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 1622938478 594 KGFSKRSATGNGRESASQPSEQWEPAQESSDSPSTSPGSVPSPPGPPGTTPTGQKSPSGPFYTPQSPVSLAQEGTTQIWK 673
Cdd:pfam16612   1 KGLSKRSGKGNGKDKAAQPGGRQEPAQSYNESSAKSPGSAESRPRPPGTTLPGQKSPSVPFSAPLSPIPHAQEGSAQIWK 80

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1622938478 674 RQSREVEAGGIQTVEDEHVAELTLMGEGDISSPNSTLLPPPSGP--------QDVPGPSRPGSGTH 731
Cdd:pfam16612  81 RQSRELEAEGIQTVEDENVADLTLVGEGDISSPNSTLLPPPPTPpsdaskltQDNPGPPRPGTGAR 146

first ubiquitin-like (Ubl) domain located at the N-terminus of coronavirus SARS-CoV non-structural protein 3 (Nsp3) and related proteins; This ubiquitin-like (Ubl) domain (Ubl1) is found at the N-terminus of coronavirus Nsp3, a large multi-functional multi-domain protein which is an essential component of the replication/transcription complex (RTC). The functions of Ubl1 in CoVs are related to single-stranded RNA (ssRNA) binding and to interacting with the nucleocapsid (N) protein. SARS-CoV Ubl1 has been shown to bind ssRNA having AUA patterns, and since the 5'-UTR of the SARS-CoV genome has a number of AUA repeats, it may bind there. In mouse hepatitis virus (MHV), this Ubl1 domain binds the cognate N protein. Adjacent to Ubl1 is a Glu-rich acidic region (also referred to as hypervariable region, HVR); Ubl1 together with HVR has been called Nsp3a. Currently, the function of HVR in CoVs is unknown. This model corresponds to one of two Ubl domains in Nsp3; the other is located N-terminal to the papain-like protease (PLpro) and is not represented by this model.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1622938478 387 RTLFRLDLVPINRSVGLKAKPTKPVTEVLRPVVAKYGLDLSGLLVRLSGEKEPLDLGAPISSLDGQRVVLEEK 459
Cdd:cd17138     1 RTLFRLDLVPINRSVGLKAKPTKPVTEVLRPVVAKYGLNLNELVARISGEKEPLDLGLPISNLDGQRVVLEEK 73

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 1622938478 461 PSRGKastDKQKGVPVKQNIAVNSSSRNHSATGEERTLGKSNSIKIKGENGKNARDPRLSKREESIAKIGKKKYQ 535
Cdd:pfam16611   1 PARGK---DKQKGVSLKQSPAVASNTRNQSTTGEERPLGKSNSIKIKGENGKNSRDARLLKREESVAKTGKRKYQ 72

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 1622938478 594 KGFSKRSATGNGRESASQPSEQWEPAQESSDSPSTSPGSVPSPPGPPGTTPTGQKSPSGPFYTPQSPVSLAQEGTTQIWK 673
Cdd:pfam16612   1 KGLSKRSGKGNGKDKAAQPGGRQEPAQSYNESSAKSPGSAESRPRPPGTTLPGQKSPSVPFSAPLSPIPHAQEGSAQIWK 80

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1622938478 674 RQSREVEAGGIQTVEDEHVAELTLMGEGDISSPNSTLLPPPSGP--------QDVPGPSRPGSGTH 731
Cdd:pfam16612  81 RQSRELEAEGIQTVEDENVADLTLVGEGDISSPNSTLLPPPPTPpsdaskltQDNPGPPRPGTGAR 146

Ras-binding domain (RBD) 2 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 1622938478 387 RTLFRLDLVPINRSVGLKAKPTKPVTEVLRPVVAKYGLDLSGLLVRLSGEKEPLDLGAPISSLDGQRVVLEEK 459
Cdd:cd17138     1 RTLFRLDLVPINRSVGLKAKPTKPVTEVLRPVVAKYGLNLNELVARISGEKEPLDLGLPISNLDGQRVVLEEK 73

