Affinage

HIF1AN

Hypoxia-inducible factor 1-alpha inhibitor · UniProt Q9NWT6

Length
349 aa
Mass
40.3 kDa
Annotated
2026-06-10
68 papers in source corpus 24 papers cited in narrative 24 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

HIF1AN (FIH-1) is an Fe(II)- and O2-dependent asparaginyl hydroxylase that functions as the principal oxygen sensor restraining HIF transcriptional activity under normoxia by hydroxylating an asparagine in the C-terminal transactivation domain of HIF-1α, blocking coactivator recruitment and binding both HIF-1α and VHL to achieve dual O2-dependent repression (PMID:12080085, PMID:11641274). Its catalytic cycle proceeds through canonical hydrogen-atom transfer on the asparagine via a ferryl intermediate, and the near-equal energy barrier between αKG decarboxylation and HAT is the mechanistic basis for its O2-sensing role; in the absence of substrate the enzyme undergoes uncoupled O2-activation with auto-hydroxylation of Trp296, and quinol inhibitors block activity by coordinating the active-site Fe and excluding 2-oxoglutarate (PMID:18805587, PMID:20396966, PMID:34714626). FIH-1 shows substrate preference for HIF-1α over HIF-2α and suppresses HIF target genes such as GLUT1 and VEGF-A even under hypoxia (PMID:24465898, PMID:21386837). Beyond HIF, FIH-1 hydroxylates ankyrin-repeat-domain substrates including ASPP2 at N986—promoting ASPP2/Par-3 binding and junctional localization—and KANK3, coupling its enzymatic activity to protein-protein interactions (PMID:23606740, PMID:29047187). It also performs HIF-1α-independent functions: hydroxylase-independent suppression of glycogen metabolism via the AKT/GSK-3β axis, cytosolic retention of pro-apoptotic Bax to suppress apoptosis, and regulation of keratinocyte migration and ΔNp63α expression through binding partners including LRRK1, Plectin1, STAT1, ASPP2 and HDAC1 (PMID:22532441, PMID:21069436, PMID:25455687, PMID:31914679). FIH-1 abundance is set transcriptionally by CDP/Cut–PKCζ repression and post-translationally by ASB9- and PML-mediated ubiquitination and degradation, and its activity is modulated by interacting proteins that either sequester it (Gankyrin) or stimulate it (ANKDD1A) to tune HIF output (PMID:17682059, PMID:36683111, PMID:40059075, PMID:23376718, PMID:30082910).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 2001 High

    Established that FIH-1 is a physical inhibitor of HIF-1α transactivation, defining a new oxygen-regulatory node distinct from the VHL/proteolysis axis.

    Evidence Co-IP, mammalian two-hybrid, and transactivation reporter assays showing FIH-1 binds HIF-1α and VHL

    PMID:11641274

    Open questions at the time
    • Did not define the enzymatic basis of inhibition
    • Mechanism of VHL-mediated HDAC recruitment not resolved
  2. 2002 High

    Identified the molecular mechanism: FIH-1 is an Fe(II)/O2-dependent asparaginyl hydroxylase that modifies the HIF-1α C-TAD asparagine to block coactivator binding, explaining O2-dependent HIF suppression.

    Evidence In vitro hydroxylase assays with Fe(II)- and molecular O2-dependence tests

    PMID:12080085

    Open questions at the time
    • Catalytic intermediates and rate-limiting steps not characterized
    • Non-HIF substrates not yet known
  3. 2007 High

    Showed FIH-1 expression itself is controlled, with CDP/Cut repressing the FIH-1 promoter in a PKCζ-dependent manner to derepress HIF activity in renal carcinoma.

    Evidence ChIP, luciferase promoter assays, PKCζ inhibition, and CDP S987 mutagenesis

    PMID:17682059

    Open questions at the time
    • Generality of CDP/Cut control beyond RCC unknown
    • Upstream signals activating PKCζ not defined
  4. 2008 High

    Defined the active-site chemistry of substrate-free FIH-1, revealing uncoupled O2-activation, Trp296 auto-hydroxylation, and high-spin Fe(III) geometry.

