Affinage

UBE2S

Ubiquitin-conjugating enzyme E2 S · UniProt Q16763

Length
222 aa
Mass
23.8 kDa
Annotated
2026-06-10
61 papers in source corpus 35 papers cited in narrative 36 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

UBE2S is a ubiquitin-conjugating (E2) enzyme that specializes in elongating Lys11 (K11)-linked polyubiquitin chains, acting principally as the chain-elongating partner of the APC/C E3 ligase to drive proteasomal turnover of cell-cycle regulators (PMID:19820702, PMID:20080579). Working downstream of the priming E2s UBCH10/UBCH5, UBE2S extends K11-linked chains whose linkage specificity is dictated by UBE2S itself and is required for substrate degradation and mitotic exit following spindle-assembly-checkpoint arrest (PMID:19820702, PMID:20080579); in a reciprocal step, UBE2S feeds back to directly stimulate the APC/C, enhancing UBE2C-dependent substrate priming and coordinating the two-step chain-building reaction (PMID:32393902). The biological importance of this APC/C-coupled activity is demonstrated in vivo, where oocyte-specific loss of UBE2S impairs APC/C function, stabilizes Cyclin B1 and securin, and arrests meiosis I (PMID:38546043). Beyond mitosis, UBE2S and the E3 RNF8 generate K11-linked ubiquitin on damaged chromatin (including H2A/H2AX) in an ATM-dependent manner to mediate DNA-damage-induced transcriptional silencing (PMID:28525740), and the APC/C–UBE2S axis K11-ubiquitinates BRCA1 via a Cdh1-recognized degron, an event reversed by the deubiquitinase Cezanne (PMID:41359628). Structurally, catalysis depends on a trans donor-ubiquitin interface formed with a covalent UBE2S~ubiquitin conjugate (PMID:26828794), and activity is autoregulated: intramolecular autoubiquitination at the Lys+5 acceptor site adjacent to the active-site cysteine blocks ubiquitin reloading and autoinhibits the enzyme (PMID:31230944), while a lysine-rich C-terminal extension drives an autoinhibited dimer that is required for APC/C recruitment and protects UBE2S from rapid turnover (PMID:33082289). UBE2S also acts independently of the APC/C, elongating E3-independent K11-linked chains on pVHL to target it for degradation and thereby stabilize HIF-1α (PMID:16819549, PMID:38915206). The enzyme is recurrently overexpressed in cancers, where its expression is driven by transcription factors and signaling inputs and where it K11-ubiquitinates a range of substrates including p27, Sox2, and β-catenin (PMID:33589597, PMID:26292759, PMID:35637955).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 2006 High

    Established the first defined substrate of UBE2S by showing it ubiquitinates the tumor suppressor pVHL, linking the enzyme to HIF-1α stabilization independently of any later cell-cycle role.

    Evidence Co-IP plus in vitro and in vivo ubiquitination assays with overexpression/knockdown in cells

    PMID:16819549

    Open questions at the time
    • Did not define the ubiquitin chain linkage on pVHL
    • E3 dependence of the reaction not resolved at this stage
  2. 2008 Medium

    Connected UBE2S expression to growth-factor signaling, showing Egr-1 and SRF transcriptionally drive UCP/UBE2S to raise HIF-1α via the pVHL axis.

    Evidence Promoter deletion, EMSA, ChIP and siRNA of Egr-1/SRF in cells

    PMID:18780286

    Open questions at the time
    • Transcriptional control in normal physiology versus cancer not distinguished
    • Does not address post-translational regulation of the enzyme
  3. 2009 High

    Defined the core mitotic function: UBE2S elongates chains on APC/C substrates pre-primed by UBCH10/UBCH5 to promote substrate degradation and mitotic exit after prolonged SAC arrest.

    Evidence RNAi screen, in vitro chain-elongation assay, epistasis via BUBR1 depletion and Aurora-B inhibition

    PMID:19820702

    Open questions at the time
    • Chain linkage type not yet assigned
    • Mechanism of APC/C recruitment unresolved
  4. 2010 High

    Assigned the linkage specificity, establishing that UBE2S builds K11-linked chains and that this linkage is essential for APC/C substrate degradation.

    Evidence Single-lysine substrate topology assay, APC/C co-purification, dominant-negative UBE2S in cell-cycle extracts

    PMID:20080579

    Open questions at the time
    • Structural basis of K11 selectivity not defined here
    • Substrate range beyond APC/C clients not addressed
  5. 2015 Medium

    Extended UBE2S beyond mitotic degradation to stem-cell fate control by showing K11 ubiquitination of Sox2 at K123 tunes pluripotency.

