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 1489866114  58 EQPVASWALSFERLLQDPLGLAYFTEFLKKEFSAENVTFWKACERFQQIPASDTQQLAQEARNIYQEFLSSQALSPVNID 137
Cdd:cd08743     1 EKSVASWAVSFERLLQDPLGVEYFTEFLKKEFSAENVNFWKACERFQQIPASDTQQLAQEARKIYNEFLSSSSQSPVNID 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*....
gi 1489866114 138 RQAWLGEEVLAEPRPDMFRAQQLQIFNLMKFDSYARFVKSPLYRECLLA 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 1489866114 373 RITFELELTALERVVRISAKPTKRLQEALQPILEKHGLSPLEVVLHRPGEKQPLDLGKLVSSVAAQRLVLDT 444
Cdd:cd17139     1 RITFELEIAFLGKTVRIVAKSSKTLQEALQPILQKYGLRPQEVVLTMSGEKQALDMNTPVSSLANKTLVLDR 72

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 1489866114  58 EQPVASWALSFERLLQDPLGLAYFTEFLKKEFSAENVTFWKACERFQQIPASDTQQLAQEARNIYQEFLSSQALSPVNID 137
Cdd:cd08743     1 EKSVASWAVSFERLLQDPLGVEYFTEFLKKEFSAENVNFWKACERFQQIPASDTQQLAQEARKIYNEFLSSSSQSPVNID 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*....
gi 1489866114 138 RQAWLGEEVLAEPRPDMFRAQQLQIFNLMKFDSYARFVKSPLYRECLLA 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 1489866114   67 SFERLLQDPLGLAYFTEFLKKEFSAENVTFWKACERFQQIPasDTQQLAQEARNIYQEFLSSQALSPVNIDRQAWlgEEV 146
Cdd:smart00315   1 SLESLLSDPIGRLLFREFLESEFSEENLEFWLAVEEFKKAE--DDEERIAKAREIYDKFLSPNAPKEVNLDSDLR--EKI 76

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|..
gi 1489866114  147 L-----AEPRPDMFRAQQLQIFNLMKFDSYARFVKSPLYREC 183
Cdd:smart00315  77 EenlesEEPPPDLFDEAQREVYELLEKDSFPRFLESDYYLRF 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 1489866114 373 RITFELELTALERVVRISAKPTKRLQEALQPILEKHGLSPLEVVLHRPGEKQPLDLGKLVSSVAAQRLVLDT 444
Cdd:cd17139     1 RITFELEIAFLGKTVRIVAKSSKTLQEALQPILQKYGLRPQEVVLTMSGEKQALDMNTPVSSLANKTLVLDR 72

Raf-like Ras-binding domain;

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1489866114  303 YCCVYLPDGTASLALARPGLTIRDMLAGICEKRGLSLPDIKVYLVGnEQKALVLDQDCTVLADQEVRLENR 373
Cdd:smart00455   1 TCKVHLPDNQRTVVKVRPGKTVRDALAKALKKRGLNPECCVVRLRG-EKKPLDLNQPISSLDGQELVVEEL 70

GoLoco motif;

                          10        20
                  ....*....|....*....|..
gi 1489866114 500 EGLVELLNRVQSSGAHDQRGLL 521
Cdd:pfam02188   1 EDFFDLLARVQSSRLDDQRCSL 22

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 1489866114  58 EQPVASWALSFERLLQDPLGLAYFTEFLKKEFSAENVTFWKACERFQQIPASDTQQLAQEARNIYQEFLSSQALSPVNID 137
Cdd:cd08743     1 EKSVASWAVSFERLLQDPLGVEYFTEFLKKEFSAENVNFWKACERFQQIPASDTQQLAQEARKIYNEFLSSSSQSPVNID 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*....
gi 1489866114 138 RQAWLGEEVLAEPRPDMFRAQQLQIFNLMKFDSYARFVKSPLYRECLLA 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 1489866114  68 FERLLQDPLGLAYFTEFLKKEFSAENVTFWKACERFQQIPASDTQQLAQEARNIYQEFLSSQALSPVNIDRQAWLGEEVL 147
Cdd:cd08742     1 FERLLQDPVGVRYFSEFLRKEFSEENILFWQACEYFNHVPAHDKKELSYRAREIFSKFLCSKATTPVNIDSQAQLADDIL 80

