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 1622828813  11 LARFYTVTEPQRHPRGYTVYKVTARVVSRRNPEDVQEIIVWKRYSDFKKLHKELWQIHKNLFRHSELFPPFAKGIVFGRF 90
Cdd:cd07287     1 LARFYTVTDPRRHPKGYTVYKVTARIVSRKNPEDVQEIVVWKRYSDFKKLHKDLWQIHKNLCRQSELFPPFAKAKVFGRF 80

                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 1622828813  91 DETVIEERRQCAEDLLQFSANIPALYNSKQLEDFFKGG 128
Cdd:cd07287    81 DESVIEERRQCAEDLLQFSANIPALYNSSQLEDFFKGG 118

Protein Kinases, catalytic domain; The protein kinase superfamily is mainly composed of the catalytic domains of serine/threonine-specific and tyrosine-specific protein kinases. It also includes RIO kinases, which are atypical serine protein kinases, aminoglycoside phosphotransferases, and choline kinases. These proteins catalyze the transfer of the gamma-phosphoryl group from ATP to hydroxyl groups in specific substrates such as serine, threonine, or tyrosine residues of proteins.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622828813 335 EELKAFRVLGVIDKVLLVMDTRTEQTFILKGLRKSSEYSRNRKTIIPRCVPNMVCLHKYIISEESVFLVLQHAEGGKLWS 414
Cdd:cd05576     1 EELKAFRVLGVIDKVLLVMDTRTQETFILKGLRKSSEYSRERKTIIPRCVPNMVCLRKYIISEESVFLVLQHAEGGKLWS 80

                  ....*..
gi 1622828813 415 YISKFLN 421
Cdd:cd05576    81 YLSKFLN 87

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 1622828813  11 LARFYTVTEPQRHPRGYTVYKVTARVVSRRNPEDVQEIIVWKRYSDFKKLHKELWQIHKNLFRHSELFPPFAKGIVFGRF 90
Cdd:cd07287     1 LARFYTVTDPRRHPKGYTVYKVTARIVSRKNPEDVQEIVVWKRYSDFKKLHKDLWQIHKNLCRQSELFPPFAKAKVFGRF 80

                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 1622828813  91 DETVIEERRQCAEDLLQFSANIPALYNSKQLEDFFKGG 128
Cdd:cd07287    81 DESVIEERRQCAEDLLQFSANIPALYNSSQLEDFFKGG 118

Catalytic domain of the Serine/Threonine Kinase, RPK118, and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. RPK118 contains an N-terminal Phox homology (PX) domain, a Microtubule Interacting and Trafficking (MIT) domain, and a kinase domain containing a long uncharacterized insert. Also included in the family is human RPK60 (or ribosomal protein S6 kinase-like 1), which also contains MIT and kinase domains but lacks a PX 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. RPK118 also binds the antioxidant peroxiredoxin-3. RPK118 may be involved in the transport of PRDX3 from the cytoplasm to its site of function in the mitochondria. The RPK118-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 1622828813 335 EELKAFRVLGVIDKVLLVMDTRTEQTFILKGLRKSSEYSRNRKTIIPRCVPNMVCLHKYIISEESVFLVLQHAEGGKLWS 414
Cdd:cd05576     1 EELKAFRVLGVIDKVLLVMDTRTQETFILKGLRKSSEYSRERKTIIPRCVPNMVCLRKYIISEESVFLVLQHAEGGKLWS 80

                  ....*..
gi 1622828813 415 YISKFLN 421
Cdd:cd05576    81 YLSKFLN 87

Microtubule Interacting and Trafficking molecule domain;

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1622828813  236 KRDYLEKAGELIKLALKKEEEDDYEAASDFYRKGVDLLLEGVQGESSPTRREAVKRRTAEYLMRAESI 303
Cdd:smart00745   1 TRDYLSKAKELISKALKADEAGNYEEALELYKKAIEYLLEGIKVESDSKRREALKAKAAEYLDRAEEI 68

