Regulator of G-protein signalling 9, also known as RGS9, is a human gene,[5] which codes for a protein involved in regulation of signal transduction inside cells. Members of the RGS family, such as RGS9, are signaling proteins that suppress the activity of G proteins by promoting their deactivation.[supplied by OMIM][5]

RGS9
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesRGS9, PERRS, RGS9L, regulator of G-protein signaling 9, regulator of G protein signaling 9
External IDsOMIM: 604067 MGI: 1338824 HomoloGene: 2845 GeneCards: RGS9
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_001081955
NM_001165933
NM_003835

NM_001165934
NM_011268

RefSeq (protein)

NP_001075424
NP_001159405
NP_003826

NP_001159406
NP_035398

Location (UCSC)Chr 17: 65.1 – 65.23 MbChr 11: 109.12 – 109.19 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

There are two splice isoforms of RGS9 with quite different properties and patterns of expression. RGS9-1 is mainly found in the eye and is involved in regulation of phototransduction in rod and cone cells of the retina, while RGS9-2 is found in the brain, and regulates dopamine and opioid signaling in the basal ganglia.[6]

RGS9-2 is of particular interest as the most important RGS protein involved in terminating signalling by the mu opioid receptor (although RGS4 and RGS17 are also involved), and is thought to be important in the development of tolerance to opioid drugs.[7][8][9][10][11][12][13] RGS9-deficient mice exhibit some motor and cognitive difficulties however, so inhibition of this protein is likely to cause similar side effects.[14]

RGS9 is differentially regulated by Guanine nucleotide-binding protein subunit beta-5 (GNB5) via the DEP domain and DEP helical-extension domain in protein stability and membrane anchor association.[15]

References edit

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000108370 - Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000020599 - Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ a b "Entrez Gene: RGS9 regulator of G-protein signalling 9".
  6. ^ Martemyanov KA, Krispel CM, Lishko PV, Burns ME, Arshavsky VY (December 2008). "Functional comparison of RGS9 splice isoforms in a living cell". Proceedings of the National Academy of Sciences of the United States of America. 105 (52): 20988–93. Bibcode:2008PNAS..10520988M. doi:10.1073/pnas.0808941106. PMC 2634932. PMID 19098104.
  7. ^ Garzón J, Rodríguez-Díaz M, López-Fando A, Sánchez-Blázquez P (February 2001). "RGS9 proteins facilitate acute tolerance to mu-opioid effects". The European Journal of Neuroscience. 13 (4): 801–11. doi:10.1046/j.0953-816x.2000.01444.x. hdl:10261/154868. PMID 11207815. S2CID 23943994.
  8. ^ Zachariou V, Georgescu D, Sanchez N, Rahman Z, DiLeone R, Berton O, Neve RL, Sim-Selley LJ, Selley DE, Gold SJ, Nestler EJ (November 2003). "Essential role for RGS9 in opiate action". Proceedings of the National Academy of Sciences of the United States of America. 100 (23): 13656–61. Bibcode:2003PNAS..10013656Z. doi:10.1073/pnas.2232594100. PMC 263869. PMID 14595021.
  9. ^ Sánchez-Blázquez P, Rodríguez-Muñoz M, Montero C, Garzón J (January 2005). "RGS-Rz and RGS9-2 proteins control mu-opioid receptor desensitisation in CNS: the role of activated Galphaz subunits". Neuropharmacology. 48 (1): 134–50. doi:10.1016/j.neuropharm.2004.08.016. PMID 15617734. S2CID 40755580.
  10. ^ Garzón J, Rodríguez-Muñoz M, López-Fando A, Sánchez-Blázquez P (March 2005). "Activation of mu-opioid receptors transfers control of Galpha subunits to the regulator of G-protein signaling RGS9-2: role in receptor desensitization". The Journal of Biological Chemistry. 280 (10): 8951–60. doi:10.1074/jbc.M407005200. PMID 15632124.
  11. ^ Psifogeorgou K, Papakosta P, Russo SJ, Neve RL, Kardassis D, Gold SJ, Zachariou V (October 2007). "RGS9-2 is a negative modulator of mu-opioid receptor function". Journal of Neurochemistry. 103 (2): 617–25. doi:10.1111/j.1471-4159.2007.04812.x. PMID 17725581. S2CID 23246884.
  12. ^ Hooks SB, Martemyanov K, Zachariou V (January 2008). "A role of RGS proteins in drug addiction". Biochemical Pharmacology. 75 (1): 76–84. doi:10.1016/j.bcp.2007.07.045. PMID 17880927.
  13. ^ Traynor JR, Terzi D, Caldarone BJ, Zachariou V (March 2009). "RGS9-2: probing an intracellular modulator of behavior as a drug target". Trends in Pharmacological Sciences. 30 (3): 105–11. doi:10.1016/j.tips.2008.11.006. PMC 3394094. PMID 19211160.
  14. ^ Blundell J, Hoang CV, Potts B, Gold SJ, Powell CM (January 2008). "Motor coordination deficits in mice lacking RGS9". Brain Research. 1190: 78–85. doi:10.1016/j.brainres.2007.11.017. PMC 2241663. PMID 18073128.
  15. ^ Masuho, I.; Wakasugi-Masuho, H.; Posokhova, E. N.; Patton, J. R.; Martemyanov, K. A. (2011). "Type 5 G Protein Subunit (G 5) Controls the Interaction of Regulator of G Protein Signaling 9 (RGS9) with Membrane Anchors". Journal of Biological Chemistry. 286 (24): 21806–21813. doi:10.1074/jbc.M111.241513. PMC 3122235. PMID 21511947.

Further reading edit

External links edit

  • Overview of all the structural information available in the PDB for UniProt: O54828 (Mouse Regulator of G-protein signaling 9) at the PDBe-KB.