RGS3 is a member of R4 subfamily of RGS family, a diverse group of multifunctional proteins that regulate cellular signalling events downstream of G-protein coupled receptors (GPCRs) []. Signalling is initiated when GPCRs bind to their ligands, triggering the replacement of GDP bound to the G-alpha subunits of heterotrimeric G proteins with GTP. RGSs inhibit signal transduction by increasing the GTPase activity of G protein alpha subunits, thereby driving them into their inactive GDP-bound form. This activity defines them as GTPase activating proteins (GAPs).Regulator of G protein signaling 3 (RGS3) contains a membrane-targeting C2 domain, one PDZ domain, and an RGS (Regulator of G-protein Signalling) domain. RGS3 has been identified to inhibit Galpha-q and Galpha-i-mediated signaling by acting as a GTPase-activating protein []. RGS3 exits as several splice isoforms []. A short form, RGS3S, induced apoptosis when overexpressed [], whereas PDZ-RGS3 has been linked to cell migration through interaction with Ephrin receptors []. RGS3 interacts with neuroligin, estrogen receptor-alpha, and 14-3-3 outside of the GPCR pathways [, , ].This entry represents the RGS domain of RGS3.
