Property Summary

NCBI Gene PubMed Count 75
PubMed Score 71.96
PubTator Score 52.81

Knowledge Summary


No data available


  Disease (2)


  Differential Expression (6)

Disease log2 FC p
psoriasis -1.700 8.4e-05
osteosarcoma -2.144 1.6e-09
medulloblastoma, large-cell -1.100 4.7e-03
intraductal papillary-mucinous adenoma (... 1.400 2.7e-04
diabetes mellitus -1.100 5.0e-03
ovarian cancer -1.700 8.4e-08

Gene RIF (59)

26752685 OTUB1 is a target for functional hydroxylation by FIH.
26205124 the levels of both miR-182 and HIF1alpha were elevated, while the expression PHD2 and FIH1 was downregulated in a mouse model of prostate cancer.
26112411 The kinetic properties of PHD2 and FIH with respect to oxygen reflect their cellular hypoxia-sensing ability.
25907805 demonstrates that miR-135b regulates ERalpha, AR and HIF1AN protein levels through interaction with their 3'UTR regions, and proliferation in ERalpha-positive BCa and AR-positive PCa cells
25837583 data support the concept that FIH-1 may interact with Notch2 and repress its activity, thereby playing a critical role in controlling the survival of vascular endothelial cells
25728779 miR-31/FIH1 pathway associates with liver fibrosis, perhaps by participation in the TGF-beta/Smad3 signalling of hepatic stellate cells.
25687434 the nuclear entry of FIH-1 depends on HIF-1alpha
25431923 The association between EGLN1 and HIF-1AN single nucleotide polymorphisms and acute mountain sickness in a Han Chinese population, was examined.
25423620 FIH follows the consensus mechanism for alphaKG oxygenases, suggesting that FIH may be an ideal enzyme to directly access steps involved in O2 activation among the broad family of alphaKG oxygenases.
25413349 Hypoxia, FIH inhibitors and mutation of asparagine 242 all potentiated TRPV3-mediated current, without altering TRPV3 protein levels, indicating that oxygen-dependent hydroxylation inhibits TRPV3 activity.
25320245 Data indicate that exosomal miR-135b directly suppressed its target factor-inhibiting hypoxia-inducible factor 1 (FIH-1) in endothelial cells.
24867948 FIH-1 activity does not represent a major mechanism by which NP cells control HIF-1-dependent transcription, a testament to their adaptation to a unique hypoxic niche.
24521875 The critical role of miR-31/FIH-1 nexus in colorectal cancer (CRC)was revealed and the contribution of miR-31 to CRC development by targeting FIH-1 was clarified.
24465898 The role of FIH-1 in regulating the transcriptional activity of HIF1A in glioblastoma multiforme.
24388053 The role of FIH expression in high-risk locally advanced renal cell carcinoma (LARCC) was explored.
24100311 Comparison of the structure of JMJD5 with that of FIH, a well characterized protein hydroxylase, reveals that human JMJD5 might function as a protein hydroxylase.
23606740 FIH-1 depletion did lead to impaired binding of Par-3 to ASPP2.
23351038 The stable Fe-OH2 bond plays an important part in FIH1's regulatory role over O2 homeostasis in humans and points toward a strategy for tightly coupling O2 activation with C-terminal transactivation domain of HIF-1alpha hydroxylation.
22891326 Our results define a previously unknown mechanism for keratinocyte fate decisions where Notch signaling potential is, in part, controlled through a miR-31/FIH-1 nexus.
22532441 Glycogen regulation in a HIF-1alpha-independent manner is a novel function for FIH-1 and provides new insight into how the corneal epithelium regulates its energy requirements.
22002313 FIH activity is essential for tumor growth through the suppression of the p53-p21 axis, the major barrier that prevents cancer progression.
21808058 Quantitative mass spectrometry reveals dynamics of factor-inhibiting hypoxia-inducible factor-catalyzed hydroxylation.
21732131 FIH1 is expressed in the majority of invasive breast carcinomas and shows distinct subcellular localization patterns.
21443853 FIH does not uncouple O2 during turnover conditions, nor does it release reactive oxygen species under any tested conditions.
21251231 Data report that histidinyl residues within the ankyrin repeat domain of tankyrase-2 can be hydroxylated by factor-inhibiting hypoxia-inducible factor.
21177872 FIH also catalyzes the hydroxylation of highly conserved Asn residues within the ubiquitous ankyrin repeat domain (ARD)-containing proteins
21069436 Bax-mediated apoptosis is suppressed by FIH1 overexpression, but accelerated by FIH1 deficiency.
20727020 Methylation-induced epigenetic silencing of FIH is unlikely to underlie up-regulated HIF-1alpha expression in human breast cancer but may play a role in other tumour types.
