HECT Protein Domain

The HECT domain (Homologous to the E6-AP Carboxyl Terminus) is an approximately 40 kDa (350 amino acid) catalytic domain found at the carboxy-terminus of HECT-class E3 ubiquitin protein ligases. This domain binds specific E2 enzymes, accepts ubiquitin from E2 to form an ubiquitin-thioester intermediate with the HECT active cysteine, and then transfers ubiquitin to either the ε-amino groups of lysine side chains of the substrate or to the growing end of multiubiquitin chains. The formation of a thioester intermediate with ubiquitin is unique to HECT E3 ligases and is not seen with other types of E3 ligase.