Affinage

UBR5

E3 ubiquitin-protein ligase UBR5 · UniProt O95071

Length
2799 aa
Mass
309.4 kDa
Annotated
2026-06-10
100 papers in source corpus 57 papers cited in narrative 57 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 9/9 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

UBR5 (EDD/HYD) is a nuclear HECT-domain E3 ubiquitin ligase that integrates protein quality control, transcriptional regulation, the DNA damage response, and cell-cycle progression by selectively modifying substrates with distinct ubiquitin chain linkages (PMID:12011095, PMID:28330927, PMID:37409633). Structurally, it is built from an α-solenoid scaffold that assembles into an antiparallel dimer with higher-order oligomers and a dynamic catalytic HECT domain; biochemically it preferentially acts as a ubiquitin chain elongator on pre-ubiquitinated substrates, and its activity is tuned by an intramolecular contact between the MLLE/PABC domain and the HECT domain (PMID:26224628, PMID:37409633). Its modular architecture combines a ubiquitin-binding UBA domain, a UBR1 zinc finger, a HECT catalytic lobe whose unique C-lobe insert dictates E2 (UBCH4) specificity, and a PAM2-recognizing MLLE/PABC domain (PMID:12011095, PMID:17897937, PMID:23027739, PMID:26224628). Catalytic substrates span cell-cycle and growth regulators (MYC degraded independently of FBXW7, SOX2 at Lys115 gated by AKT phosphorylation, CDC73, Rb, and the mitotic checkpoint complex components BubR1/Bub3/Cdc20 whose ubiquitylation drives MCC disassembly and APC/C reactivation), metabolic and stress factors (acetylated PEPCK1, OGA, MOAP-1), and the centriolar substrate CP110 and ciliary protein CSPP1, with several substrates handed to UBR5 only after priming phosphorylation by DYRK2 within an EDD-DDB1-VprBP/DYRK2 complex (PMID:21726808, PMID:23362280, PMID:27721409, PMID:29742019, PMID:30894683, PMID:32029551, PMID:33208877, PMID:35551175, PMID:35217622, PMID:39441926, PMID:28242748). In the DNA damage response UBR5 restrains RNF168-driven ubiquitin spreading, ubiquitylates ATMIN at Lys238 to bias ATM toward MRN-dependent signaling, and cooperates with PRC1/BMI1 and the FACT subunit SPT16 to silence RNA Pol II elongation at lesions (PMID:22884692, PMID:25092319, PMID:27647897, PMID:31586398). Beyond degradative chemistry, UBR5 builds non-degradative K11 chains on Smad3 and K63 chains on TRIM28 and Akirin to control transcription, ferroptosis resistance, and NF-κB- and RLR-driven immunity (PMID:32339205, PMID:38278841, PMID:39260061). UBR5 also acts independently of its ligase activity: through the MLLE/PABC domain it scaffolds miRNA silencing by recruiting GW182, DDX6, and Tob1/2, stabilizes the transcription factor myocardin, and drives IFN-γ-induced PD-L1 transcription via PKR-STAT1 (PMID:21726813, PMID:20167605, PMID:35836797). It additionally executes agonist-dependent, chromatin-coupled degradation of nuclear hormone receptors including RARA, ERα, and others through sequential exchange of coactivators and UBR5 (PMID:37478846). Genetic loss is embryonic lethal in mouse with failed extraembryonic vascular development, and UBR5 catalytic activity is required for breast tumor growth and metastasis (PMID:15282321, PMID:28330927).

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 2002 Medium

    Established UBR5 as a nuclear, multidomain protein physically coupled to hormone-receptor transcription, defining the cellular compartment and an early functional context.

    Evidence Co-IP, NLS-driven nuclear import assay, and progesterone-receptor transactivation reporter

    PMID:12011095

    Open questions at the time
    • No catalytic activity demonstrated
    • PR not shown to be a ubiquitination substrate
  2. 2004 High

    Demonstrated UBR5 is essential in vivo, establishing a non-redundant developmental requirement.

    Evidence Murine Edd knockout with embryo phenotyping

    PMID:15282321

    Open questions at the time
    • Molecular substrate underlying vascular defect unidentified
    • Catalytic dependence not tested in this model
  3. 2006 High

    Defined the biochemistry of the MLLE/PABC domain as a PAM2-peptide recognition module linking UBR5 to translation/anti-proliferative regulators, the structural basis for its later ligase-independent scaffolding roles.

    Evidence ITC, SPR, NMR, GST pulldown, Co-IP with Tob2

    PMID:16554297

    Open questions at the time
    • Functional consequence of Tob2 binding not resolved
    • Did not connect to a defined complex
  4. 2006 Medium

    Placed UBR5 upstream of CHK2 activation, implicating it in DNA-damage checkpoint signaling.

    Evidence FHA-dependent Co-IP, RNAi epistasis, kinase activity assay after IR

    PMID:17074762

    Open questions at the time
    • Whether regulation is catalytic or scaffolding unresolved
    • No direct substrate in the CHK2 axis defined
  5. 2007 High

    Resolved how UBR5 reads ubiquitin (UBA domain) and validated catalytic competence and E2 specificity of its HECT C-lobe, anchoring its mechanism as a HECT ligase.

    Evidence 1.85 Å UBA crystal structure with mutagenesis and SPR; HECT C-lobe crystal structure with thioester ubiquitination assay

    PMID:17897937 PMID:23027739

    Open questions at the time
    • No full-length structure at this stage
    • Chain-linkage preferences not defined
  6. 2007 Medium

    Showed UBR5 is required for multiple cell-cycle checkpoints and chromosomal integrity, defining a broad role in genome stability.

    Evidence RNAi knockdown with flow cytometry and DNA-damage checkpoint assays

    PMID:18073532

    Open questions at the time
    • Direct ubiquitination targets driving checkpoints not identified
  7. 2011 High

    Separated UBR5's catalytic and non-catalytic functions by showing ligase-independent scaffolding of the miRNA silencing machinery via the PABC domain.

    Evidence Mouse ES-cell genetic screen, Co-IP with GW182/DDX6/Tob1-2, domain-deletion silencing assays

    PMID:21726813

    Open questions at the time
    • Whether scaffolding requires UBR5 oligomerization unknown
  8. 2011 High

    Identified the first catalytic substrate gated by a post-translational mark, establishing acetylation as a degron trigger feeding UBR5.

    Evidence In vitro ubiquitination, Co-IP, and acetyltransferase/deacetylase assays on PEPCK1

    PMID:21726808

    Open questions at the time
    • Chain linkage on PEPCK1 not defined
    • In vivo metabolic role inferred indirectly
  9. 2012 High

    Positioned UBR5 (with TRIP12) as a negative regulator that confines RNF168-dependent ubiquitin spreading at DNA breaks, a key restraint on damage signaling.

    Evidence siRNA depletion with immunofluorescence quantification of H2A-Ub, 53BP1, and BRCA1 spreading

    PMID:22884692

    Open questions at the time
    • Direct ubiquitination of RNF168 by UBR5 versus TRIP12 not fully separated
  10. 2014 High

    Defined site-specific control of ATM pathway choice through UBR5 ubiquitylation of ATMIN at Lys238, mechanistically linking UBR5 to MRN-dependent ATM activation.

