Regulator of G protein signaling (RGS) domain superfamily; The RGS domain is an essential part of the Regulator of G-protein Signaling (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. While inactive, G-alpha-subunits bind GDP, which is released and replaced by GTP upon agonist activation. GTP binding leads to dissociation of the alpha-subunit and the beta-gamma-dimer, allowing them to interact with effectors molecules and propagate signaling cascades associated with cellular growth, survival, migration, and invasion. Deactivation of the G-protein signaling controlled by the RGS domain accelerates GTPase activity of the alpha subunit by hydrolysis of GTP to GDP, which results in the 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. RGS proteins are also involved in apoptosis and cell proliferation, as well as modulation of cardiac development. Several RGS proteins can fine-tune immune responses, while others play important roles in neuronal signals modulation. Some RGS proteins are principal elements needed for proper vision.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 195395026  54 LNHLLEDRDGVELFKKYVEEEAPAynDHLNFYFACEGLKQQTD-PEKVKQIIGAIYRFLRKSQLSISDDLRAQIKAIKSN 132
Cdd:cd08707    1 LHSLLDDQDGIELFRTYLEQEGCA--DLLDFWFACNGFRKMSDsEEKRSKLAKAIYRRYIKDNGIVSRQLKPATKSFIKE 78

                         90       100       110
                 ....*....|....*....|....*....|....*....
gi 195395026 133 EI---PLSPHIYDPMQQHVEATIRDNIYPSFLCSEMYIQ 168
Cdd:cd08707   79 CIkkqQLDPAMFDQAQTEIQTTMEENTYPSFLKSDIYLE 117

Axin beta-catenin binding motif; This motif is found on the scaffolding protein Axin which is a component of the beta-catenin destruction complex. It competes with the tumour suppressor adenomatous polyposis coli protein (APC) for binding to beta-catenin.

                          10        20        30
                  ....*....|....*....|....*....|....*.
gi 195395026  487 DNDQDILDQHVSRVWKDqTPHRSPGTMSPCPPIPSR 522
Cdd:pfam08833   1 DNPQSILDEHVSRVWKT-PGCQSPGRHSPRSRSPDS 35

Regulator of G protein signaling (RGS) domain found in the Axin protein; The RGS (Regulator of G-protein Signaling) domain is an essential part of the Axin protein. Axin is a member of the RA/RGS 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. RGS proteins regulate many aspects of embryonic development such as glial differentiation, embryonic axis formation, and skeletal and muscle development. The RGS domain of Axin is specifically interacts with the heterotrimeric G-alpha12 protein, but not with closely related G-alpha13, and provides a unique tool to regulate G-alpha12-mediated signaling processes. The RGS domain of Axin also interacts with the tumor suppressor protein APC (Adenomatous Polyposis Coli) in order to control the cytoplasmic level of the proto-oncogene, beta-catenin.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 195395026  54 LNHLLEDRDGVELFKKYVEEEAPAynDHLNFYFACEGLKQQTD-PEKVKQIIGAIYRFLRKSQLSISDDLRAQIKAIKSN 132
Cdd:cd08707    1 LHSLLDDQDGIELFRTYLEQEGCA--DLLDFWFACNGFRKMSDsEEKRSKLAKAIYRRYIKDNGIVSRQLKPATKSFIKE 78

                         90       100       110
                 ....*....|....*....|....*....|....*....
gi 195395026 133 EI---PLSPHIYDPMQQHVEATIRDNIYPSFLCSEMYIQ 168
Cdd:cd08707   79 CIkkqQLDPAMFDQAQTEIQTTMEENTYPSFLKSDIYLE 117

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 195395026    53 TLNHLLEDRDGVELFKKYVEEEAPAynDHLNFYFACEGLKQQTDPEKVKQIIGAIY-RFLRKS---QLSISDDLRAQIK- 127
Cdd:smart00315   1 SLESLLSDPIGRLLFREFLESEFSE--ENLEFWLAVEEFKKAEDDEERIAKAREIYdKFLSPNapkEVNLDSDLREKIEe 78

