Affinage

UBE2B

Ubiquitin-conjugating enzyme E2 B · UniProt P63146

Length
152 aa
Mass
17.3 kDa
Annotated
2026-04-28
55 papers in source corpus 25 papers cited in narrative 25 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

UBE2B (RAD6B/HHR6B) is a ubiquitin-conjugating (E2) enzyme that partners with multiple E3 ligases to regulate DNA damage tolerance, chromatin remodeling, protein quality control, and signal transduction. In complex with RAD18, UBE2B monoubiquitinates PCNA to activate translesion synthesis and post-replication repair, and polyubiquitinates histones H2A and H2B—functions essential for spermatogenesis and neuronal genome maintenance (PMID:18363965, PMID:31639439, PMID:25854, PMID:31507381). Through the N-end rule E3 ligase UBR1 and the structurally distinct hemiRING E3 UBR4, UBE2B mediates N-degron-dependent proteolysis, an activity down-regulated by CDK1/2 phosphorylation at Ser120 (PMID:1651502, PMID:21041297, PMID:38182926). UBE2B also stabilizes β-catenin via K63-linked polyubiquitination at K394—creating a positive-feedback loop with TCF-4/β-catenin-driven UBE2B transcription—and ubiquitinates substrates including DNMT3a, TRAF1 (with BIRC2, K63-linked), and ZMYM2 (with RAD18) to modulate Wnt, NF-κB, and epigenetic pathways (PMID:18339854, PMID:22705350, PMID:17050667, PMID:31576007, PMID:41661096, PMID:35313791).

Mechanistic history

Synthesis pass · year-by-year structured walk · 20 steps
  1. 1991 High

    Establishing that UBC2/RAD6 is the obligate E2 for N-end rule degradation and physically associates with UBR1 answered the fundamental question of which ubiquitin-conjugating enzyme mediates this proteolytic pathway.

    Evidence Genetic epistasis and co-purification of yeast Ubc2 with N-recognin/UBR1

    PMID:1651502

    Open questions at the time
    • Mammalian UBE2B–UBR1 interaction not yet demonstrated
    • Substrate scope of the complex unknown
  2. 1992 High

    Domain-swap experiments showed that the RAD6 catalytic core is modular and independently sufficient for DNA repair function, separating its repair role from its C-terminal regulatory tail.

    Evidence RAD6/CDC34 chimeric proteins tested for complementation of rad6Δ and cdc34 phenotypes in yeast

    PMID:1639076

    Open questions at the time
    • Which E3 partners require the acidic tail versus the catalytic domain
    • Structural basis of domain modularity unresolved
  3. 1993 High

    Mapping the UBR1-binding region to a C-terminal fragment and showing that the acidic tail of Ubc2 stabilizes the E2–E3 complex distinguished the catalytic and E3-interaction surfaces of the enzyme.

    Evidence Two-hybrid mapping, C88A mutagenesis, dominant-negative assays in yeast

    PMID:8505328

    Open questions at the time
    • Atomic-resolution structure of the UBE2B–UBR1 interface not determined
    • How acidic tail modulates activity kinetically not quantified
  4. 1997 High

    Demonstrating that RAD6 catalytic activity is required for telomeric silencing but neither RAD18 nor UBR1 is involved revealed a third, genetically distinct effector branch of the RAD6 pathway.

    Evidence Catalytic-dead mutants (C88A/C88S) and rad18Δ/ubr1Δ epistasis in yeast silencing assays

    PMID:9343433

    Open questions at the time
    • E3 ligase for silencing branch unidentified
    • Histone substrate specificity in silencing not shown
  5. 1999 High

    Identifying human RAD6B as the E2 that ubiquitinates and degrades cAMP-responsive transcriptional repressors (ICERII γ, ATF5) extended its substrates beyond DNA repair into mammalian transcriptional regulation.

    Evidence Ubiquitination assays, dominant-negative constructs, and elevated ICER in mHR6B−/− mouse cells

    PMID:10373550

    Open questions at the time
    • E3 partner for ICER/ATF5 degradation not identified
    • Physiological consequence of ICER stabilization beyond cAMP signaling unclear
  6. 2000 High

    Biochemical isolation of a stable human RAD18–UBE2B complex established the conserved E2–E3 partnership that channels RAD6 activity toward DNA damage tolerance in human cells.