PX domain; PX domains bind to phosphoinositides.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622828813  40 RNPEDVQEIIVWKRYSDFKKLHKELWQIHKNLFrhselFPPFAKGIVFGRFDETVIEERRQCAEDLLQFSANIPALYNSK 119
Cdd:pfam00787   1 LPTFSLEEWSVRRRYSDFVELHKKLLRKFPSVI-----IPPLPPKRWLGRYNEEFIEKRRKGLEQYLQRLLQHPELRNSE 75

                  ....*.
gi 1622828813 120 QLEDFF 125
Cdd:pfam00787  76 VLLEFL 81

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622828813  875 ALEGDKEIHQIFE-----DLDKKLalTSRFYIPEGCIQRWAAEMVVALDALHREGIVCRDLNPNNILLNDRGHIQLTYF- 948
Cdd:smart00220  65 VFEDEDKLYLVMEyceggDLFDLL--KKRGRLSEDEARFYLRQILSALEYLHSKGIVHRDLKPENILLDEDGHVKLADFg 142

                           90       100       110
                   ....*....|....*....|....*....|
gi 1622828813  949 -SRWSEVEDSCDSDAIERMYCAP-VISCSG 976
Cdd:smart00220 143 lARQLDPGEKLTTFVGTPEYMAPeVLLGKG 172

protein kinase A catalytic subunit; Provisional

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 1622828813 909 WAAEMVVALDALHREGIVCRDLNPNNILLNDRGHIQLTYFSRWSEVED 956
Cdd:PTZ00263  123 YHAELVLAFEYLHSKDIIYRDLKPENLLLDNKGHVKVTDFGFAKKVPD 170

Stk1 family PASTA domain-containing Ser/Thr kinase;

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|.
gi 1622828813 908 RWAAEMVVALDALHREGIVCRDLNPNNILLNDRGHIQLTYF 948
Cdd:NF033483  111 EIMIQILSALEHAHRNGIVHRDIKPQNILITKDGRVKVTDF 151

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 1622828813  11 LARFYTVTEPQRHPRGYTVYKVTARVVSRRNPEDVQEIIVWKRYSDFKKLHKELWQIHKNLFRHSELFPPFAKGIVFGRF 90
Cdd:cd07287     1 LARFYTVTDPRRHPKGYTVYKVTARIVSRKNPEDVQEIVVWKRYSDFKKLHKDLWQIHKNLCRQSELFPPFAKAKVFGRF 80

                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 1622828813  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 1622828813  13 RFYTVTEPQRHPRGYTVYKVTARVVSRRNPEDVQEIIVWKRYSDFKKLHKELWQIHKNLFRHSELFPPFAKGIVFGRFDE 92
Cdd:cd07288     3 RFYSVTDPRTHPKGYTEYKVTAQFISKKQPEDVKEVVVWKRYSDLKKLHGELAYTHRNLFRRQEEFPPFPRAQVFGRFEA 82

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 1622828813  93 TVIEERRQCAEDLLQFSANIPALYNSKQLEDFFKGG 128
Cdd:cd07288    83 AVIEERRNAAEAMLLFTVNIPALYNSPQLKEFFRDG 118

Catalytic domain of the Serine/Threonine Kinase, RPK118, and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. RPK118 contains an N-terminal Phox homology (PX) domain, a Microtubule Interacting and Trafficking (MIT) domain, and a kinase domain containing a long uncharacterized insert. Also included in the family is human RPK60 (or ribosomal protein S6 kinase-like 1), which also contains MIT and kinase domains but lacks a PX 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. RPK118 also binds the antioxidant peroxiredoxin-3. RPK118 may be involved in the transport of PRDX3 from the cytoplasm to its site of function in the mitochondria. The RPK118-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 1622828813 335 EELKAFRVLGVIDKVLLVMDTRTEQTFILKGLRKSSEYSRNRKTIIPRCVPNMVCLHKYIISEESVFLVLQHAEGGKLWS 414
Cdd:cd05576     1 EELKAFRVLGVIDKVLLVMDTRTQETFILKGLRKSSEYSRERKTIIPRCVPNMVCLRKYIISEESVFLVLQHAEGGKLWS 80

