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Description

Hypoxia-inducible factor 1-alpha inhibitor (UniProt: Q9NWT6, also known as EC:1.14.11.30, Factor inhibiting HIF-1, FIH-1, Hypoxia-inducible factor asparagine hydroxylase) is encoded by the HIF1AN (also known as FIH1) gene (Gene ID: 55662) in human. FIH is a widely expressed, Fe(II)-dependent, homodimeric protein that in the presence of oxygen hydroxylates HIF1 at Asn 803 in the C-terminal transactivation domain. This hydroxylation prevents interaction of HIF1 activation domain with the CH-1 domain of the transcriptional co-activator p300 and reduces the transcriptional activity of HIF1 . Its homodimerization is reported to be essential for its catalytic activity. FIH is mainly cytosolic, but its interaction with NOTCH1 results in its nuclear localization and its interaction with ABPA3 results in its perinuclear localization in macrophages. Silencing of FIH gene by RNA Interference is shown to up-regulate HIF-dependent target gene expression in normoxia. (Ref.: Soilleux, EJ., et al. (2005). Histopathology. 47(6), 602-610, Stolze, IP., et al. (2004). J. Biol. Chem. 279(41), 42719-42725, Hewitson, KS., et al. (2002). J. Biol. Chem. 277(29), 26351-26355)