    Evidence UV-Vis, EPR, XAS, Co(II) substitution, and in vitro uncoupling assays

    PMID:18805587

    Open questions at the time
    • Physiological consequence of auto-hydroxylation unclear
    • Did not capture the productive ferryl intermediate
  5. 2010 High

    Provided structural mechanism of inhibition, showing quinol compounds coordinate the active-site Fe and exclude 2OG, and revealed FIH-1 acts as a cytosolic Bax retention factor independent of its HIF role.

    Evidence X-ray crystallography of FIH-1:inhibitor complexes; Co-IP, GST pull-down, fractionation, and apoptosis assays for Bax

    PMID:20396966 PMID:21069436

    Open questions at the time
    • Whether Bax retention requires hydroxylase activity not established
    • Structural basis of Bax interaction unknown
  6. 2011 Medium

    Demonstrated FIH-1 substrate preference for HIF-1α over HIF-2α in modulating target genes and cell viability, using isogenic CCRCC lines and HIF-1α complementation.

    Evidence siRNA knockdown, retroviral HIF-1α re-introduction, qRT-PCR, and apoptosis assays

    PMID:21386837

    Open questions at the time
    • Structural basis of isoform discrimination not addressed
    • Single lab
  7. 2012 Medium

    Revealed a hydroxylase-independent, HIF-1α-independent function in glycogen metabolism via the AKT/GSK-3β pathway, broadening FIH-1 biology beyond catalysis.

    Evidence Enzyme-dead FIH-1 mutant, antagomir knockdown, glycogen assays, and pathway western blots

    PMID:22532441

    Open questions at the time
    • Molecular target linking FIH-1 to AKT not identified
    • Generality beyond corneal epithelium unknown
  8. 2013 Medium

    Extended FIH-1 substrate range to ARD proteins, showing ASPP2 N986 hydroxylation controls ASPP2/Par-3 binding and junctional localization, and identifying Gankyrin as a sequestering regulator that boosts HIF activity in vivo.

    Evidence MS site identification, in vitro hydroxylation, Co-IP, immunofluorescence (ASPP2); Co-IP and transgenic mouse (Gankyrin)

    PMID:23376718 PMID:23606740

    Open questions at the time
    • Functional consequence of ASPP2 mislocalization on tissue physiology unclear
    • Whether Gankyrin affects FIH-1 catalysis directly not shown
  9. 2014 Medium

    Expanded FIH-1 into angiogenesis, endothelial survival, keratinocyte migration and continued HIF suppression under hypoxia, linking it to Notch2, LRRK1/EGFR, and Mindbomb.

    Evidence siRNA/Notch readouts (HUVEC); scratch assays, Co-IP, KO mice (LRRK1); zebrafish morpholino, Y2H, ISV imaging (Mib); retroviral/siRNA qRT-PCR in glioblastoma

    PMID:24465898 PMID:25347788 PMID:25455687 PMID:25837583

    Open questions at the time
    • Direct FIH-1/Notch2 binding not demonstrated
    • Whether LRRK1 and Mib effects depend on hydroxylation unresolved
  10. 2017 Medium

    Confirmed KANK3 as an ARD hydroxylation substrate with three hydroxylated asparagines, reinforcing FIH-1's role as a regulator of ARD-containing tumor suppressors under oxygen control.

    Evidence In vitro hydroxylation, mass spectrometry, and normoxia-vs-hypoxia migration/invasion assays

    PMID:29047187

    Open questions at the time
    • Individual sites not validated by mutagenesis
    • Functional impact of each hydroxylation site undefined
  11. 2018 Medium

    Identified ANKDD1A as a direct activator that upregulates FIH-1 to lower HIF1α stability and activity, suppressing glycolysis and autophagy in glioblastoma.

    Evidence Co-IP, HIF1α stability assays, glucose/lactate measurement, autophagy/apoptosis assays

    PMID:30082910

    Open questions at the time
    • Mechanism by which ANKDD1A enhances catalysis unknown
    • Single lab
  12. 2019 Medium

    Mapped an interactome (Plectin1, STAT1, ASPP2, HDAC1) through which FIH-1 positively regulates ΔNp63α in keratinocytes, integrating it into epidermal gene regulation.