20720525 FIH1 appears to be a suppressor of oxygen-dependent genes in the kidney, operating through HIF-dependent and -independent mechanisms.
20453000 Observational study of gene-disease association. (HuGE Navigator)
20145132 miR-31 contributes to the development of head and neck squamous cell carcinoma by impeding FIH to activate HIF under normoxic conditions.
19726677 Mint3 binds FIH-1 and inhibits the ability of FIH-1 to modify HIF-1alpha
19696166 The interplays among HIF-1alpha and Hdm2 and HIF1 could be potential targets for treating tumors overexpressing HIF-1alpha.
19692168 Observational study of gene-disease association. (HuGE Navigator)
19625176 Observational study of gene-disease association. (HuGE Navigator)
19401150 Substrate length has a much greater influence on FIH-1-dependent hydroxylation of Notch than of HIF-1alpha, predominantly through binding affinity rather than maximal reaction velocity.
19245366 Results show that expression of MYPT1 enhances HIF-CAD activity in a manner consistent with competition for FIH and that this property extends to other ARD proteins.
19170196 Observational study of gene-disease association and gene-environment interaction. (HuGE Navigator)
19134330 The expression imbalance of HPH1 and FIH-1 in placenta may play an important role in the pathogenesis and development of severe pre-eclampsia through inhibiting HIF-1alpha.
19074848 functional inactivation of HIF-alpha by stimulation of FIH-dependent p300 contributes to the YC-1-induced deregulation of hypoxia-induced genes
18936059 The work has defined 13 new FIH-dependent hydroxylation sites with a degenerate consensus corresponding to that of the ankyrin repeat and a range of ankyrin repeat domain-containing proteins as actual and potential substrates for FIH.
18927305 Overexpression of the oxygen sensor FIH1 is associated with tumor aggressiveness in pancreatic endocrine tumors.
18676680 Observational study of gene-disease association. (HuGE Navigator)
18611856 two enzyme-derived histidine ligands are sufficient for iron binding and catalysis by factor inhibiting HIF (FIH)
18398039 Observational study of gene-disease association. (HuGE Navigator)
18299578 FIH-1 hydroxylates Notch ICD at two residues (N(1945) and N(2012)) that are critical for the function of Notch ICD as a transactivator within cells and during neurogenesis and myogenesis
18280659 These results suggest that Siah-1 might play a role as a regulator of FIH abundance under normoxic conditions.
18096060 FIH-1 is widely expressed in invasive breast carcinoma. The hypoxic response and survival suggests that tumour regulation of FIH-1 is an additional important mechanism for HIF pathway activation.
17682059 Data show that in renal cell carcinoma, the Cut-like homeodomain protein is involved in FIH-1 transcriptional regulation and is controlled by a specific signaling event involving protein kinase C zeta.
17573339 ARD proteins function as natural inhibitors of FIH and that the hydroxylation status of these proteins provides another oxygen-dependent interface that modulates HIF signaling
17003112 Human HIF asparaginyl hydroxylase, factor inhibiting HIF (FIH), also efficiently hydroxylates specific asparaginyl (Asn)-residues within proteins of the IkappaB family.
16385451 Observational study of gene-disease association. (HuGE Navigator)
14734545 Molecular modeling of the HIF-1alpha CAD V802A in complex with FIH-1 predicted an alteration in asparagine positioning providing an explanation for the impaired catalysis, confirming the importance of Val-802 in asparaginyl hydroxylation by FIH-1.
14701857 asparaginyl hydroxylase (FIH) catalytic properties in the oxygen sensing pathway are distinct from those of its prolyl 4-hydroxylases
12482756 FIH-1 has a unique active site pocket and interaction sites for HIF-1 and von Hippel-Lindau protein
12432100 present the structure of factor-inhibiting HIF-1 (FIH-1); describe the molecular details of the active site architecture mediating Fe(II) and 2-oxoglutarate binding
12080085 FIH-1 is an asparaginyl hydroxylase enzyme that regulates the transcriptional activity of hypoxia-inducible factor
11959990 Structural basis for recruitment of CBP/p300 by hypoxia-inducible factor-1 alpha
11641274 Gene name = FIH1Encoded protein (factor inhibiting HIF-1) is a co-repressor that interacts with hypoxia-inducible factor 1 (HIF-1) alpha and the von Hippel-Lindau tumor suppressor protein to mediate repression of HIF-1 transcriptional activity.

