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 966955577 328 QRVKRWGFSFDEILKDQVGRDQFLRFLESEFSSENLRFWLAVQDLKKQPLQDVAKRVEEIWQEFLAPGAPSAINLDSHSY 407
Cdd:cd08737    1 QRVKRWGFSLDEVLKDPVGRDQFLRFLESEFSSENLRFWLAVQDLKKQPLQDVAKRVEEIWQEFLAPGAPSAINLDSHSY 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*
gi 966955577 408 EITSQNVKDGGRYTFEDAQEHIYKLMKSDSYARFLRSNAYQDLLL 452
Cdd:cd08737   81 EKTSQNVKDPGRYTFEDAQEHIYKLMKSDSYARFLRSNAYQDLLL 125

DEP (Dishevelled, Egl-10, and Pleckstrin) domain found in RGS (regulator of G-protein signaling) proteins of the subfamily R7. This subgroup contains RGS7, RGS6, RGS9 and RGS11. They share a common domain architecture, containing, beside the RGS domain, a DEP domain and a GGL (G-protein gamma subunit-like ) domain. RGS proteins are GTPase-activating (GAP) proteins of heterotrimeric G proteins by increasing the rate of GTP hydrolysis of the alpha subunit. The fungal homologs, like yeast Sst2, share a related common domain architecture, containing RGS and DEP domains. Sst2 has been identified as the principal regulator of mating pheromone signaling and recently the DEP domain of Sst2 has been shown to be necessary and sufficient to mediate receptor interaction.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966955577  31 DIITKMQDDKTGgVPIRTVKSFLSKIPSVVTGTDVVQWLMKNLSIEDPVEAIHLGSLIAAQGYIFPISDHVLTMKDDGTF 110
Cdd:cd04450    1 DSVGQMQDSEVG-VRMRTEKSFLTTVPYAFTGKAIVQWLMDCTDVVDPSEALEIAALFVKYGLITPVSDHRSLLKPDETL 79

                 ....*....
gi 966955577 111 YRFQAPYFW 119
Cdd:cd04450   80 YRFQAPYFW 88

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 966955577 328 QRVKRWGFSFDEILKDQVGRDQFLRFLESEFSSENLRFWLAVQDLKKQPLQDVAKRVEEIWQEFLAPGAPSAINLDSHSY 407
Cdd:cd08737    1 QRVKRWGFSLDEVLKDPVGRDQFLRFLESEFSSENLRFWLAVQDLKKQPLQDVAKRVEEIWQEFLAPGAPSAINLDSHSY 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*
gi 966955577 408 EITSQNVKDGGRYTFEDAQEHIYKLMKSDSYARFLRSNAYQDLLL 452
Cdd:cd08737   81 EKTSQNVKDPGRYTFEDAQEHIYKLMKSDSYARFLRSNAYQDLLL 125

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 966955577  336 SFDEILKDQVGRDQFLRFLESEFSSENLRFWLAVQDLKKQPLQD-VAKRVEEIWQEFLAPGAPSAINLDSHSYEITSQNV 414
Cdd:pfam00615   1 SFDSLLEDQPGRRLFRQFLESEFSEENLEFWLACEEFKKADPDEeRLKKAKEIYNEFLAPGSPKEINLDSDLREEIRENL 80

                          90       100       110
                  ....*....|....*....|....*....|....*..
gi 966955577  415 KDG-GRYTFEDAQEHIYKLMKSDSYARFLRSNAYQDL 450
Cdd:pfam00615  81 EKEpTRDLFDEAQAEVYELMEKDSYPRFLKSPLYLRL 117

DEP (Dishevelled, Egl-10, and Pleckstrin) domain found in RGS (regulator of G-protein signaling) proteins of the subfamily R7. This subgroup contains RGS7, RGS6, RGS9 and RGS11. They share a common domain architecture, containing, beside the RGS domain, a DEP domain and a GGL (G-protein gamma subunit-like ) domain. RGS proteins are GTPase-activating (GAP) proteins of heterotrimeric G proteins by increasing the rate of GTP hydrolysis of the alpha subunit. The fungal homologs, like yeast Sst2, share a related common domain architecture, containing RGS and DEP domains. Sst2 has been identified as the principal regulator of mating pheromone signaling and recently the DEP domain of Sst2 has been shown to be necessary and sufficient to mediate receptor interaction.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966955577  31 DIITKMQDDKTGgVPIRTVKSFLSKIPSVVTGTDVVQWLMKNLSIEDPVEAIHLGSLIAAQGYIFPISDHVLTMKDDGTF 110
Cdd:cd04450    1 DSVGQMQDSEVG-VRMRTEKSFLTTVPYAFTGKAIVQWLMDCTDVVDPSEALEIAALFVKYGLITPVSDHRSLLKPDETL 79

