Affinage

UBE2O

(E3-independent) E2 ubiquitin-conjugating enzyme · UniProt Q9C0C9

Length
1292 aa
Mass
141.3 kDa
Annotated
2026-06-10
37 papers in source corpus 24 papers cited in narrative 24 extracted findings
Cross-family judge vs UniProt: tie faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

UBE2O is an atypical, self-sufficient E2-E3 hybrid ubiquitin-conjugating enzyme that directly recognizes and ubiquitinates substrates without requiring a separate E3 ligase, governing protein quality control and the targeted degradation of regulatory factors across metabolism, the cell cycle, signaling, and erythroid maturation (PMID:8634298, PMID:28774922). A defining feature is its capacity to recognize "orphan" proteins: it detects juxtaposed exposed basic and hydrophobic patches on unassembled subunits, ubiquitinating unpaired α-globin and ribosomal proteins that fail to engage their normal partners and directing them for proteasomal degradation, a function essential for proteome remodeling during reticulocyte differentiation (PMID:28774922, PMID:28774900). Catalysis proceeds through a UBC active-site cysteine that positions ubiquitin in a closed, RING-E3-like state for nucleophilic attack, with substrate recruitment occurring via an N-terminal SH3-like acidic pocket and CR1-CR2 domains; client selection is further amplified by a feed-forward ubiquitin-binding mechanism and the NAP1L1 cofactor/adapter (PMID:35915257, PMID:41419192, PMID:39740670). Through this machinery UBE2O degrades a broad substrate set with distinct physiological consequences: AMPKα2 (but not AMPKα1), activating mTOR-HIF1α signaling to drive tumorigenesis and impair insulin sensitivity in muscle (PMID:28162974, PMID:31292296); the circadian transcription factor BMAL1 (PMID:29871923); the β-oxidation enzyme HADHA, linking it to hepatic lipid metabolism and hepatocarcinogenesis (PMID:36273042); and additional substrates including c-Maf, Mxi1, RECQL4, IFIT3, and CTNNA1 that connect it to multiple myeloma, lung cancer, homologous-recombination repair, interferon responsiveness, and cell adhesion (PMID:28673317, PMID:32901121, PMID:34921745, PMID:38129382, PMID:40983751). Beyond degradation, UBE2O multi-monoubiquitinates the BAP1 NLS to sequester it in the cytoplasm and monoubiquitinates SMAD6 to modulate BMP signaling, and it dampens NF-κB activation by inhibiting TRAF6 K63-polyubiquitination independent of its UBC domain (PMID:24703950, PMID:23455153, PMID:23381138). Its own activity is constrained by allosteric zinc inhibition of the catalytic cysteine and by RSK2-mediated phosphorylation at Thr838 that destabilizes the enzyme, while GATA1 drives its transcription during erythropoiesis [PMID:bio_10.1101_2025.06.27.661974, PMID:39954933, PMID:41191526].

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 1996 High

    Established that UBE2O is mechanistically unusual—a single enzyme carrying both E2 and intrinsic E3 activity—answering whether it could conjugate ubiquitin without a partner ligase.

    Evidence In vitro thiol-ester relay and active-site cysteine protection assays with phenylarsenoxide/NEM probes

    PMID:8634298

    Open questions at the time
    • No physiological substrate identified at this stage
    • Structural basis of the two-cysteine relay not resolved
  2. 2013 High

    Identified the first defined substrates and demonstrated non-degradative outputs, showing UBE2O can monoubiquitinate SMAD6 to potentiate BMP signaling and can inhibit TRAF6 ubiquitination to dampen NF-κB.

    Evidence Co-IP, in vitro ubiquitination with catalytic (C885A) and substrate-lysine mutants, and pathway reporter assays

    PMID:23381138 PMID:23455153

    Open questions at the time
    • TRAF6 inhibition was UBC-independent, leaving the mechanistic basis distinct from catalytic ubiquitination
    • Generality of monoubiquitination vs degradation outputs unclear
  3. 2014 High

    Showed UBE2O can control substrate localization rather than only stability, multi-monoubiquitinating the BAP1 NLS to drive cytoplasmic sequestration counteracted by BAP1 autodeubiquitination.

