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Gene Review

RGS9  -  regulator of G-protein signaling 9

Homo sapiens

Synonyms: MGC111763, MGC26458, PERRS, RGS9L, Regulator of G-protein signaling 9
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Disease relevance of RGS9

  • To explore the potential role of the RGS9 gene in human retinal disease, we determined its exon/intron arrangement, and investigated its expression in human retina [1].
  • Elevated levels of DeltaFosB and RGS9 in striatum in Parkinson's disease [2].

High impact information on RGS9

  • In this issue of Neuron, Krispel et al. resolve a long-standing puzzle in phototransduction, establishing that RGS9 "GAPping" of G(t)alpha-GTP is the molecular mechanism underlying the dominant recovery time constant of mouse rod photoreceptors and that a precise level of expression of RGS9 is required for normal photoresponse timing [3].
  • Results indicate that there is global resemblance between the interaction surface of the rgRGS domain with Galpha(13) and the interactions of RGS4 and RGS9 with their Galpha substrates [4].
  • The G alpha binding sites on RGS4 and RGS9, called the "A" site, is localized to the loops between helices alpha 3 and alpha 4, alpha 5 and alpha 6, and alpha 7 and alpha 8 [5].
  • The GTPase activity of Galpha(t)G38D can be accelerated by photoreceptor regulator of G protein signaling, RGS9 [6].
  • Interestingly, levels of both DeltaFosB and RGS9 correlated inversely with putamen levels of dopamine, dopamine metabolites, and the dopamine transporter [2].

Chemical compound and disease context of RGS9


Biological context of RGS9


Associations of RGS9 with chemical compounds

  • In addition to GCAPs several other proteins including aktin, tubulin, a glutamic-acid-rich protein and a GTPase accelerating protein (RGS9) were found to interact with ROS-GC1 and probably form a multiprotein complex [7].

Physical interactions of RGS9

  • (ii) RGS9 forms a complex with a type of G-protein beta-subunit (Gbeta5) via its GGL domain, which facilitates the GAP function of RGS9 [8].

Other interactions of RGS9

  • We evaluated GGL containing RGS9 and RGS7 for functional complementation in a RGS (sst2Delta) knockout yeast strain [9].
  • Enhancement of pheromone response by RGS9 and Gbeta5 in yeast [9].
  • The experimental strategies developed in kinetic studies of interactions between RGS9 isoforms with G proteins of the Gi subfamily provide a useful framework for conducting similar studies with essentially any regulator of G-protein signaling (RGS) protein-G-protein pair [10].


  1. Structure, alternative splicing, and expression of the human RGS9 gene. Zhang, K., Howes, K.A., He, W., Bronson, J.D., Pettenati, M.J., Chen, C., Palczewski, K., Wensel, T.G., Baehr, W. Gene (1999) [Pubmed]
  2. Elevated levels of DeltaFosB and RGS9 in striatum in Parkinson's disease. Tekumalla, P.K., Calon, F., Rahman, Z., Birdi, S., Rajput, A.H., Hornykiewicz, O., Di Paolo, T., Bédard, P.J., Nestler, E.J. Biol. Psychiatry (2001) [Pubmed]
  3. RGS expression level precisely regulates the duration of rod photoresponses. Pugh, E.N. Neuron (2006) [Pubmed]
  4. Mapping the Galpha13 binding interface of the rgRGS domain of p115RhoGEF. Chen, Z., Singer, W.D., Wells, C.D., Sprang, S.R., Sternweis, P.C. J. Biol. Chem. (2003) [Pubmed]
  5. G protein-coupled receptor Kinase 2/G alpha q/11 interaction. A novel surface on a regulator of G protein signaling homology domain for binding G alpha subunits. Sterne-Marr, R., Tesmer, J.J., Day, P.W., Stracquatanio, R.P., Cilente, J.A., O'Connor, K.E., Pronin, A.N., Benovic, J.L., Wedegaertner, P.B. J. Biol. Chem. (2003) [Pubmed]
  6. Loss of the effector function in a transducin-alpha mutant associated with Nougaret night blindness. Muradov, K.G., Artemyev, N.O. J. Biol. Chem. (2000) [Pubmed]
  7. Photoreceptor specific guanylate cyclases in vertebrate phototransduction. Koch, K.W., Duda, T., Sharma, R.K. Mol. Cell. Biochem. (2002) [Pubmed]
  8. Physiological actions of regulators of G-protein signaling (RGS) proteins. Ishii, M., Kurachi, Y. Life Sci. (2003) [Pubmed]
  9. Enhancement of pheromone response by RGS9 and Gbeta5 in yeast. Ajit, S.K., Young, K.H. Biochem. Biophys. Res. Commun. (2004) [Pubmed]
  10. Kinetic approaches to study the function of RGS9 isoforms. Martemyanov, K.A., Arshavsky, V.Y. Meth. Enzymol. (2004) [Pubmed]
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