Affinage

HIF1AN

Hypoxia-inducible factor 1-alpha inhibitor · UniProt Q9NWT6

Length
349 aa
Mass
40.3 kDa
Annotated
2026-04-28
68 papers in source corpus 22 papers cited in narrative 22 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

HIF1AN (FIH-1) is an Fe(II)/α-ketoglutarate-dependent dioxygenase that functions as a cellular oxygen sensor by hydroxylating asparagine residues on HIF-1α and ankyrin repeat domain-containing substrates, thereby governing transcriptional responses, protein–protein interactions, and cell fate decisions. Under normoxia, FIH-1 hydroxylates Asn803 of the HIF-1α C-terminal transactivation domain, blocking recruitment of the coactivators CBP/p300 and suppressing HIF target gene expression; FIH-1 also binds VHL, which recruits histone deacetylases to further repress HIF-1α transactivation (PMID:12080085, PMID:11641274). Beyond HIF-1α, FIH-1 hydroxylates asparagine residues in the ankyrin repeat domains of ASPP2, KANK3, and other substrates, modulating their protein interactions and subcellular localization in an oxygen-dependent manner (PMID:23606740, PMID:29047187). FIH-1 additionally engages hydroxylase-independent functions—including negative regulation of glycogen stores via the Akt/GSK-3β pathway, cytosolic retention of pro-apoptotic Bax, and modulation of EGFR/LRRK1 and Notch signaling—that influence cell survival, migration, and proliferation (PMID:22532441, PMID:21069436, PMID:25455687, PMID:25837583).

Mechanistic history

Synthesis pass · year-by-year structured walk · 11 steps
  1. 2001 High

    Establishing that FIH-1 physically interacts with both HIF-1α and VHL to repress HIF-1α transactivation—independent of proteasomal degradation—defined a second oxygen-regulated checkpoint on HIF activity.

    Evidence Reciprocal Co-IP, transactivation reporter assays, and protein interaction mapping in mammalian cells

    PMID:11641274

    Open questions at the time
    • The enzymatic mechanism by which FIH-1 inhibits HIF-1α transactivation was not yet identified
    • Whether FIH-1 acts catalytically or purely as a scaffold was unresolved
  2. 2002 High

    Reconstitution of FIH-1 as an Fe(II)- and O₂-dependent asparaginyl hydroxylase targeting HIF-1α Asn803 explained how oxygen availability is transduced into a graded transcriptional response by blocking CBP/p300 binding.

    Evidence In vitro hydroxylase assay with Fe(II) and molecular O₂ dependence characterization

    PMID:12080085

    Open questions at the time
    • Structural details of the active site and catalytic cycle were not yet available
    • Whether FIH-1 hydroxylates substrates beyond HIF-1α was unknown
  3. 2008 High

    Spectroscopic characterization of uncoupled O₂ activation, auto-hydroxylation of Trp296, and the active-site Fe coordination geometry elucidated how the FIH-1 catalytic cycle can proceed in the absence of prime substrate.

    Evidence EPR, XAS, and UV-Vis spectroscopy with kinetic analysis

    PMID:18805587

    Open questions at the time
    • The kinetic partitioning between coupled and uncoupled turnover in vivo was not established
    • Whether auto-hydroxylation has a regulatory role was not determined
  4. 2010 High

    Crystal structures of FIH-1 bound to quinol inhibitors revealed the 2-oxoglutarate binding pocket geometry and validated Fe(II)-chelation as a pharmacological strategy, while discovery of the FIH-1–Bax interaction revealed a hydroxylase-independent anti-apoptotic function.

    Evidence X-ray crystallography of inhibitor complexes; reciprocal Co-IP, GST pull-down, and subcellular fractionation for Bax interaction

    PMID:20396966 PMID:21069436

    Open questions at the time
    • Whether Bax retention requires FIH-1 catalytic activity was not tested
    • In vivo relevance of the Bax-retention mechanism was not demonstrated
  5. 2012 High

    Demonstrating that FIH-1 negatively regulates glycogen stores via Akt/GSK-3β in a hydroxylase-independent and HIF-1α-independent manner broadened FIH-1 function beyond the HIF pathway.

