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 40548310  71 FTNLIKNDDGRKAFASFLQSEYSQENIEFWVACEDFKQTP-ADKMNLKARNIFERYIEADSPREVNLDSVTREQTRKNLE 149
Cdd:cd08714   1 LENLINHECGLAAFKAFLKSEYSEENIDFWVSCEDYKKTKsPSKLSPKARKIYEEFISVQATKEVNLDSCTREETSRNML 80

                        90       100       110
                ....*....|....*....|....*....|....
gi 40548310 150 MCDVSCFDEAQSKIFTLMEKDSYRRFLRSRLFLE 183
Cdd:cd08714  81 EPTISCFDEAQKKIFTLMEKDSYRRFLKSRFYLD 114

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 40548310  71 FTNLIKNDDGRKAFASFLQSEYSQENIEFWVACEDFKQTP-ADKMNLKARNIFERYIEADSPREVNLDSVTREQTRKNLE 149
Cdd:cd08714   1 LENLINHECGLAAFKAFLKSEYSEENIDFWVSCEDYKKTKsPSKLSPKARKIYEEFISVQATKEVNLDSCTREETSRNML 80

                        90       100       110
                ....*....|....*....|....*....|....
gi 40548310 150 MCDVSCFDEAQSKIFTLMEKDSYRRFLRSRLFLE 183
Cdd:cd08714  81 EPTISCFDEAQKKIFTLMEKDSYRRFLKSRFYLD 114

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 40548310     70 SFTNLIKNDDGRKAFASFLQSEYSQENIEFWVACEDFKQTPAD-KMNLKARNIFERYIEADSPREVNLDSVTREQTRKNL 148
Cdd:smart00315   1 SLESLLSDPIGRLLFREFLESEFSEENLEFWLAVEEFKKAEDDeERIAKAREIYDKFLSPNAPKEVNLDSDLREKIEENL 80

                           90       100       110
                   ....*....|....*....|....*....|....*...
gi 40548310    149 EMCDVS--CFDEAQSKIFTLMEKDSYRRFLRSRLFLEL 184
Cdd:smart00315  81 ESEEPPpdLFDEAQREVYELLEKDSFPRFLESDYYLRF 118

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 40548310  71 FTNLIKNDDGRKAFASFLQSEYSQENIEFWVACEDFKQTP-ADKMNLKARNIFERYIEADSPREVNLDSVTREQTRKNLE 149
Cdd:cd08714   1 LENLINHECGLAAFKAFLKSEYSEENIDFWVSCEDYKKTKsPSKLSPKARKIYEEFISVQATKEVNLDSCTREETSRNML 80

                        90       100       110
                ....*....|....*....|....*....|....
gi 40548310 150 MCDVSCFDEAQSKIFTLMEKDSYRRFLRSRLFLE 183
Cdd:cd08714  81 EPTISCFDEAQKKIFTLMEKDSYRRFLKSRFYLD 114

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 40548310    70 SFTNLIKNDDGRKAFASFLQSEYSQENIEFWVACEDFKQT-PADKMNLKARNIFERYIEADSPREVNLDSVTREQTRKNL 148
Cdd:pfam00615   1 SFDSLLEDQPGRRLFRQFLESEFSEENLEFWLACEEFKKAdPDEERLKKAKEIYNEFLAPGSPKEINLDSDLREEIRENL 80

                          90       100       110
                  ....*....|....*....|....*....|....*..
gi 40548310   149 EM-CDVSCFDEAQSKIFTLMEKDSYRRFLRSRLFLEL 184
Cdd:pfam00615  81 EKePTRDLFDEAQAEVYELMEKDSYPRFLKSPLYLRL 117

Regulator of G protein signaling (RGS) domain found in the RGS16 protein; The RGS (Regulator of G-protein Signaling) domain is an essential part of the RGS16 protein. RGS16 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. RGS16 is a member of the R4/RGS subfamily and interacts with neuronal G-alpha0. RGS16 expression is upregulated by IL-17 of the NF-kappaB signaling pathway in autoimmune B cells.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 40548310  71 FTNLIKNDDGRKAFASFLQSEYSQENIEFWVACEDFKQT-PADKMNLKARNIFERYIEADSPREVNLDSVTREQTRKNLE 149
Cdd:cd08710   1 FDLLLNSKNGVAAFHAFLKTEFSEENLEFWLACEEFKKIrSATKLASRAHHIFEEFIRSEAPKEVNIDHETRELTRTNLQ 80

                        90       100
                ....*....|....*....|....*....
gi 40548310 150 MCDVSCFDEAQSKIFTLMEKDSYRRFLRS 178
Cdd:cd08710  81 AATTSCFDVAQGKTRTLMEKDSYPRFLKS 109

