ArticleNature structural & molecular biology2024
UBE2A and UBE2B are recruited by an atypical E3 ligase module in UBR4.
Article in Nature structural & molecular biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
What it found
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
18 citing papers in PubMed, 30 citations in OpenAlex.
- UBE2A as a prognostic indicator across human cancers: Insights from multi‑omics and immune landscape analyses.Molecular medicine reports · 2026Article
- HECT-type ubiquitin ligases: Emerging principles in the era of full-length structures.The Journal of biological chemistry · 2026Review
- Survey of the human proteostasis network: the ubiquitin-proteasome system.bioRxiv : the preprint server for biology · 2026Article
- Article
- UBR4 enhances efficacy of anti-EGFR antibody by facilitating clathrin-dependent EGFR endocytosis in colorectal cancer.Journal of gastroenterology · 2026Article
- Structure-guided analysis and prediction of human E2-E3 ligase pairing specificity.bioRxiv : the preprint server for biology · 2026Article
- UBR5: A New Player in Protein Quality Control for Skeletal Muscle Growth and Remodeling.Exercise and sport sciences reviews · 2025Review
- Examination of a Chimeric Bis-Electrophile for Selective DNA-Protein Cross-Linking and Mechlorethamine Reveals an Unknown Source of Nitrogen Mustard Cytotoxicity.Journal of the American Chemical Society · 2025Article
- Architecture of the UBR4 complex, a giant E4 ligase central to eukaryotic protein quality control.Science (New York, N.Y.) · 2025Article
- Article
- Tumor-promoting UBR4 coordinates impaired mitophagy-associated senescence and lung adenocarcinoma pathogenesis.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- TRIM52 maintains cellular fitness and is under tight proteolytic control by multiple giant E3 ligases.Nature communications · 2025Article
- UBR4 should no longer be considered a candidate gene for episodic ataxia type 8.European journal of human genetics : EJHG · 2025Article
- Convergence of orphan quality control pathways at a ubiquitin chain-elongating ligase.Molecular cell · 2025Article
- Ubiquitin E3 ligases in the plant Arg/N-degron pathway.The Biochemical journal · 2024Review
- pH-Controlled Chemoselective Rapid Azo-Coupling Reaction (CRACR) Enables Global Profiling of Serotonylation Proteome in Cancer Cells.Journal of proteome research · 2024Article
- The lowdown on breakdown: Open questions in plant proteolysis.The Plant cell · 2024Review
- BIG enhances Arg/N-degron pathway-mediated protein degradation to regulate Arabidopsis hypoxia responses and suberin deposition.The Plant cell · 2024Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
UBR4 is a 574 kDa E3 ligase (E3) of the N-degron pathway with roles in neurodevelopment, age-associated muscular atrophy and cancer. The catalytic module that carries out ubiquitin (Ub) transfer remains unknown. Here we identify and characterize a distinct E3 module within human UBR4 consisting of a 'hemiRING' zinc finger, a helical-rich UBR zinc-finger interacting (UZI) subdomain, and an N-terminal region that can serve as an affinity factor for the E2 conjugating enzyme (E2). The structure of an E2-E3 complex provides atomic-level insight into the specificity determinants of the hemiRING toward the cognate E2s UBE2A/UBE2B. Via an allosteric mechanism, the UZI subdomain modestly activates the Ub-loaded E2 (E2∼Ub). We propose attenuated activation is complemented by the intrinsically high lysine reactivity of UBE2A, and their cooperation imparts a reactivity profile important for substrate specificity and optimal degradation kinetics. These findings reveal the mechanistic underpinnings of a neuronal N-degron E3, its specific recruitment of UBE2A, and highlight the underappreciated architectural diversity of cross-brace domains with Ub E3 activity.
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Registered trials
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 OpenQuestion graph.