RGS4
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| Location (UCSC) | Chr 1: 163.07 – 163.08 Mb | Chr 1: 169.57 – 169.58 Mb | |||||||
| PubMed search | [3] | [4] | |||||||
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Regulator of G protein signaling 4 also known as RGP4 is a protein that in humans is encoded by the RGS4 gene. RGP4 regulates G protein signaling.[5]
Function
Regulator of G protein signalling (RGS) family members are regulatory molecules that act as GTPase activating proteins (GAPs) for G alpha subunits of heterotrimeric G proteins.[6] RGS proteins are able to deactivate G protein subunits of the Gi alpha, Go alpha and Gq alpha subtypes. They drive G proteins into their inactive GDP-bound forms. Regulator of G protein signaling 4 belongs to this family. All RGS proteins share a conserved 120-amino acid sequence termed the RGS domain which conveys GAP activity.[7] Regulator of G protein signaling 4 protein is 37% identical to RGS1 and 97% identical to rat Rgs4. This protein negatively regulates signaling upstream or at the level of the heterotrimeric G protein and is localized in the cytoplasm.[5]
Clinical significance
A number of studies associate the RGS4 gene with schizophrenia,[8][9][10][11] while some fail to detect an association.[12]
RGS4 is also of interest as one of the three main RGS proteins (along with
mu opioid receptor,[13] and may be important in the development of tolerance to opioid drugs.[14][15][16][17][18]
Inhibitors
Interactions
RGS4 has been shown to
interact
with:
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000117152 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000038530 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ a b "Entrez Gene: RGS4 regulator of G-protein signalling 4".
- S2CID 12427406.
- PMID 9207071.
- PMID 18834502.
- PMID 19282471.
- S2CID 21346147.
- S2CID 21532854.
- S2CID 205398396.
- PMID 17880927.
- PMID 15870291.
- S2CID 21952312.
- PMID 16120478.
- PMID 19324084.
- PMID 19416973.
- PMID 15313571.
- S2CID 22699604.
- PMID 10982407.
- PMID 12840049.
- S2CID 6798899.
- PMID 9660808.
Further reading
- Berman DM, Wilkie TM, Gilman AG (1996). "GAIP and RGS4 are GTPase-activating proteins for the Gi subfamily of G protein alpha subunits". Cell. 86 (3): 445–52. S2CID 12427406.
- Levitt P, Ebert P, Mirnics K, et al. (2006). "Making the case for a candidate vulnerability gene in schizophrenia: Convergent evidence for regulator of G-protein signaling 4 (RGS4)". Biol. Psychiatry. 60 (6): 534–7. S2CID 3806917.
- Druey KM, Blumer KJ, Kang VH, Kehrl JH (1996). "Inhibition of G-protein-mediated MAP kinase activation by a new mammalian gene family". Nature. 379 (6567): 742–6. S2CID 4362632.
- Heximer SP, Watson N, Linder ME, et al. (1998). "RGS2/G0S8 is a selective inhibitor of Gqalpha function". Proc. Natl. Acad. Sci. U.S.A. 94 (26): 14389–93. PMID 9405622.
- Luo X, Popov S, Bera AK, Wilkie TM, Muallem S (March 2001). "RGS proteins provide biochemical control of agonist-evoked [Ca2+]i oscillations". Mol. Cell. 7 (3): 651–60. PMID 11463389.
- Pashkov V, Huang J, Parameswara VK, Kedzierski W, Kurrasch DM, Tall GG, Esser V, Gerard RD, Uyeda K, Towle HC, Wilkie TM (2011). "Regulator of G protein signaling (RGS16) inhibits hepatic fatty acid oxidation in a carbohydrate response element-binding protein (ChREBP)-dependent manner". J Biol Chem. 286 (17): 15116–15125. PMID 21357625.
- Popov S, Yu K, Kozasa T, Wilkie TM (July 1997). "The regulators of G protein signaling (RGS) domains of RGS4, RGS10, and GAIP retain GTPase activating protein activity in vitro". Proc. Natl. Acad. Sci. U.S.A. 94 (14): 7216–20. PMID 9207071.
- Popov SG, Krishna UM, PMID 10747990.
- Srinivasa SP, Bernstein LS, Blumer KJ, Linder ME (1998). "Plasma membrane localization is required for RGS4 function in Saccharomyces cerevisiae". Proc. Natl. Acad. Sci. U.S.A. 95 (10): 5584–9. PMID 9576926.
