Factor inhibiting HIF-1 (FIH-1) exists as a homodimer and binds to HIF-1α. Specifically, FIH-1 operates as an asparaginyl hydroxylase. It catalyzes the hydroxylation of the β-carbon of Asparagine residue 803 within the carboxy terminal transactivation domain of HIF-1α. This hydroxylation event blocks the association of HIF-1α with co-activators. FIH-1 also binds to von Hippel-Lindau (VHL) tumor suppressor protein, which represses transcriptional ac-tivity of HIF-1α. In transiently transfected human osteosarcoma cells, FIH-1 localizes to the cytoplasm. The structure of FIH-1 includes a jellyroll-like β-barrel containing ferrous-binding triad residues. The gene encoding human FIH-1 maps to chromosome 10q24.