    Evidence Co-IP, in vitro ubiquitination, subcellular fractionation/IF, NLS and cancer-mutation analysis

    PMID:24703950

    Open questions at the time
    • How UBE2O selects the NLS region for modification not defined
    • Relative contributions of localization vs degradation across substrates unresolved
  4. 2017 High

    Defined UBE2O's core biological role as an orphan-protein quality control factor and proteome remodeler, recognizing exposed basic/hydrophobic patches on unassembled subunits and clearing ribosomes during reticulocyte maturation.

    Evidence In vitro reconstitution, proteomics, substrate feature mapping, and a loss-of-function Ube2o mouse with anemia

    PMID:28774900 PMID:28774922

    Open questions at the time
    • Determinants distinguishing degradative from monoubiquitination outcomes not fully defined
    • Structural basis of patch recognition not yet solved
  5. 2017 High

    Connected UBE2O to metabolism and cancer by establishing AMPKα2 as an isoform-selective degradation target whose loss drives mTOR-HIF1α signaling and tumorigenesis, and added c-Maf as a degradation substrate in myeloma.

    Evidence Ube2o knockout cancer mouse models with isoform-selective AMPK epistasis, pharmacological rescue, and in vitro/in vivo ubiquitination assays

    PMID:28162974 PMID:28673317

    Open questions at the time
    • Structural basis for AMPKα2 vs α1 selectivity not defined
    • c-Maf finding rests on single-lab Medium-confidence evidence
  6. 2018 High

    Extended the degradation repertoire to circadian control, identifying BMAL1 as a substrate degraded via the CR2 domain and modulating clock amplitude.

    Evidence Co-IP/MS, in vitro ubiquitination with CR2 Cys→Ser mutant, and bioluminescence circadian reporter in U2OS cells

    PMID:29871923

    Open questions at the time
    • In vivo circadian phenotype of Ube2o loss not established
    • Recruitment determinants for BMAL1 not mapped
  7. 2019 High

    Confirmed the UBE2O→AMPKα2 axis as causal in tissue physiology, showing muscle-specific Ube2o loss improves insulin sensitivity in an AMPKα2-dependent manner.

    Evidence Tissue-specific Ube2o knockout mice, hyperinsulinemic-euglycemic clamp, and Prkaa2 haploinsufficiency epistasis

    PMID:31292296

    Open questions at the time
    • Mechanism of AMPKα2 isoform selectivity still unresolved
    • Other muscle substrates not surveyed
  8. 2020 Medium

    Broadened the cancer-relevant substrate set to Mxi1 and reinforced SMAD6/BMP regulation in angiogenesis.

    Evidence Co-IP, in vitro ubiquitination with substrate lysine mutants, tumor models; HUVEC/wound-healing phenotypic assays for SMAD6/BMP2

    PMID:32375794 PMID:32901121

    Open questions at the time
    • The SMAD6/angiogenesis study (Low confidence) lacks direct in vitro ubiquitination reconstitution
    • Mxi1 evidence is single-lab
  9. 2022 High

    Resolved how clients are selected and how catalysis is autoregulated, revealing a feed-forward ubiquitin-binding SH3-like domain and the NAP1L1 adapter, plus a UBC-autoinhibited, malleable client interface.

    Evidence Cryo-EM of human UBE2O–NAP1L1, biochemical reconstitution, and mutagenesis of client- and ubiquitin-binding domains

    PMID:35915257

    Open questions at the time
    • NAP1L1 recruits only a subset of clients; adapters for others unknown
    • How autoinhibition is relieved in vivo not defined
  10. 2022 High

    Expanded substrate biology into DNA repair, lipid metabolism, and caveolae/exosome control, identifying RECQL4 (antagonized by USP7), HADHA, and PTRF/CAVIN1 as targets.

