Affinage

HERC2

E3 ubiquitin-protein ligase HERC2 · UniProt O95714

Length
4834 aa
Mass
527.2 kDa
Annotated
2026-06-10
77 papers in source corpus 34 papers cited in narrative 33 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

HERC2 is a giant HECT-domain E3 ubiquitin ligase and multidomain scaffold that integrates DNA damage responses, replication-stress signaling, iron homeostasis, centrosome/cilium biology, and p53 regulation through both catalytic ubiquitination and non-catalytic protein binding (PMID:20023648, PMID:27528230, PMID:40705422). In the DNA double-strand break response, IR-induced phosphorylation at Thr4827 docks HERC2 onto the FHA domain of RNF8 and drives assembly of RNF8 with the conjugating enzyme Ubc13 to generate K63-linked ubiquitin chains, supporting retention of 53BP1, RAP80, and BRCA1 at damage sites; this recruitment is reinforced by PIAS4-dependent SUMOylation, with the HERC2 ZZ zinc finger acting as a SUMO-binding module that stabilizes the RNF8-Ubc13 complex (PMID:20023648, PMID:22508508). As a ligase, HERC2 controls the abundance of numerous substrates through its catalytic Cys4762, including BARD1-uncoupled BRCA1, the NER factor XPA in a circadian/ATR-antagonized manner, FBXL5, USP20, USP33, NCOA4, and RPA2 (PMID:20631078, PMID:20304803, PMID:23178497, PMID:24778179, PMID:25355518, PMID:25326330, PMID:24855649, PMID:26436293, PMID:31582797). Through USP20 it tunes Claspin–ATR–Chk1 checkpoint signaling under replication stress, and at the replication fork it associates with Claspin and the BLM/WRN–RPA machinery, releasing RPA onto ssDNA and ubiquitinating phospho-RPA2 to suppress G-quadruplex formation and support nucleolar helicase function (PMID:21775519, PMID:25355518, PMID:25326330, PMID:30279242, PMID:31582797, PMID:33432007). In iron homeostasis, HERC2 senses the [2Fe-2S]-loaded state of NCOA4 via its CPH and INBD domains to direct iron-dependent NCOA4 degradation, linking it to ferritinophagy and ferroptosis sensitivity downstream of NRF2 (PMID:26436293, PMID:36724221, PMID:40705422). HERC2 additionally promotes p53 oligomerization and transcriptional activity via its CPH domain and regulates MDM2 transcription, regulates centrosome architecture and ciliogenesis through NEURL4/CP110/USP33, and stimulates UBE3A (E6AP) ligase activity via its RLD2 domain, linking it to neuronal pathways (PMID:21493713, PMID:22261722, PMID:24722987, PMID:31665549, PMID:37074924). Homozygous Herc2 loss is embryonic lethal in mice independently of p53, and HERC2 hypomorphism causes Purkinje cell loss and motor defects, underscoring an essential developmental role (PMID:27528230).

Mechanistic history

Synthesis pass · year-by-year structured walk · 33 steps
  1. 2009 High

    Established HERC2 as an active participant in the DSB ubiquitin signaling cascade rather than a passive scaffold, by showing phospho-dependent recruitment of the RNF8/Ubc13 machinery.

    Evidence Co-IP, phospho-site mapping at Thr4827, siRNA, and IR-induced focus assays in human cells

    PMID:20023648

    Open questions at the time
    • Did not define how HERC2 levels of RNF168 are maintained mechanistically
    • Catalytic versus scaffold contribution of HERC2 to chain formation not separated
  2. 2010 High

    Demonstrated HERC2 as a bona fide E3 ligase with catalytic Cys4762 that degrades BARD1-uncoupled BRCA1, defining a quality-control role over BRCA1 stoichiometry.

    Evidence In vitro ubiquitination with catalytic mutant, Co-IP, and checkpoint epistasis in human cells

    PMID:20631078

    Open questions at the time
    • Physiological conditions favoring BRCA1 versus BARD1 binding not defined
    • Chain linkage type on BRCA1 not characterized
  3. 2010 Medium

    Linked HERC2 to circadian-regulated nucleotide excision repair by showing it drives oscillatory XPA turnover.

    Evidence Timed tissue-extract repair assays and XPA Western blots in mouse liver

    PMID:20304803

    Open questions at the time
    • Direct ubiquitination of XPA by HERC2 not reconstituted in this study
    • Single-lab; in vitro extract system
  4. 2011 High

    Showed a non-catalytic HERC2 function: its RLD2 domain stimulates UBE3A/E6AP ligase activity, providing a molecular link to Angelman/E6AP biology.

    Evidence Domain-mapped Co-IP and in vitro/cell ubiquitination assays with catalytic-dead HERC2

    PMID:21493713

    Open questions at the time
    • Physiological substrates affected by HERC2-stimulated E6AP not defined here
    • Structural basis of stimulation not resolved at this stage
  5. 2011 Medium

    Placed HERC2 at the replication fork through Claspin association and regulation of origin firing and MCM2 phosphorylation.

    Evidence Co-IP, DNA fiber assays, and phospho-MCM2 blots with double knockdown in human cells

    PMID:21775519

    Open questions at the time
    • Whether HERC2 ubiquitinates a fork component was not established
    • Single-lab
  6. 2012 High

    Identified the ZZ zinc finger as a SUMO-binding module and showed SUMOylation cooperates with T4827 phosphorylation to assemble the RNF8-Ubc13 complex at DSBs.

    Evidence PIAS4 knockdown, domain mutagenesis, SUMO-binding assays, and focus formation in human cells

    PMID:22508508

    Open questions at the time
    • SUMO acceptor sites on HERC2 not fully mapped
    • Quantitative interplay of SUMO and phospho signals not resolved
  7. 2012 High

    Defined a HERC2-NEURL4 module that controls centrosome architecture via CP110 and ubiquitin-dependent regulation, extending HERC2 function to the centrosome.

    Evidence AP-MS, high-resolution imaging, and RNAi rescue with structure-function transgenes

    PMID:22261722

    Open questions at the time
    • Direct ubiquitination targets at the centrosome incompletely enumerated at this stage
    • Mechanism of pericentriolar material defect not fully resolved
  8. 2012 High

    Showed ATR-mediated XPA Ser196 phosphorylation antagonizes HERC2 binding and ubiquitination, defining a damage-responsive switch controlling XPA stability.