                  ....*..
gi 1622828813 415 YISKFLN 421
Cdd:cd05576    81 YLSKFLN 87

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1622828813 895 LTSRFYIPEGCIQRWAAEMVVALDALHREGIVCRDLNPNNILLNDRGHIQLTYFSRWSEVE---DSCDSDAIERMYCAP 970
Cdd:cd05123    84 LSKEGRFPEERARFYAAEIVLALEYLHSLGIIYRDLKPENILLDSDGHIKLTDFGLAKELSsdgDRTYTFCGTPEYLAP 162

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 1622828813 344 GVIDKVLLVMDTRTEQTFILKGLRKSS-------EYSRNRKTIIPRC-VPNMVCLHKYIISEESVFLVLQHAEGGKLWSY 415
Cdd:cd05123     4 GSFGKVLLVRKKDTGKLYAMKVLRKKEiikrkevEHTLNERNILERVnHPFIVKLHYAFQTEEKLYLVLDYVPGGELFSH 83

                          90
                  ....*....|....*....
gi 1622828813 416 ISKflnrspEESFDIKEVK 434
Cdd:cd05123    84 LSK------EGRFPEERAR 96

The Phox Homology domain, a phosphoinositide binding module; The PX domain is a phosphoinositide (PI) binding module involved in targeting proteins to membranes. Proteins containing PX domains interact with PIs and have been implicated in highly diverse functions such as cell signaling, vesicular trafficking, protein sorting, lipid modification, cell polarity and division, activation of T and B cells, and cell survival. Many members of this superfamily bind phosphatidylinositol-3-phosphate (PI3P) but in some cases, other PIs such as PI4P or PI(3,4)P2, among others, are the preferred substrates. In addition to protein-lipid interaction, the PX domain may also be involved in protein-protein interaction, as in the cases of p40phox, p47phox, and some sorting nexins (SNXs). The PX domain is conserved from yeast to humans and is found in more than 100 proteins. The majority of PX domain-containing proteins are SNXs, which play important roles in endosomal sorting.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622828813  26 GYTVYKVTARvvsrrnPEDVQEIIVWKRYSDFKKLHKELwqihKNLFRHSELfPPFAKGIVFGRFDETVIEERRQCAEDL 105
Cdd:cd06093    16 KYVVYIIEVT------TQGGEEWTVYRRYSDFEELHEKL----KKKFPGVIL-PPLPPKKLFGNLDPEFIEERRKQLEQY 84

                          90       100
                  ....*....|....*....|.
gi 1622828813 106 LQFSANIPALYNSKQLEDFFK 126
Cdd:cd06093    85 LQSLLNHPELRNSEELKEFLE 105

PX domain; PX domains bind to phosphoinositides.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622828813  40 RNPEDVQEIIVWKRYSDFKKLHKELWQIHKNLFrhselFPPFAKGIVFGRFDETVIEERRQCAEDLLQFSANIPALYNSK 119
Cdd:pfam00787   1 LPTFSLEEWSVRRRYSDFVELHKKLLRKFPSVI-----IPPLPPKRWLGRYNEEFIEKRRKGLEQYLQRLLQHPELRNSE 75

                  ....*.
gi 1622828813 120 QLEDFF 125
Cdd:pfam00787  76 VLLEFL 81

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
                  ....*....|....*....|....*....|....*....|....
gi 1622828813 905 CIQRWAAEMVVALDALHREGIVCRDLNPNNILLNDRGHIQLTYF 948
Cdd:cd05581   102 CTRFYTAEIVLALEYLHSKGIIHRDLKPENILLDEDMHIKITDF 145

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 1622828813   17 VTEPQRHPRG---YTVYKVTarvvsRRNPEdvQEIIVWKRYSDFKKLHKELwqihKNLFRHSELFPPFAKGIV--FGRFD 91
Cdd:smart00312   1 VVEPEKIGDGkhyYYVIEIE-----TKTGL--EEWTVSRRYSDFLELHSKL----KKHFPRSILPPLPGKKLFgrLNNFS 69