    Evidence Co-IP, in vitro ubiquitination with E2/E3 domain mutants, HR reporter, liver-specific Ube2o KO with DEN model, and exosome quantification

    PMID:34921745 PMID:36273042 PMID:36443833

    Open questions at the time
    • RECQL4 and PTRF studies are single-lab Medium confidence
    • How the same enzyme partitions among diverse substrates in vivo unclear
  11. 2024 High

    Provided the first full-length structural framework, showing a dimeric CR1-CR2/UBC architecture and that UBE2O can build all seven polyubiquitin linkages, with these interactions required for AMPKα2 polyubiquitination.

    Evidence X-ray crystallography of a fungal ortholog and UBC domain, 7-linkage chain assays, and structure-guided mutagenesis on human UBE2O

    PMID:39740670

    Open questions at the time
    • Structure is from a fungal ortholog; full-length human conformation not crystallized
    • Physiological relevance of dimerization in cells not tested
  12. 2025 High

    Detailed the catalytic and regulatory logic of human UBE2O—SH3-like acidic-pocket substrate binding, RING-like closed-ubiquitin positioning, zinc allosteric inhibition, RSK2-mediated destabilizing phosphorylation, and GATA1 transcriptional control—and added CTNNA1, IFIT3, and HBV core protein as functionally distinct outputs.

    Evidence Structural/mutagenesis catalysis studies, zinc inhibition assays, RSK2 kinase/T838 mapping with epistasis, GATA1 ChIP, and substrate-specific co-IP/ubiquitination plus cell-biology assays

    PMID:38129382 PMID:39954933 PMID:40983751 PMID:40992660 PMID:41191526 PMID:41419192 PMID:bio_10.1101_2025.06.27.661974

    Open questions at the time
    • Several substrate and regulatory findings are single-lab Medium confidence
    • One mechanistic study (zinc/regulatory residues) is a preprint
    • Physiological role of zinc inhibition in vivo not established

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved what general code dictates whether a given client is monoubiquitinated for relocalization versus polyubiquitinated for degradation, and how the autoinhibited enzyme is selectively activated toward specific substrates in vivo.
  • No unifying determinant linking substrate features to ubiquitin output
  • In vivo activation/adapter map incomplete beyond NAP1L1
  • Few substrates validated structurally in complex with human UBE2O

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 6 GO:0016740 transferase activity 4 GO:0098772 molecular function regulator activity 1
Localization
GO:0005829 cytosol 3 GO:0005634 nucleus 1
Pathway
R-HSA-1643685 Disease 5 R-HSA-1430728 Metabolism 3 R-HSA-162582 Signal Transduction 3 R-HSA-392499 Metabolism of proteins 3 R-HSA-168256 Immune System 2 R-HSA-73894 DNA Repair 1 R-HSA-9909396 Circadian clock 1
Partners
AMPKΑ2/PRKAA2BAP1BMAL1NAP1L1RECQL4RSK2SMAD6TRAF6