    Evidence Co-expression in yeast and purification of the RAD18–HHR6B heterodimer

    PMID:10908344

    Open questions at the time
    • PCNA monoubiquitination by this complex not yet shown directly
    • Stoichiometry and structural details of the complex unresolved
  7. 2003 High

    Ube2b knockout mice revealed that UBE2B is required for periaxonemal structural assembly during spermiogenesis, defining its non-redundant role with UBE2A in male fertility.

    Evidence Immuno-electron microscopy and ultrastructural analysis of Ube2b−/− spermatids

    PMID:12784252

    Open questions at the time
    • Specific ubiquitination substrates mediating periaxonemal assembly not identified
    • Whether histone replacement defects contribute to the structural phenotype unclear
  8. 2004 High

    Showing that RAD6B peaks in late S/G2, is recruited to chromatin with RAD18 and PCNA after DNA damage, and confers chemoresistance via post-replication repair linked its cell-cycle regulation to a specific repair function.

    Evidence Chromatin fractionation, PRR assay, and gain/loss-of-function in synchronized cells treated with cisplatin/adriamycin

    PMID:14981545

    Open questions at the time
    • Whether PCNA monoubiquitination is the sole PRR-relevant substrate not resolved
    • Mechanism of cell-cycle-dependent RAD6B accumulation unknown
  9. 2005 High

    Discovery that RAD6/UBR1-mediated ubiquitination of Cut8 is required to tether proteasomes to the nuclear envelope expanded UBE2B's role to proteasome localization.

    Evidence Cut8 K-to-R mutagenesis, rhp6Δ/ubr1Δ mutants, subcellular fractionation of proteasome in fission yeast

    PMID:16096059

    Open questions at the time
    • Whether a mammalian Cut8 ortholog or analogous mechanism exists is unknown
    • Whether proteasome mis-localization explains any RAD6-null phenotypes untested
  10. 2006 High

    Identifying UBE2B as a direct transcriptional target of TCF-4/β-catenin established a positive-feedback loop coupling Wnt pathway activation to E2 enzyme abundance.

    Evidence ChIP, EMSA, and luciferase reporter assays on the RAD6B promoter with β-catenin/TCF-4

    PMID:17050667

    Open questions at the time
    • Whether this loop operates in vivo in Wnt-driven tumors not shown
    • Quantitative contribution of this loop versus other β-catenin stabilization mechanisms unknown
  11. 2008 High

    Demonstrating that the RAD18 SAP domain directs the RAD18–UBE2B complex to fork structures and is required for PCNA monoubiquitination and Pol η recruitment resolved how substrate targeting occurs in translesion synthesis.

    Evidence In vitro DNA binding with SAP domain mutants, UV sensitivity complementation, PCNA ubiquitination and Pol η foci assays

    PMID:18363965

    Open questions at the time
    • Whether UBE2B contributes to DNA-binding specificity unknown
    • Role of other RAD18 domains in complex activation uncharacterized
  12. 2008 High

    Revealing that UBE2B directly K63-polyubiquitinates β-catenin, stabilizing it against proteasomal degradation, identified a non-canonical ubiquitin signal that activates rather than degrades a key oncoprotein.

    Evidence In vitro ubiquitination, K63-linkage-specific antibodies, siRNA knockdown, TOP/Flash reporter in breast cancer cells

    PMID:18339854

    Open questions at the time
    • E3 ligase cooperating with UBE2B for β-catenin ubiquitination not identified
    • How K63-Ub renders β-catenin proteasome-resistant mechanistically unclear
  13. 2010 High

    Quantitative kinetic analysis of CDK1/2-mediated Ser120 phosphorylation showed it selectively impairs UBE2B's activity with UBR1/E3α (20-fold) without affecting E1 charging, revealing cell-cycle-dependent tuning of E2–E3 partnerships.

    Evidence In vitro kinetics (Km/Vmax) with S120D/S120A mutants, in vivo N-end rule reporter assay

    PMID:21041297

    Open questions at the time
    • Impact of Ser120 phosphorylation on RAD18 or other E3 partnerships not measured
    • In vivo stoichiometry of phosphorylated UBE2B across cell cycle unknown
  14. 2012 High

    Mapping the UBE2B-β-catenin interface and identifying K394 as the major ubiquitination site provided substrate-level resolution for the non-degradative ubiquitin signal that stabilizes β-catenin.

    Evidence Deletion mapping, K394R mutagenesis, in vitro/in vivo ubiquitination, TOP/Flash and stability assays

    PMID:22705350

    Open questions at the time
    • Other ubiquitination sites on β-catenin by UBE2B likely exist (K394R only reduces ~50%)
    • Structural basis of the UBE2B–β-catenin interaction unresolved
  15. 2013 High

    Showing that androgen receptor directly drives UBE2B transcription in Sertoli cells and that UBE2B mediates testosterone-induced H2A ubiquitylation connected hormonal regulation of spermatogenesis to chromatin ubiquitination.

