Regulator of G-protein signaling 12 Phosphotyrosine-binding (PTB) PH-like fold; RGS12 functions as a GTPase-activating protein and a transcriptional repressor. It is thought to play a role in tumorigenesis. RGS12 specifically interacts with guanine nucleotide-binding protein G(i), alpha-1 subunit and guanine nucleotide-binding protein G(k) subunit alpha. RGS proteins are multi-functional, GTPase-accelerating proteins that promote GTP hydrolysis by the alpha subunit of heterotrimeric G proteins, thereby inactivating the G protein and rapidly switching off G protein-coupled receptor signalling pathways. Upon activation by GPCRs, heterotrimeric G proteins exchange GDP for GTP, are released from the receptor, and dissociate into free, active GTP-bound alpha subunit and beta-gamma dimer, both of which activate downstream effectors. The response is terminated upon GTP hydrolysis by the alpha subunit, which can then bind the beta-gamma dimer and the receptor. RGS proteins markedly reduce the lifespan of GTP-bound alpha subunits by stabilizing the G protein transition state. PTB domains have a common PH-like fold and are found in various eukaryotic signaling molecules. This domain was initially shown to binds peptides with a NPXY motif with differing requirements for phosphorylation of the tyrosine, although more recent studies have found that some types of PTB domains can bind to peptides lack tyrosine residues altogether. In contrast to SH2 domains, which recognize phosphotyrosine and adjacent carboxy-terminal residues, PTB-domain binding specificity is conferred by residues amino-terminal to the phosphotyrosine. PTB domains are classified into three groups: phosphotyrosine-dependent Shc-like, phosphotyrosine-dependent IRS-like, and phosphotyrosine-independent Dab-like PTB domains. This cd is part of the Dab-like subgroup.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4506509   228 VAMIVGYLGSIELPSTSSNlESDSLQAIRGCMRRLRAEQKIHSLVTMKIMHDCVQLSTDKAGVVAEYPAEKLAFSAVCPD 307
Cdd:cd13162    1 VRMIVGYLGSIELPSTSSN-ESDSLQAIRGCVRRLRAEQKIHSLVLMKVMHDSVQLCDDRGGVLATYPAEKLAFSGVCPD 79

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|..
gi 4506509   308 DRRFFGLVTMQTNDDGSLAQEEEGALRTSCHVFMVDPDLFNHKIHQGIARRF 359
Cdd:cd13162   80 DRRFFGLVTMQSTDDQSEAQESEGSLRTSCHVFMVDPELFEHKIHQGIARRF 131

C-terminal unstructured region of RGS12; RGS12_usC is a region of Regulator of G-protein signalling 12 proteins that is natively unstructured and lies at the very C-terminus. It has a highly conserved central section. The function is not known.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4506509    1239 KGFSKRSATGNGRESASQPGEQWEPVQESSDSPSTSPGSASSPPGPPGTTPPGQKSPSGPFCTPQSPVSLAQEGTAQIWK 1318
Cdd:pfam16612    1 KGLSKRSGKGNGKDKAAQPGGRQEPAQSYNESSAKSPGSAESRPRPPGTTLPGQKSPSVPFSAPLSPIPHAQEGSAQIWK 80

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 4506509    1319 RQSQEVEAGGIQTVEDEHVAELTLMGEGDISSPNSTLLPPPSTP--------QEVPGPSRPGTSRF 1376
Cdd:pfam16612   81 RQSRELEAEGIQTVEDENVADLTLVGEGDISSPNSTLLPPPPTPpsdaskltQDNPGPPRPGTGAR 146

PDZ domain of regulator of G-protein signaling 12 (RGS12), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of RGS12, and related domains. RGS12 downregulates GPCR signal transduction by increasing the GTPase activity of G-protein alpha subunits, thereby driving G-proteins into their inactive GDP-bound form. The RGS12 PDZ domain can bind selectively to C-terminal (A/S)-T-X-(L/V) motifs as found within both the CXCR2 IL-8 receptor, and the alternative 3' exon form of RGS12. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This RGS12-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 4506509    21 RSVEVARGRAGYGFTLSGQAPCVLSCVMRGSPADFVGLRAGDQILAVNEINVKKASHEDVVKLIGKCSGVLHMVIA 96
Cdd:cd06710    1 RTVEIARGRAGYGFTISGQAPCVLSCVVRGSPADVAGLKAGDQILAVNGINVSKASHEDVVKLIGKCTGVLRLVIA 76