    Evidence BioID proteomics, Co-IP, siRNA, and conditional transgenic/knockout mice

    PMID:31914679

    Open questions at the time
    • Whether these interactions require hydroxylase activity unclear
    • Direct hydroxylation of new partners not tested
  13. 2021 High

    Resolved the catalytic basis of O2 sensing—partially rate-limiting HAT through a ferryl intermediate with a close barrier to αKG decarboxylation—and thermodynamically characterized disordered-substrate (Mint3) binding via disorder-to-order transition.

    Evidence KIE with deuterated substrate and ferryl detection (kinetics); CD, NMR, HDX-MS, ITC with truncations (Mint3)

    PMID:34655613 PMID:34714626

    Open questions at the time
    • In-cell relevance of the kinetic barrier not tested
    • Structure of the FIH-1/Mint3 complex not determined
  14. 2023 Medium

    Established post-translational control of FIH-1 abundance, with ASB9 directly binding and targeting HIF1AN for ubiquitin-mediated degradation in spermatogonial stem cells.

    Evidence Co-IP, HIF1AN protein-level western blots, and proliferation/apoptosis rescue assays

    PMID:36683111

    Open questions at the time
    • Ubiquitination sites not mapped
    • Generality beyond SSC lines unknown
  15. 2025 Medium

    Refined the regulatory and signaling boundaries of FIH-1: PML drives its ubiquitin-mediated degradation to promote osteogenesis, while FIH-1 was shown not to regulate the classical NF-κB pathway.

    Evidence Co-IP, ChIP, luciferase, differentiation assays (PML); IP and overexpression negative results (NF-κB)

    PMID:40024754 PMID:40059075

    Open questions at the time
    • PML and ASB9 relationship to each other unresolved
    • Negative NF-κB result is single-lab

Open questions

Synthesis pass · forward-looking unresolved questions
  • How FIH-1 selects among its many catalytic (HIF-1α, ASPP2, KANK3) and non-catalytic (Bax, LRRK1, AKT) functions in different tissues, and which depend on hydroxylase activity versus scaffolding, remains unresolved.
  • No unified rule distinguishing hydroxylation-dependent from independent functions
  • Tissue-specific substrate hierarchy undefined
  • Structural models for most non-HIF substrates lacking

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016491 oxidoreductase activity 5 GO:0098772 molecular function regulator activity 3 GO:0140096 catalytic activity, acting on a protein 3
Localization
GO:0005829 cytosol 2
Pathway
R-HSA-8953897 Cellular responses to stimuli 4 R-HSA-74160 Gene expression (Transcription) 3 R-HSA-5357801 Programmed Cell Death 2
Partners
ANKDD1AASPP2BAXHDAC1HIF1AKANK3LRRK1VHL

