RasGEF domain

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RasGEF domain
Identifiers
Symbol	RasGEF
Pfam	PF00617
InterPro	IPR001895
SMART	RasGEF
PROSITE	PDOC00594
SCOP	1bkd
OPM protein	1xd4
Available PDB structures: 1xd2C:777-963 1bkdS:777-963 1xdvB:777-963 1nvwS:777-963 1xd4A:777-963 1nvuS:777-963 1nvvS:777-963 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 GDP^[1]. 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 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 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 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.

[edit] 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;

[edit] References

^ McCormick F, Bourne HR, Sanders DA (1991). "The GTPase superfamily: conserved structure and molecular mechanism". Nature 349 (6305): 117–127. doi:10.1038/349117a0. PMID 1898771.
^ McCormick F, Boguski MS (1993). "Proteins regulating Ras and its relatives". Nature 366 (6456): 643–654. doi:10.1038/366643a0. PMID 8259209.
^ Downward J (1992). "Ras regulation: putting back the GTP". Curr. Biol. 2 (6): 329–331. doi:10.1016/0960-9822(92)90897-J. PMID 15335949.

[edit] Furter reading

[1]. Proteins regulating Ras and its relatives. Boguski MS, McCormick F; Nature 1993;366:643-654. PubMed
[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. PubMed
[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. PubMed
[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. PubMed