Inhibitors | Comment | Organism | Structure |
---|---|---|---|
additional information | temporal dynamics of hydroxylase inhibition, overview | Homo sapiens | |
N-(methoxyoxoacetyl)-glycine methyl ester | a pan-hydroxylase inhibitor, in vitro and in vivo inhibition | Homo sapiens |
Metals/Ions | Comment | Organism | Structure |
---|---|---|---|
Fe2+ | required | 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 | HIF-1alpha | hypoxia-inducible factor-(3S)-3-hydroxy-L-asparagine + succinate + CO2 | - |
? |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Homo sapiens | - |
- |
- |
Source Tissue | Comment | Organism | Textmining |
---|---|---|---|
HEK-293 cell | - |
Homo sapiens | - |
Hep-G2 cell | - |
Homo sapiens | - |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
hypoxia-inducible factor-L-asparagine + 2-oxoglutarate + O2 | HIF-1alpha | Homo sapiens | hypoxia-inducible factor-(3S)-3-hydroxy-L-asparagine + succinate + CO2 | - |
? |
Synonyms | Comment | Organism |
---|---|---|
asparaginyl-hydroxylase | - |
Homo sapiens |
factor inhibiting HIF | - |
Homo sapiens |
FIH | - |
Homo sapiens |
General Information | Comment | Organism |
---|---|---|
malfunction | silencing FIH under conditions where prolyl hydroxylases, EC 1.14.11.29/30, are inhibited results in increased HIF-1alpha transcriptional activity, but paradoxically decreases HIF-1alpha stability. Residual activity of FIH in hypoxia | Homo sapiens |
metabolism | optimal HIF-1alpha transcriptional activity requires sequential inhibition of both prolyl- and asparaginyl-hydroxylases | Homo sapiens |
additional information | modeling of the dynamic regulation of HIF-1alpha transcriptional activity by the hydroxylase. HIF-1alpha stabilisation and transcriptional activity is dependent on oxygen tension | Homo sapiens |
physiological function | key enzyme in activation of the hypoxia-inducible factor (HIF) pathway, a critical step in the transcriptional response to hypoxia, role of FIH in hydroxylase regulation of HIF-1alpha, overview. The enzyme is involved in the HIF-1alpha signalling network, overview. Asparaginyl hydroxylation confers upon HIF-1alpha resistance to proteosomal degradation, but the removal of the asparaginyl hydroxylation step is necessary for HIF-1alpha activity | Homo sapiens |