PROSITE documentation PDOC50085
Rap GTPase activating proteins domain profile


Rap small G proteins have been implicated in various cellular processes such as exocytosis, cAMP signalling, cell adhesion and cell proliferation. Rap proteins acts as molecular switches, with an active GTP-bound form and an inactive GDP-bound form [1]. The inactive GDP bound form is promoted by GTPase-activating proteins (GAPs). GAP proteins specific for Rap contain a conserved region of around 200 amino-acid residues, the RapGAP domain. This domain can accelerate the GTP hydrolysis activity of Rap by five orders of magnitude [2].

Some proteins known to contain a Rap-GAP domain are listed below:

  • RAP1 GTPase activating protein (RAP1GAP).
  • Mammalian tuberin protein, the product of a familial tuberous sclerosis gene which, when deleted, causes begnin tumours. It also have a GAP activity for Rab5 [3].
  • Drosophila Gigas protein, an homologue of tuberin involved in regulation of cell cycle.
  • Mammalian tuberin-like protein TULIP.
  • GTPase-activating protein Spa-1. It functions as a negative regulator for the activation of Rap1, thereby having a negative effect on cell adhesion [4].

The profile we developed covers the entire RapGAP domain.

Last update:

April 2003 / First entry.


Technical section

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

RAPGAP, PS50085; Rap GTPase activating proteins domain profile  (MATRIX)


1AuthorsBos J.L. de Rooij J. Reedquist K.A.
TitleRap1 signalling: adhering to new models.
SourceNat. Rev. Mol. Cell Biol. 2:369-377(2001).
PubMed ID11331911

2AuthorsKurachi H. Wada Y. Tsukamoto N. Maeda M. Kubota H. Hattori M. Iwai K. Minato N.
TitleHuman SPA-1 gene product selectively expressed in lymphoid tissues is a specific GTPase-activating protein for Rap1 and Rap2. Segregate expression profiles from a rap1GAP gene product.
SourceJ. Biol. Chem. 272:28081-28088(1997).
PubMed ID9346962

3AuthorsXiao G.H. Shoarinejad F. Jin F. Golemis E.A. Yeung R.S.
TitleThe tuberous sclerosis 2 gene product, tuberin, functions as a Rab5 GTPase activating protein (GAP) in modulating endocytosis.
SourceJ. Biol. Chem. 272:6097-6100(1997).
PubMed ID9045618

4AuthorsTsukamoto N. Hattori M. Yang H. Bos J.L. Minato N.
TitleRap1 GTPase-activating protein SPA-1 negatively regulates cell adhesion.
SourceJ. Biol. Chem. 274:18463-18469(1999).
PubMed ID10373454

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