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 4506509   962 KHCCIHLPDGTSCVVAVKAGFSIKDILSGLCERHGINGAAADLFLVGGDKPLVLHQDSSILESRDLRLEK 1031
Cdd:cd17136    1 KHCCVNLPDGSSCAVAIKPGVSIREMLSGLCEKLGINLAAVDLFLVGGDKPLVLDQDSSTLESRDLRLEK 70

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

                            10        20
                    ....*....|....*....|..
gi 4506509     1188 EEFFELISKAQSNRADDQRGLL 1209
Cdd:smart00390    2 EDLFDLLLRMQSSRMDDQRCEL 23

Regulator of G-protein signaling 12 Phosphotyrosine-binding (PTB) PH-like fold; RGS12 functions as a GTPase-activating protein and a transcriptional repressor. It is thought to play a role in tumorigenesis. RGS12 specifically interacts with guanine nucleotide-binding protein G(i), alpha-1 subunit and guanine nucleotide-binding protein G(k) subunit alpha. RGS proteins are multi-functional, GTPase-accelerating proteins that promote GTP hydrolysis by the alpha subunit of heterotrimeric G proteins, thereby inactivating the G protein and rapidly switching off G protein-coupled receptor signalling pathways. Upon activation by GPCRs, heterotrimeric G proteins exchange GDP for GTP, are released from the receptor, and dissociate into free, active GTP-bound alpha subunit and beta-gamma dimer, both of which activate downstream effectors. The response is terminated upon GTP hydrolysis by the alpha subunit, which can then bind the beta-gamma dimer and the receptor. RGS proteins markedly reduce the lifespan of GTP-bound alpha subunits by stabilizing the G protein transition state. PTB domains have a common PH-like fold and are found in various eukaryotic signaling molecules. This domain was initially shown to binds peptides with a NPXY motif with differing requirements for phosphorylation of the tyrosine, although more recent studies have found that some types of PTB domains can bind to peptides lack tyrosine residues altogether. In contrast to SH2 domains, which recognize phosphotyrosine and adjacent carboxy-terminal residues, PTB-domain binding specificity is conferred by residues amino-terminal to the phosphotyrosine. PTB domains are classified into three groups: phosphotyrosine-dependent Shc-like, phosphotyrosine-dependent IRS-like, and phosphotyrosine-independent Dab-like PTB domains. This cd is part of the Dab-like subgroup.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4506509   228 VAMIVGYLGSIELPSTSSNlESDSLQAIRGCMRRLRAEQKIHSLVTMKIMHDCVQLSTDKAGVVAEYPAEKLAFSAVCPD 307
Cdd:cd13162    1 VRMIVGYLGSIELPSTSSN-ESDSLQAIRGCVRRLRAEQKIHSLVLMKVMHDSVQLCDDRGGVLATYPAEKLAFSGVCPD 79

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|..
gi 4506509   308 DRRFFGLVTMQTNDDGSLAQEEEGALRTSCHVFMVDPDLFNHKIHQGIARRF 359
Cdd:cd13162   80 DRRFFGLVTMQSTDDQSEAQESEGSLRTSCHVFMVDPELFEHKIHQGIARRF 131

C-terminal unstructured region of RGS12; RGS12_usC is a region of Regulator of G-protein signalling 12 proteins that is natively unstructured and lies at the very C-terminus. It has a highly conserved central section. The function is not known.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4506509    1239 KGFSKRSATGNGRESASQPGEQWEPVQESSDSPSTSPGSASSPPGPPGTTPPGQKSPSGPFCTPQSPVSLAQEGTAQIWK 1318
Cdd:pfam16612    1 KGLSKRSGKGNGKDKAAQPGGRQEPAQSYNESSAKSPGSAESRPRPPGTTLPGQKSPSVPFSAPLSPIPHAQEGSAQIWK 80

