The E3-ome gene-centric compendium reveals the human E3 ligase landscape
- Author(s)
- Chua, NK; González-Robles, TJ; Reddington, CJ; Dudley-Fraser, J; Birkinshaw, RW; Han, J; Solano, A; Wong, SW; Kochańczyk, T; Peter, JJ; Nakasone, MA; Aust, F; Munro, J; Tong, YH; Iskander, J; Abeysekera, W; Garnham, A; Huckstep, H; Ritchie, ME; Wertz, I; Hymowitz, S; Kumar, S; Conaway, RC; Privé, GG; Bullock, AN; Babon, JJ; Klevit, RE; Lorenz, S; Ciulli, A; Fischer, ES; Thomä, NH; Nowak, RP; Schulman, BA; Rapé, M; Rittinger, K; Pagan, JK; Bahlo, M; Mackay, JP; Mace, PD; Lima, CD; Hay, RT; Komander, D; Lechtenberg, BC; Joazeiro, CAP; Pagano, M; Hofmann, K; Feltham, R;
- Journal Title
- Cell
- Publication Type
- Mar 20
- 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.
- Publisher
- Cell Press
- Research Division(s)
- Ubiquitin Signalling; Structural Biology; Genetics and Gene Regulation; Bioinformatics and Computational Biology
- PubMed ID
- 41864206
- Publisher's Version
- https://doi.org/10.1016/j.cell.2026.01.029
- Open Access at Publisher's Site
https://doi.org/10.1016/j.cell.2026.01.029- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2026-03-24 02:09:48
Last Modified: 2026-03-24 02:16:41