Reactome | RAS intrinsic GTPase activity hydrolyzes GTP to GDP

RAS intrinsic GTPase activity hydrolyzes GTP to GDP

Stable Identifier

R-HSA-9649736

Type

Reaction [transition]

Species

Homo sapiens

Compartment

plasma membrane

ReviewStatus

5/5

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RAS intrinsic GTPase activity hydrolyzes GTP to GDP

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RAS proteins have weak intrinsic GTPase activity in the absence of other effectors (Gibbs et al, 1984; reviewed in Pylayeva-Gupta et al, 2011). Nucleotide attack is mediated by residue Q61 and facilitated by van der Waals bonds contributed by glycine residues at position 12 and 13; these three residues account for the majority of oncogenic and pathogenic mutations found in RAS proteins (reviewed in Prior et al, 2012). GAP proteins stimulate the intrinsic GTPase activity of RAS proteins by inserting an arginine residue into the active site, which contributes to proper positioning of the critical Q61 RAS residue (reviewed in King et al, 2013).

Literature References

PubMed ID	Title	Journal	Year
21993244	RAS oncogenes: weaving a tumorigenic web Grabocka, E, Pylayeva-Gupta, Y, Bar-Sagi, D	Nat. Rev. Cancer	2011
23443682	Nonredundant functions for Ras GTPase-activating proteins in tissue homeostasis Lapinski, PE, Lubeck, BA, King, PD	Sci Signal	2013
22589270	A comprehensive survey of Ras mutations in cancer Lewis, PD, Mattos, C, Prior, IA	Cancer Res.	2012
6148751	Intrinsic GTPase activity distinguishes normal and oncogenic ras p21 molecules Sigal, IS, Scolnick, EM, Gibbs, JB, Poe, M	Proc. Natl. Acad. Sci. U.S.A.	1984