Affinage

Showing UBE2D2 — UBC4 is a alias.

UBE2D2

Ubiquitin-conjugating enzyme E2 D2 · UniProt P62837

Length
147 aa
Mass
16.7 kDa
Annotated
2026-06-10
53 papers in source corpus 23 papers cited in narrative 23 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 4/4 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

UBE2D2 (UbcH5B/UBC4) is a promiscuous ubiquitin-conjugating E2 enzyme central to proteasomal turnover of short-lived and abnormal proteins, a role first established genetically in yeast where loss of UBC4/UBC5 selectively impairs degradation of unstable substrates (PMID:2154373). After charging with ubiquitin via E1, it transfers ubiquitin to substrate lysines in cooperation with a broad array of RING and HECT E3 ligases, including E6AP for p53 (PMID:7724550), Mdm2 for p53 (PMID:15280377), the APC11 RING for securin and cyclin B (PMID:10922056), SCF complexes for IκBα and the transcription factor GCM1 (PMID:10918611, PMID:18703417), and c-Cbl for EGFR (PMID:18508924). Its catalytic mechanism is governed by conformational control: RING-domain binding (e.g., cIAP1, MUL1) and non-covalent ubiquitin engagement at the E2 backside surface stabilize a closed UbcH5B~Ub conformation that primes the thioester for transfer (PMID:30523153, PMID:35048531), and self-assembly of the UbcH5b~Ub conjugate into a spiral via backside interactions provides multiple active sites for processive ubiquitination (PMID:20152160). UBE2D2 supports diverse cellular processes, contributing to PINK1-Parkin-dependent mitophagy through ubiquitination of mitochondrial proteins (PMID:24906799), to VEGFR2 trafficking and angiogenic signaling in endothelial cells (PMID:37226882), and—via genetic analysis in yeast—it performs an essential HECT-E3-dependent function while acting as a monoubiquitinating E2 in RING-E3 pathways (PMID:21357418).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 1990 High

    Established the core physiological role of this E2 in selective protein turnover, answering whether UBC4/UBC5 activity is required for degradation of unstable proteins.

    Evidence Yeast deletion genetics with in vivo ubiquitin conjugate detection and stress phenotyping

    PMID:2154373

    Open questions at the time
    • Did not identify specific E3 partners or substrates
    • Mammalian ortholog function not directly tested
  2. 1993 High

    Defined the catalytic architecture, locating the ubiquitin-accepting cysteine in a cleft and identifying a conserved surface for E3 binding.

    Evidence X-ray crystallography of yeast Ubc4 at 2.7 Å

    PMID:8268156

    Open questions at the time
    • No substrate or E3-bound complex
    • Solution dynamics not addressed
  3. 1995 High

    Connected the E2 to specific E3-substrate pathways (E6AP/p53) and revealed intermolecular self-ubiquitination, showing how the enzyme engages HECT ligases and itself.

    Evidence In vitro reconstitution with purified components, in vivo inhibition, mutagenesis, and cross-linking

    PMID:7724550 PMID:7756256

    Open questions at the time
    • Physiological significance of K144 self-ubiquitination unclear
    • p53 work limited to the HPV E6 context
  4. 2000 High

    Demonstrated broad E3 partnership by reconstituting APC11- and SCF(β-TRCP)-dependent ubiquitination, establishing UBC4 as the preferred E2 for cell-cycle and IκBα substrates.

    Evidence In vitro ubiquitination with recombinant proteins, RING mutagenesis, and Co-IP with human SCF complex

    PMID:10918611 PMID:10922056

    Open questions at the time
    • In-cell requirement for these specific reactions not fully established
    • Chain-type selectivity not resolved
  5. 2004 High

    Mapped E2/E3 interaction surfaces and identified UbcH5B/C as the physiological E2 for Mdm2-mediated p53 degradation, linking structure to in-cell function.