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 40548310  63 ETEKWKTSFTNLIKNDDGRKAFASFLQSEYSQENIEFWVACEDFKQTPAD-KMNLKARNIFERYIEADSPREVNLDSVTR 141
Cdd:cd08711   4 EATRWADSFDVLLSHKYGVAAFRAFLKTEFSEENLEFWLACEEFKKTRSTaKLVSKAHRIFEEFVDVQAPREVNIDFQTR 83

                        90       100       110       120
                ....*....|....*....|....*....|....*....|..
gi 40548310 142 EQTRKNLEMCDVSCFDEAQSKIFTLMEKDSYRRFLRSRLFLE 183
Cdd:cd08711  84 EATRKNLQEPSLTCFDQAQGKVHSLMEKDSYPRFLRSKMYLD 125

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 40548310  67 WKTSFTNLIKNDDGRKAFASFLQSEYSQENIEFWVACEDFKQ-TPADKMNLKARNIFERYIEADSPREVNLDSVTREQTR 145
Cdd:cd08718   1 WAQSFDKLMKSPAGRNVFREFLRTEYSEENMLFWLACEELKKeANKHVIEEKARLIYEDYISILSPKEVSLDSRVREVIN 80

                        90       100       110
                ....*....|....*....|....*....|....*.
gi 40548310 146 KNLEMCDVSCFDEAQSKIFTLMEKDSYRRFLRSRLF 181
Cdd:cd08718  81 RNMLEPSPHTFDDAQLQIYTLMHRDSYPRFLNSAIY 116

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 40548310  74 LIKNDDGRKAFASFLQSEYSQENIEFWVACEDFKQTPAD-KMNLKARNIFERYIEADSPREVNLDSVTREQTRKNLEMCD 152
Cdd:cd08717   4 LLQNSYGLASFKSFLKSEFSEENIEFWEACEDYKKTKSPlKMATKAKKIYEEFIQTEAPKEVNIDHFTKDVTMKNLVEPS 83

                        90       100       110
                ....*....|....*....|....*....|.
gi 40548310 153 VSCFDEAQSKIFTLMEKDSYRRFLRSRLFLE 183
Cdd:cd08717  84 SSSFDLAQKRIFALMEKDSLPRFVRSEFYQE 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 40548310  71 FTNLIKNDDGRKAFASFLQSEYSQENIEFWVACEDFKQTPA-DKMNLKARNIFERYIEADSPREVNLDSVTREQTRKNLE 149
Cdd:cd08709   1 FDELLASKYGVAAFRAFLKSEFSEENIEFWLACEDFKKTKSpQKLTSKAKKIYTDFIEKEAPKEINIDFQTKTLIAQNIQ 80

                        90       100       110
                ....*....|....*....|....*....|....
gi 40548310 150 MCDVSCFDEAQSKIFTLMEKDSYRRFLRSRLFLE 183
Cdd:cd08709  81 EATSGCFTAAQKRVYSLMENNSYPRFLESEFYQE 114

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 40548310  80 GRKAFASFLQSEYSQENIEFWVACEDFKQTPAD--KMNLKARNIFERYIEADSPREVNLDSVTREQTRKNL--EMCDVSC 155
Cdd:cd07440   6 GLEYFRQFLKSEHCEENLEFWLAVEKFKKTTSSdeELKSKAKEIYDKYISKDAPKEINIPESIREEIEENLeePYPDPDC 85

                        90       100
                ....*....|....*....|....*...
gi 40548310 156 FDEAQSKIFTLMEKDSYRRFLRSRLFLE 183
Cdd:cd07440  86 FDEAQEHILNLLEKDSYPRFLKSDLYLK 113

Regulator of G protein signaling (RGS) domain found in the RGS13 protein; The RGS (Regulator of G-protein Signaling) domain is an essential part of the RGS13 protein. RGS13 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. RGS13 is predominantly expressed in T and B lymphocytes and in mast cells, and plays a role in adaptive immune responses. RGS13 also found in Rgs13, which is also expressed in dendritic cells and in neuroendocrine cells of the thymus, gastrointestinal, and respiratory tracts. Outside of the GPCR pathway, RGS5 interacts with the PIP3 protein.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 40548310  71 FTNLIKNDDGRKAFASFLQSEYSQENIEFWVACEDFKQTPADKMNL-KARNIFERYIEADSPREVNLDSVTREQTRKNLE 149
Cdd:cd08716   1 FENLMATKYGPIIYATYLKTEHSDENIEFWLACETYKKIASQRKRIsMARKLFASYIQPQAPREINIDSPTRKAIIRNIQ 80