    Evidence Phospho-mutant reconstitution in XPA-null cells with Co-IP, ubiquitination, and chromatin retention assays

    PMID:23178497

    Open questions at the time
    • Coordination with circadian XPA control not integrated
    • Structural basis of phospho-regulated dissociation unknown
  9. 2014 High

    Revealed a non-degradative HERC2 role in the p53 pathway, promoting p53 oligomerization and transcriptional activity via the CPH domain.

    Evidence Domain-mapped Co-IP, cross-linking oligomerization assays, and transcription reporters in human cells

    PMID:24722987

    Open questions at the time
    • How HERC2 mechanically catalyzes tetramer assembly unresolved
    • Relationship to HERC2 ligase activity not addressed
  10. 2014 Medium

    Connected HERC2 to iron homeostasis by identifying it as the E3 ligase degrading FBXL5, thereby influencing IRP2 regulation and intracellular iron.

    Evidence Proteomics-guided Co-IP, ubiquitination assay, and iron measurement with HERC2 knockdown

    PMID:24778179

    Open questions at the time
    • Iron-dependence of the FBXL5 interaction not mechanistically resolved here
    • Single-lab
  11. 2014 High

    Established a HERC2-USP20 axis controlling Claspin-ATR-Chk1 signaling, with ATR phosphorylation of USP20 dissociating HERC2 to stabilize the checkpoint.

    Evidence DUB screen, Co-IP, phospho-mapping, and Chk1 checkpoint assays (two converging papers)

    PMID:25326330 PMID:25355518

    Open questions at the time
    • Chain linkage on USP20 not detailed
    • Quantitative thresholds of stress-induced switching unknown
  12. 2014 Medium

    Linked HERC2 to histone H2A ubiquitin dynamics by regulating USP16 levels and damage-induced ubiquitin foci.

    Evidence Domain-mapped Co-IP, in vitro deubiquitination, and ubiquitin focus imaging

    PMID:25305019

    Open questions at the time
    • Whether HERC2 ubiquitinates USP16 directly not shown
    • Single-lab
  13. 2014 Medium

    Showed HERC2 directs K48 polyubiquitination of USP33 with p97-dependent processing, expanding its substrate repertoire to a centriole-relevant DUB.

    Evidence Quantitative MS, Co-IP, ubiquitination assay, and p97 inhibition in human cells

    PMID:24855649

    Open questions at the time
    • Direct catalytic ubiquitin transfer by HERC2 onto USP33 inferred from cellular assays
    • Single-lab
  14. 2015 High

    Defined HERC2 as the E3 ligase for iron-dependent NCOA4 degradation, placing it at the intersection of ferritinophagy and proteasomal control.

    Evidence Co-IP, ubiquitination assay, iron-dependent interaction, and zebrafish erythropoiesis model

    PMID:26436293

    Open questions at the time
    • Molecular basis of iron-sensing not yet resolved at this stage
    • Relative contribution of UPS versus autophagy to NCOA4 turnover unclear
  15. 2016 High

    Demonstrated HERC2 is essential for development independently of p53 and that haploinsufficiency causes Purkinje cell loss and motor impairment.

    Evidence Herc2 knockout, p53 double-knockout epistasis, behavioral and histological phenotyping in mice

    PMID:27528230

    Open questions at the time
    • Specific substrate(s) underlying lethality not identified
    • Mechanism of Purkinje cell vulnerability unresolved
  16. 2016 Medium

    Connected HERC2 to a SIRT1-driven LKB1 degradation pathway regulating arterial remodeling.

    Evidence DOC-domain Co-IP, K64 mutagenesis, ChIP, and in vivo lentiviral knockdown

    PMID:27259994

    Open questions at the time
    • Direct LKB1 ubiquitination by HERC2 inferred
    • Single-lab
  17. 2018 High

    Established the E3 ligase activity of HERC2 as required for G-quadruplex suppression by promoting RPA loading and RPA2 ubiquitination in BLM/WRN helicase complexes.

    Evidence In vitro RPA-release assay, CRISPR catalytic-site deletion, G4 imaging, and epistasis in human cells

    PMID:30279242

    Open questions at the time
    • How HERC2 mechanically releases RPA onto ssDNA unresolved
    • Genomic distribution of HERC2-dependent G4 suppression not mapped
  18. 2019 Medium

    Resolved the RPA2 regulatory loop, showing HERC2 promotes ATR-induced RPA2 Ser33 phosphorylation then ubiquitinates and degrades phospho-RPA2 to support G4 suppression.

    Evidence Co-IP, ubiquitination assay, CRISPR catalytic mutant, and phospho-RPA2 blots with ATR inhibitor epistasis

    PMID:31582797

    Open questions at the time
    • Direct catalysis of RPA2 ubiquitination not reconstituted in vitro here
    • Single-lab
  19. 2019 Medium

    Showed HERC2 transcriptionally regulates MDM2 within an oligomeric p53/HERC2/NEURL4 complex, with DNA damage dissociating MDM2 to activate p53.

    Evidence Co-IP, MDM2 promoter reporter assays, and knockdown in human cells

    PMID:31665549

    Open questions at the time
    • Mechanism by which HERC2 affects MDM2 promoter activity not defined
    • Single-lab
  20. 2019 Medium

    Placed HERC2 downstream of NudCL2 in centriole duplication control via regulation of USP33.

    Evidence CRISPR KO, rescue epistasis, Co-IP, and quantitative proteomics in human cells

    PMID:31427565

    Open questions at the time
    • How NudCL2 stabilizes HERC2 structurally unknown
    • Single-lab
  21. 2020 High

    Provided structural basis for the dual-reader function of the HERC2 ZZ domain, which binds histone H3 and SUMO1 tails at the same negatively charged site.

    Evidence Crystal structures of two complexes with NMR, mutagenesis, and fluorescence binding

    PMID:32726574

    Open questions at the time
    • Cellular consequences of H3 versus SUMO1 binding choice not resolved
    • Competition dynamics in vivo unknown
  22. 2021 Medium

    Showed HERC2 controls nucleolar localization of BLM/WRN helicases and rDNA G4-dependent rRNA transcription, extending its G4 role to the nucleolus.

    Evidence CRISPR HECT deletion, colocalization imaging, and pre-rRNA transcription/CX-5461 sensitivity assays

    PMID:33432007

    Open questions at the time
    • Direct substrate driving nucleolar helicase localization unknown
    • Single-lab
  23. 2022 Medium

    Linked HERC2 loss to C-RAF/MKK3/p38 activation and NRF2-driven oxidative stress resistance, defining a signaling axis independent of p53.

