Affinage

HECTD1

E3 ubiquitin-protein ligase HECTD1 · UniProt Q9ULT8

Length
2610 aa
Mass
289.4 kDa
Annotated
2026-06-10
49 papers in source corpus 29 papers cited in narrative 29 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

HECTD1 is a HECT-domain E3 ubiquitin ligase that controls developmental morphogenesis, cell migration, and signaling by ubiquitinating a broad set of substrates and thereby directing their degradation, localization, or function (PMID:17442300, PMID:22431752, PMID:33853758). Biochemically it preferentially assembles K29/K48-branched ubiquitin chains and depends on this branching for full ligase activity, while its own abundance is set by the deubiquitinase TRABID, defining a DUB/E3 pair (PMID:33853758). Through substrate ubiquitination HECTD1 restrains intracellular-to-extracellular HSP90 secretion to permit cranial neural tube closure—a function disrupted by rare human NTD-associated missense variants (PMID:22431752, PMID:38451291)—and degrades focal-adhesion and cytoskeletal regulators including PIPKIγ90, IQGAP1, ACF7, and DLC1 to govern adhesion dynamics, directional migration, EMT, and metastasis (PMID:23572508, PMID:28073378, PMID:29386124, PMID:35322810). It modulates Wnt signaling by K63-ubiquitinating APC to stabilize the APC-Axin destruction complex (PMID:23277359) and tunes retinoic acid signaling via RARA during aortic arch development (PMID:30578278). Additional substrates link HECTD1 to ribosomal 60S subunit assembly and protein synthesis in hematopoietic stem cells (ZNF622) (PMID:33711283), chondrocyte autophagy and osteoarthritis (Rubicon, AURKA) (PMID:36121967, PMID:40838484), histone-dependent base excision repair (stimulating APE1 incision) (PMID:31799632), and mitotic progression and spindle-assembly-checkpoint signaling (BUB3 interactor) (PMID:35915203). HECTD1 is essential for placental, neural, and brain development, with neural-lineage loss causing microcephaly, hippocampal malformation, and corpus callosum agenesis, and human variants producing dominant or haploinsufficient effects (PMID:17442300, PMID:24855001, PMID:39879987).

Mechanistic history

Synthesis pass · year-by-year structured walk · 28 steps
  1. 2007 High

    Established HECTD1's biological identity and necessity by showing an ENU-induced mutation in this HECT E3 ligase causes cranial neural tube defects, defining a dose-sensitive developmental requirement.

    Evidence ENU mutagenesis screen with two alleles and homozygous mutant embryo analysis in mouse

    PMID:17442300

    Open questions at the time
    • No substrate or enzymatic mechanism identified at this stage
    • Cell-type-specific requirement not resolved
  2. 2012 High

    Connected HECTD1 enzymatic activity to its developmental phenotype by identifying HSP90 ubiquitination as the mechanism restraining cranial mesenchyme cell emigration.

    Evidence In vitro ubiquitin ligase assay, explant emigration assays with HSP90 neutralization rescue in mouse

    PMID:22431752

    Open questions at the time
    • Ubiquitin chain linkage on HSP90 not defined
    • How ubiquitination suppresses secretion mechanistically unclear
  3. 2012 High

    Showed HECTD1 negatively regulates Wnt signaling by K63-ubiquitinating APC to promote the APC-Axin destruction complex, extending its role into signaling pathway control.

    Evidence Reciprocal Co-IP, siRNA knockdown, linkage-specific ubiquitin assays, β-catenin reporter assays

    PMID:23277359

    Open questions at the time
    • Whether APC modification is direct in cells not fully resolved
    • Link to a developmental Wnt phenotype not established here
  4. 2013 High

    Defined a focal-adhesion regulatory role by mapping HECTD1 ubiquitination of PIPKIγ90 at K97, coupling lipid kinase turnover to adhesion dynamics and metastasis.

    Evidence In vitro ubiquitination, K97R mutagenesis, FA dynamics and migration/invasion assays, metastasis mouse model

    PMID:23572508

    Open questions at the time
    • Chain type on PIPKIγ90 not specified
    • Upstream signals triggering degradation unclear
  5. 2014 Medium

    Provided structural insight by solving the N-terminal BTHB domain fold and proposing a conserved nucleic-acid-binding surface.

    Evidence NMR structure determination and comparative structural analysis

    PMID:24667607

    Open questions at the time
    • Functional role of BTHB domain in HECTD1 not experimentally tested
    • No demonstrated nucleic acid binding
  6. 2014 High

    Extended the developmental requirement to extraembryonic tissue, showing Hectd1 is needed for multiple trophoblast subtypes and placental viability.

    Evidence Homozygous mutant mouse analysis with cell-type markers, proliferation/apoptosis assays

    PMID:24855001

    Open questions at the time
    • Substrate driving placental defects not identified
    • Cell-autonomy vs. systemic effect unresolved
  7. 2017 High

    Identified additional cytoskeletal/migration control via IQGAP1 ubiquitination governing focal complex dynamics and migration directionality.