                           90       100       110
                   ....*....|....*....|....*....|....*
gi 1622828813   92 ETVIEERRQCAEDLLQFSANIPALYN-SKQLEDFF 125
Cdd:smart00312  70 EEFIEKRRRGLEKYLQSLLNHPELINhSEVVLEFL 104

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622828813  875 ALEGDKEIHQIFE-----DLDKKLalTSRFYIPEGCIQRWAAEMVVALDALHREGIVCRDLNPNNILLNDRGHIQLTYF- 948
Cdd:smart00220  65 VFEDEDKLYLVMEyceggDLFDLL--KKRGRLSEDEARFYLRQILSALEYLHSKGIVHRDLKPENILLDEDGHVKLADFg 142

                           90       100       110
                   ....*....|....*....|....*....|
gi 1622828813  949 -SRWSEVEDSCDSDAIERMYCAP-VISCSG 976
Cdd:smart00220 143 lARQLDPGEKLTTFVGTPEYMAPeVLLGKG 172

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1622828813 886 FEDLDKKLAltsRFYIpegciqrwaAEMVVALDALHREGIVCRDLNPNNILLNDRGHIQLTYF 948
Cdd:cd05573    95 YDVFPEETA---RFYI---------AELVLALDSLHKLGFIHRDIKPDNILLDADGHIKLADF 145

The phosphoinositide binding Phox Homology domain of Sorting Nexins 1 and 2; 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. This subfamily consists of SNX1, SNX2, and similar proteins. They harbor a Bin/Amphiphysin/Rvs (BAR) domain, which detects membrane curvature, C-terminal to the PX domain. Both domains have been shown to determine the specific membrane-targeting of SNX1. SNX1 and SNX2 are components of the retromer complex, a membrane coat multimeric complex required for endosomal retrieval of lysosomal hydrolase receptors to the Golgi. The retromer consists of a cargo-recognition subcomplex and a subcomplex formed by a dimer of sorting nexins (SNX1 and/or SNX2), which ensures effcient cargo sorting by facilitating proper membrane localization of the cargo-recognition subcomplex.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622828813  16 TVTEPQRHPRG---YTVYKVTARVvsrrNPEDVQ--EIIVWKRYSDFKKLHKELWQIHKNLFrhseLFPPFAKGIVfGRF 90
Cdd:cd06859     4 SVTDPVKVGDGmsaYVVYRVTTKT----NLPDFKksEFSVLRRYSDFLWLYERLVEKYPGRI----VPPPPEKQAV-GRF 74

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 1622828813  91 DETV--IEERRQCAEDLLQFSANIPALYNSKQLEDF 124
Cdd:cd06859    75 KVKFefIEKRRAALERFLRRIAAHPVLRKDPDFRLF 110

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
                  ....*....|....*....|....*....|....*....|....*....
gi 1622828813 900 YIPEGCIQRWAAEMVVALDALHREGIVCRDLNPNNILLNDRGHIQLTYF 948
Cdd:cd05611    93 GLPEDWAKQYIAEVVLGVEDLHQRGIIHRDIKPENLLIDQTGHLKLTDF 141

Catalytic domain of the Serine/Threonine Kinase, Microtubule-associated serine/threonine-like kinase (also called greatwall kinase); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The MASTL kinases in this group carry only a catalytic domain, which contains a long insertion relative to MAST kinases. MASTL, also called greatwall kinase (Gwl), is involved in the regulation of mitotic entry, which is controlled by the coordinated activities of protein kinases and opposing protein phosphatases (PPs). The cyclin B/CDK1 complex induces entry into M-phase while PP2A-B55 shows anti-mitotic activity. MASTL/Gwl is activated downstream of cyclin B/CDK1 and indirectly inhibits PP2A-B55 by phosphorylating the small protein alpha-endosulfine (Ensa) or the cAMP-regulated phosphoprotein 19 (Arpp19), resulting in M-phase progression. Gwl kinase may also play roles in mRNA stabilization and DNA checkpoint recovery. The human MASTL gene has also been named FLJ14813; a missense mutation in FLJ14813 is associated with autosomal dominant thrombocytopenia. The MASTL 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
                  ....*....|....*....|....*....|....*....|....*....
gi 1622828813 900 YIPEGCIQRWAAEMVVALDALHREGIVCRDLNPNNILLNDRGHIQLTYF 948
Cdd:cd05610   100 YFDEEMAVKYISEVALALDYLHRHGIIHRDLKPDNMLISNEGHIKLTDF 148