    Evidence K238 mutagenesis, IR-stimulated ubiquitination, ATM foci and checkpoint assays

    PMID:25092319

    Open questions at the time
    • Chain linkage on ATMIN not specified
  11. 2015 High

    Elucidated MLLE-PAM2 recognition at atomic resolution and discovered an autoinhibitory MLLE-HECT intramolecular contact, providing a structural model for regulating UBR5 ligase activity.

    Evidence Crystal structure of MLLE-Paip1 PAM2 complex, NMR, ITC, domain mapping

    PMID:26224628

    Open questions at the time
    • Physiological trigger relieving autoinhibition unknown
  12. 2017 High

    Confirmed UBR5 catalytic activity is required for tumorigenesis and revealed cross-species conserved control of Wnt and Notch outputs through substrate ubiquitylation.

    Evidence CRISPR KO with catalytic-mutant rescue in TNBC; Drosophila/human ubiquitination of Groucho/TLE; C. elegans Notch epistasis; centrosomal CP110 ubiquitylation within EDD-DYRK2-DDB1-VprBP

    PMID:27185398 PMID:28242748 PMID:28330927 PMID:28689657

    Open questions at the time
    • Tissue-specific substrate priorities in vivo unresolved
  13. 2019 High

    Expanded UBR5 substrate logic to include kinase-primed (DYRK2/AKT) targets and replication-fork/H2A-coupled functions, refining how signaling selects UBR5 cargo.

    Evidence Site-directed mutagenesis of SOX2 K115/T116 with ubiquitination assays; replication-fork Co-IP, DNA fiber and H2A-Ub epistasis

    PMID:30894683 PMID:31586398

    Open questions at the time
    • Direct UBR5 substrate at the fork beyond H2A regulation unclear
  14. 2020 High

    Established UBR5 as an FBXW7-independent regulator of MYC and as a K63-chain builder in innate immune transcription, broadening its roles in oncogenesis and immunity.

    Evidence CRISPR screen and ubiquitination assays on MYC with Drosophila validation; K63-ubiquitination of Akirin with Drosophila and human NF-κB readouts

    PMID:32029551 PMID:32339205 PMID:33208877

    Open questions at the time
    • How chain-linkage selection is determined per substrate not defined
  15. 2022 High

    Provided reconstituted mechanistic proof that UBR5 disassembles the mitotic checkpoint complex and identified K63-ubiquitination of TRIM28 as a switch de-repressing antiviral transcription.

    Evidence Reconstitution from purified components and immunodepletion for MCC disassembly; CRISPR screen, K63-Ub/SUMO assays, and Ubr5 KO mouse viral challenge

    PMID:35217622 PMID:38278841

    Open questions at the time
    • Coordination of MCC disassembly with APC/C in intact cells not fully mapped
  16. 2023 High

    Delivered the full-length architecture (antiparallel dimer, dynamic HECT) and a chain-elongation activity model, and unified UBR5 as the ligase for agonist-dependent, chromatin-coupled nuclear hormone receptor turnover.

    Evidence Cryo-EM of full-length UBR5 with chain-elongation assays and AKIRIN2 interaction; chromatin recruitment and degradation assays across RARA/ERα/GR/PR and others

    PMID:37409633 PMID:37478846

    Open questions at the time
    • Structural basis of substrate selection still incompletely defined
    • How the dimer engages diverse substrates not resolved
  17. 2024 Medium

    Showed non-degradative K11 ubiquitylation as a distinct UBR5 output and tied UBR5 to Rb-dependent G1 control and CDK4/6-inhibitor sensitivity.

    Evidence K11-linked ubiquitination of Smad3 with ferroptosis assays; CRISPR KO with single-cell Rb measurement and CDK4/6 inhibitor sensitivity

    PMID:39260061 PMID:39441926

    Open questions at the time
    • Direct ubiquitination of Rb not demonstrated
    • Determinants of degradative versus non-degradative output unclear

Open questions

Synthesis pass · forward-looking unresolved questions
  • How UBR5 oligomeric architecture, MLLE-HECT autoregulation, and priming-kinase signals jointly dictate substrate choice and chain-linkage outcome across its many pathways remains unresolved.
  • No unified model linking dimer/oligomer state to substrate or linkage selection
  • Substrate-specific recruitment determinants largely unmapped

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016740 transferase activity 9 GO:0140096 catalytic activity, acting on a protein 8 GO:0016874 ligase activity 5 GO:0060090 molecular adaptor activity 3 GO:0140110 transcription regulator activity 3 GO:0031386 protein tag activity 1
Localization
GO:0000228 nuclear chromosome 3 GO:0005634 nucleus 3
Pathway
R-HSA-392499 Metabolism of proteins 4 R-HSA-73894 DNA Repair 4 R-HSA-74160 Gene expression (Transcription) 4 R-HSA-1640170 Cell Cycle 3 R-HSA-162582 Signal Transduction 2 R-HSA-168256 Immune System 2 R-HSA-8953854 Metabolism of RNA 1
Partners
ATMINBMI1DDB1DYRK2GW182MYCRNF168TRIM28
Complex memberships
EDD-DDB1-VprBP/DYRK2 E3 ligase complexmiRNA silencing (GW182-DDX6-Tob) complex

