Regulator of G protein signaling (RGS) domain found in the RGS14 protein; RGS (Regulator of G-protein Signaling) domain is an essential part of the RGS14 protein. RGS14 is a member of the RA/RGS subfamily of RGS proteins family, a diverse group of multifunctional proteins that regulate cellular signaling events downstream of G-protein coupled receptors (GPCRs). As a major G-protein regulator, RGS domain containing proteins are involved in many crucial cellular processes such as regulation of intracellular trafficking, glial differentiation, embryonic axis formation, skeletal and muscle development, and cell migration during early embryogenesis. RGS14 belong to the R12 RGS subfamily, which includes RGS10 and RGS12, all of which are highly selective for G-alpha-i1 over G-alpha-q. RGS14 binds and regulates the subcellular localization and activities of H-Ras and Raf kinases in cells and thereby integrates G protein and Ras/Raf signaling pathways.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1342047405  58 EQPVASWAQSFERLLQDPRGLAYFTEFLKKEFSAENVTFWKACERFQQIPASDTKQLAQEAHNIYHEFLSSQALSPVNID 137
Cdd:cd08743     1 EKSVASWAVSFERLLQDPLGVEYFTEFLKKEFSAENVNFWKACERFQQIPASDTQQLAQEARKIYNEFLSSSSQSPVNID 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*....
gi 1342047405 138 RQAWLSEEVLAQPRPDMFRAQQLQIFNLMKFDSYARFVKSPLYQECLLA 186
Cdd:cd08743    81 QQAWIGEDMLATPSPDMFRAQQLQIFNLMKFDSYARFVKSPLYQDCLLA 129

Ras-binding domain (RBD) 2 of regulator of G protein signaling 14 (RGS14); RGS14 (regulator of G protein signaling 14) is a RGS protein with a multidomain structure that allows it to interact with binding partners from multiple signaling pathways. RGS proteins belong to a large family of GTPase-accelerating proteins (GAPs) which act as key inhibitors of G-protein-mediated cell responses in eukaryotes. RGS14 contains an N-terminal RGS domain, two tandem Ras-binding domains (RBDs) and a G protein regulatory (GPR, also referred to as a GoLoco) motif. RGS14 binds activated H-Ras-GTP through its first RBD and interacts with RAP2-GTP and RAF kinases by the second tandem RBD. RBD is structurally similar to the beta-grasp fold of ubiquitin, a common structure involved in protein-protein interactions. RGS14 modulates neuronal physiology and all of its binding partners have roles in synaptic plasticity.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1342047405 374 RITFQLELVGLERVVRISAKPTKRLQEALQPILAKHGLSLDQVVLHRPGEKQPMDLENPVSSVASQTLVLDTP 446
Cdd:cd17139     1 RITFELEIAFLGKTVRIVAKSSKTLQEALQPILQKYGLRPQEVVLTMSGEKQALDMNTPVSSLANKTLVLDRV 73

Regulator of G protein signaling (RGS) domain found in the RGS14 protein; RGS (Regulator of G-protein Signaling) domain is an essential part of the RGS14 protein. RGS14 is a member of the RA/RGS subfamily of RGS proteins family, a diverse group of multifunctional proteins that regulate cellular signaling events downstream of G-protein coupled receptors (GPCRs). As a major G-protein regulator, RGS domain containing proteins are involved in many crucial cellular processes such as regulation of intracellular trafficking, glial differentiation, embryonic axis formation, skeletal and muscle development, and cell migration during early embryogenesis. RGS14 belong to the R12 RGS subfamily, which includes RGS10 and RGS12, all of which are highly selective for G-alpha-i1 over G-alpha-q. RGS14 binds and regulates the subcellular localization and activities of H-Ras and Raf kinases in cells and thereby integrates G protein and Ras/Raf signaling pathways.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1342047405  58 EQPVASWAQSFERLLQDPRGLAYFTEFLKKEFSAENVTFWKACERFQQIPASDTKQLAQEAHNIYHEFLSSQALSPVNID 137
Cdd:cd08743     1 EKSVASWAVSFERLLQDPLGVEYFTEFLKKEFSAENVNFWKACERFQQIPASDTQQLAQEARKIYNEFLSSSSQSPVNID 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*....
gi 1342047405 138 RQAWLSEEVLAQPRPDMFRAQQLQIFNLMKFDSYARFVKSPLYQECLLA 186
Cdd:cd08743    81 QQAWIGEDMLATPSPDMFRAQQLQIFNLMKFDSYARFVKSPLYQDCLLA 129

