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 6174947  295 LRVERWGFSFRELLEDPVGRAHFMDFLGKEFSGENLSFWEACEELRYGAQAQVPTLVDAVYEQFLAPGAAHWVNIDSRTM 374
Cdd:cd08740   1 LRVERWGFSFRELLNDPVGRKEFLDFLEKEFSAENLSFWEACEELRYGEQSKIPELVDSVYQQFLAPGATRWVNIDSKTM 80

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*.
gi 6174947  375 EQTLEGLRQPHRYVLDDAQLHIYMLMKKDSYPRFLKSDMYKALLAE 420
Cdd:cd08740  81 ERTLEGLKQPHRYVLDDAQMHIYMLMKKDSYPRFLKSDLYKNLLAE 126

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 6174947   24 RVVVSMQDPDQGVKMRSQRLLVTVIPHAVTGSDVVQWLAQKF-CVSEEEALHLGAVLVQHGYIYPLRDPRSLmLRPDETP 102
Cdd:cd04450   1 DSVGQMQDSEVGVRMRTEKSFLTTVPYAFTGKAIVQWLMDCTdVVDPSEALEIAALFVKYGLITPVSDHRSL-LKPDETL 79

                ....*....
gi 6174947  103 YRFQTPYFW 111
Cdd:cd04450  80 YRFQAPYFW 88

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 6174947  295 LRVERWGFSFRELLEDPVGRAHFMDFLGKEFSGENLSFWEACEELRYGAQAQVPTLVDAVYEQFLAPGAAHWVNIDSRTM 374
Cdd:cd08740   1 LRVERWGFSFRELLNDPVGRKEFLDFLEKEFSAENLSFWEACEELRYGEQSKIPELVDSVYQQFLAPGATRWVNIDSKTM 80

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*.
gi 6174947  375 EQTLEGLRQPHRYVLDDAQLHIYMLMKKDSYPRFLKSDMYKALLAE 420
Cdd:cd08740  81 ERTLEGLKQPHRYVLDDAQMHIYMLMKKDSYPRFLKSDLYKNLLAE 126

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 6174947    303 SFRELLEDPVGRAHFMDFLGKEFSGENLSFWEACEELRYGA-QAQVPTLVDAVYEQFLAPGAAHWVNIDSRTMEQTLEGL 381
Cdd:pfam00615   1 SFDSLLEDQPGRRLFRQFLESEFSEENLEFWLACEEFKKADpDEERLKKAKEIYNEFLAPGSPKEINLDSDLREEIRENL 80

                          90       100       110
                  ....*....|....*....|....*....|....*..
gi 6174947    382 RQ-PHRYVLDDAQLHIYMLMKKDSYPRFLKSDMYKAL 417
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 6174947   24 RVVVSMQDPDQGVKMRSQRLLVTVIPHAVTGSDVVQWLAQKF-CVSEEEALHLGAVLVQHGYIYPLRDPRSLmLRPDETP 102
Cdd:cd04450   1 DSVGQMQDSEVGVRMRTEKSFLTTVPYAFTGKAIVQWLMDCTdVVDPSEALEIAALFVKYGLITPVSDHRSL-LKPDETL 79

                ....*....
gi 6174947  103 YRFQTPYFW 111
Cdd:cd04450  80 YRFQAPYFW 88

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 6174947      32 PDQGVKMRSQRLLVTVIPHAVTGSDVVQWLAQKFCVSE-EEALHLGAVLVQHGYIYPLRDPRSLMLRPDETPYRFQT 107
Cdd:smart00049   1 PETGLKLRDRKYFLKTYPNCFTGSELVDWLMDNLEIIDrEEAVHLGQLLLDEGLIHHVNGPNKHTFKDSKALYRFTT 77

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 6174947     35 GVKMRSQRLLVTVIPHAVTGSDVVQWLAQKFCVSE-EEALHLGAVLVQHGYIYPLRDPRSlMLRPDETPYRF 105
Cdd:pfam00610   1 GVKLKDRRKHLKTYPNCFTGSEAVDWLMDNLEIITrEEAVELGQLLLDQGLIHHVGDKHG-LFKDSYYFYRF 71

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 6174947  295 LRVERWGFSFRELLEDPVGRAHFMDFLGKEFSGENLSFWEACEELRYGAQAQVPTLVDAVYEQFLAPGAAHWVNIDSRTM 374
Cdd:cd08740   1 LRVERWGFSFRELLNDPVGRKEFLDFLEKEFSAENLSFWEACEELRYGEQSKIPELVDSVYQQFLAPGATRWVNIDSKTM 80

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*.
gi 6174947  375 EQTLEGLRQPHRYVLDDAQLHIYMLMKKDSYPRFLKSDMYKALLAE 420
Cdd:cd08740  81 ERTLEGLKQPHRYVLDDAQMHIYMLMKKDSYPRFLKSDLYKNLLAE 126