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 1489866114 148 AEPRPDMFRAQQLQIFNLMKFDSYARFVKSPLYRE 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 1489866114  68 FERLLQDPLGLAYFTEFLKKEFSAENVTFWKACERFQQipASDTQQLAQEARNIYQEFLSSQALSPVNIDRQAWLGEEVL 147
Cdd:cd08741     1 LENLLEDPEGVKRFREFLKKEFSEENVLFWLACEDFKK--MQDKTQMQEKAKEIYMTFLSSKASSQVNVEGQSRLNEKIL 78

                          90       100       110
                  ....*....|....*....|....*....|...
gi 1489866114 148 AEPRPDMFRAQQLQIFNLMKFDSYARFVKSPLY 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 1489866114  61 VASWALSFERLLQDPLGLAYFTEFLKKEFSAENVTFWKACERFQQIPASDTQQLAQEarnIYQEFLSSQALSPVNID-RQ 139
Cdd:cd08705     2 VKRWGFSFSELLKDPVGREQFLKFLEKEFSGENLRFWEACQDLKYGPQSQVPEKVQE---IYQEFLAPGAPSWINIDsKT 78

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|...
gi 1489866114 140 AWLGEEVLAEPRPDMFRAQQLQIFNLMKFDSYARFVKSPLYRE 182
Cdd:cd08705    79 MEITLKNLKDPHRYTFDAAQEHIYMLMKKDSYPRFLRSDIYKE 121

Regulator of G protein signaling (RGS) domain superfamily; The RGS domain is an essential part of the Regulator of G-protein Signaling (RGS) protein family, a diverse group of multifunctional proteins that regulate cellular signaling events downstream of G-protein coupled receptors (GPCRs). RGS proteins play critical regulatory roles as GTPase activating proteins (GAPs) of the heterotrimeric G-protein G-alpha-subunits. While inactive, G-alpha-subunits bind GDP, which is released and replaced by GTP upon agonist activation. GTP binding leads to dissociation of the alpha-subunit and the beta-gamma-dimer, allowing them to interact with effectors molecules and propagate signaling cascades associated with cellular growth, survival, migration, and invasion. Deactivation of the G-protein signaling controlled by the RGS domain accelerates GTPase activity of the alpha subunit by hydrolysis of GTP to GDP, which results in the reassociation of the alpha-subunit with the beta-gamma-dimer and thereby inhibition of downstream activity. As a major G-protein regulator, RGS domain containing proteins are involved in many crucial cellular processes such as regulation of intracellular trafficking, glial differentiation, embryonic axis formation, skeletal and muscle development, and cell migration during early embryogenesis. RGS proteins are also involved in apoptosis and cell proliferation, as well as modulation of cardiac development. Several RGS proteins can fine-tune immune responses, while others play important roles in neuronal signals modulation. Some RGS proteins are principal elements needed for proper vision.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1489866114  72 LQDPLGLAYFTEFLKKEFSAENVTFWKACERFQQIPASDTqQLAQEARNIYQEFLSSQALSPVNIDRQ-------AWLGE 144
Cdd:cd07440     1 LRDPYGLEYFRQFLKSEHCEENLEFWLAVEKFKKTTSSDE-ELKSKAKEIYDKYISKDAPKEINIPESireeieeNLEEP 79

                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 1489866114 145 evlaEPRPDMFRAQQLQIFNLMKFDSYARFVKSPLYRE 182
Cdd:cd07440    80 ----YPDPDCFDEAQEHILNLLEKDSYPRFLKSDLYLK 113

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 1489866114  44 HSLPSGPSSPFPTEEQpVASWALSFERLLQDPLGLAYFTEFLKKEFSAENVTFWKACERFQQipASDTQQLAQEARNIYQ 123
Cdd:cd08746    31 EGIPNCEESPKPTLEE-VCAWGQSFDKLMLTPAGRNAFREFLRTEFSEENMLFWMACEELKK--EANKSVIEEKARIIYE 107

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1489866114 124 EFLSsqALSPVNIDRQAWLGEEV---LAEPRPDMFRAQQLQIFNLMKFDSYARFVKSPLYRE 182
Cdd:cd08746   108 DYIS--ILSPKEVSLDSRVREVInrnMLEPSQHTFDDAQLQIYTLMHRDSYPRFMNSAIYKN 167

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 1489866114  61 VASWALSFERLLQDPLGLAYFTEFLKKEFSAENVTFWKACERFQQipaSDTQQLAQEARNIYQEFLSSQALSPVNIDRQA 140
Cdd:cd08739     2 VERWAFNFSELIRDPKGRQSFQLFLKKEFSGENLGFWEACEDLKY---GDQSKVKEKAEEIYKLFLAPGARRWINIDGKT 78

