{PDOC50200}
{PS50200; RA}
{BEGIN}
***************************************
* 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 alpha 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 2.7.1.107).
 - Fungal-type adenylate cyclase (EC 4.6.1.1).
 - Yeast STE50 protein. It is involved in growth arrest during conjugation and
   may interact with the G protein alpha 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 beta-
sheet interrupted  by a 12 residue alpha-helix and two additional small alpha-
helices (see  <PDB:1LXD>).    The  structure  of  the RA domain belongs to the
ubiquitin alpha/beta  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  beta-sheets [4]. The major
interaction between Ras and RalGDS  RA  domain occurs between two antiparallel
beta-strands: beta 2 of Ras and  beta 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.

-Sequences known to belong to this class detected by the profile: ALL.
-Other sequence(s) detected in Swiss-Prot: NONE.
-Last update: January 2003 / First entry.

[ 1] Ponting C.P., Benjamin D.R.
     "A novel family of Ras-binding domains."
     Trends Biochem. Sci. 21:422-425(1996).
     PubMed=8987396
[ 2] Kido M., Shima F., Satoh T., Asato T., Kariya K., Kataoka T.
     "Critical function of the Ras-associating domain as a primary
     Ras-binding site for regulation of Saccharomyces cerevisiae adenylyl
     cyclase."
     J. Biol. Chem. 277:3117-3123(2002).
     PubMed=11723130; DOI=10.1074/jbc.M109526200
[ 3] Liao Y., Kariya K., Hu C.-D., Shibatohge M., Goshima M., Okada T.,
     Watari Y., Gao X., Jin T.-G., Yamawaki-Kataoka Y., Kataoka T.
     J. Biol. Chem. 274:37815-37820(1999).
[ 4] Huang L., Weng X., Hofer F., Martin G.S., Kim S.-H.
     "Three-dimensional structure of the Ras-interacting domain of
     RalGDS."
     Nat. Struct. Biol. 4:609-615(1997).
     PubMed=9253406
[ 5] Wojcik J., Girault J.-A., Labesse G., Chomilier J., Mornon J.-P.,
     Callebaut I.
     "Sequence 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."
     Biochem. Biophys. Res. Commun. 259:113-120(1999).
     PubMed=10334925; DOI=10.1006/bbrc.1999.0727
[ 6] Huang L., Hofer F., Martin G.S., Kim S.-H.
     "Structural basis for the interaction of Ras with RalGDS."
     Nat. Struct. Biol. 5:422-426(1998).
     PubMed=9628477

--------------------------------------------------------------------------------
PROSITE is copyrighted by the SIB Swiss Institute of Bioinformatics and
distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives
(CC BY-NC-ND 4.0) License, see https://prosite.expasy.org/prosite_license.html
--------------------------------------------------------------------------------

{END}