trafficking processes in the endocytic pathway and the trans-Golgi network. The PX domain of SNX15 interacts with the PDGF receptor and is responsible for the membrane association of the protein.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622828809   11 LARFYTVTEPQRHPRGYTVYKVTARVVSRRNPEDVQEIIVWKRYSDFKKLHKELWQIHKNLFRHSELFPPFAKGIVFGRF 90
Cdd:cd07287      1 LARFYTVTDPRRHPKGYTVYKVTARIVSRKNPEDVQEIVVWKRYSDFKKLHKDLWQIHKNLCRQSELFPPFAKAKVFGRF 80

                           90       100       110
                   ....*....|....*....|....*....|....*...
gi 1622828809   91 DETVIEERRQCAEDLLQFSANIPALYNSKQLEDFFKGG 128
Cdd:cd07287     81 DESVIEERRQCAEDLLQFSANIPALYNSSQLEDFFKGG 118

The phosphoinositide binding Phox Homology domain of Sorting Nexin 15; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Sorting nexins (SNXs) make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway. SNX15 contains an N-terminal PX domain and a C-terminal Microtubule Interacting and Trafficking (MIT) domain. It plays a role in protein trafficking processes in the endocytic pathway and the trans-Golgi network. The PX domain of SNX15 interacts with the PDGF receptor and is responsible for the membrane association of the protein.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622828809   13 RFYTVTEPQRHPRGYTVYKVTARVVSRRNPEDVQEIIVWKRYSDFKKLHKELWQIHKNLFRHSELFPPFAKGIVFGRFDE 92
Cdd:cd07288      3 RFYSVTDPRTHPKGYTEYKVTAQFISKKQPEDVKEVVVWKRYSDLKKLHGELAYTHRNLFRRQEEFPPFPRAQVFGRFEA 82

                           90       100       110
                   ....*....|....*....|....*....|....*.
gi 1622828809   93 TVIEERRQCAEDLLQFSANIPALYNSKQLEDFFKGG 128
Cdd:cd07288     83 AVIEERRNAAEAMLLFTVNIPALYNSPQLKEFFRDG 118

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 1622828809  895 LTSRFYIPEGCIQRWAAEMVVALDALHREGIVCRDLNPNNILLNDR---------------------------------E 941
Cdd:cd05123     84 LSKEGRFPEERARFYAAEIVLALEYLHSLGIIYRDLKPENILLDSDghikltdfglakelssdgdrtytfcgtpeylapE 163

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622828809  942 VGAITEETEACDWWSLGAVLFELLTGKTLVECHPAGINTHT----TLNMPECVSEEARSLIQQLLQFNPLERLGAGvaGV 1017
Cdd:cd05123    164 VLLGKGYGKAVDWWSLGVLLYEMLTGKPPFYAENRKEIYEKilksPLKFPEYVSPEAKSLISGLLQKDPTKRLGSG--GA 241

                   ....*....
gi 1622828809 1018 EDIKSHPFF 1026
Cdd:cd05123    242 EEIKAHPFF 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 1622828809  889 LDKKLAltsRFYIpegciqrwaAEMVVALDALHREGIVCRDLNPNNILLNDR-----------EVGAITEETE------- 950
Cdd:cd05579     90 LDEDVA---RIYI---------AEIVLALEYLHSHGIIHRDLKPDNILIDANghlkltdfglsKVGLVRRQIKlsiqkks 157

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622828809  951 ------------------------------ACDWWSLGAVLFELLTGKT-LVECHPAGINTHTT---LNMPEC--VSEEA 994
Cdd:cd05579    158 ngapekedrrivgtpdylapeillgqghgkTVDWWSLGVILYEFLVGIPpFHAETPEEIFQNILngkIEWPEDpeVSDEA 237

                          170       180       190
                   ....*....|....*....|....*....|....*..
gi 1622828809  995 RSLIQQLLQFNPLERLGAGvaGVEDIKSHPFFTPVDW 1031
Cdd:cd05579    238 KDLISKLLTPDPEKRLGAK--GIEEIKNHPFFKGIDW 272

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 1622828809  897 SRFYipegciqrwAAEMVVALDALHREGIVCRDLNPNNILLND------------REVGAITEETE-------------- 950
Cdd:cd05575     98 ARFY---------AAEIASALGYLHSLNIIYRDLKPENILLDSqghvvltdfglcKEGIEPSDTTStfcgtpeylapevl 168

