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In biology, small GTPases are small (20-25 kDa) proteins that bind to guanosine triphosphate (GTP). This family of proteins is homologous to Ras GTPases and also called the Ras superfamily GTPases. Together with heterotrimeric G-proteins they constitute the G-proteins. They are all GTPases and share common features, but small GTPases have slightly different structures and mechanisms of action.
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 accelerating 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.
Small GTPases regulate a wide variety of processes in the cell, including growth, cellular differentiation, cell movement and lipid vesicle transport.
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The Ras superfamily
There are more than a hundred proteins in the Ras superfamily. Based on structure, sequence and function, the Ras superfamily is divided into eight main families, each of which is further divided into subfamilies: Ras, Rho, Rab, Rap, Arf, Ran, Rheb, Rad and Rit. 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, nuclear transport for Ran and vesicle transport for Rab and Arf:[1]
| Superfamily member | Function | |
|---|---|---|
| Ras | cell proliferation [1] | |
| Rho | cytoskeletal dynamics/morphology[1] | |
| Rab | membrane trafficking | |
| Rap | vesicular transport[1] | |
| Arf | vesicular transport[1] | |
| Ran | nuclear transport | |
| Rheb | mTOR pathway | |
| Rad | ||
| Rit | ||
| Miro | mitochondrial transport |
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