Conserved Site

Ras guanine-nucleotide exchange factor, conserved site (IPR019804)

Short name: Ras_G-nucl-exch_fac_CS


Ras proteins are membrane-associated molecular switches that bind GTP and GDP and slowly hydrolyse GTP to GDP [PMID: 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 [PMID: 8259209, PMID: 15335949]. The latter proteins are known as guanine-nucleotide dissociation stimulators (GDSs) (or also as guanine-nucleotide releasing (or exchange) factors (GRFs)). Proteins that act as GDS can be classified into at least two families, on the basis of sequence similarities, the CDC24 family (see IPR001331) and the CDC25 family.

The size of the proteins of the CDC25 family range from 309 residues (LTE1) to 1596 residues (sos). The sequence similarity shared by all these proteins is limited to a region of about 250 amino acids generally located in their C-terminal section (currently the only exceptions are sos and ralGDS where this domain makes up the central part of the protein). This domain has been shown, in CDC25 an SCD25, to be essential for the activity of these proteins.

The crystal structure of the GEF region of human Sos1 complexes with Ras has been solved [PMID: 9690470]. 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. The signature pattern for this entry spans the helical hairpin.

GO terms

Biological Process

GO:0007264 small GTPase mediated signal transduction

Molecular Function

GO:0005085 guanyl-nucleotide exchange factor activity

Cellular Component

No terms assigned in this category.

Contributing signatures

Signatures from InterPro member databases are used to construct an entry.
PROSITE patterns