PROSITE documentation PDOC51322

UEV domain profile

The N-terminal ubiquitin E2 variant (UEV) domain is ~145 amino acid residues in length and shows significant sequence similarity to E2 ubiquitin ligases (see <PDOC00163>) but is unable to catalyze ubiquitin transfer as it lacks the active site cysteine that forms the transient thioester bond with the C-terminus of ubiquitin (Ub). Nevertheless, at least some UEVs have retained the ability to bind Ub, and appear to act either as cofactors in ubiquitylation reactions, or as ubiquitin sensors. UEV domains also frequently contain other protein recognition motifs, and may generally serve to couple protein and Ub binding functions to facilitate the formation of multiprotein complexes [1,2,3,4].

The UEV domain consists of a twisted four-stranded antiparallel β-sheet having a meander topology, with four α-helices packed against one face of the sheet (see <PDB:1KPP>). The UEV fold is generally similar to canonical E2 ligases in the hydrophobic core and 'active site' regions, but differs significantly at both its N- and C-termini [3,4].

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

• Yeast vacuolar protein sorting-associated protein 23 (Vps23).
• Mammalian tumor susceptibility gene TSG101 protein, the homologue of Vps23.

The profile we developed covers the entire UEV domain.