    Evidence Enzyme-dead mutant analysis, glycogen assay, Western blot for Akt/GSK-3β signaling in corneal epithelial cells

    PMID:22532441

    Open questions at the time
    • The direct molecular target through which FIH-1 suppresses Akt phosphorylation was not identified
    • Whether this hydroxylase-independent role involves a scaffolding interaction was unresolved
  6. 2013 High

    Identification of ASPP2 and Gankyrin as FIH-1 substrates/interactors showed that ankyrin repeat domain hydroxylation modulates specific protein–protein interactions (Par-3 binding, subcellular localization) and that FIH-1 sequestration can upregulate HIF signaling in vivo.

    Evidence MS-based hydroxylation-site identification on ASPP2 with mutagenesis; Co-IP and transgenic mouse model for Gankyrin–FIH-1

    PMID:23376718 PMID:23606740

    Open questions at the time
    • The structural basis for hydroxylation-dependent changes in ARD protein interactions was not solved
    • The full scope of ARD-containing substrates was not mapped
  7. 2014 Medium

    Discovery that FIH-1 binds LRRK1 to sustain EGFR signaling and that FIH-1 null mice show delayed wound healing established a physiological role in tissue repair through MAPK/ERK signaling.

    Evidence Co-IP, scratch wound assay, ERK1/2 phosphorylation analysis, FIH-1 knockout mouse wound healing

    PMID:25455687

    Open questions at the time
    • Whether the LRRK1 interaction depends on FIH-1 hydroxylase activity was not tested
    • The wound healing phenotype was not confirmed in a conditional tissue-specific knockout
  8. 2015 Medium

    Showing that FIH-1 silencing increases Notch2 activity and induces endothelial apoptosis via survivin repression extended FIH-1's non-HIF functions to Notch pathway regulation in vascular biology.

    Evidence siRNA knockdown in HUVECs, Notch reporter assays, apoptosis assays

    PMID:25837583

    Open questions at the time
    • Whether FIH-1 directly hydroxylates Notch2 or acts via an intermediate was not determined in this system
    • Independent replication in primary endothelial cells from different vascular beds was lacking
  9. 2017 High

    In vitro reconstitution of KANK3 asparaginyl hydroxylation by FIH-1 at three sites, combined with oxygen-dependent functional effects on migration/invasion, confirmed FIH-1 as a general ARD hydroxylase with tumor-suppressive consequences.

    Evidence In vitro hydroxylation assay with MS site identification; normoxia vs. hypoxia migration/invasion assays in HCC cells

    PMID:29047187

    Open questions at the time
    • The structural or functional consequence of individual versus combinatorial site hydroxylation was not resolved
    • In vivo relevance of KANK3 hydroxylation in tumor suppression was not tested
  10. 2021 High

    Biophysical characterization of Mint3 folding-upon-binding to FIH-1 and kinetic demonstration that the hydrogen atom transfer step is partially rate-limiting (Dkcat = 10) together refined the mechanistic model for substrate recognition and O₂-sensing kinetics.

    Evidence ITC, NMR, CD, HDX-MS for Mint3 binding; deuterated substrate KIE and ferryl intermediate trapping for catalysis

    PMID:34655613 PMID:34714626

    Open questions at the time
    • Whether folding-upon-binding is a general feature of FIH-1 substrate recognition or specific to Mint3 is unknown
    • Cellular O₂ concentration thresholds for FIH-1 activity versus PHD activity were not measured side-by-side
  11. 2025 Medium

    FIH-1 deletion in intestinal epithelial cells activates PI3K-AKT signaling and confers radioprotection via cell-cycle redistribution, reinforcing the hydroxylase-independent role of FIH-1 in growth control.

