Hypoxia-inducible factor 1-alpha inhibitor (IPR027445)

Short name: FIH-1

Overlapping homologous superfamilies


Family relationships



Mammalian cells adapt to hypoxic conditions through a transcriptional response pathway mediated by hypoxia-inducible factor (HIF). HIF is composed of a heterodimer of alpha and beta subunits. Hypoxia-inducible factor 1-alpha inhibitor (FIH-1) regulates HIF-1 alpha (HIF1A) transcriptional activity by hydrolyses an asparagine residue within the HIF1A C-terminal transactivation domain. This prevents interation of HIF1A with its coactivators including Cbp/p300-interacting transactivator [PMID: 11641274, PMID: 16154531, PMID: 16139242, PMID: 16686427].

It also has been shown that FIH-1 hydrolyses asparagine residues within ankyrin repeat domains (ARD) of ARD-containing proteins such as NFKB1, NFKBIA, NOTCH1, ASB4 and PPP1R12A [PMID: 17573339, PMID: 21251231, PMID: 21177872]. FIH bind more tightly to ARD-cotaining proteins than HIF which suggests that the ARD family lead to competitive inhibition of FIH-dependent HIF hydroxylation [PMID: 19671041].

Contributing signatures

Signatures from InterPro member databases are used to construct an entry.