Evidence

Reading pass · 24 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1996 E2-230K (UBE2O) functions as an E2-E3 hybrid enzyme. Phenylarsenoxide inhibition studies demonstrated that two cysteine residues sequentially form thiol esters with ubiquitin (a 'thiol relay'), consistent with the enzyme possessing both E2 and intrinsic E3 activities without requiring a separate E3 ligase. In vitro biochemical assay with phenylarsenoxide and NEM inhibitors; E2~ubiquitin adduct formation assay; active-site cysteine protection experiments Biochemistry High 8634298
2013 UBE2O functions as an E2-E3 hybrid to monoubiquitinate SMAD6 at lysine 174; the catalytic cysteine C885 of UBE2O is essential for this activity. Monoubiquitination of SMAD6 impairs its binding to the BMP type I receptor, thereby potentiating BMP7/SMAD1 signaling and adipogenesis. Proteomic interaction screen, co-IP, in vitro ubiquitination assay, site-directed mutagenesis (K174R on SMAD6; C885A on UBE2O), SMAD1 phosphorylation reporter assays, luciferase transcriptional assays The EMBO journal High 23455153
2013 UBE2O binds TRAF6 and inhibits its K63-polyubiquitination, preventing TAB2/3-TAK1 recruitment and NF-κB activation downstream of IL-1R/TLR. The inhibitory effect is independent of the UBC domain of UBE2O and instead operates by disrupting the IL-1β-induced TRAF6–MyD88 association. Co-IP, in vitro ubiquitination assay, NF-κB luciferase reporter assay, domain-deletion constructs, IL-1β/LPS stimulation experiments Cell research Medium 23381138
2014 UBE2O multi-monoubiquitinates the nuclear localization signal (NLS) of BAP1, inducing its cytoplasmic sequestration. BAP1 autodeubiquitination via intramolecular interactions counteracts this, maintaining nuclear localization. Cancer-derived BAP1 mutations that abrogate autodeubiquitination promote cytoplasmic retention. UBE2O also promotes cytoplasmic localization of BAP1 during adipogenesis. Co-IP, in vitro ubiquitination assay, subcellular fractionation/immunofluorescence, site-directed mutagenesis of BAP1 NLS and catalytic residues, cancer mutation analysis, adipogenesis differentiation assays Molecular cell High 24703950
2017 UBE2O directly recognizes juxtaposed basic and hydrophobic patches on unassembled (orphan) proteins and mediates their ubiquitination without a separate E3 ligase. In reticulocytes, unassembled α-globin that fails to pair with β-globin is selectively ubiquitinated by UBE2O. In non-reticulocytes, ribosomal proteins that do not engage nuclear import factors are UBE2O targets, directing them to proteasomal degradation. In vitro ubiquitination reconstitution, proteomic substrate identification, cell-based ubiquitination assays, substrate feature mapping (basic/hydrophobic patches) Science (New York, N.Y.) High 28774922
2017 UBE2O is a broad-spectrum ubiquitinating enzyme that remodels the erythroid proteome during reticulocyte differentiation. A loss-of-function mutation in murine Ube2o causes anemia. UBE2O directly recognizes ribosomal proteins and other substrates, targeting them for proteasomal degradation, and ribosome elimination is defective in Ube2o mutants. Mouse genetic mutant (Ube2o loss-of-function), quantitative proteomics of reticulocyte proteome, in vivo and in vitro ubiquitination assays, ribosome content analysis Science (New York, N.Y.) High 28774900