    Evidence shRNA knockdown, RNA-seq pathway analysis, cell cycle and apoptosis assays in intestinal cells

    PMID:40762438

    Open questions at the time
    • Whether the PI3K-AKT activation upon FIH-1 loss is direct or secondary to HIF pathway changes was not fully dissected
    • In vivo radioprotection in conditional intestinal FIH-1 knockout animals was not shown

Open questions

Synthesis pass · forward-looking unresolved questions
  • A comprehensive catalog of FIH-1 substrates, the structural determinants distinguishing hydroxylase-dependent from hydroxylase-independent functions, and the in vivo O₂ thresholds at which FIH-1 activity switches remain unresolved.
  • No systematic proteomics-level map of all FIH-1 hydroxylation substrates exists
  • The molecular basis for FIH-1's hydroxylase-independent regulation of Akt/GSK-3β signaling is unknown
  • Tissue-specific phenotypes of conditional FIH-1 knockout mice are incompletely characterized

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016491 oxidoreductase activity 5 GO:0098772 molecular function regulator activity 4 GO:0140096 catalytic activity, acting on a protein 3
Localization
GO:0005634 nucleus 1 GO:0005829 cytosol 1
Pathway
R-HSA-8953897 Cellular responses to stimuli 5 R-HSA-162582 Signal Transduction 4 R-HSA-74160 Gene expression (Transcription) 4 R-HSA-5357801 Programmed Cell Death 3
Partners
ANKDD1AAPBB1ASPP2BAXHIF1ALRRK1PSMD10VHL

