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{PS01159; WW_DOMAIN_1}
{PS50020; WW_DOMAIN_2}
* WW/rsp5/WWP domain signature and profile *

The WW  domain  [1-4,E1]  (also  known  as  rsp5  or  WWP) has been originally
discovered as a  short  conserved  region  in  a number of unrelated proteins,
among them  dystrophin,  the gene responsible for Duchenne muscular dystrophy.
The domain,  which  spans about 35 residues, is repeated up to 4 times in some
proteins.  It has  been    shown [5] to bind proteins with particular proline-
motifs, [AP]-P-P-[AP]-Y, and  thus  resembles somewhat SH3 domains. It appears
to contain  beta-strands  grouped  around  four  conserved aromatic positions;
generally Trp.  The  name  WW or WWP derives from the presence of these Trp as
well as  that  of a conserved Pro.  It  is  frequently  associated  with other
domains typical for proteins in signal transduction processes.

Proteins containing the WW domain are listed below.

 - Dystrophin,  a  multidomain cytoskeletal protein. Its longest alternatively
   spliced form consists of an N-terminal actin-binding domain, followed by 24
   spectrin-like repeats,  a  cysteine-rich  calcium-binding  domain  and a C-
   terminal globular domain. Dystrophin form tetramers and is thought to have
   multiple functions   including   involvement   in    membrane    stability,
   transduction of  contractile  forces  to the extracellular  environment and
   organization of  membrane specialization. Mutations in  the dystrophin gene
   lead to muscular dystrophy of Duchenne or Becker type.  Dystrophin contains
   one WW domain C-terminal of the spectrin-repeats.
 - Utrophin, a dystrophin-like protein of unknown function.
 - Vertebrate YAP protein is a substrate of an unknown serine kinase. It binds
   to the  SH3  domain  of the Yes oncoprotein via a proline-rich region. This
   protein appears in alternatively spliced isoforms, containing either one or
   two WW domains [6].
 - Mouse NEDD-4  plays a role in the embryonic development and differentiation
   of the central nervous system.  It contains 3 WW modules followed by a HECT
   domain.  The human  ortholog contains 4 WW domains, but the third WW domain
   is probably spliced resulting in an alternate NEDD-4 protein with only 3 WW
   modules [3].
 - Yeast  RSP5 is similar to NEDD-4 in its molecular organization. It contains
   an N-terminal  C2  domain  (see  <PDOC00380>,  followed by a histidine-rich
   region, 3 WW domains and a HECT domain.
 - Rat    FE65,  a  transcription-factor activator expressed preferentially in
   liver. The  activator  domain is located within the N-terminal 232 residues
   of FE65, which also contain the WW domain.
 - Yeast ESS1/PTF1, a putative peptidyl prolyl cis-trans isomerase from family
   ppiC (see  <PDOC00840>).  A  related  protein,  dodo  (gene  dod) exists in
   Drosophila and in mammals (gene PIN1).
 - Tobacco  DB10  protein.  The  WW domain is located N-terminal to the region
   with similarity to ATP-dependent RNA helicases.
 - IQGAP,  a  human GTPase activating protein acting on ras. It contains an N-
   terminal domain  similar  to  fly  muscle mp20 protein and a C-terminal ras
   GTPase activator domain.
 - Yeast  pre-mRNA  processing  protein PRP40, Caenorhabditis elegans ZK1098.1
   and fission yeast SpAC13C5.02 are related proteins with similarity to MYO2-
   type myosin, each containing two WW-domains at the N-terminus.
 - Caenorhabditis  elegans hypothetical protein C38D4.5, which contains one WW
   module, a PH domain (see <PDOC50003>) and a C-terminal phosphatidylinositol
   3-kinase domain.
 - Yeast hypothetical protein YFL010c.

For the  sensitive  detection of WW domains, we have developed a profile which
spans the whole homology region as well as a pattern.

-Consensus pattern: W-x(9,11)-[VFY]-[FYW]-x(6,7)-[GSTNE]-[GSTQCR]-[FYW]-x(2)-P
-Sequences known to belong to this class detected by the pattern: ALL.
-Other sequence(s) detected in SWISS-PROT: 8.

-Sequences known to belong to this class detected by the profile: ALL.
-Other sequence(s) detected in SWISS-PROT: NONE.

-Note: this  documentation  entry  is linked to both a signature pattern and a
 profile. As  the  profile is much more sensitive than the pattern, you should
 use it if you have access to the necessary software tools to do so.

-Expert(s) to contact by email:
                   Peer Bork; bork@embl-heidelberg.de
                   Sudol M.; m_sudol@smtplink.mssm.edu

-Last update: July 1999 / Text revised.

[ 1] Bork P., Sudol M.
     Trends Biochem. Sci. 19:531-533(1994).
[ 2] Andre B., Springael J.Y.
     Biochem. Biophys. Res. Commun. 205:1201-1205(1994).
[ 3] Hofmann K.O., Bucher P.
     FEBS Lett. 358:153-157(1995).
[ 4] Sudol M., Chen H.I., Bougeret C., Einbond A., Bork P.
     FEBS Lett. 369:67-71(1995).
[ 5] Chen H.I., Sudol M.
     Proc. Natl. Acad. Sci. U.S.A. 92:7819-7823(1995).
[ 6] Sudol M., Bork P., Einbond A., Kastury K., Druck T., Negrini M.,
     Huebner K., Lehman D.
     J. Biol. Chem. 270:14733-14741(1995).
[E1] http://www.bork.embl-heidelberg.de/Modules/ww-gif.html

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