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 1342047405   67 SFERLLQDPRGLAYFTEFLKKEFSAENVTFWKACERFQQIPasDTKQLAQEAHNIYHEFLSSQALSPVNIDRQAWLS-EE 145
Cdd:smart00315   1 SLESLLSDPIGRLLFREFLESEFSEENLEFWLAVEEFKKAE--DDEERIAKAREIYDKFLSPNAPKEVNLDSDLREKiEE 78

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|
gi 1342047405  146 VL--AQPRPDMFRAQQLQIFNLMKFDSYARFVKSPLYQEC 183
Cdd:smart00315  79 NLesEEPPPDLFDEAQREVYELLEKDSFPRFLESDYYLRF 118

Ras-binding domain (RBD) 2 of regulator of G protein signaling 14 (RGS14); RGS14 (regulator of G protein signaling 14) is a RGS protein with a multidomain structure that allows it to interact with binding partners from multiple signaling pathways. RGS proteins belong to a large family of GTPase-accelerating proteins (GAPs) which act as key inhibitors of G-protein-mediated cell responses in eukaryotes. RGS14 contains an N-terminal RGS domain, two tandem Ras-binding domains (RBDs) and a G protein regulatory (GPR, also referred to as a GoLoco) motif. RGS14 binds activated H-Ras-GTP through its first RBD and interacts with RAP2-GTP and RAF kinases by the second tandem RBD. RBD is structurally similar to the beta-grasp fold of ubiquitin, a common structure involved in protein-protein interactions. RGS14 modulates neuronal physiology and all of its binding partners have roles in synaptic plasticity.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1342047405 374 RITFQLELVGLERVVRISAKPTKRLQEALQPILAKHGLSLDQVVLHRPGEKQPMDLENPVSSVASQTLVLDTP 446
Cdd:cd17139     1 RITFELEIAFLGKTVRIVAKSSKTLQEALQPILQKYGLRPQEVVLTMSGEKQALDMNTPVSSLANKTLVLDRV 73

Raf-like Ras-binding domain;

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1342047405  304 YCCVYLPDGTASLALARPGLTIRDMLAGICEKRGLSLPDIKVYLVGnEQKALVLDQDCTVLADQEVRLENR 374
Cdd:smart00455   1 TCKVHLPDNQRTVVKVRPGKTVRDALAKALKKRGLNPECCVVRLRG-EKKPLDLNQPISSLDGQELVVEEL 70

Regulator of G protein signaling (RGS) domain found in the RGS14 protein; RGS (Regulator of G-protein Signaling) domain is an essential part of the RGS14 protein. RGS14 is a member of the RA/RGS subfamily of RGS proteins family, a diverse group of multifunctional proteins that regulate cellular signaling events downstream of G-protein coupled receptors (GPCRs). As a major G-protein regulator, RGS domain containing proteins are involved in many crucial cellular processes such as regulation of intracellular trafficking, glial differentiation, embryonic axis formation, skeletal and muscle development, and cell migration during early embryogenesis. RGS14 belong to the R12 RGS subfamily, which includes RGS10 and RGS12, all of which are highly selective for G-alpha-i1 over G-alpha-q. RGS14 binds and regulates the subcellular localization and activities of H-Ras and Raf kinases in cells and thereby integrates G protein and Ras/Raf signaling pathways.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1342047405  58 EQPVASWAQSFERLLQDPRGLAYFTEFLKKEFSAENVTFWKACERFQQIPASDTKQLAQEAHNIYHEFLSSQALSPVNID 137
Cdd:cd08743     1 EKSVASWAVSFERLLQDPLGVEYFTEFLKKEFSAENVNFWKACERFQQIPASDTQQLAQEARKIYNEFLSSSSQSPVNID 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*....
gi 1342047405 138 RQAWLSEEVLAQPRPDMFRAQQLQIFNLMKFDSYARFVKSPLYQECLLA 186
Cdd:cd08743    81 QQAWIGEDMLATPSPDMFRAQQLQIFNLMKFDSYARFVKSPLYQDCLLA 129

