Our deepest condolences go out to his family and friends, and to all those who had the privilege of working with him. Rest in peace, Amos. Your work will live on long after you are gone.
PROSITE documentation PDOC50237HECT domain profile
View entry in original PROSITE document format
View entry in raw text format (no links)
PURL: https://purl.expasy.org/prosite/documentation/PDOC50237
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).
December 2001 / First entry.
-------------------------------------------------------------------------------
PROSITE method (with tools and information) covered by this documentation:
| 1 | Authors | Huibregtse J.M. Scheffner M. Beaudenon S. Howley P.M. |
| Title | A family of proteins structurally and functionally related to the E6-AP ubiquitin-protein ligase. | |
| Source | Proc. Natl. Acad. Sci. U.S.A. 92:2563-2567(1995). | |
| PubMed ID | 7708685 |
| 2 | Authors | Hatakeyama S. Jensen J.P. Weissman A.M. |
| Title | Subcellular localization and ubiquitin-conjugating enzyme (E2) interactions of mammalian HECT family ubiquitin protein ligases. | |
| Source | J. Biol. Chem. 272:15085-15092(1997). | |
| PubMed ID | 9182527 |
PROSITE is copyrighted by the SIB Swiss Institute of Bioinformatics and distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives (CC BY-NC-ND 4.0) License, see prosite_license.html.