    Evidence AR ChIP on Ube2b promoter, EMSA, luciferase reporter, siRNA-mediated UBE2B knockdown abolishing H2A-Ub

    PMID:23863405

    Open questions at the time
    • Specific H2A sites ubiquitinated by UBE2B in Sertoli cells not mapped
    • Whether AR-driven UBE2B is sufficient to explain spermatogenic histone replacement unknown
  16. 2018 Medium

    Genetic dissection using RNF8 and RAD6B knockout mice showed that RNF8 monoubiquitinates and RAD6B polyubiquitinates H2A/H2B during spermatogenesis, and that RAD6B loss causes spermatocyte senescence and male sterility.

    Evidence Double and single KO mice, histone ubiquitination assays, senescence markers, fertility assays

    PMID:28825854

    Open questions at the time
    • Whether RNF8 is the E3 that directs RAD6B polyubiquitination of histones or acts independently not fully resolved
    • Chain-type specificity of histone polyubiquitination in spermatogenesis not determined
  17. 2019 High

    Multiple studies converged to show UBE2B is central to the neuronal DNA damage response: it monoubiquitinates PCNA and H2AX, activates FANCD2, and supports homologous recombination; its loss causes genomic instability, neuronal senescence, and memory deficits; and it ubiquitinates DNMT3a to drive epigenetic remodeling underlying addiction-related plasticity.

    Evidence RAD6B KO mice (neurodegeneration phenotype), RAD6 inhibitor + siRNA with HR/fiber assays, in vivo heroin self-administration model with co-IP/ubiquitination/methylation analysis

    PMID:31507381 PMID:31576007 PMID:31639439

    Open questions at the time
    • Whether UBE2B-mediated H2AX monoubiquitination is direct or requires a specific E3 not established
    • Relative contributions of UBE2A versus UBE2B in neurons unclear
  18. 2022 Medium

    Identification of ZMYM2 as a substrate whose stability is increased by UBE2B/RAD18-dependent monoubiquitination (shifting it from poly- to mono-Ub) revealed that UBE2B can switch substrate fate from degradation to stabilization.

    Evidence Co-IP, cycloheximide chase, monoubiquitination assay, RAD18 knockdown, xenograft model

    PMID:35313791

    Open questions at the time
    • ZMYM2 ubiquitination site not mapped
    • Whether ZMYM2 stabilization mediates the oncogenic effects not mechanistically resolved
  19. 2024 High

    Crystal structure of UBR4's hemiRING–UBE2B complex revealed the atomic determinants of E2 selectivity and showed that the UZI subdomain allosterically activates ubiquitin-loaded UBE2B, defining a new E3 architecture for the N-degron pathway.

    Evidence X-ray crystallography, structure-guided mutagenesis, in vitro ubiquitination reconstitution

    PMID:38182926

    Open questions at the time
    • Physiological substrates of the UBR4–UBE2B complex in mammalian cells not identified
    • Whether UBR4 competes with UBR1 for UBE2B binding in vivo unknown
  20. 2025 Medium

    UBE2B was reported to cooperate with BIRC2 to K63-polyubiquitinate TRAF1, amplifying NF-κB signaling in a feedforward loop with P65-driven UBE2B transcription, connecting UBE2B to innate immune and inflammatory signaling.

    Evidence Co-IP, K63-Ub assay, ChIP on UBE2B promoter, luciferase reporter, xenograft in gastric cancer cells

    PMID:41661096

    Open questions at the time
    • Endogenous validation of BIRC2–UBE2B interaction in non-cancer contexts missing
    • Whether K63-Ub on TRAF1 is direct or scaffold-mediated not resolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • How UBE2B is selectively allocated among its numerous E3 partners in vivo—and whether Ser120 phosphorylation differentially modulates non-UBR1 partnerships (RAD18, UBR4, BIRC2)—remains the central unresolved question for understanding pathway-specific regulation.
  • Quantitative in vivo measurements of UBE2B partitioning among E3s lacking
  • Structural basis for phospho-Ser120 selectivity beyond UBR1 not determined
  • Whether UBE2A fully compensates for UBE2B loss in specific tissues remains untested