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 1342047405  68 FERLLQDPRGLAYFTEFLKKEFSAENVTFWKACERFQQIPASDTKQLAQEAHNIYHEFLSSQALSPVNIDRQAWLSEEVL 147
Cdd:cd08742     1 FERLLQDPVGVRYFSEFLRKEFSEENILFWQACEYFNHVPAHDKKELSYRAREIFSKFLCSKATTPVNIDSQAQLADDIL 80

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 1342047405 148 AQPRPDMFRAQQLQIFNLMKFDSYARFVKSPLYQE 182
Cdd:cd08742    81 NAPHPDMFKEQQLQIFNLMKFDSYTRFLKSPLYQE 115

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 1342047405  68 FERLLQDPRGLAYFTEFLKKEFSAENVTFWKACERFQQipASDTKQLAQEAHNIYHEFLSSQALSPVNIDRQAWLSEEVL 147
Cdd:cd08741     1 LENLLEDPEGVKRFREFLKKEFSEENVLFWLACEDFKK--MQDKTQMQEKAKEIYMTFLSSKASSQVNVEGQSRLNEKIL 78

                          90       100       110
                  ....*....|....*....|....*....|...
gi 1342047405 148 AQPRPDMFRAQQLQIFNLMKFDSYARFVKSPLY 180
Cdd:cd08741    79 EEPHPLMFQKLQDQIFNLMKYDSYSRFLKSDLF 111

Regulator of G protein signaling (RGS) domain found in the R7 subfamily of proteins; The RGS (Regulator of G-protein Signaling) domain is an essential part of the R7 (Neuronal RGS) protein subfamily of the RGS protein family, a diverse group of multifunctional proteins that regulate cellular signaling events downstream of G-protein coupled receptors (GPCRs). As a major G-protein regulator, RGS domain containing proteins are involved in many crucial cellular processes such as regulation of intracellular trafficking, glial differentiation, embryonic axis formation, skeletal and muscle development, and cell migration during early embryogenesis. The R7 subfamily includes RGS6, RGS7, RGS9, and RGS11, all of which, in humans, 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. In addition, R7 proteins were found to bind many other proteins outside of the G protein signaling pathways including: m-opioid receptor, beta-arrestin, alpha-actinin-2, NMDAR, polycystin, spinophilin, guanylyl cyclase, among others.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1342047405  61 VASWAQSFERLLQDPRGLAYFTEFLKKEFSAENVTFWKACERFQQIPASDTKQLAQEahnIYHEFLSSQALSPVNID-RQ 139
Cdd:cd08705     2 VKRWGFSFSELLKDPVGREQFLKFLEKEFSGENLRFWEACQDLKYGPQSQVPEKVQE---IYQEFLAPGAPSWINIDsKT 78

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|...
gi 1342047405 140 AWLSEEVLAQPRPDMFRAQQLQIFNLMKFDSYARFVKSPLYQE 182
Cdd:cd08705    79 MEITLKNLKDPHRYTFDAAQEHIYMLMKKDSYPRFLRSDIYKE 121

Ras-binding domain (RBD) 2 of regulator of G protein signaling 14 (RGS14); RGS14 (regulator of G protein signaling 14) is a RGS protein with a multidomain structure that allows it to interact with binding partners from multiple signaling pathways. RGS proteins belong to a large family of GTPase-accelerating proteins (GAPs) which act as key inhibitors of G-protein-mediated cell responses in eukaryotes. RGS14 contains an N-terminal RGS domain, two tandem Ras-binding domains (RBDs) and a G protein regulatory (GPR, also referred to as a GoLoco) motif. RGS14 binds activated H-Ras-GTP through its first RBD and interacts with RAP2-GTP and RAF kinases by the second tandem RBD. RBD is structurally similar to the beta-grasp fold of ubiquitin, a common structure involved in protein-protein interactions. RGS14 modulates neuronal physiology and all of its binding partners have roles in synaptic plasticity.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1342047405 374 RITFQLELVGLERVVRISAKPTKRLQEALQPILAKHGLSLDQVVLHRPGEKQPMDLENPVSSVASQTLVLDTP 446
Cdd:cd17139     1 RITFELEIAFLGKTVRIVAKSSKTLQEALQPILQKYGLRPQEVVLTMSGEKQALDMNTPVSSLANKTLVLDRV 73

Raf-like Ras-binding domain;

