GTPase-activator protein for Ras-like GTPase explained

GTPase-activator protein for Ras-like GTPase is a family of evolutionarily related proteins. Ras proteins are membrane-associated molecular switches that bind GTP and GDP and slowly hydrolyze GTP to GDP.^[1] This intrinsic GTPase activity of ras is stimulated by a family of proteins collectively known as 'GAP' or GTPase-activating proteins.^{[2] [3]} As it is the GTP bound form of ras which is active, these proteins are said to be down-regulators of ras.

The Ras GTPase-activating proteins are quite large (from 765 residues for sar1 to 3079 residues for IRA2) but share only a limited (about 250 residues) region of sequence similarity, referred to as the 'catalytic domain' or rasGAP domain.

Note: There are distinctly different GAPs for the rap and rho/rac subfamilies of ras-like proteins (reviewed in reference^[4]) that do not share sequence similarity with ras GAPs.

Examples

Human genes encoding proteins containing this domain include:

• DAB2IP;
• GAPVD1;
• IQGAP1; IQGAP2; IQGAP3;
• NF1;
• RASA1; RASA2; RASA3; RASA4; RASAL1; RASAL2;
• SYNGAP1;

Notes and References

1. McCormick F, Bourne HR, Sanders DA . The GTPase superfamily: conserved structure and molecular mechanism . Nature . 349 . 6305 . 117–127 . 1991 . 1898771 . 10.1038/349117a0. 1991Natur.349..117B . 4349901 .
2. Wang Y, Riggs M, Rodgers L, Wigler M, Boguski M . sar1, a gene from Schizosaccharomyces pombe encoding a protein that regulates ras1 . Cell Regul. . 2 . 6 . 453–465 . 1991 . 1883874 . 361829 . 10.1091/mbc.2.6.453.
3. Maruta H, Burgess AW . Regulation of the Ras signalling network . BioEssays . 16 . 7 . 489–496 . 1994 . 7945277 . 10.1002/bies.950160708. 22850138 .
4. McCormick F, Boguski MS . Proteins regulating Ras and its relatives . Nature . 366 . 6456 . 643–654 . 1993 . 8259209 . 10.1038/366643a0. 1993Natur.366..643B . 4338237 .