2017 UBE2O specifically targets AMPKα2 (but not AMPKα1) for ubiquitination and proteasomal degradation, thereby activating the mTOR-HIF1α pathway and promoting tumor initiation and progression. Genetic deletion of Ube2o in mouse cancer models impairs tumorigenesis, and inactivation of AMPKα2 (but not AMPKα1) abrogates the tumor-attenuating effect of UBE2O loss. Ube2o knockout mouse cancer models (MMTV-PyVT, TRAMP), in vitro ubiquitination assay, epistasis via AMPKα1/α2 isoform-selective inactivation, rapamycin treatment rescue, HIF1α inhibitor rescue Cancer cell High 28162974
2017 UBE2O interacts with and mediates polyubiquitination and proteasomal degradation of c-Maf, a transcription factor critical in multiple myeloma, thereby reducing c-Maf transcriptional activity and cyclin D2 expression. Affinity purification/tandem MS, co-IP, in vitro polyubiquitination assay, immunoblotting for c-Maf stability, luciferase transcriptional assay, lentiviral re-expression, xenograft mouse model Journal of hematology & oncology Medium 28673317
2018 UBE2O interacts with and promotes ubiquitination and proteasomal degradation of BMAL1, the core circadian clock transcription factor. The conserved region 2 (CR2) domain of UBE2O is required for BMAL1 ubiquitination, and a catalytic Cys-to-Ser substitution in CR2 abolishes this activity. UBE2O knockdown elevates circadian clock amplitude in U2OS cells. Co-IP and MS, immunoblotting for BMAL1 stability, in vitro ubiquitination assay, domain-mapping and Cys→Ser mutagenesis, bioluminescence circadian reporter assay in U2OS cells The Journal of biological chemistry High 29871923
2019 In skeletal muscle, UBE2O acts as a ubiquitin ligase that targets AMPKα2 for ubiquitin-dependent degradation. Muscle-specific knockout of Ube2o improves insulin sensitivity and energy expenditure, and muscle-specific heterozygous knockout of Prkaa2 (AMPKα2) abrogates the metabolic benefits of Ube2o loss, establishing UBE2O→AMPKα2 as the causal axis in skeletal muscle metabolic regulation. Tissue-specific (muscle, fat, liver) Ube2o knockout mice, hyperinsulinemic-euglycemic clamp, Prkaa2 heterozygous genetic epistasis, in vitro ubiquitination assay, metabolic phenotyping JCI insight High 31292296
2020 UBE2O interacts with and targets Mxi1 for ubiquitination and degradation at the K46 residue of Mxi1. This promotes lung cancer progression and radioresistance; these effects are reversed by Mxi1 inhibition. Co-IP, in vitro ubiquitination assay, site-directed mutagenesis (Mxi1 K46R), genetic/pharmacological UBE2O blockade with Mxi1 rescue, in vitro and in vivo tumor models Cell death and differentiation Medium 32901121
2020 UBE2O decreases SMAD6 protein levels, thereby activating BMP2 signaling to promote angiogenesis in wound healing; saliva exosome-delivered UBE2O mRNA reproduces this effect in endothelial cells. In vitro HUVEC proliferation/migration/angiogenesis assays, in vivo wound healing model, siRNA knockdown and overexpression, western blot for SMAD6 and BMP2 pathway Journal of nanobiotechnology Low 32375794
2022 UBE2O client selection is regulated by two mechanisms: (1) a feed-forward mechanism where a single ubiquitin added to a client enhances UBE2O binding and promotes multi-mono-ubiquitylation via a distinct SH3-like ubiquitin-binding domain; (2) the histone chaperone NAP1L1 acts as a cofactor/adapter to recruit a subset of UBE2O clients. Cryo-EM structures of human UBE2O with NAP1L1 reveal a malleable client recruitment interface autoinhibited by the reactive UBC domain. Cryo-EM structure determination of human UBE2O–NAP1L1 complex, biochemical ubiquitylation assays, identification of SH3-like ubiquitin-binding domain by mutagenesis, client ubiquitylation reconstitution Nature structural & molecular biology High 35915257