    Evidence Patient fibroblasts, Co-IP, ubiquitylation, RAF/p38 inhibitor epistasis, and NRF2 blots

    PMID:36241744

    Open questions at the time
    • Direct C-RAF ubiquitination by HERC2 not fully reconstituted
    • Single-lab
  24. 2022 Medium

    Identified the HERC2 ZZ domain as a reader of arginylated (Nt-R) cargo, connecting HERC2 to N-degron pathways and autophagy/proteasome targeting.

    Evidence NMR titration, HERC2 DOC crystal structure, mutagenesis, and immunofluorescence

    PMID:35411094

    Open questions at the time
    • Functional autophagy targeting based on imaging alone
    • In vivo arginylated substrates not identified
  25. 2023 Medium

    Showed NRF2 transcriptionally maintains HERC2, integrating HERC2 into iron and ferroptosis control via NCOA4/ferritin handling.

    Evidence NRF2 knockout, autophagy flux, iron measurement, and ferroptosis sensitivity assays

    PMID:36724221

    Open questions at the time
    • Direct NRF2 binding at the HERC2 promoter not mapped here
    • Single-lab
  26. 2023 Medium

    Defined an oncogenic HERC2 function in hepatocellular carcinoma, restraining PTP1B to sustain JAK2/STAT3 and PD-L1-mediated immune evasion.

    Evidence HERC2 KO/overexpression, Co-IP, PTP1B localization imaging, and in vivo mouse liver carcinogenesis models

    PMID:36721234

    Open questions at the time
    • Whether HERC2 ubiquitinates PTP1B not established
    • Single-lab
  27. 2023 Medium

    Showed HERC2 ubiquitinates CP110 at centriolar satellites to promote ciliogenesis, with EHD1 controlling HERC2/satellite transport to the mother centriole.

    Evidence Co-IP, ubiquitination assay, satellite localization imaging, and ciliogenesis quantification with siRNA

    PMID:37074924

    Open questions at the time
    • Mechanism of EHD1-dependent transport unresolved
    • Single-lab
  28. 2024 Medium

    Linked HERC2 to cardiac hypertrophy through K48-linked degradation of MeCP2 and downstream Lin28a derepression.

    Evidence Co-IP, K48 ubiquitination assay, and cardiac-specific overexpression in vivo

    PMID:39499120

    Open questions at the time
    • Direct ubiquitination site on MeCP2 not mapped
    • Single-lab
  29. 2024 Medium

    Showed HERC2 ubiquitinates β-catenin to govern CYP2E1 transcription and protect against acetaminophen-induced liver injury.

    Evidence Co-IP, ubiquitination assay, liver-specific KO mice, scRNA-seq, and LNP delivery in vivo

    PMID:39440550

    Open questions at the time
    • β-catenin ubiquitination linkage type not detailed
    • Single-lab
  30. 2024 Medium

    Characterized the disordered C-terminal tail of HERC2 as a stabilizer of the catalytic HECT C-lobe, implicating it as a flexible interaction scaffold.

    Evidence AlphaFold modeling, MD simulation, multidimensional NMR, and CD melting

    PMID:39565083

    Open questions at the time
    • Functional consequence of tail-C-lobe contact inferred not tested
    • Single-lab
  31. 2024 Medium

    Defined HERC2 as an autophagy regulator via the USP20-ULK1 axis, with HERC2 deficiency elevating USP20, stabilizing ULK1, and increasing autophagy flux.

    Evidence Patient fibroblasts, HERC2-USP20 Co-IP, lysosomal inhibitor assays, and p38 inhibitor epistasis

    PMID:38570483

    Open questions at the time
    • Direct ULK1 stabilization mechanism by USP20 not fully resolved here
    • Single-lab
  32. 2025 High

    Provided the structural and biochemical basis for iron-sensing, showing HERC2 recognizes [2Fe-2S]-bound NCOA4 through its CPH and newly defined INBD domains.

    Evidence Two crystal structures, in vitro reconstitution, iron-sulfur cluster biochemistry, and cellular ubiquitination/stability assays

    PMID:40705422

    Open questions at the time
    • How iron cluster occupancy is dynamically sensed in vivo not fully resolved
    • Whether other substrates use iron-dependent recognition unknown
  33. 2025 Medium

    Defined a conserved DxDKDxD motif recognized by the HERC2 RLD2 domain that mediates UBE3A binding and broadens to DOCK10 and other brain-relevant proteins, with HERC2 stimulating DOCK10 GEF activity and dendritic spine formation.

    Evidence Crystal structures of RLD2 complexes, GEF activity assays, conservation analysis, and dendritic spine imaging in neurons (preprint)

    PMID:bio_10.1101_2025.09.16.670041

    Open questions at the time
    • Preprint, not peer-reviewed
    • Physiological scope of additional DxDKDxD partners not validated

Open questions

Synthesis pass · forward-looking unresolved questions
  • How a single giant scaffold coordinates its many catalytic and non-catalytic functions across distinct subcellular compartments and selects among its diverse substrates remains unresolved.
  • No unifying regulatory logic for substrate selection across pathways
  • Full-length structural architecture not solved
  • Disease-causing mutation mapping to specific functional domains incomplete

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016874 ligase activity 6 GO:0140096 catalytic activity, acting on a protein 6 GO:0060090 molecular adaptor activity 4 GO:0098772 molecular function regulator activity 2 GO:0140299 molecular sensor activity 2 GO:0042393 histone binding 1
Localization
GO:0005815 microtubule organizing center 3 GO:0000228 nuclear chromosome 2 GO:0005634 nucleus 1 GO:0005730 nucleolus 1
Pathway
R-HSA-392499 Metabolism of proteins 5 R-HSA-1430728 Metabolism 4 R-HSA-69306 DNA Replication 4 R-HSA-73894 DNA Repair 4 R-HSA-1852241 Organelle biogenesis and maintenance 3 R-HSA-9612973 Autophagy 3
Partners
CP110NCOA4NEURL4RNF8RPA2UBE3AUSP20USP33
Complex memberships
BLM/WRN-RPA helicase complexNEURL4-HERC2-CP110 centrosomal moduleRNF8-Ubc13 DSB ubiquitin modulep53/HERC2/NEURL4/MDM2 complex

