RAS intrinsic GTPase activity hydrolyzes GTP to GDP

Stable Identifier
Reaction [transition]
Homo sapiens
Locations in the PathwayBrowser
SVG |   | PPTX  | SBGN
Click the image above or here to open this reaction in the Pathway Browser
The layout of this reaction may differ from that in the pathway view due to the constraints in pathway layout
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
Catalyst Activity

GTPase activity of p21 RAS:GTP [plasma membrane]

Orthologous Events
Cite Us!