    Evidence Linkage- and site-specific ubiquitination assays, proteasome inhibition, ES-cell differentiation assays

    PMID:26292759

    Open questions at the time
    • E3 ligase partner for Sox2 not identified
    • Single-lab finding without independent replication
  6. 2015 Medium

    Demonstrated a requirement for UBE2S (with UBE2C) in oocyte meiosis, implicating it in the first meiotic cytokinesis and spindle formation.

    Evidence siRNA/mRNA microinjection in mouse oocytes with live imaging and polar-body extrusion assays

    PMID:26207029

    Open questions at the time
    • Did not separate UBE2S-specific from UBE2C-specific contributions
    • Substrate-level mechanism not resolved
  7. 2016 High

    Provided the structural view of catalysis, capturing the trans donor-ubiquitin interface of a covalent UBE2S~ubiquitin conjugate.

    Evidence X-ray crystallography with MD validation and mutational consistency

    PMID:26828794

    Open questions at the time
    • Acceptor ubiquitin positioning not captured
    • Does not explain regulation of activity in cells
  8. 2016 Medium

    Identified upstream regulation, showing AKT1 phosphorylates UBE2S at Thr152 to stabilize it and linking UBE2S to NHEJ repair via Ku70.

    Evidence Co-IP, phosphorylation assay, Thr152 mutagenesis, DSB recruitment and NHEJ repair assays

    PMID:27593939

    Open questions at the time
    • Ubiquitination target within NHEJ not defined
    • Direct enzymatic role at DSBs versus scaffolding unclear
  9. 2019 High

    Revealed an autoinhibitory mechanism in which intramolecular autoubiquitination at the Lys+5 site adjacent to the catalytic cysteine blocks ubiquitin reloading.

    Evidence Crystal structure, MD, NMR, quantitative MS, and siRNA-rescue experiments

    PMID:31230944

    Open questions at the time
    • How autoubiquitination is reversed during mitotic exit not defined
    • Cellular enzymes controlling this modification unknown
  10. 2020 High

    Uncovered a feedback loop in which the elongating E2 UBE2S directly stimulates the APC/C to enhance UBE2C-dependent priming, coordinating two-step chain assembly.

    Evidence In vitro APC/C reconstitution with UBE2C and UBE2S plus cell-based assays

    PMID:32393902

    Open questions at the time
    • Structural basis of APC/C stimulation not defined
    • In vivo significance of the feedback loop not tested
  11. 2020 High

    Showed that the lysine-rich C-terminal extension drives an autoinhibited dimer required for APC/C recruitment and protection from rapid turnover.

    Evidence NMR, SEC, mutagenesis, co-IP, mitotic-slippage assays and quantitative proteomics

    PMID:33082289

    Open questions at the time
    • Trigger for dimer-to-active monomer transition unresolved
    • Relationship between dimerization and Lys+5 autoinhibition not integrated
  12. 2017 High

    Linked UBE2S to the DNA-damage response by showing UBE2S with RNF8 generates K11 ubiquitin on damaged chromatin for ATM-dependent transcriptional silencing.

    Evidence Linkage-specific ubiquitination assays, siRNA depletion, ATM-inhibition epistasis, transcriptional silencing readouts

    PMID:28525740

    Open questions at the time
    • Reader of chromatin K11 chains not identified
    • Relationship to APC/C-independent activity at DSBs unclear
  13. 2024 High

    Provided in vivo genetic validation of the APC/C-coupled function, showing UBE2S loss arrests oocyte meiosis I by stabilizing Cyclin B1 and securin.

    Evidence Conditional knockout mice, live imaging, immunofluorescence and Western blot for APC/C substrates

    PMID:38546043

    Open questions at the time
    • Somatic-cell consequences of knockout not addressed here
    • Embryonic lethality mechanism beyond meiosis not dissected
  14. 2025 High

    Connected the APC/C–UBE2S axis to genome stability by showing it K11-ubiquitinates BRCA1 through a Cdh1-recognized degron, with Cezanne reversing the mark to control PARPi sensitivity.

    Evidence K11-linkage-specific assays, Cezanne KO, Cdh1 co-IP, cell-cycle fractionation and PARPi sensitivity assays

    PMID:41359628

    Open questions at the time
    • Cell-cycle window of BRCA1 turnover not fully mapped
    • Therapeutic implications beyond PARPi not established
  15. 2024 Medium

    Defined the molecular detail of E3-independent pVHL ubiquitination, mapping K11 chains to VHL K171/K196 and linking VHL degradation to HIF-1α-driven glycolysis.

