PROSITE documentation PDOC50020

WW/rsp5/WWP domain signature and profile

The WW domain [1,2,3,4] (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 β-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.