C2 domain of the Regulator Of G-Protein Signaling (RGS) family; This CD contains members of the regulator of G-protein signaling (RGS) family. RGS is a GTPase activating protein which inhibits G-protein mediated signal transduction. The protein is largely cytosolic, but G-protein activation leads to translocation of this protein to the plasma membrane. A nuclear form of this protein has also been described, but its sequence has not been identified. There are multiple alternatively spliced transcript variants in this family with some members having additional domains (ex. PDZ and RGS) downstream of the C2 domain. The C2 domain was first identified in PKC. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2247794532  139 GQLRLSIDAQDRVLLLHIIEGKGLISKQPGTCDPYVKISLIPEDSRLRHQKTQTVPDCRDPAFHEHFFFPVQEEDDQKRL 218
Cdd:cd08685      1 GQLKLSIEGQNRKLTLHVLEAKGLRSTNSGTCNSYVKISLSPDKEVRFRQKTSTVPDSANPLFHETFSFDVNERDYQKRL 80

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|
gi 2247794532  219 LVTVWNRASQSRQSGLIGCMSFGVKSLLtPDKEISGWYYL 258
Cdd:cd08685     81 LVTVWNKLSKSRDSGLLGCMSFGVKSIV-NQKEISGWYYL 119

large tegument protein UL36; Provisional

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2247794532  690 EMALEEGKGPGAEDSPPSKEPSPGQELPPGQDLP-PNKDSPSGQEPAPSQEPLSSKDSATSE--GSPPGPDAP---PSKD 763
Cdd:PHA03247  2542 ELASDDAGDPPPPLPPAAPPAAPDRSVPPPRPAPrPSEPAVTSRARRPDAPPQSARPRAPVDdrGDPRGPAPPsplPPDT 2621

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2247794532  764 VPPcqePPPAQDLSPCQDLPAGQEPLPHQDPLLTKDLPAIQE-SPTR-----DLPPCQDLPPSQVSLPAkalTEDTMSSg 837
Cdd:PHA03247  2622 HAP---DPPPPSPSPAANEPDPHPPPTVPPPERPRDDPAPGRvSRPRrarrlGRAAQASSPPQRPRRRA---ARPTVGS- 2694

                          170
                   ....*....|....*
gi 2247794532  838 dlLAATGDPPAAPRP 852
Cdd:PHA03247  2695 --LTSLADPPPPPPT 2707

C2 domain of the Regulator Of G-Protein Signaling (RGS) family; This CD contains members of the regulator of G-protein signaling (RGS) family. RGS is a GTPase activating protein which inhibits G-protein mediated signal transduction. The protein is largely cytosolic, but G-protein activation leads to translocation of this protein to the plasma membrane. A nuclear form of this protein has also been described, but its sequence has not been identified. There are multiple alternatively spliced transcript variants in this family with some members having additional domains (ex. PDZ and RGS) downstream of the C2 domain. The C2 domain was first identified in PKC. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2247794532  139 GQLRLSIDAQDRVLLLHIIEGKGLISKQPGTCDPYVKISLIPEDSRLRHQKTQTVPDCRDPAFHEHFFFPVQEEDDQKRL 218
Cdd:cd08685      1 GQLKLSIEGQNRKLTLHVLEAKGLRSTNSGTCNSYVKISLSPDKEVRFRQKTSTVPDSANPLFHETFSFDVNERDYQKRL 80

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|
gi 2247794532  219 LVTVWNRASQSRQSGLIGCMSFGVKSLLtPDKEISGWYYL 258
Cdd:cd08685     81 LVTVWNKLSKSRDSGLLGCMSFGVKSIV-NQKEISGWYYL 119

Regulator of G protein signalling domain; RGS family members are GTPase-activating proteins for heterotrimeric G-protein alpha-subunits.

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2247794532  1073 SLEKLLVHKYGLAVFQAFLRTEFSEENLEFWLACEDFKKVKSQSKMASKAKKIFAEYIAIQACKEVNLDSYTREHTKDNL 1152
Cdd:smart00315    1 SLESLLSDPIGRLLFREFLESEFSEENLEFWLAVEEFKKAEDDEERIAKAREIYDKFLSPNAPKEVNLDSDLREKIEENL 80

                            90       100       110
                    ....*....|....*....|....*....|....*...
gi 2247794532  1153 QS--VTRGCFDLAQKRIFGLMEKDSYPRFLRSDLYLDL 1188
Cdd:smart00315   81 ESeePPPDLFDEAQREVYELLEKDSFPRFLESDYYLRF 118

C2 domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2247794532  151 VLLLHIIEGKGLISKQP-GTCDPYVKISLIPEDSRlrhQKTQTVPDCRDPAFHEHFFFPVQEEDDQKrLLVTVWNRASQS 229
Cdd:pfam00168    2 RLTVTVIEAKNLPPKDGnGTSDPYVKVYLLDGKQK---KKTKVVKNTLNPVWNETFTFSVPDPENAV-LEIEVYDYDRFG 77