    Evidence In vitro E3-independent ubiquitination with site- and linkage-specific mutants, ChIP for E2F2, transcriptomics/metabolomics

    PMID:38915206

    Open questions at the time
    • Whether E3-independence holds in all cell contexts unresolved
    • Single-lab mechanism

Open questions

Synthesis pass · forward-looking unresolved questions
  • How UBE2S selects its broad, context-dependent substrate repertoire in cancers and whether the many reported APC/C-independent substrates share a common recruitment logic remains unresolved.
  • Most cancer-context substrates rest on single-lab co-IP/ubiquitination assays without reconstitution
  • No unifying mechanism explains E3-dependent versus E3-independent substrate engagement
  • Some reports assign opposing oncogenic versus tumor-suppressive roles in different tissues

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 5 GO:0016874 ligase activity 3 GO:0031386 protein tag activity 2
Localization
GO:0005634 nucleus 2 GO:0005694 chromosome 2
Pathway
R-HSA-1640170 Cell Cycle 4 R-HSA-392499 Metabolism of proteins 3 R-HSA-1474165 Reproduction 2 R-HSA-73894 DNA Repair 2
Partners
KU70RNF8TRIM21TRIM28UBE2CUSP15VHL
Complex memberships
APC/C

Evidence

Reading pass · 36 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2009 UBE2S elongates ubiquitin chains on APC/C substrates that were pre-ubiquitinated by E2 enzymes UBCH10 and UBCH5, enhancing proteasomal degradation of APC/C substrates and promoting mitotic exit after prolonged spindle-assembly checkpoint (SAC) activation. UBE2S depletion prolongs drug-induced mitotic arrest and prevents degradation of APC/C substrates; bypassing the SAC via BUBR1 depletion or Aurora-B inhibition negates the requirement for UBE2S. RNAi screen, in vitro ubiquitin chain elongation assay, epistasis via BUBR1 depletion and Aurora-B inhibition Nature cell biology High 19820702
2010 UBE2S/E2-EPF drives elongation of K11-linked polyubiquitin chains on APC/C substrates after initial priming by UbcH10 or UbcH5. K11 linkage specificity is determined by UBE2S and is essential for substrate degradation. UBE2S co-purifies with APC/C, and dominant-negative UBE2S slows APC/C substrate degradation in cell-cycle extracts. Single-lysine substrate topology assay, co-purification with APC/C, dominant-negative UBE2S in functional cell-cycle extracts Proceedings of the National Academy of Sciences of the United States of America High 20080579
2006 E2-EPF UCP (UBE2S) associates with and ubiquitinates pVHL (von Hippel-Lindau tumor suppressor), targeting it for proteasomal degradation, thereby stabilizing HIF-1α. This was demonstrated in cell-based ubiquitination assays and in vitro. Co-immunoprecipitation, in vitro and in vivo ubiquitination assay, overexpression/knockdown functional studies Nature medicine High 16819549
2021 UBE2S interacts with TRIM28 in the nucleus and together they enhance K11-linked ubiquitination of p27, facilitating p27 degradation and accelerating G1/S cell cycle progression in hepatocellular carcinoma cells. Co-immunoprecipitation, ubiquitination assay, overexpression/knockdown functional assays, in vivo tumor models Signal transduction and targeted therapy Medium 33589597
2018 Ube2s modifies β-Catenin at K19 via K11-linked polyubiquitin chains, antagonizing β-TrCP-mediated β-Catenin degradation and thereby stabilizing β-Catenin, promoting its cellular accumulation, and activating the Wnt/β-Catenin pathway. Ubiquitination assay with linkage-specific ubiquitin mutants, site-directed mutagenesis of β-Catenin K19, overexpression/knockdown studies Cell death & disease Medium 29674637
2017 Ube2S and RNF8 E3 ligase are responsible for K11-linked ubiquitination on damaged chromatin, including histone H2A/H2AX, in an ATM-dependent manner. This K11-linkage modification plays a role in DNA damage-induced transcriptional silencing, distinct from K63-linked ubiquitin which recruits 53BP1 and BRCA1. Linkage-specific ubiquitination assays, siRNA depletion, epistasis with ATM inhibition, functional transcriptional silencing assays Molecular cell High 28525740
2016 Akt1 physically interacts with and phosphorylates UBE2S at Thr152, enhancing UBE2S stability by inhibiting its proteasomal degradation. UBE2S associates with Ku70 and components of the non-homologous end-joining (NHEJ) complex and participates in NHEJ-mediated DNA double-strand break repair; the UBE2S–Ku70 complex is recruited to DSB sites in response to etoposide treatment. Co-immunoprecipitation, phosphorylation assay, site-directed mutagenesis (Thr152), DSB recruitment assay, NHEJ repair assay with UBE2S knockdown Oncogene Medium 27593939
