PROSITE documentation PDOC50238
Rho GTPase-activating proteins domain profile


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:

  • Mammalian ARAP 1,2 and 3 proteins, a family of GTPase activating proteins that contains both a RhoGAP and a ARFGAP domains (see <PDOC50115>). They can regulate Rho or ARF G proteins according to their localization in the cell.
  • Vertebrate β-chimaerin protein, a GTPase activating protein for the Rho- like GTPase Rac.
  • Mammalian Nadrin protein, a neuron-specific GTPase-activating protein involved in regulated exocytosis.
  • Mammalian unconventional myosin-9b.
  • Mammalian breakpoint cluster region protein (BCR) and Drosophila Rotund protein, GTPase-activating proteins for Rac and Cdc42.
  • Mammalian Rho-GAP hematopoietic protein C1.
  • Mammalian Rho-GTPase-activating protein 6. It promotes continuous elongation of cytoplasmic processes during cell motility and simultaneous retraction of the cell body changing the cell morphology.
  • Mammalian phosphatidylinositol 3-kinase regulatory α subunit, an adapter subunit of the phosphatidylinositol 3-kinase (PI3K). It has a critical role in signal transduction pathways originating from a variety of membrane-bound receptors.
  • Mammalian Inositol polyphosphate 5-phosphatase OCRL-1 (EC 3.1.3.-). It may function in lysosomal membrane trafficking by regulating the specific pool of phosphatidylinositol 4,5-bisphosphate that is associated with lysosomes.
  • Mammalian type II inositol-1,4,5-trisphosphate 5-phosphatase involved in signal-terminating reaction (EC
  • Yeast LRG1 and SAC7 proteins, the two major Rho GTPase-activating proteins. The SAC7 protein is involved in assembly of actin.
  • Yeast BEM2 protein, a GTPase activating protein involved in the control of cellular morphogenesis.

The profile we developed covers the whole domain.

Last update:

January 2003 / First entry.


Technical section

PROSITE method (with tools and information) covered by this documentation:

RHOGAP, PS50238; Rho GTPase-activating proteins domain profile  (MATRIX)


1AuthorsGamblin S.J. Smerdon S.J.
TitleGTPase-activating proteins and their complexes.
SourceCurr. Opin. Struct. Biol. 8:195-201(1998).
PubMed ID9631293

2AuthorsBarrett T. Xiao B. Dodson E.J. Dodson G. Ludbrook S.B. Nurmahomed K. Gamblin S.J. Musacchio A. Smerdon S.J. Eccleston J.F.
TitleThe structure of the GTPase-activating domain from p50rhoGAP.
SourceNature 385:458-461(1997).
PubMed ID9009196

3AuthorsRittinger K. Walker P.A. Eccleston J.F. Nurmahomed K. Owen D. Laue E. Gamblin S.J. Smerdon S.J.
TitleCrystal structure of a small G protein in complex with the GTPase-activating protein rhoGAP.
SourceNature 388:693-697(1997).
PubMed ID9262406

4AuthorsRittinger K. Walker P.A. Eccleston J.F. Smerdon S.J. Gamblin S.J.
TitleStructure at 1.65 A of RhoA and its GTPase-activating protein in complex with a transition-state analogue.
SourceNature 389:758-762(1997).
PubMed ID9338791

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