- Druey KM, Sullivan BM, Brown D, et al. (1998). "Expression of GTPase-deficient Gialpha2 results in translocation of cytoplasmic RGS4 to the plasma membrane". J. Biol. Chem. 273 (29): 18405–10. PMID 9660808.
- Faraone SV, Matise T, Svrakic D, et al. (1998). "Genome scan of European-American schizophrenia pedigrees: results of the NIMH Genetics Initiative and Millennium Consortium". Am. J. Med. Genet. 81 (4): 290–5. PMID 9674973.
- Wang J, Ducret A, Tu Y, et al. (1998). "RGSZ1, a Gz-selective RGS protein in brain. Structure, membrane association, regulation by Galphaz phosphorylation, and relationship to a Gz gtpase-activating protein subfamily". J. Biol. Chem. 273 (40): 26014–25. PMID 9748280.
- Shaw SH, Kelly M, Smith AB, et al. (1998). "A genome-wide search for schizophrenia susceptibility genes". Am. J. Med. Genet. 81 (5): 364–76. PMID 9754621.
- Posner BA, Mukhopadhyay S, Tesmer JJ, et al. (1999). "Modulation of the affinity and selectivity of RGS protein interaction with G alpha subunits by a conserved asparagine/serine residue". Biochemistry. 38 (24): 7773–9. PMID 10387017.
- Tu Y, Popov S, Slaughter C, Ross EM (2000). "Palmitoylation of a conserved cysteine in the regulator of G protein signaling (RGS) domain modulates the GTPase-activating activity of RGS4 and RGS10". J. Biol. Chem. 274 (53): 38260–7. PMID 10608901.
- Moy FJ, Chanda PK, Cockett MI, et al. (2000). "1H, 15N, 13C, and 13CO assignments and secondary structure determination of RGS4". J. Biomol. NMR. 15 (4): 339–40. S2CID 37351864.
- Popov SG, Krishna UM, Falck JR, Wilkie TM (2000). "Ca2+/Calmodulin reverses phosphatidylinositol 3,4, 5-trisphosphate-dependent inhibition of regulators of G protein-signaling GTPase-activating protein activity". J. Biol. Chem. 275 (25): 18962–8. PMID 10747990.
- Ekelund J, Lichtermann D, Hovatta I, et al. (2000). "Genome-wide scan for schizophrenia in the Finnish population: evidence for a locus on chromosome 7q22". Hum. Mol. Genet. 9 (7): 1049–57. PMID 10767329.
- Brzustowicz LM, Hodgkinson KA, Chow EW, et al. (2000). "Location of a major susceptibility locus for familial schizophrenia on chromosome 1q21-q22". Science. 288 (5466): 678–82. PMID 10784452.
- Chatterjee TK, Fisher RA (2000). "Cytoplasmic, nuclear, and golgi localization of RGS proteins. Evidence for N-terminal and RGS domain sequences as intracellular targeting motifs". J. Biol. Chem. 275 (31): 24013–21. PMID 10791963.
- Chatterjee TK, Fisher RA (2000). "Novel alternative splicing and nuclear localization of human RGS12 gene products". J. Biol. Chem. 275 (38): 29660–71. PMID 10869340.
- Ross EM, Wilkie TM (2000). "GTPase-activating proteins for heterotrimeric G proteins: regulators of G protein signaling (RGS) and RGS-like proteins". Annual Review of Biochemistry. 69: 795–827. S2CID 11637673.
- Sierra DA, Gilbert DJ, Householder D, Grishin NV, Yu K, Ukidwe P, Barker SA, He W, Wensel TG, Otero G, Brown G, Copeland NG, Jenkins NA, Wilkie TM (2002). "Evolution of the regulators of G-protein signaling multigene family in mouse and human". Genomics. 79 (2): 177–85. S2CID 16065132.
- Sullivan BM, Harrison-Lavoie KJ, Marshansky V, et al. (2000). "RGS4 and RGS2 bind coatomer and inhibit COPI association with Golgi membranes and intracellular transport". Mol. Biol. Cell. 11 (9): 3155–68. PMID 10982407.
- Dowal L, Elliott J, Popov S, et al. (2001). "Determination of the contact energies between a regulator of G protein signaling and G protein subunits and phospholipase C beta 1". Biochemistry. 40 (2): 414–21. PMID 11148035.
- Richardson RM, Marjoram RJ, Barr AJ, Snyderman R (2001). "RGS4 inhibits platelet-activating factor receptor phosphorylation and cellular responses". Biochemistry. 40 (12): 3583–8. PMID 11297424.
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