|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 . 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:
- 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
- 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
- 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 126.96.36.199.).
- 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
The profile we developed covers the whole domain.
January 2003 / First entry.
PROSITE method (with tools and information) covered by this documentation:
|RHOGAP, PS50238; Rho GTPase-activating proteins domain profile (MATRIX)
|Sequences known to belong to this class detected by the profile:
|Other sequence(s) detected in Swiss-Prot:
|Matching PDB structures:
1AM4 1F7C 1GRN 1OW3 ... [ALL]
||Gamblin S.J., Smerdon S.J.
||GTPase-activating proteins and their complexes.
||Curr. Opin. Struct. Biol. 8:195-201(1998).
||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.
||The structure of the GTPase-activating domain from p50rhoGAP.
||Rittinger K., Walker P.A., Eccleston J.F., Nurmahomed K., Owen D., Laue E., Gamblin S.J., Smerdon S.J.
||Crystal structure of a small G protein in complex with the GTPase-activating protein rhoGAP.
||Rittinger K., Walker P.A., Eccleston J.F., Smerdon S.J., Gamblin S.J.
||Structure at 1.65 A of RhoA and its GTPase-activating protein in complex with a transition-state analogue.
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