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1342047405 304 YCCVYLPDGTASLALARPGLTIRDMLAGICEKRGLSLPDIKVYLVGNEQKALVLDQDCTVLADQEVRLE 372
Cdd:pfam02196   1 LCRVYLPDGQRTVVQVRPGETVRDALSKLCKKRGLNPEACDVYLVGGDKYPLDLDTDSSTLEGEEVRVE 69

Regulator of G protein signaling (RGS) domain found in the RGS20 protein; The RGS (Regulator of G-protein Signaling) domain is an essential part of the RGS20 protein (also known as RGSZ1), a member of the RZ subfamily of the RGS protein family. They are a diverse group of multifunctional proteins that regulate cellular signaling events downstream of G-protein coupled receptors (GPCRs). RGS proteins play critical regulatory roles as GTPase activating proteins (GAPs) of the heterotrimeric G-protein G-alpha-subunits. Deactivation of G-protein signaling is controlled by the RGS domain, which accelerates GTPase activity of the alpha subunit by hydrolysis of GTP to GDP resulting in reassociation of the alpha-subunit with the beta-gamma-dimer and inhibition of downstream activity. As a major G-protein regulator, the RGS domain containing proteins are involved in many crucial cellular processes such as regulation of intracellular trafficking, glial differentiation, embryonic axis formation, skeletal and muscle development, and cell migration during early embryogenesis. The RZ subfamily of RGS proteins include RGS17, RGS19 (former GAIP), and the splice variant of RGS20, Ret-RGS. RGS20 is expressed exclusively in brain, with the highest concentrations in the temporal lobe and the caudate nucleus and may play a role in signaling regulation in these brain regions. RGS20 acts as a GAP of both G-alpha-z and G-alpha-I and controls signaling in the mu opioid receptor pathway.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1342047405  27 TAGSQAQGEGRGSSLSI--HSLPSGPSSPFSTEEQpVASWAQSFERLLQDPRGLAYFTEFLKKEFSAENVTFWKACERFQ 104
Cdd:cd08746    12 TVRNQEDERNRRTSYEFraEGIPNCEESPKPTLEE-VCAWGQSFDKLMLTPAGRNAFREFLRTEFSEENMLFWMACEELK 90

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1342047405 105 QipASDTKQLAQEAHNIYHEFLSsqALSPVNIDRQAWLSEEV---LAQPRPDMFRAQQLQIFNLMKFDSYARFVKSPLYQ 181
Cdd:cd08746    91 K--EANKSVIEEKARIIYEDYIS--ILSPKEVSLDSRVREVInrnMLEPSQHTFDDAQLQIYTLMHRDSYPRFMNSAIYK 166

                  .
gi 1342047405 182 E 182
Cdd:cd08746   167 N 167

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 1342047405  61 VASWAQSFERLLQDPRGLAYFTEFLKKEFSAENVTFWKACERFQQipaSDTKQLAQEAHNIYHEFLSSQALSPVNID-RQ 139
Cdd:cd08740     3 VERWGFSFRELLNDPVGRKEFLDFLEKEFSAENLSFWEACEELRY---GEQSKIPELVDSVYQQFLAPGATRWVNIDsKT 79

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*...
gi 1342047405 140 AWLSEEVLAQPRPDMFRAQQLQIFNLMKFDSYARFVKSPLYQEcLLAE 187
Cdd:cd08740    80 MERTLEGLKQPHRYVLDDAQMHIYMLMKKDSYPRFLKSDLYKN-LLAE 126

Ras-binding domain (RBD) 1 of regulator of G protein signaling 12 (RGS12) and similar proteins; Regulator of G protein signaling (RGS) proteins belong to a large family of GTpase-accelerating proteins (GAPs) which act as key inhibitors of G-protein-mediated cell responses in eukaryotes. This RGS12-like subfamily is composed of RGS12 and RGS14, with multidomain architectures including a RGS domain, two tandem Ras-binding domains (RBDs), and a second Galpha interacting domain, the GoLoco motif. The RBD is structurally similar to the beta-grasp fold of ubiquitin, a common structure involved in protein-protein interactions. Ubiquitin is a protein modifier in eukaryotes that is involved in various cellular processes, including transcriptional regulation, cell cycle control, and DNA repair.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1342047405 303 KYCCVYLPDGTASLALARPGLTIRDMLAGICEKRGLSLPDIKVYLVGNEqKALVLDQDCTVLADQEVRLEN 373
Cdd:cd01817     1 KLCRVILPDGSTTVVQAKPGETIRQLLTRLLEKRGLSYAAFDVFIVGSD-KPLDLNEDSSILGGKEVRVEQ 70