                           90       100
                   ....*....|....*....|....*....
gi 2247794532  230 RqSGLIGCMSFGVKSLLtPDKEISGWYYL 258
Cdd:pfam00168   78 R-DDFIGEVRIPLSELD-SGEGLDGWYPL 104

Domain present in PSD-95, Dlg, and ZO-1/2; Also called DHR (Dlg homologous region) or GLGF (relatively well conserved tetrapeptide in these domains). Some PDZs have been shown to bind C-terminal polypeptides; others appear to bind internal (non-C-terminal) polypeptides. Different PDZs possess different binding specificities.

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2247794532   299 KITIPRGKDGFGFTIC----CDSPVRVQAVDSGGPAERAGLQQLDTVLQLNERPVEHWKCVELAHEIRSCPSEIILLVWR 374
Cdd:smart00228    4 LVELEKGGGGLGFSLVggkdEGGGVVVSSVVPGSPAAKAGLRVGDVILEVNGTSVEGLTHLEAVDLLKKAGGKVTLTVLR 83

PDZ domain; PDZ domains are found in diverse signaling proteins.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2247794532  299 KITIPRGKDG-FGFTI-----CCDSPVRVQAVDSGGPAERAGLQQLDTVLQLNERPVEHWKCVELAHEIRSCPSEIILLV 372
Cdd:pfam00595    1 QVTLEKDGRGgLGFSLkggsdQGDPGIFVSEVLPGGAAEAGGLKVGDRILSINGQDVENMTHEEAVLALKGSGGKVTLTI 80

                   .
gi 2247794532  373 W 373
Cdd:pfam00595   81 L 81

Periplasmic serine protease, S1-C subfamily, contain C-terminal PDZ domain [Posttranslational modification, protein turnover, chaperones];

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 2247794532  319 VRVQAVDSGGPAERAGLQQLDTVLQLNERPVEHWKcvELAHEIRSCP--SEIILLVWR 374
Cdd:COG0265    203 VLVARVEPGSPAAKAGLRPGDVILAVDGKPVTSAR--DLQRLLASLKpgDTVTLTVLR 258

C2 domain of the Regulator Of G-Protein Signaling (RGS) family; This CD contains members of the regulator of G-protein signaling (RGS) family. RGS is a GTPase activating protein which inhibits G-protein mediated signal transduction. The protein is largely cytosolic, but G-protein activation leads to translocation of this protein to the plasma membrane. A nuclear form of this protein has also been described, but its sequence has not been identified. There are multiple alternatively spliced transcript variants in this family with some members having additional domains (ex. PDZ and RGS) downstream of the C2 domain. The C2 domain was first identified in PKC. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2247794532  139 GQLRLSIDAQDRVLLLHIIEGKGLISKQPGTCDPYVKISLIPEDSRLRHQKTQTVPDCRDPAFHEHFFFPVQEEDDQKRL 218
Cdd:cd08685      1 GQLKLSIEGQNRKLTLHVLEAKGLRSTNSGTCNSYVKISLSPDKEVRFRQKTSTVPDSANPLFHETFSFDVNERDYQKRL 80

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|
gi 2247794532  219 LVTVWNRASQSRQSGLIGCMSFGVKSLLtPDKEISGWYYL 258
Cdd:cd08685     81 LVTVWNKLSKSRDSGLLGCMSFGVKSIV-NQKEISGWYYL 119

Regulator of G protein signaling (RGS) domain found in the RGS8 protein; The RGS (Regulator of G-protein Signaling) domain is an essential part of the RGS8 protein. RGS8 is a member of R4/RGS subfamily of RGS family, a diverse group of multifunctional proteins that regulate cellular signaling events downstream of G-protein coupled receptors (GPCRs). RGS proteins play critical regulatory roles as GTPase activating proteins (GAPs) of the heterotrimeric G-protein G-alpha subunits. The RGS domain controls G-protein signaling by accelerating the GTPase activity of the G-alpha subunit which leads to G protein deactivation and promotes desensitization. As a major G-protein regulator, RGS domain containing proteins are involved in many crucial cellular processes such as regulation of intracellular trafficking, glial differentiation, embryonic axis formation, skeletal and muscle development, and cell migration during early embryogenesis. RGS8 is involved in G-protein-gated potassium channels regulation and predominantly expressed in the brain. RGS8 also is selectively expressed in the hematopoietic system (NK cells).