2023 UBE2S interacts with TRIM21 and together they induce K11-linked (not K48- or K63-linked) polyubiquitination of LPP (lipoma preferred partner), promoting its degradation and facilitating lymphatic metastasis of bladder cancer. LPP silencing rescued the anti-metastatic phenotypes of UBE2S knockdown. Co-immunoprecipitation, linkage-specific ubiquitination assays, siRNA rescue experiments, in vivo lymphatic metastasis model Cell death & disease Medium 37422473
2018 UBE2S enhances K11-linked ubiquitination of p53 protein, facilitating its proteasomal degradation in hepatocellular carcinoma cells. Ubiquitination assay, overexpression/knockdown, p53 rescue experiments Biochemical and biophysical research communications Low 29928880
2015 Ube2s mediates K11-linked polyubiquitin chain formation on Sox2 at the K123 residue, marking Sox2 for proteasome-mediated degradation, thereby fine-tuning Sox2 levels and reinforcing the self-renewing state of embryonic stem cells while repressing neural ectodermal differentiation. Ubiquitination assay with linkage-specific and site-specific mutants (K123), proteasome inhibitor experiments, overexpression/knockdown functional assays in ES cells Cell death and differentiation Medium 26292759
2020 UBE2S feeds back on the APC/C to directly stimulate the E3 ligase for substrate priming, thereby promoting substrate ubiquitination by UBE2C (the priming E2). The chain-elongating E2 UBE2S thus activates the APC/C to coordinate the two-step ubiquitin chain formation process. In vitro reconstitution of APC/C ubiquitination, biochemical stimulation assays with UBE2C and UBE2S, functional cell-based assays Nature structural & molecular biology High 32393902
2019 UBE2S undergoes intramolecular autoubiquitination at Lys+5 (an acceptor site adjacent to the active-site cysteine), and this K+5-linked ubiquitin inhibits UBE2S by obstructing its reloading with ubiquitin. This autoubiquitination event decreases during mitotic exit but does not influence proteasomal turnover of UBE2S. Crystal structure of UBE2S catalytic domain, MD simulations, NMR showing steric obstruction, immunoprecipitation, quantitative mass spectrometry, siRNA-and-rescue experiments Structure (London, England : 1993) High 31230944
2016 Crystal structure of a covalent Ube2S–ubiquitin conjugate was determined, revealing the interface between Ube2S and the donor ubiquitin in trans; this hydrophobic crystallographic interface is stable in MD simulations and consistent with prior mutational effects. X-ray crystallography, molecular dynamics simulations PloS one High 26828794
2020 UBE2S forms an autoinhibited dimer via a catalytically critical ubiquitin binding site blocked by dimerization. The lysine-rich C-terminal extension of UBE2S stimulates dimerization and is required both for APC/C recruitment and for autoubiquitination as substrate becomes limiting. Dimerization-deficient UBE2S turns over more rapidly in cells and does not promote mitotic slippage during prolonged drug-induced mitotic arrest. NMR, size-exclusion chromatography, mutagenesis, co-immunoprecipitation, cell-based mitotic slippage assay, quantitative proteomics Science signaling High 33082289
2016 SAG/RBX2 preferentially binds E2 enzymes UBCH10 and UBE2S (K11-linkage mediators) rather than CDC34/UBCH5C (K48-linkage mediators), and SAG-CUL5 promotes K11-linked ubiquitylation of β-TrCP1 for its degradation. Silencing either UBCH10 or UBE2S, but not UBCH5C, caused accumulation of endogenous β-TrCP1. Co-immunoprecipitation, in vitro ubiquitination assay, siRNA knockdown of individual E2s, protein stability assay Scientific reports Medium 27910872
2016 E2-EPF UCP (UBE2S) possesses E3 ubiquitin ligase activity in addition to its E2 activity, operating via its Cys118 residue. Ubiquitin transfer from Cys95 to Cys118 by trans-thiolation enables polyubiquitin chain formation at Cys118; the UCPC118A mutant cannot form polyubiquitin chains. UCP elongates E3-independent polyubiquitin chains on pVHL at K159, K171, and K196, with K11 being the primary linkage but also involving K6, K48, and K63 for autoubiquitination. UCP self-association occurs through the UBC domain. In vitro ubiquitination assay with Cys and Lys mutants, trans-thiolation assay, co-immunoprecipitation PloS one Medium 27685940