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 1342047405  68 FERLLQDPRGLAYFTEFLKKEFSAENVTFWKACERFQQIpASDTKqLAQEAHNIYHEFLSSQALSPVNIDRQAW-LSEEV 146
Cdd:cd08710     1 FDLLLNSKNGVAAFHAFLKTEFSEENLEFWLACEEFKKI-RSATK-LASRAHHIFEEFIRSEAPKEVNIDHETReLTRTN 78

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 1342047405 147 LAQPRPDMFRAQQLQIFNLMKFDSYARFVKSPLYQE 182
Cdd:cd08710    79 LQAATTSCFDVAQGKTRTLMEKDSYPRFLKSPAYRD 114

Regulator of G protein signaling (RGS) domain found in the RGS4 protein; The RGS (Regulator of G-protein Signaling) domain is an essential part of the RGS4 protein. RGS4 is a member of the R4/RGS subfamily of the RGS family, a diverse group of multifunctional proteins that regulate cellular signaling events downstream of G-protein coupled receptors (GPCRs). As a major G-protein regulator, RGS domain containing proteins are involved in many crucial cellular processes such as regulation of intracellular trafficking, glial differentiation, embryonic axis formation, skeletal and muscle development, and cell migration during early embryogenesis. RGS proteins play critical regulatory roles as GTPase activating proteins (GAPs) of the heterotrimeric G-protein G-alpha subunits. The RGS domain controls G-protein signaling by accelerating the GTPase activity of the G-alpha subunit which leads to G protein deactivation and promotes desensitization. RGS4 is expressed widely in brain including prefrontal cortex, striatum, locus coeruleus (LC), and hippocampus and has been implicated in regulation of opioid, cholinergic, and serotonergic signaling. Dysfunctions in RGS4 proteins are involved in etiology of Parkinson's disease, addiction, and schizophrenia. RGS4 also is up-regulated in the failing human heart. RGS4 interacts with many binding partners outside of GPCR pathways, including calmodulin, COP, Kir3, PIP, calcium/CaM, PA, ErbB3, and 14-3-3.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1342047405  68 FERLLQDPRGLAYFTEFLKKEFSAENVTFWKACERFQQIPASDtkQLAQEAHNIYHEFLSSQALSPVNIDrqAWLSEEV- 146
Cdd:cd08714     1 LENLINHECGLAAFKAFLKSEYSEENIDFWVSCEDYKKTKSPS--KLSPKARKIYEEFISVQATKEVNLD--SCTREETs 76

                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 1342047405 147 --LAQPRPDMFRAQQLQIFNLMKFDSYARFVKSPLYQE 182
Cdd:cd08714    77 rnMLEPTISCFDEAQKKIFTLMEKDSYRRFLKSRFYLD 114

Regulator of G protein signaling (RGS) domain found in the RGS6 protein; The RGS (Regulator of G-protein Signaling) domain is an essential part of the RGS6 protein, a member of R7 subfamily of the RGS protein family. RGS is a diverse group of multifunctional proteins that regulate cellular signaling events downstream of G-protein coupled receptors (GPCRs). Other members of the R7 subfamily (Neuronal RGS) include: RGS7, RGS9, and RGS11, all of which are expressed predominantly in the nervous system, form an obligatory complex with G-beta-5, and play important roles in the regulation of crucial neuronal processes such as vision and motor control. Additionally they have been implicated in many neurological conditions such as anxiety, schizophrenia, and drug dependence. RGS6 exists in multiple splice isoforms with identical RGS domains, but possess complete or incomplete GGL domains and distinct N- and C-terminal domains. RGS6 interacts with SCG10, a neuronal growth-associated protein and therefore regulates neuronal differentiation. Another RGS6-binding protein is DMAP1, a component of the Dnmt1 complex involved in repression of newly replicated genes. Mutations of a critical residue required for interaction of RGS6 protein with G proteins did not affect the ability of RGS6 to interact with both SCG10 and DMAP1. As a major G-protein regulator, RGS domain containing proteins are involved in many crucial cellular processes such as regulation of intracellular trafficking, glial differentiation, embryonic axis formation, skeletal and muscle development, and cell migration during early embryogenesis.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1342047405  59 QPVASWAQSFERLLQDPRGLAYFTEFLKKEFSAENVTFWKACERFQQIPASDTKQLAQEahnIYHEFLSSQALSPVNIDR 138
Cdd:cd08737     1 QRVKRWGFSLDEVLKDPVGRDQFLRFLESEFSSENLRFWLAVQDLKKQPLQDVAKRVEE---IWQEFLAPGAPSAINLDS 77

