G protein gamma subunit-like motifs;

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1765945264   85 DELQQQIKYWQIQLDRHRLKMSKVADSLLSYTEQYLEYDPFLLPPDPS-NPWLSDDTTFWEL 145
Cdd:smart00224   2 DQLRKEVEQLRKELSRERIKVSKAAEELLAYCEQHAEEDPLLTGPPPSkNPFIEDKTSCWIL 63

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 1765945264 164 DEALKDPVGREQFLKFLESEFSSENLRFWLAVEDLKK-RPIKEVPSRVQEIWQEFLAPGAPSAINLDSKSYDKTTQNV-K 241
Cdd:pfam00615   3 DSLLEDQPGRRLFRQFLESEFSEENLEFWLACEEFKKaDPDEERLKKAKEIYNEFLAPGSPKEINLDSDLREEIRENLeK 82

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 1765945264 242 EPGRYTFEDAQEHIYKLMKSDSYPRFIRSSAYQEL 276
Cdd:pfam00615  83 EPTRDLFDEAQAEVYELMEKDSYPRFLKSPLYLRL 117

G protein gamma subunit-like motifs;

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1765945264   85 DELQQQIKYWQIQLDRHRLKMSKVADSLLSYTEQYLEYDPFLLPPDPS-NPWLSDDTTFWEL 145
Cdd:smart00224   2 DQLRKEVEQLRKELSRERIKVSKAAEELLAYCEQHAEEDPLLTGPPPSkNPFIEDKTSCWIL 63

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 1765945264  85 DELQQQIKYWQIQLDRHRLKMSKVADSLLSYTEQYLEYDPFLLPPD-PSNPWLSDD 139
Cdd:cd00068     2 DQLKKEVEQLRKELSRERLKVSKAAAELLKYCEQNAENDPLLTGPPsPSNPWIEKK 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 1765945264 154 QRVKRWGFGMDEALKDPVGREQFLKFLESEFSSENLRFWLAVEDLKKRPIKEVPSRVQEIWQEFLAPGAPSAINLDSKSY 233
Cdd:cd08737     1 QRVKRWGFSLDEVLKDPVGRDQFLRFLESEFSSENLRFWLAVQDLKKQPLQDVAKRVEEIWQEFLAPGAPSAINLDSHSY 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 1765945264 234 DKTTQNVKEPGRYTFEDAQEHIYKLMKSDSYPRFIRSSAYQELL 277
Cdd:cd08737    81 EKTSQNVKDPGRYTFEDAQEHIYKLMKSDSYARFLRSNAYQDLL 124

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 1765945264 155 RVKRWGFGMDEALKDPVGREQFLKFLESEFSSENLRFWLAVEDLKKRPIKEVPSRVQEIWQEFLAPGAPSAINLDSKSYD 234
Cdd:cd08740     2 RVERWGFSFRELLNDPVGRKEFLDFLEKEFSAENLSFWEACEELRYGEQSKIPELVDSVYQQFLAPGATRWVNIDSKTME 81

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|...
gi 1765945264 235 KTTQNVKEPGRYTFEDAQEHIYKLMKSDSYPRFIRSSAYQELL 277
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 1765945264 155 RVKRWGFGMDEALKDPVGREQFLKFLESEFSSENLRFWLAVEDLKKRPIKEVPSRVQEIWQEFLAPGAPSAINLDSKSYD 234
Cdd:cd08739     1 RVERWAFNFSELIRDPKGRQSFQLFLKKEFSGENLGFWEACEDLKYGDQSKVKEKAEEIYKLFLAPGARRWINIDGKTMD 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 1765945264 235 KTTQNVKEPGRYTFEDAQEHIYKLMKSDSYPRFIRSSAYQE 275
Cdd:cd08739    81 ITVKGLKHPHRYVLDAAQTHIYMLMKKDSYARYLKSPIYKE 121

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 1765945264 167 LKDPVGREQFLKFLESEFSSENLRFWLAVEDLKKRPIK--EVPSRVQEIWQEFLAPGAPSAINLDSKSYDKTTQNVKEPG 244
Cdd:cd07440     1 LRDPYGLEYFRQFLKSEHCEENLEFWLAVEKFKKTTSSdeELKSKAKEIYDKYISKDAPKEINIPESIREEIEENLEEPY 80