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 1489866114 141 wLGEEV--LAEPRPDMFRAQQLQIFNLMKFDSYARFVKSPLYRE 182
Cdd:cd08739    79 -MDITVkgLKHPHRYVLDAAQTHIYMLMKKDSYARYLKSPIYKE 121

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 1489866114  68 FERLLQDPLGLAYFTEFLKKEFSAENVTFWKACERFQQIpaSDTQQLAQEARNIYQEFLSSQALSPVNIDRqawLGEEV- 146
Cdd:cd08717     1 LDKLLQNSYGLASFKSFLKSEFSEENIEFWEACEDYKKT--KSPLKMATKAKKIYEEFIQTEAPKEVNIDH---FTKDVt 75

                          90       100       110
                  ....*....|....*....|....*....|....*....
gi 1489866114 147 ---LAEPRPDMFRAQQLQIFNLMKFDSYARFVKSPLYRE 182
Cdd:cd08717    76 mknLVEPSSSSFDLAQKRIFALMEKDSLPRFVRSEFYQE 114

Regulator of G protein signaling (RGS) domain found in the RZ protein; The RGS (Regulator of G-protein Signaling) domain is an essential part of the RZ subfamily of the RGS protein family. They are a diverse group of multifunctional proteins that regulate cellular signaling events downstream of G-protein coupled receptors (GPCRs). RGS proteins play critical regulatory roles as GTPase activating proteins (GAPs) of the heterotrimeric G-protein G-alpha-subunits. Deactivation of G-protein signaling is controlled by RGS domains, which accelerate GTPase activity of the alpha subunit by hydrolysis of GTP to GDP, which results in reassociation of the alpha-subunit with the beta-gamma-dimer and inhibition of downstream activity. As a major G-protein regulator, RGS domain containing proteins are involved in many crucial cellular processes such as regulation of intracellular trafficking, glial differentiation, embryonic axis formation, skeletal and muscle development, and cell migration during early embryogenesis. The RZ subfamily of RGS proteins includes RGS17, RGS19 (former GAIP), RGS20, and its splice variant Ret-RGS.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1489866114  64 WALSFERLLQDPLGLAYFTEFLKKEFSAENVTFWKACERFQQipASDTQQLAQEARNIYQEFLSsqALSP--VNIDRQAw 141
Cdd:cd08718     1 WAQSFDKLMKSPAGRNVFREFLRTEYSEENMLFWLACEELKK--EANKHVIEEKARLIYEDYIS--ILSPkeVSLDSRV- 75

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 1489866114 142 lgEEV----LAEPRPDMFRAQQLQIFNLMKFDSYARFVKSPLYR 181
Cdd:cd08718    76 --REVinrnMLEPSPHTFDDAQLQIYTLMHRDSYPRFLNSAIYK 117

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 1489866114  59 QPVASWALSFERLLQDPLGLAYFTEFLKKEFSAENVTFWKACERFQQIPASDTQQLAQEarnIYQEFLSSQALSPVNIDR 138
Cdd:cd08737     1 QRVKRWGFSLDEVLKDPVGRDQFLRFLESEFSSENLRFWLAVQDLKKQPLQDVAKRVEE---IWQEFLAPGAPSAINLDS 77

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*...
gi 1489866114 139 QAW-LGEEVLAEPRPDMFRAQQLQIFNLMKFDSYARFVKSPLYRECLL 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 1489866114  68 FERLLQDPLGLAYFTEFLKKEFSAENVTFWKACERFQQIPASdtQQLAQEARNIYQEFLSSQALSPVNIDRQAW-LGEEV 146
Cdd:cd08709     1 FDELLASKYGVAAFRAFLKSEFSEENIEFWLACEDFKKTKSP--QKLTSKAKKIYTDFIEKEAPKEINIDFQTKtLIAQN 78

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 1489866114 147 LAEPRPDMFRAQQLQIFNLMKFDSYARFVKSPLYRE 182
Cdd:cd08709    79 IQEATSGCFTAAQKRVYSLMENNSYPRFLESEFYQE 114

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 1489866114  68 FERLLQDPLGLAYFTEFLKKEFSAENVTFWKACERFQQIPASdtQQLAQEARNIYQEFLSSQALSPVNIDRQAW-LGEEV 146
Cdd:cd08710     1 FDLLLNSKNGVAAFHAFLKTEFSEENLEFWLACEEFKKIRSA--TKLASRAHHIFEEFIRSEAPKEVNIDHETReLTRTN 78