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|..
gi 195395026   128 AIKSNEIPlsPHIYDPMQQHVEATIRDNIYPSFLCSEMYIQY 169
Cdd:smart00315  79 NLESEEPP--PDLFDEAQREVYELLEKDSFPRFLESDYYLRF 118

Domain present in Dishevelled and axin; Domain of unknown function.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 195395026   666 ETVVVFSFCEEPVPYRIKIPG--TQPTLRQFKDFLPRRGhFRFFFKThcEDPDSP-VIQEEIVNDSDILPLFGDKAMGLV 742
Cdd:smart00021   3 ETKVIYHLDDEETPYLVKVPVpaERVTLGDFKEVLTKKN-YKYYFKS--MDDDFGgVVKEEIRDDSARLPCFNGRVVSWL 79

                   ....
gi 195395026   743 KPSD 746
Cdd:smart00021  80 VSVE 83

Regulator of G protein signaling (RGS) domain found in the Axin protein; The RGS (Regulator of G-protein Signaling) domain is an essential part of the Axin protein. Axin is a member of the RA/RGS 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. RGS proteins regulate many aspects of embryonic development such as glial differentiation, embryonic axis formation, and skeletal and muscle development. The RGS domain of Axin is specifically interacts with the heterotrimeric G-alpha12 protein, but not with closely related G-alpha13, and provides a unique tool to regulate G-alpha12-mediated signaling processes. The RGS domain of Axin also interacts with the tumor suppressor protein APC (Adenomatous Polyposis Coli) in order to control the cytoplasmic level of the proto-oncogene, beta-catenin.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 195395026  54 LNHLLEDRDGVELFKKYVEEEAPAynDHLNFYFACEGLKQQTD-PEKVKQIIGAIYRFLRKSQLSISDDLRAQIKAIKSN 132
Cdd:cd08707    1 LHSLLDDQDGIELFRTYLEQEGCA--DLLDFWFACNGFRKMSDsEEKRSKLAKAIYRRYIKDNGIVSRQLKPATKSFIKE 78

                         90       100       110
                 ....*....|....*....|....*....|....*....
gi 195395026 133 EI---PLSPHIYDPMQQHVEATIRDNIYPSFLCSEMYIQ 168
Cdd:cd08707   79 CIkkqQLDPAMFDQAQTEIQTTMEENTYPSFLKSDIYLE 117

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 195395026    53 TLNHLLEDRDGVELFKKYVEEEAPAynDHLNFYFACEGLKQQTDPEKVKQIIGAIY-RFLRKS---QLSISDDLRAQIK- 127
Cdd:smart00315   1 SLESLLSDPIGRLLFREFLESEFSE--ENLEFWLAVEEFKKAEDDEERIAKAREIYdKFLSPNapkEVNLDSDLREKIEe 78

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|..
gi 195395026   128 AIKSNEIPlsPHIYDPMQQHVEATIRDNIYPSFLCSEMYIQY 169
Cdd:smart00315  79 NLESEEPP--PDLFDEAQREVYELLEKDSFPRFLESDYYLRF 118

Domain present in Dishevelled and axin; Domain of unknown function.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 195395026   666 ETVVVFSFCEEPVPYRIKIPG--TQPTLRQFKDFLPRRGhFRFFFKThcEDPDSP-VIQEEIVNDSDILPLFGDKAMGLV 742
Cdd:smart00021   3 ETKVIYHLDDEETPYLVKVPVpaERVTLGDFKEVLTKKN-YKYYFKS--MDDDFGgVVKEEIRDDSARLPCFNGRVVSWL 79

                   ....
gi 195395026   743 KPSD 746
Cdd:smart00021  80 VSVE 83

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 195395026  50 WARTLNHLLEDRDGVELFKKYVEEEAPAYNdhLNFYFACEGLKQQtDPEKVKQIIGAIYR-FL-RKSQLSISDDLRAQIK 127
Cdd:cd08705    5 WGFSFSELLKDPVGREQFLKFLEKEFSGEN--LRFWEACQDLKYG-PQSQVPEKVQEIYQeFLaPGAPSWINIDSKTMEI 81

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|.
gi 195395026 128 AIKSNEiplSPHIY--DPMQQHVEATIRDNIYPSFLCSEMY 166
Cdd:cd08705   82 TLKNLK---DPHRYtfDAAQEHIYMLMKKDSYPRFLRSDIY 119

Axin beta-catenin binding motif; This motif is found on the scaffolding protein Axin which is a component of the beta-catenin destruction complex. It competes with the tumour suppressor adenomatous polyposis coli protein (APC) for binding to beta-catenin.