Evidence

Reading pass · 57 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2002 EDD/UBR5 contains a UBA domain, UBR1 zinc finger motif, and HECT domain; localizes to cell nuclei via importin alpha5 through consensus NLS; binds progesterone receptor (PR) and potentiates progestin-mediated gene transactivation; also binds CIB/DNAPK-interacting protein with altered association after DNA damage. Co-immunoprecipitation, nuclear localization assay, transactivation reporter assay The Journal of biological chemistry Medium 12011095
2004 Homozygous knockout of murine Edd is lethal by E10.5; Edd-deficient embryos display failed yolk sac and allantoic vascular development and defective chorioallantoic fusion, establishing an essential role in extraembryonic vascular development. Gene targeting/knockout mouse, embryo phenotyping Molecular and cellular biology High 15282321
2006 EDD/UBR5 interacts with CHK2 via a phospho-dependent interaction involving the CHK2 Forkhead-associated (FHA) domain and EDD's FHA-binding threonines; EDD is required upstream of CHK2 for efficient activating phosphorylation of CHK2 after ionizing radiation or radiomimetic treatment. Co-immunoprecipitation, RNA interference (RNAi) knockdown, kinase activity assay The Journal of biological chemistry Medium 17074762
2006 The PABC/MLLE domain of UBR5/HYD binds PAM2 peptide motifs with micromolar affinity, similar to PABP's PABC domain; UBR5 PABC domain interacts with anti-proliferative Tob2 protein, linking UBR5 to translation regulation and cell cycle control. Isothermal titration calorimetry (ITC), surface plasmon resonance (SPR), NMR chemical shift perturbation, GST pulldown, co-immunoprecipitation The Journal of biological chemistry High 16554297
2007 The UBA domain of EDD/UBR5 binds ubiquitin; crystal structure at 1.85 Å reveals recognition via UBA helices α1 and α3 with hydrogen bonds including ordered water molecules; site-directed mutagenesis confirmed functional importance of interface residues; SPR showed no strong preference for polyubiquitin chains over monoubiquitin. ITC, NMR titrations, pulldown, 1.85 Å crystal structure, site-directed mutagenesis, SPR The Journal of biological chemistry High 17897937
2007 EDD/UBR5 interacts with APC tumor suppressor protein; EDD overexpression increases APC and Axin protein levels and inhibits β-catenin/LEF1 Wnt signaling; EDD knockdown reduces APC protein level without altering its mRNA, increasing β-catenin. Mass spectrometry of APC immunocomplexes, co-immunoprecipitation, siRNA knockdown, immunofluorescence co-localization, reporter assays Genes to cells Medium 18076571
2007 EDD/UBR5 is necessary for G1/S and intra-S phase DNA damage checkpoint activation and for maintenance of G2/M arrest after DSBs; EDD depletion leads to radioresistant DNA synthesis, premature mitotic entry, polyploidy, and mitotic catastrophe. RNAi knockdown, cell cycle analysis (flow cytometry), DNA damage assays Cell cycle Medium 18073532
2010 UBR5 associates with CDK9 subunit of P-TEFb and mediates its polyubiquitination; TFIIS binds UBR5 and stimulates CDK9 polyubiquitination; UBR5, CDK9, and TFIIS co-localize along the γ-fibrinogen gene; TFIIS overexpression increases CDK9 association with gene regions and enhances RNAPII Ser2-CTD phosphorylation. Co-immunoprecipitation, chromatin immunoprecipitation (ChIP), ubiquitination assay, co-localization The Journal of biological chemistry Medium 21127351
2010 UBR5 localizes to smooth muscle cell nuclei and forms a complex with myocardin both in vivo and in vitro; UBR5 enhances transactivation of smooth muscle-specific promoters by myocardin family proteins and stabilizes myocardin protein (attenuates its degradation) independently of E3 ligase activity, requiring only HECT and UBR1 domains. Yeast two-hybrid, co-immunoprecipitation, siRNA knockdown, promoter-luciferase reporter, western blot protein stability assay The Journal of biological chemistry Medium 20167605
2010 EDD/UBR5 interacts with GSK-3β and β-catenin; EDD expression promotes nuclear accumulation of both proteins and enhances β-catenin stability and activity by ubiquitinating β-catenin through Lys29- or Lys11-linked ubiquitin chains, leading to increased β-catenin protein levels. Co-immunoprecipitation, ubiquitination assay (K29/K11 chain linkage), nuclear fractionation, luciferase reporter assay Molecular biology of the cell Medium 21118991
2011 PEPCK1 is acetylated by P300 acetyltransferase; acetylated PEPCK1 interacts with UBR5 HECT E3 ligase, promoting PEPCK1 ubiquitination and degradation; SIRT2 deacetylates PEPCK1, stabilizing it; high glucose destabilizes PEPCK1 via this acetylation-UBR5 axis. Co-immunoprecipitation, in vitro ubiquitination assay, protein stability assay, acetylation mapping Molecular cell High 21726808
2011 EDD/UBR5 is a key component of the miRNA silencing pathway; EDD interacts with GW182 proteins in Argonaute-miRNA complexes; EDD E3 ligase activity is dispensable for miRNA silencing; the PABC domain of EDD is essential for silencing function by recruiting DDX6 and Tob1/2. Genetic screen in mouse ES cells, co-immunoprecipitation, domain deletion analysis, RNAi silencing assay Molecular cell High 21726813
2011 EDD/UBR5 interacts with both HPV18 E6 and E6AP independently; EDD regulates E6AP expression levels independently of E6; loss of EDD stimulates the proteolytic activity of the E6/E6AP complex and enhances cell resistance to apoptotic stimuli. Mass spectrometry, co-immunoprecipitation, siRNA knockdown, protein stability/degradation assays Journal of virology Medium 21228227
2011 EDD/UBR5 physically interacts with p53 and this interaction blocks ATM-mediated phosphorylation of p53 at Ser15; EDD depletion induces p53 Ser15 phosphorylation and activates p53 target genes; EDD overexpression inhibits p53-Ser15 phosphorylation during DNA damage independently of E3 ligase activity; G1 arrest from EDD depletion is p53-dependent. Co-immunoprecipitation, siRNA knockdown, phospho-specific western blotting, co-depletion epistasis The Journal of biological chemistry Medium 21383020
2012 TRIP12 and UBR5 control accumulation of RNF168 by targeting it for degradation; depletion of TRIP12 and UBR5 allows supraphysiological accumulation of RNF168, leading to massive spreading of ubiquitin conjugates (H2A-Ub) and hyperaccumulation of 53BP1 and BRCA1 beyond DNA lesions. siRNA depletion, immunofluorescence, DSB-induced ubiquitin spreading assay Cell High 22884692
