{PDOC50918} {PS50918; WWE} {BEGIN} ********************** * 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 ), the classic RING or the RING-H2 domains (see ), and the ubiquitin-binding UBA domain (see ). 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 beta 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 beta-grasp fold adopted by ubiquitin and several other eukaryotic specific alpha/beta 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. -Sequences known to belong to this class detected by the profile: ALL. -Other sequence(s) detected in Swiss-Prot: NONE. -Last update: August 2003 / First entry. [ 1] Aravind L. "The WWE domain: a common interaction module in protein ubiquitination and ADP ribosylation." Trends Biochem. Sci. 26:273-275(2001). PubMed=11343911 -------------------------------------------------------------------------------- PROSITE is copyrighted by the SIB Swiss Institute of Bioinformatics and distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives (CC BY-NC-ND 4.0) License, see https://prosite.expasy.org/prosite_license.html -------------------------------------------------------------------------------- {END}