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 4506509    1319 RQSQEVEAGGIQTVEDEHVAELTLMGEGDISSPNSTLLPPPSTP--------QEVPGPSRPGTSRF 1376
Cdd:pfam16612   81 RQSRELEAEGIQTVEDENVADLTLVGEGDISSPNSTLLPPPPTPpsdaskltQDNPGPPRPGTGAR 146

PDZ domain of regulator of G-protein signaling 12 (RGS12), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of RGS12, and related domains. RGS12 downregulates GPCR signal transduction by increasing the GTPase activity of G-protein alpha subunits, thereby driving G-proteins into their inactive GDP-bound form. The RGS12 PDZ domain can bind selectively to C-terminal (A/S)-T-X-(L/V) motifs as found within both the CXCR2 IL-8 receptor, and the alternative 3' exon form of RGS12. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This RGS12-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 4506509    21 RSVEVARGRAGYGFTLSGQAPCVLSCVMRGSPADFVGLRAGDQILAVNEINVKKASHEDVVKLIGKCSGVLHMVIA 96
Cdd:cd06710    1 RTVEIARGRAGYGFTISGQAPCVLSCVVRGSPADVAGLKAGDQILAVNGINVSKASHEDVVKLIGKCTGVLRLVIA 76

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4506509     715 SFERLLQDPVGVRYFSDFLRKEFSEENILFWQACEYFNHvpAHDKKELSYRAREIFSKFLCSKATTPVNIDSQ--AQLAD 792
Cdd:pfam00615    1 SFDSLLEDQPGRRLFRQFLESEFSEENLEFWLACEEFKK--ADPDEERLKKAKEIYNEFLAPGSPKEINLDSDlrEEIRE 78

                           90       100       110
                   ....*....|....*....|....*....|....*....
gi 4506509     793 DVLRAPHPDMFKEQQLQIFNLMKFDSYTRFLKSPLYQEC 831
Cdd:pfam00615   79 NLEKEPTRDLFDEAQAEVYELMEKDSYPRFLKSPLYLRL 117

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 4506509      715 SFERLLQDPVGVRYFSDFLRKEFSEENILFWQACEYFNHvpAHDKKELSYRAREIFSKFLCSKATTPVNIDSQ--AQLAD 792
Cdd:smart00315    1 SLESLLSDPIGRLLFREFLESEFSEENLEFWLAVEEFKK--AEDDEERIAKAREIYDKFLSPNAPKEVNLDSDlrEKIEE 78

                            90       100       110       120
                    ....*....|....*....|....*....|....*....|
gi 4506509      793 DVLRA-PHPDMFKEQQLQIFNLMKFDSYTRFLKSPLYQEC 831
Cdd:smart00315   79 NLESEePPPDLFDEAQREVYELLEKDSFPRFLESDYYLRF 118

Raf-like Ras-binding domain;

                            10        20        30        40        50        60        70
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4506509      963 HCCIHLPDGTSCVVAVKAGFSIKDILSGLCERHGINGAAADLFLVGGDKPLVLHQDSSILESRDLRLEKR 1032
Cdd:smart00455    1 TCKVHLPDNQRTVVKVRPGKTVRDALAKALKKRGLNPECCVVRLRGEKKPLDLNQPISSLDGQELVVEEL 70

Phosphotyrosine-binding domain, phosphotyrosine-interaction (PI) domain; PTB/PI domain structure similar to those of pleckstrin homology (PH) and IRS-1-like PTB domains.

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4506509      228 VAMIVGYLGSIELPstssnlESDSLQAIRGCMRRLRA----EQKIHSLVTMKIMHDCVQLSTDKAG-VVAEYPAEKLAFS 302
Cdd:smart00462    4 VSFRVKYLGSVEVP------EARGLQVVQEAIRKLRAaqgsEKKEPQKVILSISSRGVKLIDEDTKaVLHEHPLRRISFC 77

                            90       100       110       120       130       140       150
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 4506509      303 AVCPDDRRFFGLVTMQTNDDgslaqeeegalRTSCHVFMVDPdlfnHKIHQGIARRFGFECTADPDTNGCLE 374
Cdd:smart00462   78 AVGPDDLDVFGYIARDPGSS-----------RFACHVFRCEK----AAEDIALAIGQAFQLAYELKLKARSE 134

Domain present in PSD-95, Dlg, and ZO-1/2; Also called DHR (Dlg homologous region) or GLGF (relatively well conserved tetrapeptide in these domains). Some PDZs have been shown to bind C-terminal polypeptides; others appear to bind internal (non-C-terminal) polypeptides. Different PDZs possess different binding specificities.