2012 Crystal structure of the C-lobe of the HECT domain of human UBR5 reveals a unique four-residue insert elongating helix 2, creating a protruding loop likely important for E2 specificity toward UBCH4; the C-lobe forms a thioester-linked E3-ubiquitin complex in ubiquitination assays. X-ray crystallography, ubiquitination thioester assay, NMR Acta crystallographica Section F High 23027739
2012 EDD/UBR5 interacts with microspherule protein Msp58 (MCRS1); EDD depletion increases Msp58 protein levels and extends its half-life, demonstrating EDD negatively regulates Msp58 stability via the ubiquitin-proteasome pathway; knockdown of either protein affects cyclin B, D, E levels and cell cycle progression. Co-immunoprecipitation, in vitro binding, confocal co-localization, protein half-life assay, siRNA knockdown, flow cytometry Biochimica et biophysica acta Medium 23069210
2013 Dyrk2 phosphorylates TERT; phosphorylated TERT associates with the EDD-DDB1-VprBP E3 ligase complex, leading to ubiquitin-mediated TERT degradation at G2/M phase; Dyrk2 depletion disrupts cell cycle-dependent TERT regulation and causes constitutive telomerase activation. Co-immunoprecipitation, ubiquitination assay, telomerase activity assay (TRAP), kinase assay, siRNA knockdown, cell cycle synchronization The Journal of biological chemistry High 23362280
2013 HIV-1 Vpr enhances interaction between TERT and the VPRBP substrate receptor of the DYRK2-associated EDD-DDB1-VPRBP E3 ligase, increasing TERT ubiquitination and degradation; a Vpr mutation found in long-term non-progressors failed to promote TERT destabilization. Co-immunoprecipitation, ubiquitination assay, telomerase activity assay, mutant Vpr analysis The Journal of biological chemistry Medium 23612978
2013 VprBP/DCAF1 serves as substrate recognition subunit for both the RING-type CRL4 and HECT-type EDD/UBR5 E3 ligase complexes; VprBP assembles into the EDD complex with DYRK2 and DDB1. Review/biochemical analysis of prior co-IP and complex assembly data (cited from primary studies) BMC molecular biology Low 24028781
2014 UBR5-mediated ubiquitination of ATMIN at lysine 238 is stimulated by ionizing radiation (IR); this ubiquitination decreases ATMIN-ATM interaction, promotes MRN-mediated ATM signaling, and NBS1/ATM foci formation; UBR5 deficiency or ATMIN K238 mutation impairs ATM checkpoint activation and increases radiosensitivity. Co-immunoprecipitation, site-directed mutagenesis (K238), ubiquitination assay, IR treatment, ATM foci formation, checkpoint assays, siRNA knockdown Proceedings of the National Academy of Sciences of the United States of America High 25092319
2014 UBR5 and DYRK2 regulate hPXR stability; UBR5 knockdown causes hPXR accumulation and increased hPXR transcriptional activity; DYRK2-dependent phosphorylation of hPXR facilitates its subsequent ubiquitination by UBR5. siRNA knockdown, MS analysis, kinome-wide siRNA screen, protein stability assay, reporter assay The Biochemical journal Medium 24438055
2015 The MLLE domain of UBR5 binds PAM2 peptides (from Paip1 and GW182) with defined network of hydrophobic and ionic interactions shown by crystal structure with Paip1 PAM2 peptide; a novel intramolecular interaction between MLLE domain and adjacent HECT domain via a PAM2-like sequence was identified, suggesting regulation of UBR5 ligase activity. X-ray crystallography (MLLE-PAM2 complex), NMR, ITC, domain interaction mapping The Journal of biological chemistry High 26224628
2015 EDD1/UBR5 interacts with TIP60 acetyltransferase and negatively regulates TIP60 stability through the proteasome pathway; HPV E6 oncogene exploits EDD1 to destabilize TIP60; depletion of EDD1 or gain-of-function of TIP60 inhibits HPV-positive cervical cancer cell growth in vitro and in vivo. Proteomics, co-immunoprecipitation, ubiquitination/turnover assay, colony formation, soft agar, xenograft Oncogene Medium 26234678
2016 UBR5 physically interacts with MOAP-1, ubiquitylates MOAP-1 in vitro, and inhibits MOAP-1 stability in cells; Dyrk2 kinase cooperates with UBR5 in MOAP-1 ubiquitylation; UBR5 knockdown increases MOAP-1 levels, enhances Bax activation, and sensitizes cisplatin-resistant ovarian cancer cells to apoptosis. Co-immunoprecipitation, in vitro ubiquitination assay, protein stability assay, siRNA knockdown, Bax activation assay, cisplatin sensitivity assay Oncogene High 27721409
2016 UBR5 forms damage-inducible nuclear foci dependent on PRC1 components BMI1, RING1a, and RING1b; UBR5 associates with BMI1 and FACT components SPT16/SSRP1; UBR5 ubiquitinates SPT16; UBR5 and BMI1 repress RNA Pol II transcription elongation at UV-damaged chromatin by negatively regulating FACT-dependent Pol II elongation; UBR5/BMI1 KO cells are hypersensitive to UV. Mass spectrometry, co-immunoprecipitation, in vitro ubiquitination assay, transcription elongation assay, immunofluorescence foci analysis, CRISPR KO, UV sensitivity assay Proceedings of the National Academy of Sciences of the United States of America High 27647897
2016 UBR5 depletion reduces primary cilia formation; CSPP1 (centrosomal/ciliary protein required for cilia formation) is a UBR5-interacting protein; UBR5 ubiquitylates CSPP1; UBR5 is required for cytoplasmic organization of CSPP1-comprising centriolar satellites in centrosomal periphery. Co-immunoprecipitation, in vitro ubiquitination assay, siRNA knockdown, ciliogenesis assay, centrosomal fractionation Molecular biology of the cell Medium 29742019
2016 C. elegans UBR-5 negatively regulates Notch-type (GLP-1/LIN-12) signaling; ubr-5 loss-of-function suppresses glp-1 and lin-12 loss-of-function defects; ubr-5 acts in germ cells (receiving cells) to limit GLP-1 signaling; UBR-5 acts redundantly with SEL-10 (SCF E3 ligase) to limit Notch signaling in certain tissues. C. elegans genetics, suppressor/enhancer epistasis, loss-of-function analysis G3 (Bethesda) Medium 27185398
2017 Hyd/UBR5 is required for Wnt signal responses downstream of activated Armadillo/β-catenin in Drosophila and human cell lines; Groucho/TLE is a functionally relevant substrate whose ubiquitylation by UBR5 is induced by Wnt signaling and conferred by β-catenin; TLE inactivation by UBR5-dependent ubiquitylation also involves VCP/p97 AAA ATPase. Drosophila genetics, siRNA knockdown in human cells, co-immunoprecipitation, ubiquitination assay, epistasis Molecular cell High 28689657
