The E3-ome gene-centric compendium reveals the human E3 ligase landscape

Chua, NK; Gonzalez-Robles, TJ; Kochanczyk, T; Reddington, CJ; Prive, GG; Dudley-Fraser, J; Thoma, NH; Birkinshaw, RW; Rape, M; Han, J; Solano, A; Wong, SW; 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; Bullock, AN; Babon, JJ; Klevit, RE; Lorenz, S; Ciulli, A; Fischer, ES; Nowak, RP; Schulman, BA; 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

Author(s): Chua, NK; Gonzalez-Robles, TJ; Kochanczyk, T; Reddington, CJ; Prive, GG; Dudley-Fraser, J; Thoma, NH; Birkinshaw, RW; Rape, M; Han, J; Solano, A; Wong, SW; 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; Bullock, AN; Babon, JJ; Klevit, RE; Lorenz, S; Ciulli, A; Fischer, ES; Nowak, RP; Schulman, BA; 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;
Details: Publication Year 2026-04-02,Volume 189,Issue #7,Page 2167-2188 e27
Journal Title: Cell
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
Keywords: Humans; *Ubiquitin-Protein Ligases/genetics/metabolism/chemistry; Genome, Human/genetics; Computational Biology/methods
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: 2026-04-27 03:54:31