    Evidence NMR structures with chemical-shift mapping and docking; in vitro E2 panel screen plus siRNA knockdown with stability assays

    PMID:15062086 PMID:15280377 PMID:15522302

    Open questions at the time
    • Redundancy among UbcH5 isoforms not fully dissected
    • Solution vs crystal conformational differences functionally unvalidated (#8 Medium)
  6. 2008 High

    Extended the substrate repertoire to receptor trafficking (EGFR via c-Cbl) and placental transcription factor turnover (GCM1 via SCF(FBXW2)), with spatial regulation at endosomes.

    Evidence siRNA knockdown, fluorescence localization, in vitro ubiquitination, Co-IP, and pulse-chase half-life measurement

    PMID:18508924 PMID:18703417

    Open questions at the time
    • Direct vs indirect contribution to endosomal sorting not separated
    • Chain linkage on these substrates not determined
  7. 2010 High

    Revealed the mechanistic basis of processivity and allosteric control through the self-assembled UbcH5b~Ub spiral and E4B U-box binding.

    Evidence Crystal structure of UbcH5b~Ub oxyester intermediate with biochemical assays; E4B U-box crystal structures with NMR and ITC

    PMID:20152160 PMID:20696396

    Open questions at the time
    • Physiological prevalence of the spiral intermediate uncertain
    • Functional consequence of E4B allostery in cells not shown
  8. 2011 High

    Resolved the division of labor between RING and HECT pathways, showing the essential cellular function depends on HECT E3 (Rsp5) transthiolation while RING E3s drive isopeptide bond formation.

    Evidence Yeast deletion/rescue with the N78S mutant, in vitro ubiquitination, and active-site mutagenesis

    PMID:21357418

    Open questions at the time
    • Identity of the essential HECT substrates not defined
    • Mammalian equivalence of this RING/HECT split untested
  9. 2014 High

    Defined a role in PINK1-Parkin mitophagy, showing the E2 is required for mitochondrial substrate ubiquitination downstream of Parkin recruitment.

    Evidence siRNA knockdown of multiple E2s, mitophagy clearance assays, immunofluorescence, and substrate ubiquitylation assays

    PMID:24906799

    Open questions at the time
    • Functional redundancy with UBE2D3/UBE2N/UBE2L3 obscures individual contribution
    • Direct vs indirect substrate ubiquitination not distinguished
  10. 2015 High

    Showed that E3 binding can be inhibitory, with the AO7/RNF25 U5BR clamp blocking the stimulatory backside ubiquitin site to slow ubiquitination.

    Evidence Co-crystallization, X-ray crystallography, ubiquitination rate assays, and RING mutagenesis

    PMID:26475854

    Open questions at the time
    • Cellular relevance of AO7-mediated inhibition not established
    • Generality across other E3s unknown
  11. 2016 Medium

    Delimited E2/E3 specificity by ruling out MuRF1 as a cognate partner, refining which ligases recruit this E2.

    Evidence Yeast two-hybrid, SPR, and cell-based degradation assays (negative result)

    PMID:27378730

    Open questions at the time
    • Negative finding for one E3 does not generalize
    • Conditions or modifications enabling weak interaction not exhaustively tested
  12. 2018 High

    Provided high-resolution mechanistic detail of how a RING dimer (cIAP1) and non-covalent backside ubiquitin together stabilize the catalytically primed closed conformation.

    Evidence X-ray crystallography at 1.7 Å of the ternary complex with ubiquitin transfer assays

    PMID:30523153

    Open questions at the time
    • Snapshot does not capture transfer dynamics
    • Substrate-bound geometry not included
  13. 2021 Medium

    Extended substrate and disease links to HECTD3 auto-ubiquitination, p62/autophagy-mediated drug resistance, and KAT2B/HMGB1-driven macrophage polarization, while identifying a small-molecule inhibitor binding the E2.

    Evidence In vitro ubiquitination, FRET inhibitor screen and direct binding, siRNA knockdown, xenograft; plus luciferase, Co-IP, ubiquitination, and flow cytometry

    PMID:33607208 PMID:33812169

    Open questions at the time
    • Pathway-level rather than direct mechanistic dissection (#19)
    • Inhibitor selectivity within the UbcH5 family not fully defined (#18)
  14. 2022 High

    Demonstrated multivalent substrate recognition, showing MUL1 RING simultaneously recruits E2 and the disordered p53-TAD and enhances substrate affinity in the conjugate complex.

