|PROSITE documentation PDOC50238|
Small G proteins of the Rho family, which includes Rho, Rac and Cdc42, regulate phosphorylation pathways that control a range of biological functions including cytoskeleton formation and cell proliferation. Rho proteins act as molecular switches, with an active GTP-bound form and an inactive GDP-bound form. The inactive GDP bound form is promoted by GTPase-activating proteins (GAPs). GAP proteins specific for Rho contain a conserved region of around 200 amino-acid residues, the Rho-GAP domain. This domain can accelerate the GTP hydrolysis activity of Rho by five orders of magnitude . RhoGAP domains are usually associated with other signaling modules like SH2 (see <PDOC50001>), SH3 (see <PDOC50002>) or PH (see <PDOC50003>).
Like other GAP domains Rho-GAP is exclusively helical (nine helices) (see <PDB:1RGP>) . The core of the domain forms a four-helix bundle. The most conserved residues across the family are located on the bundle face that interacts with the G protein . Rho-GAP domain like Ras-GAP supplies an arginine residue in trans into the active site of the G protein which confers a self-stimulatory GAP activity through homophilic interaction .
Some of the proteins containing a RhoGAP domain are listed below:
The profile we developed covers the whole domain.Last update:
January 2003 / First entry.
PROSITE method (with tools and information) covered by this documentation:
|1||Authors||Gamblin S.J., Smerdon S.J.|
|Title||GTPase-activating proteins and their complexes.|
|Source||Curr. Opin. Struct. Biol. 8:195-201(1998).|
|2||Authors||Barrett T., Xiao B., Dodson E.J., Dodson G., Ludbrook S.B., Nurmahomed K., Gamblin S.J., Musacchio A., Smerdon S.J., Eccleston J.F.|
|Title||The structure of the GTPase-activating domain from p50rhoGAP.|
|3||Authors||Rittinger K., Walker P.A., Eccleston J.F., Nurmahomed K., Owen D., Laue E., Gamblin S.J., Smerdon S.J.|
|Title||Crystal structure of a small G protein in complex with the GTPase-activating protein rhoGAP.|
|4||Authors||Rittinger K., Walker P.A., Eccleston J.F., Smerdon S.J., Gamblin S.J.|
|Title||Structure at 1.65 A of RhoA and its GTPase-activating protein in complex with a transition-state analogue.|