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 11 GO:0016874 ligase activity 3
Localization
GO:0005694 chromosome 4 GO:0005634 nucleus 3
Pathway
R-HSA-392499 Metabolism of proteins 5 R-HSA-162582 Signal Transduction 4 R-HSA-73894 DNA Repair 4 R-HSA-4839726 Chromatin organization 3 R-HSA-1474165 Reproduction 2
Partners
BIRC2CTNNB1DNMT3ARAD18RNF8UBR1UBR4ZMYM2
Complex memberships
RAD18–UBE2B heterodimerUBR1–UBE2B complexUBR4–UBE2B complex

Evidence

Reading pass · 25 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1991 UBC2/RAD6 (yeast ortholog of UBE2B) is essential for multiubiquitination and degradation of N-end rule substrates, and physically associates with UBR1 (N-recognin), the recognition component of the N-end rule pathway. Genetic epistasis, in vivo ubiquitination assays, physical co-purification Proceedings of the National Academy of Sciences of the United States of America High 1651502
1993 The acidic C-terminal region of Ubc2 is required for both physical stability and functional activity of the N-recognin (UBR1)/Ubc2 complex; the active-site Cys-88 is required for catalytic activity but not for N-recognin binding; a ~170-residue C-terminal fragment of N-recognin (UBR1) was identified as the Ubc2-interacting domain by two-hybrid assay. Mutagenesis (C88A active site mutant), two-hybrid interaction cloning, dominant-negative inhibition assay The Journal of biological chemistry High 8505328
1992 The catalytic domain of RAD6/UBC2 is essential for its DNA repair and growth functions, and these functions are distinct from those conferred by the CDC34 tail; a chimeric E2 combining the RAD6 catalytic domain with the CDC34 tail retains both RAD6 and CDC34 activities, demonstrating domain modularity. Chimeric protein construction, complementation assays in yeast The EMBO journal High 1639076
1997 Ubiquitin-conjugating activity of RAD6/UBC2 (active-site C88) is essential for telomeric silencing; neither Rad18 nor Ubr1 (N-end rule pathway component) is required, indicating silencing is a distinct branch of the RAD6 pathway. Null mutant and point mutant (C88A, C88S) complementation, genetic epistasis Molecular and cellular biology High 9343433
1999 Human Rad6B (UBE2B) mediates ubiquitin-dependent proteolysis of cAMP-induced transcriptional repressors hICERIIγ and hATF5 in mammalian cells; degradation requires active ubiquitin-conjugating enzyme activity and results in abrogation of repressor function; endogenous ICER protein is elevated in mHR6B-/- cells. Transfection ubiquitination assays, dominant-negative/antisense constructs, mHR6B knockout cells, yeast two-hybrid substrate identification Molecular and cellular biology High 10373550
2000 Human RAD18 protein interacts with both HHR6A and HHR6B (UBE2A and UBE2B), forming stable protein complexes when co-expressed in yeast cells, purified to near homogeneity. Co-expression and co-purification, complex isolation Nucleic acids research High 10908344
2004 RAD6B (UBE2B) is cell cycle-regulated with maximal protein levels in late S/G2 phase; upon DNA damage (adriamycin, cisplatin), RAD6B is recruited from nucleus to chromatin together with RAD18, PCNA, and phosphohistone H3; RAD6B overexpression confers chemoresistance via enhanced post-replication repair (PRR), while antisense depletion causes PRR deficiency and chemosensitivity. Cell cycle synchronization/flow cytometry, in vivo chromatin crosslinking/fractionation, stable transfection KO/OE, PRR assay (DNA molecular weight analysis) Oncogene High 14981545
2005 Fission yeast Rhp6/Ubc2 (RAD6 ortholog) and Ubr1 E3 ligase ubiquitinate the nuclear envelope protein Cut8, which physically interacts with and tethers the proteasome; non-ubiquitinatable Cut8 (K-all-R) fails to enrich nuclear proteasome; rhp6 and ubr1 null mutants also fail to enrich nuclear proteasome, linking RAD6/UBC2 activity to nuclear proteasome localization. Genetic knockouts, ubiquitination-site mutagenesis (K-all-R), subcellular fractionation, co-immunoprecipitation, DNA damage sensitivity assays Cell High 16096059