    Evidence NMR, crystal structure of RING(MUL1):UBE2D2, oxyester-mimetic conjugate assays, and hydrolysis kinetics with N77A mutant

    PMID:35048531

    Open questions at the time
    • Cellular evidence for MUL1-mediated p53 ubiquitination not provided
    • Applicability to other disordered substrates untested
  15. 2023 Medium

    Established a cellular role in VEGFR2 trafficking and angiogenic signaling, showing depletion enhances receptor recycling and downstream signaling.

    Evidence siRNA knockdown, cell-surface biotinylation, recycling assay, signaling Western blots, and tubulogenesis assay in endothelial cells

    PMID:37226882

    Open questions at the time
    • Cognate E3 for VEGFR2 ubiquitination not identified
    • Direct ubiquitination of VEGFR2 by UBE2D2 not shown
  16. 2024 Medium

    Developed ubiquitin-variant inhibitors that block E1 and backside-binding surfaces, providing tools to probe and inhibit chain-building activity.

    Evidence Structural/biophysical characterization, binding affinity, in vitro chain-building assay, and UBE2D-family specificity profiling

    PMID:39473070

    Open questions at the time
    • Cellular activity of UbVs not demonstrated
    • Selectivity over UBE2D1/3 only partially resolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the broad E3 promiscuity of UBE2D2 is restricted to specific substrates and chain types in distinct cellular contexts remains unresolved.
  • Cognate E3s for VEGFR2 and essential yeast HECT substrates undefined
  • Regulation of isoform redundancy (UBE2D1/2/3) in vivo unclear
  • Determinants of chain linkage specificity not established

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 3 GO:0031386 protein tag activity 2
Localization
GO:0005768 endosome 1 GO:0005829 cytosol 1
Pathway
R-HSA-392499 Metabolism of proteins 4 R-HSA-9612973 Autophagy 2 R-HSA-162582 Signal Transduction 1 R-HSA-1640170 Cell Cycle 1
Partners
APC11C-CBLCIAP1E4BE6APMDM2MUL1RNF25
Complex memberships
APC/CSCF(FBXW2)SCF(β-TRCP)