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2247794532 1063 TSEEALKWGESLEKLLVHKYGLAVFQAFLRTEFSEENLEFWLACEDFKKVKSQSKMASKAKKIFAEYIAIQACKEVNLDS 1142
Cdd:cd08711      1 STEEATRWADSFDVLLSHKYGVAAFRAFLKTEFSEENLEFWLACEEFKKTRSTAKLVSKAHRIFEEFVDVQAPREVNIDF 80

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*
gi 2247794532 1143 YTREHTKDNLQSVTRGCFDLAQKRIFGLMEKDSYPRFLRSDLYLD 1187
Cdd:cd08711     81 QTREATRKNLQEPSLTCFDQAQGKVHSLMEKDSYPRFLRSKMYLD 125

Regulator of G protein signaling (RGS) domain found in the RGS4 protein; The RGS (Regulator of G-protein Signaling) domain is an essential part of the RGS4 protein. RGS4 is a member of the R4/RGS subfamily of the RGS family, a diverse group of multifunctional proteins that regulate cellular signaling events downstream of G-protein coupled receptors (GPCRs). As a major G-protein regulator, RGS domain containing proteins are involved in many crucial cellular processes such as regulation of intracellular trafficking, glial differentiation, embryonic axis formation, skeletal and muscle development, and cell migration during early embryogenesis. RGS proteins play critical regulatory roles as GTPase activating proteins (GAPs) of the heterotrimeric G-protein G-alpha subunits. The RGS domain controls G-protein signaling by accelerating the GTPase activity of the G-alpha subunit which leads to G protein deactivation and promotes desensitization. RGS4 is expressed widely in brain including prefrontal cortex, striatum, locus coeruleus (LC), and hippocampus and has been implicated in regulation of opioid, cholinergic, and serotonergic signaling. Dysfunctions in RGS4 proteins are involved in etiology of Parkinson's disease, addiction, and schizophrenia. RGS4 also is up-regulated in the failing human heart. RGS4 interacts with many binding partners outside of GPCR pathways, including calmodulin, COP, Kir3, PIP, calcium/CaM, PA, ErbB3, and 14-3-3.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2247794532 1074 LEKLLVHKYGLAVFQAFLRTEFSEENLEFWLACEDFKKVKSQSKMASKAKKIFAEYIAIQACKEVNLDSYTREHTKDNLQ 1153
Cdd:cd08714      1 LENLINHECGLAAFKAFLKSEYSEENIDFWVSCEDYKKTKSPSKLSPKARKIYEEFISVQATKEVNLDSCTREETSRNML 80

                           90       100       110
                   ....*....|....*....|....*....|....
gi 2247794532 1154 SVTRGCFDLAQKRIFGLMEKDSYPRFLRSDLYLD 1187
Cdd:cd08714     81 EPTISCFDEAQKKIFTLMEKDSYRRFLKSRFYLD 114

Regulator of G protein signaling (RGS) domain found in the RGS2 protein; The RGS (Regulator of G-protein Signaling) domain is an essential part of the RGS2 protein. RGS2 is a member of R4/RGS subfamily of RGS family, a diverse group of multifunctional proteins that regulate cellular signaling events downstream of G-protein coupled receptors (GPCRs). RGS proteins play critical regulatory roles as GTPase activating proteins (GAPs) of the heterotrimeric G-protein G-alpha-subunits. The RGS domain controls G-protein signaling by accelerating the GTPase activity of the G- alpha subunit which leads to G protein deactivation and promotes desensitization. As a major G-protein regulator, RGS domain containing proteins are involved in many crucial cellular processes such as regulation of intracellular trafficking, glial differentiation, embryonic axis formation, skeletal and muscle development, and cell migration during early embryogenesis. RGS2 plays important roles in the regulation of blood pressure and the pathogenesis of human hypertension, as well as in bone formation in osteoblasts. Outside of the GPCR pathway RGS2 interacts with calmodulin, beta- COP, tubulin, PKG1-alpha, and TRPV6.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2247794532 1074 LEKLLVHKYGLAVFQAFLRTEFSEENLEFWLACEDFKKVKSQSKMASKAKKIFAEYIAIQACKEVNLDSYTREHTKDNLQ 1153
Cdd:cd08709      1 FDELLASKYGVAAFRAFLKSEFSEENIEFWLACEDFKKTKSPQKLTSKAKKIYTDFIEKEAPKEINIDFQTKTLIAQNIQ 80

                           90       100       110
                   ....*....|....*....|....*....|....
gi 2247794532 1154 SVTRGCFDLAQKRIFGLMEKDSYPRFLRSDLYLD 1187
Cdd:cd08709     81 EATSGCFTAAQKRVYSLMENNSYPRFLESEFYQE 114