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*...
gi 1342047405 139 QAW-LSEEVLAQPRPDMFRAQQLQIFNLMKFDSYARFVKSPLYQECLL 185
Cdd:cd08737    78 HSYeKTSQNVKDPGRYTFEDAQEHIYKLMKSDSYARFLRSNAYQDLLL 125

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 1342047405  68 FERLLQDPRGLAYFTEFLKKEFSAENVTFWKACERFQQIPASdtKQLAQEAHNIYHEFLSSQALSPVNIDRQawlSEEVL 147
Cdd:cd08709     1 FDELLASKYGVAAFRAFLKSEFSEENIEFWLACEDFKKTKSP--QKLTSKAKKIYTDFIEKEAPKEINIDFQ---TKTLI 75

                          90       100       110
                  ....*....|....*....|....*....|....*....
gi 1342047405 148 AQ----PRPDMFRAQQLQIFNLMKFDSYARFVKSPLYQE 182
Cdd:cd08709    76 AQniqeATSGCFTAAQKRVYSLMENNSYPRFLESEFYQE 114

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1342047405  68 FERLLQDPRGLAYFTEFLKKEFSAENVTFWKACERFQqipASDTKQLAQEAHNIYHEFLSSQALSPVNIDRQAWLS-EEV 146
Cdd:cd08715     1 LEKLLASQTGQNVFRSFLKSEFSEENIEFWLACEDYK---KTESDLLPCKAEEIYKEFVQSDAAKQINIDFRTREStAKK 77

                          90       100       110
                  ....*....|....*....|....*....|....
gi 1342047405 147 LAQPRPDMFRAQQLQIFNLMKFDSYARFVKSPLY 180
Cdd:cd08715    78 IKAPTPTCFDEAQKVIYILMERDSYPRFLKSDIY 111

Raf-like Ras-binding domain;

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1342047405  304 YCCVYLPDGTASLALARPGLTIRDMLAGICEKRGLSLPDIKVYLVGnEQKALVLDQDCTVLADQEVRLENR 374
Cdd:smart00455   1 TCKVHLPDNQRTVVKVRPGKTVRDALAKALKKRGLNPECCVVRLRG-EKKPLDLNQPISSLDGQELVVEEL 70

Regulator of G protein signaling (RGS) domain found in the RGS21 protein; The RGS (Regulator of G-protein Signaling) domain is an essential part RGS21 protein, a member of 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. As a major G-protein regulator, RGS domain containing proteins are involved in many crucial cellular processes. RGS proteins regulate many aspects of embryonic development such as glial differentiation, embryonic axis formation, skeletal and muscle development, cell migration during early embryogenesis, apoptosis, and cell proliferation, as well as modulation of cardiac development. RGS21 is a member of the R4/RGS subfamily and its mRNA was detected only in sensory taste cells that express sweet taste receptors and the taste G-alpha subunit, gustducin, suggesting a potential role in regulating taste transduction.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1342047405  71 LLQDPRGLAYFTEFLKKEFSAENVTFWKACERFQQipASDTKQLAQEAHNIYHEFLSSQALSPVNIDRQAW-LSEEVLAQ 149
Cdd:cd08723     1 LLANQAGLDAFRTFLKSEFSEENVEFWLACEDFKK--TKSSTEIALKAQMIYSEFIQADAPKEINIDFHTRdLISQNISE 78

                          90       100       110
                  ....*....|....*....|....*....|...
gi 1342047405 150 PRPDMFRAQQLQIFNLMKFDSYARFVKSPLYQE 182
Cdd:cd08723    79 PTLKCFDEAQSLIYCLMAKDSFPRFLKSEVYKK 111

