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]
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.
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.
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).
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.
Guanine nucleotide-binding protein G(i), alpha-1 subunit is a protein that in humans is encoded by the GNAI1 gene.
Guanine nucleotide-binding protein G(o) subunit alpha is a protein that in humans is encoded by the GNAO1 gene.
Regulator of G-protein signaling 16 is a protein that in humans is encoded by the RGS16 gene.
Regulator of G-protein signaling 19 is a protein that in humans is encoded by the RGS19 gene.
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.
Regulator of G-protein signaling 7 is a protein that in humans is encoded by the RGS7 gene.
Guanine nucleotide-binding protein G(t) subunit alpha-1 is a protein that in humans is encoded by the GNAT1 gene.
Regulator of G-protein signaling 1 is a protein that in humans is encoded by the RGS1 gene.
Regulator of G-protein signaling 20 is a protein that in humans is encoded by the RGS20 gene.
Regulator of G-protein signaling 12 is a protein that in humans is encoded by the RGS12 gene.
Regulator of G-protein signaling 8 is a protein that in humans is encoded by the RGS8 gene.
Guanine nucleotide-binding protein G(k) subunit alpha is a protein that in humans is encoded by the GNAI3 gene.
Regulator of G-protein signaling 13 (RGS13) is a protein that in humans is encoded by the RGS13 gene.
Regulator of G-protein signaling 17 is a protein that in humans is encoded by the RGS17 gene.
Regulator of G-protein signaling 11 is a protein that in humans is encoded by the RGS11 gene.
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.