2008 Transcription factors Egr-1 and SRF bind to the E2-EPF UCP (UBE2S) promoter and drive its expression in response to EGF/growth factors and serum, respectively. Egr-1- and SRF-induced UCP expression increases HIF-1α protein under non-hypoxic conditions via the UCP–pVHL axis. Promoter deletion assay, electrophoretic mobility shift assay (EMSA), chromatin immunoprecipitation (ChIP), siRNA knockdown of Egr-1/SRF, overexpression studies Journal of cellular biochemistry Medium 18780286
2015 E2-EPF UCP (UBE2S) directly ubiquitinates three pVHL missense mutants (V155A, L158Q, Q164R) in vitro; the mutant pVHLs interact with UCP directly. Elimination of all pVHL lysine residues confers resistance to ubiquitination and increases stability. UCP depletion restores mutant pVHL levels and inhibits cell growth. In vitro ubiquitination assay, co-immunoprecipitation, lysine-null pVHL mutant stability assay, adenovirus-mediated shUCP in vivo xenograft BMC cancer Medium 26503325
2019 HBV X protein (HBx) binds UCP (UBE2S) specifically and forms a ternary complex with UCP and pVHL. HBx inhibits self-ubiquitination of UCP but enhances UCP-mediated pVHL ubiquitination, resulting in stabilization of HIF-1α and HIF-2α. HBx and UCP stabilize each other by mutually inhibiting their ubiquitination. Co-immunoprecipitation, in vitro ubiquitination assay, HBx transgenic mouse model Cellular and molecular life sciences : CMLS Medium 30903204
2021 UBE2S is transcriptionally activated by FOXM1 binding to the UBE2S promoter. UBE2S promotes ubiquitination of PTEN at Lys60 and Lys327, facilitating PTEN degradation and thereby promoting AKT phosphorylation and chemoresistance in hepatocellular carcinoma. ChIP assay (FOXM1 on UBE2S promoter), in vitro ubiquitination assay with site-specific PTEN mutants (K60R, K327R), AKT inhibitor rescue experiments Cell death discovery Medium 34785642
2024 UBE2S enhances K11-linked polyubiquitination of VHL at K171 and K196 independently of an E3 ligase, promoting VHL degradation by the proteasome and thereby indirectly stabilizing HIF-1α and activating glycolysis in hepatocellular carcinoma. E2F2 transcriptionally upregulates UBE2S expression by directly binding its promoter. In vitro E3-independent ubiquitination assay with K171R/K196R VHL mutants, linkage-specific ubiquitin mutants, ChIP for E2F2, transcriptomic and metabolomics analysis Clinical and molecular hepatology Medium 38915206
2021 UBE2S directly binds IκBα (non-canonical, IKK-independent manner) as shown by immunoprecipitation, GST pull-down, and in vitro binding assays; UBE2S binding to IκBα reduces IκBα protein levels and activates NF-κB signaling, promoting EMT and metastasis of lung adenocarcinoma cells. Co-immunoprecipitation, GST pull-down, in vitro binding assay, luciferase NF-κB reporter, zebrafish xenograft model Cellular oncology (Dordrecht, Netherlands) Medium 34582005
2022 UBE2S degrades p16INK4a (p16) via K11-linked (not K48- or K63-linked) ubiquitination, accelerating G1/S transition in prostate cancer cells. UBE2S also stabilizes β-catenin via K11-linked ubiquitination, enhancing migration and invasion. Both activities contribute to bone metastasis. Linkage-specific ubiquitination assay with K11R/K48R/K63R ubiquitin mutants, co-immunoprecipitation, in vivo bone metastasis model, pharmacological inhibition International journal of biological sciences Medium 35637955
2024 UBE2S interacts with USP15 and recruits it to facilitate removal of K11-linked ubiquitination on AKIP1, thereby stabilizing AKIP1, which in turn enhances NF-κB transcriptional activity and promotes glioblastoma progression. Yeast two-hybrid, co-immunoprecipitation, laser confocal microscopy (co-localization), dual luciferase reporter for NF-κB, in vitro and in vivo functional assays International journal of biological macromolecules Medium 39098687
2024 UBE2S knockout in mouse oocytes causes meiosis I arrest with normal spindle assembly checkpoint dynamics. UBE2S loss impairs APC/C activity, leading to persistently high levels of Cyclin B1 and securin, resulting in failure of homologous chromosome separation. Fertilized UBE2S-null oocytes can implant but embryos die before embryonic day 10.5. Conditional knockout mouse model, live imaging, immunofluorescence, Western blot for APC/C substrates (Cyclin B1, securin) Development (Cambridge, England) High 38546043
