|PROSITE documentation PDOC50132
RGS domain profile
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:
- Mammalian regulator of G-protein signaling (RGS) proteins.
- Mammalian G-α interacting protein (GAIP).
- Mammalian G-protein-coupled-receptor kinases (GRK), proteins that directly
phosphorylate GPCRs to regulate signaling.
- Animal axin/conductin, an inhibitor of the wg/wnt signaling pathway. The
RGS domain of axin/conductin interacts with the tumour-suppressor
adenomatous polyposis coli (APC), a non-G-α-like molecule, which
indicates that some RGS domains can bind to proteins other than G-α.
- Caenorhabditis elegans egl-10, which regulates G protein signaling in
- Drosophila Loco, a protein required for glial differentiation.
- Saccharomyces cerevisiae SST2, a negative regulator of the G protein-
coupled mating pheromone signaling pathway.
We have developed a profile that covers the entire RGS domain.
December 2000 / First entry.
PROSITE method (with tools and information) covered by this documentation:
|RGS, PS50132; RGS domain profile (MATRIX)
|Sequences known to belong to this class detected by the profile:
|Other sequence(s) detected in Swiss-Prot:
|Matching PDB structures:
1AGR 1CMZ 1DK8 1EMU ... [ALL]
||De Vries L., Gist Farquhar M.
||Trends Cell Biol. 9:138-144(1999).
||Emerging roles for RGS proteins in cell signalling.
||Trends Pharmacol. Sci. 20:376-382(1999).
||Regulators of G protein signaling: a bestiary of modular protein binding domains.
||J. Neurochem. 75:1335-1351(2000).
||Tesmer J.J.G., Berman D.M., Gilman A.G., Sprang S.R.
||Structure of RGS4 bound to AlF4--activated G(i alpha1): stabilization of the transition state for GTP hydrolysis.
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