Evidence

Reading pass · 23 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1990 Yeast UBC4 (ortholog of UBE2D2) mediates selective degradation of short-lived and abnormal proteins by generating high molecular weight ubiquitin-protein conjugates in vivo; loss of UBC4/UBC5 markedly reduces turnover of short-lived proteins and canavanyl-peptides but not long-lived proteins. Yeast genetics (ubc4ubc5 deletion mutants), in vivo ubiquitin conjugate detection, heat stress phenotype analysis The EMBO journal High 2154373
1993 Crystal structure of yeast Ubc4 (UBE2D2 ortholog) determined at 2.7 Å; the enzyme is an α/β protein with the ubiquitin-accepting cysteine located in a cleft between two loops, and the conserved surface adjacent to the active-site cysteine is proposed to function in protein–protein binding during ubiquitin thiol ester formation. X-ray crystallography (molecular replacement, 2.7 Å resolution) Biochemistry High 8268156
1995 Human UBC4 (UBE2D2) is required for E6AP (E6-associated protein)-mediated ubiquitinylation of p53 in the HPV E6 pathway; reconstitution of p53 ubiquitinylation from purified components showed UBC4 specifically ubiquitinylates E6AP, and in vivo inhibition of UBC4 blocks E6-stimulated p53 degradation. In vitro ubiquitinylation reconstitution with purified components, in vivo inhibition assay Proceedings of the National Academy of Sciences of the United States of America High 7724550
1995 Yeast UBC4 monoubiquitinates itself in vivo at K144 in an intermolecular (E2–E2) reaction; a second lysine (K64) is required for ubiquitination at K144; cross-linking demonstrates direct UBC4–UBC4 homointeraction in vitro. In vivo epitope-tagged ubiquitin coexpression, site-directed mutagenesis, chemical mapping, in vitro cross-linking Biochemistry High 7756256
2000 The RING-H2 protein APC11 and UBC4 (UBE2D2 ortholog) are sufficient to ubiquitinate APC substrates securin and cyclin B in vitro; APC11 alone supports multi-ubiquitin chain synthesis with E1 and UBC4, and the RING-H2 finger integrity is required for this activity. In vitro ubiquitination assay with recombinant proteins expressed in E. coli, RING domain mutagenesis Proceedings of the National Academy of Sciences of the United States of America High 10922056
2000 UBC4 (UBE2D2) and Ubc3 catalyze SCF(β-TRCP)-dependent, phosphorylation-dependent ubiquitination of IκBα; both E2s associate with the SCF(β-TRCP) complex isolated from human cells, and UBC4 is 19-fold more efficient than Ubc3 in catalyzing this reaction in vitro. In vitro ubiquitination reconstitution with recombinant components, co-immunoprecipitation with human cell SCF complex Oncogene High 10918611
2004 NMR solution structure of human UbcH5B (UBE2D2) determined; residues of UbcH5B important for binding to the CNOT4 RING domain were identified by NMR chemical shift perturbation, and a structural model of the UbcH5B/CNOT4 RING complex was generated by HADDOCK docking, revealing differences from the c-Cbl/UbcH7 complex at specific residues relevant to E2/E3 specificity. NMR chemical shift perturbation, homology modeling, HADDOCK docking, mutagenesis Structure (London, England : 1993) High 15062086
2004 UbcH5B/C (UBE2D2/3) are the physiological E2 enzymes for Mdm2-mediated ubiquitination and degradation of p53 in vivo; siRNA knockdown of UbcH5B/C in cells causes accumulation of both Mdm2 and p53, inhibits p53 ubiquitination and degradation, while in vitro screening showed only UbcH5A/B/C and E2-25K support Mdm2-mediated p53 ubiquitination. In vitro E2 panel screen, siRNA knockdown in mammalian cells, p53/Mdm2 ubiquitination and stability assays The Journal of biological chemistry High 15280377
