ArticleNature2011
UBCH7 reactivity profile reveals parkin and HHARI to be RING/HECT hybrids.
Article in Nature, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 336 papers.
What it found
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Who cites it
336 citing papers in PubMed, 550 citations in OpenAlex.
- Multiple directed mutagenesis reduces enzymatic activity and antibody recognition of the African Swine Fever Virus E2 ubiquitin-conjugating protein (ASFV-pI215L).Emerging microbes & infections · 2026Article
- Fluorophore placement and size impact E2 ubiquitination efficiency.The Biochemical journal · 2026Article
- Mitophagy in neuronal health and disease: from mechanisms to neurodegeneration.The Journal of clinical investigation · 2026Review
- Design principles of a membrane-spanning ubiquitin ligase.Molecular cell · 2026Article
- Survey of the human proteostasis network: the ubiquitin-proteasome system.bioRxiv : the preprint server for biology · 2026Article
- Mechanisms and Design Principles of Proteolysis-Targeting Chimeras and Their Emerging Applications.ACS pharmacology & translational science · 2026Review
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- Highly specific intracellular ubiquitination of a small molecule.Nature chemical biology · 2026Article
- Ubiquitin-centered post-translational modification crosstalk orchestrates tumor immunity and immunotherapy response.Experimental hematology & oncology · 2026Review
- Cis or trans: a puzzle of Parkin activation mechanism.Essays in biochemistry · 2026Review
- Covalent fragment screening to inhibit the E3 ligase activity of bacterial NEL enzymes SspH1 and SspH2.RSC chemical biology · 2026Article
- E2 variants for probing E3 ubiquitin ligase activities.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Mitochondrial resilience: a convergent framework for pathogenesis and neuroprotection in Parkinson's disease.Frontiers in pharmacology · 2026Review
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- Therapeutic Promise of Mitophagy in Cancer: Advancing from Small-Molecule Regulation to Nanotechnology-Enhanced Targeting Therapy.Theranostics · 2026Review
- Targeted Protein Degradation in Lung Cancer: The Emerging Role of PROTAC Technology and E3 Ligases.Current medicinal chemistry · 2026Review
- Targeting ubiquitination in disease and therapy.Signal transduction and targeted therapy · 2025Review
- Activation of endogenous PRKN by structural derepression is linked to increased turnover of the E3 ubiquitin ligase.Autophagy · 2025Article
- Ubiquitination in the Nervous System: From Molecular Mechanisms to Disease Implications.Molecular neurobiology · 2025Review
- RING-Between-RING-Type E3 Ligase Ariadne-Like Protein 8 Negatively Regulates Plant Virus Infection by Targeting a Viral Movement Protein.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
276 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Although the functional interaction between ubiquitin-conjugating enzymes (E2s) and ubiquitin ligases (E3s) is essential in ubiquitin (Ub) signalling, the criteria that define an active E2-E3 pair are not well established. The human E2 UBCH7 (also known as UBE2L3) shows broad specificity for HECT-type E3s, but often fails to function with RING E3s in vitro despite forming specific complexes. Structural comparisons of inactive UBCH7-RING complexes with active UBCH5-RING complexes reveal no defining differences, highlighting a gap in our understanding of Ub transfer. Here we show that, unlike many E2s that transfer Ub with RINGs, UBCH7 lacks intrinsic, E3-independent reactivity with lysine, explaining its preference for HECTs. Despite lacking lysine reactivity, UBCH7 exhibits activity with the RING-in-between-RING (RBR) family of E3s that includes parkin (also known as PARK2) and human homologue of ariadne (HHARI; also known as ARIH1). Found in all eukaryotes, RBRs regulate processes such as translation and immune signalling. RBRs contain a canonical C3HC4-type RING, followed by two conserved Cys/His-rich Zn(2+)-binding domains, in-between-RING (IBR) and RING2 domains, which together define this E3 family. We show that RBRs function like RING/HECT hybrids: they bind E2s via a RING domain, but transfer Ub through an obligate thioester-linked Ub (denoted ∼Ub), requiring a conserved cysteine residue in RING2. Our results define the functional cadre of E3s for UBCH7, an E2 involved in cell proliferation and immune function, and indicate a novel mechanism for an entire class of E3s.
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What OpenQuestion holds
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.