Regulator of G protein signaling (RGS) domain found in the RGS18 protein; The RGS (Regulator of G-protein Signaling) domain is an essential part of the RGS18 protein. RGS18 is a member of the RGS protein family, a diverse group of multifunctional proteins that regulate cellular signaling events downstream of G-protein coupled receptors (GPCRs). RGS proteins play critical regulatory roles as GTPase activating proteins (GAPs) of the heterotrimeric G-protein G-alpha subunits. The RGS domain controls G-protein signaling by accelerating the GTPase activity of the G-alpha subunit which leads to G protein deactivation and promotes desensitization. As a major G-protein regulator, RGS domain containing proteins are involved in many crucial cellular processes such as regulation of intracellular trafficking, glial differentiation, embryonic axis formation, skeletal and muscle development, and cell migration during early embryogenesis. RGS18 is a member of the R4/RGS subfamily and is expressed predominantly in osteoclasts where it acts as a negative regulator of the acidosis-induced osteoclastogenic OGR1/NFAT signaling pathway. RANKL (receptor activator of nuclear factor B ligand) stimulates osteoclastogenesis by inhibiting expression of RGS18.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2247794532 1074 LEKLLVHKYGLAVFQAFLRTEFSEENLEFWLACEDFKKVKSQSKMASKAKKIFAEYIAIQACKEVNLDSYTREHTKDNLQ 1153
Cdd:cd08712      1 FDKLLSHKDGLEAFTRFLKTEFSEENIEFWIACEDYKKSKTPQQIHLKAKAIYEKFIQTDAPKEVNLDFHTKEVTTNSIE 80

                           90       100       110
                   ....*....|....*....|....*....|....
gi 2247794532 1154 SVTRGCFDLAQKRIFGLMEKDSYPRFLRSDLYLD 1187
Cdd:cd08712     81 QPTLTSFDAAQSRVYQLMEQDSYPRFLKSDIYLD 114

Regulator of G protein signaling (RGS) domain found in the RGS1 protein; The RGS (Regulator of G-protein Signaling) domain is an essential part of the RGS1 protein. RGS1 is a member of the R4/RGS subfamily of the RGS family, a diverse group of multifunctional proteins that regulate cellular signaling events downstream of G-protein coupled receptors (GPCRs). RGS proteins play critical regulatory roles as GTPase activating proteins (GAPs) of the heterotrimeric G-protein G-alpha subunits. The RGS domain controls G-protein signaling by accelerating the GTPase activity of the G-alpha subunit which leads to G protein deactivation and promotes desensitization. As a major G-protein regulator, RGS domain containing proteins are involved in many crucial cellular processes such as regulation of intracellular trafficking, glial differentiation, embryonic axis formation, skeletal and muscle development, and cell migration during early embryogenesis. RGS 1 is expressed predominantly in hematopoietic compartments, including T and B lymphocytes, and may play a major role in chemokine-mediated homing of lymphocytes to secondary lymphoid organs. In addition, RGS1 interacts with calmodulin and 14-3-3 protein outside of the GPCR pathway.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2247794532 1074 LEKLLVHKYGLAVFQAFLRTEFSEENLEFWLACEDFKKVKSQsKMASKAKKIFAEYIAIQACKEVNLDSYTREHTKDNLQ 1153
Cdd:cd08715      1 LEKLLASQTGQNVFRSFLKSEFSEENIEFWLACEDYKKTESD-LLPCKAEEIYKEFVQSDAAKQINIDFRTRESTAKKIK 79

                           90       100       110
                   ....*....|....*....|....*....|....*
gi 2247794532 1154 SVTRGCFDLAQKRIFGLMEKDSYPRFLRSDLYLDL 1188
Cdd:cd08715     80 APTPTCFDEAQKVIYILMERDSYPRFLKSDIYLNL 114

Regulator of G protein signaling (RGS) domain found in the RGS21 protein; The RGS (Regulator of G-protein Signaling) domain is an essential part RGS21 protein, a member of RGS protein family. They are a diverse group of multifunctional proteins that regulate cellular signaling events downstream of G-protein coupled receptors (GPCRs). RGS proteins play critical regulatory roles as GTPase activating proteins (GAPs) of the heterotrimeric G-protein G-alpha-subunits. As a major G-protein regulator, RGS domain containing proteins are involved in many crucial cellular processes. RGS proteins regulate many aspects of embryonic development such as glial differentiation, embryonic axis formation, skeletal and muscle development, cell migration during early embryogenesis, apoptosis, and cell proliferation, as well as modulation of cardiac development. RGS21 is a member of the R4/RGS subfamily and its mRNA was detected only in sensory taste cells that express sweet taste receptors and the taste G-alpha subunit, gustducin, suggesting a potential role in regulating taste transduction.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2247794532 1077 LLVHKYGLAVFQAFLRTEFSEENLEFWLACEDFKKVKSQSKMASKAKKIFAEYIAIQACKEVNLDSYTREHTKDNLQSVT 1156
Cdd:cd08723      1 LLANQAGLDAFRTFLKSEFSEENVEFWLACEDFKKTKSSTEIALKAQMIYSEFIQADAPKEINIDFHTRDLISQNISEPT 80

