RasGEF domain

RasGEF domain
Structure of human H-Ras. [1]
Identifiers
Symbol	RasGEF
Pfam	PF00617
InterPro	IPR001895
SMART	RasGEF
PROSITE	PDOC00594
SCOP2	1bkd / SCOPe / SUPFAM
OPM protein	1xd4
CDD	cd00155
Available protein structures: Pfam   structures / ECOD   PDB RCSB PDB; PDBe; PDBj PDBsum structure summary PDB 1xd2 C:777-963 1bkd S:777-963 1xdv B:777-963 1nvw S:777-963 1xd4 A:777-963 1nvu S:777-963 1nvv S:777-963 1nvx S:777-963

RasGEF domain is domain found in the CDC25 family of guanine nucleotide exchange factors for Ras-like small GTPases.

Main article: Ras (protein)

Ras proteins are membrane-associated molecular switches that bind GTP and GDP and slowly hydrolyze GTP to GDP. ^[2] 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. ^{[3] [4]} 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 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.

Human proteins containing this domain

KNDC1; PLCE1; RALGDS; RALGPS1; RALGPS2; RAPGEF1; RAPGEF2; RAPGEF3; RAPGEF4; RAPGEF5; RAPGEF6; RAPGEFL1; RASGEF1A; RASGEF1B; RASGEF1C; RASGRF1; RASGRF2; RASGRP1; RASGRP2; RASGRP3; RASGRP4; RGL1; RGL2; RGL3; RGL4/RGR; SOS1; SOS2;

References

1. Boriack-Sjodin PA, Margarit SM, Bar-Sagi D, Kuriyan J (July 1998). "The structural basis of the activation of Ras by Sos". Nature. 394 (6691): 337–43. Bibcode:1998Natur.394..337B. doi:10.1038/28548. PMID   9690470. S2CID   204998911.
2. McCormick F, Bourne HR, Sanders DA (1991). "The GTPase superfamily: conserved structure and molecular mechanism". Nature. 349 (6305): 117–127. Bibcode:1991Natur.349..117B. doi:10.1038/349117a0. PMID   1898771. S2CID   4349901.
3. McCormick F, Boguski MS (1993). "Proteins regulating Ras and its relatives". Nature. 366 (6456): 643–654. Bibcode:1993Natur.366..643B. doi:10.1038/366643a0. PMID   8259209. S2CID   4338237.
4. Downward J (1992). "Ras regulation: putting back the GTP". Curr. Biol. 2 (6): 329–331. Bibcode:1992CBio....2..329D. doi:10.1016/0960-9822(92)90897-J. PMID   15335949. S2CID   21826028.

Further reading

• Boguski, MS; McCormick, F (1993). "Proteins regulating Ras and its relatives". Nature. 366 (6456): 643–54. Bibcode:1993Natur.366..643B. doi:10.1038/366643a0. PMID   8259209. S2CID   4338237.
• Quilliam, LA; Khosravi-Far, R; Huff, SY; Der, CJ (1995). "Guanine nucleotide exchange factors: Activators of the Ras superfamily of proteins". BioEssays. 17 (5): 395–404. doi:10.1002/bies.950170507. PMID   7786285. S2CID   22140430.
• Li, N; Batzer, A; Daly, R; Yajnik, V; Skolnik, E; Chardin, P; Bar-Sagi, D; Margolis, B; Schlessinger, J (1993). "Guanine-nucleotide-releasing factor hSos1 binds to Grb2 and links receptor tyrosine kinases to Ras signalling". Nature. 363 (6424): 85–8. Bibcode:1993Natur.363...85L. doi:10.1038/363085a0. PMID   8479541. S2CID   4323174.
• Skolnik, EY; Batzer, A; Li, N; Lee, CH; Lowenstein, E; Mohammadi, M; Margolis, B; Schlessinger, J (1993). "The function of GRB2 in linking the insulin receptor to Ras signaling pathways". Science. 260 (5116): 1953–5. Bibcode:1993Sci...260.1953S. doi:10.1126/science.8316835. PMID   8316835.

This article incorporates text from the public domain Pfam and InterPro: IPR001895