Regulator of G protein signalling

Pfam_box
Symbol = RGS
Name = Regulator of G protein signaling domain


width =
caption =
Pfam= PF00615
InterPro= IPR000342
SMART= RGS
PROSITE = PDOC50132
SCOP = 1gia
TCDB =
OPM family=
OPM protein= 2bcj
PDB=PDB3|2af0A:83-198 PDB3|2crpA:64-179 PDB3|1agrH:62-175PDB3|1ezyA:62-177 PDB3|1eztA:62-177 PDB3|2bt2A:65-180PDB3|2bv1A:72-186 PDB3|1cmzA:90-205 PDB3|1zv4X:84-199PDB3|1fqjB:299-413 PDB3|1fqkD:299-413 PDB3|1fqiA:299-413PDB3|2a72A:333-447 PDB3|2es0A:336-441 PDB3|1emuA:88-210PDB3|1dk8A:88-210 PDB3|1ym7D:54-174 PDB3|1omwA:54-174PDB3|2bcjA:54-174

Regulators of G protein signaling (or RGS) are protein structural domains that activate GTPases for heterotrimeric G-protein alpha-subunits.

RGS 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 pathwayscite journal |author=De Vries L, Farquhar MG, Zheng B, Fischer T, Elenko E |title=The regulator of G protein signaling family |journal=Annu. Rev. Pharmacol. Toxicol. |volume=40 |issue= |pages=235–271 |year=2000 |pmid=10836135 |doi=10.1146/annurev.pharmtox.40.1.235] . 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 (InterPro|IPR001019), which can then bind the beta-gamma dimer (InterPro|IPR001632 InterPro|IPR001770) and the receptor. RGS proteins markedly reduce the lifespan of GTP-bound alpha subunits by stabilising the G protein transition state.

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 little more than an RGS domain, while others also contain additional domains that confer further functionalitycite journal |author=Burchett SA |title=Regulators of G protein signaling: a bestiary of modular protein binding domains |journal=J. Neurochem. |volume=75 |issue=4 |pages=1335–1351 |year=2000 |pmid=10987813 |doi=10.1046/j.1471-4159.2000.0751335.x] .

RGS domains can be found within the same protein in combination with a variety of other domains, including: DEP for membrane targeting (InterPro|IPR000591), PDZ for binding to GPCRs (InterPro|IPR001478), PTB for phosphotyrosine-binding (InterPro|IPR006020), RBD for Ras-binding (InterPro|IPR003116), GoLoco for guanine nucleotide inhibitor activity (InterPro|IPR003109), PX for phosphatidylinositol-binding (InterPro|IPR001683), PXA that is associated with PX (InterPro|IPR003114), PH for stimulating guanine nucleotide exchange (InterPro|IPR001849), and GGL (G protein gamma subunit-like) for binding G protein beta subunits (InterPro|IPR001770)cite journal |author=Dohlman HG, Chasse SA |title=RGS proteins: G protein-coupled receptors meet their match |journal=Assay Drug Dev Technol |volume=1 |issue=2 |pages=357–364 |year=2003 |pmid=15090201 |doi=10.1089/154065803764958649] . 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.

Human proteins containing this domain

ADRBK1; ADRBK2; AXIN1; AXIN2; GRK1; GRK4; GRK5; GRK6;
GRK7; RGS1; RGS10; RGS11; RGS12; RGS13; RGS14; RGS16;
RGS17; RGS18; RGS19; RGS2; RGS20; RGS21; RGS3; RGS4;
RGS5; RGS6; RGS7; RGS8; RGS9; RK; SNX13;

References

External links

* [http://www.expasy.org/cgi-bin/nicedoc.pl?PDOC50132 RGS domain] in PROSITE

Further reading

* [1] . Structure of RGS4 bound to AlF4--activated G(i alpha1): stabilization of the transition state for GTP hydrolysis. Tesmer JJ, Berman DM, Gilman AG, Sprang SR; Cell 1997;89:251-261. PMID|9108480
* [2] . Inhibition of G-protein signaling by dominant gain-of-function mutations in Sst2p, a pheromone desensitization factor in Saccharomyces cerevisiae. Dohlman HG, Apaniesk D, Chen Y, Song J, Nusskern D; Mol Cell Biol 1995;15:3635-3643. PMID|7791771
* [3] . RGS family members: GTPase-activating proteins for heterotrimeric G-protein alpha-subunits. Watson N, Linder ME, Druey KM, Kehrl JH, Blumer KJ; Nature 1996;383:172-175. PMID|8774882
* [4] . GAIP and RGS4 are GTPase-activating proteins for the Gi subfamily of G protein alpha subunits. Berman DM, Wilkie TM, Gilman AG; Cell 1996;86:445-452. PMID|8756726
* [5] . GAIP, a protein that specifically interacts with the trimeric G protein G alpha i3, is a member of a protein family with a highly conserved core domain. De Vries L, Mousli M, Wurmser A, Farquhar MG; Proc Natl Acad Sci U S A 1995;92:11916-11920. PMID|8524874