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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:

HECT, PS50237; HECT domain profile  (MATRIX)

Sequences known to belong to this class detected by the profile: ALL Other sequence(s) detected in Swiss-Prot: NONE

• Domain architecture view of Swiss-Prot proteins matching PS50237 • Retrieve an alignment of Swiss-Prot true positive hits:   Clustal format, color, condensed view  / Clustal format, color  / Clustal format, plain text  / Fasta format • Retrieve the sequence logo from the alignment • Taxonomic tree view of all Swiss-Prot/TrEMBL entries matching PS50237 • Retrieve a list of all Swiss-Prot/TrEMBL entries matching PS50237 • Scan Swiss-Prot/TrEMBL entries against PS50237 • view ligand binding statistics

Matching PDB structures: 1C4Z 1D5F 1ND7 1ZVD ... [ALL]

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

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