PROSITE documentation PDOC50918

WWE domain profile

The WWE domain is a ~80-residue globular domain occuring in two functional classes of proteins, namely those associated with ubiquitination and those associated with poly-ADP ribosylation. The former class includes its combinations with the HECT-type E3 ligases (see <PDOC50237>), the classic RING or the RING-H2 domains (see <PDOC00449>), and the ubiquitin-binding UBA domain (see <PDOC50030>). Analogous to the ubiquitin ligases, eukaryotic poly-ADP ribose polymerases (EC 2.4.2.30) (PARPs) covalently modify proteins through the addition of multiple ADP-ribose moieties and participate in functions such as DNA repair and chromatin dynamics. The WWE domain is present in either single or duplicate copies in a novel sub-family of PARPs. The WWE domain was named after its most conserved residues, two tryptophan (W) residues and a glutamate (E) residue. It has been suggested that the WWE domain functions in specific interactions with other proteins and could help in targeting the different kinds of E3-like and ADP-ribosylation activities to proteins participating in various signaling cascades [1].

Secondary structure prediction suggests the presence of multiple β strands that correspond to the conserved N- and C- terminal motifs of the WWE domain that are enriched in hydrophobic or aromatic residues. There is a single prominent helix that corresponds to the central motif containing the conserved glutamate. The secondary structure pattern with a two-strand hairpin at the N-terminus followed by a helix is reminiscent of the β-grasp fold adopted by ubiquitin and several other eukaryotic specific α/β domains [1].

Some proteins known to contain a WWE domain are listed below:

• Animal members of the Deltex (DTX) family, which act as Notch signaling modifiers and may also regulate transcription through interactions with specific transcription factors.
• Vertebrate thyroid receptor interacting protein 12 (TRIP12), an HECT- domain-containing E3 ubiquitin ligase.
• An eukaryotic family of poly-ADP ribose polymerases (EC 2.4.2.30) (PARPs).

The profile we developed covers the entire WWE domain.