 HECT Domain | |
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| Class:Ubiquitin processes | |
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Structure:
 The crystal structure of the HECT domain of E6AP reveals a bilobal structure with a broad catalytic cleft at the junction of the two lobes. The cleft contains conserved residues involved in the formation of the ubiquitin-thioester bond. In the co-crystal structure of E6AP with E2 UbcH7, the E2 binds to a large hydrophobic groove in an approximatley 80 amino acid sub-domain of the N-terminal lobe of the HECT domain. The combined HECT-E2 complex forms a U-shaped structure with the active site cysteine side chains approximately 41 A apart with an open line of sight. The figure shows the HECT domain of E6AP.
Structure Reference:
Huang, L. et al. (1999) Science. 286(5443):1321-1326. PDB: 1C4Z.
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Domain binding and function:
 The HECT domain, short for Homologous to the E6-AP Carboxyl Terminus, is an approximately 40 kDa (350 amino acid) catalytic domain found at the carboxy-terminus of Hect-class E3 ubiquitin protein ligases. This domain functions to bind specific E2s, accepts ubiquitin from the E2 to form a ubiquitin-thioester intermediate with the HECT active cysteine, and then transfers ubiquitin to either the e-amino groups of lysine side chains of the substrate or to the growing end of multi-ubiquitin chains. The formation of a thioester intermediate with Ub is unique to Hect E3s and has not been observed with other classes of E3s.
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Examples of Proteins:
| HECT domain protein |
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Binding partner |
| E6AP |  |
UbcH7 |
| Nedd4 | |
UbcH5 |
| HectH7 | |
UbcH7 |
| HectH6 (p532) | |
UbcH5 |
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Referenced in part on Cell Signaling Technology Website, Reference Section on Protein Domains. We gratefully acknowledge the following contributors:
Piers Nash1, Dan Lin3, Kathleen Binns2, Clark Wells2, Rob Ingham2, Terry Kubiseski2, Bernard Liu1, Matt Smith2,3, Ivan Blasutig2,3, Maria Sierra1, Caesar Lim2,3, Michael Arc1, Jim Fawcett2 and Tony Pawson2,3.
1. Ben May Institute for Cancer Research, The University of Chicago, Chicago, Illinois, 60637, USA
2. Program in Molecular Biology and Cancer, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, M5G 1X5, Canada
3. Department of Molecular and Medical Genetics, University of Toronto, Toronto, Ontario, M5S 1A8, Canada
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