Ras-binding domain (RBD) 1 of regulator of G protein signaling 12 (RGS12); RGS12 (regulator of G protein signaling 12) is a multidomain RGS protein with numerous signaling regulatory elements. In addition to a central RGS domain which is responsible for GAP activity, the long RGS12 splice variant contains a PDZ (PSD-95/Discs-large/ZO-1 homology) domain capable of binding the interleukin-8 receptor B (CXCR2) or its own C-terminal, a phosphotyrosine-binding (PTB) domain that associates with tyrosine-phosphorylated N-type calcium channel, two tandem Ras-binding domains (RBDs) that may integrate signaling pathways involving both heterotrimeric and monomeric G-proteins, and a GoLoco (G-alpha-i/o-Loco) interaction motif which has guanine nucleotide dissociation inhibitor (GDI) activity toward G-alpha-i subunits. RBD is structurally similar to the beta-grasp fold of ubiquitin, a common structure involved in protein-protein interactions. RGS proteins belong to a large family of GTpase-accelerating proteins (GAPs) which act as key inhibitors of G-protein-mediated cell responses in eukaryotes.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1342047405 303 KYCCVYLPDGTASLALARPGLTIRDMLAGICEKRGLSLPDIKVYLVGNEqKALVLDQDCTVLADQEVRLE 372
Cdd:cd17136     1 KHCCVNLPDGSSCAVAIKPGVSIREMLSGLCEKLGINLAAVDLFLVGGD-KPLVLDQDSSTLESRDLRLE 69

Raf-like Ras-binding domain;

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1342047405  385 ERVVRISAKPTKRLQEALQPILAKHGLSLDQVVLHRPGEKQPMDLENPVSSVASQTLVLDT 445
Cdd:smart00455   9 NQRTVVKVRPGKTVRDALAKALKKRGLNPECCVVRLRGEKKPLDLNQPISSLDGQELVVEE 69

Regulator of G protein signaling (RGS) domain found in the Axin protein; The RGS (Regulator of G-protein Signaling) domain is an essential part of the Axin protein. Axin is a member of the RA/RGS subfamily of the RGS protein family, a diverse group of multifunctional proteins that regulate cellular signaling events downstream of G-protein coupled receptors (GPCRs). As a major G-protein regulator, RGS domain containing proteins are involved in many crucial cellular processes such as regulation of intracellular trafficking, glial differentiation, embryonic axis formation, skeletal and muscle development, and cell migration during early embryogenesis. RGS proteins regulate many aspects of embryonic development such as glial differentiation, embryonic axis formation, and skeletal and muscle development. The RGS domain of Axin is specifically interacts with the heterotrimeric G-alpha12 protein, but not with closely related G-alpha13, and provides a unique tool to regulate G-alpha12-mediated signaling processes. The RGS domain of Axin also interacts with the tumor suppressor protein APC (Adenomatous Polyposis Coli) in order to control the cytoplasmic level of the proto-oncogene, beta-catenin.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1342047405  71 LLQDPRGLAYFTEFLKKEFSAENVTFWKACERFQQIPASDTKQlAQEAHNIYHEFLSSQALSPVNIDRQ--AWLSEEVLA 148
Cdd:cd08707     4 LLDDQDGIELFRTYLEQEGCADLLDFWFACNGFRKMSDSEEKR-SKLAKAIYRRYIKDNGIVSRQLKPAtkSFIKECIKK 82

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 1342047405 149 QP-RPDMFRAQQLQIFNLMKFDSYARFVKSPLYQE 182
Cdd:cd08707    83 QQlDPAMFDQAQTEIQTTMEENTYPSFLKSDIYLE 117

Ras-binding domain (RBD), structurally similar to a beta-grasp ubiquitin-like fold; The RBD of the serine/threonine kinase Raf is structurally similar to the beta-grasp fold of ubiquitin, a common structure involved in protein-protein interactions. Ubiquitin (Ub) is a protein modifier in eukaryotes that is involved in various cellular processes, including transcriptional regulation, cell cycle control, and DNA repair. A Raf-like RBD is also present in Regulator of G protein Signaling (RGS12 and RGS14) members of GTPase activating proteins.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1342047405 303 KYCCVYLPDGTASLALA-RPGLTIRDMLAGICEKRGLSLPDIKVYLVGnEQKALVLDQDCTVLADQEVRLE 372
Cdd:cd01760     1 NTFRLFLPNNETSVVVAvKPGKSLHEVLMPVLERHGLQLECVDVFLLG-EKAPLDLNTDASSLIGQELRLD 70

