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).