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 2021882594 438 KGFSKRSATGNGRESASQPGEQWEPVQESSDSPSTSPGSASSPPGPPGTTPPGQKSPSGPFCTPQSPVSLAQEGTAQIWK 517
Cdd:pfam16612   1 KGLSKRSGKGNGKDKAAQPGGRQEPAQSYNESSAKSPGSAESRPRPPGTTLPGQKSPSVPFSAPLSPIPHAQEGSAQIWK 80

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 2021882594 518 RQSQEVEAGGIQTVEDEHVAELTLMGEGDISSPNSTLLPPPSTP--------QEVPGPSRPGSGTH 575
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 2021882594 231 RTLFRLDLVPINRSVGLKAKPTKPVTEVLRPVVARYGLDLSGLLVRLSGEKEPLDLGAPISSLDGQRVVLEEK 303
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 2021882594 305 PSRGKasaDKQKGVPVKQNTAVNSSSRNHSATGEERTLGKSNSIKIKGENGKNARDPRLSKREESIAKIGKKKYQ 379
Cdd:pfam16611   1 PARGK---DKQKGVSLKQSPAVASNTRNQSTTGEERPLGKSNSIKIKGENGKNSRDARLLKREESVAKTGKRKYQ 72

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

                           10        20
                   ....*....|....*....|..
gi 2021882594  387 EEFFELISKAQSNRADDQRGLL 408
Cdd:smart00390   2 EDLFDLLLRMQSSRMDDQRCEL 23

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 2021882594 438 KGFSKRSATGNGRESASQPGEQWEPVQESSDSPSTSPGSASSPPGPPGTTPPGQKSPSGPFCTPQSPVSLAQEGTAQIWK 517
Cdd:pfam16612   1 KGLSKRSGKGNGKDKAAQPGGRQEPAQSYNESSAKSPGSAESRPRPPGTTLPGQKSPSVPFSAPLSPIPHAQEGSAQIWK 80

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 2021882594 518 RQSQEVEAGGIQTVEDEHVAELTLMGEGDISSPNSTLLPPPSTP--------QEVPGPSRPGSGTH 575
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 2021882594 231 RTLFRLDLVPINRSVGLKAKPTKPVTEVLRPVVARYGLDLSGLLVRLSGEKEPLDLGAPISSLDGQRVVLEEK 303
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 2021882594 305 PSRGKasaDKQKGVPVKQNTAVNSSSRNHSATGEERTLGKSNSIKIKGENGKNARDPRLSKREESIAKIGKKKYQ 379
Cdd:pfam16611   1 PARGK---DKQKGVSLKQSPAVASNTRNQSTTGEERPLGKSNSIKIKGENGKNSRDARLLKREESVAKTGKRKYQ 72

Raf-like Ras-binding domain;

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 2021882594 162 HCCIHLPDGTSCVVAVKAGFSIKDILSGLCERHGINGAAADLFLVGGDK-PLVLHQDSSILESRDLRLE 229
Cdd:pfam02196   1 LCRVYLPDGQRTVVQVRPGETVRDALSKLCKKRGLNPEACDVYLVGGDKyPLDLDTDSSTLEGEEVRVE 69

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 2021882594   1 MFKEQQLQIFNLMKFDSYTRFLKSPLYQE 29
Cdd:cd08706    85 MFQKQQLQIFNLMKFDSYSRFLKSPLYQQ 113

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

                           10        20        30
                   ....*....|....*....|....*....|
gi 2021882594    1 MFKEQQLQIFNLMKFDSYTRFLKSPLYQEC 30
Cdd:smart00315  89 LFDEAQREVYELLEKDSFPRFLESDYYLRF 118

GoLoco motif;

                          10        20
                  ....*....|....*....|..
gi 2021882594 387 EEFFELISKAQSNRADDQRGLL 408
Cdd:pfam02188   1 EDFFDLLARVQSSRLDDQRCSL 22

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 2021882594 438 KGFSKRSATGNGRESASQPGEQWEPVQESSDSPSTSPGSASSPPGPPGTTPPGQKSPSGPFCTPQSPVSLAQEGTAQIWK 517
Cdd:pfam16612   1 KGLSKRSGKGNGKDKAAQPGGRQEPAQSYNESSAKSPGSAESRPRPPGTTLPGQKSPSVPFSAPLSPIPHAQEGSAQIWK 80

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 2021882594 518 RQSQEVEAGGIQTVEDEHVAELTLMGEGDISSPNSTLLPPPSTP--------QEVPGPSRPGSGTH 575
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 2021882594 231 RTLFRLDLVPINRSVGLKAKPTKPVTEVLRPVVARYGLDLSGLLVRLSGEKEPLDLGAPISSLDGQRVVLEEK 303
Cdd:cd17138     1 RTLFRLDLVPINRSVGLKAKPTKPVTEVLRPVVAKYGLNLNELVARISGEKEPLDLGLPISNLDGQRVVLEEK 73

