Ras-binding domain (RBD) 1 of regulator of G protein signaling 14 (RGS14); RGS12 (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 2217354168 149 KYCCVYLPDGTASLALARPGLTIRDMLAGICEKRGLSLPDIKVYLVGNEQKALVLDQDCTVLADQEVRLEN 219
Cdd:cd17137     1 KYCCVYLPDGTASLASVRPGLTIRDMLSGICEKRGISLPDVKVYLVGNEKKPLVLDQDCSVLTDQEVRLEN 71

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
                  ....*....|....*....|....*....|...
gi 2217354168   1 MFRAQQLQIFNLMKFDSYARFVKSPLYRECLLA 33
Cdd:cd08743    97 MFRAQQLQIFNLMKFDSYARFVKSPLYQDCLLA 129

Ras-binding domain (RBD) 1 of regulator of G protein signaling 14 (RGS14); RGS12 (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 2217354168 149 KYCCVYLPDGTASLALARPGLTIRDMLAGICEKRGLSLPDIKVYLVGNEQKALVLDQDCTVLADQEVRLEN 219
Cdd:cd17137     1 KYCCVYLPDGTASLASVRPGLTIRDMLSGICEKRGISLPDVKVYLVGNEKKPLVLDQDCSVLTDQEVRLEN 71

Raf-like Ras-binding domain;

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 2217354168 150 YCCVYLPDGTASLALARPGLTIRDMLAGICEKRGLSLPDIKVYLVGNEQKALVLDQDCTVLADQEVRLE 218
Cdd:pfam02196   1 LCRVYLPDGQRTVVQVRPGETVRDALSKLCKKRGLNPEACDVYLVGGDKYPLDLDTDSSTLEGEEVRVE 69

Raf-like Ras-binding domain;

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217354168  223 FELELTALERVVRISAKPTKRLQEALQPILEKHGLSPLEVVLHRPGEKQPLDLGKLVSSVAAQRLVLDTL 292
Cdd:smart00455   1 TCKVHLPDNQRTVVKVRPGKTVRDALAKALKKRGLNPECCVVRLRGEKKPLDLNQPISSLDGQELVVEEL 70

Regulator of G protein signaling domain; RGS family members are GTPase-activating proteins for heterotrimeric G-protein alpha-subunits.

                          10        20        30
                  ....*....|....*....|....*....|
gi 2217354168   1 MFRAQQLQIFNLMKFDSYARFVKSPLYREC 30
Cdd:pfam00615  88 LFDEAQAEVYELMEKDSYPRFLKSPLYLRL 117

GoLoco motif;

                          10        20
                  ....*....|....*....|..
gi 2217354168 347 EGLVELLNRVQSSGAHDQRGLL 368
Cdd:pfam02188   1 EDFFDLLARVQSSRLDDQRCSL 22

Ras-binding domain (RBD) 1 of regulator of G protein signaling 14 (RGS14); RGS12 (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 2217354168 149 KYCCVYLPDGTASLALARPGLTIRDMLAGICEKRGLSLPDIKVYLVGNEQKALVLDQDCTVLADQEVRLEN 219
Cdd:cd17137     1 KYCCVYLPDGTASLASVRPGLTIRDMLSGICEKRGISLPDVKVYLVGNEKKPLVLDQDCSVLTDQEVRLEN 71

Raf-like Ras-binding domain;

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 2217354168 150 YCCVYLPDGTASLALARPGLTIRDMLAGICEKRGLSLPDIKVYLVGNEQKALVLDQDCTVLADQEVRLE 218
Cdd:pfam02196   1 LCRVYLPDGQRTVVQVRPGETVRDALSKLCKKRGLNPEACDVYLVGGDKYPLDLDTDSSTLEGEEVRVE 69

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 2217354168 221 ITFELELTALERVVRISAKPTKRLQEALQPILEKHGLSPLEVVLHRPGEKQPLDLGKLVSSVAAQRLVLDT 291
Cdd:cd01760     1 NTFRLFLPNNETSVVVAVKPGKSLHEVLMPVLERHGLQLECVDVFLLGEKAPLDLNTDASSLIGQELRLDF 71

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 2217354168 149 KYCCVYLPDGTASLALARPGLTIRDMLAGICEKRGLSLPDIKVYLVGNEqKALVLDQDCTVLADQEVRLE 218
Cdd:cd17136     1 KHCCVNLPDGSSCAVAIKPGVSIREMLSGLCEKLGINLAAVDLFLVGGD-KPLVLDQDSSTLESRDLRLE 69

Raf-like Ras-binding domain;

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217354168  223 FELELTALERVVRISAKPTKRLQEALQPILEKHGLSPLEVVLHRPGEKQPLDLGKLVSSVAAQRLVLDTL 292
Cdd:smart00455   1 TCKVHLPDNQRTVVKVRPGKTVRDALAKALKKRGLNPECCVVRLRGEKKPLDLNQPISSLDGQELVVEEL 70

Regulator of G protein signaling (RGS) domain found in the R12 subfamily of proteins; The RGS (Regulator of G-protein Signaling) domain is an essential part of the R12 (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). RGS proteins play a critical regulatory role as GTPase activating proteins (GAPs) of the heterotrimeric G-protein G-alpha-subunits. Deactivation of G-protein signaling, controlled by RGS domain, accelerates GTPase activity of the alpha subunit by hydrolysis of GTP to GDP that 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 such as regulation of intracellular trafficking, glial differentiation, embryonic axis formation, skeletal and muscle development, and cell migration during early embryogenesis. The R12 RGS subfamily includes RGS10, RGS12 and RGS14 all of which are highly selective for G-alpha-i1 over G-alpha-q.