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 6174947  296 RVERWGFSFRELLEDPVGRAHFMDFLGKEFSGENLSFWEACEELRYGAQAQVPTLVDAVYEQFLAPGAAHWVNIDSRTME 375
Cdd:cd08739   1 RVERWAFNFSELIRDPKGRQSFQLFLKKEFSGENLGFWEACEDLKYGDQSKVKEKAEEIYKLFLAPGARRWINIDGKTMD 80

                        90       100       110       120
                ....*....|....*....|....*....|....*....|
gi 6174947  376 QTLEGLRQPHRYVLDDAQLHIYMLMKKDSYPRFLKSDMYK 415
Cdd:cd08739  81 ITVKGLKHPHRYVLDAAQTHIYMLMKKDSYARYLKSPIYK 120

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 6174947     303 SFRELLEDPVGRAHFMDFLGKEFSGENLSFWEACEELRYGAQ-AQVPTLVDAVYEQFLAPGAAHWVNIDSRTMEQTLEGL 381
Cdd:smart00315   1 SLESLLSDPIGRLLFREFLESEFSEENLEFWLAVEEFKKAEDdEERIAKAREIYDKFLSPNAPKEVNLDSDLREKIEENL 80

                           90       100       110
                   ....*....|....*....|....*....|....*...
gi 6174947     382 --RQPHRYVLDDAQLHIYMLMKKDSYPRFLKSDMYKAL 417
Cdd:smart00315  81 esEEPPPDLFDEAQREVYELLEKDSFPRFLESDYYLRF 118

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 6174947  296 RVERWGFSFRELLEDPVGRAHFMDFLGKEFSGENLSFWEACEELRYGAQAQVPTLVDAVYEQFLAPGAAHWVNIDSRTME 375
Cdd:cd08738   1 RVKRWGFGMDEALKDPVGREQFLKFLESEFSSENLRFWLAVEDLKKRPIREVPSRVQEIWQEFLAPGAPSAINLDSKSYD 80

                        90       100       110       120
                ....*....|....*....|....*....|....*....|
gi 6174947  376 QTLEGLRQPHRYVLDDAQLHIYMLMKKDSYPRFLKSDMYK 415
Cdd:cd08738  81 KTTQNVKDPGRYTFEDAQEHIYKLMKSDSYPRFIRSSAYQ 120

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 6174947   24 RVVVSMQDPDQGVKMRSQRLLVTVIPHAVTGSDVVQWLAQKF-CVSEEEALHLGAVLVQHGYIYPLRDPRSLmLRPDETP 102
Cdd:cd04450   1 DSVGQMQDSEVGVRMRTEKSFLTTVPYAFTGKAIVQWLMDCTdVVDPSEALEIAALFVKYGLITPVSDHRSL-LKPDETL 79

                ....*....
gi 6174947  103 YRFQTPYFW 111
Cdd:cd04450  80 YRFQAPYFW 88

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 6174947  308 LEDPVGRAHFMDFLGKEFSGENLSFWEACEELR--YGAQAQVPTLVDAVYEQFLAPGAAHWVNIDSRTMEQTLEGLR--Q 383
Cdd:cd07440   1 LRDPYGLEYFRQFLKSEHCEENLEFWLAVEKFKktTSSDEELKSKAKEIYDKYISKDAPKEINIPESIREEIEENLEepY 80

                        90       100       110
                ....*....|....*....|....*....|..
gi 6174947  384 PHRYVLDDAQLHIYMLMKKDSYPRFLKSDMYK 415
Cdd:cd07440  81 PDPDCFDEAQEHILNLLEKDSYPRFLKSDLYL 112

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 6174947  300 WGFSFRELLEDPVGRAHFMDFLGKEFSGENLSFWEACEELRYGA-QAQVPTLVDAVYEQFLAPGAAHWVNIDSRTMEQTL 378
Cdd:cd08745   1 WAQSFDKLMKSPAGRNVFREFLRTEYSEENMLFWLACEELKAEAnKHVIDEKARLIYEDYISILSPKEVSLDSRVREGIN 80

                        90       100       110
                ....*....|....*....|....*....|....*...
gi 6174947  379 EGLRQPHRYVLDDAQLHIYMLMKKDSYPRFLKSDMYKA 416
Cdd:cd08745  81 RKMQEPSSHTFDDAQLQIYTLMHRDSYPRFLNSPIYKA 118

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 6174947  306 ELLEDPVGRAHFMDFLGKEFSGENLSFWEACEELRYGAQAQVPTLVDAVYEQFLAPGAAHWVNIDSRTMEQTLEGLRQPH 385
Cdd:cd08715   3 KLLASQTGQNVFRSFLKSEFSEENIEFWLACEDYKKTESDLLPCKAEEIYKEFVQSDAAKQINIDFRTRESTAKKIKAPT 82

