|PROSITE documentation PDOC00594 [for PROSITE entry PS50009]|
Ras proteins are membrane-associated molecular switches that bind GTP and GDP and slowly hydrolyze GTP to GDP . The balance between the GTP bound (active) and GDP bound (inactive) states is regulated by the opposite action of proteins activating the GTPase activity and that of proteins which promote the loss of bound GDP and the uptake of fresh GTP [2,3]. The latter proteins are known as guanine-nucleotide exchange (or releasing) factors (GEFs or GRFs) (or also as guanine-nucleotide dissociation stimulators (GDSs)).
The crystal structure of the GEF region of human Sos1 complexes with Ras has been solved (see <PDB:1BKD>) . The structure consists of two distinct α helical structural domains: the N-terminal domain which seems to have a purely structural role and the C-terminal domain which is sufficient for catalytic activity and contains all residues that interact with Ras. A main feature of the catalytic domain is the protrusion of a helical hairpin important for the nucleotide-exchange mechanism. The N-terminal domain is likely to be important for the stability and correct placement of the hairpin structure.
Some proteins known to contain a Ras-GEF domain are listed below:
To identify Ras-GEF domains we developed two profiles. The first one recognizes the catalytic domain and the second profile is directed against the N-terminal domain. We also developed a pattern that spans the helical hairpin.Last update:
April 2003 / Pattern and text revised and profiles added.
PROSITE methods (with tools and information) covered by this documentation:
|1||Authors||Bourne H.R., Sanders D.A., McCormick F.|
|Title||The GTPase superfamily: conserved structure and molecular mechanism.|
|2||Authors||Boguski M.S., McCormick F.|
|Title||Proteins regulating Ras and its relatives.|
|Title||Ras regulation: putting back the GTP.|
|Source||Curr. Biol. 2:329-331(1992).|
|4||Authors||Boriack-Sjodin P.A., Margarit S.M., Bar-Sagi D., Kuriyan J.|
|5||Authors||Albright C.F., Giddings B.W., Liu J., Vito M., Weinberg R.A.|
|Title||Characterization of a guanine nucleotide dissociation stimulator for a ras-related GTPase.|
|Source||EMBO J. 12:339-347(1993).|