Evidence

Reading pass · 22 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2002 FIH-1 (HIF1AN) is an Fe(II)-dependent asparaginyl hydroxylase that hydroxylates an asparagine residue within the C-terminal transactivation domain (C-TAD) of HIF-1α, blocking its association with transcriptional coactivators CBP/p300 and thereby suppressing HIF transcriptional activity under normoxia. In vitro hydroxylase assay, Fe(II)-dependence demonstration, molecular O2 requirement assay Genes & development High 12080085
2001 FIH-1 binds directly to HIF-1α and inhibits its transactivation function; FIH-1 also binds to VHL, and VHL recruits histone deacetylases to further repress HIF-1α transactivation, providing a mechanism for O2-dependent regulation of HIF-1α transcriptional activity independent of proteasomal degradation. Co-immunoprecipitation (Co-IP), transactivation reporter assays, protein interaction mapping Genes & development High 11641274
2008 FIH-1 is an Fe(II)/α-ketoglutarate-dependent dioxygenase that can undergo uncoupled O2-activation in the absence of HIF-1α substrate, leading to auto-hydroxylation of Trp296 (forming an Fe(III)-O-Trp296 chromophore) or oxidation of Met275; EPR and XAS revealed distorted octahedral Fe(III) centers in the resulting enzyme forms, clarifying the active-site coordination chemistry. EPR spectroscopy, X-ray absorption spectroscopy (XAS), UV-Vis spectrophotometry, kinetic analysis Journal of inorganic biochemistry High 18805587
2010 Quinol family inhibitors (Clioquinol and 8-hydroxyquinoline) bind to the active site of FIH-1 by coordinating the Fe(II) ion, thereby competitively blocking binding of the co-substrate 2-oxoglutarate; crystal structures revealed the inhibitor-binding mode. X-ray crystallography of FIH-1 in complex with inhibitors Molecules and cells High 20396966
2021 The N-terminal disordered region of Mint3 (residues 78–88 form the core binding site) binds FIH-1; the interaction involves a large enthalpy/entropy change consistent with folding-upon-binding of the intrinsically disordered Mint3 region, as characterized by ITC, NMR, CD, and HDX-MS. Isothermal titration calorimetry (ITC), NMR, circular dichroism, hydrogen/deuterium exchange-mass spectrometry The Journal of biological chemistry High 34655613
2021 FIH-1 catalysis follows the canonical hydrogen atom transfer (HAT) step of αKG/Fe(II) dioxygenases; a large kinetic isotope effect (Dkcat = 10 ± 1) with deuterated substrate demonstrates HAT is partially rate-limiting on kcat, and uncoupling of O2 activation allowed spectroscopic observation of the ferryl intermediate. The close energy barrier between αKG decarboxylation and HAT is proposed to underlie FIH-1's function as an O2 sensor. Steady-state kinetics with deuterated peptide substrate, KIE measurement, spectroscopic detection of ferryl intermediate Biochemistry High 34714626
2013 FIH-1 hydroxylates asparagine 986 within the ankyrin repeat domain (ARD) of ASPP2; FIH-1 depletion impairs binding of Par-3 to ASPP2 and causes relocation of ASPP2 from cell-cell contacts to the cytosol, without affecting ASPP2 stability or its interaction with p53, demonstrating that FIH-1-dependent ARD hydroxylation modulates specific protein interactions of ankyrin repeat-containing substrates. Mass spectrometry substrate identification, Co-IP, siRNA knockdown, immunofluorescence localization, hydroxylase inhibitor (DMOG) treatment Journal of cell science High 23606740
2017 KANK3 is a substrate of HIF1AN; in vitro hydroxylation assay and mass spectrometry revealed asparaginyl hydroxylation of KANK3 at three asparagine residues within its ankyrin repeat domain, and the tumor-suppressive effects of KANK3 on HCC cell migration and invasion were only observed under normoxic (not hypoxic) conditions, indicating oxygen-dependent activity. In vitro hydroxylation assay, mass spectrometry, knockdown/overexpression with migration and invasion readouts Cell biology international High 29047187
2015 FIH-1 silencing in HUVECs leads to increased Notch2 activity, enhanced expression of the Notch target Hey-1, and selective repression of survivin, resulting in increased apoptosis and growth arrest; these data indicate FIH-1 represses Notch2 activity to promote endothelial cell survival. siRNA knockdown, Western blot, apoptosis assays, Notch reporter assays FASEB journal Medium 25837583
2012 FIH-1 negatively regulates glycogen stores in corneal epithelial cells via the Akt/GSK-3β/glycogen synthase pathway in a hydroxylase-independent and HIF-1α-independent manner; an enzyme-dead FIH-1 mutant failed to restore glycogen, while miR-31-resistant FIH-1 overexpression reduced glycogen and suppressed Akt signaling. Retroviral transduction, antagomir treatment, enzyme-dead mutant analysis, glycogen assay, Western blot for Akt/GSK-3β, HIF-1α reporter FASEB journal High 22532441
2014 FIH-1 binds LRRK1 (an ankyrin repeat domain-containing protein and regulator of EGFR endosomal trafficking); this interaction prevents formation of the EGFR/LRRK1 complex, sustaining EGFR signaling and promoting keratinocyte migration via the MAPK/ERK1/2 pathway. FIH-1 null mice exhibit delayed wound healing. Co-IP, in vitro scratch wound assay, FIH-1 null mouse wound healing assay, ERK1/2 phosphorylation analysis The American journal of pathology Medium 25455687