2004 NMR solution structure of UbcH5B (UBE2D2) solved; the N-terminal helix involved in E3 binding displays a different orientation compared to crystal structures; Asn77 adopts multiple side-chain conformations in solution (contrasting single conformation in crystals), with implications for catalytic function. NMR spectroscopy (relaxation data, automated NOE assignments, homology modeling) Journal of molecular biology Medium 15522302
2008 Ubc4/5 (UBE2D2 ortholog) cooperates with the E3 c-Cbl to ubiquitinate EGFR; upon EGF stimulation Ubc4/5 and c-Cbl co-relocalize from plasma membrane to Hrs-positive endosomes, indicating EGFR continues to be ubiquitinated after internalization to facilitate polyubiquitination and subsequent lysosomal sorting. Localization (fluorescence microscopy), siRNA knockdown, in vitro ubiquitination assay, dominant-negative ubiquitin mutant experiments, EGFR degradation assay Molecular biology of the cell High 18508924
2008 UBE2D2 is the E2 ubiquitin-conjugating enzyme responsible for SCF(FBXW2)-mediated ubiquitination and proteasomal degradation of the placental transcription factor GCM1; UBE2D2 enzyme activity is required for GCM1 ubiquitination and association with the SCF(FBXW2) complex, and UBE2D2 knockdown prolongs GCM1 half-life in vivo. In vitro ubiquitination assay, Co-IP with SCF complex, RNA interference knockdown, pulse-chase half-life measurement Biology of reproduction High 18703417
2010 Crystal structure of UbcH5b~ubiquitin intermediate (oxyester-linked) determined at 2.2 Å; the conjugate self-assembles into an infinite spiral through backside interaction, providing multiple E2 active sites; biochemical assays show the self-assembled UbcH5b~Ub bridges the gap between substrate lysine and the E2 catalytic cysteine to enable efficient ubiquitination. X-ray crystallography (2.2 Å), in vitro ubiquitination biochemical assays Structure (London, England : 1993) High 20152160
2010 Crystal structures of E4B U box domain free and bound to UbcH5c and Ubc4 (UBE2D2 ortholog) determined by X-ray crystallography; the E4B U box is monomeric (unlike other U box domains), stabilized by a hydrogen-bond network; structural and calorimetric/NMR binding data suggest allosteric regulation of UbcH5c/Ubc4 by E4B U box. X-ray crystallography, NMR spectroscopy, isothermal titration calorimetry Structure (London, England : 1993) High 20696396
2011 The essential function of Ubc4/Ubc5 (UBE2D2 orthologs) in yeast is HECT E3-dependent (likely Rsp5); mutation N78S that specifically abolishes RING E3-catalyzed isopeptide bond formation but not HECT E3 transthiolation rescues lethality of ubc4/ubc5 deletion, establishing that Ubc4 acts as a monoubiquitinating E2 in RING E3 pathways while performing a critical function with a HECT E3. Yeast genetics (deletion and rescue with point mutants), in vitro ubiquitination assay, active-site and E3-binding mutagenesis The Journal of biological chemistry High 21357418
2014 UBE2D2 (along with UBE2D3, UBE2N, UBE2L3) is essential for Parkin-dependent mitophagy; UBE2D2/3 knockdown reduces autophagic clearance of depolarized mitochondria without affecting PINK1 stabilization or Parkin translocation; combined knockdown of all these E2s reduces mitochondrial polyubiquitylation and p62 recruitment, and UBE2D2/3 contribute to ubiquitination of mitofusins, TOM20, TOM70, VDAC1, and Parkin. siRNA knockdown in mammalian cells, mitophagy assay (autophagic clearance), immunofluorescence, ubiquitylation assays for specific substrates Journal of cell science High 24906799
