Affinage

UBE2N

Ubiquitin-conjugating enzyme E2 N · UniProt P61088

Length
152 aa
Mass
17.1 kDa
Annotated
2026-06-10
100 papers in source corpus 56 papers cited in narrative 52 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 10/10 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

UBE2N (Ubc13) is the dedicated E2 ubiquitin-conjugating enzyme for Lys63-linked polyubiquitin chain synthesis, a non-proteolytic signal that drives DNA double-strand break responses, innate and adaptive immune signaling, and additional cellular programs (PMID:11504715, PMID:17349954, PMID:17404240). Catalysis requires heterodimerization with a catalytically inactive ubiquitin-conjugating enzyme variant (UEV): Mms2 or Uev1A binds a pocket on Ubc13 and orients an untethered acceptor ubiquitin so that its Lys63 is positioned into the Ubc13 active site for selective chain elongation, as defined by NMR models and the crystal structure of the covalent UEV–Ubc13–ubiquitin intermediate (PMID:11440714, PMID:11504715, PMID:16980971). The choice of UEV partner partitions Ubc13 between pathways — Ubc13-Mms2 supports DNA repair while Ubc13-Uev1A supports NF-κB activation — and tunes chain length (PMID:16129784). Ubc13 is recruited and allosterically activated by multiple RING E3 ligases that wrap around the Ubc13~ubiquitin conjugate to lock the closed, discharge-competent conformation, including RNF8 in the DNA damage response, TRAF6 in inflammatory signaling, and TRIM21 (PMID:22589545, PMID:26903517, PMID:28993672, PMID:31582740). In the nucleus, RNF8-Ubc13 builds K63 chains at break sites that recruit the RAP80/Abraxas/BRCA1/BRCC36 complex and 53BP1, license homologous recombination through BRCA1 activation and Rad51 filament formation, and is opposed by the Rap80-BRCC36 deubiquitinase to set steady-state ubiquitin levels (PMID:18077395, PMID:17349954, PMID:19202061); Ubc13-Mms2 with the E3 SHPRH also polyubiquitinates PCNA in postreplication repair (PMID:17108083). In immune cells, Ubc13 mediates TRAF6/TRAF2-dependent K63 ubiquitination to activate MAP kinases and NF-κB, controlling B cell, macrophage, and regulatory T cell function, and is essential for hematopoietic stem cell maintenance and embryonic viability (PMID:16862162, PMID:17404240, PMID:12591926, PMID:22484734, PMID:19926860). Beyond canonical chains, Ube2N generates unanchored K63 polyubiquitin required for RIG-I-driven MAVS aggregation in antiviral signaling and promotes NLRP3 inflammasome activation (PMID:28469175, PMID:33893171). Ubc13 activity is restrained by diverse mechanisms: ISGylation at Lys92 blocks thioester formation, OTUB1 non-catalytically caps di-ubiquitin on the E2-UEV complex, and the direct binders GPS2 and LGP2 sequester the enzyme (PMID:16112642, PMID:16122702, PMID:22679021, PMID:28039360, PMID:34965427). Bacterial effectors hijack Ubc13 to dampen inflammation — Shigella OspI deamidates Gln100 to disrupt TRAF6 RING engagement, and Legionella MavC transglutaminates ubiquitin onto the charged Ube2N~Ub conjugate, a modification reversed by the deamidase MvcA (PMID:22407319, PMID:31638574, PMID:30420781, PMID:31825121). Pharmacological inhibitors such as NSC697923 covalently target the Ubc13 active-site cysteine and suppress NF-κB-dependent malignancies (PMID:22791293, PMID:25909880, PMID:35263148, PMID:40371639).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 2001 High

    Establishing how a single E2 achieves Lys63 linkage specificity was the founding mechanistic question; the Mms2/Ubc13 heterodimer structure and reconstituted activity showed the enzyme requires an inactive UEV partner that orients the acceptor ubiquitin so only Lys63 reaches the active site.

    Evidence X-ray crystallography, in vitro thioester/chain-assembly assays, and NMR mapping of the acceptor ubiquitin surface, with UV-sensitivity validation

    PMID:11440714 PMID:11504715

    Open questions at the time
    • Did not resolve the donor ubiquitin geometry in the covalent intermediate
    • Left open how distinct UEV partners select different pathways
  2. 2003 High

    Quantitative and structural definition of the Mms2·Ubc13·di-ubiquitin assembly answered how tightly the partners engage and how the heterodimer enhances acceptor binding, converting a qualitative model into a thermodynamic one.

    Evidence NMR structural modeling with isothermal titration calorimetry of heterodimer and ubiquitin affinities

    PMID:12569095 PMID:12834344

    Open questions at the time
    • Solution model rather than a covalent intermediate structure
    • Did not address E3-driven activation
  3. 2005 High

    Identifying the precise interface residues and demonstrating that two UEVs (Mms2 vs Uev1A) route Ubc13 to DNA repair versus NF-κB resolved how one E2 serves divergent pathways and which contacts confer variant selectivity.

    Evidence Structure-guided interface mutagenesis with complementation, plus functional separation in yeast, NF-κB reporters, and siRNA knockdown

    PMID:15749714 PMID:16129784

    Open questions at the time
    • Did not define how UEV identity is selected at specific cellular sites
    • Chain-length control by UEVs left mechanistically incomplete
  4. 2006 High

    The covalent Mms2-Ubc13-ubiquitin crystal structure visualized the catalytic intermediate, directly showing how the acceptor Lys63 is positioned for elongation and closing the central mechanistic question of linkage specificity.

    Evidence X-ray crystallography of the covalent UEV-E2-Ub intermediate

    PMID:16980971

    Open questions at the time
    • Did not include an activating E3 RING in the structure
    • Donor conformational dynamics during discharge not captured
  5. 2006 High

    Genetic and biochemical work placed Ubc13 within immune signaling and the DNA damage response in vivo, showing it drives MAP kinase activation via NEMO ubiquitination and operates with RNF8 and SHPRH as E3 partners.

    Evidence Conditional knockout mice, signaling/ubiquitination assays, reciprocal Co-IP, and in vitro ubiquitination with knockdown

    PMID:12591926 PMID:16862162 PMID:17108083 PMID:18077395

    Open questions at the time
    • Did not establish the structural basis of RING-driven activation
    • Substrate-specific chain architecture in vivo not resolved
  6. 2007 High

    Loss-of-function studies defined Ubc13 as required for HR-based DSB repair and for TRAF6-dependent inflammatory signaling organismally, with homozygous null being embryonic lethal, establishing physiological essentiality.

    Evidence DT40 gene disruption and siRNA with HR and focus-formation readouts; mouse knockout with in vivo ubiquitination and cytokine assays

    PMID:17349954 PMID:17404240

    Open questions at the time
    • Did not separate developmental from signaling roles in the lethal phenotype
    • Direct substrates at DSBs only partially defined
  7. 2009 High

    Identification of the Rap80-BRCC36 deubiquitinase as an antagonist of RNF8-Ubc13 reframed DSB ubiquitin signaling as a dynamic balance of ligase and DUB activities.