                           90       100
                   ....*....|....*....|....*....
gi 2247794532 1157 RGCFDLAQKRIFGLMEKDSYPRFLRSDLY 1185
Cdd:cd08723     81 LKCFDEAQSLIYCLMAKDSFPRFLKSEVY 109

Regulator of G protein signaling (RGS) domain found in the RGS20 protein; The RGS (Regulator of G-protein Signaling) domain is an essential part of the RGS20 protein (also known as RGSZ1), a member of the RZ subfamily of the RGS protein family. They are a diverse group of multifunctional proteins that regulate cellular signaling events downstream of G-protein coupled receptors (GPCRs). RGS proteins play critical regulatory roles as GTPase activating proteins (GAPs) of the heterotrimeric G-protein G-alpha-subunits. Deactivation of G-protein signaling is controlled by the RGS domain, which accelerates GTPase activity of the alpha subunit by hydrolysis of GTP to GDP resulting in reassociation of the alpha-subunit with the beta-gamma-dimer and inhibition of downstream activity. As a major G-protein regulator, the RGS domain containing proteins are involved in many crucial cellular processes such as regulation of intracellular trafficking, glial differentiation, embryonic axis formation, skeletal and muscle development, and cell migration during early embryogenesis. The RZ subfamily of RGS proteins include RGS17, RGS19 (former GAIP), and the splice variant of RGS20, Ret-RGS. RGS20 is expressed exclusively in brain, with the highest concentrations in the temporal lobe and the caudate nucleus and may play a role in signaling regulation in these brain regions. RGS20 acts as a GAP of both G-alpha-z and G-alpha-I and controls signaling in the mu opioid receptor pathway.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2247794532 1058 KSFKPTSEEALKWGESLEKLLVHKYGLAVFQAFLRTEFSEENLEFWLACEDFKKVKSQSKMASKAKKIFAEYIAIQACKE 1137
Cdd:cd08746     38 ESPKPTLEEVCAWGQSFDKLMLTPAGRNAFREFLRTEFSEENMLFWMACEELKKEANKSVIEEKARIIYEDYISILSPKE 117

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|
gi 2247794532 1138 VNLDSYTREHTKDNLQSVTRGCFDLAQKRIFGLMEKDSYPRFLRSDLYLD 1187
Cdd:cd08746    118 VSLDSRVREVINRNMLEPSQHTFDDAQLQIYTLMHRDSYPRFMNSAIYKN 167

Regulator of G protein signaling (RGS) domain found in the R7 subfamily of proteins; The RGS (Regulator of G-protein Signaling) domain is an essential part of the R7 (Neuronal RGS) protein subfamily of the RGS protein family, a diverse group of multifunctional proteins that regulate cellular signaling events downstream of G-protein coupled receptors (GPCRs). As a major G-protein regulator, RGS domain containing proteins are involved in many crucial cellular processes such as regulation of intracellular trafficking, glial differentiation, embryonic axis formation, skeletal and muscle development, and cell migration during early embryogenesis. The R7 subfamily includes RGS6, RGS7, RGS9, and RGS11, all of which, in humans, are expressed predominantly in the nervous system, form an obligatory complex with G-beta-5, and play important roles in the regulation of crucial neuronal processes. In addition, R7 proteins were found to bind many other proteins outside of the G protein signaling pathways including: m-opioid receptor, beta-arrestin, alpha-actinin-2, NMDAR, polycystin, spinophilin, guanylyl cyclase, among others.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2247794532 1069 KWGESLEKLLVHKYGLAVFQAFLRTEFSEENLEFWLACEDFKKVkSQSKMASKAKKIFAEYIAIQACKEVNLDSYTREHT 1148
Cdd:cd08705      4 RWGFSFSELLKDPVGREQFLKFLEKEFSGENLRFWEACQDLKYG-PQSQVPEKVQEIYQEFLAPGAPSWINIDSKTMEIT 82

                           90       100       110
                   ....*....|....*....|....*....|....*....
gi 2247794532 1149 KDNLQSVTRGCFDLAQKRIFGLMEKDSYPRFLRSDLYLD 1187
Cdd:cd08705     83 LKNLKDPHRYTFDAAQEHIYMLMKKDSYPRFLRSDIYKE 121