    Evidence Hectd1 mutant MEFs, Co-IP, ubiquitination assay, IQGAP1 phenocopy and siRNA rescue, live imaging

    PMID:28073378

    Open questions at the time
    • Chain type and direct in vitro ubiquitination of IQGAP1 not shown
    • Relationship to PIPKIγ90 pathway unclear
  8. 2017 Medium

    Showed HECTD1 stability is post-translationally controlled, with USP15 deubiquitinating and stabilizing it to modulate Wnt activity in glioblastoma.

    Evidence MS interaction screen, Co-IP, siRNA knockdown, Wnt reporter and stability assays

    PMID:29299163

    Open questions at the time
    • Direct deubiquitination not reconstituted
    • Single-lab study
  9. 2018 High

    Linked HECTD1 to EMT and metastasis suppression through ACF7 ubiquitination and degradation.

    Evidence shRNA screens, Co-IP, ubiquitination and stability assays, EMT markers, in vivo metastasis models

    PMID:29386124

    Open questions at the time
    • Chain linkage on ACF7 not defined
    • Interplay with other migration substrates not integrated
  10. 2019 High

    Established HECTD1 as a modulator of retinoic acid signaling via RARA, with a genetic interaction with Raldh2 controlling aortic arch artery development.

    Evidence Co-IP, RARE reporter assays in cells and embryos, double-heterozygous mouse crosses

    PMID:30578278

    Open questions at the time
    • Whether RARA is a degradation substrate vs. modulated unclear
    • Direct in vitro ubiquitination not shown
  11. 2020 High

    Defined a chromatin/DNA-repair function showing HECTD1 ubiquitylates histones to stimulate APE1 incision during base excision repair.

    Evidence Reconstituted mononucleosome BER assay, purified recombinant HECTD1, siRNA and irradiation survival assay

    PMID:31799632

    Open questions at the time
    • Specific histone residues ubiquitylated not fully mapped
    • How HECTD1 is recruited to damaged chromatin unknown
  12. 2020 Medium

    Implicated HECTD1 in NF-κB signaling and colitis through an LXN-HECTD1-Rps3 complex driving IκBα degradation.

    Evidence Co-IP/proteomics, IκBα ubiquitination assay, siRNA, DSS colitis mouse model

    PMID:32555320

    Open questions at the time
    • Direct vs. complex-dependent ubiquitination of IκBα unresolved
    • Single-lab study
  13. 2020 Medium

    Showed HECTD1 controls SNAIL stability and shuttles between nucleus and cytoplasm under EGF control, with miR-210 reducing its expression under hypoxia.

    Evidence Co-IP, ubiquitination assay, fractionation, leptomycin B, miR-210 overexpression, migration assays

    PMID:32319576

    Open questions at the time
    • NLS/NES sequences not mapped
    • Direct ubiquitination of SNAIL not reconstituted
  14. 2021 High

    Revealed a translational/stem-cell role by showing HECTD1 degrades the 60S assembly factor ZNF622 to enable ribosomal subunit joining and HSC function under stress.

    Evidence Conditional KO mice, Znf622-depletion epistasis rescue, ubiquitination assay, polysome/protein synthesis and HSC transplantation

    PMID:33711283

    Open questions at the time
    • Whether ZNF622 ubiquitination is direct in vivo across tissues unclear
    • Role outside hematopoietic stress not defined
  15. 2021 High

    Defined HECTD1's intrinsic enzymology and stability control: it builds K29/K48-branched chains requiring branching for activity, and TRABID is its stabilizing deubiquitinase.

    Evidence In vitro autoubiquitination with ubiquitin mutants, UbiCREST, Ub-AQUA MS, TRABID trapping and knockout/stability assays

    PMID:33853758

    Open questions at the time
    • Whether substrate chains are also K29/K48-branched not established for each substrate
    • Structural basis of branch specificity unknown
  16. 2021 Medium

    Identified transcriptional control of HECTD1 via the σ-1R-JNK/p38-FOXJ2 axis driving its expression during LPS-induced astrocyte activation.

    Evidence siRNA/overexpression, pharmacological inhibitors, nuclear translocation assays, in vivo astrocyte knockdown

    PMID:33781347

    Open questions at the time
    • Direct FOXJ2 binding to HECTD1 promoter not mapped
    • Substrates in astrocyte activation not defined
  17. 2021 Medium

    Showed EGF-JNK signaling protects BIRC6 from HECTD1-mediated ubiquitination, linking HECTD1 to apoptosis regulation in TNBC.

    Evidence Co-IP, ubiquitination assay, JNK inhibitor and EGF stimulation, stability assays

    PMID:34729249

    Open questions at the time
    • Mechanism by which JNK blocks ubiquitination unclear
    • Single-lab study
  18. 2022 Medium

    Implicated HECTD1 in mitotic progression and spindle-assembly-checkpoint function, identifying BUB3 as a new interactor.