Evidence

Reading pass · 24 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2002 FIH-1 is an asparaginyl hydroxylase (Fe(II)-dependent, O2-dependent dioxygenase) that hydroxylates an asparagine residue within the C-terminal transactivation domain (C-TAD) of HIF-1α, blocking its association with transcriptional coactivators and suppressing HIF transcriptional activity under normoxia. In vitro hydroxylase assay, Fe(II)-dependence tests, molecular O2 substrate assays Genes & development High 12080085
2001 FIH-1 physically binds 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 dual mechanism for O2-dependent regulation of HIF-1α activity. Co-immunoprecipitation, mammalian two-hybrid, transactivation reporter assays Genes & development High 11641274
2008 FIH-1 undergoes uncoupled O2-activation in the absence of its HIF-1α substrate, resulting in auto-hydroxylation of Trp296 (forming an Fe(III)-O-Trp296 chromophore) and oxidation of Met275; the enzyme active site contains high-spin Fe(III) in both outcomes, with distorted octahedral geometry as shown by XAS and EPR. Co(II)-substituted FIH-1 exists in a mixture of 5- and 6-coordinate forms, indicating the resting enzyme can readily undergo uncoupled O2-activation by loss of an H2O ligand. UV-Vis spectroscopy, EPR, XAS, in vitro uncoupling assay, Co(II) substitution Journal of inorganic biochemistry High 18805587
2010 Crystal structures of human FIH-1 in complex with quinol inhibitors (Clioquinol and 8-Hydroxyquinoline) show that these compounds bind the FIH-1 active site by coordinating the Fe(II) ion, thereby blocking binding of the co-substrate 2-oxoglutarate (2OG) and inhibiting hydroxylase activity. X-ray crystallography (crystal structures of FIH-1:inhibitor complexes) Molecules and cells High 20396966
2021 Kinetic isotope effect (KIE) studies with deuterated peptide substrate demonstrate that FIH performs canonical hydrogen atom transfer (HAT) on the asparagine substrate (Dkcat = 10 ± 1), that this step is partially rate-limiting on kcat, and that the deuterated substrate causes uncoupled O2-activation allowing spectroscopic observation of the ferryl intermediate. The close energy barrier between αKG decarboxylation and HAT is identified as the mechanistic basis for FIH's role as an O2-sensing enzyme. Steady-state kinetics with deuterated substrate, KIE measurements, spectroscopic detection of ferryl intermediate Biochemistry High 34714626
2007 FIH-1 transcription in renal cell carcinoma is repressed by the homeodomain protein CDP/Cut, which binds a defined site on the FIH-1 promoter in a PKCζ-dependent manner (with Ser987 phosphorylation of CDP as the regulatory phosphosite); this repression reduces FIH-1 levels and permits increased HIF-1 activity and downstream target gene (VEGF, GLUT-1) expression. Chromatin immunoprecipitation, luciferase promoter assay, PKCζ inhibition, site-directed mutagenesis (CDP S987) Molecular and cellular biology High 17682059
2013 FIH-1 hydroxylates the ankyrin repeat domain (ARD)-containing protein ASPP2 at asparagine 986 (N986); this hydroxylation promotes binding of ASPP2 to the cell polarity regulator Par-3. FIH-1 depletion or hydroxylase inhibition (DMOG) causes ASPP2 to relocate from cell-cell contacts to the cytosol without affecting ASPP2 stability, p53 interaction, apoptosis, or proliferation. Mass spectrometry substrate identification, Co-IP, in vitro hydroxylation assay, immunofluorescence localization, DMOG pharmacological inhibition Journal of cell science High 23606740
2013 Gankyrin binds to and sequesters FIH-1, reducing FIH-1/HIF-1α interaction, thereby increasing HIF-1 transcriptional activity and VEGF production, and promoting vascular tumor formation in transgenic mouse livers. Co-immunoprecipitation, transgenic mouse model, cell-based HIF activity assays Biochemical and biophysical research communications Medium 23376718
2014 FIH-1 positively regulates keratinocyte migration by binding to LRRK1 (a regulator of EGFR endosomal trafficking), preventing EGFR/LRRK1 complex formation, thereby enhancing EGFR signaling and downstream ERK1/2 activation. FIH-1 null mice show delayed wound healing. In vitro scratch wound assays, Co-IP (FIH-1/LRRK1 interaction), FIH-1 knockout mice, EGFR/MAPK pathway analysis The American journal of pathology Medium 25455687
2012 FIH-1 negatively regulates glycogen metabolism in corneal epithelial cells through the AKT/GSK-3β/glycogen synthase pathway in a hydroxylase-independent manner (enzyme-dead FIH-1 fails to reduce glycogen), and independently of HIF-1α. Retroviral transduction of enzyme-dead FIH-1 mutant, antagomir knockdown, glycogen assay, AKT/GSK-3β western blot, HIF-1α reporter (negative result for HIF-1α dependence) FASEB journal Medium 22532441
2014 FIH-1 silencing in human vascular endothelial cells (HUVECs) leads to increased Notch2 activity, enhanced Hey-1 expression, and selective repression of survivin, resulting in apoptosis and growth arrest. FIH-1 is proposed to repress Notch2 activity, controlling endothelial cell survival. siRNA knockdown, western blot (Notch2, Hey-1, survivin), apoptosis assays FASEB journal Medium 25837583
2010 FIH-1 directly interacts with the pro-apoptotic protein Bax and functions as a cytosolic retention factor for Bax, preventing its translocation to mitochondria in response to apoptotic stimuli; FIH-1 overexpression suppresses Bax-mediated apoptosis, while FIH-1 deficiency accelerates it. Co-immunoprecipitation, GST pull-down, apoptosis assays, subcellular fractionation Molecular and cellular biochemistry Medium 21069436
