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 124001566  51 DFSSLCDKQPIGRLLFRQFCDTKPDLKRCIEFLDAVAEYEVTIEEEQREFGLAIFSRFFKEKSEVPLPEIPPDIVKECKW 130
Cdd:cd08750    1 DYSSLCDKQPIGRLLFRQFCDTRPTLKRCIEFLDAVAEYEVAPDEKRSDCGLSILDTYFNNGSAAHLPEIPQDVVTECRL 80

                         90
                 ....*....|....*
gi 124001566 131 NLKQNsPSQNVFEEC 145
Cdd:cd08750   81 KLEEN-PSKELFEEC 94

Regulator of G protein signaling domain (RGS) found in G protein-coupled receptor kinase 4 (GRK4); The RGS domain is an essential part of the GRK4 (G protein-coupled receptor kinase4) proteins, which are membrane-associated serine/threonine protein kinases that phosphorylate G protein-coupled receptors (GPCRs) upon agonist stimulation. This phosphorylation initiates beta-arrestin-mediated receptor desensitization, internalization, and signaling events. GRK4 is a member of the GRK kinase family which includes 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. GRK4 plays a key role in regulating dopaminergic-mediated natriuresis and is associated with essential hypertension and/or salt-sensitive hypertension. GRK4 exists in four splice variants involved in hyperphosphorylation, desensitization, and internalization of two dopamine receptors (D1R and D3R). GRK4 also increases the expression of a key receptor of the renin-angiotensin system, the AT1R (angiotensin type 1 receptor). 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 124001566  51 DFSSLCDKQPIGRLLFRQFCDTKPDLKRCIEFLDAVAEYEVTIEEEQREFGLAIFSRFFKEKSEVPLPEIPPDIVKECKW 130
Cdd:cd08750    1 DYSSLCDKQPIGRLLFRQFCDTRPTLKRCIEFLDAVAEYEVAPDEKRSDCGLSILDTYFNNGSAAHLPEIPQDVVTECRL 80

                         90
                 ....*....|....*
gi 124001566 131 NLKQNsPSQNVFEEC 145
Cdd:cd08750   81 KLEEN-PSKELFEEC 94

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 124001566   51 DFSSLCDKQPiGRLLFRQFCDTKPDlKRCIEFLDAVAEYEVTIEEEQR-EFGLAIFSRFFKEKSEVPLpEIPPDIVKECK 129
Cdd:pfam00615   1 SFDSLLEDQP-GRRLFRQFLESEFS-EENLEFWLACEEFKKADPDEERlKKAKEIYNEFLAPGSPKEI-NLDSDLREEIR 77

                          90
                  ....*....|....*.
gi 124001566  130 WNLKQNsPSQNVFEEC 145
Cdd:pfam00615  78 ENLEKE-PTRDLFDEA 92

Regulator of G protein signaling domain (RGS) found in G protein-coupled receptor kinase 4 (GRK4); The RGS domain is an essential part of the GRK4 (G protein-coupled receptor kinase4) proteins, which are membrane-associated serine/threonine protein kinases that phosphorylate G protein-coupled receptors (GPCRs) upon agonist stimulation. This phosphorylation initiates beta-arrestin-mediated receptor desensitization, internalization, and signaling events. GRK4 is a member of the GRK kinase family which includes 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. GRK4 plays a key role in regulating dopaminergic-mediated natriuresis and is associated with essential hypertension and/or salt-sensitive hypertension. GRK4 exists in four splice variants involved in hyperphosphorylation, desensitization, and internalization of two dopamine receptors (D1R and D3R). GRK4 also increases the expression of a key receptor of the renin-angiotensin system, the AT1R (angiotensin type 1 receptor). 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 124001566  51 DFSSLCDKQPIGRLLFRQFCDTKPDLKRCIEFLDAVAEYEVTIEEEQREFGLAIFSRFFKEKSEVPLPEIPPDIVKECKW 130
Cdd:cd08750    1 DYSSLCDKQPIGRLLFRQFCDTRPTLKRCIEFLDAVAEYEVAPDEKRSDCGLSILDTYFNNGSAAHLPEIPQDVVTECRL 80

