| Small monomeric GTPase | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Identifiers | |||||||||
| EC no. | 3.6.5.2 | ||||||||
| Databases | |||||||||
| IntEnz | IntEnz view | ||||||||
| BRENDA | BRENDA entry | ||||||||
| ExPASy | NiceZyme view | ||||||||
| KEGG | KEGG entry | ||||||||
| MetaCyc | metabolic pathway | ||||||||
| PRIAM | profile | ||||||||
| PDB structures | RCSB PDBPDBePDBsum | ||||||||
| |||||||||
Small GTPases (EC3.6.5.2), also known assmall G-proteins, are a family ofhydrolaseenzymes that canbind andhydrolyzeguanosine triphosphate (GTP). They are a type ofG-protein found in thecytosol that arehomologous to the alpha subunit ofheterotrimeric G-proteins, but unlike the alpha subunit of G proteins, a small GTPase can function independently as a hydrolase enzyme to bind to and hydrolyze a guanosine triphosphate (GTP) to formguanosine diphosphate (GDP). The best-known members are theRas GTPases and hence they are sometimes called asRas superfamily GTPases.
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 then be replaced by free GTP. Therefore, a G-protein can be switched on and off. GTP hydrolysis is accelerated byGTPase activating proteins (GAPs), while GTP exchange is catalyzed byguanine 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 GTPases in the inactive state.
Small GTPases regulate a wide variety of processes in thecell, including growth,cellular differentiation, cell movement andlipidvesicle transport.
There are more than a hundred proteins in the Ras superfamily.[1] Based on structure, sequence and function, the Ras superfamily is divided into five main families, (Ras,Rho,Ran,Rab andArf GTPases).[2] The Ras family itself is further divided into 6 subfamilies:Ras, Ral (Ral-A andRal-B), Rit (Rit1 andRit2),Rap,Rheb, andRad.Miro is a recent contributor to the superfamily.[citation needed]
Each subfamily shares the common core G domain, which provides essential GTPase and nucleotide exchange activity.[citation needed]
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 asIQGAP andWASP.[citation needed]
The Ras family is generally responsible for cell proliferation, Rho for cell morphology, Ran for nuclear transport and Rab and Arf for vesicle transport.[3]
