RGS9

Last updated
RGS9
Protein RGS9 PDB 1fqi.png
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases RGS9 , PERRS, RGS9L, regulator of G-protein signaling 9, regulator of G protein signaling 9
External IDs OMIM: 604067 MGI: 1338824 HomoloGene: 2845 GeneCards: RGS9
Orthologs
SpeciesHumanMouse
Entrez

8787

19739

Ensembl

ENSG00000108370

ENSMUSG00000020599

UniProt

O75916

O54828

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 Mb Chr 11: 109.12 – 109.19 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/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]

Contents

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]

Related Research Articles

μ-opioid receptor Protein-coding gene in the species Homo sapiens, named for its ligand morphine

The μ-opioid receptors (MOR) are a class of opioid receptors with a high affinity for enkephalins and beta-endorphin, but a low affinity for dynorphins. They are also referred to as μ(mu)-opioid peptide (MOP) receptors. The prototypical μ-opioid receptor agonist is morphine, the primary psychoactive alkaloid in opium and for which the receptor was named, with mu being the Greek letter m. It is an inhibitory G-protein coupled receptor that activates the Gi alpha subunit, inhibiting adenylate cyclase activity, lowering cAMP levels.

<span class="mw-page-title-main">RGS4</span>

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.

<span class="mw-page-title-main">RGS2</span>

Regulator of G-protein signaling 2 is a protein that in humans is encoded by the RGS2 gene. It is part of a larger family of RGS proteins that control signalling through G-protein coupled receptors (GPCR).

<span class="mw-page-title-main">GNAQ</span> Protein-coding gene in the species Homo sapiens

Guanine nucleotide-binding protein G(q) subunit alpha is a protein that in humans is encoded by the GNAQ gene. Together with GNA11, it functions as a Gq alpha subunit.

<span class="mw-page-title-main">GNAI1</span> Protein-coding gene in the species Homo sapiens

Guanine nucleotide-binding protein G(i), alpha-1 subunit is a protein that in humans is encoded by the GNAI1 gene.

<span class="mw-page-title-main">GNAO1</span>

Guanine nucleotide-binding protein G(o) subunit alpha is a protein that in humans is encoded by the GNAO1 gene.

<span class="mw-page-title-main">RGS16</span>

Regulator of G-protein signaling 16 is a protein that in humans is encoded by the RGS16 gene.

<span class="mw-page-title-main">RGS19</span>

Regulator of G-protein signaling 19 is a protein that in humans is encoded by the RGS19 gene.

<span class="mw-page-title-main">GNB5</span>

Guanine nucleotide-binding protein subunit beta-5 is a protein that in humans is encoded by the GNB5 gene. Alternatively spliced transcript variants encoding different isoforms exist.

<span class="mw-page-title-main">RGS7</span> Protein-coding gene in the species Homo sapiens

Regulator of G-protein signaling 7 is a protein that in humans is encoded by the RGS7 gene.

<span class="mw-page-title-main">GNAT1</span>

Guanine nucleotide-binding protein G(t) subunit alpha-1 is a protein that in humans is encoded by the GNAT1 gene.

<span class="mw-page-title-main">RGS1</span> Protein-coding gene in the species Homo sapiens

Regulator of G-protein signaling 1 is a protein that in humans is encoded by the RGS1 gene.

<span class="mw-page-title-main">RGS20</span> Protein-coding gene in the species Homo sapiens

Regulator of G-protein signaling 20 is a protein that in humans is encoded by the RGS20 gene.

<span class="mw-page-title-main">RGS12</span>

Regulator of G-protein signaling 12 is a protein that in humans is encoded by the RGS12 gene.

<span class="mw-page-title-main">RGS8</span> Protein-coding gene in the species Homo sapiens

Regulator of G-protein signaling 8 is a protein that in humans is encoded by the RGS8 gene.

<span class="mw-page-title-main">GNAI3</span>

Guanine nucleotide-binding protein G(k) subunit alpha is a protein that in humans is encoded by the GNAI3 gene.

<span class="mw-page-title-main">RGS13</span> Protein-coding gene in the species Homo sapiens

Regulator of G-protein signaling 13 (RGS13) is a protein that in humans is encoded by the RGS13 gene.

<span class="mw-page-title-main">RGS17</span>

Regulator of G-protein signaling 17 is a protein that in humans is encoded by the RGS17 gene.

<span class="mw-page-title-main">RGS11</span>

Regulator of G-protein signaling 11 is a protein that in humans is encoded by the RGS11 gene.

<span class="mw-page-title-main">CCG-4986</span>

CCG-4986 is a drug which is the first non-peptide compound discovered that acts as a selective inhibitor of the regulator of G protein signalling protein subtype RGS4. Regulators of G protein signalling are proteins which act to limit and shorten the response produced inside a cell following activation of a G protein-coupled receptor. Since different RGS subtypes are expressed in different tissues and are associated with particular receptors, this makes it possible for selective inhibitors of RGS proteins to be developed, which should be able to enhance the activity of a particular receptor in a defined target tissue, but not elsewhere in the body.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000108370 - Ensembl, May 2017
  2. 1 2 3 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. 1 2 "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



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