Regulator of G protein signaling (RGS) domain found in the R12 subfamily of proteins; The RGS (Regulator of G-protein Signaling) domain is an essential part of the R12 (Neuronal RGS) protein subfamily of the RGS protein family, a diverse group of multifunctional proteins that regulate cellular signaling events downstream of G-protein coupled receptors (GPCRs). RGS proteins play a critical regulatory role as GTPase activating proteins (GAPs) of the heterotrimeric G-protein G-alpha-subunits. Deactivation of G-protein signaling, controlled by RGS domain, accelerates GTPase activity of the alpha subunit by hydrolysis of GTP to GDP that results in reassociation of the alpha-subunit with the beta-gamma-dimer and thereby inhibition of downstream activity. As a major G-protein regulator, RGS domain containing proteins are involved in many crucial cellular processes such as regulation of intracellular trafficking, glial differentiation, embryonic axis formation, skeletal and muscle development, and cell migration during early embryogenesis. The R12 RGS subfamily includes RGS10, RGS12 and RGS14 all of which are highly selective for G-alpha-i1 over G-alpha-q.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2247794532 1074 LEKLLVHKYGLAVFQAFLRTEFSEENLEFWLACEDFKKVKSQSKMASKAKKIFAEYIAIQACKEVNLDSyTREHTKDNLQ 1153
Cdd:cd08706      1 FERLLQDPVGVKYFTEFLKKEFSEENILFWQACEKFKKIPDKKQLVQEAREIYDTFLSSKASSPVNIDS-QAQLAEEMLE 79

                           90       100       110
                   ....*....|....*....|....*....|....
gi 2247794532 1154 SVTRGCFDLAQKRIFGLMEKDSYPRFLRSDLYLD 1187
Cdd:cd08706     80 EPHPDMFQKQQLQIFNLMKFDSYSRFLKSPLYQQ 113

Regulator of G protein signaling (RGS) domain found in the RGS17 protein; The RGS (Regulator of G-protein Signaling) domain is an essential part of the RGS17 protein, a member of the RZ subfamily of the RGS protein family. They are a diverse group of multifunctional proteins that regulate cellular signaling events downstream of G-protein coupled receptors (GPCRs). As a major G-protein regulator, the RGS domain containing proteins are involved in many crucial cellular processes such as regulation of intracellular trafficking, glial differentiation, embryonic axis formation, skeletal and muscle development, and cell migration during early embryogenesis. RGS proteins play critical regulatory roles as GTPase activating proteins (GAPs) of the heterotrimeric G-protein G-alpha-subunits. Deactivation of the G-protein signaling controlled by the RGS domain, which accelerates GTPase activity of the alpha subunit by hydrolysis of GTP to GDP, results in reassociation of the alpha-subunit with the beta-gamma-dimer and inhibition of downstream activity. The RZ subfamily of RGS proteins includes RGS19 (former GAIP), RGS20, and its splice variant Ret-RGS. RGS17 is a relatively non-selective GAP for G-alpha-z and other G-alpha-i/o proteins. RGS17 blocks dopamine receptor-mediated inhibition of cAMP accumulation; it also blocks thyrotropin releasing hormone-stimulated Ca++ mobilization. RGS17, like other members of RZ subfamily, can act either as a GAP or as G-protein effector antogonist.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2247794532 1070 WGESLEKLLVHKYGLAVFQAFLRTEFSEENLEFWLACEDFKKVKSQSKMASKAKKIFAEYIAIQACKEVNLDSYTREHTK 1149
Cdd:cd08744      1 WSQNFDKMMKTPAGRNLFREFLRTEYSEENLLFWLACEDLKKEQNKKVIEEKARLIYEDYISILSPKEVSLDSRVREVIN 80

                           90       100       110
                   ....*....|....*....|....*....|....*.
gi 2247794532 1150 DNLQSVTRGCFDLAQKRIFGLMEKDSYPRFLRSDLY 1185
Cdd:cd08744     81 RNLLDPNPHMYEDAQLQIYTLMHRDSFPRFLNSQIY 116

C2 domain in Protein Kinase C (PKC) alpha and gamma; A single C2 domain is found in PKC alpha and gamma. The PKC family of serine/threonine kinases regulates apoptosis, proliferation, migration, motility, chemo-resistance, and differentiation. There are 3 groups: group 1(alpha, betaI, beta II, gamma) which require phospholipids and calcium, group 2 (delta, epsilon, theta, eta) which do not require calcium for activation, and group 3 (xi, iota/lambda) which are atypical and can be activated in the absence of diacylglycerol and calcium. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. Members here have a type-I topology.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2247794532  139 GQLRLSIDAQDRVLLLHIIEGKGLISKQP-GTCDPYVKISLIPEDSRLRHQKTQTVPDCRDPAFHEHFFFPVQEEDDQKR 217
Cdd:cd04026      2 GRIYLKISVKDNKLTVEVREAKNLIPMDPnGLSDPYVKLKLIPDPKNETKQKTKTIKKTLNPVWNETFTFDLKPADKDRR 81

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|.
gi 2247794532  218 LLVTVWNRASQSRQSgLIGCMSFGVKSLLtpDKEISGWYYLLGEHLGRTKH 268
Cdd:cd04026     82 LSIEVWDWDRTTRND-FMGSLSFGVSELI--KMPVDGWYKLLNQEEGEYYN 129