2008 Human RAD18 complexed with RAD6B (UBE2B) preferentially binds forked and single-stranded DNA structures via the SAP domain of RAD18 (residues 248-282); SAP domain mutation abolishes RAD18 accumulation at DNA damage sites, prevents guidance of DNA Pol η to stalled replication forks, and impairs PCNA monoubiquitination. In vitro DNA binding assays, SAP domain mutagenesis, in vivo localization (fluorescence microscopy), UV sensitivity complementation Genes to cells : devoted to molecular & cellular mechanisms High 18363965
2008 Rad6B (UBE2B) overexpression in breast cells induces β-catenin accumulation via K63-linked polyubiquitination that renders β-catenin insensitive to 26S proteasome degradation; in vitro ubiquitination assays confirm Rad6B directly mediates β-catenin polyubiquitination; Rad6B silencing suppresses β-catenin mono- and polyubiquitination and transcriptional activity. Stable overexpression/siRNA knockdown, in vitro ubiquitination assay, chromatin immunoprecipitation (ubiquitinated β-catenin on chromatin), cycloheximide chase, TOP/Flash reporter assay Cancer research High 18339854
2010 CDK1/2-dependent phosphorylation of UBE2B/Ubc2 at Ser120 downregulates N-end rule-dependent degradation: S120D (phosphomimetic) mutant shows 20-fold reduced activity with E3α/Ubr1 (8-fold increase in Km, 2.5-fold decrease in Vmax) while S120A mutant shows 8-fold reduction in Vmax for polyubiquitin chain elongation; phosphorylation does not affect E1-catalyzed E2 transthiolation. In vitro kinetics of E3α-catalyzed ubiquitination, site-directed mutagenesis (S120D/S120A), in vivo N-end rule reporter assays in T47D cells The Journal of biological chemistry High 21041297
2012 Rad6B (UBE2B) ubiquitinates β-catenin at lysine 394 (K394) as the major site; Rad6B-interacting region maps to amino acids 131-181 of β-catenin and 50-116 of Rad6B; K394R mutation abolishes ~50% of Rad6B-induced β-catenin ubiquitination and reduces β-catenin transcriptional activity and stability (not rescued by proteasome inhibitor MG132). GST pulldown with deletion mutants, in vitro and in vivo ubiquitination assays, site-directed mutagenesis (K394R), TOP/Flash luciferase reporter, co-immunoprecipitation Biochimica et biophysica acta High 22705350
2013 UBE2B (Ube2b) is a direct transcriptional target of androgen receptor (AR) in mouse Sertoli cells; AR binds androgen-responsive elements in the Ube2b promoter; testosterone-induced UBE2B upregulates H2A ubiquitylation, and UBE2B knockdown blocks testosterone-induced H2A ubiquitylation. Luciferase reporter assay, EMSA, ChIP assay, Western blot, qRT-PCR, siRNA knockdown, AR knockout mouse model Biology of reproduction High 23863405
2015 UBE2B is upregulated in catabolic myotubes (dexamethasone-treated C2C12); UBE2B knockdown causes a sharp decrease in total (-18%) and K48-linked (-28%) ubiquitin conjugates, implicating UBE2B in proteasome-mediated myofibrillar protein degradation in muscle catabolism. siRNA knockdown, ubiquitin conjugate immunoblotting (total and K48-linked), E2 expression screen Journal of cachexia, sarcopenia and muscle Medium 27239408
2019 RAD6B (UBE2B) mediates PCNA monoubiquitination (translesion synthesis marker) and FANCD2 activation (Fanconi anemia pathway); RAD6B also monoubiquitinates H2AX to modulate γH2AX levels; RAD6B silencing or inhibition impairs homologous recombination and restart of cisplatin-stalled replication forks. RAD6-selective inhibitor (SMI#9), RAD6B siRNA knockdown, DR-GFP homologous recombination assay, DNA fiber assay, immunofluorescence foci (γH2AX, RAD51, FANCD2, POL η), Western blot Biochimica et biophysica acta. Molecular basis of disease High 31639439
2019 Ube2b (UBE2B) mediates ubiquitination and degradation of DNMT3a in dorsal hippocampus neurons during repeated opiate self-administration; DNMT3a degradation leads to demethylation of the CaMKK1 gene promoter, facilitating CaMKK1/CaMKIα/βPIX/Rac1 cascade activation and actin cytoskeleton remodeling underlying behavioral plasticity. In vivo rat model (heroin self-administration), co-immunoprecipitation, ubiquitination assay, promoter methylation analysis, viral vector-mediated Ube2b overexpression/knockdown, behavioral tests Molecular psychiatry High 31576007