Evidence

Reading pass · 33 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2009 HERC2 forms a complex with the ubiquitin ligase RNF8 in response to ionising radiation; this interaction requires IR-inducible phosphorylation of HERC2 at Thr4827, which binds to the FHA domain of RNF8. HERC2 facilitates assembly of the ubiquitin-conjugating enzyme Ubc13 with RNF8, promoting DNA damage-induced formation of Lys63-linked ubiquitin chains. HERC2 also interacts with and maintains levels of RNF168, and HERC2 knockdown abrogates ubiquitin-dependent retention of 53BP1, RAP80, and BRCA1 at damage sites. Co-immunoprecipitation, phosphorylation mapping, siRNA knockdown, IR-induced focus formation assays, radiosensitivity assays Nature cell biology High 20023648
2010 HERC2 acts as an E3 ubiquitin ligase that targets BARD1-uncoupled BRCA1 for degradation. The HECT domain of HERC2 interacts with an N-terminal degron domain in BRCA1, and ubiquitination depends on Cys4762 (catalytic site) of HERC2. HERC2 depletion restores BRCA1 expression and G2/M checkpoint activity when BARD1 is depleted; BARD1 protects BRCA1 from HERC2-mediated ubiquitination. Co-immunoprecipitation, in vitro ubiquitination assay, catalytic mutant analysis (Cys4762), siRNA knockdown, cell-cycle checkpoint assays Cancer research High 20631078
2010 HERC2 ubiquitin ligase mediates circadian oscillation of the NER factor XPA in mouse liver tissue extracts. HERC2 promotes XPA ubiquitination and degradation, and this is regulated in concert with transcriptional control by core circadian clock proteins including cryptochrome. Tissue extract repair assays (timed), Western blot for XPA oscillation, functional ubiquitination in extracts Proceedings of the National Academy of Sciences of the United States of America Medium 20304803
2011 HERC2 stimulates the ubiquitin-protein ligase activity of E6AP (UBE3A) in vitro and in cells. The interaction is mediated by the RCC1-like domain 2 (RLD2) of HERC2 and residues 150-200 of E6AP. This stimulatory effect does not require the ubiquitin ligase activity of HERC2 itself. Co-immunoprecipitation, domain mapping, in vitro ubiquitination assay, cell-based ubiquitination assay The Journal of biological chemistry High 21493713
2011 HERC2 interacts with Claspin and is a component of the DNA replication fork complex. HERC2 depletion alleviated slow replication fork progression in Claspin-deficient cells, suppressed enhanced origin firing, and decreased MCM2 phosphorylation. In a HERC2-dependent manner, aphidicolin treatment enhanced MCM2 phosphorylation. Co-immunoprecipitation, DNA fiber assay, siRNA knockdown, phospho-MCM2 Western blot Cancer research Medium 21775519
2012 HERC2 and RNF168 are SUMOylated at DNA double-strand break sites in a PIAS4-dependent manner. SUMOylation of HERC2 is required for its DSB-induced association with RNF8 and for stabilizing the RNF8-Ubc13 complex. The ZZ zinc finger of HERC2 functions as a novel SUMO-specific binding module; together with concomitant phosphorylation at T4827, it promotes RNF8 binding. Co-immunoprecipitation, domain mutagenesis, SUMO-specific binding assays, siRNA knockdown of PIAS4, focus formation assays at DSBs The Journal of cell biology High 22508508
2012 HERC2 and NEURL4 are novel interaction partners of the centrosomal protein CP110. HERC2 and NEURL4 localize to the centrosome, and interfering with their function causes aberrant filamentous pericentriolar material structures. NEURL4 is a substrate of HERC2, and the NEURL4-HERC2 complex participates in ubiquitin-dependent regulation of centrosome architecture. CP110 binding to HERC2 (mediated via nonoverlapping NEURL4 regions) is required for normal centrosome integrity. Interaction proteomics (AP-MS), high-resolution imaging, RNAi, structure-function analysis with RNAi-resistant transgene Molecular & cellular proteomics : MCP High 22261722
2012 ATR-mediated phosphorylation of XPA at Ser196 enhances XPA stability by inhibiting HERC2-mediated ubiquitination and degradation. Upon UV damage, ATR facilitates HERC2 dissociation from XPA; phosphomimetic S196D shows reduced HERC2 binding and decreased ubiquitination, while S196A shows persistent HERC2 association and enhanced ubiquitination. Co-immunoprecipitation, site-directed mutagenesis (S196D/S196A), ubiquitination assay, XPA-deficient cell complementation, chromatin retention assay Oncogene High 23178497
2014 HERC2 interacts with p53 via its CPH domain (binding the last 43 amino acids of p53). HERC2 depletion reduces p53 transcriptional activity and p53 oligomerization without affecting p53 stability or MDM2 activity. The HERC2-p53 interaction requires the p53 tetramerization domain, and HERC2 promotes p53 oligomerization as shown by cross-linking assays. Co-immunoprecipitation, domain mapping, RNA interference, transcriptional reporter assays, chemical cross-linking, focus formation assay The Journal of biological chemistry High 24722987
2014 HERC2 is the E3 ubiquitin ligase responsible for polyubiquitination and proteasomal degradation of FBXL5, the F-box protein that targets IRP2 for degradation. HERC2 depletion stabilizes FBXL5 and leads to a decrease in intracellular ferrous iron. Proteomics/Co-IP to identify HERC2-FBXL5 interaction, siRNA knockdown of HERC2, ubiquitination assay, iron measurement The Journal of biological chemistry Medium 24778179
2014 USP20 deubiquitinates and stabilizes Claspin to promote ATR-Chk1 signaling. Under normal conditions, HERC2 promotes ubiquitination-mediated degradation of USP20. Under replication stress, ATR-mediated phosphorylation of USP20 causes disassociation of HERC2 from USP20, stabilizing USP20 and consequently Claspin to enhance CHK1 checkpoint activation. DUB screen, Co-immunoprecipitation, phosphorylation mapping, siRNA knockdown, checkpoint signaling assays (Chk1 phosphorylation) Nucleic acids research High 25326330 25355518
2014 The histone H2A deubiquitinase USP16 interacts with HERC2 via USP16's coiled-coil domain and HERC2's C-terminal HECT domain. HERC2 knockdown affects ubiquitinated H2A levels through USP16. DNA damage increases USP16 levels in a HERC2-dependent manner; elevated USP16 acts as a negative regulator of damage-induced ubiquitin foci formation. USP16 can deubiquitinate both H2A Lys119 and H2A Lys15 in vitro. Co-immunoprecipitation, domain mapping, siRNA knockdown, in vitro deubiquitination assay, ubiquitin focus formation imaging The Journal of biological chemistry Medium 25305019
