HIF1AN
Description
The HIF1AN (hypoxia inducible factor 1 subunit alpha inhibitor) is a protein-coding gene located on chromosome 10.
Hypoxia-inducible factor 1-alpha inhibitor (HIF1AN) is a protein encoded by the HIF1AN gene in humans. HIF1AN has been shown to interact with HIF1A and Von Hippel-Lindau tumor suppressor. Additionally, asparaginyl hydroxylation of HIF1α by FIH-1 (HIF1AN) at N803 impairs its interaction with CBP/P300.
HIF1AN hydroxylates HIF-1 alpha at 'Asn-803' within the C-terminal transactivation domain (CAD). Acting as an oxygen sensor, HIF1AN prevents the interaction of HIF-1 with transcriptional coactivators like Cbp/p300-interacting transactivator under normoxic conditions. This protein participates in transcriptional repression through interactions with HIF1A, VHL, and histone deacetylases. Additionally, HIF1AN hydroxylates specific Asn residues within ankyrin repeat domains (ARD) of NFKB1, NFKBIA, NOTCH1, ASB4, PPP1R12A, and various other ARD-containing proteins. HIF1AN also hydroxylates Asp and His residues within ARDs of ANK1 and TNKS2, respectively. It negatively regulates NOTCH1 activity, accelerating myogenic differentiation, and positively regulates ASB4 activity, promoting vascular differentiation.
HIF1AN is also known as FIH1.
Associated Diseases
- mitochondrial complex I deficiency
- breast cancer
- hyperinsulinism due to HNF1A deficiency
- autosomal dominant hyperinsulinism due to SUR1 deficiency
- hepatorenocardiac degenerative fibrosis
- hyperinsulinism due to UCP2 deficiency