2019 RAD6B (UBE2B) mediates polyubiquitination of histones H2A and H2B; RAD6B deficiency in neurons results in increased genomic instability (γH2AX), elevated p53/p21 levels, neuronal senescence, and neurodegeneration with learning/memory deficits in mice. RAD6B knockout mouse, X-ray irradiation, immunofluorescence, histone ubiquitination assays, behavioral experiments Frontiers in cellular neuroscience Medium 31507381
2019 RAD6B (UBE2B) splice variants (RAD6BΔexon4 and RAD6Bintron5ins) retain intact catalytic domains and exhibit functional in vivo ubiquitin-conjugating activity, expressed as 14 and 15 kDa proteins specifically in melanomas but not normal melanocytes. RT-PCR splice variant characterization, in vivo ubiquitination activity assay, Western blot, whole exome sequencing Cells Medium 31683936
2022 UBE2B forms a heterodimer complex with E3 ligase RAD18; the UBE2B/RAD18 complex monoubiquitinates ZMYM2, increasing its protein stability; RAD18 knockdown impairs UBE2B-induced ZMYM2 monoubiquitination; UBE2B overexpression shifts ZMYM2 from polyubiquitinated (degraded) to monoubiquitinated (stabilized) form. Co-immunoprecipitation, immunofluorescence colocalization, cycloheximide chase assay, monoubiquitination assay, in vivo xenograft tumor model, RAD18 siRNA knockdown Bioengineered Medium 35313791
2024 UBR4 contains a distinct E3 module with a 'hemiRING' zinc finger, a UBR zinc-finger interacting (UZI) subdomain, and an N-terminal affinity region that specifically recruits UBE2A and UBE2B as cognate E2s; crystal structure of the E2-E3 complex reveals atomic-level specificity determinants; the UZI subdomain allosterically and modestly activates the Ub-loaded UBE2A/UBE2B. X-ray crystallography (E2-E3 complex structure), mutagenesis, in vitro ubiquitination reconstitution, biochemical binding assays Nature structural & molecular biology High 38182926
2006 The human RAD6B (UBE2B) gene is a direct transcriptional target of TCF-4/β-catenin/p300; β-catenin assembled on TCF binding elements in the Rad6B promoter drives its transcription; this creates a positive feedback loop where Rad6B stabilizes β-catenin and β-catenin drives Rad6B expression. EMSA, Western blot of EMSA, UV cross-linking, chromatin immunoprecipitation, luciferase reporter assay, co-transfection Molecular cancer research : MCR High 17050667
2026 UBE2B interacts with E3 ligase BIRC2 to catalyze K63-linked ubiquitination of TRAF1, amplifying NF-κB signaling; NF-κB subunit P65 directly binds the UBE2B promoter to enhance its transcription, creating a feedforward loop; UBE2B promotes gastric cancer cell proliferation in vitro and in vivo. Co-immunoprecipitation, K63-linked ubiquitination assay, ChIP assay, luciferase reporter assay, in vivo xenograft, bioinformatics/clinical validation Molecular cancer research : MCR Medium 41661096
2003 Mouse Ube2b (UBE2B) null mutant spermatids show nuclear and sperm periaxonemal structural anomalies; transition proteins, protamines, and actin distribute normally, but periaxonemal structures are abnormally distributed, demonstrating UBE2B is required for periaxonemal assembly during spermatogenesis. Ube2b knockout mouse, immuno-electron microscopy, in situ hybridization, electron microscopy Molecular reproduction and development High 12784252
2018 RAD6B (UBE2B) polyubiquitinates histones H2A and H2B in mouse spermatogenesis; RNF8 monoubiquitinates H2A and H2B; loss of RAD6B leads to male sterility associated with absent histone polyubiquitination; RAD6B-deficient spermatocytes show senescence contributing to germ cell loss. RNF8 and RAD6B knockout mice, histone ubiquitination assays, fertility/offspring count assays, senescence markers Cell cycle (Georgetown, Tex.) Medium 28825854
2025 UBE2B promotes ubiquitination and degradation of U2AF1 (splicing factor), thereby modulating the p53/p21 signaling pathway to induce endothelial apoptosis during renal ischemia-reperfusion injury. UBE2B overexpression/knockdown in endothelial cells, co-immunoprecipitation, ubiquitination assay, apoptosis/proliferation assays Molecular biology reports Low 41186784