2014 HERC2 degrades the deubiquitinating enzyme USP33 through K48-linked polyubiquitination. p97 (with Ufd1-Npl4 adaptor) is required for post-ubiquitination processing of USP33. Inhibition of p97 causes accumulation of polyubiquitinated USP33. Quantitative mass spectrometry, Co-immunoprecipitation, p97 knockdown/inhibition, ubiquitination assay The Journal of biological chemistry Medium 24855649
2015 HERC2 ubiquitin ligase promotes ubiquitin-dependent proteasomal degradation of NCOA4 (the ferritinophagy receptor) in an iron-dependent manner. Excess iron induces an interaction between NCOA4 and HERC2, leading to NCOA4 degradation. NCOA4 abundance is thus under dual control by autophagy and the ubiquitin-proteasome system, with HERC2 acting as the E3 ligase for iron-dependent NCOA4 turnover. Co-immunoprecipitation, ubiquitination assay, iron-dependent interaction assays, zebrafish erythropoiesis model, cell culture knockdown eLife High 26436293
2016 SIRT1 binds to the DOC domain of HERC2 via its amino-terminus; HERC2 then ubiquitinates LKB1 for proteasomal degradation in the nuclear compartment of endothelial cells. Acetylation of LKB1 at K64 triggers formation of the SIRT1/HERC2/LKB1 complex. HERC2 knockdown increases association of LKB1 with the TGFβ1 promoter and abolishes the protective effects of SIRT1 on arterial remodeling. Co-immunoprecipitation, site-directed mutagenesis (K64), chromatin immunoprecipitation (ChIP-qPCR), siRNA knockdown, lentiviral knockdown in vivo Oncotarget Medium 27259994
2016 Homozygous Herc2 knockout mice are not viable (embryonic lethal). p53 depletion does not rescue lethality, indicating HERC2's essential developmental role is p53-independent. Heterozygous mice show ~50% reduced HERC2 levels, reduced ubiquitin ligase activity and p53 stimulation, and display loss of Purkinje cells with impaired motor coordination. HERC2 is detected in Purkinje cells and autophagosomes/lysosomes accumulate in heterozygous cerebella. Targeted gene knockout (homozygous lethal), p53 double-knockout epistasis, behavioral analysis, immunohistochemistry of cerebellum, quantitative ubiquitin ligase assay Oncotarget High 27528230
2018 HERC2 interacts with BLM, WRN RecQ helicases and RPA complexes during S-phase. HERC2 depletion dissociates RPA from BLM and WRN complexes and significantly increases G-quadruplex (G4) DNA formation. In vitro, HERC2 releases RPA onto ssDNA. CRISPR deletion of the HERC2 catalytic ubiquitin-binding site inhibited RPA2 ubiquitination, caused RPA accumulation in helicase complexes, and increased G4 formation—establishing the E3 ligase activity as required for G4 suppression. HERC2 has an epistatic relationship with BLM and WRN in G4 suppression. Co-immunoprecipitation, in vitro RPA-release assay, CRISPR/Cas9 catalytic-site deletion, G4 immunofluorescence, siRNA epistasis, sensitivity to G4 stabilizers Cancer research High 30279242
2019 HERC2 interacts with RPA2 through its C-terminal HECT domain. HERC2 promotes ATR-induced phosphorylation of RPA2 at Ser33 under low-level replication stress, and subsequently mediates ubiquitination and degradation of phosphorylated RPA2. Cells lacking HERC2 catalytic residues constitutively accumulate Ser33-phosphorylated RPA2. This regulatory loop is required for suppression of G-quadruplex DNA structures. Co-immunoprecipitation, ubiquitination assay, HERC2 catalytic mutant (CRISPR), phospho-RPA2 Western blot, ATR inhibitor epistasis, G4 immunofluorescence Scientific reports Medium 31582797
2019 MDM2 forms a complex with oligomeric p53, HERC2, and NEURL4. HERC2 knockdown reduces MDM2 mRNA and protein levels by inhibiting MDM2 promoter activation (not by affecting MDM2 protein stability). DNA damage dissociates MDM2 from the p53/HERC2/NEURL4 complex, leading to increased phosphorylation and acetylation of p53 oligomers, which then compete for MDM2 promoter binding. Co-immunoprecipitation, siRNA knockdown, MDM2 promoter luciferase/reporter assay, Western blot for MDM2 stability Molecular oncology Medium 31665549
2019 NudCL2 interacts with and stabilizes HERC2. NudCL2 knockout leads to centriole amplification, and ectopic HERC2 expression rescues this phenotype while NudCL2 overexpression cannot rescue HERC2 depletion, establishing HERC2 as epistatic downstream of NudCL2. HERC2 controls levels of USP33 (a positive regulator of centriole duplication); USP33 knockdown reverses centriole amplification in both NudCL2 KO and HERC2-depleted cells. CRISPR/Cas9 knockout, siRNA knockdown, Co-immunoprecipitation, rescue experiments, quantitative proteomics Cell death & disease Medium 31427565
2020 The ZZ domain of HERC2 (HERC2ZZ) binds to the histone H3 tail and to the N-terminal tail of SUMO1 via the same negatively charged site, with comparable affinities. Crystal structures of HERC2ZZ:H3 and HERC2ZZ:SUMO1 complexes reveal the molecular basis: a critical role for the negatively charged site in capturing A1 of H3, while SUMO1 adopts an α-helical conformation at the same site. HERC2ZZ tolerates common H3 PTMs. X-ray crystallography, NMR titration, mutagenesis, fluorescence binding assays Structure (London, England : 1993) High 32726574
2021 HERC2 inactivation (depletion or homozygous HECT deletion) prevents nucleolar localization of BLM and WRN RecQ helicases and inhibits relocalization of BLM to replication stress-induced RPA foci. HERC2 co-localizes with fibrillarin and RNA Pol I subunit RPA194. HERC2 dysfunction enhances the suppressive effects of the rDNA G4 stabilizer CX-5461 on pre-rRNA transcription. CRISPR/Cas9 HECT domain deletion, siRNA knockdown, immunofluorescence/colocalization, pre-rRNA transcription assay, CX-5461 sensitivity assay Scientific reports Medium 33432007
2022 HERC2 deficiency activates the C-RAF/MKK3/p38 signaling pathway. HERC2 forms molecular complexes with RAF proteins, regulates C-RAF ubiquitylation, and p38 activation in HERC2-deficient cells is RAF/MKK3-dependent. This results in increased resistance to oxidative stress and elevated NRF2 and antioxidant target gene expression, independent of p53. Patient-derived fibroblast analysis, HERC2 knockdown, Co-immunoprecipitation, proteomics, ubiquitylation assay, RAF/p38 inhibitor epistasis, NRF2 Western blot Cellular and molecular life sciences : CMLS Medium 36241744