    Evidence siRNA/KO, flow cytometry, time-lapse microscopy, Co-IP in HEK293T/HeLa

    PMID:35915203

    Open questions at the time
    • No mitotic ubiquitination substrate established
    • Whether BUB3 is a substrate vs. binding partner unclear
  19. 2022 Medium

    Showed HECTD1 degrades the RhoGAP tumor suppressor DLC1, opposed by USP7, linking it to focal-adhesion-localized DLC1 abundance.

    Evidence MS interaction, siRNA knockdown, stability and immunofluorescence assays

    PMID:35322810

    Open questions at the time
    • Direct ubiquitination not reconstituted
    • Single-lab study
  20. 2022 Medium

    Extended HECTD1 substrate range to the glutamate transporter GLT-1 in astrocytes, with vitamin C lowering HECTD1 to preserve GLT-1.

    Evidence siRNA/overexpression, ubiquitination assay, transcriptome sequencing, in vivo PD model

    PMID:35148069

    Open questions at the time
    • Direct ubiquitination site not mapped
    • Mechanism of vitamin C effect on HECTD1 unclear
  21. 2023 High

    Defined a cartilage-protective role through K534 ubiquitination and degradation of Rubicon, activating chondrocyte autophagy and limiting osteoarthritis.

    Evidence Co-IP, K534 mutagenesis, conditional KO and AAV overexpression, autophagy flux and OA histology

    PMID:36121967

    Open questions at the time
    • Upstream regulation of HECTD1 in chondrocytes only partly defined
    • Chain linkage on Rubicon not specified
  22. 2023 Low

    Suggested a centrosomal mitotic substrate by showing cell-cycle-dependent HectD1-centriolin co-localization and inverse expression.

    Evidence Co-IP, immunofluorescence co-localization, cell-cycle-staged expression

    PMID:38115153

    Open questions at the time
    • No direct ubiquitination assay for centriolin — degradation claim is inferential
    • Single Co-IP without functional validation
  23. 2023 Medium

    Identified HECTD1 as a tumor suppressor in esophageal squamous cell carcinoma acting through ubiquitination and degradation of NUP93.

    Evidence Co-IP, ubiquitination assay, siRNA/overexpression, proliferation/migration/invasion assays

    PMID:37993750

    Open questions at the time
    • Direct ubiquitination site not mapped
    • Single-lab study
  24. 2024 Medium

    Provided human genetic support for the HSP90 mechanism, showing rare NTD-associated HECTD1 missense variants impair suppression of extracellular HSP90 secretion.

    Evidence Targeted NGS and HEK293T eHSP90 secretion functional assays

    PMID:38451291

    Open questions at the time
    • Causality in patients not proven beyond functional assay
    • Variant effects on catalytic activity only partly characterized
  25. 2024 Medium

    Showed exosomal miR-16-5p targets HECTD1 mRNA to alter HSP90 ubiquitination in microglia, linking HECTD1 to neuropathic pain.

    Evidence Co-IP, ubiquitination western blot, RNA pull-down/luciferase, in vivo SNL behavioral assays

    PMID:38750549

    Open questions at the time
    • Direct microglial HSP90 ubiquitination consequence not fully resolved
    • Single-lab study
  26. 2025 Medium

    Connected HECTD1 to chondrocyte ECM degradation, with DNMT1-driven methylation downregulating HECTD1 to release AURKA, which phosphorylates eIF4E to enhance ADAMTS12 translation.

    Evidence Co-IP/GST pull-down, ubiquitination assay, methylation analysis, cap-dependent translation reporter, OA mouse model

    PMID:40838484

    Open questions at the time
    • Direct AURKA ubiquitination site not mapped
    • Single-lab study
  27. 2025 Medium

    Showed hypothermia-induced HECTD1 ubiquitinates VDAC3 to mediate neuroprotection after cardiac arrest.

    Evidence Co-IP, immunofluorescence, AAV siRNA knockdown, ubiquitination western blot, rat cardiac arrest model

    PMID:42158826

    Open questions at the time
    • Direct ubiquitination site not defined
    • Single-lab study
  28. 2025 Medium

    Established HECTD1 as a human neurodevelopmental disease gene, with neural-lineage knockout causing brain malformations and patient variants showing dominant or haploinsufficient mechanisms.

    Evidence Neural-lineage conditional KO mouse brain morphology, C. elegans variant assays, clinical cohort sequencing

    PMID:39879987

    Open questions at the time
    • Substrate driving brain phenotype not identified
    • Genotype-phenotype correlation across variants incomplete

Open questions

Synthesis pass · forward-looking unresolved questions
  • How HECTD1's K29/K48-branched chain specificity is structurally achieved and which substrate-specific chain architectures and recruitment mechanisms direct its many context-dependent functions remains unresolved.
  • No full-length structure with substrate
  • Substrate selection rules across tissues unknown
  • Whether branched chains apply to all substrates undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 7 GO:0016874 ligase activity 3 GO:0042393 histone binding 1
Localization
GO:0005634 nucleus 1 GO:0005815 microtubule organizing center 1 GO:0005829 cytosol 1
Pathway
R-HSA-1266738 Developmental Biology 4 R-HSA-392499 Metabolism of proteins 4 R-HSA-162582 Signal Transduction 2 R-HSA-1640170 Cell Cycle 1 R-HSA-73894 DNA Repair 1 R-HSA-8953854 Metabolism of RNA 1 R-HSA-9612973 Autophagy 1
Partners
ACF7APCBUB3HSP90IQGAP1PIPKIΓ90RARATRABID