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 1489866114 147 LAEPRPDMFRAQQLQIFNLMKFDSYARFVKSPLYRE 182
Cdd:cd08710    79 LQAATTSCFDVAQGKTRTLMEKDSYPRFLKSPAYRD 114

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 1489866114  69 ERLLQDPLGLAYFTEFLKKEFSAENVTFWKACERFQQIPASdtQQLAQEARNIYQEFLSSQALSPVNID-RQAWLGEEVL 147
Cdd:cd08713     2 EKLLLHKYGLAVFRAFLQTEFSEENLEFWLACEEYKKIKSQ--SKMASRAKKIFAEYIAIQSCKEVNLDsYTREHTKENL 79

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 1489866114 148 AEPRPDMFRAQQLQIFNLMKFDSYARFVKSPLYRE 182
Cdd:cd08713    80 QNPTRGCFDLAQKRIYGLMEKDSYPRFLRSDLYQD 114

Regulator of G protein signaling (RGS) domain found in the RGS7 protein; The RGS (Regulator of G-protein Signaling) domain is an essential part of the RGS7 protein, a member of R7 subfamily of the RGS protein family. RGS is a diverse group of multifunctional proteins that regulate cellular signaling events downstream of G-protein coupled receptors (GPCRs). As a major G-protein regulator, RGS domain containing proteins are involved in many crucial cellular processes such as regulation of intracellular trafficking, glial differentiation, embryonic axis formation, skeletal and muscle development, and cell migration during early embryogenesis. As a major G-protein regulator, RGS domain containing proteins are involved in many crucial cellular processes such as regulation of intracellular trafficking, glial differentiation, embryonic axis formation, skeletal and muscle development, and cell migration during early embryogenesis. Other members of the R7 subfamily (Neuronal RGS) include: RGS6, RGS9, and RGS11, all of which are expressed predominantly in the nervous system, form an obligatory complex with G-beta-5, and play important roles in the regulation of crucial neuronal processes such as vision and motor control. Additionally they have been implicated in many neurological conditions such as anxiety, schizophrenia, and drug dependence. R7 RGS proteins are key modulators of the pharmacological effects of drugs involved in the development of tolerance and addiction. In addition, RGS7 was found to bind a component of the synaptic fusion complex, snapin, and some other proteins outside of G protein signaling pathways.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1489866114  61 VASWALSFERLLQDPLGLAYFTEFLKKEFSAENVTFWKACERFQQIPASDTQQLAQEarnIYQEFLSSQALSPVNIDRQA 140
Cdd:cd08738     2 VKRWGFGMDEALKDPVGREQFLKFLESEFSSENLRFWLAVEDLKKRPIREVPSRVQE---IWQEFLAPGAPSAINLDSKS 78

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|...
gi 1489866114 141 W-LGEEVLAEPRPDMFRAQQLQIFNLMKFDSYARFVKSPLYRE 182
Cdd:cd08738    79 YdKTTQNVKDPGRYTFEDAQEHIYKLMKSDSYPRFIRSSAYQE 121

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 1489866114  71 LLQDPLGLAYFTEFLKKEFSAENVTFWKACERFQQipASDTQQLAQEARNIYQEFLSSQALSPVNIDRQAW-LGEEVLAE 149
Cdd:cd08723     1 LLANQAGLDAFRTFLKSEFSEENVEFWLACEDFKK--TKSSTEIALKAQMIYSEFIQADAPKEINIDFHTRdLISQNISE 78

                          90       100       110
                  ....*....|....*....|....*....|...
gi 1489866114 150 PRPDMFRAQQLQIFNLMKFDSYARFVKSPLYRE 182
Cdd:cd08723    79 PTLKCFDEAQSLIYCLMAKDSFPRFLKSEVYKK 111

Raf-like Ras-binding domain;

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1489866114  303 YCCVYLPDGTASLALARPGLTIRDMLAGICEKRGLSLPDIKVYLVGnEQKALVLDQDCTVLADQEVRLENR 373
Cdd:smart00455   1 TCKVHLPDNQRTVVKVRPGKTVRDALAKALKKRGLNPECCVVRLRG-EKKPLDLNQPISSLDGQELVVEEL 70

Ras-binding domain (RBD) 2 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. The 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 in eukaryotes.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1489866114 373 RITFELELTAlERVVRISAKPTKRLQEALQPILEKHGLSPLEVVLHRPGEKQPLDLGKLVSSVAAQRLVLDT 444
Cdd:cd17067     1 RVLFRLDLPN-KKIIGVKAKPTKTLAEVLRPILAKYGYKLDQVVVHLAGTQVPLDLGIPVSSIDNQRLVVET 71