2017 CRISPR/Cas9 deletion of UBR5 in murine TNBC model abrogates tumor growth and metastasis in vivo; reconstitution with wild-type UBR5 but not a catalytically inactive mutant rescues this phenotype, demonstrating E3 ligase activity is required for tumor growth and metastasis functions. CRISPR/Cas9 knockout, catalytically inactive mutant rescue, in vivo tumor model Cancer research High 28330927
2018 UBR5 is highly expressed in iPSCs and is required for proteasomal degradation of both normal and polyQ-expanded mutant huntingtin (HTT); UBR5 loss increases HTT levels and triggers polyQ-expanded aggregation in HD-iPSCs; UBR5 overexpression induces polyubiquitination and degradation of mutant HTT, reducing aggregates. siRNA knockdown, overexpression, ubiquitination assay, aggregation assay, invertebrate model (C. elegans/Drosophila) knockdown Nature communications High 30038412
2018 UBR5 is required for cytoplasmic organization of CSPP1-comprising centriolar satellites; UBR5 ubiquitylates CSPP1 and is required for primary cilia formation. Co-immunoprecipitation, ubiquitination assay, ciliogenesis assay, siRNA knockdown Molecular biology of the cell Medium 29742019
2019 OTUD5 deubiquitinase stabilizes UBR5 E3 ligase; OTUD5 localizes to DSBs and interacts with UBR5; the OTUD5-UBR5 complex represses RNA Pol II elongation and RNA synthesis at DSBs; OTUD5 interacts with FACT component SPT16 via a separate region; both UBR5 stabilization (catalytic) and FACT binding (scaffolding) activities of OTUD5 are required for Pol II arrest. DUB RNAi screen, co-immunoprecipitation, transcription elongation assay, domain mapping, co-localization Nucleic acids research Medium 30508113
2019 AKT phosphorylates SOX2 at Thr116, which inhibits UBR5 interaction with SOX2; UBR5 ubiquitinates SOX2 at Lys115, promoting its degradation; AKT-mediated phosphorylation stabilizes SOX2 by blocking this UBR5-mediated ubiquitination. Co-immunoprecipitation, ubiquitination assay, site-directed mutagenesis (K115, T116), kinase assay, protein stability assay Oncogene High 30894683
2019 PPARγ promotes ATM signaling through interaction with MRN complex and UBR5; PPARγ is essential for UBR5 activity targeting ATMIN; PPARγ depletion increases ATMIN protein and suppresses DDR-induced ATM signaling; disrupted PPARγ-UBR5 interaction is observed in PAH patient endothelial cells. Proteomic interaction screen, co-immunoprecipitation, siRNA knockdown, ATM signaling assays Cell reports Medium 30699358
2019 UBR5 interacts with components of the replication fork including TLS polymerase polη; UBR5 depletion causes S-phase progression defects, ssDNA accumulation, and mis-regulation of H2A ubiquitination (UbiH2A); blocking H2A ubiquitination rescues replication problems in UBR5-depleted cells; polη is the main cause of replication defects when UBR5 is silenced; polη interacts with H2A, suggesting UbiH2A regulates polη recruitment. Co-immunoprecipitation, siRNA knockdown, DNA fiber assay (S-phase progression), ssDNA accumulation assay, epistasis with H2A modification Nucleic acids research Medium 31586398
2019 UBR5 interacts with H/ACA ribonucleoprotein complex components in ESCs; loss of UBR5 induces abnormal accumulation of rRNA processing intermediates, diminished ribosomal levels, increased p53 levels, and decreased cell proliferation. Protein interactome (MS), co-immunoprecipitation, rRNA processing assay, western blot, proliferation assay FEBS letters Medium 31365120
2020 UBR5 ubiquitinates MYC and promotes its degradation independently of FBXW7; UBR5 silencing induces MYC protein accumulation; UBR5 and MYC are co-amplified in MYC-driven cancers; in p53-mutant MYC-amplified cells, UBR5 suppresses MYC-mediated apoptosis; Drosophila HYD suppresses dMYC-dependent overgrowth. CRISPR/Cas9 screen, co-immunoprecipitation, ubiquitination assay (K48-linked), siRNA knockdown, protein stability assay, Drosophila genetics Cancer research / Scientific reports High 32029551 33208877
2020 Drosophila Hyd/UBR5 mediates Lys63-linked polyubiquitination of the NF-κB cofactor Akirin, which is required for efficient Akirin-Relish (NF-κB) interaction and transcription of immune-induced anti-microbial peptide genes; human UBR5 is also required for IL-6 transcription downstream of NF-κB signaling by LPS or IL-1β. RNAi screen, ubiquitination assay (K63 chain), co-immunoprecipitation, Drosophila survival assay, human cell siRNA knockdown, luciferase reporter PLoS pathogens High 32339205
2020 Loss of UBR5 HECT domain in B cells causes a block in B-cell maturation in spleen and upregulation of spliceosome components; UBR5 is required for B-cell maturation by promoting degradation/destabilization of spliceosome components during B-cell development. Conditional knockout (HECT domain deletion), flow cytometry, western blot, gene expression analysis Blood Medium 32325489
2020 UBR5 controls β-catenin-mediated signaling and regulates p53 protein level in ovarian cancer; tumor-derived UBR5 promotes macrophage recruitment via chemokines/cytokines. siRNA knockdown, CRISPR KO, protein stability assay, cytokine/chemokine profiling Nature communications Medium 33293516
2021 UBR5 interacts with and promotes degradation of CAPZA1 (F-actin capping protein α subunit) via ubiquitin-proteasome system; UBR5 overexpression induces F-actin accumulation; CAPZA1 downregulation reverses UBR5-knockdown-mediated suppression of pancreatic cancer cell migration/invasion. Co-immunoprecipitation with mass spectrometry, ubiquitination assay, protein stability assay, siRNA knockdown, F-actin staining, migration/invasion assay, in vivo liver metastasis model Frontiers in oncology Medium 33777788
2022 UBR5 promotes antiviral immunity by mediating Lys63-linked ubiquitination of TRIM28 (epigenetic repressor of RLRs); this modification prevents intramolecular SUMOylation of TRIM28, disengaging TRIM28-imposed transcriptional repression of RIG-I-like receptor genes; Ubr5 KO mice are more susceptible to RNA virus infection. CRISPR KO screen (375 E3 ligases), ubiquitination assay (K63-linked), SUMOylation assay, co-immunoprecipitation, Ubr5 KO mice, viral challenge Nature communications High 38278841