2017 KANK3 is a substrate for HIF1AN asparaginyl hydroxylation; in vitro hydroxylation assay confirmed hydroxylation, and mass spectrometry identified three hydroxylated asparagine residues within the ankyrin repeat domain of KANK3. KANK3 tumor-suppressive effects on cell migration/invasion were not observed under hypoxic conditions, consistent with oxygen-dependent HIF1AN activity. In vitro hydroxylation assay, mass spectrometry, cell migration/invasion assays under normoxia vs. hypoxia Cell biology international Medium 29047187
2014 FIH-1 inhibits HIF-1-mediated transcription of GLUT1 and VEGF-A even under hypoxic conditions in glioblastoma cells, and FIH-1 is more potent than PTEN in inhibiting HIF function in this context. Retroviral FIH-1 expression, siRNA knockdown, quantitative RT-PCR for HIF target genes (GLUT1, VEGF-A) under hypoxia PloS one Medium 24465898
2011 In VHL-defective CCRCC cells expressing both HIF-1α and HIF-2α, FIH-1 knockdown increases HIF target gene expression and apoptosis. In 786-O cells expressing only HIF-2α, FIH-1 knockdown has no effect; re-introduction of HIF-1α restores sensitivity to FIH-1 knockdown. This establishes FIH-1's substrate preference for HIF-1α over HIF-2α in modulating both target gene expression and cell viability. siRNA knockdown, retroviral gene expression, qRT-PCR, Annexin V/propidium iodide apoptosis assay British journal of cancer Medium 21386837
2019 FIH-1 interacts with Plectin1 and STAT1 (novel binding partners identified by BioID proteomics), as well as known partners ASPP2 and HDAC1, to positively regulate ΔNp63α expression in keratinocytes. ASPP2 knockdown upregulates ΔNp63α; FIH-1 regulates GADD45α (a negative regulator of ΔNp63α) via HDAC1 interaction. BioID proteomics, Co-IP, siRNA knockdown, FIH-1 conditional transgenic and knockout mouse FASEB journal Medium 31914679
2018 ANKDD1A directly interacts with FIH1 and upregulates FIH1 activity, leading to decreased HIF1α transcriptional activity and reduced HIF1α protein half-life. This decreases glucose uptake, lactate production, and autophagy while inducing apoptosis in glioblastoma cells under hypoxia. Co-immunoprecipitation (ANKDD1A-FIH1 interaction), HIF1α stability assay, glucose/lactate measurement, autophagy and apoptosis assays Oncogene Medium 30082910
2021 The N-terminal disordered region of Mint3 (amino acids 78–88 as core binding site) binds FIH-1 with a large enthalpy and entropy change consistent with disorder-to-order transition upon binding; thermodynamic mapping by ITC with truncated Mint3 constructs identified the core binding site and distinguished affinity-contributing from enthalpy-only-contributing regions. Circular dichroism, NMR, hydrogen/deuterium exchange-MS, isothermal titration calorimetry (ITC) with truncation series The Journal of biological chemistry High 34655613
2022 FIH-1 knockout in intestinal epithelial cells (FIH-1 silencing in HIEC-6 cells) activates the PI3K-AKT signaling pathway and cell cycle redistribution into S-phase, conferring radioprotection by mitigating radiation-induced cell damage. shRNA knockdown, colony formation assay, cell cycle analysis, apoptosis assay, RNA-Seq, western blot FASEB journal Medium 40762438
2023 ASB9 (E3 ubiquitin ligase) directly interacts with HIF1AN and promotes its ubiquitination and degradation; ASB9 overexpression inhibits human SSC line proliferation and increases apoptosis, effects reversed by HIF1AN re-expression. Co-immunoprecipitation, western blot (HIF1AN protein level), functional proliferation/apoptosis assays with rescue Biological research Medium 36683111
2022 FIH-1 knockout in colon epithelial cells (Vil1-Cre/FIH+f/+f mice) attenuates chronic colitis severity and reduces infiltrating macrophages and immune-response gene expression, but does not alter colorectal tumor occurrence in an AOM/DSS model. Conditional knockout mouse (Vil1-Cre), AOM/DSS colitis-cancer model, RNA-seq of colon tissue, histology, immunohistochemistry Journal of immunology Medium 35121641
2025 FIH-1 does not interact with IKKα/β or IκBα (negative result by immunoprecipitation), and FIH-1 overexpression does not affect IKKα/β or p65 protein levels, indicating FIH-1 does not regulate the classical NF-κB pathway. Immunoprecipitation, western blot, FIH-1 overexpression The Journal of toxicological sciences Medium 40024754
2014 FIH-1 (HIF1AN) physically interacts with Mindbomb (Mib) E3 ubiquitin ligase in zebrafish and cultured cells (co-localization confirmed); depletion of fih-1 in zebrafish embryos induces ectopic VEGF-A expression and ectopic intersegmental vessel sprouting, while fih-1 overexpression attenuates ISV formation in a VEGF-A-rescuable manner, establishing FIH-1 as an anti-angiogenic regulator of VEGF-A signaling. Yeast two-hybrid (Mib interaction), co-localization in cultured cells, zebrafish morpholino knockdown, fih-1 mRNA overexpression, ISV imaging PloS one Medium 25347788
2025 PML (promyelocytic leukemia protein) directly binds HIF1AN and promotes its ubiquitination-mediated degradation; PML knockdown or HIF1AN upregulation suppresses osteogenic differentiation of BMSCs; HIF1α directly binds the SOD3 promoter; PML overexpression promotes osteogenesis via HIF1AN/HIF1α/SOD3 axis and PI3K/AKT pathway. Co-immunoprecipitation, immunofluorescence, ChIP, dual-luciferase reporter, western blot, ALP/Alizarin red staining International journal of stem cells Medium 40059075