    Evidence siRNA, catalytic mutants, and epistasis with immunofluorescence at DSBs

    PMID:19202061

    Open questions at the time
    • Did not quantify in vivo chain turnover kinetics
    • Spatial regulation of the opposing activities unresolved
  8. 2006 Medium

    Work outside the canonical chain-signaling roles showed Ubc13 K63-ubiquitinates p53 to alter its stability, localization, and oligomeric state, expanding the substrate repertoire; JNK-dependent p53 Thr81 phosphorylation later defined the trigger for Ubc13 release.

    Evidence Co-IP, K63-specific ubiquitination, fractionation, reporter assays, and polysome fractionation with p53 T81 mutants

    PMID:17000756 PMID:19651615

    Open questions at the time
    • Single-lab observations without independent reciprocal validation
    • The E3 ligase directing p53 K63 ubiquitination not identified in these studies
  9. 2012 High

    Structural and biochemical dissection of regulation answered how Ubc13 is restrained, revealing RNF8 dimer-driven activation, OTUB1 non-catalytic capping of di-ubiquitin, and the Shigella OspI deamidation strategy.

    Evidence Crystal structures of RNF8-Ubc13/Mms2, OTUB1-Ubc13-Mms2, and OspI, with SPR, mutagenesis, and NF-κB/DSB assays

    PMID:22407319 PMID:22589545 PMID:22679021

    Open questions at the time
    • Did not define how these regulators are spatially deployed in cells
    • Cross-talk among inhibitory mechanisms not addressed
  10. 2016 High

    Capturing the activated RNF8-Ubc13~ubiquitin complex with separation-of-function mutations explained how RING E3s allosterically lock the donor ubiquitin conformation to enable processive K63 chain formation and selective BRCA1 recruitment.

    Evidence X-ray crystallography plus SAXS, separation-of-function mutagenesis, and cellular immunofluorescence

    PMID:26903517

    Open questions at the time
    • Did not generalize the allosteric model across all Ubc13 E3 partners in cells
    • Did not resolve how 53BP1 versus BRCA1 outcomes are encoded
  11. 2017 High

    Defining how oligomeric TRAF6 and RING anchor points engage the charged conjugate established that E3s recognize Ubc13~Ub (not free Ubc13) to achieve processivity and E2-specific catalysis, and extended Ubc13 to antiviral MAVS aggregation and neuronal synapse suppression.

    Evidence Processivity assays with CC-domain mutagenesis and domain fusions; RIG-I/MAVS aggregation reconstitution; in vivo neuronal KO with electrophysiology and proteomics

    PMID:28469175 PMID:28993672 PMID:29097665

    Open questions at the time
    • Did not fully define unanchored versus conjugated chain roles in all pathways
    • Cytoplasmic RNF8-Ubc13 complex composition only partly mapped
  12. 2019 High

    Mechanistic studies of bacterial effectors and the OspI mechanism revealed precise chemical strategies to disable Ubc13: salt-bridge competition blocking TRAF6 RING binding, transglutaminase crosslinking of ubiquitin onto the charged conjugate (MavC), and its enzymatic reversal (MvcA), plus the TRIM21 tri-ionic anchoring mechanism.

    Evidence NMR and crystallography of effector-Ube2N complexes, transglutamination/deamidation assays, mutagenesis, and bacterial replication and immune readouts

    PMID:30420781 PMID:31582740 PMID:31638574 PMID:31825121 PMID:32398758

    Open questions at the time
    • Host enzymes (if any) reversing these effector modifications endogenously not identified
    • In vivo dynamics of effector-mediated Ube2N silencing during infection incompletely defined
  13. 2021 Medium

    Later work expanded Ubc13's substrate and regulator network — NLRP3 K63 ubiquitination, RNF213 and TRIM21 partnerships, LGP2/GPS2/FAM177A1 sequestration, and SET7/STAT3 layered regulation — and exploited Ube2N inhibition therapeutically in AML and ferroptosis contexts.

    Evidence Co-IP, MS site mapping, CRISPR and conditional knockouts, in vitro inhibition assays, and inhibitor-resistance crystallography

    PMID:24906799 PMID:25189770 PMID:25503582 PMID:28039360 PMID:32024978 PMID:33842849 PMID:33893171 PMID:34799425 PMID:34965427 PMID:35263148 PMID:36822329

    Open questions at the time
    • Many partner and substrate claims rest on single-lab Co-IP or knockdown without reciprocal structural validation
    • Selectivity and on-target specificity of inhibitors across pathways incompletely characterized

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the cell selects among UEV partners, competing E3 ligases, and the many negative regulators to assign Ubc13 to a specific pathway at a specific subcellular location in real time remains unresolved.
  • No integrated spatiotemporal model of partner selection
  • Quantitative competition among regulators in living cells not measured
  • In vivo chain architecture per substrate largely uncharacterized

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 4 GO:0016740 transferase activity 2 GO:0140657 ATP-dependent activity 2
Localization
GO:0005634 nucleus 2 GO:0005739 mitochondrion 2 GO:0005829 cytosol 1
Pathway
R-HSA-168256 Immune System 5 R-HSA-162582 Signal Transduction 4 R-HSA-1643685 Disease 4 R-HSA-73894 DNA Repair 4 R-HSA-9612973 Autophagy 1
Partners
LGP2MMS2OTUB1RNF8SHPRHTRAF6TRIM21UEV1A
Complex memberships
RNF8-Ubc13/Mms2 ternary complexUbc13-Mms2 heterodimerUbc13-Uev1A heterodimer