Evidence

Reading pass · 29 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2007 HECTD1 (identified via the ENU-induced 'open mind' mutation) is a ubiquitously expressed HECT-domain E3 ubiquitin ligase required for cranial neural tube closure; loss-of-function causes exencephaly associated with abnormal head mesenchyme development and dorsal-lateral hinge point formation. Two different Hectd1 alleles cause neural tube defects in heterozygotes, indicating a critical threshold requirement. ENU mutagenesis screen, genetic complementation, homozygous mutant embryo analysis, molecular marker expression Developmental biology High 17442300
2012 HECTD1 is a functional E3 ubiquitin ligase that ubiquitinates HSP90, promoting its intracellular retention and suppressing its secretion. Loss of HECTD1 in cranial mesenchyme leads to enhanced extracellular HSP90 secretion, which drives increased cell emigration and underlies the neural tube defect (exencephaly) in Hectd1 mutant mice. In vitro ubiquitin ligase assay (demonstrating ubiquitination of HSP90), cranial mesenchyme explant emigration assays, rescue experiments with HSP90 neutralization, mutant mouse analysis The Journal of cell biology High 22431752
2012 HECTD1 (HectD1) modifies APC with Lys-63-linked polyubiquitin chains. This modification promotes the APC-Axin interaction within the destruction complex, thereby negatively regulating Wnt signaling. Knockdown of HectD1 diminishes APC ubiquitylation, disrupts the APC-Axin interaction, and augments Wnt3a-induced β-catenin stabilization and signaling. Co-immunoprecipitation, siRNA knockdown, ubiquitin linkage-specific assays, β-catenin signaling reporter assays The Journal of biological chemistry High 23277359
2013 HECTD1 ubiquitinates PIPKIγ90 (phosphatidylinositol 4-phosphate 5-kinase type I γ) at lysine 97, leading to its proteasomal degradation. This cycling of PIPKIγ90 removes it from the PIPKIγ90-talin complex after on-site PIP2 production, providing a regulatory mechanism for focal adhesion assembly/disassembly and cell migration. The PIPKIγ90(K97R) ubiquitination-resistant mutant enhanced PIP2/PIP3 production and inhibited FA dynamics and cancer cell migration/invasion/metastasis. In vitro ubiquitination assay, site-directed mutagenesis (K97R), Co-IP, cell migration/invasion assays, FA dynamics analysis, metastasis mouse model Journal of cell science High 23572508
2014 The N-terminal domain of HectD1 adopts a novel 5-helix bundle fold termed the Basic Tilted Helix Bundle (BTHB) domain, structurally related to FKBP25. A positively charged surface patch centered on the tilted helix H4 is conserved in both proteins, suggesting a conserved functional role, possibly in nucleic acid binding. NMR structure determination, comparative structural analysis Biochemical and biophysical research communications Medium 24667607
2014 Hectd1 is required for development of multiple trophoblast cell subtypes in the mouse placenta junctional zone, including trophoblast giant cells (TGCs), spongiotrophoblasts, and glycogen trophoblasts. Loss of Hectd1 results in mid-gestation lethality and intrauterine growth restriction, with differential changes in proliferation and apoptosis across placental layers. Homozygous mutant mouse analysis, immunohistochemistry, in situ hybridization with cell-type-specific markers, proliferation and apoptosis assays Developmental biology High 24855001
2017 HECTD1 interacts with IQGAP1 and regulates its degradation through ubiquitination, thereby controlling focal complex (FX) dynamics and directionality of cell migration. Loss of Hectd1 in MEF cells causes accelerated spreading and migration but impaired directionality, mislocalization of paxillin and zyxin, and increased focal complexes. Overexpression of IQGAP1 phenocopies Hectd1 loss; siRNA-mediated knockdown of IQGAP1 rescues migration defects of Hectd1 mutant cells. Hectd1 mutant MEF cell line, Co-IP, ubiquitination assay, siRNA rescue, IQGAP1 overexpression phenocopy, live cell imaging of migration and adhesion dynamics Cell communication and signaling : CCS High 28073378
2017 USP15 deubiquitinates and stabilizes HECTD1 in glioblastoma cells. Depletion of USP15 leads to decreased HECTD1 protein levels. USP15 expression attenuates Wnt pathway activity in a HECTD1-dependent manner; modulation of HECTD1 expression phenocopies USP15 effects on the Wnt pathway. Mass spectrometry protein interaction screen, Co-IP, siRNA knockdown, Wnt reporter assays, protein stability assays Oncotarget Medium 29299163
2018 HectD1 ubiquitinates and promotes proteasome-mediated degradation of the microtubule plus-end tracking protein ACF7. Depletion of HectD1 stabilizes ACF7, which enhances the EMT program and cell migration. Decreased HectD1 expression increased metastases in mouse models. shRNA screens, Co-IP, ubiquitination assays, ACF7 protein stability assays, EMT marker analysis, in vivo metastasis mouse models Cell reports High 29386124
2019 HECTD1 binds to and influences ubiquitination of the retinoic acid receptor alpha (RARA). Loss of HECTD1 reduces activation of a retinoic acid response element (RARE) reporter in mutant cells and embryos. Genetic interaction between Hectd1 and Raldh2 (retinoic acid synthesis enzyme) in double-heterozygous embryos causes 4th pharyngeal arch artery hypoplasia, establishing HECTD1 as a novel modulator of retinoic acid signaling during aortic arch development. Co-IP (HECTD1-RARA interaction), RARE reporter assays in cells and embryos, genetic epistasis (double heterozygous mouse crosses), embryo phenotype analysis Disease models & mechanisms High 30578278
