ArticleCell2026
The E3-ome gene-centric compendium reveals the human E3 ligase landscape.
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Article in Cell, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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11citing papers in PubMed
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Who cites it
11 citing papers in PubMed.
- AbioRxiv : the preprint server for biology · 2026Article
- Pan-cancer proteogenomic interrogation of the ubiquitin-proteasome system.Cell death and differentiation · 2026Article
- UbiDash: A UPS proteomic atlas for tissue-aware degrader design.Cell death and differentiation · 2026Article
- Review
- Comparative analysis of Cdc48-dependent proteolysis at the ER, mitochondria and chloroplasts.Nature communications · 2026Review
- Ubiquitin beyond the proteome: lipids, glycans, metabolites, nucleic acids, and an expanding molecular landscape.Biochemical Society transactions · 2026Review
- HECT-type ubiquitin ligases: Emerging principles in the era of full-length structures.The Journal of biological chemistry · 2026Review
- The landscape of the ubiquitin-proteasome system in cancer.Cell death and differentiation · 2026Article
- Methods to Study the Molecular Mechanism and Drive the Design of Protein Degraders.Chemical reviews · 2026Review
- Review
- E3 ubiquitin ligases in bone homeostasis: from regulatory mechanisms to skeletal diseases and therapeutic targeting.Frontiers in cell and developmental biology · 2026Review
Corrections and comments
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Authors and funding
47 authors.
Ngee Kiat ChuaWalter and Eliza Hall Institute of Medical Research, Parkville, Melbourne, VIC 3052, Australia; Department of Medical Biology, University of Melbourne, Parkville, Melbourne, VIC 3010, Australia. Electronic address: chua.n@wehi.edu.au.
Tania J González-RoblesDepartment of Biochemistry and Molecular Pharmacology, New York University Grossman School of Medicine, New York, NY 10016, USA; Laura and Isaac Perlmutter Cancer Center, New York University Grossman School of Medicine, New York, NY 10016, USA; Howard Hughes Medical Institute, New York University Grossman School of Medicine, New York, NY 10016, USA; Department of Precision Medicine, New York University Grossman School of Medicine, New York, NY 10016, USA.
Cameron J ReddingtonBiochemistry Department, School of Biomedical Sciences, University of Otago, Dunedin 9054, New Zealand.
Jane Dudley-FraserMolecular Structure of Cell Signalling Laboratory, the Francis Crick Institute, London NW1 1AT, UK.
Richard W BirkinshawWalter and Eliza Hall Institute of Medical Research, Parkville, Melbourne, VIC 3052, Australia; Department of Medical Biology, University of Melbourne, Parkville, Melbourne, VIC 3010, Australia.
Jiru HanWalter and Eliza Hall Institute of Medical Research, Parkville, Melbourne, VIC 3052, Australia; Department of Medical Biology, University of Melbourne, Parkville, Melbourne, VIC 3010, Australia.
Ashleigh SolanoWalter and Eliza Hall Institute of Medical Research, Parkville, Melbourne, VIC 3052, Australia; Department of Medical Biology, University of Melbourne, Parkville, Melbourne, VIC 3010, Australia.
Soon Wei WongRobinson Research Institute and Adelaide Medical School, the University of Adelaide, Adelaide, SA 5006, Australia; College of Medicine and Public Health, Flinders Health and Medical Research Institute, Flinders University, Adelaide, SA 5042, Australia.
Tomasz KochańczykStructural Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Joshua J PeterStructural Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Mark A NakasoneCentre for Targeted Protein Degradation, School of Life Sciences, University of Dundee, Dundee DD1 5JJ, UK.
Florian AustResearch Group 'Ubiquitin Signaling Specificity', Max Planck Institute for Multidisciplinary Sciences, 37077 Göttingen, Germany.
Jacob MunroWalter and Eliza Hall Institute of Medical Research, Parkville, Melbourne, VIC 3052, Australia; Department of Medical Biology, University of Melbourne, Parkville, Melbourne, VIC 3010, Australia.
Yeh Huei TongWalter and Eliza Hall Institute of Medical Research, Parkville, Melbourne, VIC 3052, Australia; Department of Medical Biology, University of Melbourne, Parkville, Melbourne, VIC 3010, Australia.
Julie IskanderWalter and Eliza Hall Institute of Medical Research, Parkville, Melbourne, VIC 3052, Australia; Department of Medical Biology, University of Melbourne, Parkville, Melbourne, VIC 3010, Australia.
Waruni AbeysekeraWalter and Eliza Hall Institute of Medical Research, Parkville, Melbourne, VIC 3052, Australia; Department of Medical Biology, University of Melbourne, Parkville, Melbourne, VIC 3010, Australia.
Alex GarnhamWalter and Eliza Hall Institute of Medical Research, Parkville, Melbourne, VIC 3052, Australia; Department of Medical Biology, University of Melbourne, Parkville, Melbourne, VIC 3010, Australia.
Hannah HuckstepWalter and Eliza Hall Institute of Medical Research, Parkville, Melbourne, VIC 3052, Australia; Department of Medical Biology, University of Melbourne, Parkville, Melbourne, VIC 3010, Australia.
Matthew E RitchieWalter and Eliza Hall Institute of Medical Research, Parkville, Melbourne, VIC 3052, Australia; Department of Medical Biology, University of Melbourne, Parkville, Melbourne, VIC 3010, Australia.
Ingrid WertzLyterian Therapeutics, 630 Gateway Blvd, South San Francisco, CA 94080, USA.
Sarah HymowitzThe Column Group, 1 Letterman Drive Building D, Suite DM-900, San Francisco, CA 94129, USA.