Regulator of G protein signaling (RGS) domain found in the RGS9 protein; The RGS (Regulator of G-protein Signaling) domain is an essential part of the RGS9 protein, a member of R7 subfamily of the RGS protein family. RGS is a diverse group of multifunctional proteins that regulate cellular signaling events downstream of G-protein coupled receptors (GPCRs). As a major G-protein regulator, RGS domain containing proteins are involved in many crucial cellular processes such as regulation of intracellular trafficking, glial differentiation, embryonic axis formation, skeletal and muscle development, and cell migration during early embryogenesis. Other members of the R7 subfamily (Neuronal RGS) include: RGS6, RGS7, and RGS11, all of which are expressed predominantly in the nervous system, form an obligatory complex with G-beta-5, and play important roles in the regulation of crucial neuronal processes such as vision and motor control. Additionally they have been implicated in many neurological conditions such as anxiety, schizophrenia, and drug dependence. RGS9 forms constitutive complexes with G-beta-5 subunit and controls such fundamental functions as vision and behavior. RGS9 exists in two splice isoforms: RGS9-1 which regulates phototransduction in rods and cones and RGS9-2 which regulates dopamine and opioid signaling in the basal ganglia. In addition, RGS9 was found to bind many other proteins outside of G protein signaling pathways including: mu-opioid receptor, beta-arrestin, alpha-actinin-2, NMDAR, polycystin, spinophilin, and guanylyl cyclase, among others.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2247794532 1069 KWGESLEKLLVHKYGLAVFQAFLRTEFSEENLEFWLACEDFKkVKSQSKMASKAKKIFAEYIAIQACKEVNLDSYTREHT 1148
Cdd:cd08739      4 RWAFNFSELIRDPKGRQSFQLFLKKEFSGENLGFWEACEDLK-YGDQSKVKEKAEEIYKLFLAPGARRWINIDGKTMDIT 82

                           90       100       110
                   ....*....|....*....|....*....|....*..
gi 2247794532 1149 KDNLQSVTRGCFDLAQKRIFGLMEKDSYPRFLRSDLY 1185
Cdd:cd08739     83 VKGLKHPHRYVLDAAQTHIYMLMKKDSYARYLKSPIY 119

Regulator of G protein signaling (RGS) domain found in the RGS7 protein; The RGS (Regulator of G-protein Signaling) domain is an essential part of the RGS7 protein, a member of R7 subfamily of the RGS protein family. RGS is a diverse group of multifunctional proteins that regulate cellular signaling events downstream of G-protein coupled receptors (GPCRs). As a major G-protein regulator, RGS domain containing proteins are involved in many crucial cellular processes such as regulation of intracellular trafficking, glial differentiation, embryonic axis formation, skeletal and muscle development, and cell migration during early embryogenesis. As a major G-protein regulator, RGS domain containing proteins are involved in many crucial cellular processes such as regulation of intracellular trafficking, glial differentiation, embryonic axis formation, skeletal and muscle development, and cell migration during early embryogenesis. Other members of the R7 subfamily (Neuronal RGS) include: RGS6, RGS9, and RGS11, all of which are expressed predominantly in the nervous system, form an obligatory complex with G-beta-5, and play important roles in the regulation of crucial neuronal processes such as vision and motor control. Additionally they have been implicated in many neurological conditions such as anxiety, schizophrenia, and drug dependence. R7 RGS proteins are key modulators of the pharmacological effects of drugs involved in the development of tolerance and addiction. In addition, RGS7 was found to bind a component of the synaptic fusion complex, snapin, and some other proteins outside of G protein signaling pathways.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2247794532 1069 KWGESLEKLLVHKYGLAVFQAFLRTEFSEENLEFWLACEDFKKvKSQSKMASKAKKIFAEYIAIQACKEVNLDSYTREHT 1148
Cdd:cd08738      4 RWGFGMDEALKDPVGREQFLKFLESEFSSENLRFWLAVEDLKK-RPIREVPSRVQEIWQEFLAPGAPSAINLDSKSYDKT 82

                           90       100       110
                   ....*....|....*....|....*....|....*..
gi 2247794532 1149 KDNLQSVTRGCFDLAQKRIFGLMEKDSYPRFLRSDLY 1185
Cdd:cd08738     83 TQNVKDPGRYTFEDAQEHIYKLMKSDSYPRFIRSSAY 119

C2 domain; The C2 domain was first identified in PKC. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2247794532  152 LLLHIIEGKGLISK-QPGTCDPYVKISLIPEdsrlRHQKTQTVPDCRDPAFHEHFFFPVQEEDDQkRLLVTVWNRASQSR 230
Cdd:cd00030      1 LRVTVIEARNLPAKdLNGKSDPYVKVSLGGK----QKFKTKVVKNTLNPVWNETFEFPVLDPESD-TLTVEVWDKDRFSK 75

                           90       100
                   ....*....|....*....|....*...
gi 2247794532  231 QSgLIGCMSFGVKSLLTPDKEISGWYYL 258
Cdd:cd00030     76 DD-FLGEVEIPLSELLDSGKEGELWLPL 102

Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, protein kinases C, and synaptotagmins (among others). Some do not appear to contain Ca2+-binding sites. Particular C2s appear to bind phospholipids, inositol polyphosphates, and intracellular proteins. Unusual occurrence in perforin. Synaptotagmin and PLC C2s are permuted in sequence with respect to N- and C-terminal beta strands. SMART detects C2 domains using one or both of two profiles.

