RasGEF

Guanine nucleotide exchange factor for Ras-like small GTPases
RasGEF
SMART accession number:SM00147
Description: -
Interpro abstract (IPR001895):

Ras proteins are membrane-associated molecular switches that bind GTP and GDP and slowly hydrolyze GTP to GDP [(PUBMED:1898771)]. 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 [(PUBMED:8259209), (PUBMED:15335949)]. 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 [(PUBMED:8094051)]. The structure consists of two distinct alpha 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:

  • Cdc25 from yeast.
  • Scd25 from yeast.
  • Ste6 from fission yeast.
  • Son of sevenless (gene sos) from Drosophila and mammals.
  • p140-RAS GRF (cdc25Mm) from mammals. This protein possesses both a domain belonging to the CDC25 family and one belonging to the CDC24 family.
  • Bud5 from yeast, that may interact with the ras-like protein RSR1/BUD1.
  • Lte1 from yeast, whose target protein is not yet known.
  • ralGDS from mammals, which interacts with the ras-like proteins ralA and ralB [(PUBMED:8094051)].

This entry represents the catalytic domain of the Ras guanine-nucleotide exchange factors.

GO process:small GTPase mediated signal transduction (GO:0007264)
GO function:guanyl-nucleotide exchange factor activity (GO:0005085)
Family alignment:
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There are 5508 RasGEF domains in 5503 proteins in SMART's nrdb database.

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