Source papers

Stage 0 corpus · 55 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1991 The N-end rule is mediated by the UBC2(RAD6) ubiquitin-conjugating enzyme. Proceedings of the National Academy of Sciences of the United States of America 230 1651502
1997 The ubiquitin-conjugating enzyme Rad6 (Ubc2) is required for silencing in Saccharomyces cerevisiae. Molecular and cellular biology 109 9343433
1992 A chimeric ubiquitin conjugating enzyme that combines the cell cycle properties of CDC34 (UBC3) and the DNA repair properties of RAD6 (UBC2): implications for the structure, function and evolution of the E2s. The EMBO journal 87 1639076
2016 Up-regulation of miR-455-5p by the TGF-β-SMAD signalling axis promotes the proliferation of oral squamous cancer cells by targeting UBE2B. The Journal of pathology 81 27235675
2020 E2 conjugases UBC1 and UBC2 regulate MYB42-mediated SOS pathway in response to salt stress in Arabidopsis. The New phytologist 76 32167578
1993 N-recognin/Ubc2 interactions in the N-end rule pathway. The Journal of biological chemistry 76 8505328
2005 Regulation of nuclear proteasome by Rhp6/Ubc2 through ubiquitination and destruction of the sensor and anchor Cut8. Cell 71 16096059
1999 Human Cdc34 and Rad6B ubiquitin-conjugating enzymes target repressors of cyclic AMP-induced transcription for proteolysis. Molecular and cellular biology 69 10373550
2000 The human RAD18 gene product interacts with HHR6A and HHR6B. Nucleic acids research 61 10908344
2008 Recognition of forked and single-stranded DNA structures by human RAD18 complexed with RAD6B protein triggers its recruitment to stalled replication forks. Genes to cells : devoted to molecular & cellular mechanisms 56 18363965
2001 The ubc2 gene of Ustilago maydis encodes a putative novel adaptor protein required for filamentous growth, pheromone response and virulence. Molecular microbiology 54 11580841
2008 Rad6B is a positive regulator of beta-catenin stabilization. Cancer research 51 18339854
1992 Localization of two human homologs, HHR6A and HHR6B, of the yeast DNA repair gene RAD6 to chromosomes Xq24-q25 and 5q23-q31. Genomics 49 1559696
1993 The ubc-2 gene of Caenorhabditis elegans encodes a ubiquitin-conjugating enzyme involved in selective protein degradation. Molecular and cellular biology 41 8441382
2004 RAD6B overexpression confers chemoresistance: RAD6 expression during cell cycle and its redistribution to chromatin during DNA damage-induced response. Oncogene 37 14981545
2003 Spermatid nuclear and sperm periaxonemal anomalies in the mouse Ube2b null mutant. Molecular reproduction and development 37 12784252
2020 Leishmania differentiation requires ubiquitin conjugation mediated by a UBC2-UEV1 E2 complex. PLoS pathogens 26 33108402
2012 Lysine 394 is a novel Rad6B-induced ubiquitination site on beta-catenin. Biochimica et biophysica acta 25 22705350
2018 Function of RAD6B and RNF8 in spermatogenesis. Cell cycle (Georgetown, Tex.) 24 28825854
2015 UBE2B is implicated in myofibrillar protein loss in catabolic C2C12 myotubes. Journal of cachexia, sarcopenia and muscle 24 27239408
2008 Novel variants in UBE2B gene and idiopathic male infertility. Journal of andrology 23 18497339
2006 Essential role of T-cell factor/beta-catenin in regulation of Rad6B: a potential mechanism for Rad6B overexpression in breast cancer cells. Molecular cancer research : MCR 23 17050667
2019 RAD6B is a major mediator of triple negative breast cancer cisplatin resistance: Regulation of translesion synthesis/Fanconi anemia crosstalk and BRCA1 independence. Biochimica et biophysica acta. Molecular basis of disease 22 31639439
2013 Identification of Ube2b as a novel target of androgen receptor in mouse sertoli cells. Biology of reproduction 22 23863405
2011 Rad6B acts downstream of Wnt signaling to stabilize β-catenin: Implications for a novel Wnt/β-catenin target. Journal of molecular signaling 22 21767405
2008 Novel UBE2B-associated polymorphisms in an azoospermic/oligozoospermic population. Asian journal of andrology 21 18385908
2015 Cellular Ubc2/Rad6 E2 ubiquitin-conjugating enzyme facilitates tombusvirus replication in yeast and plants. Virology 19 26135843