                          90       100       110
                  ....*....|....*....|....*....|...
gi 1765945264 245 --RYTFEDAQEHIYKLMKSDSYPRFIRSSAYQE 275
Cdd:cd07440    81 pdPDCFDEAQEHILNLLEKDSYPRFLKSDLYLK 113

Regulator of G protein signaling (RGS) domain found in the RGS3 protein; The RGS (Regulator of G-protein Signaling) domain is an essential part of the RGS3 protein. RGS3 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. As a major G-protein regulator, RGS domain containing proteins are involved in many crucial cellular processes. RGS3 induces apoptosis when overexpressed and is involved in cell migration through interaction with the Ephrin receptor. RGS3 exits as several splice isoforms and interacts with neuroligin, estrogen receptor-alpha, and 14-3-3 outside of the GPCR pathways.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1765945264 172 GREQFLKFLESEFSSENLRFWLAVEDLKK-RPIKEVPSRVQEIWQEFLAPGAPSAINLDSKSYDKTTQNVKEPGRYTFED 250
Cdd:cd08713    10 GLAVFRAFLQTEFSEENLEFWLACEEYKKiKSQSKMASRAKKIFAEYIAIQSCKEVNLDSYTREHTKENLQNPTRGCFDL 89

                          90       100
                  ....*....|....*....|....*
gi 1765945264 251 AQEHIYKLMKSDSYPRFIRSSAYQE 275
Cdd:cd08713    90 AQKRIYGLMEKDSYPRFLRSDLYQD 114

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1765945264 163 MDEALKDPVGREQFLKFLESEFSSENLRFWLAVEDLKKRPIKEVPSRVQEIWQEFLAPGAPSAINLDSKSYDKTTQNVKE 242
Cdd:cd08715     1 LEKLLASQTGQNVFRSFLKSEFSEENIEFWLACEDYKKTESDLLPCKAEEIYKEFVQSDAAKQINIDFRTRESTAKKIKA 80

                          90       100       110
                  ....*....|....*....|....*....|....
gi 1765945264 243 PGRYTFEDAQEHIYKLMKSDSYPRFIRSSAYQEL 276
Cdd:cd08715    81 PTPTCFDEAQKVIYILMERDSYPRFLKSDIYLNL 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 1765945264 164 DEALKDPVGREQFLKFLESEFSSENLRFWLAVEDLKK-RPIKEVPSRVQEIWQEFLAPGAPSAINLDSKSYDKTTQNVKE 242
Cdd:cd08709     2 DELLASKYGVAAFRAFLKSEFSEENIEFWLACEDFKKtKSPQKLTSKAKKIYTDFIEKEAPKEINIDFQTKTLIAQNIQE 81

                          90       100       110
                  ....*....|....*....|....*....|...
gi 1765945264 243 PGRYTFEDAQEHIYKLMKSDSYPRFIRSSAYQE 275
Cdd:cd08709    82 ATSGCFTAAQKRVYSLMENNSYPRFLESEFYQE 114

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 1765945264 159 WGFGMDEALKDPVGREQFLKFLESEFSSENLRFWLAVEDLKKRPIKE-VPSRVQEIWQEFLAPGAPSAINLDSKSYDKTT 237
Cdd:cd08718     1 WAQSFDKLMKSPAGRNVFREFLRTEYSEENMLFWLACEELKKEANKHvIEEKARLIYEDYISILSPKEVSLDSRVREVIN 80

                          90       100       110
                  ....*....|....*....|....*....|....*..
gi 1765945264 238 QNVKEPGRYTFEDAQEHIYKLMKSDSYPRFIRSSAYQ 274
Cdd:cd08718    81 RNMLEPSPHTFDDAQLQIYTLMHRDSYPRFLNSAIYK 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 1765945264 164 DEALKDPVGREQFLKFLESEFSSENLRFWLAVEDLKK-RPIKEVPSRVQEIWQEFLAPGAPSAINLDSKSYDKTTQNVKE 242
Cdd:cd08712     2 DKLLSHKDGLEAFTRFLKTEFSEENIEFWIACEDYKKsKTPQQIHLKAKAIYEKFIQTDAPKEVNLDFHTKEVTTNSIEQ 81

                          90       100       110
                  ....*....|....*....|....*....|.
gi 1765945264 243 PGRYTFEDAQEHIYKLMKSDSYPRFIRSSAY 273
Cdd:cd08712    82 PTLTSFDAAQSRVYQLMEQDSYPRFLKSDIY 112