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4506509       19 RVRSVEVARGRAGYGFTLSG----QAPCVLSCVMRGSPADFVGLRAGDQILAVNEINVKKASHEDVVKLIGKCSGVLHMV 94
Cdd:smart00228    1 EPRLVELEKGGGGLGFSLVGgkdeGGGVVVSSVVPGSPAAKAGLRVGDVILEVNGTSVEGLTHLEAVDLLKKAGGKVTLT 80

                    .
gi 4506509       95 I 95
Cdd:smart00228   81 V 81

C-terminal processing protease CtpA/Prc, contains a PDZ domain [Posttranslational modification, protein turnover, chaperones];

                         10        20        30
                 ....*....|....*....|....*....|....*...
gi 4506509    47 VMRGSPADFVGLRAGDQILAVNEINVKKASHEDVVKLI 84
Cdd:COG0793   78 VIPGSPAEKAGIKPGDIILAIDGKSVAGLTLDDAVKLL 115

GoLoco motif;

                           10        20
                   ....*....|....*....|..
gi 4506509    1188 EEFFELISKAQSNRADDQRGLL 1209
Cdd:pfam02188    1 EDFFDLLARVQSSRLDDQRCSL 22

C-terminal peptidase (prc); A C-terminal peptidase with different substrates in different species including processing of D1 protein of the photosystem II reaction center in higher plants and cleavage of a peptide of 11 residues from the precursor form of penicillin-binding protein in E.coli E.coli and H influenza have the most distal branch of the tree and their proteins have an N-terminal 200 amino acids that show no homology to other proteins in the database. [Protein fate, Degradation of proteins, peptides, and glycopeptides, Protein fate, Protein modification and repair]

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|.
gi 4506509      47 VMRGSPADFVGLRAGDQILAVNEINVKKASHEDVVKLI-GK 86
Cdd:TIGR00225   69 PFEGSPAEKAGIKPGDKIIKINGKSVAGMSLDDAVALIrGK 109

Regulator of G-protein signaling 12 Phosphotyrosine-binding (PTB) PH-like fold; RGS12 functions as a GTPase-activating protein and a transcriptional repressor. It is thought to play a role in tumorigenesis. RGS12 specifically interacts with guanine nucleotide-binding protein G(i), alpha-1 subunit and guanine nucleotide-binding protein G(k) subunit alpha. RGS proteins are multi-functional, GTPase-accelerating proteins that promote GTP hydrolysis by the alpha subunit of heterotrimeric G proteins, thereby inactivating the G protein and rapidly switching off G protein-coupled receptor signalling pathways. Upon activation by GPCRs, heterotrimeric G proteins exchange GDP for GTP, are released from the receptor, and dissociate into free, active GTP-bound alpha subunit and beta-gamma dimer, both of which activate downstream effectors. The response is terminated upon GTP hydrolysis by the alpha subunit, which can then bind the beta-gamma dimer and the receptor. RGS proteins markedly reduce the lifespan of GTP-bound alpha subunits by stabilizing the G protein transition state. PTB domains have a common PH-like fold and are found in various eukaryotic signaling molecules. This domain was initially shown to binds peptides with a NPXY motif with differing requirements for phosphorylation of the tyrosine, although more recent studies have found that some types of PTB domains can bind to peptides lack tyrosine residues altogether. In contrast to SH2 domains, which recognize phosphotyrosine and adjacent carboxy-terminal residues, PTB-domain binding specificity is conferred by residues amino-terminal to the phosphotyrosine. PTB domains are classified into three groups: phosphotyrosine-dependent Shc-like, phosphotyrosine-dependent IRS-like, and phosphotyrosine-independent Dab-like PTB domains. This cd is part of the Dab-like subgroup.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4506509   228 VAMIVGYLGSIELPSTSSNlESDSLQAIRGCMRRLRAEQKIHSLVTMKIMHDCVQLSTDKAGVVAEYPAEKLAFSAVCPD 307
Cdd:cd13162    1 VRMIVGYLGSIELPSTSSN-ESDSLQAIRGCVRRLRAEQKIHSLVLMKVMHDSVQLCDDRGGVLATYPAEKLAFSGVCPD 79