2015 Depletion of Ube2C, Ube2S, and Ube2D3 reduces completion of the first meiotic cytokinesis by 50% in mouse oocytes; overexpression doubles and accelerates first polar body extrusion. High Ube2C overexpression drives resumption of meiosis I regardless of spindle formation, overriding the spindle assembly checkpoint. Ube2C and Ube2S also control spindle formation. siRNA/mRNA microinjection in mouse oocytes, live-cell imaging, first polar body extrusion assay FASEB journal Medium 26207029
2025 APC/C and Ube2S mediate K11-linked ubiquitination of BRCA1 in a cell cycle-dependent manner through a degron on BRCA1 recognized by APC/C cofactor Cdh1. The deubiquitinase Cezanne counteracts this modification by removing K11-linked ubiquitin from BRCA1, thereby stabilizing BRCA1. Cezanne deficiency leads to increased BRCA1 K11-ubiquitination, decreased BRCA1 protein, and increased sensitivity to PARPi. K11-linkage-specific ubiquitination assays, Cezanne KO, co-immunoprecipitation with Cdh1, cell cycle fractionation, PARPi sensitivity assay PLoS biology High 41359628
2021 UBE2S knockdown inhibited NHEJ-mediated DSB repair and sensitized glioblastoma cells to etoposide. The UBE2S–Ku70 complex is specifically recruited to double-strand break sites in response to etoposide treatment. Co-immunoprecipitation, chromatin recruitment assay at DSBs, NHEJ repair assay, drug sensitivity assay with UBE2S knockdown Oncogene Medium 27593939
2017 UBE2S knockdown in oral squamous cell carcinoma (OSCC) cells increased P21 protein levels due to lower APC3 (E3) activity, and caused G2/M arrest, indicating UBE2S-dependent promotion of P21 degradation via the ubiquitin-proteasome system through the APC/C. shRNA knockdown, flow cytometry, Western blot for P21 and APC3 Biochemical and biophysical research communications Low 28257844
2023 UBE2S directly targets RPL26 for ubiquitination and proteasomal degradation; RPL26 degradation by UBE2S upregulates c-Myc, enhancing NSCLC cell proliferation, migration, and stemness. Immunoprecipitation combined with mass spectrometry to identify RPL26 as substrate, ubiquitination assay, overexpression/knockdown, xenograft American journal of cancer research Medium 37693154
2021 UBE2S directly targets TSC1 for ubiquitin-mediated degradation, resulting in activation of the mTORC1 pathway and promotion of urinary bladder cancer progression. Co-immunoprecipitation, ubiquitination assay, gain/loss-of-function experiments, in vivo xenograft, MG132 proteasome inhibitor rescue Biochemical and biophysical research communications Medium 34520980
2025 STAT3 (downstream of IL-6 signaling) transcriptionally upregulates UBE2S expression, and UBE2S promotes ubiquitin-mediated degradation of NKp30 in NK cells, leading to NK cell dysfunction in NSCLC. In vitro IL-6 stimulation, STAT3 inhibition, UBE2S knockdown/overexpression, NKp30 ubiquitination assay, functional NK cell assay NPJ precision oncology Medium 41254082
2025 UBE2S interacts with USP10 and mediates K48-linked deubiquitination of GLUT1 through USP10, stabilizing GLUT1 protein and enhancing glycolytic activity in endometriosis stromal cells; this leads to lactate accumulation promoting M2 macrophage polarization and fibrosis. IP-MS to identify GLUT1 and USP10 as UBE2S interactors, co-immunoprecipitation, K48-linkage ubiquitination assay, glycolysis assay, macrophage polarization assay Journal of translational medicine Low 41351058
2022 UBE2S knockout by CRISPR/Cas9 inhibits ubiquitination and degradation of p53 in gastric cancer cells, leading to upregulation of FAS and activation of the FAS-mediated apoptotic pathway. CRISPR/Cas9 knockout, RNA-seq, quantitative proteomics (TMT), ubiquitination assay, FAS expression correlation Experimental cell research Medium 35863455
2025 UBE2S promotes ubiquitination and degradation of TRAF6, an upstream activator of both MAPK/ERK and PI3K/AKT pathways, thereby inhibiting colorectal cancer cell proliferation (tumor-suppressive role in this context). This ubiquitination was blocked by proteasome inhibitor MG132. Overexpression/knockdown, co-immunoprecipitation, ubiquitination assay, MG132 treatment, RNA sequencing, in vivo xenograft Scientific reports Low 41083491
2024 NSUN2 RNA methyltransferase stabilizes UBE2S mRNA through m5C modification in an m5C-dependent manner, increasing UBE2S protein levels. UBE2S in turn interacts with and ubiquitinates β-catenin, enhancing its stability and promoting osteosarcoma metastasis. RNA-seq correlation, m5C-specific RNA immunoprecipitation, UBE2S mRNA stability assay, co-immunoprecipitation of UBE2S with β-catenin, ubiquitination assay, rescue experiments Cellular signalling Low 40819747

