PROSITE documentation PDOC50237
HECT domain profile


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 target proteins. The site of ubiquitin thioester formation is a conserved cysteine residue located in the last 32-36 aa of the HECT domain [1]. The amino-terminal part of the HECT domain has been involved in E2 binding [2]. 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 mediated proteolysis.
  • Yeast RSP5 (EC 6.3.2.-). It is involved in the degradation of several cell surface proteins.
  • 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 regulator.
  • Human thyroid receptor interacting protein 12 (TRIP12).
Last update:

December 2001 / First entry.


Technical section

PROSITE method (with tools and information) covered by this documentation:

HECT, PS50237; HECT domain profile  (MATRIX)


1AuthorsHuibregtse J.M. Scheffner M. Beaudenon S. Howley P.M.
TitleA family of proteins structurally and functionally related to the E6-AP ubiquitin-protein ligase.
SourceProc. Natl. Acad. Sci. U.S.A. 92:2563-2567(1995).
PubMed ID7708685

2AuthorsHatakeyama S. Jensen J.P. Weissman A.M.
TitleSubcellular localization and ubiquitin-conjugating enzyme (E2) interactions of mammalian HECT family ubiquitin protein ligases.
SourceJ. Biol. Chem. 272:15085-15092(1997).
PubMed ID9182527

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