                 ....*....
gi 966955577 111 YRFQAPYFW 119
Cdd:cd04450   80 YRFQAPYFW 88

Domain found in Dishevelled, Egl-10, and Pleckstrin (DEP); The DEP domain is responsible for mediating intracellular protein targeting and regulation of protein stability in the cell. The DEP domain is present in a number of signaling molecules, including Regulator of G protein Signaling (RGS) proteins, and has been implicated in membrane targeting. New findings in yeast, however, demonstrate a major role for a DEP domain in mediating the interaction of an RGS protein to the C-terminal tail of a GPCR, thus placing RGS in close proximity with its substrate G protein alpha subunit.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 966955577   43 GVPIRTVKSFLSKIPSVVTGTDVVQWLMKNLSIEDPVEAIHLGSLIAAQGYIFPISDHVLTMKDDGTFYRF 113
Cdd:pfam00610   1 GVKLKDRRKHLKTYPNCFTGSEAVDWLMDNLEIITREEAVELGQLLLDQGLIHHVGDKHGLFKDSYYFYRF 71

G protein gamma subunit-like motifs, the alpha-helical G-gamma chain dimerizes with the G-beta propeller subunit as part of the heterotrimeric G-protein complex; involved in signal transduction via G-protein-coupled receptors

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 966955577 258 KEDIRKQITFLNTQIDRHCLKMSKVAESLIAYTEQYMEYDPLITPA-EPSNPWISDD 313
Cdd:cd00068    1 VDQLKKEVEQLRKELSRERLKVSKAAAELLKYCEQNAENDPLLTGPpSPSNPWIEKK 57

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 966955577 328 QRVKRWGFSFDEILKDQVGRDQFLRFLESEFSSENLRFWLAVQDLKKQPLQDVAKRVEEIWQEFLAPGAPSAINLDSHSY 407
Cdd:cd08737    1 QRVKRWGFSLDEVLKDPVGRDQFLRFLESEFSSENLRFWLAVQDLKKQPLQDVAKRVEEIWQEFLAPGAPSAINLDSHSY 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*
gi 966955577 408 EITSQNVKDGGRYTFEDAQEHIYKLMKSDSYARFLRSNAYQDLLL 452
Cdd:cd08737   81 EKTSQNVKDPGRYTFEDAQEHIYKLMKSDSYARFLRSNAYQDLLL 125

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 966955577 329 RVKRWGFSFDEILKDQVGRDQFLRFLESEFSSENLRFWLAVQDLKKQPLQDVAKRVEEIWQEFLAPGAPSAINLDSHSYE 408
Cdd:cd08738    1 RVKRWGFGMDEALKDPVGREQFLKFLESEFSSENLRFWLAVEDLKKRPIREVPSRVQEIWQEFLAPGAPSAINLDSKSYD 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|.
gi 966955577 409 ITSQNVKDGGRYTFEDAQEHIYKLMKSDSYARFLRSNAYQD 449
Cdd:cd08738   81 KTTQNVKDPGRYTFEDAQEHIYKLMKSDSYPRFIRSSAYQE 121

Regulator of G protein signaling (RGS) domain found in the RGS11 protein; The RGS (Regulator of G-protein Signaling) domain is an essential part of the RGS11 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 RGS9, 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. RGS11 is expressed exclusively in retinal ON-bipolar neurons in which it forms complexes with G-beta-5 and R7AP (RGS7 anchor protein ) and plays crucial roles in processing the light responses of retinal neurons.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966955577 329 RVKRWGFSFDEILKDQVGRDQFLRFLESEFSSENLRFWLAVQDLKKQPLQDVAKRVEEIWQEFLAPGAPSAINLDSHSYE 408
Cdd:cd08740    2 RVERWGFSFRELLNDPVGRKEFLDFLEKEFSAENLSFWEACEELRYGEQSKIPELVDSVYQQFLAPGATRWVNIDSKTME 81