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 1622828813 896 TSRFYIpegciqrwaAEMVVALDALHREGIVCRDLNPNNILLNDRGHIQLTYFSRWSEvedSCDSDAIERMYC------A 969
Cdd:cd05584   101 TACFYL---------AEITLALGHLHSLGIIYRDLKPENILLDAQGHVKLTDFGLCKE---SIHDGTVTHTFCgtieymA 168

                  ...
gi 1622828813 970 PVI 972
Cdd:cd05584   169 PEI 171

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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622828813 882 IHQIFEDlDKKL-------------ALTSRFYIPEGCIQRWAAEMVVALDALHREGIVCRDLNPNNILLNDRGHIQLTYF 948
Cdd:cd05596    91 LHYAFQD-DKYLymvmdympggdlvNLMSNYDVPEKWARFYTAEVVLALDAIHSMGFVHRDVKPDNMLLDASGHLKLADF 169

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
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1622828813 897 SRFYipegciqrwAAEMVVALDALHREGIVCRDLNPNNILLNDRGHIQLTYF 948
Cdd:cd05575    98 ARFY---------AAEIASALGYLHSLNIIYRDLKPENILLDSQGHVVLTDF 140

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
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1622828813 898 RFyiPEGCIQRWAAEMVVALDALHREGIVCRDLNPNNILLNDRGHIQLTYF 948
Cdd:cd05580    97 RF--PNDVAKFYAAEVVLALEYLHSLDIVYRDLKPENLLLDSDGHIKITDF 145

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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1622828813 889 LDKKLALT---SRFYIpegciqrwaAEMVVALDALHREGIVCRDLNPNNILLNDRGHIQLTYF 948
Cdd:cd05599    92 LMKKDTLTeeeTRFYI---------AETVLAIESIHKLGYIHRDIKPDNLLLDARGHIKLSDF 145

Catalytic domain of STE family Protein Kinases; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. This family is composed of STKs, and some dual-specificity PKs that phosphorylate both threonine and tyrosine residues of target proteins. Most members are kinases involved in mitogen-activated protein kinase (MAPK) signaling cascades, acting as MAPK kinases (MAPKKs), MAPKK kinases (MAPKKKs), or MAPKKK kinases (MAP4Ks). The MAPK signaling pathways are important mediators of cellular responses to extracellular signals. The pathways involve a triple kinase core cascade comprising of the MAPK, which is phosphorylated and activated by a MAPKK, which itself is phosphorylated and activated by a MAPKKK. Each MAPK cascade is activated either by a small GTP-binding protein or by an adaptor protein, which transmits the signal either directly to a MAPKKK to start the triple kinase core cascade or indirectly through a mediator kinase, a MAP4K. Other STE family members include p21-activated kinases (PAKs) and class III myosins, among others. PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. Class III myosins are motor proteins containing an N-terminal kinase catalytic domain and a C-terminal actin-binding domain, which can phosphorylate several cytoskeletal proteins, conventional myosin regulatory light chains, as well as autophosphorylate the C-terminal motor domain. They play an important role in maintaining the structural integrity of photoreceptor cell microvilli. The STE 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
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1622828813 901 IPEGCIQRWAAEMVVALDALHREGIVCRDLNPNNILLNDRGHIQLTYFSRWSEVEDSCDSD 961
Cdd:cd05122    95 LTEQQIAYVCKEVLKGLEYLHSHGIIHRDIKAANILLTSDGEVKLIDFGLSAQLSDGKTRN 155

Catalytic domain of Fungal Sid2p-like Protein Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This group contains fungal kinases including Schizosaccharomyces pombe Sid2p and Saccharomyces cerevisiae Dbf2p. Group members show similarity to NDR kinases in that they contain an N-terminal regulatory (NTR) domain and an insert within the catalytic domain that contains an auto-inhibitory sequence. Sid2p plays a crucial role in the septum initiation network (SIN) and in the initiation of cytokinesis. Dbf2p is important in regulating the mitotic exit network (MEN) and in cytokinesis. The Sid2p-like group 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.