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 1489866114  68 FERLLQDPLGLAYFTEFLKKEFSAENVTFWKACERFQQIpASDTQQLAQeARNIYQEFLSSQALSPVNID---RQAWLGE 144
Cdd:cd08716     1 FENLMATKYGPIIYATYLKTEHSDENIEFWLACETYKKI-ASQRKRISM-ARKLFASYIQPQAPREINIDsptRKAIIRN 78

                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 1489866114 145 evLAEPRPDMFRAQQLQIFNLMKFDSYARFVKSPLYRE 182
Cdd:cd08716    79 --IQEPTQSCFDEAQRIVYMHMERDSYPRFLESKFYQK 114

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 1489866114  71 LLQDPLgLAYFTEFLKKEFSAENVTFWKACERFQ-QIPASDTQQLAQEARN----IYQEFLSSQALSPVNIDRQAWLGEE 145
Cdd:cd08721     2 LYCESA-LFYFMEYMEQEGARNLLQFWLAADNFQsQLAAKEGQYDGQQAQNdamiIYDKYFSLQATEPLGFDDKTRLEVE 80

                          90       100       110
                  ....*....|....*....|....*....|....*....
gi 1489866114 146 --VLAE--PRPDMFRAQQLQIFNLMKFDSYARFVKSPLY 180
Cdd:cd08721    81 snICREggPLPSCFEAPLLQALTTLEQHYLPGFLSSQLY 119

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 1489866114  72 LQDPLGLAYFTEFLKKEFSAENVTFWKACERF-----QQIPASDTQQLAQE-------------ARNIYQEFLSSQALSP 133
Cdd:cd08719     2 LVNNVALSYFIDFMQSVGGQAYLFFWLTVEGYrvsaeQQLSELHLRQRGGEhqrsdvyemlraaALNIYDQYLSEKASPR 81

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1489866114 134 VNIDRQ---AWLGEEVLAEPRPDMFRAQQLQIFNLMKFDS--YARFVKSPLY 180
Cdd:cd08719    82 VPLDDSlvkKLLNRLRNDTPSDLWFDDIQQKVFDIMQEDErfYPAFKKSPAY 133

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 1489866114  71 LLQDPLGLAYFTEFLKKEFSAENVTFWKACERFQQIPASDTQQLAQEarnIYQEFLSSQAlSPVNIDRQAWLGEE--VLA 148
Cdd:cd08720     1 ILANVFGRKYLSQFLERMDSQALIGFWEAVEELRSANKSEWHQLGAE---IFYTFIVEPT-AEIKVDKSLRKRIEqfLLG 76

                          90       100       110
                  ....*....|....*....|....*....|....
gi 1489866114 149 EPRPDMFRAQQLQIFNLMKFDSYARFVKSPLYRE 182
Cdd:cd08720    77 DKGPEVFYEVQENVVETLEEKYYPSFVVSDQYKQ 110

Ras-binding domain (RBD) found in pleckstrin homology (PH) and RhoGEF domain containing G5 (PLEKHG5) and similar proteins; PLEKHG5, is also termed PH domain-containing family G member 5, or guanine nucleotide exchange factor 720 (GEF720), Syx, or Tech, is a novel Dbl-like protein related to p115Rho-GEF. It functions as a Rho guanine nucleotide exchange factor directly activating RhoA in vivo and potentially involved in the control of neuronal cell differentiation. It also regulates the balance of the RhoA downstream effector Dia and ROCK activities to promote polarized-cancer-cell migration. Moreover, PLEKHG5 activates the nuclear factor kappaB (NFkappaB) signaling pathway. Mutations in the PLEKHG5 gene are relevant with autosomal recessive intermediate Charcot-Marie-Tooth disease (CMT) and lower motor neuron disease (LMND).

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1489866114 318 ARPGLTIRDMLAGICEKRGLSLPDIKVYLVGNeQKALVLDQDCTVLADQEVRL 370
Cdd:cd17068    21 AVKGKTLRDVLEPLLERRGLDLDRVNVFLDSS-NTPLPLEFDTYFLGGHTLRV 72

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 1489866114 306 VYLPDGTASLALARPGLTIRDMLAGICEKRGLSLPDIKVYLVGNeqKALVL-DQDCTVLADQEVRLE 371
Cdd:cd01816     5 AHLPNQQRTTVEVKPGQTLREALEKAMKRRGLTPEMCVVYRKGT--REPVSwDTDISTLEGEEISVE 69