2022 The ZZ domain of HERC2 (HERC2ZZ) recognizes arginylated substrates via the Nt-R cargo degradation signal. NMR titration and mutagenesis identify a well-defined binding site on HERC2ZZ comprising negatively charged aspartate residues. The DOC domain adjacent to ZZ shows a conformational rearrangement when linked to ZZ. Stimulation of autophagy promotes HERC2 targeting to the proteasome. NMR titration, X-ray crystallography (HERC2DOC), mutagenesis, immunofluorescence microscopy Scientific reports Medium 35411094
2023 NRF2 maintains HERC2 expression (HERC2 is transcriptionally regulated by NRF2). NRF2 knockout reduces HERC2 levels, causing simultaneous accumulation of ferritin and NCOA4 and apoferritin accumulation in autophagosomes. This elevates the labile iron pool and sensitizes cells to ferroptosis. NRF2 also controls VAMP8 (for autophagosome-lysosome fusion) in the same pathway. NRF2 knockout (genetic), Western blot, autophagy flux assays, iron measurement, ferroptosis sensitivity assays Science advances Medium 36724221
2023 HERC2 promotes cancer stemness and PD-L1-mediated immune evasion in hepatocellular carcinoma by activating the JAK2/STAT3 pathway. Mechanistically, HERC2 interacts with the ER-resident phosphatase PTP1B and limits PTP1B translocation from the ER to the ER-plasma membrane junction, thereby reducing PTP1B's inhibitory effect on JAK2 phosphorylation. HERC2 knockout and overexpression in HCC cells, Co-immunoprecipitation, immunofluorescence for PTP1B localization, DEN-induced mouse liver carcinogenesis (hepatocyte-specific KO), orthotopic transplantation model Journal of experimental & clinical cancer research : CR Medium 36721234
2023 HERC2 ubiquitinates CP110 to promote its degradation during ciliogenesis. HERC2 localizes to centriolar satellites. EHD1 regulates the transport of centriolar satellites and HERC2 to the mother centriole during ciliogenesis, and EHD1 is required for CP110 ubiquitination. HERC2 knockdown impairs ciliogenesis. Co-immunoprecipitation, ubiquitination assay, immunofluorescence (HERC2 to centriolar satellites), siRNA knockdown (HERC2, EHD1), ciliogenesis quantification EMBO reports Medium 37074924
2024 HERC2 promotes cardiac hypertrophy by directly binding MeCP2 and promoting its K48-linked polyubiquitination and proteasomal degradation. Reduced MeCP2 (a transcriptional suppressor) elevates Lin28a expression, driving hypertrophy. Knockdown of Lin28a attenuates Ang II-induced hypertrophy and abolishes HERC2 overexpression effects. Co-immunoprecipitation, ubiquitination assay (K48-linkage), siRNA knockdown, cardiomyocyte overexpression, cardiac-specific OE in vivo Journal of cardiovascular pharmacology Medium 39499120
2024 HERC2 interacts with β-catenin and promotes its ubiquitination, thereby governing CYP2E1 transcriptional regulation. HERC2 deficiency exacerbates APAP-induced liver damage through increased CYP2E1 expression. Lipid nanoparticle delivery of HERC2-overexpressing plasmid reduces liver damage caused by APAP overdose. Co-immunoprecipitation, ubiquitination assay, liver-specific HERC2 KO mice, single-cell RNA-seq, LNP delivery in vivo Advanced science Medium 39440550
2024 The disordered, negatively charged C-terminal tail of HERC2 is intrinsically disordered but provides thermal and structural stability to the HECT C-lobe. MD simulations identify the D4829-R4728 non-bonded contact as prevalent between tail and C-lobe. The C-lobe is the catalytic ubiquitin-transfer domain, and the C-terminal tail may function as a flexible scaffold for protein-protein interactions. AlphaFold modeling, molecular dynamics simulation, multidimensional NMR (1H-15N HSQC, resonance assignment), circular dichroism melting curves Protein science : a publication of the Protein Society Medium 39565083
2024 HERC2 deficiency in patients with the HERC2-related disorder leads to increased USP20 protein levels (HERC2 normally destabilizes USP20). Elevated USP20 stabilizes the autophagy-initiating kinase ULK1, upregulating autophagy flux. p38 activation disrupts HERC2-USP20 interaction, further elevating USP20 and LC3-II levels. This defines HERC2 as an autophagy regulator via the USP20-ULK1 axis. Patient-derived fibroblast analysis, Co-immunoprecipitation (HERC2-USP20), lysosomal inhibitor assay, USP20/ULK1/LC3 Western blot, p38 inhibitor epistasis Cell death discovery Medium 38570483
2025 NCOA4's HERC2-binding domain (HBD) harbors a [2Fe-2S] iron-sulfur cluster and can exist in apo- or [2Fe-2S]-bound states. HERC2 specifically recognizes the [2Fe-2S] cluster-bound NCOA4 HBD through a synergistic interaction involving both the CPH domain and a newly defined iron-sulfur cluster-dependent NCOA4-binding domain (INBD) of HERC2. Crystal structures of HERC2(2540-2700) alone and in complex with [2Fe-2S]-bound NCOA4 HBD provide the molecular basis for iron-dependent NCOA4 recognition and degradation. X-ray crystallography (two structures), biochemical reconstitution, iron-sulfur cluster characterization, mutagenesis, cellular ubiquitination and stability assays Proceedings of the National Academy of Sciences of the United States of America High 40705422
2025 HERC2 binds to the RLD2 domain interface with UBE3A (E6AP) via a conserved 'DxDKDxD' motif in UBE3A; this interaction is conserved across most animals with a central nervous system. HERC2 also recognizes similar DxDKDxD motifs in DOCK10, PCM1, USP35, and other brain-relevant proteins. HERC2 binding to DOCK10 stimulates DOCK10 GEF activity (RAC1/CDC42 activation) through a conformational change; disruption of the HERC2-binding motif in DOCK10 or HERC2 knockdown reduces DOCK10 GEF activity and impairs DOCK10-induced dendritic spine formation in hippocampal neurons. Quantitative binding assays, X-ray crystallography (RLD2-UBE3A and RLD2-DOCK10 complexes), sequence conservation analysis, GEF activity assay, siRNA knockdown, dendritic spine morphogenesis imaging in neurons bioRxivpreprint Medium bio_10.1101_2025.09.16.670041

