Regulator of G protein signaling 20 (RGS20)

Regulator of G protein signaling 20 (RGS20, also called RGSZ1) is a member of the RGS family of proteins that act as GTPase-activating proteins (GAPs) for G protein alpha subunits, specifically interacting with G(z)-alpha and G(alpha)-i2 subunits to accelerate the termination of G protein-coupled receptor (GPCR) signals. RGS20 is involved in the modulation and timing of intracellular responses to GPCR activation and is highly expressed in the central nervous system, where it regulates signaling events crucial for neuronal activity and pain processing. RGS20 plays a negative role in opioid receptor signaling, modulating the analgesic efficacy and tolerance profiles of drugs such as morphine through its effects on mu-opioid receptor (MOPR) pathways. It has been implicated in various diseases, including multiple types of cancer (e.g., hepatocellular carcinoma, hematological cancers), epilepsy, and neuropsychiatric disorders, and is a potential target for therapeutic intervention, particularly in contexts where precise regulation of GPCR signaling is relevant. Currently, although peptide and nonpeptide modulators have been investigated in preclinical settings, there are no approved drugs specifically targeting RGS20.

Other names

RGS20RGSZ1ZGAP1G(z)GAPGz-GAPGz-selective GTPase-activating proteinRegulator of G-protein signaling Z1Regulator of Gz-selective protein signaling 1g(z)GAPgz-GAPregulator of Gz-selective protein signaling 1RGS20_HUMAN

Increases GTPase activity of Gα subunits to accelerate signal termination, modulates GPCR signaling cascades, affects opioid analgesic efficacy and tolerance by regulating receptor-mediated G protein activation