AA Sequence


Text Mined References (86)

PMID Year Title
26972000 2016 Substrate-Trapped Interactors of PHD3 and FIH Cluster in Distinct Signaling Pathways.
26752685 2016 FIH Regulates Cellular Metabolism through Hydroxylation of the Deubiquitinase OTUB1.
26205124 2015 Hypoxia-inducible miR-182 enhances HIF1? signaling via targeting PHD2 and FIH1 in prostate cancer.
26112411 2015 Kinetic Investigations of the Role of Factor Inhibiting Hypoxia-inducible Factor (FIH) as an Oxygen Sensor.
25907805 2015 MicroRNA-135b regulates ER?, AR and HIF1AN and affects breast and prostate cancer cell growth.
25837583 2015 Factor-inhibiting HIF-1 (FIH-1) is required for human vascular endothelial cell survival.
25728779 2015 The role of the miR-31/FIH1 pathway in TGF-?-induced liver fibrosis.
25687434 2015 Featured Article: Hypoxia-inducible factor-1? dependent nuclear entry of factor inhibiting HIF-1.
25431923 2014 Variants of the low oxygen sensors EGLN1 and HIF-1AN associated with acute mountain sickness.
25423620 2014 The rate-limiting step of O2 activation in the ?-ketoglutarate oxygenase factor inhibiting hypoxia inducible factor.
25413349 2015 Oxygen-dependent hydroxylation by FIH regulates the TRPV3 ion channel.
25320245 2014 Exosomal miR-135b shed from hypoxic multiple myeloma cells enhances angiogenesis by targeting factor-inhibiting HIF-1.
24867948 2014 FIH-1-Mint3 axis does not control HIF-1 transcriptional activity in nucleus pulposus cells.
24521875 2014 MicroRNA-31 contributes to colorectal cancer development by targeting factor inhibiting HIF-1? (FIH-1).
24465898 2014 The role of factor inhibiting HIF (FIH-1) in inhibiting HIF-1 transcriptional activity in glioblastoma multiforme.
24388053 2014 Factor-inhibiting hypoxia-inducible factor expression in patients with high-risk locally advanced renal cell carcinoma and its relationship with tumor progression.
24100311 2013 Structure of the JmjC-domain-containing protein JMJD5.
23606740 2013 Factor inhibiting HIF-1 (FIH-1) modulates protein interactions of apoptosis-stimulating p53 binding protein 2 (ASPP2).
23362303 2013 Genome-wide association study identifies novel loci associated with concentrations of four plasma phospholipid fatty acids in the de novo lipogenesis pathway: results from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium.
23351038 2013 Inverse solvent isotope effects arising from substrate triggering in the factor inhibiting hypoxia inducible factor.
22891326 2012 microRNA-31/factor-inhibiting hypoxia-inducible factor 1 nexus regulates keratinocyte differentiation.
22814378 2012 N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB.
22645313 2012 Identification and proteomic analysis of distinct UBE3A/E6AP protein complexes.
22532441 2012 MicroRNA-31 targets FIH-1 to positively regulate corneal epithelial glycogen metabolism.
22223895 2012 Comparative large scale characterization of plant versus mammal proteins reveals similar and idiosyncratic N-?-acetylation features.
22002313 2012 The asparaginyl hydroxylase factor-inhibiting HIF is essential for tumor growth through suppression of the p53-p21 axis.
21808058 2011 Quantitative mass spectrometry reveals dynamics of factor-inhibiting hypoxia-inducible factor-catalyzed hydroxylation.
21732131 2011 Subcellular FIH-1 expression patterns in invasive breast cancer in relation to HIF-1? expression.
21460794 2011 The oncometabolite 2-hydroxyglutarate inhibits histone lysine demethylases.