Source papers

Stage 0 corpus · 61 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2009 UBE2S elongates ubiquitin chains on APC/C substrates to promote mitotic exit. Nature cell biology 223 19820702
2010 UBE2S drives elongation of K11-linked ubiquitin chains by the anaphase-promoting complex. Proceedings of the National Academy of Sciences of the United States of America 203 20080579
2006 E2-EPF UCP targets pVHL for degradation and associates with tumor growth and metastasis. Nature medicine 106 16819549
2021 UBE2S interacting with TRIM28 in the nucleus accelerates cell cycle by ubiquitination of p27 to promote hepatocellular carcinoma development. Signal transduction and targeted therapy 77 33589597
2018 Ube2s stabilizes β-Catenin through K11-linked polyubiquitination to promote mesendoderm specification and colorectal cancer development. Cell death & disease 63 29674637
2017 Dietary flavonoids, luteolin and quercetin, inhibit invasion of cervical cancer by reduction of UBE2S through epithelial-mesenchymal transition signaling. Food & function 60 28277581
2017 RNF8- and Ube2S-Dependent Ubiquitin Lysine 11-Linkage Modification in Response to DNA Damage. Molecular cell 55 28525740
2016 UBE2S, a novel substrate of Akt1, associates with Ku70 and regulates DNA repair and glioblastoma multiforme resistance to chemotherapy. Oncogene 51 27593939
2023 UBE2S interacting with TRIM21 mediates the K11-linked ubiquitination of LPP to promote the lymphatic metastasis of bladder cancer. Cell death & disease 48 37422473
2018 UBE2S enhances the ubiquitination of p53 and exerts oncogenic activities in hepatocellular carcinoma. Biochemical and biophysical research communications 48 29928880
2015 Ube2s regulates Sox2 stability and mouse ES cell maintenance. Cell death and differentiation 48 26292759
2007 The ubiquitin-conjugating enzyme E2-EPF is overexpressed in primary breast cancer and modulates sensitivity to topoisomerase II inhibition. Neoplasia (New York, N.Y.) 46 17710163
2015 UBE2S is associated with malignant characteristics of breast cancer cells. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 42 26245992
2022 UBE2S as a novel ubiquitinated regulator of p16 and β-catenin to promote bone metastasis of prostate cancer. International journal of biological sciences 38 35637955
2016 SAG/RBX2 E3 ligase complexes with UBCH10 and UBE2S E2s to ubiquitylate β-TrCP1 via K11-linkage for degradation. Scientific reports 37 27910872
2011 Deregulation of E2-EPF ubiquitin carrier protein in papillary renal cell carcinoma. The American journal of pathology 36 21281817
2019 UBE2S mediates tumor progression via SOX6/β-Catenin signaling in endometrial cancer. The international journal of biochemistry & cell biology 35 30690078
2021 UBE2S promotes cell chemoresistance through PTEN-AKT signaling in hepatocellular carcinoma. Cell death discovery 34 34785642
2020 Ubiquitin chain-elongating enzyme UBE2S activates the RING E3 ligase APC/C for substrate priming. Nature structural & molecular biology 34 32393902
2021 UBE2S promotes the progression and Olaparib resistance of ovarian cancer through Wnt/β-catenin signaling pathway. Journal of ovarian research 32 34535173
2022 UBE2S promotes the development of ovarian cancer by promoting PI3K/AKT/mTOR signaling pathway to regulate cell cycle and apoptosis. Molecular medicine (Cambridge, Mass.) 31 35658829
2020 Ube2S regulates Wnt/β-catenin signaling and promotes the progression of non-small cell lung cancer. International journal of medical sciences 31 32038111
2019 Oncogenic Activities Of UBE2S Mediated By VHL/HIF-1α/STAT3 Signal Via The Ubiquitin-Proteasome System In PDAC. OncoTargets and therapy 30 31814735
2015 Appropriate expression of Ube2C and Ube2S controls the progression of the first meiotic division. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 28 26207029
2008 The predictive role of E2-EPF ubiquitin carrier protein in esophageal squamous cell carcinoma. Journal of molecular medicine (Berlin, Germany) 28 19083192
2019 Autoinhibition Mechanism of the Ubiquitin-Conjugating Enzyme UBE2S by Autoubiquitination. Structure (London, England : 1993) 26 31230944
2016 Crystal Structure of a Ube2S-Ubiquitin Conjugate. PloS one 25 26828794
2017 UBE2S associated with OSCC proliferation by promotion of P21 degradation via the ubiquitin-proteasome system. Biochemical and biophysical research communications 24 28257844
2012 The ubiquitin-conjugating enzyme E2-EPF is overexpressed in cervical cancer and associates with tumor growth. Oncology reports 24 22895574
2018 UBE2S promotes the proliferation and survival of human lung adenocarcinoma cells. BMB reports 23 30545437
2024 UBE2S promotes glycolysis in hepatocellular carcinoma by enhancing E3 enzyme-independent polyubiquitination of VHL. Clinical and molecular hepatology 21 38915206
