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 221139707  77 LDNLLSSKCGLNFFRLFIKSELCEENLDFWLACEEFRKIRSRSKLKSKAKSIYNEFIKPDSPKEINLDYNMKEMLQQSLL 156
Cdd:cd08709    1 FDELLASKYGVAAFRAFLKSEFSEENIEFWLACEDFKKTKSPQKLTSKAKKIYTDFIEKEAPKEINIDFQTKTLIAQNIQ 80

                         90       100       110
                 ....*....|....*....|....*....|...
gi 221139707 157 IPTPCTFKVAQHRVLYLMEHNSYPRFLESELYQ 189
Cdd:cd08709   81 EATSGCFTAAQKRVYSLMENNSYPRFLESEFYQ 113

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 221139707  77 LDNLLSSKCGLNFFRLFIKSELCEENLDFWLACEEFRKIRSRSKLKSKAKSIYNEFIKPDSPKEINLDYNMKEMLQQSLL 156
Cdd:cd08709    1 FDELLASKYGVAAFRAFLKSEFSEENIEFWLACEDFKKTKSPQKLTSKAKKIYTDFIEKEAPKEINIDFQTKTLIAQNIQ 80

                         90       100       110
                 ....*....|....*....|....*....|...
gi 221139707 157 IPTPCTFKVAQHRVLYLMEHNSYPRFLESELYQ 189
Cdd:cd08709   81 EATSGCFTAAQKRVYSLMENNSYPRFLESEFYQ 113

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 221139707    76 SLDNLLSSKCGLNFFRLFIKSELCEENLDFWLACEEFRKIRSRSKLKSKAKSIYNEFIKPDSPKEINLDYNMKEMLQQSL 155
Cdd:smart00315   1 SLESLLSDPIGRLLFREFLESEFSEENLEFWLAVEEFKKAEDDEERIAKAREIYDKFLSPNAPKEVNLDSDLREKIEENL 80

                           90       100       110
                   ....*....|....*....|....*....|....*.
gi 221139707   156 LIPTPC--TFKVAQHRVLYLMEHNSYPRFLESELYQ 189
Cdd:smart00315  81 ESEEPPpdLFDEAQREVYELLEKDSFPRFLESDYYL 116

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 221139707  77 LDNLLSSKCGLNFFRLFIKSELCEENLDFWLACEEFRKIRSRSKLKSKAKSIYNEFIKPDSPKEINLDYNMKEMLQQSLL 156
Cdd:cd08709    1 FDELLASKYGVAAFRAFLKSEFSEENIEFWLACEDFKKTKSPQKLTSKAKKIYTDFIEKEAPKEINIDFQTKTLIAQNIQ 80

                         90       100       110
                 ....*....|....*....|....*....|...
gi 221139707 157 IPTPCTFKVAQHRVLYLMEHNSYPRFLESELYQ 189
Cdd:cd08709   81 EATSGCFTAAQKRVYSLMENNSYPRFLESEFYQ 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 221139707  77 LDNLLSSKCGLNFFRLFIKSELCEENLDFWLACEEFRKIRSRSKLKSKAKSIYNEFIKPDSPKEINLDYNMKEMLQQSLL 156
Cdd:cd08713    1 LEKLLLHKYGLAVFRAFLQTEFSEENLEFWLACEEYKKIKSQSKMASRAKKIFAEYIAIQSCKEVNLDSYTREHTKENLQ 80

                         90       100       110
                 ....*....|....*....|....*....|...
gi 221139707 157 IPTPCTFKVAQHRVLYLMEHNSYPRFLESELYQ 189
Cdd:cd08713   81 NPTRGCFDLAQKRIYGLMEKDSYPRFLRSDLYQ 113

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 221139707  77 LDNLLSSKCGLNFFRLFIKSELCEENLDFWLACEEFRKIRSRSKLKSKAKSIYNEFIKPDSPKEINLDYNMKEMLQQSLL 156
Cdd:cd08710    1 FDLLLNSKNGVAAFHAFLKTEFSEENLEFWLACEEFKKIRSATKLASRAHHIFEEFIRSEAPKEVNIDHETRELTRTNLQ 80

