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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 [1]. 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>) [2]. 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 [3]. 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 [4].
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.
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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). | |
PubMed ID | 9631293 |
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. | |
Source | Nature 385:458-461(1997). | |
PubMed ID | 9009196 |
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. | |
Source | Nature 388:693-697(1997). | |
PubMed ID | 9262406 | |
DOI | 10.1038/41805 |
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. | |
Source | Nature 389:758-762(1997). | |
PubMed ID | 9338791 | |
DOI | 10.1038/39651 |