InterPro domain: IPR035983

The HECT (Homologous to the E6-AP Carboxyl Terminus) domain is an around 350 amino acids motif that has been identified in proteins that all belong to a particular E3 ubiquitin-protein ligase family [ 1 ]. HECT domain containing proteins accept ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then transfer it to lysine side chains of target proteins, and transfers additional ubiquitin molecules to the end of growing ubiquitin chains. The site of ubiquitin thioester formation is a conserved cysteine residue located in the last 32-36 aa of the HECT domain [ 2 ]. The amino-terminal part of the HECT domain has been involved in E2 binding [ 2 , 3 ]. Once linked to ubiquitin, the target proteins are degraded in the 26 S proteasome.

1. A family of proteins structurally and functionally related to the E6-AP ubiquitin-protein ligase. Proc. Natl. Acad. Sci. U.S.A. 92, 2563-7
2. Subcellular localization and ubiquitin-conjugating enzyme (E2) interactions of mammalian HECT family ubiquitin protein ligases. J. Biol. Chem. 272, 15085-92
3. Physical interaction between specific E2 and Hect E3 enzymes determines functional cooperativity. J. Biol. Chem. 272, 13548-54