2022 UBE2O physically interacts with RECQL4 and mediates its multi-monoubiquitinylation, leading to proteasomal degradation. This inhibits homologous recombination (HR)-mediated DSB repair by attenuating RECQL4 interactions with MRE11-RAD50-NBS1 and CtIP. The deubiquitinase USP7 antagonizes UBE2O by interacting with both UBE2O and RECQL4 to stabilize RECQL4. Co-IP, in vitro ubiquitination assay, HR reporter assay, UBE2O catalytic mutant (E2 activity-dead), rescue experiments with RECQL4 overexpression, USP7 co-IP and functional antagonism assay FASEB journal Medium 34921745
2022 UBE2O interacts with and ubiquitinates PTRF/CAVIN1, inhibiting caveolae formation and reducing exosome secretion, thereby decreasing exosome-associated PTRF release. SDPR/CAVIN2 interacts with both UBE2O and PTRF and promotes PTRF incorporation into exosomes, but UBE2O still suppresses this in the presence of SDPR. Exogenous and endogenous co-IP, in vitro ubiquitination assay, exosome isolation by ultracentrifugation, nanoparticle tracking analysis, western blot for exosome markers Cell communication and signaling Medium 36443833
2022 UBE2O interacts with and mediates ubiquitination and proteasomal degradation of HADHA (a mitochondrial β-oxidation enzyme), modulating lipid metabolic reprogramming. Both E2 and E3 enzymatic activities of UBE2O are required. Liver-specific Ube2o deletion in mice increases HADHA levels, reduces hepatic lipid accumulation, and confers resistance to DEN-induced hepatocarcinogenesis. Co-IP, in vitro ubiquitination assay with E2/E3 domain mutants, liver-specific Ube2o knockout mice, DEN hepatocarcinogenesis model, lipidomics/metabolic profiling Oncogene High 36273042
2023 UBE2O interacts with IFIT3, a mediator of interferon signaling, and mediates its ubiquitination and proteasomal degradation at lysine K236, thereby reducing cellular responsiveness to interferon-α. Knockdown of UBE2O enhances interferon-α efficacy by upregulating IFIT3. ATO (arsenic trioxide) inhibits UBE2O and increases IFIT3, increasing interferon-α sensitivity. Co-IP and MS, in vitro ubiquitination assay, site-directed mutagenesis (IFIT3 K236R), rescue experiments, in vitro and in vivo IFN-α efficacy assays, ATO pharmacological inhibition Cell death & disease Medium 38129382
2024 Crystal structures of full-length UBE2O (from Trametes pubescens, a fungal ortholog) and its UBC domain revealed a dimeric architecture with interdomain interactions between CR1-CR2 and UBC. Dimeric intermolecular and canonical ubiquitin/UBC interactions are mechanistically important for polyubiquitin chain formation and substrate ubiquitination. UBE2O catalyzes all seven types of polyubiquitin chains in vitro. Autoubiquitination within CR1-CR2 also regulates activity. CR1-CR2/UBC interactions are required for AMPKα2 polyubiquitination by human UBE2O. X-ray crystallography (full-length and UBC domain structures), in vitro ubiquitin chain formation assays for all 7 Ub linkage types, structure-guided mutagenesis, AMPKα2 ubiquitination assay with human UBE2O Structure (London, England : 1993) High 39740670
