A typical G-protein is active when bound to GTP and inactive when bound to GDP (i.e. when the GTP is hydrolyzed to GDP). The GDP can be then replaced by free GTP. Therefore, a G-protein can be switched on and off. GTP hydrolysis is accelerated by GTPase activating proteins (GAPs), while GTP exchange is catalyzed by Guanine nucleotide exchange factors (GEFs). Activation of a GEF typically activates its cognate G-protein, while activation of a GAP results in inactivation of the cognate G-protein. Guanosine nucleotide dissociation inhibitors (GDI) maintain small GTP-ases in the inactive state.
There are more than a hundred proteins in the Ras superfamily. Based on structure, sequence and function, the Ras superfamily is divided into five main families, (Ras, Rho, Ran, Rab and Arf GTPases). The Ras family itself is further divided into 6 subfamilies: Ras, Ral, Rit, Rap, Rheb, and Rad. Miro is a recent contributor to the superfamily.
Each subfamily shares the common core G domain, which provides essential GTPase and nucleotide exchange activity.
The surrounding sequence helps determine the functional specificity of the small GTPase, for example the 'Insert Loop', common to the Rho subfamily, specifically contributes to binding to effector proteins such as IQGAP and WASP.
The Ras family is generally responsible for cell proliferation, Rho for cell morphology, Ran for nuclear transport and Rab and Arf for vesicle transport.