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                  ....*....|....*....|....*....|....*....|....*....|.
gi 1622828813 898 RFYIpegciqrwaAEMVVALDALHREGIVCRDLNPNNILLNDRGHIQLTYF 948
Cdd:cd05600   114 RFYI---------AEMFAAISSLHQLGYIHRDLKPENFLIDSSGHIKLTDF 155

Catalytic domain of the Protein Serine/Threonine Kinase, Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase Kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MEKK4 is a MAPK kinase kinase that phosphorylates and activates the c-Jun N-terminal kinase (JNK) and p38 MAPK signaling pathways by directly activating their respective MAPKKs, MKK4/MKK7 and MKK3/MKK6. JNK and p38 are collectively known as stress-activated MAPKs, as they are activated in response to a variety of environmental stresses and pro-inflammatory cytokines. MEKK4 also plays roles in the re-polarization of the actin cytoskeleton in response to osmotic stress, in the proper closure of the neural tube, in cardiovascular development, and in immune responses. The MEKK4 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.

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                  ....*....|....*....|....*....|....*....|....*..
gi 1622828813 902 PEGCIQRWAAEMVVALDALHREGIVCRDLNPNNILLNDRGHIQLTYF 948
Cdd:cd06626    97 DEAVIRVYTLQLLEGLAYLHENGIVHRDIKPANIFLDSNGLIKLGDF 143

MIT: domain contained within Microtubule Interacting and Trafficking molecules. This sub-family of MIT domains is found in intracellular protein transport proteins of the AAA-ATPase family. The molecular function of the MIT domain is unclear.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1622828813 238 DYLEKAGELIKLALKKEEEDDYEAASDFYRKGVDLLLEGVQGESSPTRREAVKRRTAEYLMRAESI 303
Cdd:cd02678     1 DFLQKAIELVKKAIEEDNAGNYEEALRLYQHALEYFMHALKYEKNPKSKESIRAKCTEYLDRAEKL 66

Catalytic domain of the Serine/Threonine Kinase, cGMP-dependent protein kinase (cGK or PKG); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Mammals have two cGK isoforms from different genes, cGKI and cGKII. cGKI exists as two splice variants, cGKI-alpha and cGKI-beta. cGK consists of an N-terminal regulatory domain containing a dimerization and an autoinhibitory pseudosubstrate region, two cGMP-binding domains, and a C-terminal catalytic domain. Binding of cGMP to both binding sites releases the inhibition of the catalytic center by the pseudosubstrate region, allowing autophosphorylation and activation of the kinase. cGKI is a soluble protein expressed in all smooth muscles, platelets, cerebellum, and kidney. It is also expressed at lower concentrations in other tissues. cGKII is a membrane-bound protein that is most abundantly expressed in the intestine. It is also present in the brain nuclei, adrenal cortex, kidney, lung, and prostate. cGKI is involved in the regulation of smooth muscle tone, smooth cell proliferation, and platelet activation. cGKII plays a role in the regulation of secretion, such as renin secretion by the kidney and aldosterone secretion by the adrenal. It also regulates bone growth and the circadian rhythm. The cGK 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.

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                  ....*....|....*....|....*....|....*....|....*....|...
gi 1622828813 896 TSRFYIpegciqrwaAEMVVALDALHREGIVCRDLNPNNILLNDRGHIQLTYF 948
Cdd:cd05572    94 TARFYT---------ACVVLAFEYLHSRGIIYRDLKPENLLLDSNGYVKLVDF 137

Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase 6; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. GRK6 is widely expressed in many tissues and is expressed as multiple splice variants with different domain architectures. It is post-translationally palmitoylated and localized in the membrane. GRK6 plays important roles in the regulation of dopamine, M3 muscarinic, opioid, and chemokine receptor signaling. It also plays maladaptive roles in addiction and Parkinson's disease. GRK6-deficient mice exhibit altered dopamine receptor regulation, decreased lymphocyte chemotaxis, and increased acute inflammation and neutrophil chemotaxis. 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 GRK6 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
                  ....*....|....*....|....*....|....*....|....*
gi 1622828813 902 PEGCIQRWAAEMVVALDALHREGIVCRDLNPNNILLNDRGHIQLT 946
Cdd:cd05630   100 PEARAVFYAAEICCGLEDLHRERIVYRDLKPENILLDDHGHIRIS 144

Catalytic domain of Fungal Nuclear Dbf2-Related kinase-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This group is composed of fungal NDR-like proteins including Saccharomyces cerevisiae CBK1 (or CBK1p), Schizosaccharomyces pombe Orb6 (or Orb6p), Ustilago maydis Ukc1 (or Ukc1p), and Neurospora crassa Cot1. Like NDR kinase, group members contain an N-terminal regulatory (NTR) domain and an insert within the catalytic domain that contains an auto-inhibitory sequence. CBK1 is an essential component in the RAM (regulation of Ace2p activity and cellular morphogenesis) network. CBK1 and Orb6 play similar roles in coordinating cell morphology with cell cycle progression. Ukc1 is involved in morphogenesis, pathogenicity, and pigment formation. Cot1 plays a role in polar tip extension.The fungal NDR 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
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1622828813 897 SRFYIpegciqrwaAEMVVALDALHREGIVCRDLNPNNILLNDRGHIQLTYF 948
Cdd:cd05629   103 TRFYM---------AECVLAIEAVHKLGFIHRDIKPDNILIDRGGHIKLSDF 145

Catalytic domain of the Serine/Threonine Kinase, Rho-associated coiled-coil containing protein kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. ROCK1 is preferentially expressed in the liver, lung, spleen, testes, and kidney. It mediates signaling from Rho to the actin cytoskeleton. It is implicated in the development of cardiac fibrosis, cardiomyocyte apoptosis, and hyperglycemia. Mice deficient with ROCK1 display eyelids open at birth (EOB) and omphalocele phenotypes due to the disorganization of actin filaments in the eyelids and the umbilical ring. ROCK contains an N-terminal extension, a catalytic kinase domain, and a 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, and is activated via interaction with Rho GTPases. The ROCK1 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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1622828813 875 ALEGDKEIHQIFE-----DLdkkLALTSRFYIPEGCIQRWAAEMVVALDALHREGIVCRDLNPNNILLNDRGHIQLTYF 948
Cdd:cd05622   141 AFQDDRYLYMVMEympggDL---VNLMSNYDVPEKWARFYTAEVVLALDAIHSMGFIHRDVKPDNMLLDKSGHLKLADF 216

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
                  ....*....|....*....|....*....|....*...
gi 1622828813 909 WAAEMVVALDALHREGIVCRDLNPNNILLNDRGHIQLT 946
Cdd:cd05632   109 YAAEILCGLEDLHRENTVYRDLKPENILLDDYGHIRIS 146

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.

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                  ....*....|....*....|....*....|....*....|....*....|..
gi 1622828813 897 SRFYipegciqrwAAEMVVALDALHREGIVCRDLNPNNILLNDRGHIQLTYF 948
Cdd:cd05570    98 ARFY---------AAEICLALQFLHERGIIYRDLKLDNVLLDAEGHIKIADF 140

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
                  ....*....|....*....|....*....|....*...
gi 1622828813 909 WAAEMVVALDALHREGIVCRDLNPNNILLNDRGHIQLT 946
Cdd:cd05577   100 YAAEIICGLEHLHNRFIVYRDLKPENILLDDHGHVRIS 137

protein kinase A catalytic subunit; Provisional

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 1622828813 909 WAAEMVVALDALHREGIVCRDLNPNNILLNDRGHIQLTYFSRWSEVED 956
Cdd:PTZ00263  123 YHAELVLAFEYLHSKDIIYRDLKPENLLLDNKGHVKVTDFGFAKKVPD 170