                         90       100       110
                 ....*....|....*....|....*....|...
gi 221139707 157 IPTPCTFKVAQHRVLYLMEHNSYPRFLESELYQ 189
Cdd:cd08710   81 AATTSCFDVAQGKTRTLMEKDSYPRFLKSPAYR 113

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 221139707  66 TTEEVSQWAQSLDNLLSSKCGLNFFRLFIKSELCEENLDFWLACEEFRKIRSRSKLKSKAKSIYNEFIKPDSPKEINLDY 145
Cdd:cd08711    1 STEEATRWADSFDVLLSHKYGVAAFRAFLKTEFSEENLEFWLACEEFKKTRSTAKLVSKAHRIFEEFVDVQAPREVNIDF 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|...
gi 221139707 146 NMKEMLQQSLLIPTPCTFKVAQHRVLYLMEHNSYPRFLESELY 188
Cdd:cd08711   81 QTREATRKNLQEPSLTCFDQAQGKVHSLMEKDSYPRFLRSKMY 123

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 221139707  77 LDNLLSSKCGLNFFRLFIKSELCEENLDFWLACEEFRKIRSRSKLKSKAKSIYNEFIKPDSPKEINLDYNMKEMLQQSLL 156
Cdd:cd08717    1 LDKLLQNSYGLASFKSFLKSEFSEENIEFWEACEDYKKTKSPLKMATKAKKIYEEFIQTEAPKEVNIDHFTKDVTMKNLV 80

                         90       100       110
                 ....*....|....*....|....*....|...
gi 221139707 157 IPTPCTFKVAQHRVLYLMEHNSYPRFLESELYQ 189
Cdd:cd08717   81 EPSSSSFDLAQKRIFALMEKDSLPRFVRSEFYQ 113

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 221139707    76 SLDNLLSSKCGLNFFRLFIKSELCEENLDFWLACEEFRKIRSRSKLKSKAKSIYNEFIKPDSPKEINLDYNMKEMLQQSL 155
Cdd:smart00315   1 SLESLLSDPIGRLLFREFLESEFSEENLEFWLAVEEFKKAEDDEERIAKAREIYDKFLSPNAPKEVNLDSDLREKIEENL 80

                           90       100       110
                   ....*....|....*....|....*....|....*.
gi 221139707   156 LIPTPC--TFKVAQHRVLYLMEHNSYPRFLESELYQ 189
Cdd:smart00315  81 ESEEPPpdLFDEAQREVYELLEKDSFPRFLESDYYL 116

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 221139707  77 LDNLLSSKCGLNFFRLFIKSELCEENLDFWLACEEFRKIRSRSKLKSKAKSIYNEFIKPDSPKEINLDYNMKEMLQQSLL 156
Cdd:cd08714    1 LENLINHECGLAAFKAFLKSEYSEENIDFWVSCEDYKKTKSPSKLSPKARKIYEEFISVQATKEVNLDSCTREETSRNML 80

                         90       100       110
                 ....*....|....*....|....*....|..
gi 221139707 157 IPTPCTFKVAQHRVLYLMEHNSYPRFLESELY 188
Cdd:cd08714   81 EPTISCFDEAQKKIFTLMEKDSYRRFLKSRFY 112

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 221139707  81 LSSKCGLNFFRLFIKSELCEENLDFWLACEEFRKI-RSRSKLKSKAKSIYNEFIKPDSPKEINLDYNMKEMLQQSLL--I 157
Cdd:cd07440    1 LRDPYGLEYFRQFLKSEHCEENLEFWLAVEKFKKTtSSDEELKSKAKEIYDKYISKDAPKEINIPESIREEIEENLEepY 80

                         90       100       110
                 ....*....|....*....|....*....|..
gi 221139707 158 PTPCTFKVAQHRVLYLMEHNSYPRFLESELYQ 189
Cdd:cd07440   81 PDPDCFDEAQEHILNLLEKDSYPRFLKSDLYL 112

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 221139707  78 DNLLSSKCGLNFFRLFIKSELCEENLDFWLACEEFRKIRSRSKLKSKAKSIYNEFIKPDSPKEINLDYNMKEMLQQSLLI 157
Cdd:cd08716    2 ENLMATKYGPIIYATYLKTEHSDENIEFWLACETYKKIASQRKRISMARKLFASYIQPQAPREINIDSPTRKAIIRNIQE 81

