Activating Compound | Comment | Organism | Structure |
---|---|---|---|
ascorbate | required | Homo sapiens |
Cloned (Comment) | Organism |
---|---|
expression of dox-inducible FLAG-tagged FIH in U2-OS cells | Homo sapiens |
Protein Variants | Comment | Organism |
---|---|---|
additional information | FIH silencing by siRNA | Homo sapiens |
Inhibitors | Comment | Organism | Structure |
---|---|---|---|
H2O2 | peroxide rapidly inhibits hydroxlation of diverse FIH substrates and inhibits FIH in a range of cell types. Preferential inhibition of N803-hydroxylation compared with P402/P564 hydroxylation by PHDs, EC 1.14.11.29. Cysteine 800 in HIF-1alpha does not regulate N803 or N847 hydroxylation. FIH activity is not restored by exogenous Fe2+ | Homo sapiens |
Metals/Ions | Comment | Organism | Structure |
---|---|---|---|
Fe2+ | dependent on | Homo sapiens |
Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
---|---|---|---|---|---|---|
hypoxia-inducible factor-L-asparagine + 2-oxoglutarate + O2 | Homo sapiens | - |
hypoxia-inducible factor-(3S)-3-hydroxy-L-asparagine + succinate + CO2 | - |
? |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Homo sapiens | - |
- |
- |
Purification (Comment) | Organism |
---|---|
recombinant dox-inducible FLAG-tagged FIH from U2-OS cells by immunoaffinity chromatography | Homo sapiens |
Source Tissue | Comment | Organism | Textmining |
---|---|---|---|
U2-OS cell | - |
Homo sapiens | - |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
hypoxia-inducible factor-L-asparagine + 2-oxoglutarate + O2 | - |
Homo sapiens | hypoxia-inducible factor-(3S)-3-hydroxy-L-asparagine + succinate + CO2 | - |
? | |
rabankyrin-5 + 2-oxoglutarate + O2 | hydroxylation at N316, N485 and N649 | Homo sapiens | trihydroxy-rabankyrin-5 + succinate + CO2 | - |
? |
Synonyms | Comment | Organism |
---|---|---|
factor inhibiting HIF | - |
Homo sapiens |
FIH hydroxylase | - |
Homo sapiens |
HIF asparaginyl hydroxylase | - |
Homo sapiens |
General Information | Comment | Organism |
---|---|---|
metabolism | hypoxia and oxidant stress can interact functionally as distinct regulators of HIF transcriptional output involving the enzyme. Oxidant stress activates hypoxia pathways through the inactivation of the oxygen-sensing hypoxia-inducible factor prolyl and asparaginyl hydroxylases | Homo sapiens |
additional information | HIF asparaginyl hydroxylase is strikingly more sensitive to peroxide than the HIF prolyl hydroxylases, EC 1.14.11.29. Inhibition of FIH by peroxide persists in hypoxia | Homo sapiens |
physiological function | the FIH hydroxylase is a cellular peroxide sensor that modulates HIF transcriptional activity. Cysteine 800 in HIF-1alpha does not regulate N803 or N847 hydroxylation | Homo sapiens |