2019 FIH-1 interacts with Plectin1 and STAT1 (identified by BioID proteomics) as well as previously known partners ASPP2 and HDAC1; through these interactions FIH-1 positively regulates ΔNp63α expression in keratinocytes — via ASPP2-dependent suppression and via HDAC1/GADD45α signaling — and promotes epidermal proliferation. BioID proximity proteomics, siRNA knockdown, Co-IP, conditional transgenic mouse, Western blot FASEB journal Medium 31914679
2010 FIH-1 directly interacts with Bax and functions as a cytosol retention factor for Bax, blocking Bax translocation from the cytosol to mitochondria in response to apoptotic stimuli; FIH-1 overexpression suppresses Bax-mediated apoptosis while FIH-1 deficiency accelerates it. Mass spectrometry interactor identification, Co-immunoprecipitation, GST pull-down, overexpression and knockdown with apoptosis readouts, subcellular fractionation Molecular and cellular biochemistry Medium 21069436
2013 Gankyrin (PSMD10) binds to and sequesters FIH-1, decreasing the interaction between FIH-1 and HIF-1α, thereby increasing HIF-1 transcriptional activity and VEGF production; transgenic hepatocyte overexpression of gankyrin caused hepatic hemangioma/hemangiosarcomas, an effect mediated through FIH-1 sequestration. Co-immunoprecipitation, transgenic mouse model, reporter gene assays, tumor formation assay Biochemical and biophysical research communications Medium 23376718
2014 FIH-1 interacts with Mindbomb (Mib) E3 ubiquitin ligase (identified in yeast two-hybrid screen and confirmed by colocalization); in zebrafish, FIH-1 depletion induces ectopic VEGF-A expression and ectopic vascular sprouting, while FIH-1 overexpression attenuates intersegmental vessel formation — rescued by co-overexpression of VEGF-A — indicating FIH-1/HIF1AN fine-tunes VEGF-A signaling during vascular development. Yeast two-hybrid, colocalization in cultured cells, zebrafish morpholino knockdown, zebrafish overexpression, ISV phenotype analysis PloS one Medium 25347788
2007 The homeodomain protein CDP/Cut binds the FIH-1 promoter in a PKCζ-dependent manner and transcriptionally represses FIH-1 expression; a PKCζ-dependent phosphorylation site on CDP (Ser987) modulates this repression, leading to decreased FIH-1 levels and consequent increased HIF-1 activity in renal cell carcinoma. Chromatin immunoprecipitation, promoter reporter assays, PKC inhibition/activation, mutagenesis of CDP phosphorylation site Molecular and cellular biology Medium 17682059
2011 In VHL-defective clear cell renal cell carcinoma expressing both HIF-1α and HIF-2α (RCC10, RCC4), FIH-1 knockdown increases HIF target gene expression and increases apoptosis; suppressing HIF-1α expression prevents FIH-1 knockdown from increasing apoptosis, indicating that FIH-1 promotes CCRCC cell survival by restraining HIF-1α-mediated apoptotic activity. siRNA knockdown, retroviral gene expression, qRT-PCR, Western blot, Annexin V/PI apoptosis assay British journal of cancer Medium 21386837
2018 ANKDD1A directly interacts with FIH1 and, by upregulating FIH1, inhibits HIF1α transcriptional activity and decreases the half-life of HIF1α, thereby reducing glucose uptake, lactate production, and autophagy while inducing apoptosis in GBM cells under hypoxia. Co-immunoprecipitation, siRNA knockdown, Western blot, glucose/lactate assays, autophagy and apoptosis assays Oncogene Medium 30082910
2023 ASB9, an E3 ubiquitin ligase, directly interacts with HIF1AN and promotes its ubiquitination and degradation; re-expression of HIF1AN in ASB9-overexpressing spermatogonial stem cells reverses the proliferation inhibition and apoptosis induction caused by ASB9, placing HIF1AN downstream of ASB9. Co-immunoprecipitation, Western blot (ubiquitination), overexpression rescue experiments, single-cell sequencing analysis Biological research Medium 36683111
2025 FIH-1 deletion in intestinal epithelial cells activates the PI3K-AKT pathway and redistributes cells into S-phase, resulting in radioprotection; RNA-seq and Western blot confirmed PI3K-AKT and cell cycle signaling upregulation upon FIH-1 loss. shRNA knockdown, colony formation assay, cell cycle analysis, apoptosis assay, RNA-seq, Western blot FASEB journal Medium 40762438
2005 Nickel(II) and cobalt(II) downregulate FIH-1 (and ARD-1) mRNA in human lung adenocarcinoma A549 cells, providing a mechanism by which these metals activate HIF-1 transcriptional activity by reducing levels of its negative regulator. qRT-PCR measurement of FIH-1 mRNA after metal treatment International journal of environmental research and public health Low 16705796
2025 FIH-1 does not interact with IKKα/β or IκBα and does not affect NF-κB classical pathway components (IKKα/β or p65 protein levels), distinguishing it from PHD1-3 which do interact with IKK and attenuate LPS-activated NF-κB. Co-immunoprecipitation, Western blot after FIH-1 overexpression The Journal of toxicological sciences Low 40024754