                          10        20        30
                  ....*....|....*....|....*....|....*.
gi 195395026  487 DNDQDILDQHVSRVWKDqTPHRSPGTMSPCPPIPSR 522
Cdd:pfam08833   1 DNPQSILDEHVSRVWKT-PGCQSPGRHSPRSRSPDS 35

Regulator of G protein signaling (RGS) domain found in the RGS19 protein; The RGS (Regulator of G-protein Signaling) domain is an essential part of the RGS19 protein (also known as GAIP), 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 RGS domains, which accelerate GTPase activity of the alpha subunit by hydrolysis of GTP to GDP, resulting in a reassociation of the alpha-subunit with the beta-gamma-dimer and an 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 includes RGS17, RGS20, and its splice variant Ret-RGS. RGS19 participates in regulation of dopamine receptor D2R and D3R, as well as beta-adrenergic receptors .

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 195395026  50 WARTLNHLLEDRDGVELFKKYVEEEAPAYNdhLNFYFACEGLK----QQTDPEKVKQIIGAIYRFLRKSQLSISDDLRAQ 125
Cdd:cd08745    1 WAQSFDKLMKSPAGRNVFREFLRTEYSEEN--MLFWLACEELKaeanKHVIDEKARLIYEDYISILSPKEVSLDSRVREG 78

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|.
gi 195395026 126 IKaiKSNEIPlSPHIYDPMQQHVEATIRDNIYPSFLCSEMY 166
Cdd:cd08745   79 IN--RKMQEP-SSHTFDDAQLQIYTLMHRDSYPRFLNSPIY 116

Regulator of G protein signaling (RGS) domain found in the RZ protein; The RGS (Regulator of G-protein Signaling) domain is an essential part 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 RGS domains, which accelerate GTPase activity of the alpha subunit by hydrolysis of GTP to GDP, which results in reassociation of the alpha-subunit with the beta-gamma-dimer and 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 RZ subfamily of RGS proteins includes RGS17, RGS19 (former GAIP), RGS20, and its splice variant Ret-RGS.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 195395026  50 WARTLNHLLEDRDGVELFKKYVEEEAPAYNdhLNFYFACEGLKQQTDPEKVKQIIGAIYR----FLRKSQLSISDDLRaq 125
Cdd:cd08718    1 WAQSFDKLMKSPAGRNVFREFLRTEYSEEN--MLFWLACEELKKEANKHVIEEKARLIYEdyisILSPKEVSLDSRVR-- 76

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|.
gi 195395026 126 iKAIKSNEIPLSPHIYDPMQQHVEATIRDNIYPSFLCSEMY 166
Cdd:cd08718   77 -EVINRNMLEPSPHTFDDAQLQIYTLMHRDSYPRFLNSAIY 116

Regulator of G protein signaling (RGS) domain found in the RGS14 protein; RGS (Regulator of G-protein Signaling) domain is an essential part of the RGS14 protein. RGS14 is a member of the RA/RGS subfamily of RGS proteins 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. RGS14 belong to the R12 RGS subfamily, which includes RGS10 and RGS12, all of which are highly selective for G-alpha-i1 over G-alpha-q. RGS14 binds and regulates the subcellular localization and activities of H-Ras and Raf kinases in cells and thereby integrates G protein and Ras/Raf signaling pathways.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 195395026  46 SYLNWARTLNHLLEDRDGVELFKKYVEEEAPAYNdhLNFYFACEGLKQ--QTDPEKVKQIIGAIY-RFLRKSQLS-ISDD 121
Cdd:cd08743    3 SVASWAVSFERLLQDPLGVEYFTEFLKKEFSAEN--VNFWKACERFQQipASDTQQLAQEARKIYnEFLSSSSQSpVNID 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*
gi 195395026 122 LRAQIKAiKSNEIPlSPHIYDPMQQHVEATIRDNIYPSFLCSEMY 166
Cdd:cd08743   81 QQAWIGE-DMLATP-SPDMFRAQQLQIFNLMKFDSYARFVKSPLY 123