2025 UBE2O mediates monoubiquitination of hypophosphorylated cytoplasmic hepatitis B virus core protein (HBc) and capsids, promoting capsid recognition by the ESCRT machinery and enveloped virion secretion via CD63-positive multivesicular bodies (MVBs). Enzymatically inactive UBE2O mutant inhibits this process; UBE2O overexpression enhances virion secretion. Knockdown/overexpression in HBV-infected primary human hepatocytes and HepG2-NTCP cells, catalytically inactive UBE2O mutant, confocal microscopy, proximity ligation assay (PLA), co-localization with MVB marker CD63, HBV DNA/pgRNA/capsid quantification The Journal of biological chemistry Medium 40992660
2025 RSK2 is a kinase that directly interacts with UBE2O and phosphorylates it at Thr838, leading to UBE2O degradation. RSK2 inhibition increases UBE2O levels and promotes HCC tumor proliferation and radioresistance; these effects are abrogated by UBE2O knockdown, establishing RSK2 as a negative regulator of UBE2O. Co-IP, in vitro kinase assay identifying Thr838 phosphorylation site, site-directed mutagenesis (T838A), epistasis by combined RSK2 inhibition and UBE2O knockdown, in vitro and in vivo tumor models Cancer letters Medium 39954933
2025 Structural and biochemical analyses of human UBE2O showed that substrate binding occurs through a conserved acidic pocket formed by N-terminal SH3-like domains, enabling broad substrate recruitment. Specific residues in the UBC domain position ubiquitin in a 'closed' state for nucleophilic attack, and a tryptophan residue protects the activated E2~Ub conjugate from premature hydrolysis—mechanistically analogous to RING E3 ligase catalysis. Structural analysis (combined crystallography/biochemistry), systematic mutagenesis of UBC domain residues and SH3-like domain, in vitro ubiquitination assays, comparison with BIRC6 UBC domain The Journal of biological chemistry High 41419192
2025 UBE2O selectively ubiquitylates cytosolic (but not membrane-associated) CTNNA1 in a phosphorylation-independent manner. Ubiquitylation of CTNNA1 diminishes its interaction with β-catenin while enabling interaction with vinculin, thereby promoting focal adhesion maturation, cell extension, and cell-to-ECM adhesion during cell spreading. Co-IP, MS-based interactome of ubiquitylated CTNNA1, in vitro ubiquitination assay, focal adhesion imaging, cell spreading assay, β-catenin and vinculin binding assays EMBO reports Medium 40983751
2025 Domain truncation and systematic mutagenesis of human UBE2O revealed that the coiled-coil (CC) and C-terminal regulatory (CTR) domains are required for catalytic competence, while N-terminal regions impose activity constraints. Zinc ions act as potent allosteric inhibitors by binding cysteines of UBE2O and sterically blocking access of catalytic C1040 to ubiquitin. Specific non-cysteine residues (H939, T995, S1042, S1046, S1060, H1130) are critical regulators of substrate selectivity and catalytic optimization. UBE2O activity is insensitive to its own self-ubiquitination and phosphorylation state. Domain truncation analysis, systematic mutagenesis, biochemical ubiquitination assays, zinc ion inhibition experiments, AMPKα2 substrate ubiquitination assays bioRxivpreprint Medium bio_10.1101_2025.06.27.661974
2026 GATA1 binds to the UBE2O promoter, directly regulating UBE2O transcription and expression during erythroid differentiation; this was validated by chromatin immunoprecipitation (ChIP) in the context of erythropoiesis and myelodysplastic syndrome treatment. Bioinformatic promoter analysis, ChIP assay confirming GATA1 binding to UBE2O promoter, expression analysis in K562 cells and MDS patient bone marrow Blood advances Medium 41191526