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 2021882594 231 RTLFRLDLvPINRSVGLKAKPTKPVTEVLRPVVARYGLDLSGLLVRLSGEKEPLDLGAPISSLDGQRVVLEEK 303
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 2021882594 161 KHCCIHLPDGTSCVVAVKAGFSIKDILSGLCERHGINGAAADLFLVGGDKPLVLHQDSSILESRDLRLEK 230
Cdd:cd01817     1 KLCRVILPDGSTTVVQAKPGETIRQLLTRLLEKRGLSYAAFDVFIVGSDKPLDLNEDSSILGGKEVRVEQ 70

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 2021882594 161 KHCCIHLPD-GTSCVVAVKAGFSIKDILSGLCERHGINGAAADLFLVGGDKPLVLHQDSSILESRDLRLEK 230
Cdd:cd01760     1 NTFRLFLPNnETSVVVAVKPGKSLHEVLMPVLERHGLQLECVDVFLLGEKAPLDLNTDASSLIGQELRLDF 71

Raf-like Ras-binding domain;

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 2021882594 162 HCCIHLPDGTSCVVAVKAGFSIKDILSGLCERHGINGAAADLFLVGGDK-PLVLHQDSSILESRDLRLE 229
Cdd:pfam02196   1 LCRVYLPDGQRTVVQVRPGETVRDALSKLCKKRGLNPEACDVYLVGGDKyPLDLDTDSSTLEGEEVRVE 69

Raf-like Ras-binding domain;

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2021882594  234 FRLDLVPINRSVGLKAKPTKPVTEVLRPVVARYGLDLSGLLVRLSGEKEPLDLGAPISSLDGQRVVLEEK 303
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 2021882594   1 MFKEQQLQIFNLMKFDSYTRFLKSPLYQE 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 2021882594   1 MFKEQQLQIFNLMKFDSYTRFLKSPLYQE 29
Cdd:cd08742    87 MFKEQQLQIFNLMKFDSYTRFLKSPLYQE 115

Regulator of G protein signaling (RGS) domain found in the RGS10 protein; RGS (Regulator of G-protein Signaling) domain is an essential part of the RGS10 protein. RGS10 is a member of the RA/RGS subfamily of RGS proteins family, a diverse group of multifunctional proteins that regulate cellular signaling events downstream of G-protein coupled receptors (GPCRs). As a major G-protein regulator, RGS domain containing proteins are involved in many crucial cellular processes such as regulation of intracellular trafficking, glial differentiation, embryonic axis formation, skeletal and muscle development, and cell migration during early embryogenesis. RGS10 belong to the R12 RGS subfamily, which includes RGS12 and RGS14, all of which are highly selective for G-alpha-i1 over G-alpha-q. RGS10 exists in 2 splice isoforms. RGS10A is specifically expressed in osteoclasts and is a key component in the RANKL signaling mechanism for osteoclast differentiation, whereas RGS10B expressed in brain and in immune tissues and has been implicated in diverse processes including: promoting of dopaminergic neuron survival via regulation of the microglial inflammatory response, modulation of presynaptic and postsynaptic G-protein signalling, as well as a possible role in regulation of gene expression.

                          10        20
                  ....*....|....*....|....*..
gi 2021882594   1 MFKEQQLQIFNLMKFDSYTRFLKSPLY 27
Cdd:cd08741    85 MFQKLQDQIFNLMKYDSYSRFLKSDLF 111

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

                           10        20        30
                   ....*....|....*....|....*....|
gi 2021882594    1 MFKEQQLQIFNLMKFDSYTRFLKSPLYQEC 30
Cdd:smart00315  89 LFDEAQREVYELLEKDSFPRFLESDYYLRF 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
                  ....*....|....*....|....*....
gi 2021882594   1 MFKEQQLQIFNLMKFDSYTRFLKSPLYQE 29
Cdd:cd07440    85 CFDEAQEHILNLLEKDSYPRFLKSDLYLK 113

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

                          10        20
                  ....*....|....*....|....*...
gi 2021882594   1 MFKEQQLQIFNLMKFDSYTRFLKSPLYQ 28
Cdd:cd08718    90 TFDDAQLQIYTLMHRDSYPRFLNSAIYK 117

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 2021882594   2 FKEQQLQIFNLMKFDSYTRFLKSPLYQE 29
Cdd:cd08714    87 FDEAQKKIFTLMEKDSYRRFLKSRFYLD 114

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

                          10        20        30
                  ....*....|....*....|....*....|.
gi 2021882594   2 FKEQQLQIFNLMKFDSYTRFLKSPLYQECIL 32
Cdd:cd08737    95 FEDAQEHIYKLMKSDSYARFLRSNAYQDLLL 125

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
                  ....*....|....*....|....
gi 2021882594   6 QLQIFNLMKFDSYTRFLKSPLYQE 29
Cdd:cd08739    98 QTHIYMLMKKDSYARYLKSPIYKE 121

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.

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gi 2021882594   4 EQQLQIFNLMKFDSYTRFLKSPLYQEcILAE 34
Cdd:cd08740    97 DAQMHIYMLMKKDSYPRFLKSDLYKN-LLAE 126