Source papers

Stage 0 corpus · 77 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2015 Ferritinophagy via NCOA4 is required for erythropoiesis and is regulated by iron dependent HERC2-mediated proteolysis. eLife 465 26436293
2023 NRF2 controls iron homeostasis and ferroptosis through HERC2 and VAMP8. Science advances 423 36724221
2008 A single SNP in an evolutionary conserved region within intron 86 of the HERC2 gene determines human blue-brown eye color. American journal of human genetics 265 18252222
2009 HERC2 coordinates ubiquitin-dependent assembly of DNA repair factors on damaged chromosomes. Nature cell biology 229 20023648
2008 Blue eye color in humans may be caused by a perfectly associated founder mutation in a regulatory element located within the HERC2 gene inhibiting OCA2 expression. Human genetics 227 18172690
2012 HERC2 rs12913832 modulates human pigmentation by attenuating chromatin-loop formation between a long-range enhancer and the OCA2 promoter. Genome research 209 22234890
2010 Circadian control of XPA and excision repair of cisplatin-DNA damage by cryptochrome and HERC2 ubiquitin ligase. Proceedings of the National Academy of Sciences of the United States of America 188 20304803
2008 Three genome-wide association studies and a linkage analysis identify HERC2 as a human iris color gene. American journal of human genetics 173 18252221
2010 HERC2 is an E3 ligase that targets BRCA1 for degradation. Cancer research 127 20631078
2012 DNA damage-inducible SUMOylation of HERC2 promotes RNF8 binding via a novel SUMO-binding Zinc finger. The Journal of cell biology 113 22508508
2011 A global view of the OCA2-HERC2 region and pigmentation. Human genetics 99 22065085
2009 Interactions between HERC2, OCA2 and MC1R may influence human pigmentation phenotype. Annals of human genetics 92 19208107
2012 A homozygous missense mutation in HERC2 associated with global developmental delay and autism spectrum disorder. Human mutation 82 23065719
2011 Physical and functional interaction of the HECT ubiquitin-protein ligases E6AP and HERC2. The Journal of biological chemistry 67 21493713
2014 HERC2-USP20 axis regulates DNA damage checkpoint through Claspin. Nucleic acids research 65 25355518
2023 HERC2 promotes inflammation-driven cancer stemness and immune evasion in hepatocellular carcinoma by activating STAT3 pathway. Journal of experimental & clinical cancer research : CR 63 36721234
2014 The histone H2A deubiquitinase USP16 interacts with HERC2 and fine-tunes cellular response to DNA damage. The Journal of biological chemistry 62 25305019
2021 LncRNA-Fendrr protects against the ubiquitination and degradation of NLRC4 protein through HERC2 to regulate the pyroptosis of microglia. Molecular medicine (Cambridge, Mass.) 61 33858325
2012 Interaction proteomics identify NEURL4 and the HECT E3 ligase HERC2 as novel modulators of centrosome architecture. Molecular & cellular proteomics : MCP 60 22261722
2012 Mutation of HERC2 causes developmental delay with Angelman-like features. Journal of medical genetics 60 23243086
2014 The E3 ubiquitin protein ligase HERC2 modulates the activity of tumor protein p53 by regulating its oligomerization. The Journal of biological chemistry 57 24722987
2012 Coordinated regulation of XPA stability by ATR and HERC2 during nucleotide excision repair. Oncogene 56 23178497
2014 HERC2/USP20 coordinates CHK1 activation by modulating CLASPIN stability. Nucleic acids research 55 25326330
2010 Human eye colour and HERC2, OCA2 and MATP. Forensic science international. Genetics 53 20457063
2018 HERC2 Facilitates BLM and WRN Helicase Complex Interaction with RPA to Suppress G-Quadruplex DNA. Cancer research 51 30279242
2014 HERC2 targets the iron regulator FBXL5 for degradation and modulates iron metabolism. The Journal of biological chemistry 48 24778179
2000 Structure of the highly conserved HERC2 gene and of multiple partially duplicated paralogs in human. Genome research 48 10720573
2014 Proteomic analysis and identification of cellular interactors of the giant ubiquitin ligase HERC2. Journal of proteome research 45 25476789
2016 Endothelial SIRT1 prevents adverse arterial remodeling by facilitating HERC2-mediated degradation of acetylated LKB1. Oncotarget 40 27259994
2011 HERC2 Interacts with Claspin and regulates DNA origin firing and replication fork progression. Cancer research 40 21775519
2019 Regulation of the MDM2-p53 pathway by the ubiquitin ligase HERC2. Molecular oncology 34 31665549
2016 Complete loss of function of the ubiquitin ligase HERC2 causes a severe neurodevelopmental phenotype. European journal of human genetics : EJHG 34 27759030
2010 Genetic analysis of three important genes in pigmentation and melanoma susceptibility: CDKN2A, MC1R and HERC2/OCA2. Experimental dermatology 34 20629734
2013 Gender is a major factor explaining discrepancies in eye colour prediction based on HERC2/OCA2 genotype and the IrisPlex model. Forensic science international. Genetics 30 23601698
2014 Degradation of the deubiquitinating enzyme USP33 is mediated by p97 and the ubiquitin ligase HERC2. The Journal of biological chemistry 29 24855649
1999 Molecular characterization of radiation- and chemically induced mutations associated with neuromuscular tremors, runting, juvenile lethality, and sperm defects in jdf2 mice. Mammalian genome : official journal of the International Mammalian Genome Society 29 10441737
2016 The HERC2 ubiquitin ligase is essential for embryonic development and regulates motor coordination. Oncotarget 28 27528230
2016 Combinatory effect of BRCA1 and HERC2 expression on outcome in advanced non-small-cell lung cancer. BMC cancer 23 27179511
2012 RNF8 and RNF168 but not HERC2 are required for DNA damage-induced ubiquitylation in chicken DT40 cells. DNA repair 22 23010445
2020 Novel loss-of-function mutation in HERC2 is associated with severe developmental delay and paediatric lethality. Journal of medical genetics 20 32571899
2016 The role of HERC2 and RNF8 ubiquitin E3 ligases in the promotion of translesion DNA synthesis in the chicken DT40 cell line. DNA repair 20 26994443
2023 Pharmacological inhibition of BAP1 recruits HERC2 to competitively dissociate BRCA1-BARD1, suppresses DNA repair and sensitizes CRC to radiotherapy. Acta pharmaceutica Sinica. B 19 37655321
