The HECT ligases are a major group of E3 enzymes which contain the HECT (Homologous to the E6-AP Carboxyl Terminus) domain of ~350 AA at the C-terminus (1). HECT domain is a bifunctional, which binds the E2 enzyme through its N-terminal region while forms the thioester complexes with ubiquitin though the C-terminal cysteine (2). The ubiquitination is catalyzed by directly transferring the ubiquitin to the targeted substrates, which is binded with the N-terminal domain of the HECT ligases. Although the C-terminal cysteines and the HECT domains are conserved in the HECT ligases, the N-terminal domains of the HECT ligases are various, which determine its diversity of the substrate specificity. Furthermore, based on various N-terminal domain, the HECT ligases could be divided into 3 groups of Nedd4, HERC and others. The HECT ligases are involved in various cellular and physiological processes such as mitochondrial inheritance, chromatin remodeling, regulation of transcription, tumorigenesis (2).

1. http://pfam.sanger.ac.uk/family/PF01388

2. Rotin, D. and S. Kumar (2009). Physiological functions of the HECT family of ubiquitin ligases. Nat. Rev. Mol. Cell Biol., 10(6): 398-409. PMID: 19436320