Evidence

Reading pass · 52 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2001 Crystal structure of the Mms2/Ubc13 heterodimer reveals that the active site of Ubc13 sits at the intersection of two channels that are potential binding sites for the two substrate ubiquitins; mutations that destabilize the heterodimer interface confer marked UV sensitivity, demonstrating that the intact heterodimer is necessary for DNA repair. X-ray crystallography + mutagenesis + UV sensitivity assay Cell High 11440714
2001 Human Mms2 and Ubc13 form a stable heterodimer; the activated heterodimer transfers ubiquitin via the Ubc13 active-site thioester exclusively to Lys63 of an untethered acceptor ubiquitin; NMR mapping identifies a surface on acceptor ubiquitin that interacts with Mms2, indicating Mms2 orients the acceptor ubiquitin to place Lys63 near the Ubc13 active site. In vitro ubiquitin thioester/chain-assembly assay + 1H-15N HSQC NMR mapping The Journal of biological chemistry High 11504715
2003 NMR-based structural model of the human Mms2·Ubc13 heterodimer bound to both acceptor and donor ubiquitins defines the molecular basis for Lys63-linked chain synthesis; thermodynamic/kinetic measurements show Mms2 and Ubc13 interact with a Kd ~49 nM and the heterodimer binds acceptor ubiquitin with a Kd ~28 µM, markedly tighter than Mms2 alone (~98 µM). 1H-15N NMR spectroscopy + isothermal titration calorimetry The Journal of biological chemistry / Biochemistry High 12569095 12834344
2005 Mms2 and Ubc13 interact through a single key Mms2 residue that inserts into a pocket on Ubc13; structure-guided mutations at the heterodimer interface abolish Lys63-linked polyubiquitination and DNA repair complementation, demonstrating that specific interface residues determine E2-variant selectivity. Yeast two-hybrid, GST pull-down, surface plasmon resonance, in vitro ubiquitin conjugation, functional complementation The Journal of biological chemistry High 15749714
2005 Mammalian Ubc13 pairs with two distinct UEV proteins (Mms2 and Uev1A) that direct it to different cellular processes: Ubc13-Mms2 is required for DNA damage repair but not NF-κB activation, whereas Ubc13-Uev1A is required for NF-κB activation but not DNA repair; the two UEVs also differentially modulate the length of Lys63-linked polyubiquitin chains. Functional complementation in yeast, NF-κB reporter assays, siRNA knockdown, in vitro ubiquitin chain-length analysis The Journal of cell biology High 16129784
2006 Crystal structure of the Mms2-Ubc13-ubiquitin covalent intermediate (donor ubiquitin linked to Ubc13 active-site Cys) reveals at atomic resolution how Mms2 positions the acceptor ubiquitin Lys63 into the Ubc13 active site for selective chain elongation. X-ray crystallography of covalent UEV-E2-Ub intermediate Nature structural & molecular biology High 16980971
2006 Conditional ablation of Ubc13 in B cells and macrophages causes defective B cell development and impaired activation; in response to all tested stimuli except TNF, Ubc13-deficient cells show near-normal NF-κB activation but markedly impaired MAP kinase activation; Ubc13-induced MAP kinase activation requires ubiquitination of the adaptor IKKγ (NEMO). Conditional knockout mice, NF-κB and MAPK signaling assays, ubiquitination assays Nature immunology High 16862162
2006 RNF8, an FHA-RING ubiquitin ligase, physically interacts with Ubc13 and is required, together with Ubc13, to recruit the Rap80/Abraxas/BRCA1/BRCC36 A complex to DNA damage foci; this constitutes a sequential E3 ubiquitin ligase cascade generating K63-linked polyubiquitin chains at damage sites. siRNA knockdown, Co-IP, immunofluorescence focus formation assay Proceedings of the National Academy of Sciences High 18077395
2006 SHPRH, the human Rad5 homolog, physically interacts with both Rad6-Rad18 and Mms2-Ubc13 complexes and acts as the E3 ubiquitin ligase indispensable for Mms2-Ubc13-dependent polyubiquitination of PCNA. Co-IP, in vitro ubiquitination assay, siRNA knockdown Proceedings of the National Academy of Sciences High 17108083
2006 The RING finger protein RNF8 binds UBC13 through its RING domain and stimulates K63-linked (and K48-linked) self-polyubiquitylation; RNF8 co-localizes with UBC13 in the nucleus. Co-IP/pull-down, in vitro ubiquitination assay, immunofluorescence co-localization Journal of cellular biochemistry Medium 16215985
2006 Ubc13 elicits K63-linked ubiquitination of p53, which attenuates Hdm2-induced polyubiquitination; Ubc13 increases p53 stability while decreasing its transcriptional activity and promoting its cytoplasmic localization; these effects require Ubc13 catalytic activity and involve increasing monomeric (non-tetrameric) p53. Co-IP, K63-specific ubiquitination assay, subcellular fractionation, reporter assay, mutagenesis Molecular and cellular biology Medium 17000756
2007 Disruption or siRNA depletion of UBC13 in DT40 or human cells causes chromosome instability, hypersensitivity to UV and ionizing radiation, and impaired DNA double-strand break repair by homologous recombination; specifically, BRCA1 E3 ligase function activation, Rad51 nucleoprotein filament formation, and ssDNA/RPA complex generation at DSBs are abolished in Ubc13-deficient cells. Gene disruption (DT40), siRNA knockdown, HR assay, immunofluorescence (BRCA1/Rad51/RPA foci) Molecular cell High 17349954
2007 Ubc13 is an essential component of TRAF-mediated inflammatory signaling; heterozygous Ubc13 knockout mice show reduced TRAF6 ubiquitination in vivo, reduced cytokine secretion, and impaired NF-κB, JNK, and p38 MAPK activation in macrophages/splenocytes; homozygous knockout is embryonic lethal. Gene ablation in mice, in vivo ubiquitination assay, cytokine ELISA, signaling pathway analysis Proceedings of the National Academy of Sciences High 17404240