2008 Linkage and association analysis of spectrophotometrically quantified hair color in Australian adolescents: the effect of OCA2 and HERC2. The Journal of investigative dermatology 18 18528436
2019 Proteomic investigations of human HERC2 mutants: Insights into the pathobiology of a neurodevelopmental disorder. Biochemical and biophysical research communications 17 30902390
2023 EHD1 promotes CP110 ubiquitination by centriolar satellite delivery of HERC2 to the mother centriole. EMBO reports 16 37074924
2020 Structural Insight into Binding of the ZZ Domain of HERC2 to Histone H3 and SUMO1. Structure (London, England : 1993) 16 32726574
2019 HERC2 regulates RPA2 by mediating ATR-induced Ser33 phosphorylation and ubiquitin-dependent degradation. Scientific reports 16 31582797
2025 Mechanistic insights into the iron-sulfur cluster-dependent interaction of the autophagy receptor NCOA4 with the E3 ligase HERC2. Proceedings of the National Academy of Sciences of the United States of America 15 40705422
2021 Exploring the Roles of HERC2 and the NEDD4L HECT E3 Ubiquitin Ligase Subfamily in p53 Signaling and the DNA Damage Response. Frontiers in oncology 15 33869064
2009 Genotyping of five single nucleotide polymorphisms in the OCA2 and HERC2 genes associated with blue-brown eye color in the Japanese population. Cell biochemistry and function 13 19472299
2021 HERC2 inactivation abrogates nucleolar localization of RecQ helicases BLM and WRN. Scientific reports 12 33432007
2022 The Downregulation of Both Giant HERCs, HERC1 and HERC2, Is an Unambiguous Feature of Chronic Myeloid Leukemia, and HERC1 Levels Are Associated with Leukemic Cell Differentiation. Journal of clinical medicine 11 35054018
2022 HERC2 deficiency activates C-RAF/MKK3/p38 signalling pathway altering the cellular response to oxidative stress. Cellular and molecular life sciences : CMLS 11 36241744
2019 NudC-like protein 2 restrains centriole amplification by stabilizing HERC2. Cell death & disease 11 31427565
2017 Variants at the OCA2/HERC2 locus affect time to first cutaneous squamous cell carcinoma in solid organ transplant recipients collected using two different study designs. The British journal of dermatology 10 28456133
2021 Delineating the expanding phenotype of HERC2-related disorders: The impact of biallelic loss of function versus missense variation. Clinical genetics 9 34370298
2020 Identification of rare missense mutations in NOTCH2 and HERC2 associated with familial central precocious puberty via whole-exome sequencing. Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology 8 32400230
2019 Resolving the Insertion Sites of Polymorphic Duplications Reveals a HERC2 Haplotype under Selection. Genome biology and evolution 8 31124564
2025 Perfluorooctane sulfonate induced ferritinophagy via detyrosinated alpha tubulin-TRIM21-HERC2-regulated NCOA4 degradation in hepatocytes. Environmental pollution (Barking, Essex : 1987) 7 40120846
2024 Hesperidin alleviated dendritic spines through inhibiting ferritinophagy via HERC2-NCOA4 ubiquitination in CUMS mice. Phytomedicine : international journal of phytotherapy and phytopharmacology 7 39522250
2024 Survival in Patients with Uveal Melanoma Is Linked to Genetic Variation at HERC2 Single Nucleotide Polymorphism rs12913832. Ophthalmology 6 39245076
2024 Hepatocyte-Targeted Lipid Nanoparticle Delivery of HERC2 Plasmid Controls Drug-Induced Hepatotoxicity by Limiting β-Catenin-Regulated CYP2E1 Expression. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 5 39440550
2023 Association between Variants in the OCA2-HERC2 Region and Blue Eye Colour in HERC2 rs12913832 AA and AG Individuals. Genes 5 36980970
2023 Identification of Polymorphisms in the HERC2-OCA2 Gene Locus and their Association with Feather Color in Quail. The journal of poultry science 4 37234755
2021 Blended phenotype of combination of HERC2 and AP3B2 deficiency and Angelman syndrome caused by paternal isodisomy of chromosome 15. American journal of medical genetics. Part A 4 34042275
2025 Association of Genetic Polymorphisms in SLC45A2, TYR, HERC2, and SLC24A in African Women with Melasma: A Pilot Study. International journal of molecular sciences 3 39940926
2024 Autophagy dysregulation via the USP20-ULK1 axis in the HERC2-related neurodevelopmental disorder. Cell death discovery 3 38570483
2022 The ZZ domain of HERC2 is a receptor of arginylated substrates. Scientific reports 3 35411094
2025 SV2B Promotes the Progression of TFE3-Rearranged Renal Cell Carcinoma by Interacting with HERC2 to Impede the Degradation of NF-κB Subunits. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 2 41199339
2025 Cigarette smoke disrupts osteogenic-adipogenic balance via Nrf2/HERC2 axis-driven ferroptosis. Free radical biology & medicine 1 40939850
2025 Nephroprotective mechanism of Kunkui Baoshen decoction in diabetic kidney disease: Targeting the HERC2/NCOA4-mediated autophagy-dependent ferroptosis pathway. World journal of diabetes 1 41113495
2024 The disordered negatively charged C-terminus of the large HECT E3 ubiquitin ligase HERC2 provides structural and thermal stability to the HECT C-lobe. Protein science : a publication of the Protein Society 1 39565083
2026 Disruption of iron homeostasis by HERC2-FTL axis leads to chondrocyte loss and exacerbates osteoarthritis. Apoptosis : an international journal on programmed cell death 0 41854786
2026 A comparative GWAS of eye colour in light and dark eye genetic backgrounds defined by HERC2 rs12913832 polymorphism in a Canadian cohort of European ancestry. Scientific reports 0 41872255
2026 Ubiquitination of DDX21 by HERC2 induces a dormancy-like phenotype via the NUCKS1-p21/p27 axis to promote radio-resistance in colorectal cancer cells. Cell death & disease 0 42071007
2025 The Ubiquitin Ligase HERC2 Promotes Ang II-Induced Cardiac Hypertrophy Through Destabilization of MeCP2 to Enhance Lin28a Expression. Journal of cardiovascular pharmacology 0 39499120
2024 A Novel HERC2 Variant in Two Siblings with Autosomal Recessive Intellectual Developmental Disorder-38 and Cardiomyopathy. Molecular syndromology 0 41059448

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