2020 HECTD1 interacts with SNAIL and regulates its stability through ubiquitination; knockdown of HECTD1 increases SNAIL expression levels. HECTD1 shuttles between cytoplasm and nucleus via nuclear localization and export signals, regulated by EGF. Nuclear retention of HECTD1 (by leptomycin B) is associated with loss of SNAIL expression. Under hypoxia, HECTD1 expression is decreased by miR-210. Co-IP, ubiquitination assay, siRNA knockdown, nuclear/cytoplasmic fractionation, leptomycin B treatment, miR-210 overexpression, cell migration assay International journal of oncology Medium 32319576
2020 HECTD1 promotes base excision repair (BER) in chromatin by ubiquitylating histones, which stimulates AP endonuclease 1 (APE1) incision of abasic sites (THF) when the DNA damage is facing the histone core. A recombinant truncated form of HECTD1 directly stimulates THF incision by APE1 in reconstituted mononucleosome assays. siRNA depletion of HECTD1 leads to deficiencies in DNA damage repair and decreased cell survival following x-ray irradiation. Reconstituted mononucleosome BER assay with site-specific synthetic abasic sites, purification of HECTD1 activity from HeLa extracts, recombinant protein in vitro assay, siRNA knockdown, x-ray irradiation cell survival assay Nucleic acids research High 31799632
2020 Latexin (LXN) forms a functional complex with HECTD1 and ribosomal protein subunit 3 (Rps3). IκBα is a substrate of HECTD1. LXN knockdown enhances the HECTD1-Rps3 interaction, contributing to ubiquitination-mediated degradation of IκBα and subsequent NF-κB activation, promoting colitis severity. Proteomics/Co-IP (LXN-HECTD1-Rps3 complex), ubiquitination assay of IκBα, siRNA knockdown, ectopic expression, DSS-induced colitis mouse model Scientific reports Medium 32555320
2021 HectD1 ubiquitinates and degrades ZNF622, an assembly factor for the ribosomal 60S subunit. Loss of HectD1 causes accumulation of ZNF622 and the anti-association factor eIF6 on 60S, resulting in 60S/40S ribosomal subunit joining defects, reduced protein synthesis, and impaired hematopoietic stem cell (HSC) function under stress. Znf622 depletion in Hectd1-deficient HSCs restored ribosomal subunit joining, protein synthesis, and HSC reconstitution capacity. Conditional knockout mice, genetic epistasis (Hectd1 KO + Znf622 knockdown double mutant rescue), ubiquitination assay, ribosome profiling/polysome analysis, protein synthesis measurement, HSC transplantation assays Cell stem cell High 33711283
2021 The deubiquitinase TRABID stabilizes HECTD1 by removing ubiquitin chains. HECTD1 preferentially assembles K29- and K48-linked ubiquitin chains and requires branching at K29/K48 for full ligase activity. TRABID depletion leads to rapid HECTD1 degradation, establishing TRABID-HECTD1 as a DUB/E3 pair. TRABID catalytic-dead construct interactome (trapping assay), UbiCREST assay, Ub-AQUA proteomics, in vitro autoubiquitination assay with ubiquitin mutants, siRNA knockdown and genetic knockout of TRABID, protein stability assays The Journal of biological chemistry High 33853758
2021 HECTD1 is upregulated in astrocytes following LPS treatment. Its expression is transcriptionally controlled by the σ-1R-JNK/p38-FOXJ2 signaling axis: LPS activates σ-1R, which activates JNK/p38, which promotes nuclear translocation of the transcription factor FOXJ2 to drive HECTD1 expression. Knockdown of HECTD1 suppresses LPS-induced astrocyte activation; overexpression facilitates it. siRNA knockdown, overexpression, pharmacological inhibition (σ-1R antagonist, JNK inhibitor, p38 inhibitor), nuclear translocation assays, in vivo astrocyte-specific knockdown Cell & bioscience Medium 33781347
2021 BIRC6 protein stability is regulated by HECTD1: EGF-JNK signaling prevents HECTD1-mediated ubiquitination and proteasomal degradation of BIRC6. Activation of JNK by EGF blocks HECTD1 from ubiquitinating BIRC6, leading to BIRC6 accumulation in TNBC cells. Co-IP, ubiquitination assay, JNK inhibitor treatment, EGF stimulation, siRNA knockdown, protein stability/half-life assay Molecular therapy. Nucleic acids Medium 34729249
2022 HECTD1 depletion in HEK293T and HeLa cells decreases cell number by slowing mitotic progression. HECTD1 depletion increases the proportion of cells in prometaphase/metaphase and prolongs NEBD-to-anaphase onset time. HECTD1 depletion reduces Spindle Assembly Checkpoint activity, and BUB3 (a component of the Mitosis Checkpoint Complex) is identified as a novel HECTD1 interactor. siRNA knockdown and genetic knockout, flow cytometry (pH3-Ser28 mitotic marker), time-lapse microscopy, Co-IP (BUB3 interaction), cell counting assays Scientific reports Medium 35915203
2022 HECTD1 ubiquitinates and targets DLC1 (a RhoGAP tumor suppressor) for proteasomal degradation. siRNA-mediated knockdown of HECTD1 increases DLC1 protein levels and impairs its degradation. HECTD1 modulation alters DLC1 abundance at focal adhesions. USP7 deubiquitinates and stabilizes DLC1, acting oppositely to HECTD1. Mass spectrometry identification of DLC1-HECTD1 interaction, siRNA knockdown, protein stability assay, immunofluorescence microscopy of focal adhesion localization Scientific reports Medium 35322810