Source papers

Stage 0 corpus · 68 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 FIH-1 is an asparaginyl hydroxylase enzyme that regulates the transcriptional activity of hypoxia-inducible factor. Genes & development 1247 12080085
2001 FIH-1: a novel protein that interacts with HIF-1alpha and VHL to mediate repression of HIF-1 transcriptional activity. Genes & development 1170 11641274
2015 MicroRNA-455 regulates brown adipogenesis via a novel HIF1an-AMPK-PGC1α signaling network. EMBO reports 133 26303948
2019 MiR-135-5p promotes osteoblast differentiation by targeting HIF1AN in MC3T3-E1 cells. Cellular & molecular biology letters 96 31410089
2015 Hypoxia-inducible miR-182 enhances HIF1α signaling via targeting PHD2 and FIH1 in prostate cancer. Scientific reports 87 26205124
2013 Transcriptional regulation of hypoxia inducible factors alpha (HIF-α) and their inhibiting factor (FIH-1) of channel catfish (Ictalurus punctatus) under hypoxia. Comparative biochemistry and physiology. Part B, Biochemistry & molecular biology 67 24384398
2021 Exosomes from adipose-derived stem cells alleviate myocardial infarction via microRNA-31/FIH1/HIF-1α pathway. Journal of molecular and cellular cardiology 66 34474073
2004 Molecular genetic analysis of FIH-1, FH, and SDHB candidate tumour suppressor genes in renal cell carcinoma. Journal of clinical pathology 57 15220362
2014 MicroRNA-31 contributes to colorectal cancer development by targeting factor inhibiting HIF-1α (FIH-1). Cancer biology & therapy 54 24521875
2012 MicroRNA-31 targets FIH-1 to positively regulate corneal epithelial glycogen metabolism. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 53 22532441
2015 MicroRNA-135b regulates ERα, AR and HIF1AN and affects breast and prostate cancer cell growth. Molecular oncology 50 25907805
2015 The role of the miR-31/FIH1 pathway in TGF-β-induced liver fibrosis. Clinical science (London, England : 1979) 49 25728779
2013 Factor inhibiting HIF-1 (FIH-1) modulates protein interactions of apoptosis-stimulating p53 binding protein 2 (ASPP2). Journal of cell science 45 23606740
2022 Regulation of Transactivation at C-TAD Domain of HIF-1α by Factor-Inhibiting HIF-1α (FIH-1): A Potential Target for Therapeutic Intervention in Cancer. Oxidative medicine and cellular longevity 43 35592530
2014 The role of factor inhibiting HIF (FIH-1) in inhibiting HIF-1 transcriptional activity in glioblastoma multiforme. PloS one 43 24465898
2023 M2 macrophage-derived exosomes induce angiogenesis and increase skin flap survival through HIF1AN/HIF-1α/VEGFA control. Archives of biochemistry and biophysics 39 38030054
2018 Hypermethylated gene ANKDD1A is a candidate tumor suppressor that interacts with FIH1 and decreases HIF1α stability to inhibit cell autophagy in the glioblastoma multiforme hypoxia microenvironment. Oncogene 39 30082910
2016 MicroRNA-125a-5p Contributes to Hepatic Stellate Cell Activation through Targeting FIH1. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 35 27074047
2011 Factor inhibiting HIF (FIH-1) promotes renal cancer cell survival by protecting cells from HIF-1α-mediated apoptosis. British journal of cancer 35 21386837
2015 Factor inhibiting HIF1α (FIH-1) functions as a tumor suppressor in human colorectal cancer by repressing HIF1α pathway. Cancer biology & therapy 34 25602156
2015 Factor-inhibiting HIF-1 (FIH-1) is required for human vascular endothelial cell survival. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 27 25837583
2014 FIH-1, a novel interactor of mindbomb, functions as an essential anti-angiogenic factor during zebrafish vascular development. PloS one 26 25347788
2017 Downregulation of microRNA-31 inhibits proliferation and induces apoptosis by targeting HIF1AN in human keloid. Oncotarget 25 29088812
2014 Upregulation of miR-184 enhances the malignant biological behavior of human glioma cell line A172 by targeting FIH-1. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 24 25277131