                        90       100
                ....*....|....*....|....*....
gi 6174947  386 RYVLDDAQLHIYMLMKKDSYPRFLKSDMY 414
Cdd:cd08715  83 PTCFDEAQKVIYILMERDSYPRFLKSDIY 111

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 6174947  306 ELLEDPVGRAHFMDFLGKEFSGENLSFWEACEELR-YGAQAQVPTLVDAVYEQFLAPGAAHWVNIDSRTMEQTLEGLRQP 384
Cdd:cd08717   3 KLLQNSYGLASFKSFLKSEFSEENIEFWEACEDYKkTKSPLKMATKAKKIYEEFIQTEAPKEVNIDHFTKDVTMKNLVEP 82

                        90       100       110
                ....*....|....*....|....*....|.
gi 6174947  385 HRYVLDDAQLHIYMLMKKDSYPRFLKSDMYK 415
Cdd:cd08717  83 SSSSFDLAQKRIFALMEKDSLPRFVRSEFYQ 113

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 6174947  304 FRELLEDPVGRAHFMDFLGKEFSGENLSFWEACEELRygaQAQVPTLVD----AVYEQFLAPGAAHWVNIDSRTMEQTLE 379
Cdd:cd08712   1 FDKLLSHKDGLEAFTRFLKTEFSEENIEFWIACEDYK---KSKTPQQIHlkakAIYEKFIQTDAPKEVNLDFHTKEVTTN 77

                        90       100       110
                ....*....|....*....|....*....|....*
gi 6174947  380 GLRQPHRYVLDDAQLHIYMLMKKDSYPRFLKSDMY 414
Cdd:cd08712  78 SIEQPTLTSFDAAQSRVYQLMEQDSYPRFLKSDIY 112

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 6174947  299 RWGFSFRELLEDPVGRAHFMDFLGKEFSGENLSFWEACEELRYG-AQAQVPTLVDAVYEQFLAPGAAHWVNIDSRTMEQT 377
Cdd:cd08711   7 RWADSFDVLLSHKYGVAAFRAFLKTEFSEENLEFWLACEEFKKTrSTAKLVSKAHRIFEEFVDVQAPREVNIDFQTREAT 86

                        90       100       110
                ....*....|....*....|....*....|....*..
gi 6174947  378 LEGLRQPHRYVLDDAQLHIYMLMKKDSYPRFLKSDMY 414
Cdd:cd08711  87 RKNLQEPSLTCFDQAQGKVHSLMEKDSYPRFLRSKMY 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 6174947  300 WGFSFRELLEDPVGRAHFMDFLGKEFSGENLSFWEACEELRYGAQAQV-PTLVDAVYEQFLAPGAAHWVNIDSRTMEQTL 378
Cdd:cd08744   1 WSQNFDKMMKTPAGRNLFREFLRTEYSEENLLFWLACEDLKKEQNKKViEEKARLIYEDYISILSPKEVSLDSRVREVIN 80

                        90       100       110
                ....*....|....*....|....*....|....*...
gi 6174947  379 EGLRQPHRYVLDDAQLHIYMLMKKDSYPRFLKSDMYKA 416
Cdd:cd08744  81 RNLLDPNPHMYEDAQLQIYTLMHRDSFPRFLNSQIYKS 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 6174947  304 FRELLEDPVGRAHFMDFLGKEFSGENLSFWEACEELR-YGAQAQVPTLVDAVYEQFLAPGAAHWVNIDSRTMEQTLEGLR 382
Cdd:cd08714   1 LENLINHECGLAAFKAFLKSEYSEENIDFWVSCEDYKkTKSPSKLSPKARKIYEEFISVQATKEVNLDSCTREETSRNML 80

                        90       100       110
                ....*....|....*....|....*....|..
gi 6174947  383 QPHRYVLDDAQLHIYMLMKKDSYPRFLKSDMY 414
Cdd:cd08714  81 EPTISCFDEAQKKIFTLMEKDSYRRFLKSRFY 112

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 6174947  304 FRELLEDPVGRAHFMDFLGKEFSGENLSFWEACEELRYGAQAQVPTL-VDAVYEQFLAPGAAHWVNIDSRTMEQTLEGLR 382
Cdd:cd08709   1 FDELLASKYGVAAFRAFLKSEFSEENIEFWLACEDFKKTKSPQKLTSkAKKIYTDFIEKEAPKEINIDFQTKTLIAQNIQ 80