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|...
gi 966955577 409 ITSQNVKDGGRYTFEDAQEHIYKLMKSDSYARFLRSNAYQDLL 451
Cdd:cd08740   82 RTLEGLKQPHRYVLDDAQMHIYMLMKKDSYPRFLKSDLYKNLL 124

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 966955577 329 RVKRWGFSFDEILKDQVGRDQFLRFLESEFSSENLRFWLAVQDLKKQPLQDVAKRVEEIWQEFLAPGAPSAINLDSHSYE 408
Cdd:cd08739    1 RVERWAFNFSELIRDPKGRQSFQLFLKKEFSGENLGFWEACEDLKYGDQSKVKEKAEEIYKLFLAPGARRWINIDGKTMD 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|.
gi 966955577 409 ITSQNVKDGGRYTFEDAQEHIYKLMKSDSYARFLRSNAYQD 449
Cdd:cd08739   81 ITVKGLKHPHRYVLDAAQTHIYMLMKKDSYARYLKSPIYKE 121

DEP (Dishevelled, Egl-10, and Pleckstrin) domain found in RGS (regulator of G-protein signaling) proteins of the subfamily R7. This subgroup contains RGS7, RGS6, RGS9 and RGS11. They share a common domain architecture, containing, beside the RGS domain, a DEP domain and a GGL (G-protein gamma subunit-like ) domain. RGS proteins are GTPase-activating (GAP) proteins of heterotrimeric G proteins by increasing the rate of GTP hydrolysis of the alpha subunit. The fungal homologs, like yeast Sst2, share a related common domain architecture, containing RGS and DEP domains. Sst2 has been identified as the principal regulator of mating pheromone signaling and recently the DEP domain of Sst2 has been shown to be necessary and sufficient to mediate receptor interaction.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966955577  31 DIITKMQDDKTGgVPIRTVKSFLSKIPSVVTGTDVVQWLMKNLSIEDPVEAIHLGSLIAAQGYIFPISDHVLTMKDDGTF 110
Cdd:cd04450    1 DSVGQMQDSEVG-VRMRTEKSFLTTVPYAFTGKAIVQWLMDCTDVVDPSEALEIAALFVKYGLITPVSDHRSLLKPDETL 79

                 ....*....
gi 966955577 111 YRFQAPYFW 119
Cdd:cd04450   80 YRFQAPYFW 88

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 966955577 306 SNPWISDDVALWdiEMSKEPSQQRVKRWGFSFDEILKDQVGRDQFLRFLESEFSSENLRFWLAVQDLKKQPLQDVakrVE 385
Cdd:cd08746   25 SYEFRAEGIPNC--EESPKPTLEEVCAWGQSFDKLMLTPAGRNAFREFLRTEFSEENMLFWMACEELKKEANKSV---IE 99

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 966955577 386 E----IWQEFLAPGAPSAINLDSHSYEITSQNVKDGGRYTFEDAQEHIYKLMKSDSYARFLRSNAYQD 449
Cdd:cd08746  100 EkariIYEDYISILSPKEVSLDSRVREVINRNMLEPSQHTFDDAQLQIYTLMHRDSYPRFMNSAIYKN 167

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 966955577 333 WGFSFDEILKDQVGRDQFLRFLESEFSSENLRFWLAVQDLKKQPLQD-VAKRVEEIWQEFLAPGAPSAINLDSHSYEITS 411
Cdd:cd08745    1 WAQSFDKLMKSPAGRNVFREFLRTEYSEENMLFWLACEELKAEANKHvIDEKARLIYEDYISILSPKEVSLDSRVREGIN 80

                         90       100       110
                 ....*....|....*....|....*....|....*..
gi 966955577 412 QNVKDGGRYTFEDAQEHIYKLMKSDSYARFLRSNAYQ 448
Cdd:cd08745   81 RKMQEPSSHTFDDAQLQIYTLMHRDSYPRFLNSPIYK 117