2008 Coordination changes and auto-hydroxylation of FIH-1: uncoupled O2-activation in a human hypoxia sensor. Journal of inorganic biochemistry 23 18805587
2021 TMEM161B-AS1 suppresses proliferation, invasion and glycolysis by targeting miR-23a-3p/HIF1AN signal axis in oesophageal squamous cell carcinoma. Journal of cellular and molecular medicine 22 34046994
2014 Variants of the low oxygen sensors EGLN1 and HIF-1AN associated with acute mountain sickness. International journal of molecular sciences 22 25431923
2013 Overexpression of gankyrin in mouse hepatocytes induces hemangioma by suppressing factor inhibiting hypoxia-inducible factor-1 (FIH-1) and activating hypoxia-inducible factor-1. Biochemical and biophysical research communications 22 23376718
2005 Down-regulation of the expression of the FIH-1 and ARD-1 genes at the transcriptional level by nickel and cobalt in the human lung adenocarcinoma A549 cell line. International journal of environmental research and public health 22 16705796
2023 Ubiquitin protein E3 ligase ASB9 suppresses proliferation and promotes apoptosis in human spermatogonial stem cell line by inducing HIF1AN degradation. Biological research 20 36683111
2011 Subcellular FIH-1 expression patterns in invasive breast cancer in relation to HIF-1α expression. Cellular oncology (Dordrecht, Netherlands) 19 21732131
2022 METTL3 m6A-dependently promotes miR-21-5p maturation to accelerate choriocarcinoma progression via the HIF1AN-induced inactivation of the HIF1A/VEGF pathway. Genes & genomics 17 36074324
2018 The miRNA-184 drives renal fibrosis by targeting HIF1AN in vitro and in vivo. International urology and nephrology 17 30536131
2015 microRNA-98 mediated microvascular hyperpermeability during burn shock phase via inhibiting FIH-1. European journal of medical research 15 25903459
2007 Protein kinase C-mediated modulation of FIH-1 expression by the homeodomain protein CDP/Cut/Cux. Molecular and cellular biology 15 17682059
2010 Crystal structures of human FIH-1 in complex with quinol family inhibitors. Molecules and cells 14 20396966
2021 CircCDR1as Suppresses Bone Microvascular Endothelial Cell Activity and Angiogenesis Through Targeting miR-135b/ FIH-1 Axis. Orthopaedic surgery 13 33619902
2021 Silencing of SNHG6 alleviates hypoxia/reoxygenation-induced cardiomyocyte apoptosis by modulating miR-135a-5p/HIF1AN to activate Shh/Gli1 signalling pathway. The Journal of pharmacy and pharmacology 13 33791813
2017 A novel HIF1AN substrate KANK3 plays a tumor-suppressive role in hepatocellular carcinoma. Cell biology international 13 29047187
2020 MicroRNA-1-3p enhances osteoblast differentiation of MC3T3-E1 cells by interacting with hypoxia-inducible factor 1 α inhibitor (HIF1AN). Mechanisms of development 12 32387587
2020 CASC2 inhibits the growth, migration, and invasion of thyroid cancer cells through sponging miR-18a-5p/FIH1 axis. The Kaohsiung journal of medical sciences 12 33336500
2019 Molecular characterization and expression regulation of the factor-inhibiting HIF-1 (FIH-1) gene under hypoxic stress in bighead carp (Aristichthys nobilis). Fish physiology and biochemistry 10 30607683
2019 FIH-1 engages novel binding partners to positively influence epithelial proliferation via p63. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 10 31914679
2014 FIH-1 disrupts an LRRK1/EGFR complex to positively regulate keratinocyte migration. The American journal of pathology 10 25455687
2023 Hepatitis B Virus-Encoded MicroRNA (HBV-miR-3) Inhibits FIH-1 Expression to Promote Tumor Angiogenesis in HBV-Related Hepatocellular Carcinoma. Journal of hepatocellular carcinoma 9 38163053
2019 Polymorphisms in microRNA let-7 binding sites of the HIF1AN and CLDN12 genes can predict pathologic complete response to taxane- and platinum-based neoadjuvant chemotherapy in breast cancer. Annals of translational medicine 9 31157259