21443853 2011 Uncoupled O2-activation in the human HIF-asparaginyl hydroxylase, FIH, does not produce reactive oxygen species.
21269460 2011 Initial characterization of the human central proteome.
21251231 2011 Factor-inhibiting hypoxia-inducible factor (FIH) catalyses the post-translational hydroxylation of histidinyl residues within ankyrin repeat domains.
21177872 2011 Asparagine and aspartate hydroxylation of the cytoskeletal ankyrin family is catalyzed by factor-inhibiting hypoxia-inducible factor.
21069436 2011 Prevention of apoptosis by the interaction between FIH1 and Bax.
20822901 2010 Structural basis for binding of cyclic 2-oxoglutarate analogues to factor-inhibiting hypoxia-inducible factor.
20727020 2010 DNA methylation analysis of the HIF-1? prolyl hydroxylase domain genes PHD1, PHD2, PHD3 and the factor inhibiting HIF gene FIH in invasive breast carcinomas.
20720525 2010 Factor inhibiting HIF limits the expression of hypoxia-inducible genes in podocytes and distal tubular cells.
20453000 2010 A Large-scale genetic association study of esophageal adenocarcinoma risk.
20396966 2010 Crystal structures of human FIH-1 in complex with quinol family inhibitors.
20145132 2010 miR-31 ablates expression of the HIF regulatory factor FIH to activate the HIF pathway in head and neck carcinoma.
19726677 2009 Mint3 enhances the activity of hypoxia-inducible factor-1 (HIF-1) in macrophages by suppressing the activity of factor inhibiting HIF-1.
19696166 2009 Nutlin-3, an Hdm2 antagonist, inhibits tumor adaptation to hypoxia by stimulating the FIH-mediated inactivation of HIF-1alpha.
19692168 2010 Genetic susceptibility to distinct bladder cancer subphenotypes.
19625176 2009 PTEN identified as important risk factor of chronic obstructive pulmonary disease.
19413330 2009 Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach.
19401150 2009 Differences in hydroxylation and binding of Notch and HIF-1alpha demonstrate substrate selectivity for factor inhibiting HIF-1 (FIH-1).
19245366 2009 MYPT1, the targeting subunit of smooth-muscle myosin phosphatase, is a substrate for the asparaginyl hydroxylase factor inhibiting hypoxia-inducible factor (FIH).
19170196 2009 Polymorphisms in innate immunity genes and lung cancer risk in Xuanwei, China.
19134330 2008 [Clinical significance of hypoxia inducible factor-prolyl hydroxylase 1 and factor inhibiting hypoxia inducible factor-1 expression in placentas of women with severe pre-eclampsia].
19074848 2008 A novel mode of action of YC-1 in HIF inhibition: stimulation of FIH-dependent p300 dissociation from HIF-1{alpha}.
19071119 2009 Transcriptional activation of hypoxia-inducible factor-1alpha by HDAC4 and HDAC5 involves differential recruitment of p300 and FIH-1.
19060904 2009 An empirical framework for binary interactome mapping.
18936059 2009 Proteomics-based identification of novel factor inhibiting hypoxia-inducible factor (FIH) substrates indicates widespread asparaginyl hydroxylation of ankyrin repeat domain-containing proteins.
18927305 2008 Overexpression of the oxygen sensors PHD-1, PHD-2, PHD-3, and FIH Is associated with tumor aggressiveness in pancreatic endocrine tumors.
18676680 2008 Pathway-based evaluation of 380 candidate genes and lung cancer susceptibility suggests the importance of the cell cycle pathway.
18611856 2008 Evidence that two enzyme-derived histidine ligands are sufficient for iron binding and catalysis by factor inhibiting HIF (FIH).
18398039 2008 Polymorphisms in angiogenesis-related genes and prostate cancer.