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 1765945264 164 DEALKDPVGREQFLKFLESEFSSENLRFWLAVEDLKK-RPIKEVPSRVQEIWQEFLAPGAPSAINLDSKSYDKTTQNVKE 242
Cdd:cd08710     2 DLLLNSKNGVAAFHAFLKTEFSEENLEFWLACEEFKKiRSATKLASRAHHIFEEFIRSEAPKEVNIDHETRELTRTNLQA 81

                          90       100       110
                  ....*....|....*....|....*....|...
gi 1765945264 243 PGRYTFEDAQEHIYKLMKSDSYPRFIRSSAYQE 275
Cdd:cd08710    82 ATTSCFDVAQGKTRTLMEKDSYPRFLKSPAYRD 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 1765945264 172 GREQFLKFLESEFSSENLRFWLAVEDLKKRPIKE-VPSRVQEIWQEFLAPGAPSAINLDSKSYDKTTQNVKEPGRYTFED 250
Cdd:cd08714    10 GLAAFKAFLKSEYSEENIDFWVSCEDYKKTKSPSkLSPKARKIYEEFISVQATKEVNLDSCTREETSRNMLEPTISCFDE 89

                          90       100
                  ....*....|....*....|....*
gi 1765945264 251 AQEHIYKLMKSDSYPRFIRSSAYQE 275
Cdd:cd08714    90 AQKKIFTLMEKDSYRRFLKSRFYLD 114

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 1765945264 163 MDEALKDPVGREQFLKFLESEFSSENLRFWLAVEDLKK-RPIKEVPSRVQEIWQEFLAPGAPSAINLDSKSYDKTTQnVK 241
Cdd:cd08741     1 LENLLEDPEGVKRFREFLKKEFSEENVLFWLACEDFKKmQDKTQMQEKAKEIYMTFLSSKASSQVNVEGQSRLNEKI-LE 79

                          90       100       110
                  ....*....|....*....|....*....|..
gi 1765945264 242 EPGRYTFEDAQEHIYKLMKSDSYPRFIRSSAY 273
Cdd:cd08741    80 EPHPLMFQKLQDQIFNLMKYDSYSRFLKSDLF 111

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 1765945264 179 FLESEFSSENLRFWLAVEDLKK-RPIKEVPSRVQEIWQEFLAPGAPSAINLDSKSYDKTTQNVKEPGRYTFEDAQEHIYK 257
Cdd:cd08716    17 YLKTEHSDENIEFWLACETYKKiASQRKRISMARKLFASYIQPQAPREINIDSPTRKAIIRNIQEPTQSCFDEAQRIVYM 96

                          90
                  ....*....|....*...
gi 1765945264 258 LMKSDSYPRFIRSSAYQE 275
Cdd:cd08716    97 HMERDSYPRFLESKFYQK 114

GGL domain; G-protein gamma like domains (GGL) are found in the gamma subunit of the heterotrimeric G protein complex and in regulators of G protein signaling (RGS) proteins. It is also found fused to an inactive Galpha in the Dictyostelium protein gbqA. G-gamma likely shares a common origin with the helical N-terminal unit of G-beta. All organizms that posses a G-beta possess a G-gamma.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1765945264  85 DELQQQIKYWQIQLDRHRLKMSKVADSLLSYTEQYLEYDPFL----LPPDPSNPWLSDDTTFWEL 145
Cdd:pfam00631   5 LKLKREIEQLREELKRERIKVSKACEELIDYCEQRSTKDPLLpgvwGPPAGENPWREDDGCCWIL 69

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 1765945264 163 MDEALKDPVGREQFLKFLESEFSSENLRFWLAVEDLKKR-------------------PIKEVPSRVQEIWQEFLAPGAP 223
Cdd:cd08708     2 LDKILKDPGLRYLFREHLEKEFCEENLSFYLEVKEFLKKmtilsklldfkssqaadedLDRESLAQAYHIYNTYLAPGSP 81

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1765945264 224 SAINLDSKSYDKTTQNVKEPGR--------------YTFEDAQEHIYK-LMKSDSYPRFIRSSAY 273
Cdd:cd08708    82 CELNIDHNLRNRITTIMTEKIVgeddsmaeslqgveALFEEAQNAVFKpLMAGDSVPKFLKQPEY 146

