|PROSITE documentation PDOC50132|
Regulators of G-protein signaling (RGS) proteins are a family of highly diverse, multifunctional signaling proteins that are found in eukaryotic species ranging from yeast to mammals. They act as GTPase activating proteins (GAPs) that reduce the signal transmitted by the receptor-activated (GTP bound) G-α subunit by rapidly returning it to the inactive state (GDP bound). Although they are a diverse group of proteins, all RGS family members share a conserved 120 amino acid domain, the RGS domain. The RGS domain binds to activated G-α subunits and is responsible for GAP function. Apart from the RGS domain, RGS proteins differ widely in their overall size and amino acid identity and possess a remarkable variety of structural domains and motifs. These additional domains, like DEP (see <PDOC50186>, PDZ (see <PDOC50106> or PH (see <PDOC50003>, link the RGS proteins to other signaling network, where they constitute effector type molecules [1,2,3].
RGS domains are broken up into three highly conserved GH (GAIP or GOS homology) subdomains (GH1, GH2 and GH3), which can be either nearly contiguous or widely dispersed within nonconserved sequences . Resolution of the crystal structure of the RGS4 protein complexed with a stable transition state mimic of G-α-GTP has revealed that the RGS domain forms nine α-helices that fold into two small subdomains. These subdomains each contact the G-α surface at three distinct sites .
Some proteins known to contain a RGS domain are listed below:
We have developed a profile that covers the entire RGS domain.Last update:
December 2000 / First entry.
PROSITE method (with tools and information) covered by this documentation:
|1||Authors||De Vries L. Gist Farquhar M.|
|Source||Trends Cell Biol. 9:138-144(1999).|
|Title||Emerging roles for RGS proteins in cell signalling.|
|Source||Trends Pharmacol. Sci. 20:376-382(1999).|
|Title||Regulators of G protein signaling: a bestiary of modular protein binding domains.|
|Source||J. Neurochem. 75:1335-1351(2000).|
|4||Authors||Tesmer J.J.G. Berman D.M. Gilman A.G. Sprang S.R.|
|Title||Structure of RGS4 bound to AlF4--activated G(i alpha1): stabilization of the transition state for GTP hydrolysis.|