                        90       100       110
                ....*....|....*....|....*....|..
gi 40548310 150 MCDVSCFDEAQSKIFTLMEKDSYRRFLRSRLF 181
Cdd:cd08716  81 EPTQSCFDEAQRIVYMHMERDSYPRFLESKFY 112

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 40548310  65 EKWKTSFTNLIKNDDGRKAFASFLQSEYSQENIEFWVACEDFKQTPADKMNLKARNIFERYIEADSPREVNLDSVTREQT 144
Cdd:cd08737   4 KRWGFSLDEVLKDPVGRDQFLRFLESEFSSENLRFWLAVQDLKKQPLQDVAKRVEEIWQEFLAPGAPSAINLDSHSYEKT 83

                        90       100       110       120
                ....*....|....*....|....*....|....*....|
gi 40548310 145 RKNLEMCDVSCFDEAQSKIFTLMEKDSYRRFLRSRLFLEL 184
Cdd:cd08737  84 SQNVKDPGRYTFEDAQEHIYKLMKSDSYARFLRSNAYQDL 123

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 40548310  67 WKTSFTNLIKNDDGRKAFASFLQSEYSQENIEFWVACEDFKQTPADK-MNLKARNIFERYIEADSPREVNLDSVTREQTR 145
Cdd:cd08744   1 WSQNFDKMMKTPAGRNLFREFLRTEYSEENLLFWLACEDLKKEQNKKvIEEKARLIYEDYISILSPKEVSLDSRVREVIN 80

                        90       100       110
                ....*....|....*....|....*....|....*.
gi 40548310 146 KNLEMCDVSCFDEAQSKIFTLMEKDSYRRFLRSRLF 181
Cdd:cd08744  81 RNLLDPNPHMYEDAQLQIYTLMHRDSFPRFLNSQIY 116

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 40548310  65 EKWKTSFTNLIKNDDGRKAFASFLQSEYSQENIEFWVACEDFKQTPADKMNLKARNIFERYIEADSPREVNLDSVTREQT 144
Cdd:cd08738   3 KRWGFGMDEALKDPVGREQFLKFLESEFSSENLRFWLAVEDLKKRPIREVPSRVQEIWQEFLAPGAPSAINLDSKSYDKT 82

                        90       100       110
                ....*....|....*....|....*....|....*....
gi 40548310 145 RKNLEMCDVSCFDEAQSKIFTLMEKDSYRRFLRSRLFLE 183
Cdd:cd08738  83 TQNVKDPGRYTFEDAQEHIYKLMKSDSYPRFIRSSAYQE 121

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 40548310  67 WKTSFTNLIKNDDGRKAFASFLQSEYSQENIEFWVACEDFKQTPAD---KMNLKARNIFERYIEADSPREVNLDSVTReQ 143
Cdd:cd08743   7 WAVSFERLLQDPLGVEYFTEFLKKEFSAENVNFWKACERFQQIPASdtqQLAQEARKIYNEFLSSSSQSPVNIDQQAW-I 85

                        90       100       110       120
                ....*....|....*....|....*....|....*....|
gi 40548310 144 TRKNLEMCDVSCFDEAQSKIFTLMEKDSYRRFLRSRLFLE 183
Cdd:cd08743  86 GEDMLATPSPDMFRAQQLQIFNLMKFDSYARFVKSPLYQD 125

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 40548310  74 LIKNDDGRKAFASFLQSEYSQENIEFWVACEDFKQ-TPADKMNLK-ARNIFERYIEADSPREVNLDSVTREQTRKNL--E 149
Cdd:cd08707   4 LLDDQDGIELFRTYLEQEGCADLLDFWFACNGFRKmSDSEEKRSKlAKAIYRRYIKDNGIVSRQLKPATKSFIKECIkkQ 83

                        90       100       110
                ....*....|....*....|....*....|....
gi 40548310 150 MCDVSCFDEAQSKIFTLMEKDSYRRFLRSRLFLE 183
Cdd:cd08707  84 QLDPAMFDQAQTEIQTTMEENTYPSFLKSDIYLE 117

Regulator of G protein signaling (RGS) domain 1 found in the A-kinase anchoring protein, D-AKAP2; The RGS (Regulator of G-protein Signaling) domain is an essential part of the D-AKAP2 (A-kinase anchoring protein), a member 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 regulate many aspects of embryonic development such as glial differentiation, embryonic axis formation, skeletal and muscle development, cell migration during early embryogenesis, as well as apoptosis, cell proliferation, and modulation of cardiac development. D-AKAP2 contains two RGS domains which play an important role in spatiotemporal localization of cAMP-dependent PKA (cyclic AMP-dependent protein kinase) that regulates many different signaling pathways by phosphorylation of target proteins. This cd contains the first RGS domain.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 40548310 118 ARNIFERYIEADSPREVNLDSVTREQTRKNL----EMCDVSCFDEAQSKIFTLMEKDSYRRFLRSRLF 181
Cdd:cd08735 102 AVSIYTKYISPDAAKPIPITEEIRNDIVAKIcgedGQVDPNCFVEAQSFVFSAMEQDHFTEFLRSHFF 169

