The E3-ome gene-centric compendium reveals the human E3 ligase landscape
To define and systematically characterize the human E3 ubiquitin ligase (E3) landscape, we generated the E3-ome, a compendium of E3s encoded by the human genome. The E3-ome integrates experimental data, bioinformatics, and published research, revealing 672 high-confidence E3s. We standardized E3 classifications to create a unified framework for annotation and comparative analysis. The E3-ome identified several previously unrecognized domains, motifs, E3 candidates, and relationships, expanding the diversity of E3s. Furthermore, the E3-ome mapped the spatial and physiological organization of E3s across human tissues and cell types, revealing context-dependent E3s. Genetic analyses identified disease-associated variants across the E3-ome, linking E3s to diverse human pathologies. Together, these analyses define the human E3 landscape at high resolution and deliver a foundational resource to drive mechanistic and therapeutic discovery.
Citation
@article{kiat_chua2026,
author = {Kiat Chua, Ngee and J González-Robles, Tania and J
Reddington, Cameron and Dudley-Fraser, Jane and W Birkinshaw,
Richard and Han, Jiru and Solano, Ashleigh and Wei Wong, Soon and
Kochańczyk, Tomasz and J Peter, Joshua and A Nakasone, Mark and
Aust, Florian and Munro, Jacob and Huei Tong, Yeh and Iskander,
Julie and Abeysekera, Waruni and Garnham, Alex and Huckstep, Hannah
and E Ritchie, Matthew and Wertz, Ingrid and Hymowitz, Sarah and
Kumar, Sharad and C Conaway, Ron and G Privé, Gilbert and N Bullock,
Alex and J Babon, Jeffrey and E Klevit, Rachel and Lorenz, Sonja and
Ciulli, Alessio and S Fischer, Eric and H Thomä, Nicolas and P
Nowak, Radosław and A Schulman, Brenda and Rapé, Michael and
Rittinger, Katrin and K Pagan, Julia and Bahlo, Melanie and P
Mackay, Joel and D Mace, Peter and D Lima, Christopher and T Hay,
Ronald and Komander, David and C Lechtenberg, Bernhard and A P
Joazeiro, Claudio and Pagano, Michele and Hofmann, Kay and Feltham,
Rebecca},
title = {The {E3-ome} Gene-Centric Compendium Reveals the Human {E3}
Ligase Landscape},
journal = {Cell},
volume = {189},
number = {7},
date = {2026-04-02},
url = {https://doi.org/10.1016/j.cell.2026.01.029},
doi = {10.1016/j.cell.2026.01.029},
langid = {en},
abstract = {To define and systematically characterize the human E3
ubiquitin ligase (E3) landscape, we generated the E3-ome, a
compendium of E3s encoded by the human genome. The E3-ome integrates
experimental data, bioinformatics, and published research, revealing
672 high-confidence E3s. We standardized E3 classifications to
create a unified framework for annotation and comparative analysis.
The E3-ome identified several previously unrecognized domains,
motifs, E3 candidates, and relationships, expanding the diversity of
E3s. Furthermore, the E3-ome mapped the spatial and physiological
organization of E3s across human tissues and cell types, revealing
context-dependent E3s. Genetic analyses identified
disease-associated variants across the E3-ome, linking E3s to
diverse human pathologies. Together, these analyses define the human
E3 landscape at high resolution and deliver a foundational resource
to drive mechanistic and therapeutic discovery.}
}