                          10        20
                  ....*....|....*....|....*....
gi 2217354168   1 MFRAQQLQIFNLMKFDSYARFVKSPLYRE 29
Cdd:cd08706    85 MFQKQQLQIFNLMKFDSYSRFLKSPLYQQ 113

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
                  ....*....|....*....|....*....
gi 2217354168   1 MFRAQQLQIFNLMKFDSYARFVKSPLYRE 29
Cdd:cd08742    87 MFKEQQLQIFNLMKFDSYTRFLKSPLYQE 115

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
                  ....*....|....*....|....*....
gi 2217354168   1 MFRAQQLQIFNLMKFDSYARFVKSPLYRE 29
Cdd:cd08705    93 TFDAAQEHIYMLMKKDSYPRFLRSDIYKE 121

Regulator of G protein signaling domain; RGS family members are GTPase-activating proteins for heterotrimeric G-protein alpha-subunits.

                          10        20        30
                  ....*....|....*....|....*....|
gi 2217354168   1 MFRAQQLQIFNLMKFDSYARFVKSPLYREC 30
Cdd:pfam00615  88 LFDEAQAEVYELMEKDSYPRFLKSPLYLRL 117

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 2217354168 165 ARPGLTIRDMLAGICEKRGLSLPDIKVYLVGNeQKALVLDQDCTVLADQEVRL 217
Cdd:cd17068    21 AVKGKTLRDVLEPLLERRGLDLDRVNVFLDSS-NTPLPLEFDTYFLGGHTLRV 72

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
                  ....*....|....*....|....*....
gi 2217354168   1 MFRAQQLQIFNLMKFDSYARFVKSPLYRE 29
Cdd:cd07440    85 CFDEAQEHILNLLEKDSYPRFLKSDLYLK 113

Regulator of G protein signaling (RGS) domain found in the RGS19 protein; The RGS (Regulator of G-protein Signaling) domain is an essential part of the RGS19 protein (also known as GAIP), a member of the RZ subfamily of the RGS protein family. They are a diverse group of multifunctional proteins that regulate cellular signaling events downstream of G-protein coupled receptors (GPCRs). RGS proteins play critical regulatory roles as GTPase activating proteins (GAPs) of the heterotrimeric G-protein G-alpha-subunits. Deactivation of G-protein signaling is controlled by RGS domains, which accelerate GTPase activity of the alpha subunit by hydrolysis of GTP to GDP, resulting in a reassociation of the alpha-subunit with the beta-gamma-dimer and an inhibition of downstream activity. As a major G-protein regulator, the RGS domain containing proteins are involved in many crucial cellular processes such as regulation of intracellular trafficking, glial differentiation, embryonic axis formation, skeletal and muscle development, and cell migration during early embryogenesis. The RZ subfamily of RGS proteins includes RGS17, RGS20, and its splice variant Ret-RGS. RGS19 participates in regulation of dopamine receptor D2R and D3R, as well as beta-adrenergic receptors .

                          10        20
                  ....*....|....*....|....*..
gi 2217354168   2 FRAQQLQIFNLMKFDSYARFVKSPLYR 28
Cdd:cd08745    91 FDDAQLQIYTLMHRDSYPRFLNSPIYK 117

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
                  ....*....|....*....|....*...
gi 2217354168   2 FRAQQLQIFNLMKFDSYARFVKSPLYRE 29
Cdd:cd08746   140 FDDAQLQIYTLMHRDSYPRFMNSAIYKN 167

LGN motif, putative GEFs specific for G-alpha GTPases; GEF specific for Galpha_i proteins

                           10        20
                   ....*....|....*....|...
gi 2217354168  346 IEGLVELLNRVQSSGAHDQRGLL 368
Cdd:smart00390   1 DEDLFDLLLRMQSSRMDDQRCEL 23

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
                  ....*....|....*....|....*....
gi 2217354168   6 QLQIFNLMKFDSYARFVKSPLYREcLLAE 34
Cdd:cd08740    99 QMHIYMLMKKDSYPRFLKSDLYKN-LLAE 126

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
                  ....*....|....*....|....*...
gi 2217354168   2 FRAQQLQIFNLMKFDSYARFVKSPLYRE 29
Cdd:cd08714    87 FDEAQKKIFTLMEKDSYRRFLKSRFYLD 114