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|..
gi 4506509   308 DRRFFGLVTMQTNDDGSLAQEEEGALRTSCHVFMVDPDLFNHKIHQGIARRF 359
Cdd:cd13162   80 DRRFFGLVTMQSTDDQSEAQESEGSLRTSCHVFMVDPELFEHKIHQGIARRF 131

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        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4506509   716 FERLLQDPVGVRYFSDFLRKEFSEENILFWQACEYFNHVPahDKKELSYRAREIFSKFLCSKATTPVNIDSQAQLADDVL 795
Cdd:cd08706    1 FERLLQDPVGVKYFTEFLKKEFSEENILFWQACEKFKKIP--DKKQLVQEAREIYDTFLSSKASSPVNIDSQAQLAEEML 78

                         90       100       110
                 ....*....|....*....|....*....|....*
gi 4506509   796 RAPHPDMFKEQQLQIFNLMKFDSYTRFLKSPLYQE 830
Cdd:cd08706   79 EEPHPDMFQKQQLQIFNLMKFDSYSRFLKSPLYQQ 113

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 4506509   706 ERRVASWAVSFERLLQDPVGVRYFSDFLRKEFSEENILFWQACEYFNHVPAHDKKELSYRAREIFSKFLCSKATTPVNID 785
Cdd:cd08743    1 EKSVASWAVSFERLLQDPLGVEYFTEFLKKEFSAENVNFWKACERFQQIPASDTQQLAQEARKIYNEFLSSSSQSPVNID 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*....
gi 4506509   786 SQAQLADDVLRAPHPDMFKEQQLQIFNLMKFDSYTRFLKSPLYQECILA 834
Cdd:cd08743   81 QQAWIGEDMLATPSPDMFRAQQLQIFNLMKFDSYARFVKSPLYQDCLLA 129

PDZ domain of regulator of G-protein signaling 12 (RGS12), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of RGS12, and related domains. RGS12 downregulates GPCR signal transduction by increasing the GTPase activity of G-protein alpha subunits, thereby driving G-proteins into their inactive GDP-bound form. The RGS12 PDZ domain can bind selectively to C-terminal (A/S)-T-X-(L/V) motifs as found within both the CXCR2 IL-8 receptor, and the alternative 3' exon form of RGS12. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This RGS12-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 4506509    21 RSVEVARGRAGYGFTLSGQAPCVLSCVMRGSPADFVGLRAGDQILAVNEINVKKASHEDVVKLIGKCSGVLHMVIA 96
Cdd:cd06710    1 RTVEIARGRAGYGFTISGQAPCVLSCVVRGSPADVAGLKAGDQILAVNGINVSKASHEDVVKLIGKCTGVLRLVIA 76

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 4506509   716 FERLLQDPVGVRYFSDFLRKEFSEENILFWQACEYFNHvpAHDKKELSYRAREIFSKFLCSKATTPVNIDSQAQLADDVL 795
Cdd:cd08741    1 LENLLEDPEGVKRFREFLKKEFSEENVLFWLACEDFKK--MQDKTQMQEKAKEIYMTFLSSKASSQVNVEGQSRLNEKIL 78

                         90       100       110
                 ....*....|....*....|....*....|...
gi 4506509   796 RAPHPDMFKEQQLQIFNLMKFDSYTRFLKSPLY 828
Cdd:cd08741   79 EEPHPLMFQKLQDQIFNLMKYDSYSRFLKSDLF 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 4506509   962 KHCCIHLPDGTSCVVAVKAGFSIKDILSGLCERHGINGAAADLFLVGGDKPLVLHQDSSILESRDLRLEK 1031
Cdd:cd17136    1 KHCCVNLPDGSSCAVAIKPGVSIREMLSGLCEKLGINLAAVDLFLVGGDKPLVLDQDSSTLESRDLRLEK 70