                        90       100       110
                ....*....|....*....|....*....|...
gi 6174947  383 QPHRYVLDDAQLHIYMLMKKDSYPRFLKSDMYK 415
Cdd:cd08709  81 EATSGCFTAAQKRVYSLMENNSYPRFLESEFYQ 113

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 6174947      32 PDQGVKMRSQRLLVTVIPHAVTGSDVVQWLAQKFCVSE-EEALHLGAVLVQHGYIYPLRDPRSLMLRPDETPYRFQT 107
Cdd:smart00049   1 PETGLKLRDRKYFLKTYPNCFTGSELVDWLMDNLEIIDrEEAVHLGQLLLDEGLIHHVNGPNKHTFKDSKALYRFTT 77

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 6174947  304 FRELLEDPVGRAHFMDFLGKEFSGENLSFWEACEELRYGA-QAQVPTLVDAVYEQFLAPGAAHWVNIDSRTMEQTLEGLR 382
Cdd:cd08716   1 FENLMATKYGPIIYATYLKTEHSDENIEFWLACETYKKIAsQRKRISMARKLFASYIQPQAPREINIDSPTRKAIIRNIQ 80

                        90       100       110
                ....*....|....*....|....*....|...
gi 6174947  383 QPHRYVLDDAQLHIYMLMKKDSYPRFLKSDMYK 415
Cdd:cd08716  81 EPTQSCFDEAQRIVYMHMERDSYPRFLESKFYQ 113

DEP domain, named after Dishevelled, Egl-10, and Pleckstrin, where this domain was first discovered. The function of this domain is still not clear, but it is believed to be important for the membrane association of the signaling proteins in which it is present. New studies show that the DEP domain of Sst2, a yeast RGS protein is necessary and sufficient for receptor interaction.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6174947   24 RVVVSMQDPDQGVKMRSQRLLVTVIPHAVTGSDVVQWLAQKF-CVSEEEALHLGAVLVQHGYIYPLRDPRSLmLRPDETP 102
Cdd:cd04371   1 DLVRIMLDSDSGVPIKDRKYHLKTYPNCFTGSELVDWLLDNLeAITREEAVELGQALLKHGLIHHVSDDKHT-FRDSYAL 79

                ..
gi 6174947  103 YR 104
Cdd:cd04371  80 YR 81

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 6174947    227 KREIEYFRKALGRTRVKSSVCLEAYLSFCGQRGPHDPLVSGC-LPS---NPWISDNDAYWVM 284
Cdd:pfam00631   8 KREIEQLREELKRERIKVSKACEELIDYCEQRSTKDPLLPGVwGPPageNPWREDDGCCWIL 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 6174947  305 RELLEDPVGRAHFMDFLGKEFSGENLSFW-EACEELRY-----------GAQAQVPTLVDA-------VYEQFLAPGAAH 365
Cdd:cd08708   3 DKILKDPGLRYLFREHLEKEFCEENLSFYlEVKEFLKKmtilsklldfkSSQAADEDLDREslaqayhIYNTYLAPGSPC 82

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 6174947  366 WVNIDSRT-------MEQTLEG-------LRQPHRYVLDDAQLHIY-MLMKKDSYPRFLKSDMYKA 416
Cdd:cd08708  83 ELNIDHNLrnrittiMTEKIVGeddsmaeSLQGVEALFEEAQNAVFkPLMAGDSVPKFLKQPEYLG 148

DEP (Dishevelled, Egl-10, and Pleckstrin) domain found in pleckstrin 1-like proteins. Pleckstrin 1 plays a role in cell spreading and reorganization of actin cytoskeleton in platelets and leukocytes. Its activity is highly regulated by phosphorylation, mainly by protein kinase C. Pleckstrin-like proteins contain a central DEP domain, flanked by 2 PH (pleckstrin homology) domains.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 6174947   27 VSMQDPDQGVKMRSQRLLVTVIPHAVTGSDVVQWL-AQKFCVSEEEALHLGAVLVQHGYIYPLRD 90
Cdd:cd04445   7 LSMKDPEKGIKELNLEKDKKVFNHCFTGSCVIDWLvSNQSVRNRQEGLMLASSLLNEGYLQPAGD 71

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 6174947  317 FMDFLGKEFSGENLSFWEACEELRY----------GAQAQVPTLVdaVYEQFLAPGAAHWVNIDSRT---MEQTL--EGL 381
Cdd:cd08721  11 FMEYMEQEGARNLLQFWLAADNFQSqlaakegqydGQQAQNDAMI--IYDKYFSLQATEPLGFDDKTrleVESNIcrEGG 88

                        90       100       110
                ....*....|....*....|....*....|...
gi 6174947  382 RQPHryVLDDAQLHIYMLMKKDSYPRFLKSDMY 414
Cdd:cd08721  89 PLPS--CFEAPLLQALTTLEQHYLPGFLSSQLY 119