2023 Activation of PI3K/AKT/mTOR signaling axis by UBE2S inhibits autophagy leading to cisplatin resistance in ovarian cancer. Journal of ovarian research 21 38115063
2021 UBE2S activates NF-κB signaling by binding with IκBα and promotes metastasis of lung adenocarcinoma cells. Cellular oncology (Dordrecht, Netherlands) 21 34582005
2020 Dimerization regulates the human APC/C-associated ubiquitin-conjugating enzyme UBE2S. Science signaling 18 33082289
2022 BMP4 preserves the developmental potential of mESCs through Ube2s- and Chmp4b-mediated chromosomal stability safeguarding. Protein & cell 15 35147915
2020 Ube2s-stabilized β-catenin protects against myocardial ischemia/reperfusion injury by activating HIF-1α signaling. Aging 15 32250966
2018 Contributions of UBE2C and UBE2S to meiotic progression of porcine oocytes. The Journal of reproduction and development 14 29576589
2015 E2-EPF UCP regulates stability and functions of missense mutant pVHL via ubiquitin mediated proteolysis. BMC cancer 14 26503325
2023 UBE2S promotes malignant properties via VHL/HIF-1α and VHL/JAK2/STAT3 signaling pathways and decreases sensitivity to sorafenib in hepatocellular carcinoma. Cancer medicine 13 37563971
2021 UBE2S exerts oncogenic activities in urinary bladder cancer by ubiquitinating TSC1. Biochemical and biophysical research communications 12 34520980
2008 Egr-1 and serum response factor are involved in growth factors- and serum-mediated induction of E2-EPF UCP expression that regulates the VHL-HIF pathway. Journal of cellular biochemistry 12 18780286
2019 Stabilization of E2-EPF UCP protein is implicated in hepatitis B virus-associated hepatocellular carcinoma progression. Cellular and molecular life sciences : CMLS 11 30903204
2024 Diverse roles of UBE2S in cancer and therapy resistance: Biological functions and mechanisms. Heliyon 9 38312603
2006 pVHL's kryptonite: E2-EPF UCP. Cancer cell 9 16904608
2024 Loss of UBE2S causes meiosis I arrest with normal spindle assembly checkpoint dynamics in mouse oocytes. Development (Cambridge, England) 8 38546043
2024 UBE2S facilitates glioblastoma progression through activation of the NF-κB pathway via attenuating K11-linked ubiquitination of AKIP1. International journal of biological macromolecules 6 39098687
2016 E2-EPF UCP Possesses E3 Ubiquitin Ligase Activity via Its Cysteine 118 Residue. PloS one 6 27685940
2023 UBE2S targets RPL26 for ubiquitination and degradation to promote non-small cell lung cancer progression via regulating c-Myc. American journal of cancer research 5 37693154
2022 Knockout of UBE2S inhibits the proliferation of gastric cancer cells and induces apoptosis by FAS-mediated death receptor pathway. Experimental cell research 5 35863455
2020 Hug and hold tight: Dimerization controls the turnover of the ubiquitin-conjugating enzyme UBE2S. Science signaling 4 33082290
2012 Adenovirus-mediated E2-EPF UCP gene transfer prevents autoamputation in a mouse model of hindlimb ischemia. Molecular therapy : the journal of the American Society of Gene Therapy 3 22294149
2025 UBE2S, downregulated by miR-152-3p, facilitates prostate cancer progression through the PTEN-mediated AKT/mTOR pathway. Human molecular genetics 2 39807632
2025 UBE2S inhibits colorectal cancer proliferation by regulating the PI3K/AKT and MAPK/ERK pathways via TRAF6. Scientific reports 2 41083491
2025 Mechanistic insights into IL-6-mediated NK cell dysfunction in NSCLC via the IRE1α-XBP1s-STAT3-UBE2S axis. NPJ precision oncology 2 41254082
2023 As a potential predictor of pan-cancer, UBE2S is related to tumor-associated macrophage infiltration. Future oncology (London, England) 2 37791471
2025 NSUN2 promotes osteosarcoma metastasis via stabilizing UBE2S mRNA in an m5C-dependent manner. Cellular signalling 1 40819747
2025 UBE2S-mediated deubiquitination of GLUT1 via USP10 regulates glucose metabolic reprogramming and immune microenvironment to promote fibrosis in endometriosis. Journal of translational medicine 1 41351058
2014 WITHDRAWN: Production of a novel UBE2S anti-body and significance of its expression in some tumors. Pathology, research and practice 1 25613697
2025 The deubiquitinating enzyme Cezanne stabilizes BRCA1 by counteracting APC/C and Ube2S-dependent Lys11-linked ubiquitination. PLoS biology 0 41359628
2024 [High expression of UBE2S promotes progression of hepatocellular carcinoma by increasing cancer cell stemness]. Nan fang yi ke da xue xue bao = Journal of Southern Medical University 0 38597436
2019 UBE2S Learns Self-Control. Structure (London, England : 1993) 0 31390542

Missed literature

Know a paper Affinage missed for UBE2S? Flag it for the maintainers and the community.

No submissions yet.