DIRAS Family, GTP Binding RAS Like 1 (DIRAS1)

DIRAS1 belongs to a distinct branch of the functionally diverse Ras superfamily of monomeric GTPases. DIRAS1 and DIRAS2 have substitutions in regions highly conserved within the Ras family, including changes in a region critical for GTP hydrolysis in HRAS, and a change in an effector domain residue that, in HRAS, is important for interaction with RAF. As predicted by these changes, DIRAS1 and DIRAS2 displayed low GTPase activity and existed predominantly in the GTP-bound form in transfected cells. Neither protein interacted with the Ras-binding domain of RAF, resulting in no stimulation of mitogen-activated protein kinase. When expressed at low levels as fluorescent-labeled proteins, DIRAS1 and DIRAS2 showed plasma membrane localization.