EC Number   |
General Information |
Reference |
|---|
   1.14.11.30 | evolution |
the enzyme belongs to the 2-oxoglutarate- and iron-dependent dioxygenase family of enzymes |
724225 |
| 1.14.11.30 | malfunction |
FIH silencing leads to spacial displacement of the expression pattern of HIF target genes that depend on the C-TAD, such as carbonic anhydrase IX, to more oxygenated areas, whereas overexpression of FIH restricts this pattern to more hypoxic areas. Silencing of gene fih severely reduced in vitro cell proliferation and in vivo tumor growth of LS174 colon adenocarcinoma and A375 melanoma cells. Silencing of fih also significantly increases both the total and phosphorylated forms of the tumor suppressor p53, leading to an increase in its direct target, the cell cycle inhibitor p21. p53-deficient or mutant cells are totally insensitive to FIH expression. FIH activity is essential for tumor growth through the suppression of the p53-p21 axis, the major barrier that prevents cancer progression |
726079 |
| 1.14.11.30 | 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 |
725596 |
| 1.14.11.30 | malfunction |
the lower enzyme expression in tumor is associated with incomplete tumor encapsulation, vascular invasion, and microvascular density |
743379 |
| 1.14.11.30 | metabolism |
HIF transcriptional activity is controlled by the asparaginyl hydroxylase factor inhibiting HIF-1. Hypoxia-induced HIF signalling, mathematical modelling of the pathway, temporal dynamics of the HIF response to hypoxia, and molecular interaction map for the HIF network, overview. The hypoxia inducible factor is switched on and promotes adaptation to hypoxia by upregulating genes involved in angiogenesis, erythropoiesis and glycolysis |
724696 |
| 1.14.11.30 | 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 |
724847 |
| 1.14.11.30 | metabolism |
optimal HIF-1alpha transcriptional activity requires sequential inhibition of both prolyl- and asparaginyl-hydroxylases |
725596 |
| 1.14.11.30 | more |
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 |
724847 |
| 1.14.11.30 | more |
modeling of the dynamic regulation of HIF-1alpha transcriptional activity by the hydroxylase. HIF-1alpha stabilisation and transcriptional activity is dependent on oxygen tension |
725596 |
| 1.14.11.30 | more |
PHD, EC 1.14.11.29, has a higher affinity for oxygen than FIH |
724696 |