                         90       100       110
                 ....*....|....*....|....*....|..
gi 221139707 158 PTPCTFKVAQHRVLYLMEHNSYPRFLESELYQ 189
Cdd:cd08716   82 PTQSCFDEAQRIVYMHMERDSYPRFLESKFYQ 113

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 221139707  73 WAQSLDNLLSSKCGLNFFRLFIKSELCEENLDFWLACEEFRKIRSRSKLKSKAKSIYNEFIKPDSPKEINLDYNMKEMLQ 152
Cdd:cd08744    1 WSQNFDKMMKTPAGRNLFREFLRTEYSEENLLFWLACEDLKKEQNKKVIEEKARLIYEDYISILSPKEVSLDSRVREVIN 80

                         90       100       110
                 ....*....|....*....|....*....|....*...
gi 221139707 153 QSLLIPTPCTFKVAQHRVLYLMEHNSYPRFLESELYQT 190
Cdd:cd08744   81 RNLLDPNPHMYEDAQLQIYTLMHRDSFPRFLNSQIYKS 118

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 221139707  77 LDNLLSSKCGLNFFRLFIKSELCEENLDFWLACEEFRKIRSRSKLKSKAKSIYNEFIKPDSPKEINLDyNMKEMLQQSLL 156
Cdd:cd08741    1 LENLLEDPEGVKRFREFLKKEFSEENVLFWLACEDFKKMQDKTQMQEKAKEIYMTFLSSKASSQVNVE-GQSRLNEKILE 79

                         90       100       110
                 ....*....|....*....|....*....|..
gi 221139707 157 IPTPCTFKVAQHRVLYLMEHNSYPRFLESELY 188
Cdd:cd08741   80 EPHPLMFQKLQDQIFNLMKYDSYSRFLKSDLF 111

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 221139707  70 VSQWAQSLDNLLSSKCGLNFFRLFIKSELCEENLDFWLACEEFrKIRSRSKLKSKAKSIYNEFIKPDSPKEINLDYNMKE 149
Cdd:cd08739    2 VERWAFNFSELIRDPKGRQSFQLFLKKEFSGENLGFWEACEDL-KYGDQSKVKEKAEEIYKLFLAPGARRWINIDGKTMD 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|
gi 221139707 150 MLQQSLLIPTPCTFKVAQHRVLYLMEHNSYPRFLESELYQ 189
Cdd:cd08739   81 ITVKGLKHPHRYVLDAAQTHIYMLMKKDSYARYLKSPIYK 120

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 221139707  70 VSQWAQSLDNLLSSKCGLNFFRLFIKSELCEENLDFWLACEEFRKiRSRSKLKSKAKSIYNEFIKPDSPKEINLDYNMKE 149
Cdd:cd08740    3 VERWGFSFRELLNDPVGRKEFLDFLEKEFSAENLSFWEACEELRY-GEQSKIPELVDSVYQQFLAPGATRWVNIDSKTME 81

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|..
gi 221139707 150 MLQQSLLIPTPCTFKVAQHRVLYLMEHNSYPRFLESELYQTL 191
Cdd:cd08740   82 RTLEGLKQPHRYVLDDAQMHIYMLMKKDSYPRFLKSDLYKNL 123

Regulator of G protein signaling (RGS) domain found in the RGS12 protein; RGS (Regulator of G-protein Signaling) domain is an essential part of the RGS12 protein. RGS12 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. RGS12 belong to the R12 RGS subfamily, which includes RGS10 and RGS14, all of which are highly selective for G-alpha-i1 over G-alpha-q. RGS12 exist in multiple splice variants: RGS12s (short) contains the core RGS/RBD/GoLoco domains, while RGS12L (long) has additional N-terminal PDZ and PTB domains. RGS12 splice variants show distinct expression patterns, suggesting that they have discrete functions during mouse embryogenesis. RGS12 also may play a critical role in coordinating Ras-dependent signals that are required for promoting and maintaining neuronal differentiation.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221139707  77 LDNLLSSKCGLNFFRLFIKSELCEENLDFWLACEEFRKIRSRSK--LKSKAKSIYNEFIKPDSPKEINLDyNMKEMLQQS 154
Cdd:cd08742    1 FERLLQDPVGVRYFSEFLRKEFSEENILFWQACEYFNHVPAHDKkeLSYRAREIFSKFLCSKATTPVNID-SQAQLADDI 79