2015 RING E3 AO7 (RNF25) binds UbcH5B (UBE2D2) with unusually high affinity via a unique UbcH5B-binding region (U5BR) connected by a linker to its RING domain, forming a clamp around the E2; the U5BR contacts the backside of UbcH5B distinct from both the active site and RING-interacting region; high-affinity clamp binding blocks stimulatory non-covalent ubiquitin binding to the UbcH5B backside, thereby decreasing ubiquitination rate. Co-crystallization, X-ray crystallography, ubiquitination rate assays, RING domain mutagenesis The Journal of biological chemistry High 26475854
2016 UBE2D2 does not interact with the muscle E3 ligase MuRF1 and is not the cognate E2 for MuRF1-dependent muscle wasting; yeast two-hybrid, surface plasmon resonance, and cell-based assays all showed no functional interaction between UBE2D2 and MuRF1, and UBE2D2 was unable to promote MuRF1-dependent α-actin degradation. Yeast two-hybrid, surface plasmon resonance (SPR), HEK293T cell-based ubiquitination/degradation assay, mRNA quantification during atrophy The international journal of biochemistry & cell biology Medium 27378730
2018 Crystal structure of cIAP1 RING dimer bound to UbcH5B covalently linked to ubiquitin (UbcH5B-Ub) and a non-covalent ubiquitin at 1.7 Å; cIAP1 RING promotes a closed UbcH5B-Ub conformation priming the thioester for transfer; non-covalent ubiquitin binding to the UbcH5B backside abuts the α1β1-loop and further stabilizes the closed active conformation. X-ray crystallography (1.7 Å), biochemical ubiquitin transfer assays The Journal of biological chemistry High 30523153
2021 UbcH5b (UBE2D2) supports HECTD3 auto-ubiquitination in vitro; the triterpenoid PC3-15 directly binds UbcH5b and inhibits UbcH5b-mediated p62 ubiquitination; the UbcH5b–p62 axis confers TNBC cell resistance to lapatinib by promoting autophagy. In vitro ubiquitination assay, FRET-based inhibitor screen, direct binding assay, siRNA knockdown, in vivo mouse xenograft Cancer letters Medium 33607208
2021 miR-30b-5p upregulation by ox-LDL reduces UBE2D2 ubiquitination activity, stabilizing KAT2B; elevated KAT2B then acetylates HMGB1, causing its nuclear exit and secretion, which promotes M1 macrophage polarization and recruitment. Luciferase reporter assay, co-immunoprecipitation, ubiquitination assay, qRT-PCR, flow cytometry, transwell assay Atherosclerosis Medium 33812169
2022 MUL1 RING domain recruits both UBE2D2 and the substrate p53-TAD simultaneously; RING(MUL1) binding induces the closed conformation of UBE2D2~Ub and accelerates its hydrolysis (suppressed by N77A mutation); TADp53 binding affinity to MUL1-RING is enhanced in complex with UBE2D2~Ub, indicating multivalent substrate recognition underlies ubiquitination of this intrinsically disordered protein. NMR, crystal structure determination of RING(MUL1):UBE2D2 complex, oxyester mimetic UBE2D2~Ub assays, hydrolysis kinetics, binding affinity measurements The FEBS journal High 35048531
2023 Depletion of UBE2D2 (or UBE2D1) in endothelial cells increases steady-state VEGFR2 levels at the plasma membrane, enhances VEGFR2 recycling, amplifies VEGF-A-stimulated MAPK/PLCγ1/Akt signaling, and stimulates endothelial tubulogenesis; establishing UBE2D2 as a regulator of VEGFR2 ubiquitination, trafficking, and angiogenic signaling. siRNA knockdown (reverse genetics screen), flow cytometry, cell-surface biotinylation, recycling assay, Western blot signaling analysis, tubulogenesis assay Journal of cell science Medium 37226882
2024 Ubiquitin variants (UbVs) that inhibit Ube2d2 (UbcH5b) were identified; two characterized UbVs bind Ube2d2 with low micromolar affinity at a site overlapping with E1 binding, and the more inhibitory UbV additionally blocks the non-covalent ubiquitin-binding backside site, inhibiting ubiquitin chain building. Structural characterization (crystallography/biophysics implied), binding affinity measurements, in vitro ubiquitin chain building assay, specificity profiling within Ube2d family The FEBS journal Medium 39473070

