<p>RGS (Regulator of G Protein Signalling) proteins are multi-functional, GTPase-accelerating proteins that promote GTP hydrolysis by the alpha subunit of heterotrimeric G proteins, thereby inactivating the G protein and rapidly switching off G protein-coupled receptor signalling pathways [<cite idref="PUB00006536"/>]. Upon activation by GPCRs, heterotrimeric G proteins exchange GDP for GTP, are released from the receptor, and dissociate into free, active GTP-bound alpha subunit and beta-gamma dimer, both of which activate downstream effectors. The response is terminated upon GTP hydrolysis by the alpha subunit (<db_xref db="INTERPRO" dbkey="IPR001019"/>), which can then bind the beta-gamma dimer (<db_xref db="INTERPRO" dbkey="IPR001632"/>, <db_xref db="INTERPRO" dbkey="IPR001770"/>) and the receptor. RGS proteins markedly reduce the lifespan of GTP-bound alpha subunits by stabilising the G protein transition state.</p><p>All RGS proteins contain an 'RGS-box' (or RGS domain), which is required for activity. Some small RGS proteins such as RGS1 and RGS4 are comprised of little more than an RGS domain, while others also contain additional domains that confer further functionality [<cite idref="PUB00015163"/>]. RGS domains can be found in conjunction with a variety of domains, including: DEP for membrane targeting (<db_xref db="INTERPRO" dbkey="IPR000591"/>), PDZ for binding to GPCRs (<db_xref db="INTERPRO" dbkey="IPR001478"/>), PTB for phosphotyrosine-binding (<db_xref db="INTERPRO" dbkey="IPR006020"/>), RBD for Ras-binding (<db_xref db="INTERPRO" dbkey="IPR003116"/>), GoLoco for guanine nucleotide inhibitor activity (<db_xref db="INTERPRO" dbkey="IPR003109"/>), PX for phosphatidylinositol-binding (<db_xref db="INTERPRO" dbkey="IPR001683"/>), PXA that is associated with PX (<db_xref db="INTERPRO" dbkey="IPR003114"/>), PH for stimulating guanine nucleotide exchange (<db_xref db="INTERPRO" dbkey="IPR001849"/>), and GGL (G protein gamma subunit-like) for binding G protein beta subunits (<db_xref db="INTERPRO" dbkey="IPR001770"/>) [<cite idref="PUB00015162"/>]. Those RGS proteins that contain GGL domains can interact with G protein beta subunits to form novel dimers that prevent G protein gamma subunit binding and G protein alpha subunit association, thereby preventing heterotrimer formation.</p> Regulator of G protein signalling