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 966955577 337 FDEILKDQVGRDQFLRFLESEFSSENLRFWLAVQDLKK-QPLQDVAKRVEEIWQEFLAPGAPSAINLDSHSYEITSQNVK 415
Cdd:cd08712    1 FDKLLSHKDGLEAFTRFLKTEFSEENIEFWIACEDYKKsKTPQQIHLKAKAIYEKFIQTDAPKEVNLDFHTKEVTTNSIE 80

                         90       100       110
                 ....*....|....*....|....*....|....
gi 966955577 416 DGGRYTFEDAQEHIYKLMKSDSYARFLRSNAYQD 449
Cdd:cd08712   81 QPTLTSFDAAQSRVYQLMEQDSYPRFLKSDIYLD 114

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 966955577 337 FDEILKDQVGRDQFLRFLESEFSSENLRFWLAVQDLKKQP-LQDVAKRVEEIWQEFLAPGAPSAINLDSHSyEITSQNVK 415
Cdd:cd08706    1 FERLLQDPVGVKYFTEFLKKEFSEENILFWQACEKFKKIPdKKQLVQEAREIYDTFLSSKASSPVNIDSQA-QLAEEMLE 79

                         90       100       110
                 ....*....|....*....|....*....|....
gi 966955577 416 DGGRYTFEDAQEHIYKLMKSDSYARFLRSNAYQD 449
Cdd:cd08706   80 EPHPDMFQKQQLQIFNLMKFDSYSRFLKSPLYQQ 113

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 966955577 337 FDEILKDQVGRDQFLRFLESEFSSENLRFWLAVQDLKKQPLQDVAKRVEEIWQEFLAPGAPSAINLDSHSYEITSQNVKD 416
Cdd:cd08715    1 LEKLLASQTGQNVFRSFLKSEFSEENIEFWLACEDYKKTESDLLPCKAEEIYKEFVQSDAAKQINIDFRTRESTAKKIKA 80

                         90       100       110
                 ....*....|....*....|....*....|....
gi 966955577 417 GGRYTFEDAQEHIYKLMKSDSYARFLRSNAYQDL 450
Cdd:cd08715   81 PTPTCFDEAQKVIYILMERDSYPRFLKSDIYLNL 114

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 966955577 326 SQQRVKRWGFSFDEILKDQVGRDQFLRFLESEFSSENLRFWLAVQDLKK-QPLQDVAKRVEEIWQEFLAPGAPSAINLDS 404
Cdd:cd08711    1 STEEATRWADSFDVLLSHKYGVAAFRAFLKTEFSEENLEFWLACEEFKKtRSTAKLVSKAHRIFEEFVDVQAPREVNIDF 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*
gi 966955577 405 HSYEITSQNVKDGGRYTFEDAQEHIYKLMKSDSYARFLRSNAYQD 449
Cdd:cd08711   81 QTREATRKNLQEPSLTCFDQAQGKVHSLMEKDSYPRFLRSKMYLD 125

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 966955577 327 QQRVKRWGFSFDEILKDQVGRDQFLRFLESEFSSENLRFWLAVQDLKKQPLQDVAKRVEE---IWQEFLAPGAPSAINLD 403
Cdd:cd08743    1 EKSVASWAVSFERLLQDPLGVEYFTEFLKKEFSAENVNFWKACERFQQIPASDTQQLAQEarkIYNEFLSSSSQSPVNID 80

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|
gi 966955577 404 SHSYeITSQNVKDGGRYTFEDAQEHIYKLMKSDSYARFLRSNAYQDLLLA 453
Cdd:cd08743   81 QQAW-IGEDMLATPSPDMFRAQQLQIFNLMKFDSYARFVKSPLYQDCLLA 129

Domain found in Dishevelled, Egl-10, and Pleckstrin; Domain of unknown function present in signalling proteins that contain PH, rasGEF, rhoGEF, rhoGAP, RGS, PDZ domains. DEP domain in Drosophila dishevelled is essential to rescue planar polarity defects and induce JNK signalling (Cell 94, 109-118).