Source papers

Stage 0 corpus · 53 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1990 Ubiquitin-conjugating enzymes UBC4 and UBC5 mediate selective degradation of short-lived and abnormal proteins. The EMBO journal 447 2154373
2000 The RING-H2 finger protein APC11 and the E2 enzyme UBC4 are sufficient to ubiquitinate substrates of the anaphase-promoting complex. Proceedings of the National Academy of Sciences of the United States of America 156 10922056
2004 Regulation of p53 by the ubiquitin-conjugating enzymes UbcH5B/C in vivo. The Journal of biological chemistry 131 15280377
2004 Structural model of the UbcH5B/CNOT4 complex revealed by combining NMR, mutagenesis, and docking approaches. Structure (London, England : 1993) 111 15062086
1995 Reconstitution of p53-ubiquitinylation reactions from purified components: the role of human ubiquitin-conjugating enzyme UBC4 and E6-associated protein (E6AP). Proceedings of the National Academy of Sciences of the United States of America 100 7724550
2014 The ubiquitin-conjugating enzymes UBE2N, UBE2L3 and UBE2D2/3 are essential for Parkin-dependent mitophagy. Journal of cell science 96 24906799
2010 Crystal structure of UbcH5b~ubiquitin intermediate: insight into the formation of the self-assembled E2~Ub conjugates. Structure (London, England : 1993) 90 20152160
2008 Ubc4/5 and c-Cbl continue to ubiquitinate EGF receptor after internalization to facilitate polyubiquitination and degradation. Molecular biology of the cell 87 18508924
1993 Tertiary structures of class I ubiquitin-conjugating enzymes are highly conserved: crystal structure of yeast Ubc4. Biochemistry 83 8268156
2000 The Ustilago maydis ubc4 and ubc5 genes encode members of a MAP kinase cascade required for filamentous growth. Molecular plant-microbe interactions : MPMI 78 10875339
2020 Exosomes Mediated Transfer of Circ_UBE2D2 Enhances the Resistance of Breast Cancer to Tamoxifen by Binding to MiR-200a-3p. Medical science monitor : international medical journal of experimental and clinical research 73 32756532
1999 Activation of a UBC4-dependent pathway of ubiquitin conjugation during postnatal development of the rat testis. Developmental biology 54 10419697
1996 A novel rat homolog of the Saccharomyces cerevisiae ubiquitin-conjugating enzymes UBC4 and UBC5 with distinct biochemical features is induced during spermatogenesis. Molecular and cellular biology 50 8754804
1993 A major ubiquitin conjugation system in wheat germ extracts involves a 15-kDa ubiquitin-conjugating enzyme (E2) homologous to the yeast UBC4/UBC5 gene products. The Journal of biological chemistry 42 8419375
2010 Molecular basis for the association of human E4B U box ubiquitin ligase with E2-conjugating enzymes UbcH5c and Ubc4. Structure (London, England : 1993) 41 20696396
2000 SCF(beta-TRCP) and phosphorylation dependent ubiquitinationof I kappa B alpha catalyzed by Ubc3 and Ubc4. Oncogene 39 10918611
2005 Saccharomyces cerevisiae Ub-conjugating enzyme Ubc4 binds the proteasome in the presence of translationally damaged proteins. Genetics 35 16118187
2004 Solution structure of the ubiquitin-conjugating enzyme UbcH5B. Journal of molecular biology 30 15522302
2015 Insights into Ubiquitination from the Unique Clamp-like Binding of the RING E3 AO7 to the E2 UbcH5B. The Journal of biological chemistry 29 26475854
2003 Two ubiquitin-conjugating enzymes, UbcP1/Ubc4 and UbcP4/Ubc11, have distinct functions for ubiquitination of mitotic cyclin. Molecular and cellular biology 29 12724408
2021 Targeting ubiquitin conjugating enzyme UbcH5b by a triterpenoid PC3-15 from Schisandra plants sensitizes triple-negative breast cancer cells to lapatinib. Cancer letters 27 33607208
2011 Nuclear protein quality is regulated by the ubiquitin-proteasome system through the activity of Ubc4 and San1 in fission yeast. The Journal of biological chemistry 26 21324894
2007 Yeast Chfr homologs retard cell cycle at G1 and G2/M via Ubc4 and Ubc13/Mms2-dependent ubiquitination. Cell cycle (Georgetown, Tex.) 25 18202552
2011 The essential Ubc4/Ubc5 function in yeast is HECT E3-dependent, and RING E3-dependent pathways require only monoubiquitin transfer by Ubc4. The Journal of biological chemistry 24 21357418
2005 Expression, purification, and properties of the Ubc4/5 family of E2 enzymes. Methods in enzymology 24 16275319
2010 Ubc4 and Not4 regulate steady-state levels of DNA polymerase-α to promote efficient and accurate DNA replication. Molecular biology of the cell 23 20660159
