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 . HECT domain containing
proteins accept ubiquitin from an E2 ubiquitin-conjugating enzyme in the form
of a thioester and then transfer it to target proteins. The site of ubiquitin
thioester formation is a conserved cysteine residue located in the last 32-36
aa of the HECT domain . The amino-terminal part of the HECT domain has been
involved in E2 binding . Once linked to ubiquitin, the target proteins are
degraded in the 26 S proteasome.
Some proteins known to contain a HECT domain are listed below:
Mammalian E6-AP (EC 6.3.2.-). It interacts with the E6 protein of the
cancer-associated human papillomavirus types16 and 18. The E6/E6-AP complex
binds to and targets the p53 tumor-suppressor protein for ubiquitin
Yeast RSP5 (EC 6.3.2.-). It is involved in the degradation of several cell
S.pombe pub1 (EC 6.3.2.-). It regulates ubiquitination of cdc25.
Yeast HUL4 and HUL5 (EC 6.3.2.-).
Drosophila hyperplastic discs (HYD) protein (EC 6.3.2.-). It is required
for regulation of cell proliferation in imaginal discs and germ cells.
Mammalian NEDD4 (EC 6.3.2.-). It is involved in the embryonic development
and differentiation of the central nervous system.
Rat 100 kDa protein (EC 6.3.2.-). This protein may be involved in
maturation and/or post-transcriptional regulation of mRNA.
Rat UreB1. It contains only a portion of the HECT domain (310 aa), without
any amino-terminal extension. It could be a DNA-binding transcriptional
Human thyroid receptor interacting protein 12 (TRIP12).
December 2001 / First entry.
PROSITE method (with tools and information) covered by this documentation:
Huibregtse J.M. Scheffner M. Beaudenon S. Howley P.M.
A family of proteins structurally and functionally related to the E6-AP ubiquitin-protein ligase.
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