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2247794532   151 VLLLHIIEGKGLISKQP-GTCDPYVKISLIPEDSRLRhqKTQTVPDCRDPAFHEHFFFPVQEEDDQkRLLVTVWNRASQS 229
Cdd:smart00239    1 TLTVKIISARNLPPKDKgGKSDPYVKVSLDGDPKEKK--KTKVVKNTLNPVWNETFEFEVPPPELA-ELEIEVYDKDRFG 77

                            90
                    ....*....|....*...
gi 2247794532   230 RqSGLIGCMSFGVKSLLT 247
Cdd:smart00239   78 R-DDFIGQVTIPLSDLLL 94

canonical PDZ domain; Canonical PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain. PDZ domains usually bind to short specific peptide sequences located at the C-terminal end of their partner proteins known as PDZ binding motifs. These domains can also interact with internal peptide motifs and certain lipids, and can take part in a head-to-tail oligomerization with other PDZ domains. The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. The canonical PDZ domain contains six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2247794532  299 KITIPRGK-DGFGFTIC----CDSPVRVQAVDSGGPAERAG-LQQLDTVLQLNERPVEHWKCVELAHEIRSCPSEIILLV 372
Cdd:cd00136      1 TVTLEKDPgGGLGFSIRggkdGGGGIFVSRVEPGGPAARDGrLRVGDRILEVNGVSLEGLTHEEAVELLKSAGGEVTLTV 80

PDZ domain 2 of delphilin (L-delphilin isoform), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 2 of delphilin (also known as glutamate receptor, ionotropic, delta 2-interacting protein 1, L-delphilin). Delphilin, a postsynaptic protein which it is selectively expressed at cerebellar Purkinje cells, links the glutamate receptor delta 2 subunit (GluRdelta2) with the actin cytoskeleton and various signaling molecules. Two alternatively spliced isoforms of delphilin have been characterized: L-delphilin has two PDZ domains, PDZ1 and PDZ2, and S-delphilin has a single PDZ domain (PDZ2). These two isoforms are differently palmitoylated and may be involved in controlling GluRdelta2 signaling in Purkinje cells. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This delphilin-like family PDZ2 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2247794532  300 ITIPRGKDGFGFTICCDSPVRVQAVDSGGPAERAGLQQLDTVLQLNE---RPVEHWKCVELAHEIRSCPS 366
Cdd:cd06744      2 VRVYRGNGSFGFTLRGHAPVYIESVDPGSAAERAGLKPGDRILFLNGldvRNCSHDKVVSLLQGSGSMPT 71

C2 domain third repeat present in uncharacterized human KIAA1228-like proteins; KIAA proteins are uncharacterized human proteins. They were compiled by the Kazusa mammalian cDNA project which identified more than 2000 human genes. They are identified by 4 digit codes that precede the KIAA designation. Many KIAA genes are still functionally uncharacterized including KIAA1228. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the third C2 repeat, C2C, and has a type-II topology.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2247794532  137 GAGQLRLSI--DAQDRVLLLHIIEGKGLISKQP-GTCDPYVKISLIPEDSRLRHQKTQTVPDCRDPAFHEHFFFPVQEED 213
Cdd:cd04030      1 PLGRIQLTIrySSQRQKLIVTVHKCRNLPPCDSsDIPDPYVRLYLLPDKSKSTRRKTSVKKDNLNPVFDETFEFPVSLEE 80

                           90       100
                   ....*....|....*....|....*
gi 2247794532  214 DQKRLL-VTVWN-RASQSRQSGLIG 236
Cdd:cd04030     81 LKRRTLdVAVKNsKSFLSREKKLLG 105

C2 domain second repeat present in Synaptotagmin; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. There are several classes of Synaptotagmins. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2247794532  140 QLRLSIDAQDRVLLLHIIEGKGL-ISKQPGTCDPYVKISLIPEDSRLRHQKTQTVPDCRDPAFHEHFFFPV-QEEDDQKR 217
Cdd:cd00276      4 LLSLSYLPTAERLTVVVLKARNLpPSDGKGLSDPYVKVSLLQGGKKLKKKKTSVKKGTLNPVFNEAFSFDVpAEQLEEVS 83