2022 UBR5 polyubiquitinates CDC73 at Lys243, Lys247, and Lys257 in a non-canonical manner dependent on non-phosphorylated CDC73 (Ser465); CDC73 destabilization by UBR5 regulates β-catenin and E-cadherin expression and tumor cell apoptosis and CD8+ T cell infiltration in TNBC. Co-immunoprecipitation, ubiquitination assay, site-directed mutagenesis (K243/247/257, S465), protein stability assay, in vivo tumor model Cell death & disease High 35551175
2022 UBR5 ubiquitinates BubR1, Bub3, and Cdc20 (MCC components); UBR5 promotes dissociation of the Bub3•BubR1 subcomplex from APC/C via ubiquitylation, facilitated by ATP hydrolysis; UBR5 immunodepletion slows MCC disassembly and prolongs lag period in APC/C activity recovery; a reconstituted system from purified components shows UBR5- and ubiquitylation-dependent Bub3•BubR1 dissociation. Co-immunoprecipitation from nocodazole-arrested HeLa cells, in vitro ubiquitination assay, immunodepletion, reconstitution from purified components, APC/C activity assay Proceedings of the National Academy of Sciences of the United States of America High 35217622
2022 UBR5 enhances IFN-γ-induced PD-L1 transcription through its PABC domain by upregulating PKR and downstream STAT1/IRF1, in an E3 ubiquitin activity-independent manner. RNA-seq, qPCR, ChIP-qPCR, luciferase reporter, siRNA/CRISPR knockdown and reconstitution, domain deletion analysis Theranostics Medium 35836797
2023 Cryo-EM structure of full-length human UBR5 reveals an α-solenoid scaffold assembled into an antiparallel dimer with further oligomeric states; the catalytic HECT domain is dynamic; AKIRIN2 (proteasomal nuclear import factor) was identified as an interacting protein; UBR5 preferentially acts as a ubiquitin chain elongator on pre-ubiquitinated substrates. Cryo-EM (full-length human UBR5), negative stain EM (UBR5-RARA/RXRA complex), co-immunoprecipitation, in vitro ubiquitin chain elongation assay The EMBO journal High 37409633
2023 UBR5 drives agonist-dependent degradation of multiple nuclear hormone receptors (RARA, RXRA, GR, ERα, LXR, PR, VDR); cryo-EM structure of full-length human UBR5 obtained; agonist ligands induce sequential, mutually exclusive recruitment of NCOAs and UBR5 to chromatin; SERDs degrade ERα through differential recruitment of UBR5 or RNF111. Cryo-EM structure, negative-stain EM with RARA/RXRA complex, co-immunoprecipitation, chromatin recruitment assays, siRNA knockdown, protein stability assay Molecular cell High 37478846
2024 UBR5 is required for Rb protein concentration decrease during G1; UBR5 KO cells have increased Rb concentration in early G1, lower G1-S transition rate, and increased sensitivity to CDK4/6 inhibitors. UBR5 CRISPR KO, single-cell protein concentration measurement, cell cycle analysis, CDK4/6 inhibitor sensitivity assay Science advances Medium 39441926
2024 UBR5 acts as an E3 ubiquitin ligase for OGA (O-GlcNAcase); UBR5 binds and promotes OGA ubiquitination and degradation, leading to increased O-GlcNAcylation; this promotes EMT-mediated gemcitabine resistance in pancreatic cancer. Co-immunoprecipitation, ubiquitination assay, protein stability assay, siRNA knockdown, OGA level rescue experiments Cell death & disease Medium 38755129
2024 UBR5 stabilizes oxaliplatin-activated Smad3 via Lys11-linked polyubiquitination (non-degradative), which facilitates transcriptional repression of ATF3, induction of SLC7A11, and inhibition of ferroptosis, conferring chemoresistance in colorectal cancer. Co-immunoprecipitation, ubiquitination assay (Lys11-linked chain), siRNA knockdown, ferroptosis assay, transcriptional reporter Redox biology Medium 39260061
2015 RanGTP promotes the dissociation of importin-β from BuGZ and Bub3 in metaphase, resulting in increased binding of BuGZ and Bub3 to Ubr5; this leads to Ubr5-dependent ubiquitination and turnover of BuGZ and Bub3, facilitating metaphase-to-anaphase transition (SAC silencing). Co-immunoprecipitation, ubiquitination assay, siRNA knockdown, cell cycle analysis The Journal of cell biology Medium 26438829
2017 Cep78 localizes to mature centrioles and directly interacts with VprBP, a component of the EDD-DYRK2-DDB1VprBP E3 ligase; Cep78 binds specifically to EDD-DYRK2-DDB1VprBP (not CRL4VprBP) and inhibits its activity; EDD-DYRK2-DDB1VprBP ubiquitinates CP110 (novel centrosomal substrate) after DYRK2-dependent phosphorylation; Cep78 impedes ubiquitin transfer from EDD to CP110 without affecting CP110 phosphorylation. Co-immunoprecipitation, in vitro ubiquitination assay, centrosome fractionation, domain interaction mapping, centriole length measurement, cilia assay EMBO reports High 28242748
2018 UBR5 interacts with HTLV-1 HBZ protein; UBR5 knockdown enhances HBZ steady-state levels by stabilizing HBZ; Co-IP assays confirmed HBZ ubiquitination that is reduced upon UBR5 knockdown; MS/MS identified seven ubiquitinated lysines in HBZ. Affinity-tagged protein pulldown, shotgun proteomics, co-immunoprecipitation, shRNA knockdown, protein stability assay, MS/MS ubiquitin site mapping Frontiers in microbiology Medium 29441057
2022 UBR5 ubiquitinates MERS-CoV ORF4b at Lys36, promoting its degradation; UBR5 can translocate into the nucleus via its NLS to regulate ORF4b stability in both cytoplasm and nucleus; UBR5 knockdown enhances ORF4b anti-immune activity and increases MERS-CoV replication. Co-immunoprecipitation, ubiquitination assay, site-directed mutagenesis (K36), siRNA knockdown, viral replication assay, subcellular localization assay Journal of virology Medium 35980206
2020 UBR5 regulates FBP1 expression in pancreatic cancer by binding to C/EBPα transcription factor and promoting its ubiquitination and degradation; UBR5-induced aerobic glycolysis is dependent on this FBP1-C/EBPα axis. Co-immunoprecipitation, ubiquitination assay, siRNA knockdown, protein stability assay, glycolysis assay Oncogene Medium 33122826
2013 EDD/UBR5 physically interacts with alpha4 phosphoprotein; Co-IP confirmed EDD-alpha4 interaction; EDD knockdown leads to decreased PP2Ac polyubiquitination and accumulation of PP2Ac protein, identifying PP2Ac as an EDD substrate regulated via alpha4 as scaffold. Co-immunoprecipitation using deletion mutants, siRNA knockdown, proteasome inhibitor treatment, polyubiquitination assay Molecular and cellular endocrinology Medium 24145130