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 1622938478 317 KHCCIHLPDGTSCVVAVKAGFSIKDILSGLCERHGINGAAADLFLVGGDKPLVLHQDSSILESRDLRLEK 386
Cdd:cd17136     1 KHCCVNLPDGSSCAVAIKPGVSIREMLSGLCEKLGINLAAVDLFLVGGDKPLVLDQDSSTLESRDLRLEK 70

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 1622938478 461 PSRGKastDKQKGVPVKQNIAVNSSSRNHSATGEERTLGKSNSIKIKGENGKNARDPRLSKREESIAKIGKKKYQ 535
Cdd:pfam16611   1 PARGK---DKQKGVSLKQSPAVASNTRNQSTTGEERPLGKSNSIKIKGENGKNSRDARLLKREESVAKTGKRKYQ 72

Raf-like Ras-binding domain;

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1622938478 318 HCCIHLPDGTSCVVAVKAGFSIKDILSGLCERHGINGAAADLFLVGGDK-PLVLHQDSSILESRDLRLE 385
Cdd:pfam02196   1 LCRVYLPDGQRTVVQVRPGETVRDALSKLCKKRGLNPEACDVYLVGGDKyPLDLDTDSSTLEGEEVRVE 69

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

                           10        20
                   ....*....|....*....|..
gi 1622938478  543 EEFFELISKAQSNRADDQRGLL 564
Cdd:smart00390   2 EDLFDLLLRMQSSRMDDQRCEL 23

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 1622938478  71 FERLLQDPVGVRYFSDFLRKEFSEENILFWQACEYFNHVPahDKKELSYRAREIFSKFLCSKATTPVNIDSQAQLADDVL 150
Cdd:cd08706     1 FERLLQDPVGVKYFTEFLKKEFSEENILFWQACEKFKKIP--DKKQLVQEAREIYDTFLSSKASSPVNIDSQAQLAEEML 78

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 1622938478 151 RAPHPDMFKEQQLQIFNLMKFDSYTRFLKSPLYQE 185
Cdd:cd08706    79 EEPHPDMFQKQQLQIFNLMKFDSYSRFLKSPLYQQ 113

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 1622938478 594 KGFSKRSATGNGRESASQPSEQWEPAQESSDSPSTSPGSVPSPPGPPGTTPTGQKSPSGPFYTPQSPVSLAQEGTTQIWK 673
Cdd:pfam16612   1 KGLSKRSGKGNGKDKAAQPGGRQEPAQSYNESSAKSPGSAESRPRPPGTTLPGQKSPSVPFSAPLSPIPHAQEGSAQIWK 80

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1622938478 674 RQSREVEAGGIQTVEDEHVAELTLMGEGDISSPNSTLLPPPSGP--------QDVPGPSRPGSGTH 731
Cdd:pfam16612  81 RQSRELEAEGIQTVEDENVADLTLVGEGDISSPNSTLLPPPPTPpsdaskltQDNPGPPRPGTGAR 146

Ras-binding domain (RBD) 2 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 1622938478 387 RTLFRLDLVPINRSVGLKAKPTKPVTEVLRPVVAKYGLDLSGLLVRLSGEKEPLDLGAPISSLDGQRVVLEEK 459
Cdd:cd17138     1 RTLFRLDLVPINRSVGLKAKPTKPVTEVLRPVVAKYGLNLNELVARISGEKEPLDLGLPISNLDGQRVVLEEK 73

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 1622938478  70 SFERLLQDPVGVRYFSDFLRKEFSEENILFWQACEYFNHvpAHDKKELSYRAREIFSKFLCSKATTPVNIDSQ--AQLAD 147
Cdd:pfam00615   1 SFDSLLEDQPGRRLFRQFLESEFSEENLEFWLACEEFKK--ADPDEERLKKAKEIYNEFLAPGSPKEINLDSDlrEEIRE 78

                          90       100       110
                  ....*....|....*....|....*....|....*....
gi 1622938478 148 DVLRAPHPDMFKEQQLQIFNLMKFDSYTRFLKSPLYQEC 186
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 1622938478   70 SFERLLQDPVGVRYFSDFLRKEFSEENILFWQACEYFNHvpAHDKKELSYRAREIFSKFLCSKATTPVNIDSQ--AQLAD 147
Cdd:smart00315   1 SLESLLSDPIGRLLFREFLESEFSEENLEFWLAVEEFKK--AEDDEERIAKAREIYDKFLSPNAPKEVNLDSDlrEKIEE 78

