Regulator of G protein signaling
Regulator of G-Protein Signaling Domain | |||||||||
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CDD | cd07440 | ||||||||
Membranome | 36 | ||||||||
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Regulators of G protein signaling (RGS) are protein
RGS proteins are multi-functional, GTPase-accelerating proteins that promote GTP hydrolysis by the α-subunit of heterotrimeric G proteins, thereby inactivating the G protein and rapidly switching off G protein-coupled receptor signaling pathways.[2] Upon activation by receptors, G proteins exchange GDP for GTP, are released from the receptor, and dissociate into a free, active GTP-bound α-subunit and βγ-dimer, both of which activate downstream effectors. The response is terminated upon GTP hydrolysis by the α-subunit (InterPro: IPR001019), which can then re-bind the βγ-dimer (InterPro: IPR001632 InterPro: IPR001770) and the receptor. RGS proteins markedly reduce the lifespan of GTP-bound α-subunits by stabilising the G protein transition state. Whereas receptors stimulate GTP binding, RGS proteins stimulate GTP hydrolysis.
RGS proteins have been conserved in evolution. The first to be identified was Sst2 ("SuperSensiTivity to pheromone") in yeast (Saccharomyces cerevisiae).[3] 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 functionality.[4]
RGS domains in the
Plants have RGS proteins but do not have canonical G protein-coupled receptors. Thus G proteins and GTPase accelerating proteins appear to have evolved before any known G protein activator.
RGS domains can be found within the same protein in combination with a variety of other domains, including:
Examples
Human proteins containing this domain include:
- AXIN1, AXIN2
- RGS1, RGS2, RGS3, RGS4, RGS5, RGS6, RGS7, RGS8, RGS9, RGS10, RGS11, RGS12, RGS13, RGS14, RGS16, RGS17, RGS18, RGS19, RGS20, RGS21
- SNX13
See also
GTP-binding protein regulators:
References
Further reading
- Tesmer, JJ; Berman, DM; Gilman, AG; Sprang, SR (1997). "Structure of RGS4 bound to AlF4--activated G(i alpha1): Stabilization of the transition state for GTP hydrolysis". Cell. 89 (2): 251–61. S2CID 2628150.
- Hunt TW, Fields TA, Casey PJ, Peralta EG (September 1996). "RGS10 is a selective activator of G alpha i GTPase activity". Nature. 383 (6596): 175–7. S2CID 4318445.
- Watson N, Linder ME, Druey KM, Kehrl JH, Blumer KJ (September 1996). "RGS family members: GTPase-activating proteins for heterotrimeric G-protein alpha-subunits". Nature. 383 (6596): 172–5. S2CID 4318239.
- Berman DM, Wilkie TM, Gilman AG (August 1996). "GAIP and RGS4 are GTPase-activating proteins for the Gi subfamily of G protein alpha subunits". Cell. 86 (3): 445–52. S2CID 12427406.
- Koelle MR, Horvitz HR (January 1996). "EGL-10 regulates G protein signaling in the C. elegans nervous system and shares a conserved domain with many mammalian proteins". Cell. 84 (1): 115–25. S2CID 7815240.
- De Vries L, Mousli M, Wurmser A, Farquhar MG (December 1995). "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". Proc. Natl. Acad. Sci. U.S.A. 92 (25): 11916–20. PMID 8524874.
- Dohlman H, Apaniesk D, Chen Y, Song J, Nusskern D (July 1995). "Inhibition of G-protein signaling by dominant gain-of-function mutations in Sst2p, a pheromone desensitization factor in Saccharomyces cerevisiae". Mol Cell Biol. 15 (7): 3635–43. PMID 7791771.
- Siderovski DP, Hessel A, Chung S, Mak TW, Tyers M (February 1996). "A new family of regulators of G-protein-coupled receptors?". Curr Biol. 6 (2): 211–2. S2CID 17214806.