RGS9

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Regulator of G-protein signaling 9
Protein RGS9 PDB 1fqi.png
PDB rendering based on 1fqi.
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols RGS9 ; PERRS; RGS9L
External IDs OMIM604067 HomoloGene2845 GeneCards: RGS9 Gene
RNA expression pattern
PBB GE RGS9 206518 s at tn.png
PBB GE RGS9 gnf1h07360 at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 8787 19739
Ensembl ENSG00000108370 ENSMUSG00000020599
UniProt O75916 O54828
RefSeq (mRNA) NM_001081955 NM_001165934
RefSeq (protein) NP_001075424 NP_001159406
Location (UCSC) Chr 17:
63.13 – 63.22 Mb
Chr 11:
109.23 – 109.3 Mb
PubMed search [1] [2]

Regulator of G-protein signalling 9, also known as RGS9, is a human gene,[1] 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][1]

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.[2]

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.[3][4][5][6][7][8][9] RGS9-deficient mice exhibit some motor and cognitive difficulties however, so inhibition of this protein is likely to cause similar side effects.[10]

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.[11]


References[edit]

  1. ^ a b "Entrez Gene: RGS9 regulator of G-protein signalling 9". 
  2. ^ 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 2634932. PMID 19098104. 
  3. ^ 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. 
  4. ^ 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 263869. PMID 14595021. 
  5. ^ 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. 
  6. ^ 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. 
  7. ^ 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. 
  8. ^ 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. 
  9. ^ 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. 
  10. ^ 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. 
  11. ^ 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.  edit

Further reading[edit]