Regulator of G protein signaling (RGS) domain 2 found in the A-kinase anchoring protein, D-AKAP2; The RGS (Regulator of G-protein Signaling) domain is an essential part of the D-AKAP2 (A-kinase anchoring protein), a member 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 regulate many aspects of embryonic development such as glial differentiation, embryonic axis formation, skeletal and muscle development, cell migration during early embryogenesis, as well as apoptosis, cell proliferation, and modulation of cardiac development. D-AKAP2 contains two RGS domains which play an important role in spatiotemporal localization of cAMP-dependent PKA (cyclic AMP-dependent protein kinase) that regulates many different signaling pathways by phosphorylation of target proteins. This cd contains the second RGS domain.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 40548310  77 NDDGRKAFASFLQSEYSQENIEFWVACEDFKQTPADKMNL--------KARNIFERYIEADSPREVNLDSVTREQTRKNL 148
Cdd:cd08721   4 CESALFYFMEYMEQEGARNLLQFWLAADNFQSQLAAKEGQydgqqaqnDAMIIYDKYFSLQATEPLGFDDKTRLEVESNI 83

                        90       100       110
                ....*....|....*....|....*....|....*...
gi 40548310 149 emCD-----VSCFDEAQSKIFTLMEKDSYRRFLRSRLF 181
Cdd:cd08721  84 --CReggplPSCFEAPLLQALTTLEQHYLPGFLSSQLY 119

Regulator of G protein signaling (RGS) domain found in the Sorting Nexin 25 (SNX25) protein; The RGS (Regulator of G-protein Signaling) domain is an essential part of the SNX25 (Sorting Nexin 25) protein, a member 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 regulate many aspects of embryonic development such as glial differentiation, embryonic axis formation, skeletal and muscle development, cell migration during early embryogenesis, as well as apoptosis, cell proliferation, and modulation of cardiac development. SNX25 is a member of the Dopamine receptors (DAR) signalplex and regulates the trafficking of D1 and D2 DARs.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 40548310  74 LIKNDDGRKAFASFLQSEYSQENIEFWVACEDFKQtpADKMNLK--ARNIFERYIeADSPREVNLDsvtrEQTRKNLEMC 151
Cdd:cd08720   1 ILANVFGRKYLSQFLERMDSQALIGFWEAVEELRS--ANKSEWHqlGAEIFYTFI-VEPTAEIKVD----KSLRKRIEQF 73

                        90       100       110
                ....*....|....*....|....*....|....*
gi 40548310 152 -----DVSCFDEAQSKIFTLMEKDSYRRFLRSRLF 181
Cdd:cd08720  74 llgdkGPEVFYEVQENVVETLEEKYYPSFVVSDQY 108

Regulator of G protein signaling (RGS) domain found in the FLBA (Fluffy Low BrlA) protein; The RGS (Regulator of G-protein Signaling) domain is an essential part of the FLBA (Fluffy Low BrlA) protein. FLBA 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). 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 a critical regulatory role as GTPase activating proteins (GAPs) of the heterotrimeric G-protein G-alpha-subunits. Deactivation of the G-protein signaling controlled by the RGS domain accelerates the 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 thereby inhibition of downstream activity. As a major G-protein regulator, RGS domain containing proteins are involved in many crucial cellular processes. The RGS domain of the FLBA protein antagonizes G protein signaling to block proliferation and allow development. It is required for control of mycelial proliferation and activation of asexual sporulation in yeast.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 40548310  75 IKNDDG-RKAFASFLQSEYSQENIEFWVACEDF-------KQTPADKMNLK------------ARNIFERYIEADSPREV 134
Cdd:cd08708   5 ILKDPGlRYLFREHLEKEFCEENLSFYLEVKEFlkkmtilSKLLDFKSSQAadedldreslaqAYHIYNTYLAPGSPCEL 84

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*...
gi 40548310 135 NLDSVTREQTRKNL----EMCDVSCFD----------EAQSKIF-TLMEKDSYRRFLR 177
Cdd:cd08708  85 NIDHNLRNRITTIMtekiVGEDDSMAEslqgvealfeEAQNAVFkPLMAGDSVPKFLK 142