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 966955577    41 TGGVPIRTVKSFLSKIPSVVTGTDVVQWLMKNLSIEDPVEAIHLGSLIAAQGYIFPISD-HVLTMKDDGTFYRFQ 114
Cdd:smart00049   2 ETGLKLRDRKYFLKTYPNCFTGSELVDWLMDNLEIIDREEAVHLGQLLLDEGLIHHVNGpNKHTFKDSKALYRFT 76

Domain found in Dishevelled, Egl-10, and Pleckstrin (DEP); The DEP domain is responsible for mediating intracellular protein targeting and regulation of protein stability in the cell. The DEP domain is present in a number of signaling molecules, including Regulator of G protein Signaling (RGS) proteins, and has been implicated in membrane targeting. New findings in yeast, however, demonstrate a major role for a DEP domain in mediating the interaction of an RGS protein to the C-terminal tail of a GPCR, thus placing RGS in close proximity with its substrate G protein alpha subunit.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 966955577   43 GVPIRTVKSFLSKIPSVVTGTDVVQWLMKNLSIEDPVEAIHLGSLIAAQGYIFPISDHVLTMKDDGTFYRF 113
Cdd:pfam00610   1 GVKLKDRRKHLKTYPNCFTGSEAVDWLMDNLEIITREEAVELGQLLLDQGLIHHVGDKHGLFKDSYYFYRF 71

Regulator of G protein signaling (RGS) domain found in the RGS10 protein; RGS (Regulator of G-protein Signaling) domain is an essential part of the RGS10 protein. RGS10 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. RGS10 belong to the R12 RGS subfamily, which includes RGS12 and RGS14, all of which are highly selective for G-alpha-i1 over G-alpha-q. RGS10 exists in 2 splice isoforms. RGS10A is specifically expressed in osteoclasts and is a key component in the RANKL signaling mechanism for osteoclast differentiation, whereas RGS10B expressed in brain and in immune tissues and has been implicated in diverse processes including: promoting of dopaminergic neuron survival via regulation of the microglial inflammatory response, modulation of presynaptic and postsynaptic G-protein signalling, as well as a possible role in regulation of gene expression.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966955577 337 FDEILKDQVGRDQFLRFLESEFSSENLRFWLAVQDLKK-QPLQDVAKRVEEIWQEFLAPGAPSAINLDSHSyEITSQNVK 415
Cdd:cd08741    1 LENLLEDPEGVKRFREFLKKEFSEENVLFWLACEDFKKmQDKTQMQEKAKEIYMTFLSSKASSQVNVEGQS-RLNEKILE 79

                         90       100       110
                 ....*....|....*....|....*....|..
gi 966955577 416 DGGRYTFEDAQEHIYKLMKSDSYARFLRSNAY 447
Cdd:cd08741   80 EPHPLMFQKLQDQIFNLMKYDSYSRFLKSDLF 111

G protein gamma subunit-like motifs, the alpha-helical G-gamma chain dimerizes with the G-beta propeller subunit as part of the heterotrimeric G-protein complex; involved in signal transduction via G-protein-coupled receptors

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 966955577 258 KEDIRKQITFLNTQIDRHCLKMSKVAESLIAYTEQYMEYDPLITPA-EPSNPWISDD 313
Cdd:cd00068    1 VDQLKKEVEQLRKELSRERLKVSKAAAELLKYCEQNAENDPLLTGPpSPSNPWIEKK 57

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 966955577 337 FDEILKDQVGRDQFLRFLESEFSSENLRFWLAVQDLKKQPLQ-DVAKRVEEIWQEFLAPGAPSAINLDSHSYEITSQNVK 415
Cdd:cd08716    1 FENLMATKYGPIIYATYLKTEHSDENIEFWLACETYKKIASQrKRISMARKLFASYIQPQAPREINIDSPTRKAIIRNIQ 80

                         90       100       110
                 ....*....|....*....|....*....|...
gi 966955577 416 DGGRYTFEDAQEHIYKLMKSDSYARFLRSNAYQ 448
Cdd:cd08716   81 EPTQSCFDEAQRIVYMHMERDSYPRFLESKFYQ 113

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 966955577 338 DEILKDQVGRDQFLRFLESEFSSENLRFWLAVQDLKK--QPLQDVAKRVEE-----------------IWQEFLAPGAPS 398
Cdd:cd08708    3 DKILKDPGLRYLFREHLEKEFCEENLSFYLEVKEFLKkmTILSKLLDFKSSqaadedldreslaqayhIYNTYLAPGSPC 82