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 1258 12080085
2001 FIH-1: a novel protein that interacts with HIF-1alpha and VHL to mediate repression of HIF-1 transcriptional activity. Genes & development 1174 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 98 31410089
2015 Hypoxia-inducible miR-182 enhances HIF1α signaling via targeting PHD2 and FIH1 in prostate cancer. Scientific reports 87 26205124
2021 Exosomes from adipose-derived stem cells alleviate myocardial infarction via microRNA-31/FIH1/HIF-1α pathway. Journal of molecular and cellular cardiology 68 34474073
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
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
2023 M2 macrophage-derived exosomes induce angiogenesis and increase skin flap survival through HIF1AN/HIF-1α/VEGFA control. Archives of biochemistry and biophysics 51 38030054
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
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 40 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 24 18805587
2014 Variants of the low oxygen sensors EGLN1 and HIF-1AN associated with acute mountain sickness. International journal of molecular sciences 23 25431923
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
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 18 36074324
2018 The miRNA-184 drives renal fibrosis by targeting HIF1AN in vitro and in vivo. International urology and nephrology 18 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
2014 FIH-1 disrupts an LRRK1/EGFR complex to positively regulate keratinocyte migration. The American journal of pathology 11 25455687
2022 Enhanced BPGM/2,3-DPG pathway activity suppresses glycolysis in hypoxic astrocytes via FIH-1 and TET2. Brain research bulletin 10 36334804
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
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 Pinoresinol diglucoside ameliorates H/R-induced injury of cardiomyocytes by regulating miR-142-3p and HIF1AN. Journal of biochemical and molecular toxicology 8 35962614
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 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) 4 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

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