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RGS9

{{Short description|Protein-coding gene in the species Homo sapiens}}

{{Infobox_gene}}

Regulator of G-protein signalling 9, also known as RGS9, is a human gene,{{cite web | title = Entrez Gene: RGS9 regulator of G-protein signalling 9| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=8787}} 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]

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; genetic mutations in RGS9-1 cause the eye disease bradyopsia. RGS9-2 is found in the brain, and regulates dopamine and opioid signaling in the basal ganglia.{{cite journal |vauthors=Martemyanov KA, Krispel CM, Lishko PV, Burns ME, Arshavsky VY |title=Functional comparison of RGS9 splice isoforms in a living cell |journal=Proceedings of the National Academy of Sciences of the United States of America |volume=105 |issue=52 |pages=20988–93 |date=December 2008 |pmid=19098104 |pmc=2634932 |doi=10.1073/pnas.0808941106 |bibcode=2008PNAS..10520988M |doi-access=free }}

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.{{cite journal |vauthors=Garzón J, Rodríguez-Díaz M, López-Fando A, Sánchez-Blázquez P |title=RGS9 proteins facilitate acute tolerance to mu-opioid effects |journal=The European Journal of Neuroscience |volume=13 |issue=4 |pages=801–11 |date=February 2001 |pmid=11207815 |doi= 10.1046/j.0953-816x.2000.01444.x|hdl=10261/154868 |s2cid=23943994 |hdl-access=free }}{{cite journal |vauthors=Zachariou V, Georgescu D, Sanchez N, Rahman Z, DiLeone R, Berton O, Neve RL, Sim-Selley LJ, Selley DE, Gold SJ, Nestler EJ |title=Essential role for RGS9 in opiate action |journal=Proceedings of the National Academy of Sciences of the United States of America |volume=100 |issue=23 |pages=13656–61 |date=November 2003 |pmid=14595021 |pmc=263869 |doi=10.1073/pnas.2232594100 |bibcode=2003PNAS..10013656Z |doi-access=free }}{{cite journal |vauthors=Sánchez-Blázquez P, Rodríguez-Muñoz M, Montero C, Garzón J |title=RGS-Rz and RGS9-2 proteins control mu-opioid receptor desensitisation in CNS: the role of activated Galphaz subunits |journal=Neuropharmacology |volume=48 |issue=1 |pages=134–50 |date=January 2005 |pmid=15617734 |doi=10.1016/j.neuropharm.2004.08.016 |s2cid=40755580 }}{{cite journal |vauthors=Garzón J, Rodríguez-Muñoz M, López-Fando A, Sánchez-Blázquez P |title=Activation of mu-opioid receptors transfers control of Galpha subunits to the regulator of G-protein signaling RGS9-2: role in receptor desensitization |journal=The Journal of Biological Chemistry |volume=280 |issue=10 |pages=8951–60 |date=March 2005 |pmid=15632124 |doi=10.1074/jbc.M407005200 |doi-access=free }}{{cite journal |vauthors=Psifogeorgou K, Papakosta P, Russo SJ, Neve RL, Kardassis D, Gold SJ, Zachariou V |title=RGS9-2 is a negative modulator of mu-opioid receptor function |journal=Journal of Neurochemistry |volume=103 |issue=2 |pages=617–25 |date=October 2007 |pmid=17725581 |doi=10.1111/j.1471-4159.2007.04812.x |s2cid=23246884 |doi-access=free }}{{cite journal |vauthors=Hooks SB, Martemyanov K, Zachariou V |title=A role of RGS proteins in drug addiction |journal=Biochemical Pharmacology |volume=75 |issue=1 |pages=76–84 |date=January 2008 |pmid=17880927 |doi=10.1016/j.bcp.2007.07.045 }}{{cite journal |vauthors=Traynor JR, Terzi D, Caldarone BJ, Zachariou V |title=RGS9-2: probing an intracellular modulator of behavior as a drug target |journal=Trends in Pharmacological Sciences |volume=30 |issue=3 |pages=105–11 |date=March 2009 |pmid=19211160 |doi=10.1016/j.tips.2008.11.006 |pmc=3394094}} RGS9-deficient mice exhibit some motor and cognitive difficulties however, so inhibition of this protein is likely to cause similar side effects.{{cite journal |vauthors=Blundell J, Hoang CV, Potts B, Gold SJ, Powell CM |title=Motor coordination deficits in mice lacking RGS9 |journal=Brain Research |volume=1190 |pages=78–85 |date=January 2008 |pmid=18073128 |pmc=2241663 |doi=10.1016/j.brainres.2007.11.017 }}

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.{{Cite journal

| last1 = Masuho | first1 = I.

| last2 = Wakasugi-Masuho | first2 = H.

| last3 = Posokhova | first3 = E. N.