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|
gi 1622938478  148 DVLRA-PHPDMFKEQQLQIFNLMKFDSYTRFLKSPLYQEC 186
Cdd:smart00315  79 NLESEePPPDLFDEAQREVYELLEKDSFPRFLESDYYLRF 118

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 1622938478  75 LQDPVGVRYFSDFLRKEFSEENILFWQACEYFnHVPAHDKKELSYRAREIFSKFLCSKATTPVNIDSQA-QLADDVLRAP 153
Cdd:cd07440     1 LRDPYGLEYFRQFLKSEHCEENLEFWLAVEKF-KKTTSSDEELKSKAKEIYDKYISKDAPKEINIPESIrEEIEENLEEP 79

                          90       100       110
                  ....*....|....*....|....*....|....
gi 1622938478 154 --HPDMFKEQQLQIFNLMKFDSYTRFLKSPLYQE 185
Cdd:cd07440    80 ypDPDCFDEAQEHILNLLEKDSYPRFLKSDLYLK 113

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 1622938478 387 RTLFRLDLvPINRSVGLKAKPTKPVTEVLRPVVAKYGLDLSGLLVRLSGEKEPLDLGAPISSLDGQRVVLEEK 459
Cdd:cd17067     1 RVLFRLDL-PNKKIIGVKAKPTKTLAEVLRPILAKYGYKLDQVVVHLAGTQVPLDLGIPVSSIDNQRLVVETK 72

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

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622938478 317 KHCCIHLPDGTSCVVAVKAGFSIKDILSGLCERHGINGAAADLFLVGGDKPLVLHQDSSILESRDLRLEK 386
Cdd:cd01817     1 KLCRVILPDGSTTVVQAKPGETIRQLLTRLLEKRGLSYAAFDVFIVGSDKPLDLNEDSSILGGKEVRVEQ 70

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 1622938478  62 RRVASWAVSFERLLQDPVGVRYFSDFLRKEFSEENILFWQACEYFNHVPAHDkkeLSYRAREIFSKFLCSKATTPVNIDS 141
Cdd:cd08737     1 QRVKRWGFSLDEVLKDPVGRDQFLRFLESEFSSENLRFWLAVQDLKKQPLQD---VAKRVEEIWQEFLAPGAPSAINLDS 77

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*...
gi 1622938478 142 QA-QLADDVLRAPHPDMFKEQQLQIFNLMKFDSYTRFLKSPLYQECIL 188
Cdd:cd08737    78 HSyEKTSQNVKDPGRYTFEDAQEHIYKLMKSDSYARFLRSNAYQDLLL 125

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 1622938478 317 KHCCIHLPD-GTSCVVAVKAGFSIKDILSGLCERHGINGAAADLFLVGGDKPLVLHQDSSILESRDLRLEK 386
Cdd:cd01760     1 NTFRLFLPNnETSVVVAVKPGKSLHEVLMPVLERHGLQLECVDVFLLGEKAPLDLNTDASSLIGQELRLDF 71

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 1622938478 388 TLFRLDLVPINRSVGLKAKPTKPVTEVLRPVVAKYGLDLSGLLVRLSGEKEPLDLGAPISSLDGQRVVLEE 458
Cdd:cd01760     1 NTFRLFLPNNETSVVVAVKPGKSLHEVLMPVLERHGLQLECVDVFLLGEKAPLDLNTDASSLIGQELRLDF 71

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 1622938478  71 FERLLQDPVGVRYFSDFLRKEFSEENILFWQACEYFNHVpaHDKKELSYRAREIFSKFLCSKATTPVNIDSQA-QLADDV 149
Cdd:cd08710     1 FDLLLNSKNGVAAFHAFLKTEFSEENLEFWLACEEFKKI--RSATKLASRAHHIFEEFIRSEAPKEVNIDHETrELTRTN 78

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 1622938478 150 LRAPHPDMFKEQQLQIFNLMKFDSYTRFLKSPLYQE 185
Cdd:cd08710    79 LQAATTSCFDVAQGKTRTLMEKDSYPRFLKSPAYRD 114

