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Literature summary for 1.14.11.29 extracted from

  • Bruick, R.K.; McKnight, S.L.
    A conserved family of prolyl-4-hydroxylases that modify HIF (2001), Science, 294, 1337-1340.
    View publication on PubMed

Cloned(Commentary)

Cloned (Comment) Organism
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Homo sapiens
expression in Escherichia coli Homo sapiens

Protein Variants

Protein Variants Comment Organism
D137A mutation eliminates prolyl hydroxylase activity of HPH-1 Homo sapiens
H135A mutation eliminates prolyl hydroxylase activity of HPH-1 Homo sapiens
H196A mutation eliminates prolyl hydroxylase activity of HPH-1 Homo sapiens

Inhibitors

Inhibitors Comment Organism Structure
oxygen the transiently overexpressed HPH-1 enzyme is inhibited by a low-oxygen environment Homo sapiens

Metals/Ions

Metals/Ions Comment Organism Structure
Fe2+ the enzyme contains Fe2+ 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 mammalian cells respond to changes in oxygen availability through a conserved pathway that is regulated by the hypoxia-inducible factor (HIF). The alpha subunit of the hypoxia-inducible factor is targeted for degradation under normoxic conditions by a ubiquitin-ligase complex that recognizes a hydroxylated proline residue in hypoxia-inducible factor. HIF prolyl hydroxylase is responsible for this posttranslational modification hypoxia-inducible factor-(4R)-4-hydroxy-L-proline + succinate + CO2
-
?
hypoxia-inducible factor-L-proline + 2-oxoglutarate + O2 Homo sapiens mammalian cells respond to changes in oxygen availability through a conserved pathway that is regulated by the hypoxia-inducible factor (HIF). The alpha subunit of the hypoxia-inducible factor is targeted for degradation under normoxic conditions by a ubiquitin-ligase complex that recognizes a hydroxylated proline residue in hypoxia-inducible factor. HIF prolyl is responsible for this posttranslational modification hypoxia-inducible factor-(4R)-4-hydroxy-L-proline + succinate + CO2
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?

Organism

Organism UniProt Comment Textmining
Drosophila melanogaster
-
-
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Homo sapiens
-
-
-
Homo sapiens Q96KS0 HPH-3
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Homo sapiens Q9GZT9 HPH-2
-

Purification (Commentary)

Purification (Comment) Organism
-
Homo sapiens

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
hypoxia-inducible factor-L-proline + 2-oxoglutarate + O2 mammalian cells respond to changes in oxygen availability through a conserved pathway that is regulated by the hypoxia-inducible factor (HIF). The alpha subunit of the hypoxia-inducible factor is targeted for degradation under normoxic conditions by a ubiquitin-ligase complex that recognizes a hydroxylated proline residue in hypoxia-inducible factor. HIF prolyl hydroxylase is responsible for this posttranslational modification Homo sapiens hypoxia-inducible factor-(4R)-4-hydroxy-L-proline + succinate + CO2
-
?
hypoxia-inducible factor-L-proline + 2-oxoglutarate + O2 mammalian cells respond to changes in oxygen availability through a conserved pathway that is regulated by the hypoxia-inducible factor (HIF). The alpha subunit of the hypoxia-inducible factor is targeted for degradation under normoxic conditions by a ubiquitin-ligase complex that recognizes a hydroxylated proline residue in hypoxia-inducible factor. HIF prolyl is responsible for this posttranslational modification Homo sapiens hypoxia-inducible factor-(4R)-4-hydroxy-L-proline + succinate + CO2
-
?
hypoxia-inducible factor-L-proline + 2-oxoglutarate + O2 target proline residue: Pro564 in human HIF-alpha. A control peptide in which the target proline residue is replaced by alanine is not modified Homo sapiens hypoxia-inducible factor-(4R)-4-hydroxy-L-proline + succinate + CO2
-
?
hypoxia-inducible factor-L-proline + 2-oxoglutarate + O2 target proline residue: Pro564 in human HIF-alpha. A control peptide in which the target proline residue is replaced by alanine is not modified. The endogenous HIF prolyl hydroxylase, HPH-1 generates by in vitro transcription/translation does not modify peptides containing the L562A, A563G, or Y565A mutations. However, a peptide containing the Pro567 to Gly mutation is an equal, if not better, substrate for the human HPH enzymes Homo sapiens hypoxia-inducible factor-(4R)-4-hydroxy-L-proline + succinate + CO2
-
?
hypoxia-inducible factor-L-proline + 2-oxoglutarate + O2 target proline residue: Pro564 in human HIF-alpha. A control peptide in which the target proline residue is replaced by alanine is not modified. The recombinant HPH-2 purified from Escherichia coli does not modify peptides containing the L562A, A563G, or Y565A mutations. However, a peptide containing the Pro567 to Gly mutation is an equal, if not better, substrate for the human HPH enzymes Homo sapiens hypoxia-inducible factor-(4R)-4-hydroxy-L-proline + succinate + CO2
-
?

Synonyms

Synonyms Comment Organism
HIF prolyl
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Homo sapiens
HIF prolyl hydroxylase
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Drosophila melanogaster
HIF prolyl hydroxylase
-
Homo sapiens
HPH-1
-
Homo sapiens
HPH-2
-
Homo sapiens
HPH-3
-
Homo sapiens

General Information

General Information Comment Organism
physiological function in cultured mammalian cells, inappropriate accumulation of hypoxia-inducible factor caused by forced expression of the hypoxia-inducible factor-1alpha subunit under normoxic conditions is attenuated by coexpression of HIF prolyl hydroxylase. Suppression of HIF prolyl hydroxylase in cultured Drosophila melanogaster cells by RNA interference results in elevated expression of a hypoxia-inducible gene (LDH, encoding lactate dehydrogenase) under normoxic conditions. HIF prolyl hydroxylase is an essential component of the pathway through which cells sense oxygen Homo sapiens
physiological function in cultured mammalian cells, inappropriate accumulation of hypoxia-inducible factor caused by forced expression of the hypoxia-inducible factor-1alpha subunit under normoxic conditions is attenuated by coexpression of HIF prolyl. Suppression of HIF prolyl in cultured Drosophila melanogaster cells by RNA interference results in elevated expression of a hypoxia-inducible gene (LDH, encoding lactate dehydrogenase) under normoxic conditions. HIF prolyl is an essential component of the pathway through which cells sense oxygen Homo sapiens