PROSITE documentation PDOC50200
Ras-associating (RA) domain profile


Ras proteins are signal-transducing GTPases that cycle between inactive GDP-bound and active GTP-bound forms. Ras is a prolific signalling molecule interacting with a spectrum of effector molecules and acting through more than one signalling pathway. A domain of about 100 residues, termed RA for RalGDS/AF-6 or Ras-Associating, interacts with Ras and other small GTPases. It occurs in one or two copies in a variety of signalling molecules. It can be found associated with many other domains, such as PDZ (see <PDOC50106>), Dilute (DIL), GEF (see <PDOC00594>), myosin motor, IQ (see <PDOC50096>), C1 (see <PDOC00379>), C2 (see <PDOC00380>), protein kinase (see <PDOC00100>), VPS9 or sterile α motif (SAM) (see <PDOC50105>) [1,2,3].

Some proteins known to contain a RA domain are listed below:

  • Mammalian Ral guanine nucleotide dissociation stimulator (RalGDS).
  • Human AF-6 protein and Drosophila CNO protein, two orthologous modular proteins containing myosin- and kinesin-like cargo-binding domains.
  • Mammalian Ral guanine nucleotide dissociation stimulator-like 1 and 2 (RGL1 and RGL2).
  • Mammalian Ras and Rab interactor 1 (RIN1), 2 (RIN2) and 3 (RIN3).
  • Mammalian adapter proteins of the Grb7/10/14 family. They bind, through their C-terminal SH2 domain (see <PDOC50001>), phosphotyrosine-containing sequences on a variety of activated tyrosine kinase receptors.
  • Caenorhabditis elegans protein mig-10.
  • Animal phosphoinositide-specific phospholipase C PLC-epsilon.
  • Animal unconventional myosins IX.
  • Mammalian diacylglycerol kinases, theta (EC
  • Fungal-type adenylate cyclase (EC
  • Yeast STE50 protein. It is involved in growth arrest during conjugation and may interact with the G protein α subunit.
  • Fission yeast sexual differentiation protein ste4. It is essential for mating and meiosis.
  • Smut fungus MAP kinase pathway-interacting protein Ubc2.

Structurally, the RA domain of RalGDS consists of a five-stranded mixed β-sheet interrupted by a 12 residue α-helix and two additional small α-helices (see <PDB:1LXD>). The structure of the RA domain belongs to the ubiquitin α/β roll superfold and is similar to that of the RBD domain and the N-terminal third of the FERM domain (see <PDOC00566>) [4,5]. The RA domain forms a homodimer where the interdimer surface is composed of two cysteines (Cys 2 in each monomer) forming an intermolecular disulfide bond and two interacting intermolecular antiparallel β-sheets [4]. The major interaction between Ras and RalGDS RA domain occurs between two antiparallel β-strands: β 2 of Ras and β 2 of RA. This interaction occurs both at the backbone as well as the side chain level (see <PDB:1LFD>) [6].

The profile we developed covers the entire RA domain.

Last update:

January 2003 / First entry.


Technical section

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

RA, PS50200; Ras-associating (RA) domain profile  (MATRIX)


1AuthorsPonting C.P. Benjamin D.R.
TitleA novel family of Ras-binding domains.
SourceTrends Biochem. Sci. 21:422-425(1996).
PubMed ID8987396

2AuthorsKido M. Shima F. Satoh T. Asato T. Kariya K. Kataoka T.
TitleCritical function of the Ras-associating domain as a primary Ras-binding site for regulation of Saccharomyces cerevisiae adenylyl cyclase.
SourceJ. Biol. Chem. 277:3117-3123(2002).
PubMed ID11723130

3AuthorsLiao Y. Kariya K. Hu C.-D. Shibatohge M. Goshima M. Okada T. Watari Y. Gao X. Jin T.-G. Yamawaki-Kataoka Y. Kataoka T.
SourceJ. Biol. Chem. 274:37815-37820(1999).

4AuthorsHuang L. Weng X. Hofer F. Martin G.S. Kim S.-H.
TitleThree-dimensional structure of the Ras-interacting domain of RalGDS.
SourceNat. Struct. Biol. 4:609-615(1997).
PubMed ID9253406

5AuthorsWojcik J. Girault J.-A. Labesse G. Chomilier J. Mornon J.-P. Callebaut I.
TitleSequence analysis identifies a ras-associating (RA)-like domain in the N-termini of band 4.1/JEF domains and in the Grb7/10/14 adapter family.
SourceBiochem. Biophys. Res. Commun. 259:113-120(1999).
PubMed ID10334925

6AuthorsHuang L. Hofer F. Martin G.S. Kim S.-H.
TitleStructural basis for the interaction of Ras with RalGDS.
SourceNat. Struct. Biol. 5:422-426(1998).
PubMed ID9628477

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