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622938478  71 FERLLQDPVGVRYFSDFLRKEFSEENILFWQACEYFNHVPAHDKkeLSYRAREIFSKFLCSKATTPVNIDS--QAQLADD 148
Cdd:cd08714     1 LENLINHECGLAAFKAFLKSEYSEENIDFWVSCEDYKKTKSPSK--LSPKARKIYEEFISVQATKEVNLDSctREETSRN 78

                          90       100       110
                  ....*....|....*....|....*....|....*..
gi 1622938478 149 VLRaPHPDMFKEQQLQIFNLMKFDSYTRFLKSPLYQE 185
Cdd:cd08714    79 MLE-PTISCFDEAQKKIFTLMEKDSYRRFLKSRFYLD 114

Regulator of G protein signaling (RGS) domain found in the RGS17 protein; The RGS (Regulator of G-protein Signaling) domain is an essential part of the RGS17 protein, a member of the RZ subfamily of the RGS protein family. They are a diverse group of multifunctional proteins that regulate cellular signaling events downstream of G-protein coupled receptors (GPCRs). As a major G-protein regulator, the RGS domain containing proteins are involved in many crucial cellular processes such as regulation of intracellular trafficking, glial differentiation, embryonic axis formation, skeletal and muscle development, and cell migration during early embryogenesis. RGS proteins play critical regulatory roles as GTPase activating proteins (GAPs) of the heterotrimeric G-protein G-alpha-subunits. Deactivation of the G-protein signaling controlled by the RGS domain, which accelerates GTPase activity of the alpha subunit by hydrolysis of GTP to GDP, results in reassociation of the alpha-subunit with the beta-gamma-dimer and inhibition of downstream activity. The RZ subfamily of RGS proteins includes RGS19 (former GAIP), RGS20, and its splice variant Ret-RGS. RGS17 is a relatively non-selective GAP for G-alpha-z and other G-alpha-i/o proteins. RGS17 blocks dopamine receptor-mediated inhibition of cAMP accumulation; it also blocks thyrotropin releasing hormone-stimulated Ca++ mobilization. RGS17, like other members of RZ subfamily, can act either as a GAP or as G-protein effector antogonist.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622938478  67 WAVSFERLLQDPVGVRYFSDFLRKEFSEENILFWQACEYFNHvpAHDKKELSYRAREIFSKFLCSKATTPVNIDSQA-QL 145
Cdd:cd08744     1 WSQNFDKMMKTPAGRNLFREFLRTEYSEENLLFWLACEDLKK--EQNKKVIEEKARLIYEDYISILSPKEVSLDSRVrEV 78

                          90       100       110
                  ....*....|....*....|....*....|....*....
gi 1622938478 146 ADDVLRAPHPDMFKEQQLQIFNLMKFDSYTRFLKSPLYQ 184
Cdd:cd08744    79 INRNLLDPNPHMYEDAQLQIYTLMHRDSFPRFLNSQIYK 117

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 1622938478  71 FERLLQDPVGVRYFSDFLRKEFSEENILFWQACEYFNHVPAHDKkeLSYRAREIFSKFLCSKATTPVNIDsqaQLADDV- 149
Cdd:cd08717     1 LDKLLQNSYGLASFKSFLKSEFSEENIEFWEACEDYKKTKSPLK--MATKAKKIYEEFIQTEAPKEVNID---HFTKDVt 75

                          90       100       110
                  ....*....|....*....|....*....|....*....
gi 1622938478 150 ---LRAPHPDMFKEQQLQIFNLMKFDSYTRFLKSPLYQE 185
Cdd:cd08717    76 mknLVEPSSSSFDLAQKRIFALMEKDSLPRFVRSEFYQE 114

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622938478  71 FERLLQDPVGVRYFSDFLRKEFSEENILFWQACEYFNhvpAHDKKELSYRAREIFSKFLCSKATTPVNIDSQAQ--LADD 148
Cdd:cd08715     1 LEKLLASQTGQNVFRSFLKSEFSEENIEFWLACEDYK---KTESDLLPCKAEEIYKEFVQSDAAKQINIDFRTResTAKK 77