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 966955577 399 AINLDSHSYE-ITS--------QNV-----KDGGRYTFEDAQEHIYK-LMKSDSYARFLRSNAY 447
Cdd:cd08708   83 ELNIDHNLRNrITTimtekivgEDDsmaesLQGVEALFEEAQNAVFKpLMAGDSVPKFLKQPEY 146

Uncharacterized Regulator of G protein Signaling (RGS) domain subfamily, child 1; These uncharacterized RGS-like domains consists largely of hypothetical proteins. 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 role as GTPase activating proteins (GAPs) of the heterotrimeric G-protein G-alpha-subunits. As a major G-protein regulator, the RGS domain containing proteins that are involved in many crucial cellular processes. RGS proteins play critical regulatory role as GTPase activating proteins (GAPs) of the heterotrimeric G-protein G-alpha-subunits. 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. Several RGS proteins can fine-tune immune responses, while others play an important role in neuronal signal modulation. Some RGS proteins are the principal elements needed for proper vision.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966955577 349 QFLRFLESEFSSENLRFWLAVQDLKKQPLQDVAK-RVEEIWQEFLAPGAPSAINLDS-------HSYEITSQNVKDGGRY 420
Cdd:cd08734    7 LFGFSAESDFSGENLSFLTLVKEYKRLSNPAEKFtLASKIYKEFISSESPFQINISSamlrrldNDFELLTGAFANVDSG 86

                         90       100
                 ....*....|....*....|...
gi 966955577 421 TFEDAQEHIYKLMKSDSYARFLR 443
Cdd:cd08734   87 LNTPFNEEISKIEASDLYPAFVK 109

DEP (Dishevelled, Egl-10, and Pleckstrin) domain 1 found in P-Rex-like proteins. The P-Rex family is the guanine-nucleotide exchange factor (GEF) for the small GTPase Rac that contains an N-terminal RhoGEF domain, two DEP and PDZ domains. Rac-GEF activity is stimulated by phosphatidylinositol (3,4,5)-trisphosphate (PtdIns(3,4,5)P3), a lipid second messenger, and by the G beta-gamma subunits of heterotrimeric G proteins. The DEP domains are not involved in mediating these stimuli, but may be of importance for basal and stimulated levels Rac-GEF activity.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 966955577  46 IRTVKSFLSKIPSVVTGTDVVQWLMKNLSIEDPVEAIHLGSLIAAQGYIFPISDHvLTMKDDGTFYRF 113
Cdd:cd04439   15 IKDRRRKLSTFPKCFLGNEFVSWLLEIGEISKPEEGVNLGQALLENGIIHHVSDK-HQFKNEQVLYRF 81

Regulator of G protein signaling (RGS) domain found in the Sorting Nexin14 (SNX14) protein; The RGS (Regulator of G-protein Signaling) domain is an essential part of the SNX14 (Sorting Nexin14) 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. SNX14 is believed to regulates membrane trafficking in motor neurons.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966955577 340 ILKDQVGRDQFLRFLESEFSSENLRFWLAVQD---------LKKQPLQDVAKRVEEIWQEFLAPGAPSAINLDSHSYEIT 410
Cdd:cd08722    1 ILDDQRLLFPFMQFLKEEGAVHLLQFCLTVEDfnrrilnpdLTDEEKQSLHKEAQEIYKTYFLPEAPDRIHFPPDIVEEI 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*.
gi 966955577 411 SQNVKDG---------GRYTFEdAQEHIYKLMKSDSYARFLRSNAY 447
Cdd:cd08722   81 KQILEGGpekivklrtSRPLFE-AYEHVYSLLESVFCPLFCHSDEY 125

DEP (Dishevelled, Egl-10, and Pleckstrin) domain found in fungal RhoGAP (GTPase-activator protein) Rgd2-like proteins. Rgd2-like proteins share a common domain architecture, containing, beside the RhoGAP domain, a DEP and a FCH (Fes/CIP4 homology) domain. Yeast Rgd2 is a GAP protein for Cdc42 and Rho5.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 966955577  35 KMQDDKtggVPIrtvksfLSKIPSVVTGTDVVQWLMKNLSIEDPVEAIHLGSLIAAQGYI 94
Cdd:cd04436   14 PLADYK---VPI------LGTYQNTSSGSEIVSWLQENMPEKDLDAAEAFGQDLLNQGFL 64