Regulator of G protein signaling (RGS) domain found in the RGS6 protein; The RGS (Regulator of G-protein Signaling) domain is an essential part of the RGS6 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). Other members of the R7 subfamily (Neuronal RGS) include: RGS7, 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. RGS6 exists in multiple splice isoforms with identical RGS domains, but possess complete or incomplete GGL domains and distinct N- and C-terminal domains. RGS6 interacts with SCG10, a neuronal growth-associated protein and therefore regulates neuronal differentiation. Another RGS6-binding protein is DMAP1, a component of the Dnmt1 complex involved in repression of newly replicated genes. Mutations of a critical residue required for interaction of RGS6 protein with G proteins did not affect the ability of RGS6 to interact with both SCG10 and DMAP1. 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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 195395026  50 WARTLNHLLEDRDGVELFKKYVEEEAPAYNdhLNFYFACEGLKQQTDPEKVKQIIGAIYRFLRK-SQLSISDDLRAQIKA 128
Cdd:cd08737    6 WGFSLDEVLKDPVGRDQFLRFLESEFSSEN--LRFWLAVQDLKKQPLQDVAKRVEEIWQEFLAPgAPSAINLDSHSYEKT 83

                         90       100       110
                 ....*....|....*....|....*....|....*...
gi 195395026 129 IKSNEIPlSPHIYDPMQQHVEATIRDNIYPSFLCSEMY 166
Cdd:cd08737   84 SQNVKDP-GRYTFEDAQEHIYKLMKSDSYARFLRSNAY 120

Regulator of G protein signaling (RGS) domain found in the RGS5 protein; The RGS (Regulator of G-protein Signaling) domain is an essential part of the RGS5 protein. RGS5 is 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. Two splice isoforms of RGS5 has been found: RGS5L (long) which is expressed in smooth muscle cells (pericytes) and heart and RGS5S (short) which is highly expressed in the ciliary body of the eye, kidney, brain, spleen, skeletal muscle, and small intestine. Outside of the GPCR pathway, RGS5 interacts with the 14-3-3 protein.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 195395026  54 LNHLLEDRDGVELFKKYVEEEAPAYNdhLNFYFACEGLKQQTDPEKVKQIIGAIYRFLRKSQLSISDDLRAQIKAIK-SN 132
Cdd:cd08717    1 LDKLLQNSYGLASFKSFLKSEFSEEN--IEFWEACEDYKKTKSPLKMATKAKKIYEEFIQTEAPKEVNIDHFTKDVTmKN 78

                         90       100       110
                 ....*....|....*....|....*....|....
gi 195395026 133 EIPLSPHIYDPMQQHVEATIRDNIYPSFLCSEMY 166
Cdd:cd08717   79 LVEPSSSSFDLAQKRIFALMEKDSLPRFVRSEFY 112

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 195395026  50 WARTLNHLLEDRDGVELFKKYVEEEAPAYNdhLNFYFACEGLKQQTDPEKVKQIIGAIYRFLRKSQLS-ISDDLRAQIKA 128
Cdd:cd08738    5 WGFGMDEALKDPVGREQFLKFLESEFSSEN--LRFWLAVEDLKKRPIREVPSRVQEIWQEFLAPGAPSaINLDSKSYDKT 82

                         90       100       110
                 ....*....|....*....|....*....|....*...
gi 195395026 129 IKSNEIPlSPHIYDPMQQHVEATIRDNIYPSFLCSEMY 166
Cdd:cd08738   83 TQNVKDP-GRYTFEDAQEHIYKLMKSDSYPRFIRSSAY 119