2022 HECTD1 ubiquitinates GLT-1 (glutamate transporter 1) in astrocytes, promoting its degradation. Knockdown of HECTD1 restores GLT-1 expression impaired by MPP+ treatment. Vitamin C reduces HECTD1 expression, thereby reducing GLT-1 ubiquitination and restoring its expression. Overexpression of HECTD1 abolishes the protective effect of vitamin C on GLT-1. siRNA knockdown, overexpression, ubiquitination assay, transcriptome sequencing, western blot, in vivo murine PD model ACS chemical neuroscience Medium 35148069
2023 HECTD1 ubiquitinates Rubicon at lysine residue 534, targeting it for proteasomal degradation. HECTD1-mediated Rubicon degradation activates chondrocyte autophagy, mitigating stress-induced chondrocyte death and OA progression. Overexpression of HECTD1 in mouse joints alleviated OA, while cartilage-specific Hectd1 knockout aggravated OA in surgery- and aging-induced models. Co-IP, ubiquitination assay with site-specific mutagenesis (K534), conditional knockout mice, adeno-associated virus overexpression in joints, autophagy flux assays, OA histology scoring Arthritis & rheumatology (Hoboken, N.J.) High 36121967
2023 HectD1 co-localizes with centriolin at the centrosome during mitosis, and binds to centriolin in a cell-cycle-dependent manner. HectD1 expression fluctuates through the cell cycle, with highest levels during mitosis coinciding with a marked reduction in centriolin expression, suggesting HectD1-mediated degradation of centriolin. Co-IP (HectD1-centriolin interaction), immunofluorescence co-localization, cell-cycle-staged protein expression analysis BMC research notes Low 38115153
2023 HECTD1 contributes to ubiquitination and proteasomal degradation of NUP93 (Nucleoporin 93) in esophageal squamous cell carcinoma cells. HECTD1 acts as an upstream regulator of NUP93 and functions as a tumor suppressor in ESCC. Co-IP, ubiquitination assay, siRNA knockdown and overexpression, cell proliferation/migration/invasion assays Human cell Medium 37993750
2024 Five rare HECTD1 missense variants identified in human NTD cases reduce HECTD1's ability to suppress extracellular HSP90 secretion in HEK293T cells. One variant (A1084T) also shows reduced protein expression. These functional data support the role of HECTD1-mediated control of eHSP90 secretion in human NTD etiology. Targeted next-generation sequencing, HEK293T functional assays for eHSP90 secretion, protein expression analysis of missense variants Human genetics Medium 38451291
2024 HECTD1 ubiquitinates HSP90, and this ubiquitination is regulated by miR-16-5p delivered via DRG-derived exosomes: miR-16-5p targets HECTD1 mRNA, reducing HECTD1 levels and consequently altering ubiquitination of HSP90 in microglia, thereby promoting microglial activation and neuropathic pain. Co-IP, western blot for HSP90 ubiquitination, RNA pull-down and dual-luciferase reporter (miR-16-5p/HECTD1 interaction), miR-16-5p knockdown in DRG-exosomes, behavioral NP assays in SNL mice, immunofluorescence Biological research Medium 38750549
2025 HECTD1 ubiquitinates AURKA, promoting its proteasomal degradation. Inflammatory conditions (IL-1β) cause DNMT1-mediated methylation-driven downregulation of HECTD1, which releases AURKA from ubiquitination-mediated degradation. Elevated AURKA then phosphorylates eIF4E, enhancing cap-dependent mRNA translation of ADAMTS12, resulting in extracellular matrix degradation in OA chondrocytes. Co-IP, GST pull-down (HECTD1-AURKA interaction), ubiquitination assay, DNMT1 methylation analysis, cap-dependent translation reporter assay, OA mouse model (ACL-T), siRNA knockdown/overexpression FASEB journal Medium 40838484
2025 HECTD1 ubiquitinates VDAC3, promoting its degradation. Hypothermia upregulates HECTD1 and increases VDAC3 ubiquitination in a rat cardiac arrest/CPR model. Hectd1 knockdown reduces VDAC3 ubiquitination, abolishes hypothermia-induced neuroprotection, and worsens neurological outcomes. Co-immunoprecipitation (HECTD1-VDAC3 interaction), immunofluorescence co-localization, siRNA knockdown (adeno-associated viral vector), western blot for ubiquitination, neurological deficit scoring, rat cardiac arrest model International journal of medical sciences Medium 42158826
2018 In SiO2-exposed macrophages, HECTD1 protein expression is increased concomitantly with decreased circHECTD1. HECTD1 is involved in ZC3H12A-dependent ubiquitination during macrophage activation, contributing to SiO2-induced inflammatory responses. HECTD1 upregulation in macrophages promotes fibroblast proliferation and migration. siRNA knockdown, western blot, Co-IP, cell functional assays (proliferation, migration), in vivo silicosis tissue validation Theranostics Low 29290828
2025 Conditional knockout of Hectd1 in the neural lineage in mice results in microcephaly, severe hippocampal malformations, and complete agenesis of the corpus callosum, supporting a role for Hectd1 in embryonic brain development. Functional studies of select HECTD1 variants in C. elegans revealed dominant effects including change-of-function or loss-of-function/haploinsufficient mechanisms. Neural lineage-specific conditional knockout mice, brain morphology analysis, C. elegans functional variant assays, clinical cohort sequencing (GeneMatcher) American journal of human genetics Medium 39879987