| last4 = Patton | first4 = J. R.

| last5 = Martemyanov | first5 = K. A.

| title = Type 5 G Protein Subunit (G 5) Controls the Interaction of Regulator of G Protein Signaling 9 (RGS9) with Membrane Anchors

| doi = 10.1074/jbc.M111.241513

| journal = Journal of Biological Chemistry

| volume = 286

| issue = 24

| pages = 21806–21813

| year = 2011

| pmid = 21511947

| pmc =3122235

| doi-access = free

}}

References

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Further reading

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  • {{cite journal |vauthors=Bonaldo MF, Lennon G, Soares MB |title=Normalization and subtraction: two approaches to facilitate gene discovery |journal=Genome Res. |volume=6 |issue= 9 |pages= 791–806 |year= 1997 |pmid= 8889548 |doi=10.1101/gr.6.9.791 |doi-access=free }}
  • {{cite journal |vauthors=Cowan CW, Fariss RN, Sokal I, etal |title=High expression levels in cones of RGS9, the predominant GTPase accelerating protein of rods |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=95 |issue= 9 |pages= 5351–6 |year= 1998 |pmid= 9560279 |doi=10.1073/pnas.95.9.5351 | pmc=20264 |bibcode=1998PNAS...95.5351C |doi-access=free }}
  • {{cite journal |vauthors=Granneman JG, Zhai Y, Zhu Z, etal |title=Molecular characterization of human and rat RGS 9L, a novel splice variant enriched in dopamine target regions, and chromosomal localization of the RGS 9 gene |journal=Mol. Pharmacol. |volume=54 |issue= 4 |pages= 687–94 |year= 1998 |pmid= 9765512 }}
  • {{cite journal |vauthors=Zhang K, Howes KA, He W, etal |title=Structure, alternative splicing, and expression of the human RGS9 gene |journal=Gene |volume=240 |issue= 1 |pages= 23–34 |year= 2000 |pmid= 10564809 |doi=10.1016/S0378-1119(99)00393-5 }}
  • {{cite journal |vauthors=Yu H, Bondarenko VA, Yamazaki A |title=Inhibition of retinal guanylyl cyclase by the RGS9-1 N-terminus |journal=Biochem. Biophys. Res. Commun. |volume=286 |issue= 1 |pages= 12–9 |year= 2001 |pmid= 11485301 |doi= 10.1006/bbrc.2001.5346 }}
  • {{cite journal |vauthors=Hu G, Wensel TG |title=R9AP, a membrane anchor for the photoreceptor GTPase accelerating protein, RGS9-1 |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |issue= 15 |pages= 9755–60 |year= 2002 |pmid= 12119397 |doi= 10.1073/pnas.152094799 | pmc=125004 |bibcode=2002PNAS...99.9755H |doi-access=free }}
  • {{cite journal |vauthors=Strausberg RL, Feingold EA, Grouse LH, etal |title=Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |issue= 26 |pages= 16899–903 |year= 2003 |pmid= 12477932 |doi= 10.1073/pnas.242603899 | pmc=139241 |bibcode=2002PNAS...9916899M |doi-access=free }}
  • {{cite journal |vauthors=Martemyanov KA, Lishko PV, Calero N, etal |title=The DEP domain determines subcellular targeting of the GTPase activating protein RGS9 in vivo |journal=J. Neurosci. |volume=23 |issue= 32 |pages= 10175–81 |year= 2003 |pmid= 14614075 |doi= 10.1523/JNEUROSCI.23-32-10175.2003|pmc= 6741003 }}
  • {{cite journal |vauthors=Nishiguchi KM, Sandberg MA, Kooijman AC, etal |title=Defects in RGS9 or its anchor protein R9AP in patients with slow photoreceptor deactivation |journal=Nature |volume=427 |issue= 6969 |pages= 75–8 |year= 2004 |pmid= 14702087 |doi= 10.1038/nature02170 |bibcode=2004Natur.427...75N |s2cid=953980 }}
  • {{cite journal |vauthors=Ajit SK, Young KH |title=Enhancement of pheromone response by RGS9 and Gbeta5 in yeast |journal=Biochem. Biophys. Res. Commun. |volume=324 |issue= 2 |pages= 686–91 |year= 2004 |pmid= 15474482 |doi= 10.1016/j.bbrc.2004.09.100 }}
  • {{cite journal |vauthors=Cheng JY, Luu CD, Yong VH, etal |title=Bradyopsia in an Asian man |journal=Arch. Ophthalmol. |volume=125 |issue= 8 |pages= 1138–40 |year= 2007 |pmid= 17698770 |doi= 10.1001/archopht.125.8.1138 }}

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External links

  • {{PDBe-KB2|O54828|Mouse Regulator of G-protein signaling 9}}

{{PDB Gallery|geneid=8787}}

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