Sharad KumarCenter for Cancer Biology, University of South Australia, Adelaide, SA 5001, Australia; Adelaide Medical School, the University of Adelaide, Adelaide, SA 5005, Australia; Center for Cancer Biology, College of Health, Adelaide University, Adelaide, SA 5000, Australia.
Ron C ConawayLyda Hill Department of Bioinformatics, University of Texas Southwestern Medical Center, Dallas, TX 75390-9046, USA.
Gilbert G PrivéPrincess Margaret Cancer Centre, Toronto, ON M5G 1L7, Canada; Department of Medical Biophysics, University of Toronto, Toronto, ON M5G 1L7, Canada; Department of Biochemistry, University of Toronto, Toronto, Ontario M5S 1A8, Canada.
Alex N BullockCentre for Medicines Discovery, Nuffield Department of Medicine Research Building, University of Oxford, Roosevelt Drive, Oxford OX3 7FZ, UK.
Jeffrey J BabonWalter and Eliza Hall Institute of Medical Research, Parkville, Melbourne, VIC 3052, Australia; Department of Medical Biology, University of Melbourne, Parkville, Melbourne, VIC 3010, Australia.
Rachel E KlevitDepartment of Biochemistry, University of Washington, Seattle, WA 98195, USA.
Sonja LorenzResearch Group 'Ubiquitin Signaling Specificity', Max Planck Institute for Multidisciplinary Sciences, 37077 Göttingen, Germany.
Alessio CiulliCentre for Targeted Protein Degradation, School of Life Sciences, University of Dundee, Dundee DD1 5JJ, UK.
Eric S FischerDepartment of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02115, USA; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA.
Nicolas H ThomäSwiss Institute for Experimental Cancer Research (ISREC), École Polytechnique Fédérale de Lausanne, 1015 Lausanne, Switzerland.
Radosław P NowakInstitute of Structural Biology, Medical Faculty, University of Bonn, DE-53127 Bonn, Germany.
Brenda A SchulmanDepartment of Molecular Machines and Signaling, Max Planck Institute of Biochemistry, D-82152 Martinsried, Germany.
Michael RapéDepartment of Molecular and Cell Biology, University of California at Berkeley, Berkeley, CA 94720, USA; Howard Hughes Medical Institute, University of California at Berkeley, Berkeley, CA 94720, USA; California Institute for Quantitative Biosciences (QB3), University of California at Berkeley, Berkeley, CA 94720-3220, USA.
Katrin RittingerMolecular Structure of Cell Signalling Laboratory, the Francis Crick Institute, London NW1 1AT, UK.
Julia K PaganSchool of Biomedical Sciences, Faculty of Health, Medicine and Behavioural Sciences, The University of Queensland, Brisbane, QLD 4072, Australia; Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD 4072, Australia.
Melanie BahloWalter and Eliza Hall Institute of Medical Research, Parkville, Melbourne, VIC 3052, Australia; Department of Medical Biology, University of Melbourne, Parkville, Melbourne, VIC 3010, Australia.
Joel P MackaySchool of Life and Environmental Sciences, University of Sydney, Sydney, NSW 2006, Australia.
Peter D MaceBiochemistry Department, School of Biomedical Sciences, University of Otago, Dunedin 9054, New Zealand.
Christopher D LimaStructural Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Howard Hughes Medical Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Ronald T HayDivision of Molecular, Cellular and Developmental Biology, School of Life Sciences, University of Dundee, Dow Street, Dundee DD1 5EH, UK.
David KomanderWalter and Eliza Hall Institute of Medical Research, Parkville, Melbourne, VIC 3052, Australia; Department of Medical Biology, University of Melbourne, Parkville, Melbourne, VIC 3010, Australia.
Bernhard C LechtenbergWalter and Eliza Hall Institute of Medical Research, Parkville, Melbourne, VIC 3052, Australia; Department of Medical Biology, University of Melbourne, Parkville, Melbourne, VIC 3010, Australia.
Claudio A P JoazeiroCenter for Molecular Biology of Heidelberg University (ZMBH), DKFZ-ZMBH-Alliance, 69120 Heidelberg, Germany; Department of Molecular Medicine, the Herbert Wertheim UF Scripps Institute for Biomedical Innovation & Technology, Jupiter, FL 33458, USA.
Michele PaganoDepartment of Biochemistry and Molecular Pharmacology, New York University Grossman School of Medicine, New York, NY 10016, USA; Laura and Isaac Perlmutter Cancer Center, New York University Grossman School of Medicine, New York, NY 10016, USA; Howard Hughes Medical Institute, New York University Grossman School of Medicine, New York, NY 10016, USA.
Kay HofmannInstitute for Genetics, University of Cologne, 50674 Cologne, Germany.
Rebecca FelthamWalter and Eliza Hall Institute of Medical Research, Parkville, Melbourne, VIC 3052, Australia; Department of Medical Biology, University of Melbourne, Parkville, Melbourne, VIC 3010, Australia. Electronic address: feltham.r@wehi.edu.au.
Funding
X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Michael Jason de la Cruz · 1985 to 2026
$347.4MStructural studies of RNA processing and ubiquitin-like protein modificationR35GM118080 · NIGMS · SLOAN-KETTERING INST CAN RESEARCH · PI CHRISTOPHER D. LIMA · 2016 to 2026
$5.0MExpanding Mechanistic Insights into Protein UbiquitylationR35GM144127 · NIGMS · UNIVERSITY OF WASHINGTON · PI Rachel E Klevit · 2022 to 2026
$3.2MNCI NIH HHS P30 CA008748NIGMS NIH HHS R35 GM118080NIGMS NIH HHS R35 GM144127
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.
Indexed as
Genome, HumanUbiquitin-Protein LigasesHumansUbiquitin-Protein Ligases
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LicenceCC BY
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.