Source papers

Stage 0 corpus · 49 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2018 Novel insight into circular RNA HECTD1 in astrocyte activation via autophagy by targeting MIR142-TIPARP: implications for cerebral ischemic stroke. Autophagy 320 29938598
2018 circRNA Mediates Silica-Induced Macrophage Activation Via HECTD1/ZC3H12A-Dependent Ubiquitination. Theranostics 121 29290828
2018 circHECTD1 promotes the silica-induced pulmonary endothelial-mesenchymal transition via HECTD1. Cell death & disease 109 29540674
2020 Downregulation of circular RNA HECTD1 induces neuroprotection against ischemic stroke through the microRNA-133b/TRAF3 pathway. Life sciences 66 33148417
2012 Hectd1 regulates intracellular localization and secretion of Hsp90 to control cellular behavior of the cranial mesenchyme. The Journal of cell biology 65 22431752
2021 HectD1 controls hematopoietic stem cell regeneration by coordinating ribosome assembly and protein synthesis. Cell stem cell 59 33711283
2007 The Hectd1 ubiquitin ligase is required for development of the head mesenchyme and neural tube closure. Developmental biology 57 17442300
2013 Ubiquitylation of phosphatidylinositol 4-phosphate 5-kinase type I γ by HECTD1 regulates focal adhesion dynamics and cell migration. Journal of cell science 56 23572508
2012 HectD1 E3 ligase modifies adenomatous polyposis coli (APC) with polyubiquitin to promote the APC-axin interaction. The Journal of biological chemistry 54 23277359
2023 HECTD1-Mediated Ubiquitination and Degradation of Rubicon Regulates Autophagy and Osteoarthritis Pathogenesis. Arthritis & rheumatology (Hoboken, N.J.) 47 36121967
2019 The role of circular RNA HECTD1 expression in disease risk, disease severity, inflammation, and recurrence of acute ischemic stroke. Journal of clinical laboratory analysis 47 31257675
2019 circDLPAG4/HECTD1 mediates ischaemia/reperfusion injury in endothelial cells via ER stress. RNA biology 43 31607223
2018 The E3 Ubiquitin Ligase HectD1 Suppresses EMT and Metastasis by Targeting the +TIP ACF7 for Degradation. Cell reports 40 29386124
2022 Circular RNA HECTD1 Mitigates Ulcerative Colitis by Promoting Enterocyte Autophagy Via miR-182-5p/HuR Axis. Inflammatory bowel diseases 31 34427642
2019 CircHECTD1 mediates pulmonary fibroblast activation via HECTD1. Therapeutic advances in chronic disease 30 31832126
2017 Ubiquitin Specific Peptidase 15 (USP15) suppresses glioblastoma cell growth via stabilization of HECTD1 E3 ligase attenuating WNT pathway activity. Oncotarget 30 29299163
2014 Hectd1 is required for development of the junctional zone of the placenta. Developmental biology 30 24855001
2021 Circular RNA circ_HECTD1 regulates cell injury after cerebral infarction by miR-27a-3p/FSTL1 axis. Cell cycle (Georgetown, Tex.) 29 33843447
2020 Latexin deficiency in mice up-regulates inflammation and aggravates colitis through HECTD1/Rps3/NF-κB pathway. Scientific reports 29 32555320
2018 The E3 ubiquitin ligase, HECTD1, is involved in ABCA1-mediated cholesterol export from macrophages. Biochimica et biophysica acta. Molecular and cell biology of lipids 27 29306077
2021 The deubiquitinase TRABID stabilizes the K29/K48-specific E3 ubiquitin ligase HECTD1. The Journal of biological chemistry 24 33853758
2020 HECTD1 regulates the expression of SNAIL: Implications for epithelial‑mesenchymal transition. International journal of oncology 23 32319576
2017 HECTD1 controls the protein level of IQGAP1 to regulate the dynamics of adhesive structures. Cell communication and signaling : CCS 22 28073378
2020 HECTD1 promotes base excision repair in nucleosomes through chromatin remodelling. Nucleic acids research 21 31799632
2022 The E3 ubiquitin ligase HECTD1 contributes to cell proliferation through an effect on mitosis. Scientific reports 18 35915203