2003 TNF-induced GCKR and SAPK/JNK activation depends on TRAF2 and the Ubc13-Uev1A complex; Ubc13 interference inhibits TNF- and TRAF2-mediated GCKR and SAPK activation; TNF signaling leads to TRAF2 K63-linked polyubiquitination and oligomerization, and GCKR ubiquitination and activation, all sensitive to Ubc13 disruption. Dominant-negative interference, siRNA knockdown, co-IP, ubiquitination assay, kinase activity assay The Journal of biological chemistry High 12591926
2007 The HTLV-1 Tax oncoprotein is K63-polyubiquitinated in a Ubc13-dependent manner; Tax interacts with Ubc13; Ubc13 knockdown abrogates Tax ubiquitination and NF-κB activation; Tax ubiquitination is required for its interaction with NEMO. Co-IP, siRNA knockdown, K63-specific ubiquitination assay, NF-κB reporter assay Journal of virology Medium 17942533
2005 ISG15 covalently modifies Ubc13 at Lys92, and this ISGylation suppresses Ubc13's ability to form a thioester intermediate with ubiquitin, thereby inhibiting its ubiquitin-conjugating activity. In vitro ISGylation assay, ubiquitin thioester formation assay, biochemical purification of ISGylated Ubc13 Biochemical and biophysical research communications (two independent papers) High 16112642 16122702
2004 The TRAF6 RING finger domain directly binds Ubc13; either a single Cys-to-Ser substitution in the TRAF6 RING or a surface mutation on Ubc13 predicted to contact RING finger proteins abolishes the interaction; TRAF6 also self-interacts through its N-terminal RING-containing domain. Yeast two-hybrid, mutagenesis FEBS letters Medium 15147900
2008 The RNF8 RING domain anchors UBC13 at DNA damage sites independently of E2 variant proteins (Mms2/Uev1A); RNF8-UBC13 without E2 variants is sufficient to catalyze ubiquitin conjugation and promote 53BP1 accumulation at DSBs; only RING domains from UBC13-binding E3s enable this activity. Mutagenesis, immunofluorescence foci assay, in vitro ubiquitination assay, siRNA knockdown Molecular and cellular biology Medium 18678647
2009 The Rap80-BRCC36 deubiquitinating enzyme complex antagonizes RNF8-Ubc13-dependent ubiquitination at DSBs; BRCC36 knockdown or catalytic mutant restores 53BP1 recruitment and γH2AX ubiquitination following RNF8 depletion, revealing that opposing RNF8-Ubc13 ligase and Rap80-BRCC36 DUB activities determine steady-state ubiquitin levels at DSBs. siRNA knockdown, expression of catalytic mutants, immunofluorescence, epistasis analysis Proceedings of the National Academy of Sciences High 19202061
2009 JNK phosphorylates p53 at Thr81 on polysomes, which is required for dissociation of Ubc13 from p53; without JNK activity or with a non-phosphorylatable p53 T81 mutant, the Ubc13-p53 complex is maintained, inhibiting p53 multimerization and transcriptional activation; thus JNK and Ubc13 cooperate to regulate p53 multimerization on polysomes. Co-IP, polysome fractionation, site-directed mutagenesis of p53 T81, JNK inhibition Proceedings of the National Academy of Sciences Medium 19651615
2009 Conditional knockout of the Ubc13 gene causes severe loss of hematopoietic stem cells and immune cell lineages, thymus/bone marrow atrophy, and mouse lethality; loss of Ubc13 results in accumulation of β-catenin and hyperexpression of Wnt target genes, placing Ubc13 upstream of Wnt signaling in hematopoietic stem cell maintenance. Conditional knockout mice, flow cytometry, Western blot for β-catenin, Wnt target gene expression Proceedings of the National Academy of Sciences Medium 19926860
2012 The Shigella effector OspI is a glutamine deamidase that specifically deamidates Gln100 of UBC13 to glutamic acid (Q100E), abolishing its E2 ubiquitin-conjugating activity required for TRAF6 activation, thereby dampening NF-κB inflammatory signaling; crystal structure of OspI reveals a Cys-His-Asp catalytic triad required for deamidation. Crystal structure of OspI (2.0 Å), mass spectrometry identification of Q100E, in vitro E2 activity assay, catalytic triad mutagenesis, NF-κB signaling assay Nature High 22407319
2012 Crystal structure of RNF8 RING domain in complex with Ubc13/Mms2 (ternary complex) reveals that RNF8 dimerizes via a coiled-coil and binds Ubc13/Mms2 to stimulate K63 ubiquitin chain formation; RNF168, in contrast, is a RING monomer and does not catalyze K63 polyubiquitylation with Ubc13/Mms2. X-ray crystallography, in vitro ubiquitination assay, mutagenesis disrupting RNF8-Ubc13 interface or RNF8 coiled-coil The Journal of biological chemistry High 22589545
2012 Crystal structure of human OTUB1 in complex with UBC13 and MMS2 (3.15 Å) shows OTUB1 inhibits UBC13 E2 activity non-catalytically; OTUB1 strongly suppresses K63-linked tri-ubiquitin but allows di-ubiquitin production by capping the di-ubiquitin on the UBC13-MMS2 complex; structure-guided OTUB1 mutants that disrupt the UBC13 interface fail to inhibit K63 ubiquitination in vitro and in vivo. X-ray crystallography (3.15 Å), surface plasmon resonance, mutagenesis, in vitro ubiquitination assay, cellular DSB response assay The Journal of biological chemistry High 22679021
2012 Ubc13-specific ablation in regulatory T cells impairs their suppressive function in vivo and renders them susceptible to acquiring TH1 and TH17 effector phenotypes; this function involves downstream IKK activation; the Ubc13-IKK axis controls IL-10 and SOCS1 expression in Treg cells. Treg cell-specific conditional knockout mice, in vivo suppression assay, cytokine profiling, kinase activity assay Nature immunology High 22484734
2012 The small molecule NSC697923 inhibits Ubc13-Uev1A by blocking formation of the Ubc13-ubiquitin thioester conjugate, suppresses constitutive NF-κB activity in DLBCL cells, and inhibits DLBCL cell proliferation and survival. Biochemical thioester formation assay, NF-κB reporter, cell proliferation/viability assay, siRNA knockdown Blood Medium 22791293
2013 Crystal structures of OspI-Ubc13 complexes (2.96 Å and 2.3 Å) show OspI uses hydrophobic and charged surfaces to engage the α1 helix, L1 and L2 loops of Ubc13, with Gln100 positioned in the OspI catalytic pocket; Ubc13 binding induces structural rearrangement of the OspI catalytic pocket; the OspI-binding surface on Ubc13 largely overlaps with E3 ligase and DUB binding surfaces. X-ray crystallography (2.96 Å and 2.3 Å), mutagenesis, binding assays Journal of molecular biology / PLoS pathogens High 23542009 23633953