2016 Investigation of FIH-1 and SOCS3 expression in KRAS mutant and wild-type patients with colorectal cancer. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 9 26749281
2022 CircSLC8A1 targets miR-181a-5p/HIF1AN pathway to inhibit the growth, migration and extracellular matrix deposition of human keloid fibroblasts. Burns : journal of the International Society for Burn Injuries 8 35610079
2022 Enhanced BPGM/2,3-DPG pathway activity suppresses glycolysis in hypoxic astrocytes via FIH-1 and TET2. Brain research bulletin 8 36334804
2021 Structural and thermodynamical insights into the binding and inhibition of FIH-1 by the N-terminal disordered region of Mint3. The Journal of biological chemistry 8 34655613
2010 Prevention of apoptosis by the interaction between FIH1 and Bax. Molecular and cellular biochemistry 8 21069436
2022 Pinoresinol diglucoside ameliorates H/R-induced injury of cardiomyocytes by regulating miR-142-3p and HIF1AN. Journal of biochemical and molecular toxicology 7 35962614
2022 Knockout of Factor-Inhibiting HIF (Hif1an) in Colon Epithelium Attenuates Chronic Colitis but Does Not Reduce Colorectal Cancer in Mice. Journal of immunology (Baltimore, Md. : 1950) 6 35121641
2017 Interactions between RASA2, CADM1, HIF1AN gene polymorphisms and body fatness with breast cancer: a population-based case-control study in China. Oncotarget 6 29228687
2016 Molecular response and association analysis of Megalobrama amblycephala fih-1 with hypoxia. Molecular genetics and genomics : MGG 6 27112926
2023 Withdrawn: Y. Yin, X. Lu, M. Yang, J. Shangguan, Y. Zhang. Inhibition of lncRNA MALAT1 reduces myocardial ischemia-reperfusion injury of rat cardiomyocytes through regulating the miR-135a-5p/HIF1AN axis, published in The Journal of Gene Medicine. The journal of gene medicine 4 34626458
2023 Upregulated microRNA-429 confers endometrial stromal cell dysfunction by targeting HIF1AN and regulating the HIF1A/VEGF pathway. Open medicine (Warsaw, Poland) 3 37854282
2022 Danlou Tablet May Alleviate Vascular Injury Caused by Chronic Intermittent Hypoxia through Regulating FIH-1, HIF-1, and Angptl4. Evidence-based complementary and alternative medicine : eCAM 3 36285165
2021 Kinetic Studies of the Hydrogen Atom Transfer in a Hypoxia-Sensing Enzyme, FIH-1: KIE and O2 Reactivity. Biochemistry 3 34714626
2025 CircPVT1 promotes periodontitis progression by regulating miR-24-3p/HIF1AN pathway. Journal of stomatology, oral and maxillofacial surgery 2 39986587
2024 The mechanism of lncRNA SNHG1 in osteogenic differentiation via miR-497-5p/ HIF1AN axis. Connective tissue research 2 37966352
2024 Molecular characterization and function of hif1a and fih1 in response to acute thermal stress in American shad (Alosa sapidissima). Fish physiology and biochemistry 2 38789648
2025 Prolyl hydroxylase domain enzymes (isoforms 1-3, PHD1-3), but not factor-inhibiting HIF-1 (FIH-1), interact with the IKK complex and attenuate LPS-activated NF-kappa-B. The Journal of toxicological sciences 1 40024754
2024 Rynchopeterine inhibits the formation of hypertrophic scars by regulating the miR-21/HIF1AN axis. Experimental cell research 1 38823472
2024 Cancer cell-derived exosomes promote NSCLC progression via the miR-199b-5p/HIF1AN axis. Molecular immunology 1 39154583
2026 Hypoxia‑induced miR‑135b‑5p promotes neuroendocrine differentiation of prostate cancer cells through HIF1AN‑HIF1α axis. Oncology reports 0 41716025
2025 PML Regulated HIF1AN Ubiquitination and Activated PI3K/AKT Pathway to Promote Bone Marrow Mesenchymal Stem Cells Osteogenic Differentiation. International journal of stem cells 0 40059075
2025 FIH-1 Deletion in Intestinal Epithelial Cells Causes Radioprotection by Activating PI3K-AKT Pathway. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 0 40762438