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622828809  951 -------ACDWWSLGAVLFELLTG------KTLVECHPAGIntHTTLNMPECVSEEARSLIQQLLQFNPLERLGAGvAGV 1017
Cdd:cd05575    169 rkqpydrTVDWWCLGAVLYEMLYGlppfysRDTAEMYDNIL--HKPLRLRTNVSPSARDLLEGLLQKDRTKRLGSG-NDF 245

                          170
                   ....*....|....*....
gi 1622828809 1018 EDIKSHPFFTPVDWAELMR 1036
Cdd:cd05575    246 LEIKNHSFFRPINWDDLEA 264

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

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622828809   875 ALEGDKEIHQIFE-----DLDKKLalTSRFYIPEGCIQRWAAEMVVALDALHREGIVCRDLNPNNILLNDR--------- 940
Cdd:smart00220   65 VFEDEDKLYLVMEyceggDLFDLL--KKRGRLSEDEARFYLRQILSALEYLHSKGIVHRDLKPENILLDEDghvkladfg 142

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622828809   941 -----------------------EVgaITEE--TEACDWWSLGAVLFELLTGKTL--------VECHPAGINTHTTLNMP 987
Cdd:smart00220  143 larqldpgeklttfvgtpeymapEV--LLGKgyGKAVDIWSLGVILYELLTGKPPfpgddqllELFKKIGKPKPPFPPPE 220

                           170       180       190
                    ....*....|....*....|....*....|....*....
gi 1622828809   988 ECVSEEARSLIQQLLQFNPLERLGAgvagvEDIKSHPFF 1026
Cdd:smart00220  221 WDISPEAKDLIRKLLVKDPEKRLTA-----EEALQHPFF 254

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 1622828809  900 YIPEGCIQRWAAEMVVALDALHREGIVCRDLNPNNILLNDR-----------EVGAITEE-------------------- 948
Cdd:cd05611     93 GLPEDWAKQYIAEVVLGVEDLHQRGIIHRDIKPENLLIDQTghlkltdfglsRNGLEKRHnkkfvgtpdylapetilgvg 172

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622828809  949 -TEACDWWSLGAVLFELLTGKTlvechPAGINT---------HTTLNMPECV----SEEARSLIQQLLQFNPLERLGAGv 1014
Cdd:cd05611    173 dDKMSDWWSLGCVIFEFLFGYP-----PFHAETpdavfdnilSRRINWPEEVkefcSPEAVDLINRLLCMDPAKRLGAN- 246

                          170
                   ....*....|....*..
gi 1622828809 1015 aGVEDIKSHPFFTPVDW 1031
Cdd:cd05611    247 -GYQEIKSHPFFKSINW 262

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 1622828809  900 YIPEGCIQRWAAEMVVALDALHREGIVCRDLNPNNILLndREVGAI---------------------------------- 945
Cdd:cd05574     99 RLPEEVARFYAAEVLLALEYLHLLGFVYRDLKPENILL--HESGHImltdfdlskqssvtpppvrkslrkgsrrssvksi 176

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622828809  946 ------------------TEE------------TEACDWWSLGAVLFELLTGKTlvechP-AGINTHTT--------LNM 986
Cdd:cd05574    177 eketfvaepsarsnsfvgTEEyiapevikgdghGSAVDWWTLGILLYEMLYGTT-----PfKGSNRDETfsnilkkeLTF 251

                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1622828809  987 PE--CVSEEARSLIQQLLQFNPLERLGAGvAGVEDIKSHPFFTPVDWAeLMR 1036
Cdd:cd05574    252 PEspPVSSEAKDLIRKLLVKDPSKRLGSK-RGASEIKRHPFFRGVNWA-LIR 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 1622828809  889 LDKKLALT---SRFYIpegciqrwaAEMVVALDALHREGIVCRDLNPNNILLNDR------------------------- 940
Cdd:cd05599     92 LMKKDTLTeeeTRFYI---------AETVLAIESIHKLGYIHRDIKPDNLLLDARghiklsdfglctglkkshlaystvg 162

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622828809  941 -------EVGAITEETEACDWWSLGAVLFELLTG------KTLVECHPAGINTHTTLNMPECV--SEEARSLIQQLLQfN 1005
Cdd:cd05599    163 tpdyiapEVFLQKGYGKECDWWSLGVIMYEMLIGyppfcsDDPQETCRKIMNWRETLVFPPEVpiSPEAKDLIERLLC-D 241