2013 UBC13 mediates K63-linked ubiquitination of TAK1 at Lys158 during H. pylori CagA-induced NF-κB activation; mutation of TAK1 K158R prevents its ubiquitination and impairs NF-κB activation; dominant-negative Ubc13 or siRNA knockdown abolishes CagA-facilitated TAK1 and NF-κB activation. Site-directed mutagenesis (TAK1 K158R), siRNA knockdown, dominant-negative Ubc13, ubiquitination assay, NF-κB reporter Journal of cellular biochemistry Medium 23606331
2013 MDC1 is ubiquitylated on Lys1977 of its tandem BRCT domain in a UBC13-dependent manner, and this ubiquitylation is required for direct MDC1 binding to RAP80 through RAP80's ubiquitin-interacting motifs. Co-IP, UBC13 knockdown, mutagenesis (K1977 identification), immunofluorescence DNA repair Medium 21622030
2014 UBE2N knockdown specifically prevents K63-linked ubiquitylation at mitochondrial sites during PINK1/Parkin-dependent mitophagy; combined knockdown of UBE2N, UBE2L3, and UBE2D2/3 substantially reduces mitochondrial polyubiquitylation, p62 recruitment, and autophagic clearance of depolarized mitochondria. siRNA knockdown, linkage-specific ubiquitin antibodies, immunofluorescence, autophagic flux assay Journal of cell science Medium 24906799
2014 Ubc13 is required for breast cancer metastasis but is largely dispensable for primary tumor growth; Ubc13 is required for TGFβ-induced TAK1 and p38 MAPK activation (non-SMAD signaling) to control metastasis-promoting gene expression; pharmacological p38 inhibition attenuates BCa metastasis in mice. Conditional knockout in mouse model, lung colonization assay, TGFβ signaling analysis (SMAD vs. non-SMAD), p38 inhibitor in vivo Proceedings of the National Academy of Sciences High 25189770
2014 STAT3 acts as a transcriptional repressor of the Ube2n (Ubc13) gene; in RANKL-activated macrophages, STAT3 is stimulated by autocrine IL-6 and inhibits Ets-1/Set1 methyltransferase/H3K4me3 accumulation at the Ube2n promoter; depletion of Ubc13 in Stat3-deficient macrophages suppresses excessive TRAF6-mediated K63 ubiquitination and NF-κB responses. ChIP (Ets-1, Set1, H3K4me3 at Ube2n promoter), siRNA knockdown, NF-κB reporter, macrophage activation assay Nature communications Medium 25503582
2015 NSC697923 and BAY 11-7082 both inhibit Ubc13 by covalent Michael addition at the Ubc13 active-site cysteine; crystal structures of both Ubc13-inhibitor adducts reveal that both exploit a binding groove unique to Ubc13; a Ubc13 mutant resistant to NSC697923 shows that NF-κB and DNA damage signaling inhibition by NSC697923 is largely due to specific Ubc13 inhibition. X-ray crystallography of inhibitor-Ubc13 adducts, resistance mutant, cellular NF-κB and DNA damage signaling assays ACS chemical biology High 25909880
2016 RNF8 stimulates Ubc13 polyubiquitination activity by modulating the conformation of ubiquitin covalently linked to the Ubc13 active site; crystal structure of the activated RNF8-Ubc13~ubiquitin complex shows this allosteric activation; structure-guided separation-of-function mutations that impair E2 stimulation abolish DSB signaling, 53BP1 recruitment, and specifically BRCA1 (but not 53BP1) recruitment by chromatin-targeted RNF168. X-ray crystallography + SAXS solution conformation, separation-of-function mutagenesis, cellular immunofluorescence The Journal of biological chemistry High 26903517
2016 GPS2 (G-protein Pathway Suppressor 2) directly inhibits Ubc13 enzymatic activity in B cells; GPS2 B cell-specific deletion causes developmental defects at multiple stages of B cell differentiation by derepressing TLR, BCR, and AKT/FOXO1 signaling through elevated Ubc13-mediated K63 ubiquitination. In vitro Ubc13 activity assay with GPS2, conditional knockout mice, B cell developmental analysis The Journal of biological chemistry Medium 28039360
2017 In cerebellar granule neurons, RNF8 and UBC13 form a cytoplasmic (not nuclear) complex that suppresses synapse differentiation in vivo; knockdown or conditional KO increases parallel fiber presynaptic boutons and functional synapses; RNF8 interacts with HERC2 and NEURL4, and knockdown of these phenocopies RNF8/UBC13 loss. In vivo knockdown, conditional knockout, electrophysiology (PF/PC synapse), proteomics, immunofluorescence Nature communications High 29097665
2017 TRAF6 coiled-coil (CC) domain mediates TRAF6 oligomerization, which primes interaction with the Ubc13~Ub conjugate (not unloaded Ubc13); this interaction is required for processive assembly of long K63-linked polyubiquitin chains and TAK1 activation in IL-1R/TLR pathways; fusion of the CC domain to CHIP/STUB1 confers NF-κB activation capacity. Mutagenesis of CC domain, in vitro ubiquitination processivity assay, co-IP, NF-κB reporter, domain fusion experiments Nature communications High 28993672
2017 Ubc13 K63-linked ubiquitination of RHBDF2 (iRhom2) is promoted by the Uev1A-Ubc13 complex together with CHIP, facilitating TACE maturation and subsequent shedding of the TNFα receptor, thereby acting as a negative regulator of TNFα-induced NF-κB signaling. Co-IP, in vitro ubiquitination assay, TACE maturation assay, NF-κB reporter Cellular signalling Medium 29069608
2017 Ube2N preferentially facilitates production of unanchored K63-linked polyubiquitin chains (while Ube2D3 promotes covalent conjugation) downstream of RIG-I/Riplet; both types of polyubiquitin chains are required for RIG-I to induce MAVS aggregation on mitochondria, triggering innate immune signaling. Chromatographic purification, in vitro ubiquitination assay, MAVS aggregation assay, siRNA knockdown Nature communications High 28469175
2018 Legionella pneumophila effector MavC is a transglutaminase that catalyzes monoubiquitination of UBE2N by covalent crosslinking of ubiquitin Gln40 to UBE2N Lys92 (and Lys94) via a γ-glutamyl-ε-Lys isopeptide bond; the catalytic residue is Cys74; this modification abolishes UBE2N's ability to form K63-type polyubiquitin chains and dampens NF-κB signaling. Biochemical transglutaminase assay, mass spectrometry (modification site), mutagenesis of Cys74, K63-chain formation assay, NF-κB reporter Nature microbiology High 30420781