                         90
                 ....*....|....*
gi 124001566 131 NLKQNsPSQNVFEEC 145
Cdd:cd08750   81 KLEEN-PSKELFEEC 94

Regulator of G protein signaling domain (RGS) found in G protein-coupled receptor kinase (GRK); The RGS domain is found in G protein-coupled receptor kinases (GRKs). These proteins play a key role in phosphorylation-dependent desensitization/resensitization of GPCRs (G protein-coupled receptors), intracellular trafficking, endocytosis, as well as in the modulation of important intracellular signaling cascades by GPCR. GRKs also modulate cellular response in phosphorylation-independent manner using their ability to interact with multiple signaling proteins involved in many essential cellular pathways. 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. Based on sequence homology the GRK family consists of 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). 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 124001566  55 LCDKQPIGRLLFRQFCDTKPDLKRCIEFLDAVAEYEVTIEEEQREFGLAIFSRFFKEKSEVPLPEIPPDIVKECKWNLKQ 134
Cdd:cd08724    1 ICEQQPIGRLLFRQFCETRPELVPQIEFLDEIKEYEVAEDEERAKKAREIYDKYIMKESLAHSHEFSKDAVEHVQENLEK 80

                         90
                 ....*....|.
gi 124001566 135 NsPSQNVFEEC 145
Cdd:cd08724   81 E-VPKDLFQPY 90

Regulator of G protein signaling domain (RGS) found in G protein-coupled receptor kinase 7 (GRK7); The RGS domain is an essential part of the GRK7 (G protein-coupled receptor kinases 7) proteins which together with GRK1 (Rhodopsin kinase) have been implicated in the shutoff of the photoresponse and adaptation to changing light conditions via rod and cone opsin phosphorylation. GRK7 is a member of the GRK kinase family which includes 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. GRK7 is expressed in all vertebrate cones except that of mice and rats, which do not have the gene for GRK7. Lack of either GRK7 or both GRK1 and GRK7 in human leads to a vision defect called Enhanced S Cone syndrome. 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 124001566  36 PPVSMCTELRWSIEKDFSSLCDKQPIGRLLFRQFCDTKPDLKRCIEFLDAVAEYEVTIEEEQREFGLAIFSRFFKEKSEV 115
Cdd:cd08749    1 PKPEQCAELRQSLSKDFESLCEQQPIGKRLFRDFLATVPEYTVAADFLDDVQNWELAEEAAKDKARQNIIANFCKAGSKN 80

                         90
                 ....*....|....
gi 124001566 116 PLPEIPPDIVKECK 129
Cdd:cd08749   81 PLSFLSGDVATKCK 94

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 124001566   51 DFSSLCDKQPiGRLLFRQFCDTKPDlKRCIEFLDAVAEYEVTIEEEQR-EFGLAIFSRFFKEKSEVPLpEIPPDIVKECK 129
Cdd:pfam00615   1 SFDSLLEDQP-GRRLFRQFLESEFS-EENLEFWLACEEFKKADPDEERlKKAKEIYNEFLAPGSPKEI-NLDSDLREEIR 77

                          90
                  ....*....|....*.
gi 124001566  130 WNLKQNsPSQNVFEEC 145
Cdd:pfam00615  78 ENLEKE-PTRDLFDEA 92

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 124001566  59 QPIGRLLFRQFCDTKPDLKrCIEFLDAVAEYEVTIEEEQREFGLA--IFSRFFKEKSEVPLPeIPPDIVKECKWNLKQNS 136
Cdd:cd07440    3 DPYGLEYFRQFLKSEHCEE-NLEFWLAVEKFKKTTSSDEELKSKAkeIYDKYISKDAPKEIN-IPESIREEIEENLEEPY 80

                 ....*...
gi 124001566 137 PSQNVFEE 144
Cdd:cd07440   81 PDPDCFDE 88