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 4506509   708 RVASWAVSFERLLQDPVGVRYFSDFLRKEFSEENILFWQACEYFNHVPAHDKKElsyRAREIFSKFLCSKATTPVNIDSQ 787
Cdd:cd08705    1 RVKRWGFSFSELLKDPVGREQFLKFLEKEFSGENLRFWEACQDLKYGPQSQVPE---KVQEIYQEFLAPGAPSWINIDSK 77

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....
gi 4506509   788 -AQLADDVLRAPHPDMFKEQQLQIFNLMKFDSYTRFLKSPLYQE 830
Cdd:cd08705   78 tMEITLKNLKDPHRYTFDAAQEHIYMLMKKDSYPRFLRSDIYKE 121

Unstructured region between RBD and GoLoco; RGs12_us2 is a region of Regulator of G-protein signalling 12 proteins that is natively unstructured and lies between an RBD domain and a GoLoco motif, pfam02196 and pfam02188. The function is not known.

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 4506509    1106 PSRGKasaDKQKGVPVKQNTAVNSSSRNHSATGEERTLGKSNSIKIKGENGKNARDPRLSKREESIAKIGKKKYQ 1180
Cdd:pfam16611    1 PARGK---DKQKGVSLKQSPAVASNTRNQSTTGEERPLGKSNSIKIKGENGKNSRDARLLKREESVAKTGKRKYQ 72

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 4506509   708 RVASWAVSFERLLQDPVGVRYFSDFLRKEFSEENILFWQACEYFNHvpaHDKKELSYRAREIFSKFLCSKATTPVNIDSQ 787
Cdd:cd08740    2 RVERWGFSFRELLNDPVGRKEFLDFLEKEFSAENLSFWEACEELRY---GEQSKIPELVDSVYQQFLAPGATRWVNIDSK 78

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*....
gi 4506509   788 A-QLADDVLRAPHPDMFKEQQLQIFNLMKFDSYTRFLKSPLYQEcILAE 835
Cdd:cd08740   79 TmERTLEGLKQPHRYVLDDAQMHIYMLMKKDSYPRFLKSDLYKN-LLAE 126

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 4506509   708 RVASWAVSFERLLQDPVGVRYFSDFLRKEFSEENILFWQACEYFNHVPAHDKKElsyRAREIFSKFLCSKATTPVNIDSQ 787
Cdd:cd08739    1 RVERWAFNFSELIRDPKGRQSFQLFLKKEFSGENLGFWEACEDLKYGDQSKVKE---KAEEIYKLFLAPGARRWINIDGK 77

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....
gi 4506509   788 A-QLADDVLRAPHPDMFKEQQLQIFNLMKFDSYTRFLKSPLYQE 830
Cdd:cd08739   78 TmDITVKGLKHPHRYVLDAAQTHIYMLMKKDSYARYLKSPIYKE 121

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 4506509   962 KHCCIHLPD-GTSCVVAVKAGFSIKDILSGLCERHGINGAAADLFLVGGDKPLVLHQDSSILESRDLRLEK 1031
Cdd:cd01760    1 NTFRLFLPNnETSVVVAVKPGKSLHEVLMPVLERHGLQLECVDVFLLGEKAPLDLNTDASSLIGQELRLDF 71

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        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4506509   712 WAVSFERLLQDPVGVRYFSDFLRKEFSEENILFWQACEYFNhvPAHDKKELSYRAREIFSKFLCSKATTPVNIDSQA-QL 790
Cdd:cd08745    1 WAQSFDKLMKSPAGRNVFREFLRTEYSEENMLFWLACEELK--AEANKHVIDEKARLIYEDYISILSPKEVSLDSRVrEG 78