2019 MavC targets the thioester-linked Ube2N~ubiquitin conjugate (not free Ube2N) for intramolecular transglutamination; ubiquitin shows increased affinity for MavC when tethered to Ube2N; crystal structures of MavC with substrate mimic and crosslinked product reveal the insertion domain is crucial for substrate recognition and that transamidation is favored over deamidation. Crystal structures of MavC-Ube2N~Ub complexes, biochemical transglutamination/deamidation assay, binding affinity measurements Nature communications High 32398758
2019 A tri-ionic motif in TRIM21 (and TRIM5) RING domain provides anchor points that wrap the Ube2N~Ub complex around the RING, locking the closed conformation required for ubiquitin discharge; mutation of these anchor points specifically inhibits ubiquitination with Ube2N/Ube2V2 but not Ube2D1, establishing an E2-specific catalytic mechanism for this class of RING E3s. NMR, mutagenesis, in vitro ubiquitination assay, viral neutralization assay, immune signaling assay Nature communications High 31582740
2019 L. pneumophila effector MvcA (50% identity to MavC) uses its deamidase catalytic triad to remove the MavC-installed ubiquitin from UBE2N (deubiquitination), restoring UBE2N activity; structural analysis of MvcA-UBE2N-Ub reveals the insertion domain is critical for substrate recognition; this temporal regulation of UBE2N activity is required for efficient intracellular bacterial replication. Biochemical deubiquitination assay, crystal/structural analysis, mutagenesis of catalytic triad, bacterial replication assay The EMBO journal High 31825121
2019 Deamidation of UBC13 at Gln100 (Q100E by OspI) inhibits interaction with TRAF6 RING domain by forming a new intramolecular salt bridge in UBC13 that competes with a critical intermolecular salt bridge at the UBC13/TRAF6 RING interface; this additionally prevents transient interactions needed for the closed E2-RING complex. NMR chemical shift perturbation, mutagenesis, binding affinity measurement, in vitro ubiquitination assay eLife High 31638574
2020 OTUB1 deubiquitinase is stabilized by K48-linked deubiquitination in dendritic cells, leading to increased K63-linked ubiquitination of IRAK1 and TRAF6 via UBC13, thereby augmenting NF-κB activation and inflammatory cytokine production; DC-specific OTUB1 deletion impairs IL-12 production and immune defense against T. gondii. Conditional knockout mice, co-IP, linkage-specific ubiquitination assay, cytokine measurement, infection model Cellular & molecular immunology Medium 32024978
2020 UBC13-mediated K63-linked polyubiquitination promotes MRE11 recruitment to TOP2-DNA adduct-blocked DSBs via RAP80/BRCA1 localization and BRCA1-MRE11 complex formation, facilitating nucleolytic removal of blocking adducts before NHEJ; UBC13 and MRE11 are dispensable for repair of clean DSBs but responsible for >50% and >70% of NHEJ-dependent repair of radiation-induced dirty DSBs, respectively. Auxin-inducible degron knockdown, NHEJ assay, immunofluorescence (RAP80, BRCA1, MRE11 foci), epistasis analysis iScience Medium 32283528
2021 Ubc13 associates with NLRP3 and promotes K63-linked polyubiquitination at Lys565 and Lys687 of NLRP3; Ubc13 knockdown/knockout or catalytic inhibition dramatically impairs NLRP3 inflammasome activation in macrophages, indicating K63 ubiquitination of NLRP3 is required for its activation. Co-IP, siRNA/CRISPR knockout, mass spectrometry (ubiquitination site identification), inflammasome activation assay (IL-1β, ASC speck formation) Journal of immunology Medium 33893171
2021 LGP2 helicase inhibits K63-linked polyubiquitination by directly associating with and sequestering Ubc13/UBE2N via its Hel2i subdomain, thereby inactivating multiple K63-Ub ligases (TRAF6, TRIM25, RNF125) and broadly suppressing innate immune signaling. Co-IP/pull-down of LGP2-Ubc13, in vitro ubiquitination assay, K63-Ub immunoblot, signaling reporter assay Cell reports Medium 34965427
2021 RNF213 is a K63-linked E3 ubiquitin ligase that interacts with UBC13 (identified by yeast two-hybrid with RNF213 RING domain as bait); RNF213 undergoes K63-linked autoubiquitination in a UBC13-dependent manner; this axis is required for angiogenic cell motility and invasion in HUVEC cells. Yeast two-hybrid, Co-IP, K63-specific ubiquitination assay, UBC13 knockdown, HUVEC cell migration/invasion assay FASEB BioAdvances Medium 33842849
2022 In AML, TRIM21 is identified as the E3 ligase that partners with activated UBE2N to modulate UBE2N-dependent proteostasis; UBE2N inhibition reduces levels of K63-ubiquitinated target proteins, leading to their increased K48-linked ubiquitination and degradation through the immunoproteasome; this is selective for immunoproteasome-positive AML cells. Interactome screen, proteomic analysis, whole-genome CRISPR-activation screen, K48/K63 ubiquitination assays, enzymatically defective mouse model Science translational medicine / Journal of clinical investigation Medium 35263148 40371639
2023 SET7 methyltransferase methylates OTUB1 at Lys122; this methylation does not affect OTUB1 DUB activity but impairs its non-canonical binding to UBC13, relieving OTUB1-mediated suppression of K63-linked ubiquitination and promoting ferroptosis. In vitro methylation assay, Co-IP (OTUB1-UBC13 interaction), methylation-mimic mutant, cell viability and ROS assay The Journal of biological chemistry Medium 36822329
2018 FAM177A1 competitively binds TRAF6 and impairs its interaction with Ubc13, thereby inhibiting TRAF6-mediated K63 polyubiquitination, downstream recruitment of signaling molecules, and NF-κB activation in response to IL-1β. Co-IP, competition binding assay (TRAF6-Ubc13 displacement), NF-κB reporter, siRNA knockdown Journal of immunology Medium 34799425

