Biology:RGS4

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Short description: Protein-coding gene in the species Homo sapiens


A representation of the 3D structure of the protein myoglobin showing turquoise α-helices.
Generic protein structure example

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.[1]

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.[2] 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.[3] 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.[1]

Clinical significance

A number of studies associate the RGS4 gene with schizophrenia,[4][5][6][7] while some fail to detect an association.[8]

RGS4 is also of interest as one of the three main RGS proteins (along with RGS9 and RGS17) involved in terminating signalling by the mu opioid receptor,[9] and may be important in the development of tolerance to opioid drugs.[10][11][12][13][14]

Inhibitors

Interactions

RGS4 has been shown to interact with:

References

  1. ↑ 1.0 1.1 "Entrez Gene: RGS4 regulator of G-protein signalling 4". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=5999. 
  2. ↑ "GAIP and RGS4 are GTPase-activating proteins for the Gi subfamily of G protein alpha subunits.". Cell 86 (3): 445–52. 1996. doi:10.1016/S0092-8674(00)80117-8. PMID 8756726. 
  3. ↑ "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. July 1997. doi:10.1073/pnas.94.14.7216. PMID 9207071. Bibcode: 1997PNAS...94.7216P. 
  4. ↑ "Association of RGS4 variants with schizotypy and cognitive endophenotypes at the population level". Behavioral and Brain Functions 4: 46. 2008. doi:10.1186/1744-9081-4-46. PMID 18834502. 
  5. ↑ "RGS4 Polymorphisms Associated With Variability of Cognitive Performance in a Family-Based Schizophrenia Sample". Schizophrenia Bulletin 36 (5): 983–90. March 2009. doi:10.1093/schbul/sbp002. PMID 19282471. 
  6. ↑ "Recent advances in postmortem pathology and neurochemistry in schizophrenia". Current Opinion in Psychiatry 22 (2): 154–60. March 2009. doi:10.1097/YCO.0b013e328323d52e. PMID 19553869. 
  7. ↑ "Expression of RGS4 splice variants in dorsolateral prefrontal cortex of schizophrenic and bipolar disorder patients". Biological Psychiatry 65 (6): 541–5. March 2009. doi:10.1016/j.biopsych.2008.10.026. PMID 19041089. 
  8. ↑ "Regulator of G-protein signalling 4 expression is not altered in the prefrontal cortex in schizophrenia". The Australian and New Zealand Journal of Psychiatry 42 (8): 740–5. August 2008. doi:10.1080/00048670802206338. PMID 18622782. 
  9. ↑ "A role of RGS proteins in drug addiction". Biochemical Pharmacology 75 (1): 76–84. January 2008. doi:10.1016/j.bcp.2007.07.045. PMID 17880927. 
  10. ↑ "Generation and characterization of Rgs4 mutant mice". Molecular and Cellular Biology 25 (10): 4221–8. May 2005. doi:10.1128/MCB.25.10.4221-4228.2005. PMID 15870291. 
  11. ↑ "Effector antagonism by the regulators of G protein signalling (RGS) proteins causes desensitization of mu-opioid receptors in the CNS". Psychopharmacology 180 (1): 1–11. June 2005. doi:10.1007/s00213-005-2248-9. PMID 15830230. 
  12. ↑ "Selective interactions between G protein subunits and RGS4 with the C-terminal domains of the mu- and delta-opioid receptors regulate opioid receptor signaling". Cellular Signalling 18 (6): 771–82. June 2006. doi:10.1016/j.cellsig.2005.07.003. PMID 16120478. 
  13. ↑ "Regulator of G protein signaling 4 confers selectivity to specific G proteins to modulate mu- and delta-opioid receptor signaling". Cellular Signalling 21 (7): 1218–28. July 2009. doi:10.1016/j.cellsig.2009.03.013. PMID 19324084. 
  14. ↑ "Differential Modulation of {micro}- and {delta}-Opioid Receptor Agonists by Endogenous RGS4 Protein in SH-SY5Y Cells". The Journal of Biological Chemistry 284 (27): 18357–67. July 2009. doi:10.1074/jbc.M109.015453. PMID 19416973. 
  15. ↑ "Structure-based design, synthesis, and activity of peptide inhibitors of RGS4 GAP activity". Regulators of G-Protein Signaling, Part A. Methods in Enzymology. 389. 2004. pp. 266–77. doi:10.1016/S0076-6879(04)89016-5. ISBN 9780121827946. 
  16. ↑ "Identification of small-molecule inhibitors of RGS4 using a high-throughput flow cytometry protein interaction assay". Molecular Pharmacology 71 (1): 169–75. January 2007. doi:10.1124/mol.106.028670. PMID 17012620. 
  17. ↑ "RGS4 and RGS2 bind coatomer and inhibit COPI association with Golgi membranes and intracellular transport". Mol. Biol. Cell 11 (9): 3155–68. 2000. doi:10.1091/mbc.11.9.3155. PMID 10982407. 
  18. ↑ "Identification of novel ErbB3-interacting factors using the split-ubiquitin membrane yeast two-hybrid system". Genome Res. 13 (7): 1744–53. 2003. doi:10.1101/gr.1276503. PMID 12840049. 
  19. ↑ "RGS16 inhibits signalling through the G alpha 13-Rho axis". Nat. Cell Biol. 5 (12): 1095–103. December 2003. doi:10.1038/ncb1065. PMID 14634662. https://zenodo.org/record/1233351. 
  20. ↑ "Expression of GTPase-deficient Gialpha2 results in translocation of cytoplasmic RGS4 to the plasma membrane". J. Biol. Chem. 273 (29): 18405–10. 1998. doi:10.1074/jbc.273.29.18405. PMID 9660808. 

Further reading



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