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2011 Acetylation regulates gluconeogenesis by promoting PEPCK1 degradation via recruiting the UBR5 ubiquitin ligase. Molecular cell 339 21726808
2012 TRIP12 and UBR5 suppress spreading of chromatin ubiquitylation at damaged chromosomes. Cell 300 22884692
2010 The first-in-human study of the hydrogen sulfate (Hyd-sulfate) capsule of the MEK1/2 inhibitor AZD6244 (ARRY-142886): a phase I open-label multicenter trial in patients with advanced cancer. Clinical cancer research : an official journal of the American Association for Cancer Research 183 20179232
2020 Tumor derived UBR5 promotes ovarian cancer growth and metastasis through inducing immunosuppressive macrophages. Nature communications 137 33293516
2013 The E3 ubiquitin ligase UBR5 is recurrently mutated in mantle cell lymphoma. Blood 118 23407552
2004 Somatic mutations and altered expression of the candidate tumor suppressors CSNK1 epsilon, DLG1, and EDD/hHYD in mammary ductal carcinoma. Cancer research 112 14871824
2015 Functional Roles of the E3 Ubiquitin Ligase UBR5 in Cancer. Molecular cancer research : MCR 107 26464214
2002 EDD, the human hyperplastic discs protein, has a role in progesterone receptor coactivation and potential involvement in DNA damage response. The Journal of biological chemistry 96 12011095
2010 The EDD E3 ubiquitin ligase ubiquitinates and up-regulates beta-catenin. Molecular biology of the cell 93 21118991
2017 E3 Ubiquitin Ligase UBR5 Drives the Growth and Metastasis of Triple-Negative Breast Cancer. Cancer research 90 28330927
2003 EDD, the human orthologue of the hyperplastic discs tumour suppressor gene, is amplified and overexpressed in cancer. Oncogene 87 12902990
2019 MicroRNA-1224 Splicing CircularRNA-Filip1l in an Ago2-Dependent Manner Regulates Chronic Inflammatory Pain via Targeting Ubr5. The Journal of neuroscience : the official journal of the Society for Neuroscience 86 30651325
2018 The ubiquitin ligase UBR5 suppresses proteostasis collapse in pluripotent stem cells from Huntington's disease patients. Nature communications 85 30038412
2019 AKT drives SOX2 overexpression and cancer cell stemness in esophageal cancer by protecting SOX2 from UBR5-mediated degradation. Oncogene 82 30894683
1992 Molecular characterization of the Entner-Doudoroff pathway in Escherichia coli: sequence analysis and localization of promoters for the edd-eda operon. Journal of bacteriology 71 1624451
2019 PPARγ Interaction with UBR5/ATMIN Promotes DNA Repair to Maintain Endothelial Homeostasis. Cell reports 70 30699358
2010 Top-down mass spectrometry for sequencing of larger (up to 61 nt) RNA by CAD and EDD. Journal of the American Society for Mass Spectrometry 65 20363646
2004 Edd, the murine hyperplastic disc gene, is essential for yolk sac vascularization and chorioallantoic fusion. Molecular and cellular biology 63 15282321
2019 The OTUD5-UBR5 complex regulates FACT-mediated transcription at damaged chromatin. Nucleic acids research 62 30508113
2022 UBR5 promotes tumor immune evasion through enhancing IFN-γ-induced PDL1 transcription in triple negative breast cancer. Theranostics 61 35836797
2013 Dyrk2-associated EDD-DDB1-VprBP E3 ligase inhibits telomerase by TERT degradation. The Journal of biological chemistry 61 23362280
2023 UBR5 forms ligand-dependent complexes on chromatin to regulate nuclear hormone receptor stability. Molecular cell 60 37478846
2007 Structural basis of ubiquitin recognition by the ubiquitin-associated (UBA) domain of the ubiquitin ligase EDD. The Journal of biological chemistry 60 17897937
2019 UBR5 is a novel E3 ubiquitin ligase involved in skeletal muscle hypertrophy and recovery from atrophy. The Journal of physiology 59 31093990
2017 Wnt-Dependent Inactivation of the Groucho/TLE Co-repressor by the HECT E3 Ubiquitin Ligase Hyd/UBR5. Molecular cell 58 28689657
2016 Downregulation of the proapoptotic protein MOAP-1 by the UBR5 ubiquitin ligase and its role in ovarian cancer resistance to cisplatin. Oncogene 58 27721409
2014 UBR5-mediated ubiquitination of ATMIN is required for ionizing radiation-induced ATM signaling and function. Proceedings of the National Academy of Sciences of the United States of America 58 25092319
2016 BMI1-UBR5 axis regulates transcriptional repression at damaged chromatin. Proceedings of the National Academy of Sciences of the United States of America 56 27647897
2011 Mammalian hyperplastic discs homolog EDD regulates miRNA-mediated gene silencing. Molecular cell 56 21726813
2011 Regulation of the human papillomavirus type 18 E6/E6AP ubiquitin ligase complex by the HECT domain-containing protein EDD. Journal of virology 55 21228227
2020 E3 ubiquitin ligase UBR5 promotes pancreatic cancer growth and aerobic glycolysis by downregulating FBP1 via destabilization of C/EBPα. Oncogene 54 33122826
2015 E3 ligase EDD1/UBR5 is utilized by the HPV E6 oncogene to destabilize tumor suppressor TIP60. Oncogene 54 26234678
2006 EDD mediates DNA damage-induced activation of CHK2. The Journal of biological chemistry 53 17074762
2007 The E3 ubiquitin ligase EDD regulates S-phase and G(2)/M DNA damage checkpoints. Cell cycle (Georgetown, Tex.) 50 18073532
2022 CANT-HYD: A Curated Database of Phylogeny-Derived Hidden Markov Models for Annotation of Marker Genes Involved in Hydrocarbon Degradation. Frontiers in microbiology 49 35069469
2017 Cep78 controls centrosome homeostasis by inhibiting EDD-DYRK2-DDB1VprBP. EMBO reports 48 28242748
2013 Identification of a recurrent transforming UBR5-ZNF423 fusion gene in EBV-associated nasopharyngeal carcinoma. The Journal of pathology 47 23878065
2006 Comparative peptide binding studies of the PABC domains from the ubiquitin-protein isopeptide ligase HYD and poly(A)-binding protein. Implications for HYD function. The Journal of biological chemistry 45 16554297
2018 Circ-UBR5: An exonic circular RNA and novel small nuclear RNA involved in RNA splicing. Biochemical and biophysical research communications 44 29944885
2013 HIV-1 Vpr protein inhibits telomerase activity via the EDD-DDB1-VPRBP E3 ligase complex. The Journal of biological chemistry 42 23612978
2013 VprBP (DCAF1): a promiscuous substrate recognition subunit that incorporates into both RING-family CRL4 and HECT-family EDD/UBR5 E3 ubiquitin ligases. BMC molecular biology 40 24028781
2008 Effect of cra gene knockout together with edd and iclR genes knockout on the metabolism in Escherichia coli. Archives of microbiology 40 18648770
2020 UBR5 Is Coamplified with MYC in Breast Tumors and Encodes an Ubiquitin Ligase That Limits MYC-Dependent Apoptosis. Cancer research 39 32029551
2013 EDD enhances cell survival and cisplatin resistance and is a therapeutic target for epithelial ovarian cancer. Carcinogenesis 38 24379240
2011 EDD inhibits ATM-mediated phosphorylation of p53. The Journal of biological chemistry 37 21383020
2010 Transcription factor IIS cooperates with the E3 ligase UBR5 to ubiquitinate the CDK9 subunit of the positive transcription elongation factor B. The Journal of biological chemistry 37 21127351
2023 Cryo-EM structure of the chain-elongating E3 ubiquitin ligase UBR5. The EMBO journal 35 37409633
2014 Stability of the human pregnane X receptor is regulated by E3 ligase UBR5 and serine/threonine kinase DYRK2. The Biochemical journal 35 24438055
2010 Modulation of myocardin function by the ubiquitin E3 ligase UBR5. The Journal of biological chemistry 35 20167605
2020 Knockdown of the E3 ubiquitin ligase UBR5 and its role in skeletal muscle anabolism. American journal of physiology. Cell physiology 33 33052072
2017 UBR5 Contributes to Colorectal Cancer Progression by Destabilizing the Tumor Suppressor ECRG4. Digestive diseases and sciences 32 28856538
2012 EDD induces cell cycle arrest by increasing p53 levels. Cell cycle (Georgetown, Tex.) 32 22374670