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2007 Ubc13/Rnf8 ubiquitin ligases control foci formation of the Rap80/Abraxas/Brca1/Brcc36 complex in response to DNA damage. Proceedings of the National Academy of Sciences of the United States of America 357 18077395
2006 Mms2-Ubc13 covalently bound to ubiquitin reveals the structural basis of linkage-specific polyubiquitin chain formation. Nature structural & molecular biology 290 16980971
2001 Molecular insights into polyubiquitin chain assembly: crystal structure of the Mms2/Ubc13 heterodimer. Cell 270 11440714
2006 Key function for the Ubc13 E2 ubiquitin-conjugating enzyme in immune receptor signaling. Nature immunology 226 16862162
2006 Human SHPRH is a ubiquitin ligase for Mms2-Ubc13-dependent polyubiquitylation of proliferating cell nuclear antigen. Proceedings of the National Academy of Sciences of the United States of America 200 17108083
2007 A critical role for the ubiquitin-conjugating enzyme Ubc13 in initiating homologous recombination. Molecular cell 188 17349954
2009 The Rap80-BRCC36 de-ubiquitinating enzyme complex antagonizes RNF8-Ubc13-dependent ubiquitination events at DNA double strand breaks. Proceedings of the National Academy of Sciences of the United States of America 184 19202061
2014 miR-205 acts as a tumour radiosensitizer by targeting ZEB1 and Ubc13. Nature communications 155 25476932
2005 Distinct regulation of Ubc13 functions by the two ubiquitin-conjugating enzyme variants Mms2 and Uev1A. The Journal of cell biology 151 16129784
2003 Tumor necrosis factor (TNF)-induced germinal center kinase-related (GCKR) and stress-activated protein kinase (SAPK) activation depends upon the E2/E3 complex Ubc13-Uev1A/TNF receptor-associated factor 2 (TRAF2). The Journal of biological chemistry 149 12591926
2012 The Shigella flexneri effector OspI deamidates UBC13 to dampen the inflammatory response. Nature 147 22407319
2012 Inhibition of proliferation and survival of diffuse large B-cell lymphoma cells by a small-molecule inhibitor of the ubiquitin-conjugating enzyme Ubc13-Uev1A. Blood 130 22791293
2000 UBC13, a DNA-damage-inducible gene, is a member of the error-free postreplication repair pathway in Saccharomyces cerevisiae. Current genetics 128 10794173
2012 Ubc13 maintains the suppressive function of regulatory T cells and prevents their conversion into effector-like T cells. Nature immunology 123 22484734
2001 Noncovalent interaction between ubiquitin and the human DNA repair protein Mms2 is required for Ubc13-mediated polyubiquitination. The Journal of biological chemistry 115 11504715
2007 The human T-cell leukemia virus type 1 Tax oncoprotein requires the ubiquitin-conjugating enzyme Ubc13 for NF-kappaB activation. Journal of virology 100 17942533
2007 Ubiquitin-conjugating enzyme Ubc13 is a critical component of TNF receptor-associated factor (TRAF)-mediated inflammatory responses. Proceedings of the National Academy of Sciences of the United States of America 97 17404240
2014 The ubiquitin-conjugating enzymes UBE2N, UBE2L3 and UBE2D2/3 are essential for Parkin-dependent mitophagy. Journal of cell science 96 24906799
2014 Ubiquitin-conjugating enzyme Ubc13 controls breast cancer metastasis through a TAK1-p38 MAP kinase cascade. Proceedings of the National Academy of Sciences of the United States of America 95 25189770
2014 A small-molecule inhibitor of UBE2N induces neuroblastoma cell death via activation of p53 and JNK pathways. Cell death & disease 93 24556694
2006 Mms2-Ubc13-dependent and -independent roles of Rad5 ubiquitin ligase in postreplication repair and translesion DNA synthesis in Saccharomyces cerevisiae. Molecular and cellular biology 93 16908531
2006 The RING finger protein RNF8 recruits UBC13 for lysine 63-based self polyubiquitylation. Journal of cellular biochemistry 87 16215985
2006 Regulation of p53 localization and activity by Ubc13. Molecular and cellular biology 86 17000756
2003 An NMR-based model of the ubiquitin-bound human ubiquitin conjugation complex Mms2.Ubc13. The structural basis for lysine 63 chain catalysis. The Journal of biological chemistry 85 12569095
2017 Ube2D3 and Ube2N are essential for RIG-I-mediated MAVS aggregation in antiviral innate immunity. Nature communications 81 28469175
2003 The Chfr mitotic checkpoint protein functions with Ubc13-Mms2 to form Lys63-linked polyubiquitin chains. Oncogene 79 14562038
2005 ISG15 modification of Ubc13 suppresses its ubiquitin-conjugating activity. Biochemical and biophysical research communications 75 16112642
2006 Cutting Edge: Pivotal function of Ubc13 in thymocyte TCR signaling. Journal of immunology (Baltimore, Md. : 1950) 73 17114420
2016 Ubc13: the Lys63 ubiquitin chain building machine. Oncotarget 72 27486774
2005 ISG15 modification of ubiquitin E2 Ubc13 disrupts its ability to form thioester bond with ubiquitin. Biochemical and biophysical research communications 71 16122702
2020 The deubiquitinase OTUB1 augments NF-κB-dependent immune responses in dendritic cells in infection and inflammation by stabilizing UBC13. Cellular & molecular immunology 64 32024978
2018 UBE2N Promotes Melanoma Growth via MEK/FRA1/SOX10 Signaling. Cancer research 64 30224375
2014 STAT3 restrains RANK- and TLR4-mediated signalling by suppressing expression of the E2 ubiquitin-conjugating enzyme Ubc13. Nature communications 64 25503582
2012 Molecular insights into the function of RING finger (RNF)-containing proteins hRNF8 and hRNF168 in Ubc13/Mms2-dependent ubiquitylation. The Journal of biological chemistry 64 22589545
2008 Leucettamol A: a new inhibitor of Ubc13-Uev1A interaction isolated from a marine sponge, Leucetta aff. microrhaphis. Bioorganic & medicinal chemistry letters 63 19006668
2012 Molecular basis of Lys-63-linked polyubiquitination inhibition by the interaction between human deubiquitinating enzyme OTUB1 and ubiquitin-conjugating enzyme UBC13. The Journal of biological chemistry 62 22679021
2015 Covalent Inhibition of Ubc13 Affects Ubiquitin Signaling and Reveals Active Site Elements Important for Targeting. ACS chemical biology 61 25909880
2017 Oligomerization-primed coiled-coil domain interaction with Ubc13 confers processivity to TRAF6 ubiquitin ligase activity. Nature communications 56 28993672
2014 hsa-miR-4516 mediated downregulation of STAT3/CDK6/UBE2N plays a role in PUVA induced apoptosis in keratinocytes. Journal of cellular physiology 56 24610393
2018 Legionella pneumophila inhibits immune signalling via MavC-mediated transglutaminase-induced ubiquitination of UBE2N. Nature microbiology 54 30420781
2004 The TRAF6 RING finger domain mediates physical interaction with Ubc13. FEBS letters 52 15147900
2014 UBC13, an E2 enzyme for Lys63-linked ubiquitination, functions in root development by affecting auxin signaling and Aux/IAA protein stability. The Plant journal : for cell and molecular biology 48 25142088
2009 Control of p53 multimerization by Ubc13 is JNK-regulated. Proceedings of the National Academy of Sciences of the United States of America 47 19651615
2019 Legionella pneumophila regulates the activity of UBE2N by deamidase-mediated deubiquitination. The EMBO journal 46 31825121
2019 A tri-ionic anchor mechanism drives Ube2N-specific recruitment and K63-chain ubiquitination in TRIM ligases. Nature communications 44 31582740
2007 Substrate modification with lysine 63-linked ubiquitin chains through the UBC13-UEV1A ubiquitin-conjugating enzyme. The Journal of biological chemistry 43 17709375
2008 Noncanonical E2 variant-independent function of UBC13 in promoting checkpoint protein assembly. Molecular and cellular biology 42 18678647
2005 A single Mms2 "key" residue insertion into a Ubc13 pocket determines the interface specificity of a human Lys63 ubiquitin conjugation complex. The Journal of biological chemistry 41 15749714