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 1622938478 149 vLRAPHPDMFKEQQLQIFNLMKFDSYTRFLKSPLY 183
Cdd:cd08715    78 -IKAPTPTCFDEAQKVIYILMERDSYPRFLKSDIY 111

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 1622938478  63 RVASWAVSFERLLQDPVGVRYFSDFLRKEFSEENILFWQACEYFNHVPAhdkKELSYRAREIFSKFLCSKATTPVNIDSQ 142
Cdd:cd08738     1 RVKRWGFGMDEALKDPVGREQFLKFLESEFSSENLRFWLAVEDLKKRPI---REVPSRVQEIWQEFLAPGAPSAINLDSK 77

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 1622938478 143 A-QLADDVLRAPHPDMFKEQQLQIFNLMKFDSYTRFLKSPLYQE 185
Cdd:cd08738    78 SyDKTTQNVKDPGRYTFEDAQEHIYKLMKSDSYPRFIRSSAYQE 121

Regulator of G protein signaling (RGS) domain found in the RGS18 protein; The RGS (Regulator of G-protein Signaling) domain is an essential part of the RGS18 protein. RGS18 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. RGS18 is a member of the R4/RGS subfamily and is expressed predominantly in osteoclasts where it acts as a negative regulator of the acidosis-induced osteoclastogenic OGR1/NFAT signaling pathway. RANKL (receptor activator of nuclear factor B ligand) stimulates osteoclastogenesis by inhibiting expression of RGS18.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622938478  71 FERLLQDPVGVRYFSDFLRKEFSEENILFWQACEYFNHVPAhdKKELSYRAREIFSKFLCSKATTPVNID-SQAQLADDV 149
Cdd:cd08712     1 FDKLLSHKDGLEAFTRFLKTEFSEENIEFWIACEDYKKSKT--PQQIHLKAKAIYEKFIQTDAPKEVNLDfHTKEVTTNS 78

                          90       100       110
                  ....*....|....*....|....*....|....
gi 1622938478 150 LRAPHPDMFKEQQLQIFNLMKFDSYTRFLKSPLY 183
Cdd:cd08712    79 IEQPTLTSFDAAQSRVYQLMEQDSYPRFLKSDIY 112

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 1622938478  74 LLQDPVGVRYFSDFLRKEFSEENILFWQACEYFNHvpAHDKKELSYRAREIFSKFLCSKATTPVNID-SQAQLADDVLRA 152
Cdd:cd08723     1 LLANQAGLDAFRTFLKSEFSEENVEFWLACEDFKK--TKSSTEIALKAQMIYSEFIQADAPKEINIDfHTRDLISQNISE 78

                          90       100       110
                  ....*....|....*....|....*....|...
gi 1622938478 153 PHPDMFKEQQLQIFNLMKFDSYTRFLKSPLYQE 185
Cdd:cd08723    79 PTLKCFDEAQSLIYCLMAKDSFPRFLKSEVYKK 111

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 1622938478  71 FERLLQDPVGVRYFSDFLRKEFSEENILFWQACEYFNHVPAHDKKelSYRAREIFSKFLCSKATTPVNIDSQAQLAddVL 150
Cdd:cd08716     1 FENLMATKYGPIIYATYLKTEHSDENIEFWLACETYKKIASQRKR--ISMARKLFASYIQPQAPREINIDSPTRKA--II 76

                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 1622938478 151 R---APHPDMFKEQQLQIFNLMKFDSYTRFLKSPLYQE 185
Cdd:cd08716    77 RniqEPTQSCFDEAQRIVYMHMERDSYPRFLESKFYQK 114

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 1622938478  75 LQDPVGVRYFSDFLRKEFSEENILFWQACEYF------------------NHVPAHDKKELSYRAREIFSKFLCSKATTP 136
Cdd:cd08719     2 LVNNVALSYFIDFMQSVGGQAYLFFWLTVEGYrvsaeqqlselhlrqrggEHQRSDVYEMLRAAALNIYDQYLSEKASPR 81

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1622938478 137 VNIDSqaQLADDVLR-----APHPDMFKEQQLQIFNLMKFDS--YTRFLKSPLY 183
Cdd:cd08719    82 VPLDD--SLVKKLLNrlrndTPSDLWFDDIQQKVFDIMQEDErfYPAFKKSPAY 133