The -4 phenylalanine is required for substrate ubiquitination catalyzed by HECT ubiquitin ligases.

@article{Salvat2004TheP,
  title={The -4 phenylalanine is required for substrate ubiquitination catalyzed by HECT ubiquitin ligases.},
  author={Catherine Salvat and Guangli Wang and Anahita Dastur and Nancy A Lyon and Jon M. Huibregtse},
  journal={The Journal of biological chemistry},
  year={2004},
  volume={279 18},
  pages={18935-43}
}
The reaction cycle of HECT domain ubiquitin ligases consists of three steps: 1) binding of an E2 protein, 2) transfer of ubiquitin from E2 to the HECT domain, and 3) transfer of ubiquitin to the substrate. We report the identification of a determinant that is specifically required for the last step of this cycle, a phenylalanine residue located four amino acids from the C terminus of most HECT domains, referred to here as the -4F. Alteration of this residue in human E6AP and Saccharomyces… CONTINUE READING

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