2008 Ubc2, an ortholog of the yeast Ste50p adaptor, possesses a basidiomycete-specific carboxy terminal extension essential for pathogenicity independent of pheromone response. Molecular plant-microbe interactions : MPMI 18 18052888
2024 UBE2A and UBE2B are recruited by an atypical E3 ligase module in UBR4. Nature structural & molecular biology 17 38182926
2019 RAD6B Plays a Critical Role in Neuronal DNA Damage Response to Resist Neurodegeneration. Frontiers in cellular neuroscience 17 31507381
2010 Ser(120) of Ubc2/Rad6 regulates ubiquitin-dependent N-end rule targeting by E3{alpha}/Ubr1. The Journal of biological chemistry 17 21041297
2000 Characterization of novel rad6/ubc2 ubiquitin-conjugating enzyme mutants in yeast. Current genetics 17 10803884
1999 Heat-induced cell cycle arrest of Saccharomyces cerevisiae: involvement of the RAD6/UBC2 and WSC2 genes in its reversal. Molecular microbiology 14 10361277
2013 UBE2B mRNA alterations are associated with severe oligozoospermia in infertile men. Molecular human reproduction 13 23378580
2011 A mutation in the Cc.ubc2 gene affects clamp cell morphogenesis as well as nuclear migration for dikaryosis in Coprinopsis cinerea. Fungal genetics and biology : FG & B 13 21281729
2015 A functional variant in the UBE2B gene promoter is associated with idiopathic azoospermia. Reproductive biology and endocrinology : RB&E 12 26223869
1995 Characterization of novel yeast RAD6 (UBC2) ubiquitin-conjugating enzyme mutants constructed by charge-to-alanine scanning mutagenesis. Journal of bacteriology 12 7836290
2022 UBE2B promotes ovarian cancer growth via promoting RAD18 mediated ZMYM2 monoubiquitination and stabilization. Bioengineered 11 35313791
1995 Caenorhabditis elegans UBC-1, a ubiquitin-conjugating enzyme homologous to yeast RAD6/UBC2, contains a novel carboxy-terminal extension that is conserved in nematodes. DNA and cell biology 11 7546294
2023 From tuberculosis bedside to bench: UBE2B splicing as a potential biomarker and its regulatory mechanism. Signal transduction and targeted therapy 10 36828823
2019 Ube2b-dependent degradation of DNMT3a relieves a transcriptional brake on opiate-induced synaptic and behavioral plasticity. Molecular psychiatry 10 31576007
2020 RAD6B Loss Disrupts Expression of Melanoma Phenotype in Part by Inhibiting WNT/β-Catenin Signaling. The American journal of pathology 9 33181138
2004 Caenorhabditis elegans UBC-2 functions with the anaphase-promoting complex but also has other activities. Journal of cell science 9 15466891
2013 Deletion of the ubiquitin-conjugating enzyme Ubc2 confers resistance to methylmercury in budding yeast by promoting Whi2 degradation. The Journal of toxicological sciences 8 23535409
2019 Alternative Splicing of RAD6B and Not RAD6A is Selectively Increased in Melanoma: Identification and Functional Characterization. Cells 7 31683936
2012 Genetic association of UBE2B variants with susceptibility to male infertility in a Northeast Chinese population. Genetics and molecular research : GMR 7 23079972
2009 Utility of DNA postreplication repair protein Rad6B in neoadjuvant chemotherapy response. Medical oncology (Northwood, London, England) 7 19466589
2021 Upregulation of ubiquitin conjugating enzyme E2B (Ube2b) ameliorates neuropathic pain by regulating Kcna2 (potassium voltage-gated channel subfamily A member 2) in primary afferent neurons. Bioengineered 6 34632937
2024 Formation of functional E3 ligase complexes with UBC2 and UEV1 of Leishmania mexicana. Molecular and biochemical parasitology 4 38556171
2020 Loss of RAD6B induces degeneration of the cochlea in mice. Biochemical and biophysical research communications 4 32868078
2021 The Role of RAD6B and PEDF in Retinal Degeneration. Neuroscience 3 34774969
2014 [UBE2B gene and male infertility: an update]. Zhonghua nan ke xue = National journal of andrology 1 24873167
2026 UBE2B Drives NF-κB Signaling and Gastric Cancer Progression through BIRC2-Mediated K63-Linked Ubiquitination of TRAF1. Molecular cancer research : MCR 0 41661096
2025 Targeting UBE2B-mediated U2AF1 degradation to alleviate endothelial dysfunction in renal ischemia-reperfusion injury: therapeutic potential of semaglutide. Molecular biology reports 0 41186784
2009 [Effect of hydroquinone on the expression of ubiquitin-conjugating enzyme Rad6B in human L-02 hepatic cells]. Wei sheng yan jiu = Journal of hygiene research 0 19548583