2021 HYD-PEP06 suppresses hepatocellular carcinoma metastasis, epithelial-mesenchymal transition and cancer stem cell-like properties by inhibiting PI3K/AKT and WNT/β-catenin signaling activation. Acta pharmaceutica Sinica. B 31 34221870
2018 The E3 ubiquitin ligase UBR5 regulates centriolar satellite stability and primary cilia. Molecular biology of the cell 31 29742019
2016 The E3 ligase UBR5 regulates gastric cancer cell growth by destabilizing the tumor suppressor GKN1. Biochemical and biophysical research communications 30 27590582
1989 hyd gamma, a gene from Desulfovibrio vulgaris (Hildenborough) encodes a polypeptide homologous to the periplasmic hydrogenase. FEMS microbiology letters 30 2663634
2019 Folate-PEG/Hyd-curcumin/C18-g-PSI micelles for site specific delivery of curcumin to colon cancer cells via Wnt/β-catenin signaling pathway. Materials science & engineering. C, Materials for biological applications 29 31029341
2015 The MLLE domain of the ubiquitin ligase UBR5 binds to its catalytic domain to regulate substrate binding. The Journal of biological chemistry 28 26224628
2024 UBR5 mediates colorectal cancer chemoresistance by attenuating ferroptosis via Lys 11 ubiquitin-dependent stabilization of Smad3-SLC7A11 signaling. Redox biology 26 39260061
2021 CSN6 promotes melanoma proliferation and metastasis by controlling the UBR5-mediated ubiquitination and degradation of CDK9. Cell death & disease 25 33483464
2012 Structure of the HECT C-lobe of the UBR5 E3 ubiquitin ligase. Acta crystallographica. Section F, Structural biology and crystallization communications 25 23027739
2019 UBR5 interacts with the replication fork and protects DNA replication from DNA polymerase η toxicity. Nucleic acids research 24 31586398
2014 Systems level-based RNAi screening by high content analysis identifies UBR5 as a regulator of estrogen receptor-α protein levels and activity. Oncogene 24 24441042
2022 Targeting UBR5 in hepatocellular carcinoma cells and precise treatment via echinacoside nanodelivery. Cellular & molecular biology letters 23 36224534
2021 E3 Ubiquitin Ligase UBR5 Promotes the Metastasis of Pancreatic Cancer via Destabilizing F-Actin Capping Protein CAPZA1. Frontiers in oncology 23 33777788
2020 UBR5 regulates proliferation and radiosensitivity in human laryngeal carcinoma via the p38/MAPK signaling pathway. Oncology reports 23 32468011
2020 Identification of the HECT E3 ligase UBR5 as a regulator of MYC degradation using a CRISPR/Cas9 screen. Scientific reports 22 33208877
2019 The E3 ubiquitin ligase UBR5 interacts with the H/ACA ribonucleoprotein complex and regulates ribosomal RNA biogenesis in embryonic stem cells. FEBS letters 22 31365120
2018 HIV-1 Vpr hijacks EDD-DYRK2-DDB1DCAF1 to disrupt centrosome homeostasis. The Journal of biological chemistry 22 29724823
2020 Hyd ubiquitinates the NF-κB co-factor Akirin to operate an effective immune response in Drosophila. PLoS pathogens 21 32339205
2012 The novel interaction between microspherule protein Msp58 and ubiquitin E3 ligase EDD regulates cell cycle progression. Biochimica et biophysica acta 21 23069210
1992 The polycistronic mRNA of the Zymomonas mobilis glf-zwf-edd-glk operon is subject to complex transcript processing. Journal of bacteriology 21 1569014
2022 UBR5 targets tumor suppressor CDC73 proteolytically to promote aggressive breast cancer. Cell death & disease 20 35551175
2020 Growth associated polyhydroxybutyrate production by the novel Zobellellae tiwanensis strain DD5 from banana peels under submerged fermentation. International journal of biological macromolecules 20 32142847
2020 UBR5 HECT domain mutations identified in mantle cell lymphoma control maturation of B cells. Blood 20 32325489
2019 Overexpression of UBR5 promotes tumor growth in gallbladder cancer via PTEN/PI3K/Akt signal pathway. Journal of cellular biochemistry 20 30775814
2019 Activated Wnt/β-Catenin signaling contributes to E3 ubiquitin ligase EDD-conferred docetaxel resistance in prostate cancer. Life sciences 20 31472148
2017 UBR5 promotes cell proliferation and inhibits apoptosis in colon cancer by destablizing P21. Die Pharmazie 20 29441938
2012 UBR5 Gene Mutation Is Associated with Familial Adult Myoclonic Epilepsy in a Japanese Family. ISRN neurology 20 23029623
2010 alpha4 phosphoprotein interacts with EDD E3 ubiquitin ligase and poly(A)-binding protein. Journal of cellular biochemistry 20 20544796
2007 Putative tumor suppressor EDD interacts with and up-regulates APC. Genes to cells : devoted to molecular & cellular mechanisms 20 18076571
2001 The DD5 gene of the decapod crustacean Penaeus japonicus encodes a putative exoskeletal protein with a novel tandem repeat structure. Comparative biochemistry and physiology. Part B, Biochemistry & molecular biology 20 11250533
2020 UBR7 functions with UBR5 in the Notch signaling pathway and is involved in a neurodevelopmental syndrome with epilepsy, ptosis, and hypothyroidism. American journal of human genetics 19 33340455
1992 The Zymomonas mobilis glf, zwf, edd, and glk genes form an operon: localization of the promoter and identification of a conserved sequence in the regulatory region. Journal of bacteriology 19 1569013
2016 Use of a Conditional Ubr5 Mutant Allele to Investigate the Role of an N-End Rule Ubiquitin-Protein Ligase in Hedgehog Signalling and Embryonic Limb Development. PloS one 18 27299863
2016 UBR-5, a Conserved HECT-Type E3 Ubiquitin Ligase, Negatively Regulates Notch-Type Signaling in Caenorhabditis elegans. G3 (Bethesda, Md.) 17 27185398
2015 Human Herpesvirus-6 U14 Induces Cell-Cycle Arrest in G2/M Phase by Associating with a Cellular Protein, EDD. PloS one 17 26340541
2011 Transcription of fdh and hyd in Syntrophobacter spp. and Methanospirillum spp. as a diagnostic tool for monitoring anaerobic sludge deprived of molybdenum, tungsten and selenium. Environmental microbiology 17 21332622
2015 RanGTP aids anaphase entry through Ubr5-mediated protein turnover. The Journal of cell biology 15 26438829
2005 Effects of edd and pgi disruptions on inosine accumulation in Escherichia coli. Bioscience, biotechnology, and biochemistry 15 16041126
2024 UBR5 promotes antiviral immunity by disengaging the transcriptional brake on RIG-I like receptors. Nature communications 14 38278841
2023 Harnessing UBR5 for targeted protein degradation of key transcriptional regulators. Trends in pharmacological sciences 14 37770316
2022 Role of ubiquitin-protein ligase UBR5 in the disassembly of mitotic checkpoint complexes. Proceedings of the National Academy of Sciences of the United States of America 14 35217622
2018 Stability of the HTLV-1 Antisense-Derived Protein, HBZ, Is Regulated by the E3 Ubiquitin-Protein Ligase, UBR5. Frontiers in microbiology 14 29441057
2005 EDD, a novel phosphotransferase domain common to mannose transporter EIIA, dihydroxyacetone kinase, and DegV. Protein science : a publication of the Protein Society 14 15632288
2022 UBR5 Acts as an Antiviral Host Factor against MERS-CoV via Promoting Ubiquitination and Degradation of ORF4b. Journal of virology 13 35980206
2017 The p90 ribosomal S6 kinase-UBR5 pathway controls Toll-like receptor signaling via miRNA-induced translational inhibition of tumor necrosis factor receptor-associated factor 3. The Journal of biological chemistry 13 28559278
2013 Progestin-inducible EDD E3 ubiquitin ligase binds to α4 phosphoprotein to regulate ubiquitination and degradation of protein phosphatase PP2Ac. Molecular and cellular endocrinology 13 24145130
2024 E3 ubiquitin ligase UBR5 promotes gemcitabine resistance in pancreatic cancer by inducing O-GlcNAcylation-mediated EMT via destabilization of OGA. Cell death & disease 12 38755129
2024 The G1-S transition is promoted by Rb degradation via the E3 ligase UBR5. Science advances 12 39441926

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