                         90       100       110
                 ....*....|....*....|....*....|....*....
gi 4506509   791 ADDVLRAPHPDMFKEQQLQIFNLMKFDSYTRFLKSPLYQ 829
Cdd:cd08745   79 INRKMQEPSSHTFDDAQLQIYTLMHRDSYPRFLNSPIYK 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        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4506509   658 ITRSLDDLESATVSDGELTGADLKDCvsnnslsSNASLPSVQScrrlrerrVASWAVSFERLLQDPVGVRYFSDFLRKEF 737
Cdd:cd08746   11 LTVRNQEDERNRRTSYEFRAEGIPNC-------EESPKPTLEE--------VCAWGQSFDKLMLTPAGRNAFREFLRTEF 75

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4506509   738 SEENILFWQACEYFNHvpAHDKKELSYRAREIFSKFLCSKATTPVNIDSQA-QLADDVLRAPHPDMFKEQQLQIFNLMKF 816
Cdd:cd08746   76 SEENMLFWMACEELKK--EANKSVIEEKARIIYEDYISILSPKEVSLDSRVrEVINRNMLEPSQHTFDDAQLQIYTLMHR 153

                        170
                 ....*....|....
gi 4506509   817 DSYTRFLKSPLYQE 830
Cdd:cd08746  154 DSYPRFMNSAIYKN 167

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 4506509   716 FERLLQDPVGVRYFSDFLRKEFSEENILFWQACEYFNHVPAHDKkeLSYRAREIFSKFLCSKATTPVNIDS--QAQLADD 793
Cdd:cd08714    1 LENLINHECGLAAFKAFLKSEYSEENIDFWVSCEDYKKTKSPSK--LSPKARKIYEEFISVQATKEVNLDSctREETSRN 78

                         90       100       110
                 ....*....|....*....|....*....|....*..
gi 4506509   794 VLRaPHPDMFKEQQLQIFNLMKFDSYTRFLKSPLYQE 830
Cdd:cd08714   79 MLE-PTISCFDEAQKKIFTLMEKDSYRRFLKSRFYLD 114

Raf-like Ras-binding domain;

                            10        20        30        40        50        60        70
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4506509      963 HCCIHLPDGTSCVVAVKAGFSIKDILSGLCERHGINGAAADLFLVGGDKPLVLHQDSSILESRDLRLEKR 1032
Cdd:smart00455    1 TCKVHLPDNQRTVVKVRPGKTVRDALAKALKKRGLNPECCVVRLRGEKKPLDLNQPISSLDGQELVVEEL 70

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 4506509   716 FERLLQDPVGVRYFSDFLRKEFSEENILFWQACEYFNHVPAHDKkeLSYRAREIFSKFLCSKATTPVNIDsqaQLADDV- 794
Cdd:cd08717    1 LDKLLQNSYGLASFKSFLKSEFSEENIEFWEACEDYKKTKSPLK--MATKAKKIYEEFIQTEAPKEVNID---HFTKDVt 75

                         90       100       110
                 ....*....|....*....|....*....|....*....
gi 4506509   795 ---LRAPHPDMFKEQQLQIFNLMKFDSYTRFLKSPLYQE 830
Cdd:cd08717   76 mknLVEPSSSSFDLAQKRIFALMEKDSLPRFVRSEFYQE 114

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 4506509   962 KHCCIHLPDGTSCVVAVKAGFSIKDILSGLCERHGINGAAADLFLVGG-DKPLVLHQDSSILESRDLRLEK 1031
Cdd:cd17137    1 KYCCVYLPDGTASLASVRPGLTIRDMLSGICEKRGISLPDVKVYLVGNeKKPLVLDQDCSVLTDQEVRLEN 71

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 4506509   716 FERLLQDPVGVRYFSDFLRKEFSEENILFWQACEYFNhvpAHDKKELSYRAREIFSKFLCSKATTPVNIDSQAQ--LADD 793
Cdd:cd08715    1 LEKLLASQTGQNVFRSFLKSEFSEENIEFWLACEDYK---KTESDLLPCKAEEIYKEFVQSDAAKQINIDFRTResTAKK 77

                         90       100       110
                 ....*....|....*....|....*....|....*
gi 4506509   794 vLRAPHPDMFKEQQLQIFNLMKFDSYTRFLKSPLY 828
Cdd:cd08715   78 -IKAPTPTCFDEAQKVIYILMERDSYPRFLKSDIY 111