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Literature summary for 1.14.11.29 extracted from

  • Jaakkola, P.; Mole, D.R.; Tian, Y.M.; Wilson, M.I.; Gielbert, J.; Gaskell, S.J.; von Kriegsheim, A.; Hebestreit, H.F.; Mukherji, M.; Schofield, C.J.; Maxwell, P.H.; Pugh, C.W.; Ratcliffe, P.J.
    Targeting of HIF-alpha to the von Hippel-Lindau ubiquitylation complex by O2-regulated prolyl hydroxylation (2001), Science, 292, 468-472.
    View publication on PubMed

Activating Compound

Activating Compound Comment Organism Structure
ascorbate enhances activity Homo sapiens

Inhibitors

Inhibitors Comment Organism Structure
N-oxalyl-(2S)-alanine competed by 2-oxoglutarate, no inhibition by the enantiomer N-oxalyl-(2R)-alanine Homo sapiens
N-oxalylglycine competed by 2-oxoglutarate Homo sapiens

Metals/Ions

Metals/Ions Comment Organism Structure
Fe2+ required. the enzyme activity is inhibited by substitution of Fe2+ with Co2+ or Ni2+ Homo sapiens

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
hypoxia-inducible factor-L-proline + 2-oxoglutarate + O2 Homo sapiens hypoxia-inducible factor (HIF) is a transcriptional complex that plays a central role in the regulation of gene expression by oxygen. In oxygenated and iron replete cells, HIF-alpha subunits are rapidly destroyed by a mechanism that involves ubiquitylation by the von Hippel-Lindau tumor suppressor (pVHL) E3 ligase complex. This process is suppressed by hypoxia and iron chelation, allowing transcriptional activation. The interaction between human pVHL and a specific domain of the HIF-1alpha subunit is regulated through hydroxylation of a proline residue (HIF-1alpha P564) by HIF-alpha prolyl-hydroxylase (HIF-PH). HIF-PH functions directly as a cellular oxygen sensor hypoxia-inducible factor-(4R)-4-hydroxy-L-proline + succinate + CO2
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Organism

Organism UniProt Comment Textmining
Homo sapiens
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-
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
hypoxia-inducible factor-L-proline + 2-oxoglutarate + O2
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Homo sapiens hypoxia-inducible factor-(4R)-4-hydroxy-L-proline + succinate + CO2
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hypoxia-inducible factor-L-proline + 2-oxoglutarate + O2 hypoxia-inducible factor (HIF) is a transcriptional complex that plays a central role in the regulation of gene expression by oxygen. In oxygenated and iron replete cells, HIF-alpha subunits are rapidly destroyed by a mechanism that involves ubiquitylation by the von Hippel-Lindau tumor suppressor (pVHL) E3 ligase complex. This process is suppressed by hypoxia and iron chelation, allowing transcriptional activation. The interaction between human pVHL and a specific domain of the HIF-1alpha subunit is regulated through hydroxylation of a proline residue (HIF-1alpha P564) by HIF-alpha prolyl-hydroxylase (HIF-PH). HIF-PH functions directly as a cellular oxygen sensor Homo sapiens hypoxia-inducible factor-(4R)-4-hydroxy-L-proline + succinate + CO2
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?

Synonyms

Synonyms Comment Organism
HIF-alpha prolyl-hydroxylase
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Homo sapiens
HIF-PH
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Homo sapiens

General Information

General Information Comment Organism
physiological function hypoxia-inducible factor (HIF) is a transcriptional complex that plays a central role in the regulation of gene expression by oxygen. In oxygenated and iron replete cells, HIF-alpha subunits are rapidly destroyed by a mechanism that involves ubiquitylation by the von Hippel-Lindau tumor suppressor (pVHL) E3 ligase complex. This process is suppressed by hypoxia and iron chelation, allowing transcriptional activation. The interaction between human pVHL and a specific domain of the HIF-1alpha subunit is regulated through hydroxylation of a proline residue (HIF-1alpha P564) by HIF-alpha prolyl-hydroxylase (HIF-PH). HIF-PH functions directly as a cellular oxygen sensor. Exposure of cells to dimethyl-oxalylglycine, that penetrates cells readily, results in rapid induction of HIF-1alpha Homo sapiens