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Literature summary for 1.14.11.30 extracted from

  • Masson, N.; Singleton, R.S.; Sekirnik, R.; Trudgian, D.C.; Ambrose, L.J.; Miranda, M.X.; Tian, Y.M.; Kessler, B.M.; Schofield, C.J.; Ratcliffe, P.J.
    The FIH hydroxylase is a cellular peroxide sensor that modulates HIF transcriptional activity (2012), EMBO Rep., 13, 251-257.
    View publication on PubMedView publication on EuropePMC

Activating Compound

Activating Compound Comment Organism Structure
ascorbate required Homo sapiens

Cloned(Commentary)

Cloned (Comment) Organism
expression of dox-inducible FLAG-tagged FIH in U2-OS cells Homo sapiens

Protein Variants

Protein Variants Comment Organism
additional information FIH silencing by siRNA Homo sapiens

Inhibitors

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

Metals/Ions Comment Organism Structure
Fe2+ dependent on Homo sapiens

Natural Substrates/ Products (Substrates)

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

Organism UniProt Comment Textmining
Homo sapiens
-
-
-

Purification (Commentary)

Purification (Comment) Organism
recombinant dox-inducible FLAG-tagged FIH from U2-OS cells by immunoaffinity chromatography Homo sapiens

Source Tissue

Source Tissue Comment Organism Textmining
U2-OS cell
-
Homo sapiens
-

Substrates and Products (Substrate)

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

Synonyms Comment Organism
factor inhibiting HIF
-
Homo sapiens
FIH hydroxylase
-
Homo sapiens
HIF asparaginyl hydroxylase
-
Homo sapiens

General Information

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