Regulator of G protein signaling (RGS) domain found in the Sorting Nexin 13 (SNX13) protein; The RGS (Regulator of G-protein Signaling) domain is an essential part of the SNX13 (Sorting Nexin 13) 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. The RGS-domain of SNX13 plays a major role through attenuation of Galphas-mediated signaling and regulates endocytic trafficking and degradation of the epidermal growth factor receptor. Snx13-null mice were embryonic lethal around midgestation which supports an essential role for SNX13 in mouse development and regulation of endocytosis dynamics.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1765945264 166 ALKDPVGREQFLKFLESEFSSENLRFWLAVEDLK-------------KRPIKEVPSRVQE--------IWQEFLAPGAPS 224
Cdd:cd08719     1 ILVNNVALSYFIDFMQSVGGQAYLFFWLTVEGYRvsaeqqlselhlrQRGGEHQRSDVYEmlraaalnIYDQYLSEKASP 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1765945264 225 AINLDSKSYDKTTQ--NVKEPGRYTFEDAQEHIYKLMKSDS--YPRFIRSSAY 273
Cdd:cd08719    81 RVPLDDSLVKKLLNrlRNDTPSDLWFDDIQQKVFDIMQEDErfYPAFKKSPAY 133

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 1765945264 167 LKDPVGREQFLKFLESEFSSENLRFWLAVEDLKKR-PIKEVPSRV-QEIWQEFLAPGAPSAINL--DSKSYDKTTQNVKE 242
Cdd:cd08707     5 LDDQDGIELFRTYLEQEGCADLLDFWFACNGFRKMsDSEEKRSKLaKAIYRRYIKDNGIVSRQLkpATKSFIKECIKKQQ 84

                          90       100       110
                  ....*....|....*....|....*....|...
gi 1765945264 243 PGRYTFEDAQEHIYKLMKSDSYPRFIRSSAYQE 275
Cdd:cd08707    85 LDPAMFDQAQTEIQTTMEENTYPSFLKSDIYLE 117

Regulator of G protein signaling domain (RGS) found in G protein-coupled receptor kinase 5 (GRK5); The RGS domain is an essential part of the GRK5 (G protein-coupled receptor kinase 5) protein, a membrane-associated serine/threonine protein kinases which phosphorylates G protein-coupled receptors (GPCRs) upon agonist stimulation. This phosphorylation initiates beta-arrestin-mediated receptor desensitization, internalization, and signaling events. GRK5 is a member of the GRK kinase family which include three major subfamilies: the GRK4 subfamily (GRK4, GRK5 and GRK6), the rhodopsin kinase or visual GRK subfamily (GRK1 and GRK7), and the beta-adrenergic receptor kinases subfamily (GRK2/GRK3). The RGS domain of the GRKs has very little sequence similarity with the canonical RGS domain of the RGS proteins and therefore is often refered to as the RH (RGS Homology) domain. 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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1765945264 168 KDPVGREQFLKFLESEFSSEN-LRFWLAVEDLKKRPIKEVPSRVQEIWQEFLAPGAPSAINLDSKSYDKTTQN--VKEPG 244
Cdd:cd08752     7 KQPIGRLLFRQFCETRPGLECyIQFLDSVAEYEVTPDEKLGEKGKEIMTKYLTPKSPVFIPQVGQDLVSQTEEklLQKPC 86

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 1765945264 245 RYTFEDAQEHIYKLMKSDSYPRFIRSSAYQELLQAK 280
Cdd:cd08752    87 KELFSACTQSVHDYLRGEPFHEYLDSMYFDRFLQWK 122

Uncharacterized Regulator of G protein Signaling (RGS) domain subfamily, child 4; 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. 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 1765945264 187 ENLRFWLAVEDLKKRPIKEVPSRV---QEIWQEFLAPGAPSAINLDSKSYDKTTQNVKEPGRYT---FEDAQEHIYKLMK 260
Cdd:cd08732    38 EDDDFDEQVEELRYILDTDQILLKdqwRHIMNTYIHHDSPLQINLSHTMRKEIVEEDDNPNIHTpdlLLNAYNEVLRLLK 117

                          90       100
                  ....*....|....*....|..
gi 1765945264 261 SDSYPRFIRSSAYQELLQAKKK 282
Cdd:cd08732   118 ENFYPEFKNLPKYRKLKEEESK 139