RasGEF domain

Pfam_box
Symbol = RasGEF
Name = RasGEF domain


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caption =
Pfam= PF00617
InterPro= IPR001895
SMART= RasGEF
PROSITE = PDOC00594
SCOP = 1bkd
TCDB =
OPM family=
OPM protein= 1xd4
PDB=PDB3|1xd2C:777-963 PDB3|1bkdS:777-963 PDB3|1xdvB:777-963PDB3|1nvwS:777-963 PDB3|1xd4A:777-963 PDB3|1nvuS:777-963PDB3|1nvvS:777-963 PDB3|1nvxS:777-963

RasGEF domain is a family of guanine nucleotide exchange factors for Ras-like small GTPases.

Ras proteins are membrane-associated molecular switches that bind GTP and GDP and slowly hydrolyze GTP to GDPcite journal |author=McCormick F, Bourne HR, Sanders DA |title=The GTPase superfamily: conserved structure and molecular mechanism |journal=Nature |volume=349 |issue=6305 |pages=117–127 |year=1991 |pmid=1898771 |doi=10.1038/349117a0] . 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 GTPcite journal |author=McCormick F, Boguski MS |title=Proteins regulating Ras and its relatives |journal=Nature |volume=366 |issue=6456 |pages=643–654 |year=1993 |pmid=8259209 |doi=10.1038/366643a0] cite journal |author=Downward J |title=Ras regulation: putting back the GTP |journal=Curr. Biol. |volume=2 |issue=6 |pages=329–331 |year=1992 |pmid=15335949 |doi=10.1016/0960-9822(92)90897-J] . 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 InterPro|IPR001331) and this CDC25 (RasGEF) 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 domainmakes 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.

Human proteins containing this domain

KNDC1; PLCE1; RALGDS; RALGPS1; RALGPS2; RAPGEF1; RAPGEF2; RAPGEF3;
RAPGEF4; RAPGEF5; RAPGEF6; RAPGEFL1; RASGEF1A; RASGEF1B; RASGEF1C; RASGRF1;
RASGRP; RASGRP1; RASGRP2; RASGRP3; RASGRP4; RGL1; RGL2; RGL3;
RGR; Rgr; SOS1; SOS2;

References

Furter reading

* [1] . Proteins regulating Ras and its relatives. Boguski MS, McCormick F; Nature 1993;366:643-654. PMID|8259209
* [2] . Guanine nucleotide exchange factors: activators of the Ras superfamily of proteins. Quilliam LA, Khosravi-Far R, Huff SY, Der CJ; Bioessays 1995;17:395-404. PMID|7786285
* [3] . Guanine-nucleotide-releasing factor hSos1 binds to Grb2 and links receptor tyrosine kinases to Ras signalling. Li N, Batzer A, Daly R, Yajnik V, Skolnik E, Chardin P, Bar-Sagi D, Margolis B, Schlessinger J; Nature 1993;363:85-88. PMID|8479541
* [4] . The function of GRB2 in linking the insulin receptor to Ras signaling pathways. Skolnik EY, Batzer A, Li N, Lee CH, Lowenstein E, Mohammadi M, Margolis B, Schlessinger J; Science 1993;260:1953-1955. PMID|8316835