Source papers

Stage 0 corpus · 37 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2014 Autodeubiquitination protects the tumor suppressor BAP1 from cytoplasmic sequestration mediated by the atypical ubiquitin ligase UBE2O. Molecular cell 163 24703950
2017 UBE2O remodels the proteome during terminal erythroid differentiation. Science (New York, N.Y.) 142 28774900
2017 A UBE2O-AMPKα2 Axis that Promotes Tumor Initiation and Progression Offers Opportunities for Therapy. Cancer cell 114 28162974
2017 UBE2O is a quality control factor for orphans of multiprotein complexes. Science (New York, N.Y.) 106 28774922
2013 UBE2O negatively regulates TRAF6-mediated NF-κB activation by inhibiting TRAF6 polyubiquitination. Cell research 83 23381138
2013 Fine-tuning BMP7 signalling in adipogenesis by UBE2O/E2-230K-mediated monoubiquitination of SMAD6. The EMBO journal 80 23455153
2020 Saliva exosomes-derived UBE2O mRNA promotes angiogenesis in cutaneous wounds by targeting SMAD6. Journal of nanobiotechnology 71 32375794
2020 UBE2O targets Mxi1 for ubiquitination and degradation to promote lung cancer progression and radioresistance. Cell death and differentiation 62 32901121
1996 Mechanism of ubiquitin conjugating enzyme E2-230K: catalysis involving a thiol relay? Biochemistry 53 8634298
2018 Ubiquitin-conjugating enzyme UBE2O regulates cellular clock function by promoting the degradation of the transcription factor BMAL1. The Journal of biological chemistry 46 29871923
2018 Diverse roles of the E2/E3 hybrid enzyme UBE2O in the regulation of protein ubiquitination, cellular functions, and disease onset. The FEBS journal 43 30468556
2017 The ubiquitin-conjugating enzyme UBE2O modulates c-Maf stability and induces myeloma cell apoptosis. Journal of hematology & oncology 42 28673317
2018 New Insights into the Role of E2s in the Pathogenesis of Diseases: Lessons Learned from UBE2O. Molecules and cells 39 29562734
2020 UBE2O promotes the proliferation, EMT and stemness properties of breast cancer cells through the UBE2O/AMPKα2/mTORC1-MYC positive feedback loop. Cell death & disease 35 31907353
2022 UBE2O promotes lipid metabolic reprogramming and liver cancer progression by mediating HADHA ubiquitination. Oncogene 28 36273042
2001 Identification, tissue expression, and chromosomal position of a novel gene encoding human ubiquitin-conjugating enzyme E2-230k. Gene 22 11311559
2022 UBE2O and USP7 co-regulate RECQL4 ubiquitinylation and homologous recombination-mediated DNA repair. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 21 34921745
2021 Long Noncoding RNA HCG18 Promotes Malignant Phenotypes of Breast Cancer Cells via the HCG18/miR-103a-3p/UBE2O/mTORC1/HIF-1α-Positive Feedback Loop. Frontiers in cell and developmental biology 19 34976998
2022 Mechanism of client selection by the protein quality-control factor UBE2O. Nature structural & molecular biology 17 35915257
2022 UBE2O ubiquitinates PTRF/CAVIN1 and inhibits the secretion of exosome-related PTRF/CAVIN1. Cell communication and signaling : CCS 17 36443833
2021 UBE2O promotes hepatocellular carcinoma cell proliferation and invasion by regulating the AMPKα2/mTOR pathway. International journal of medical sciences 16 34790050
2019 A muscle-specific UBE2O/AMPKα2 axis promotes insulin resistance and metabolic syndrome in obesity. JCI insight 16 31292296
2023 UBE2O reduces the effectiveness of interferon-α via degradation of IFIT3 in hepatocellular carcinoma. Cell death & disease 12 38129382
2020 UBE2O Promotes Progression and Epithelial-Mesenchymal Transition in Head and Neck Squamous Cell Carcinoma. OncoTargets and therapy 11 32636643
2022 Arborinine from Glycosmis parva leaf extract inhibits clear-cell renal cell carcinoma by inhibiting KDM1A/UBE2O signaling. Food & nutrition research 9 36185617
2017 An Oncogenic Role for the Ubiquitin Ligase UBE2O by Targeting AMPK-α2 for Degradation. Cancer cell 8 28196589
2017 A new duet in cancer biology: AMPK the typical and UBE2O the atypical. Molecular & cellular oncology 8 28616582
2023 Age-Associated UBE2O Reduction Promotes Neuronal Death in Alzheimer's Disease. Journal of Alzheimer's disease : JAD 7 37182872
2024 The Ubiquitin-Conjugating Enzyme E2 O (UBE2O) and Its Therapeutic Potential in Human Leukemias and Solid Tumors. Cancers 6 39272922
2025 RSK2-mediated phosphorylation and degradation of UBE2O inhibits hepatocellular carcinoma growth and resistance to radiotherapy. Cancer letters 4 39954933
2024 Structural insights into the biochemical mechanism of the E2/E3 hybrid enzyme UBE2O. Structure (London, England : 1993) 4 39740670
2025 The Emerging Role and Mechanism of E2/E3 Hybrid Enzyme UBE2O in Human Diseases. Biomedicines 3 40426910
2025 UBE2O-mediated ubiquitylation directs cytoplasmic CTNNA1 to promote cell-to-ECM adhesions. EMBO reports 1 40983751
2022 Regulatory roles of an atypical ubiquitin ligase UBE2O in orphans of multiprotein complexes for degradation. Turkish journal of biology = Turk biyoloji dergisi 1 37533513
2026 UBE2O as a key regulator of drug-induced erythropoiesis in the context of myelodysplastic syndromes. Blood advances 0 41191526
2025 UBE2O, a host ubiquitin-conjugating enzyme, is a key regulator of hepatitis B virus maturation and egress. The Journal of biological chemistry 0 40992660
2025 Structural basis for substrate recruitment and catalytic ubiquitin transfer by the E2/E3 hybrid enzyme UBE2O. The Journal of biological chemistry 0 41419192

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