2008 Ubiquitin-conjugating enzyme UBE2D2 is responsible for FBXW2 (F-box and WD repeat domain containing 2)-mediated human GCM1 (glial cell missing homolog 1) ubiquitination and degradation. Biology of reproduction 23 18703417
2005 Mice lacking the UBC4-testis gene have a delay in postnatal testis development but normal spermatogenesis and fertility. Molecular and cellular biology 23 16024774
1995 The yeast UBC4 ubiquitin conjugating enzyme monoubiquitinates itself in vivo: evidence for an E2-E2 homointeraction. Biochemistry 23 7756256
2021 miR-30b-5p releases HMGB1 via UBE2D2/KAT2B/HMGB1 pathway to promote pro-inflammatory polarization and recruitment of macrophages. Atherosclerosis 21 33812169
2018 Structural insights into non-covalent ubiquitin activation of the cIAP1-UbcH5B∼ubiquitin complex. The Journal of biological chemistry 19 30523153
2016 UBE2D2 is not involved in MuRF1-dependent muscle wasting during hindlimb suspension. The international journal of biochemistry & cell biology 15 27378730
2001 Yeast 2 microm plasmid copy number is elevated by a mutation in the nuclear gene UBC4. Yeast (Chichester, England) 15 11255249
1993 Selective ubiquitination of calmodulin by UBC4 and a putative ubiquitin protein ligase (E3) from Saccharomyces cerevisiae. FEBS letters 15 8391479
1995 Schizosaccharomyces pombe and Candida albicans cDNA homologues of the Saccharomyces cerevisiae UBC4 gene. Gene 12 7698660
2022 Circular RNA-UBE2D2 accelerates the proliferation and metastasis of non-small cell lung cancer cells via modulating microRNA-376a-3p/Eukaryotic Translation Initiation Factor 4γ2 axis. Bioengineered 10 35196197
2022 MUL1-RING recruits the substrate, p53-TAD as a complex with UBE2D2-UB conjugate. The FEBS journal 9 35048531
2008 The ubiquitin-conjugating enzymes, Ubc4 and Cdc34, mediate cadmium resistance in budding yeast through different mechanisms. Life sciences 8 18466927
2022 Circ_UBE2D2 Attenuates the Progression of Septic Acute Kidney Injury in Rats by Targeting miR-370-3p/NR4A3 Axis. Journal of microbiology and biotechnology 7 35722711
2009 A functional analysis of the yeast ubiquitin ligase Rsp5: the involvement of the ubiquitin-conjugating enzyme Ubc4 and poly-ubiquitination in ethanol-induced down-regulation of targeted proteins. Bioscience, biotechnology, and biochemistry 7 19809202
2007 Dosage rescue by UBC4 restores cell wall integrity in Saccharomyces cerevisiae lacking the myosin type II gene MYO1. Yeast (Chichester, England) 7 17397110
2023 The E2 ubiquitin-conjugating enzymes UBE2D1 and UBE2D2 regulate VEGFR2 dynamics and endothelial function. Journal of cell science 6 37226882
2022 Ubiquitin-Conjugating Enzymes Ubc1 and Ubc4 Mediate the Turnover of Hap4, a Master Regulator of Mitochondrial Biogenesis in Saccharomyces cerevisiae. Microorganisms 6 36557625
2022 RPS12 and UBC4 Are Related to Senescence Signal Production in the Ribosomal RNA Gene Cluster. Molecular and cellular biology 5 35384721
2020 The RING domain of mitochondrial E3 ubiquitin ligase 1 and its complex with Ube2D2: crystallization and X-ray diffraction. Acta crystallographica. Section F, Structural biology communications 5 31929179
2015 Rad25 protein is targeted for degradation by the Ubc4-Ufd4 pathway. The Journal of biological chemistry 4 25670855
2022 E2UbcH5B-derived peptide ligands target HECT E3-E2 binding site and block the Ub-dependent SARS-CoV-2 egression: A computational study. Computers in biology and medicine 2 35751189
2025 Rad5 and Ubc4 directly ubiquitinate PCNA at Lys164 in vitro. The Journal of biological chemistry 1 39826694
2025 UBE2D2 promotes gastric cancer progression by inhibiting ferroptosis through autophagy-dependent stabilization of CST1. International journal of biological macromolecules 1 40912429
2022 Quantitative proteome dataset profiling of UBC4 and UBC5 deletion strains in Saccharomyces cerevisiae. Data in brief 1 36426069
2019 Construction and Characterization of UBC4 Mutants with Single Residues Swapped from UBC5. Cell biochemistry and biophysics 1 31820282
2024 Structural and biophysical characterisation of ubiquitin variants that inhibit the ubiquitin conjugating enzyme Ube2d2. The FEBS journal 0 39473070
2024 Proteome Profiling of S. cerevisiae Strains Lacking the Ubiquitin-Conjugating Enzymes Ubc4 and Ubc5 During Exponential Growth and After Heat Shock Treatment. Microorganisms 0 39597624

Missed literature

Know a paper Affinage missed for UBE2D2? Flag it for the maintainers and the community.

No submissions yet.