PROSITE: PDOC50020 (documentation)
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* 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  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 .
- 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
- 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
- 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; email@example.com
Sudol M.; firstname.lastname@example.org
-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).
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