2019 The ubiquitin ligase HECTD1 promotes retinoic acid signaling required for development of the aortic arch. Disease models & mechanisms 18 30578278
2021 Overexpression of BIRC6 driven by EGF-JNK-HECTD1 signaling is a potential therapeutic target for triple-negative breast cancer. Molecular therapy. Nucleic acids 15 34729249
2021 Involvement of HECTD1 in LPS-induced astrocyte activation via σ-1R-JNK/p38-FOXJ2 axis. Cell & bioscience 14 33781347
2014 Basic Tilted Helix Bundle - a new protein fold in human FKBP25/FKBP3 and HectD1. Biochemical and biophysical research communications 13 24667607
2024 Dorsal root ganglion-derived exosomes deteriorate neuropathic pain by activating microglia via the microRNA-16-5p/HECTD1/HSP90 axis. Biological research 12 38750549
2023 Circ-Bnc2 alleviates neuroinflammation in LPS-stimulated microglial cells to inhibit neuron cell apoptosis through regulating miR-497a-5p/HECTD1 axis. Brain and behavior 12 36960892
2019 Hectd1 is essential for embryogenesis in mice. Gene expression patterns : GEP 12 31301385
2015 Abnormal labyrinthine zone in the Hectd1-null placenta. Placenta 11 26907377
2022 Circular RNA HECTD1 knockdown inhibits transforming growth factor-beta/ small mothers against decapentaplegic (TGF-β/Smad) signaling to reduce hypertrophic scar fibrosis. Bioengineered 10 35246019
2022 CircUCK2 regulates HECTD1-mediated endothelial-mesenchymal transition inhibition by interacting with FUS and protects the blood-brain barrier in ischemic stroke. The Kaohsiung journal of medical sciences 10 36326248
2021 Hsa_circ_0090002 regulates miR-186-5p/HECTD1 axis to mediate brain microvascular endothelial cell dysfunction. Brain research bulletin 7 34801649
2025 Hsa_circ_0002301 inhibits ferroptosis in gastric cancer by encoding the de novo protein HECTD1-463aa. Journal of translational medicine 6 40022084
2022 Vitamin C Inhibits Ubiquitination of Glutamate Transporter 1 (GLT-1) in Astrocytes by Downregulating HECTD1. ACS chemical neuroscience 6 35148069
2022 Circ_HECTD1 regulates cerebral ischemia injury via mechanisms involving the regulation of let-7c-5p/ROCK1 axis. Neuroreport 5 34874325
2025 Sequence variants in HECTD1 result in a variable neurodevelopmental disorder. American journal of human genetics 4 39879987
2023 Centriolin interacts with HectD1 in a cell cycle dependent manner. BMC research notes 4 38115153
2022 Proteasomal turnover of the RhoGAP tumor suppressor DLC1 is regulated by HECTD1 and USP7. Scientific reports 4 35322810
2025 Inflammation Inhibits HECTD1-Mediated AURKA Ubiquitination to Cause Extracellular Matrix Degradation in Osteoarthritis via Enhancing Cap-Dependent mRNA Translation of ADAMTS12. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 2 40838484
2024 Identification and functional analysis of rare HECTD1 missense variants in human neural tube defects. Human genetics 2 38451291
2023 Nucleoporin 93, a new substrate of the E3 ubiquitin protein ligase HECTD1, promotes esophageal squamous cell carcinoma progression. Human cell 2 37993750
2026 Therapeutic Hypothermia Ameliorates Apoptosis and Cerebral Injury by Upregulating HECTD1-mediated Ubiquitination and VDAC3 Degradation in a Rat CPR Model. International journal of medical sciences 0 42158826
2026 HECTD1 promotes pulmonary fibrosis by targeting EMT and subsequent fibroblasts activation. Toxicology letters 0 42167616
2025 HECTD1-mediated SFTPB overexpression in fibrotic lung induced by silica. Biochemistry and biophysics reports 0 41311373
2024 Identification and Functional Analysis of Rare HECTD1 Missense Variants in Human Neural Tube Defects. Research square 0 38260607

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