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. [5]
Regulator of G protein signalling (RGS) family members are regulatory molecules that act as GTPase activating proteins (GAPs) for G alpha subunits of heterotrimeric G proteins. [6] RGS proteins are able to deactivate G protein subunits of the Gi alpha, Go alpha and Gq alpha subtypes. They drive G proteins into their inactive GDP-bound forms. Regulator of G protein signaling 4 belongs to this family. All RGS proteins share a conserved 120-amino acid sequence termed the RGS domain which conveys GAP activity. [7] Regulator of G protein signaling 4 protein is 37% identical to RGS1 and 97% identical to rat Rgs4. This protein negatively regulates signaling upstream or at the level of the heterotrimeric G protein and is localized in the cytoplasm. [5]
A number of studies associate the RGS4 gene with schizophrenia, [8] [9] [10] [11] while some fail to detect an association. [12]
RGS4 is also of interest as one of the three main RGS proteins (along with RGS9 and RGS17) involved in terminating signalling by the mu opioid receptor, [13] and may be important in the development of tolerance to opioid drugs. [14] [15] [16] [17] [18]
RGS4 has been shown to interact with:
G-protein-coupled receptor kinase 2 (GRK2) is an enzyme that in humans is encoded by the ADRBK1 gene. GRK2 was initially called Beta-adrenergic receptor kinase, and is a member of the G protein-coupled receptor kinase subfamily of the Ser/Thr protein kinases that is most highly similar to GRK3(βARK2).
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.
Regulators of G protein signaling (RGS) are protein structural domains or the proteins that contain these domains, that function to activate the GTPase activity of heterotrimeric G-protein α-subunits.
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 3 is a protein that in humans is encoded by the RGS3 gene.
Regulator of G-protein signaling 7 is a protein that in humans is encoded by the RGS7 gene.
Coatomer subunit beta is a protein that is encoded by the COPB2 gene in humans.
Regulator of G-protein signaling 5 is a protein that in humans is encoded by the RGS5 gene.
Regulator of G-protein signaling 1 is a protein that in humans is encoded by the RGS1 gene.
Regulator of G-protein signaling 10 is a protein that in humans is encoded by the RGS10 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.
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.