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 1342047405  69 ERLLQDPrGLAY-FTEFLKKEFSAENVTFWKACERFQ-----------------QIPASDTKQLAQeAHNIYHEFLSSQA 130
Cdd:cd08708     3 DKILKDP-GLRYlFREHLEKEFCEENLSFYLEVKEFLkkmtilsklldfkssqaADEDLDRESLAQ-AYHIYNTYLAPGS 80

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1342047405 131 LSPVNIDRQ------AWLSEEVLAQPRP----------DMFRAQQLQIFNLMKFDSYARFVKSPLY 180
Cdd:cd08708    81 PCELNIDHNlrnritTIMTEKIVGEDDSmaeslqgveaLFEEAQNAVFKPLMAGDSVPKFLKQPEY 146

Ras-binding domain (RBD) found in RAF family serine/threonine kinases; The RAF family includes three RAF serine/threonine kinases ARAF, BRAF, and RAF1/CRAF. These are encoded by proto-oncogenes, and activate the mitogen-activated protein kinase/extracellular-signal-regulated kinase (MAPK/ERK) cascade downstream of RAS. They share a common structure consisting of an N-terminal regulatory domain and a C-terminal kinase domain. There are three conserved regions (CR1-3) in the regulatory domain, CR1 contains a Ras-binding domain (RBD) and a cysteine-rich domain (CRD), CR2 is a serine/threonine-rich domain, and CR3 encodes the kinase domain required for RAF. The RBD of RAF has a beta-grasp ubiquitin-like fold, a common structure involved in protein-protein interactions.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1342047405 307 VYLPDGTASLALARPGLTIRDMLAGICEKRGLSLPDIKVYLVGNeqKALVL-DQDCTVLADQEVRLE 372
Cdd:cd01816     5 AHLPNQQRTTVEVKPGQTLREALEKAMKRRGLTPEMCVVYRKGT--REPVSwDTDISTLEGEEISVE 69

Regulator of G protein signaling (RGS) domain found in the Sorting Nexin 25 (SNX25) protein; The RGS (Regulator of G-protein Signaling) domain is an essential part of the SNX25 (Sorting Nexin 25) 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. SNX25 is a member of the Dopamine receptors (DAR) signalplex and regulates the trafficking of D1 and D2 DARs.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1342047405  71 LLQDPRGLAYFTEFLKKEFSAENVTFWKACERFQQIPASDTKQLAQEahnIYHEFLSSQAlSPVNIDRQAWLSEE--VLA 148
Cdd:cd08720     1 ILANVFGRKYLSQFLERMDSQALIGFWEAVEELRSANKSEWHQLGAE---IFYTFIVEPT-AEIKVDKSLRKRIEqfLLG 76

                          90       100       110
                  ....*....|....*....|....*....|....
gi 1342047405 149 QPRPDMFRAQQLQIFNLMKFDSYARFVKSPLYQE 182
Cdd:cd08720    77 DKGPEVFYEVQENVVETLEEKYYPSFVVSDQYKQ 110

Regulator of G protein signaling domain; These uncharacterized RGS-like domains are found in proteins that also contain one or more PX domains. The RGS domain is an essential part of the Regulator of G-protein Signaling (RGS) protein family, a diverse group of multifunctional proteins that regulate cellular signaling events downstream of G-protein coupled receptors (GPCRs). RGS proteins play critical regulatory role as GTPase activating proteins (GAPs) of the heterotrimeric G-protein G-alpha-subunits. As a major G-protein regulator, the RGS domain containing proteins that are involves in many crucial cellular processes. RGS proteins regulate intracellular trafficking and provide vital support for signal transduction. 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, others RGS proteins play important role in neuronal signals modulation. Some RGS proteins are the principal elements needed for proper vision.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1342047405  72 LQDPRGLAYFTEFLKKEFSAENVTFWKACERFQ--------------QIPASDTKQLAQEAHNIY---------HEFLSS 128
Cdd:cd08729     1 LRDPSSLSYFMEFMDRRNRSQLVQFWLVVEGFKnpledtendysldsSQSRSWIDSDKEDIAMIYetyfsdpspSLNVPK 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1342047405 129 QALSPV----NIDRQAWLSEEVlAQPRPDMFRAQQlQIFNLMKFDSYARFVKSPLY 180
Cdd:cd08729    81 ASRDPIrlflNAGVNASPNEQY-RKARRAVLMAQR-AVYEEMEEEDFPEFKKSELF 134