                          170       180
                   ....*....|....*....|....*....
gi 1622828809 1006 PLERLGAGvaGVEDIKSHPFFTPVDWAEL 1034
Cdd:cd05599    242 AEHRLGAN--GVEEIKSHPFFKGVDWDHI 268

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 1622828809  885 IFEdldKKLAltsRFYIpegciqrwaAEMVVALDALHREGIVCRDLNPNNILLnDR------------------------ 940
Cdd:cd05598     97 IFE---EDLA---RFYI---------AELVCAIESVHKMGFIHRDIKPDNILI-DRdghikltdfglctgfrwthdskyy 160

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622828809  941 --------------EVGAITEETEACDWWSLGAVLFELLTGK------TLVECHPAGINTHTTLNMPECV--SEEARSLI 998
Cdd:cd05598    161 lahslvgtpnyiapEVLLRTGYTQLCDWWSVGVILYEMLVGQppflaqTPAETQLKVINWRTTLKIPHEAnlSPEAKDLI 240

                          170       180       190
                   ....*....|....*....|....*....|....*...
gi 1622828809  999 QQLLQfNPLERLGAGvaGVEDIKSHPFFTPVDWAELMR 1036
Cdd:cd05598    241 LRLCC-DAEDRLGRN--GADEIKAHPFFAGIDWEKLRK 275

N-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MSK2 and MSK1 play nonredundant roles in activating histone H3 kinases, which play pivotal roles in compaction of the chromatin fiber. MSK2 is the required H3 kinase in response to stress stimuli and activation of the p38 MAPK pathway. MSK2 also plays a role in the pathogenesis of psoriasis. MSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family, similar to 90 kDa ribosomal protein S6 kinases (RSKs). 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 MSK2 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 1622828809  875 ALEGDKEIHQIFEDLDKKLALT---SRFYIPEGCIQRWAAEMVVALDALHREGIVCRDLNPNNILLNDR------EVGA- 944
Cdd:cd05614     73 AFQTDAKLHLILDYVSGGELFThlyQRDHFSEDEVRFYSGEIILALEHLHKLGIVYRDIKLENILLDSEghvvltDFGLs 152

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622828809  945 ---ITEETE-------------------------ACDWWSLGAVLFELLTG-----------------KTLVECHPAgin 979
Cdd:cd05614    153 kefLTEEKErtysfcgtieymapeiirgksghgkAVDWWSLGILMFELLTGaspftlegekntqsevsRRILKCDPP--- 229

                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1622828809  980 thttlnMPECVSEEARSLIQQLLQFNPLERLGAGVAGVEDIKSHPFFTPVDWAEL 1034
Cdd:cd05614    230 ------FPSFIGPVARDLLQKLLCKDPKKRLGAGPQGAQEIKEHPFFKGLDWEAL 278

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 1622828809  897 SRFYipegciqrwAAEMVVALDALHREGIVCRDLNPNNILLnDRE---------------VGAITEET------------ 949
Cdd:cd05570     98 ARFY---------AAEICLALQFLHERGIIYRDLKLDNVLL-DAEghikiadfgmckegiWGGNTTSTfcgtpdyiapei 167

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622828809  950 -------EACDWWSLGAVLFELLTGKT---------LVEChpagINTHTTLnMPECVSEEARSLIQQLLQFNPLERLGAG 1013
Cdd:cd05570    168 lreqdygFSVDWWALGVLLYEMLAGQSpfegddedeLFEA----ILNDEVL-YPRWLSREAVSILKGLLTKDPARRLGCG 242

                          170       180
                   ....*....|....*....|...
gi 1622828809 1014 VAGVEDIKSHPFFTPVDWAELMR 1036
Cdd:cd05570    243 PKGEADIKAHPFFRNIDWDKLEK 265

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 1622828809  897 SRFYipegciqrwAAEMVVALDALHREGIVCRDLNPNNILLnDRE----------------VGAIT-------------- 946
Cdd:cd05571     97 TRFY---------GAEIVLALGYLHSQGIVYRDLKLENLLL-DKDghikitdfglckeeisYGATTktfcgtpeylapev 166

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622828809  947 -EETE---ACDWWSLGAVLFELLTGKTlvechPAGINTHTTL---------NMPECVSEEARSLIQQLLQFNPLERLGAG 1013
Cdd:cd05571    167 lEDNDygrAVDWWGLGVVMYEMMCGRL-----PFYNRDHEVLfelilmeevRFPSTLSPEAKSLLAGLLKKDPKKRLGGG 241

