Anti-HIF1AN

Factor inhibiting HIF-1 (FIH-1) exists as a homodimer and binds to HIF-1alpha. Specifically, FIH-1 operates as an asparaginyl hydroxylase. It catalyzes the hydroxylation of the beta-carbon of Asparagine residue 803 within the carboxy terminal transactivation domain of HIF-1alpha. This hydroxylation event blocks the association of HIF-1alpha with co-activators. FIH-1 also binds to von Hippel-Lindau (VHL) tumor suppressor protein, which represses transcriptional ac-tivity of HIF-1alpha. In transiently transfected human osteosarcoma cells, FIH-1 localizes to the cytoplasm. Protein function: Hydroxylates HIF-1 alpha at 'Asn-803' in the C-terminal transactivation domain (CAD). Functions as an oxygen sensor and, under normoxic conditions, the hydroxylation prevents interaction of HIF-1 with transcriptional coactivators including Cbp/p300- interacting transactivator. Involved in transcriptional repression through interaction with HIF1A, VHL and histone deacetylases. Hydroxylates specific Asn residues within ankyrin repeat domains (ARD) of NFKB1, NFKBIA, NOTCH1, ASB4, PPP1R12A and several other ARD-containing proteins. Also hydroxylates Asp and His residues within ARDs of ANK1 and TNKS2, respectively. Negatively regulates NOTCH1 activity, accelerating myogenic differentiation. Positively regulates ASB4 activity, promoting vascular differentiation. [The UniProt Consortium]