2014 Ubiquitin-conjugating enzyme complex Uev1A-Ubc13 promotes breast cancer metastasis through nuclear factor-кB mediated matrix metalloproteinase-1 gene regulation. Breast cancer research : BCR 40 25022892
2003 Energetics and specificity of interactions within Ub.Uev.Ubc13 human ubiquitin conjugation complexes. Biochemistry 39 12834344
2021 The lncRNA 'UCA1' modulates the response to chemotherapy of ovarian cancer through direct binding to miR-27a-5p and control of UBE2N levels. Molecular oncology 38 34160887
2021 TRIM11 suppresses ferritinophagy and gemcitabine sensitivity through UBE2N/TAX1BP1 signaling in pancreatic ductal adenocarcinoma. Journal of cellular physiology 35 33629745
2017 RNF8/UBC13 ubiquitin signaling suppresses synapse formation in the mammalian brain. Nature communications 35 29097665
2010 Rad8Rad5/Mms2-Ubc13 ubiquitin ligase complex controls translesion synthesis in fission yeast. The EMBO journal 35 20453833
2016 RNF8 E3 Ubiquitin Ligase Stimulates Ubc13 E2 Conjugating Activity That Is Essential for DNA Double Strand Break Signaling and BRCA1 Tumor Suppressor Recruitment. The Journal of biological chemistry 34 26903517
2011 TR-FRET-based high-throughput screening assay for identification of UBC13 inhibitors. Journal of biomolecular screening 33 22034497
2018 The inhibition of UBC13 expression and blockage of the DNMT1-CHFR-Aurora A pathway contribute to paclitaxel resistance in ovarian cancer. Cell death & disease 32 29367628
2022 Blocking UBE2N abrogates oncogenic immune signaling in acute myeloid leukemia. Science translational medicine 31 35263148
2002 Roles of mouse UBC13 in DNA postreplication repair and Lys63-linked ubiquitination. Gene 31 12039045
2021 Ubc13 Promotes K63-Linked Polyubiquitination of NLRP3 to Activate Inflammasome. Journal of immunology (Baltimore, Md. : 1950) 30 33893171
2009 The ubiquitin ligase Triad1 inhibits myelopoiesis through UbcH7 and Ubc13 interacting domains. Leukemia 29 19340006
2020 Legionella effector MavC targets the Ube2N~Ub conjugate for noncanonical ubiquitination. Nature communications 28 32398758
2009 Regulation of hematopoiesis by the K63-specific ubiquitin-conjugating enzyme Ubc13. Proceedings of the National Academy of Sciences of the United States of America 28 19926860
2017 MicroRNA miR-147b promotes tumor growth via targeting UBE2N in hepatocellular carcinoma. Oncotarget 27 29371970
2012 Ubc13 and COOH terminus of Hsp70-interacting protein (CHIP) are required for growth hormone receptor endocytosis. The Journal of biological chemistry 27 22433856
2019 Inhibition of UBE2N-dependent CDK6 protein degradation by miR-934 promotes human bladder cancer cell growth. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 26 31373842
2014 Aged monkey brains reveal the role of ubiquitin-conjugating enzyme UBE2N in the synaptosomal accumulation of mutant huntingtin. Human molecular genetics 26 25343992
2021 Immune regulator LGP2 targets Ubc13/UBE2N to mediate widespread interference with K63 polyubiquitination and NF-κB activation. Cell reports 25 34965427
2007 Characterization of a UBC13 kinase in Plasmodium falciparum. Proceedings of the National Academy of Sciences of the United States of America 25 17452636
2007 Yeast Chfr homologs retard cell cycle at G1 and G2/M via Ubc4 and Ubc13/Mms2-dependent ubiquitination. Cell cycle (Georgetown, Tex.) 25 18202552
2018 Uev1A-Ubc13 promotes colorectal cancer metastasis through regulating CXCL1 expression via NF-кB activation. Oncotarget 23 29662619
2016 Inhibition of Ubc13-mediated Ubiquitination by GPS2 Regulates Multiple Stages of B Cell Development. The Journal of biological chemistry 22 28039360
2013 Structural basis for the recognition of Ubc13 by the Shigella flexneri effector OspI. Journal of molecular biology 22 23542009
2013 Complex structure of OspI and Ubc13: the molecular basis of Ubc13 deamidation and convergence of bacterial and host E2 recognition. PLoS pathogens 21 23633953
2013 Proteasome inhibition promotes Parkin-Ubc13 interaction and lysine 63-linked ubiquitination. PloS one 21 24023840
2017 Uev1A-Ubc13 catalyzes K63-linked ubiquitination of RHBDF2 to promote TACE maturation. Cellular signalling 20 29069608
2013 Helicobacter pylori activates NF-κB by inducing Ubc13-mediated ubiquitination of lysine 158 of TAK1. Journal of cellular biochemistry 20 23606331
2021 UBC13 is an RNF213-associated E2 ubiquitin-conjugating enzyme, and Lysine 63-linked ubiquitination by the RNF213-UBC13 axis is responsible for angiogenic activity. FASEB bioAdvances 18 33842849
2012 Rice UBC13, a candidate housekeeping gene, is required for K63-linked polyubiquitination and tolerance to DNA damage. Rice (New York, N.Y.) 18 27234244
2020 UBC13-Mediated Ubiquitin Signaling Promotes Removal of Blocking Adducts from DNA Double-Strand Breaks. iScience 17 32283528
2023 SET7 methylates the deubiquitinase OTUB1 at Lys 122 to impair its binding to E2 enzyme UBC13 and relieve its suppressive role on ferroptosis. The Journal of biological chemistry 16 36822329
2019 Deamidation disrupts native and transient contacts to weaken the interaction between UBC13 and RING-finger E3 ligases. eLife 16 31638574
2016 Three Brachypodium distachyon Uev1s Promote Ubc13-Mediated Lys63-Linked Polyubiquitination and Confer Different Functions. Frontiers in plant science 16 27803708
2011 The roles of PCNA SUMOylation, Mms2-Ubc13 and Rad5 in translesion DNA synthesis in Saccharomyces cerevisiae. Molecular microbiology 16 21362066
2020 Ubc13-Mms2 cooperates with a family of RING E3 proteins in budding yeast membrane protein sorting. Journal of cell science 15 32265276
2011 MDC1 is ubiquitylated on its tandem BRCT domain and directly binds RAP80 in a UBC13-dependent manner. DNA repair 15 21622030
2024 Suppressing UBE2N ameliorates Alzheimer's disease pathology through the clearance of amyloid beta. Alzheimer's & dementia : the journal of the Alzheimer's Association 14 39015037
2023 ALDOC promotes non-small cell lung cancer through affecting MYC-mediated UBE2N transcription and regulating Wnt/β-catenin pathway. Aging 14 37724906
2020 UBE2N Regulates Paclitaxel Sensitivity of Ovarian Cancer via Fos/P53 Axis. OncoTargets and therapy 14 33363381
2024 UBE2N promotes cell viability and glycolysis by promoting Axin1 ubiquitination in prostate cancer cells. Biology direct 13 38715121
2021 Functional interaction of ubiquitin ligase RNF167 with UBE2D1 and UBE2N promotes ubiquitination of AMPA receptor. The FEBS journal 13 33650289
2018 Structure of LNX1:Ubc13~Ubiquitin Complex Reveals the Role of Additional Motifs for the E3 Ligase Activity of LNX1. Journal of molecular biology 13 29496391
2014 The endoplasmic reticulum adaptor protein ERAdP initiates NK cell activation via the Ubc13-mediated NF-κB pathway. Journal of immunology (Baltimore, Md. : 1950) 13 25548215
2022 S-Nitrosylation of OTUB1 Alters Its Stability and Ubc13 Binding. ACS chemical neuroscience 12 35500217
2018 A novel requirement for ubiquitin-conjugating enzyme UBC-13 in retrograde recycling of MIG-14/Wntless and Wnt signaling. Molecular biology of the cell 12 29927348
2016 Molecular Cloning and Functional Characterization of Two Brachypodium distachyon UBC13 Genes Whose Products Promote K63-Linked Polyubiquitination. Frontiers in plant science 12 26779244
2010 E2 Polyubiquitin-conjugating enzyme Ubc13 in keratinocytes is essential for epidermal integrity. The Journal of biological chemistry 12 20663875
2021 FAM177A1 Inhibits IL-1β-Induced Signaling by Impairing TRAF6-Ubc13 Association. Journal of immunology (Baltimore, Md. : 1950) 11 34799425
2018 Structural insights into the nanomolar affinity of RING E3 ligase ZNRF1 for Ube2N and its functional implications. The Biochemical journal 11 29626159
2025 Ubiquitin-conjugating enzyme UBE2N modulates proteostasis in immunoproteasome-positive acute myeloid leukemia. The Journal of clinical investigation 9 40371639

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