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Protein RGS9 PDB 1fqi.png
Available structures
PDBOrtholog search: PDBe RCSB
AliasesRGS9, PERRS, RGS9L, regulator of G-protein signaling 9, regulator of G protein signaling 9
External IDsMGI: 1338824 HomoloGene: 2845 GeneCards: RGS9
Gene location (Human)
Chromosome 17 (human)
Chr.Chromosome 17 (human)[1]
Chromosome 17 (human)
Genomic location for RGS9
Genomic location for RGS9
Band17q24.1Start65,100,812 bp[1]
End65,227,703 bp[1]
RNA expression pattern
PBB GE RGS9 gnf1h07360 at fs.png

PBB GE RGS9 206518 s at fs.png
More reference expression data
RefSeq (mRNA)



RefSeq (protein)



Location (UCSC)Chr 17: 65.1 – 65.23 MbChr 11: 109.23 – 109.3 Mb
PubMed search[3][4]
View/Edit HumanView/Edit Mouse

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]

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]


  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:". 
  4. ^ "Mouse PubMed Reference:". 
  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. doi:10.1073/pnas.0808941106. PMC 2634932Freely accessible. 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. PMID 11207815. 
  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. doi:10.1073/pnas.2232594100. PMC 263869Freely accessible. 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. 
  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. 
  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 3394094Freely accessible. 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 2241663Freely accessible. 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 3122235Freely accessible. PMID 21511947. 

Further reading[edit]