                          170       180
                   ....*....|....*....|...
gi 1622828809 1014 VAGVEDIKSHPFFTPVDWAELMR 1036
Cdd:cd05571    242 PRDAKEIMEHPFFASINWDDLYQ 264

Catalytic domain of the Serine/Threonine Kinase, Rho-associated coiled-coil containing protein kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. ROCK is also referred to as Rho-associated kinase or simply as Rho kinase. It contains an N-terminal extension, a catalytic kinase domain, and a long C-terminal extension, which contains a coiled-coil region encompassing a Rho-binding domain (RBD) and a pleckstrin homology (PH) domain. ROCK is auto-inhibited by the RBD and PH domain interacting with the catalytic domain. It is activated via interaction with Rho GTPases and is involved in many cellular functions including contraction, adhesion, migration, motility, proliferation, and apoptosis. The ROCK subfamily consists of two isoforms, ROCK1 and ROCK2, which may be functionally redundant in some systems, but exhibit different tissue distributions. Both isoforms are ubiquitously expressed in most tissues, but ROCK2 is more prominent in brain and skeletal muscle while ROCK1 is more pronounced in the liver, testes, and kidney. Studies in knockout mice result in different phenotypes, suggesting that the two isoforms do not compensate for each other during embryonic development. The ROCK 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 1622828809  882 IHQIFEDlDKKL-------------ALTSRFYIPEGCIQRWAAEMVVALDALHREGIVCRDLNPNNILLN---------- 938
Cdd:cd05596     91 LHYAFQD-DKYLymvmdympggdlvNLMSNYDVPEKWARFYTAEVVLALDAIHSMGFVHRDVKPDNMLLDasghlkladf 169

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622828809  939 --------------DREVGA---ITEET-----------EACDWWSLGAVLFELLTGKT------LVECHPAGINTHTTL 984
Cdd:cd05596    170 gtcmkmdkdglvrsDTAVGTpdyISPEVlksqggdgvygRECDWWSVGVFLYEMLVGDTpfyadsLVGTYGKIMNHKNSL 249

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....*....
gi 1622828809  985 NMPE--CVSEEARSLIQQLLQfNPLERLGAGvaGVEDIKSHPFFTPVDW 1031
Cdd:cd05596    250 QFPDdvEISKDAKSLICAFLT-DREVRLGRN--GIEEIKAHPFFKNDQW 295

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 1622828809  909 WAAEMVVALDALHREGIVCRDLNPNNILLNDREVGAITEETEAC---------------------------------DWW 955
Cdd:cd05577    100 YAAEIICGLEHLHNRFIVYRDLKPENILLDDHGHVRISDLGLAVefkggkkikgrvgthgymapevlqkevaydfsvDWF 179

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622828809  956 SLGAVLFELLTGKTLVECHPAGINTHT----TLNM----PECVSEEARSLIQQLLQFNPLERLGAGVAGVEDIKSHPFFT 1027
Cdd:cd05577    180 ALGCMLYEMIAGRSPFRQRKEKVDKEElkrrTLEMaveyPDSFSPEARSLCEGLLQKDPERRLGCRGGSADEVKEHPFFR 259

                   ....*..
gi 1622828809 1028 PVDWAEL 1034
Cdd:cd05577    260 SLNWQRL 266

Catalytic domain of the Serine/Threonine Kinase, Phosphoinositide-dependent kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PDK1 carries an N-terminal catalytic domain and a C-terminal pleckstrin homology (PH) domain that binds phosphoinositides. It phosphorylates the activation loop of AGC kinases that are regulated by PI3K such as PKB, SGK, and PKC, among others, and is crucial for their activation. Thus, it contributes in regulating many processes including metabolism, growth, proliferation, and survival. PDK1 also has the ability to autophosphorylate and is constitutively active in mammalian cells. It is essential for normal embryo development and is important in regulating cell volume. The PDK1 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 1622828809  905 CIQRWAAEMVVALDALHREGIVCRDLNPNNILLND---------------------REVGAITEETE------------- 950
Cdd:cd05581    102 CTRFYTAEIVLALEYLHSKGIIHRDLKPENILLDEdmhikitdfgtakvlgpdsspESTKGDADSQIaynqaraasfvgt 181

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622828809  951 ----------------ACDWWSLGAVLFELLTGKTLVEchpaGINTHTTL--------NMPECVSEEARSLIQQLLQFNP 1006
Cdd:cd05581    182 aeyvspellnekpagkSSDLWALGCIIYQMLTGKPPFR----GSNEYLTFqkivkleyEFPENFPPDAKDLIQKLLVLDP 257