                         90       100       110
                 ....*....|....*....|....*....|....*
gi 221139707 155 LLIPTPCTFKVAQHRVLYLMEHNSYPRFLESELYQ 189
Cdd:cd08742   80 LNAPHPDMFKEQQLQIFNLMKFDSYTRFLKSPLYQ 114

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 221139707 100 EENLDFWLACEEFRKIRSRSK--LKSKAKSIYNEFIKPDSPKEINLDYNM-KEMLQQS--LLIPTPCTFKVAQHRVLYLM 174
Cdd:cd08732   37 GEDDDFDEQVEELRYILDTDQilLKDQWRHIMNTYIHHDSPLQINLSHTMrKEIVEEDdnPNIHTPDLLLNAYNEVLRLL 116

                         90
                 ....*....|....*
gi 221139707 175 EHNSYPRFLESELYQ 189
Cdd:cd08732  117 KENFYPEFKNLPKYR 131

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 221139707  81 LSSKCGLNFFRLFIKSELCEENLDFWLACEEFR-----KIRSRSK---------------LKSKAKSIYNEFIKPDSPKE 140
Cdd:cd08719    2 LVNNVALSYFIDFMQSVGGQAYLFFWLTVEGYRvsaeqQLSELHLrqrggehqrsdvyemLRAAALNIYDQYLSEKASPR 81

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|..
gi 221139707 141 INLDYNMKEMLQQSLLI--PTPCTFKVAQHRVLYLMEHNS--YPRFLESELY 188
Cdd:cd08719   82 VPLDDSLVKKLLNRLRNdtPSDLWFDDIQQKVFDIMQEDErfYPAFKKSPAY 133

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 221139707  87 LNFFRLFIKSELCEENLDFWLACEEFRKIR-------SRSKLKSKAKSIYNEFIKPDSPKEINLDYNMKEMLQQSLLI-- 157
Cdd:cd08721    8 LFYFMEYMEQEGARNLLQFWLAADNFQSQLaakegqyDGQQAQNDAMIIYDKYFSLQATEPLGFDDKTRLEVESNICReg 87

                         90       100       110
                 ....*....|....*....|....*....|..
gi 221139707 158 -PTPCTFKVAQHRVLYLMEHNSYPRFLESELY 188
Cdd:cd08721   88 gPLPSCFEAPLLQALTTLEQHYLPGFLSSQLY 119

Regulator of G protein signaling domain RGS_RGS22_2; The RGS (Regulator of G-protein Signaling) domain found in the RGS22 protein, a member of the RA/RGS 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 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. RGS22 contains at least 3 copies of the RGS domain in vertebrata and exists in multiple splicing variants. RGS22 is predominantly expressed in testis and believed to play an important role in spermatogenesis.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221139707  81 LSSKCGlNFFRLFIKSELCEE---NLDFWLACEEFRK-----IRSRSKLKSKAKSIYNEFIKPDSPKEINLDYNMKEMLQ 152
Cdd:cd08727    1 LENRAG-NFFTQFCEKSGNKLwknAVYFWFDLQEYHQlfyteTFQPFKVCRKAQRLFSTYIVPGARHNIGCSVRKRKEII 79

                         90       100
                 ....*....|....*....|....
gi 221139707 153 QSLLIPTPCTFK-VAQHRVLYLME 175
Cdd:cd08727   80 KKLSPPFEDLFDaAEEHILLLLLE 103

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221139707 114 KIRSRSKLKSKAKSIYNEFIKPDSPKEINLDYNMKEMLqqSLLI------PTPCTFKVAQHRVLYLMEHNSYPRFLESEL 187
Cdd:cd08735   91 DEKSMKSIERDAVSIYTKYISPDAAKPIPITEEIRNDI--VAKIcgedgqVDPNCFVEAQSFVFSAMEQDHFTEFLRSHF 168

                 .
gi 221139707 188 Y 188
Cdd:cd08735  169 F 169