InterPro domain: IPR001202

Synonym(s): Rsp5 or WWP domain

The WW domain is a short conserved region in a number of unrelated proteins, which folds as a stable, triple stranded beta-sheet. This short domain of approximately 40 amino acids, may be repeated up to four times in some proteins [ 1 , 2 , 3 , 4 ]. The name WW or WWP derives from the presence of two signature tryptophan residues that are spaced 20-23 amino acids apart and are present in most WW domains known to date, as well as that of a conserved Pro. The WW domain binds to proteins with particular proline-motifs, [AP]-P-P-[AP]-Y, and/or phosphoserine- phosphothreonine-containing motifs [ 5 , 6 ]. It is frequently associated with other domains typical for proteins in signal transduction processes.

A large variety of proteins containing the WW domain are known. These include; dystrophin, a multidomain cytoskeletal protein; utrophin, a dystrophin-like protein of unknown function; vertebrate YAP protein, substrate of an unknown serine kinase; Mus musculus (Mouse) NEDD-4, involved in the embryonic development and differentiation of the central nervous system; Saccharomyces cerevisiae (Baker's yeast) RSP5, similar to NEDD-4 in its molecular organisation; Rattus norvegicus (Rat) FE65, a transcription-factor activator expressed preferentially in liver; Nicotiana tabacum (Common tobacco) DB10 protein, amongst others.

1. The WW domain: a signalling site in dystrophin? Trends Biochem. Sci. 19, 531-3
2. WWP, a new amino acid motif present in single or multiple copies in various proteins including dystrophin and the SH3-binding Yes-associated protein YAP65. Biochem. Biophys. Res. Commun. 205, 1201-5
3. The rsp5-domain is shared by proteins of diverse functions. FEBS Lett. 358, 153-7
4. Characterization of a novel protein-binding module--the WW domain. FEBS Lett. 369, 67-71
5. The WW domain of Yes-associated protein binds a proline-rich ligand that differs from the consensus established for Src homology 3-binding modules. Proc. Natl. Acad. Sci. U.S.A. 92, 7819-23
6. WW and SH3 domains, two different scaffolds to recognize proline-rich ligands. FEBS Lett. 513, 30-7