18299578 2008 Interaction with factor inhibiting HIF-1 defines an additional mode of cross-coupling between the Notch and hypoxia signaling pathways.
18280659 2008 Abundance of aspargynyl-hydroxylase FIH is regulated by Siah-1 under normoxic conditions.
18096060 2007 Cytoplasmic location of factor-inhibiting hypoxia-inducible factor is associated with an enhanced hypoxic response and a shorter survival in invasive breast cancer.
17974005 2007 The full-ORF clone resource of the German cDNA Consortium.
17682059 2007 Protein kinase C-mediated modulation of FIH-1 expression by the homeodomain protein CDP/Cut/Cux.
17636018 2007 ASB4 is a hydroxylation substrate of FIH and promotes vascular differentiation via an oxygen-dependent mechanism.
17573339 2007 Asparaginyl hydroxylation of the Notch ankyrin repeat domain by factor inhibiting hypoxia-inducible factor.
17135241 2007 Structural and mechanistic studies on the inhibition of the hypoxia-inducible transcription factor hydroxylases by tricarboxylic acid cycle intermediates.
17003112 2006 Posttranslational hydroxylation of ankyrin repeats in IkappaB proteins by the hypoxia-inducible factor (HIF) asparaginyl hydroxylase, factor inhibiting HIF (FIH).
16385451 2006 A scan of chromosome 10 identifies a novel locus showing strong association with late-onset Alzheimer disease.
16189514 2005 Towards a proteome-scale map of the human protein-protein interaction network.
15913349 2005 Selective inhibition of factor inhibiting hypoxia-inducible factor.
15489334 2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).
15280364 2004 Histone deacetylase 7 associates with hypoxia-inducible factor 1alpha and increases transcriptional activity.
15239670 2004 Disruption of dimerization and substrate phosphorylation inhibit factor inhibiting hypoxia-inducible factor (FIH) activity.
15164054 2004 The DNA sequence and comparative analysis of human chromosome 10.
14734545 2004 Substrate requirements of the oxygen-sensing asparaginyl hydroxylase factor-inhibiting hypoxia-inducible factor.
14702039 2004 Complete sequencing and characterization of 21,243 full-length human cDNAs.
14701857 2004 Catalytic properties of the asparaginyl hydroxylase (FIH) in the oxygen sensing pathway are distinct from those of its prolyl 4-hydroxylases.
12482756 2003 Structure of human FIH-1 reveals a unique active site pocket and interaction sites for HIF-1 and von Hippel-Lindau.
12477932 2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.
12446723 2003 Structure of factor-inhibiting hypoxia-inducible factor (HIF) reveals mechanism of oxidative modification of HIF-1 alpha.
12432100 2002 Structure of factor-inhibiting hypoxia-inducible factor 1: An asparaginyl hydroxylase involved in the hypoxic response pathway.
12215170 2002 Hypoxia-inducible factor asparaginyl hydroxylase (FIH-1) catalyses hydroxylation at the beta-carbon of asparagine-803.
12080085 2002 FIH-1 is an asparaginyl hydroxylase enzyme that regulates the transcriptional activity of hypoxia-inducible factor.
12042299 2002 Hypoxia-inducible factor (HIF) asparagine hydroxylase is identical to factor inhibiting HIF (FIH) and is related to the cupin structural family.
11959990 2002 Structural basis for recruitment of CBP/p300 by hypoxia-inducible factor-1 alpha.
11823643 2002 Asparagine hydroxylation of the HIF transactivation domain a hypoxic switch.
11641274 2001 FIH-1: a novel protein that interacts with HIF-1alpha and VHL to mediate repression of HIF-1 transcriptional activity.