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Literature summary extracted from

  • Koivunen, P.; Hirsilae, M.; Guenzler, V.; Kivirikko, K.I.; Myllyharju, J.
    Catalytic properties of the asparaginyl hydroxylase (FIH) in the oxygen sensing pathway are distinct from those of its prolyl 4-hydroxylases (2004), J. Biol. Chem., 279, 9899-9904.
    View publication on PubMed

Activating Compound

EC Number Activating Compound Comment Organism Structure
1.14.11.16 ascorbate required Homo sapiens
1.14.11.30 ascorbate required, Km: 0.26 mM Homo sapiens

Cloned(Commentary)

EC Number Cloned (Comment) Organism
1.14.11.16 expressed in Sf9 insect cells as His-tag and GST-fusion protein Homo sapiens
1.14.11.30 HIF asparaginyl hydroxylase (FIH), His-FIH, FIH-FLAGHis, FIH-V5His, and GST-FIH polypeptides are expressed in Spodoptera frugiperda Sf9 cells Homo sapiens

Inhibitors

EC Number Inhibitors Comment Organism Structure
1.14.11.16 additional information several 2-oxoglutarate analogs inhibits enzyme activity Homo sapiens
1.14.11.30 3,4-dihydroxybenzoate
-
Homo sapiens
1.14.11.30 additional information the Ki-value for 3-hydroxypyridine-2-carbonylglycine and N-((3-hydroxy-6-chloroquinolin-2-yl)carbonyl)glycine are above 0.3 mM Homo sapiens
1.14.11.30 oxalylglycine
-
Homo sapiens
1.14.11.30 Pyridine-2,4-dicarboxylate
-
Homo sapiens
1.14.11.30 Pyridine-2,5-dicarboxylate
-
Homo sapiens

KM Value [mM]

EC Number KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
1.14.11.16 0.025
-
2-oxoglutarate pH 7.8, 30°C Homo sapiens
1.14.11.16 0.09
-
O2 pH 7.8, 30°C Homo sapiens
1.14.11.16 0.1
-
HIF-1alpha peptide Asp788-Leu822 (L-asparagine803) pH 7.8, 30°C Homo sapiens
1.14.11.30 0.025
-
2-oxoglutarate pH 7.8, 37°C, Km-value is determined using soluble extracts of cells expressing enzyme-FLAGHis Homo sapiens
1.14.11.30 0.09
-
O2 pH 7.8, 37°C. The Km of FIH for O2 is about 40% of its atmospheric concentration, Km-value is determined using soluble extracts of cells expressing enzyme-FLAGHis Homo sapiens

Metals/Ions

EC Number Metals/Ions Comment Organism Structure
1.14.11.16 Fe2+ required Homo sapiens
1.14.11.30 Fe2+ required, Km: 0.0005 mM Homo sapiens

Natural Substrates/ Products (Substrates)

EC Number Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
1.14.11.16 peptide L-asparagine + 2-oxoglutarate + O2 Homo sapiens hydroxylation of Asn803 in hypoxia-inducible transcription factor, converted protein is incapable in interacting with the transcripitonal coactivator p300 peptide 3-hydroxy-L-asparagine + succinate + CO2
-
?
1.14.11.30 hypoxia-inducible factor-L-asparagine + 2-oxoglutarate + O2 Homo sapiens the activity of hypoxia-inducible transcription factor HIF, an alphabeta heterodimer that has an essential role in adaptation to low oxygen availability, is regulated by two oxygen-dependent hydroxylation events. Hydroxylation of specific proline residues by HIF prolyl 4-hydroxylases targets the HIF-alpha subunit for proteasomal destruction, whereas hydroxylation of an asparagine in the C-terminal transactivation domain prevents its interaction with the transcriptional coactivator p300 hypoxia-inducible factor-(3S)-3-hydroxy-L-asparagine + succinate + CO2
-
?

Organism

EC Number Organism UniProt Comment Textmining
1.14.11.16 Homo sapiens Q9NWT6
-
-
1.14.11.30 Homo sapiens
-
-
-

Purification (Commentary)

EC Number Purification (Comment) Organism
1.14.11.16 recombinant enzymes Homo sapiens
1.14.11.30
-
Homo sapiens

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
1.14.11.16 HIF-1alpha peptide Asp788-Leu822 (L-Asn803) + 2-oxoglutarate + O2 much lower activity with peptides lacking residues 819-822, 807-822, and 815-822 Homo sapiens HIF-1alpha peptide Asp788-Leu822 (3-hydroxy-L-Asn803) + succinate + CO2
-
?
1.14.11.16 HIF-1alpha peptide Asp788-Leu822 (L-asparagine803) + 2-oxoglutarate + O2
-
Homo sapiens ?
-
r
1.14.11.16 peptide L-asparagine + 2-oxoglutarate + O2
-
Homo sapiens peptide 3-hydroxy-L-asparagine + succinate + CO2
-
?
1.14.11.16 peptide L-asparagine + 2-oxoglutarate + O2 hydroxylation of Asn803 in hypoxia-inducible transcription factor, converted protein is incapable in interacting with the transcripitonal coactivator p300 Homo sapiens peptide 3-hydroxy-L-asparagine + succinate + CO2
-
?
1.14.11.30 DESGLPQLTSYDCEVNAPI + 2-oxoglutarate + O2 hypoxia-inducible factor-1alpha peptide 788-806. 9% of the activity obtained with the 35-amino-acid HIF-1alpha peptide DES35 (DESGLPQLTSYDCEVNAPIQGSRNLLQGEELLRAL) Homo sapiens ?
-
?
1.14.11.30 DESGLPQLTSYDCEVNAPIQGSR + 2-oxoglutarate + O2 hypoxia-inducible factor-1alpha peptide 788-810. 15% of the activity obtained with the 35-amino-acid HIF-1alpha peptide DES35 (DESGLPQLTSYDCEVNAPIQGSRNLLQGEELLRAL) Homo sapiens ?
-
?
1.14.11.30 DESGLPQLTSYDCEVNAPIQGSRNLLQ + 2-oxoglutarate + O2 hypoxia-inducible factor-1alpha peptide 788-814. 37% of the activity obtained with the 35-amino-acid HIF-1alpha peptide DES35 (DESGLPQLTSYDCEVNAPIQGSRNLLQGEELLRAL) Homo sapiens ?
-
?
1.14.11.30 DESGLPQLTSYDCEVNAPIQGSRNLLQGEEL + 2-oxoglutarate + O2 hypoxia-inducible factor-1alpha peptide 788-818. 26% of the activity obtained with the 35-amino-acid HIF-1alpha peptide DES35 (DESGLPQLTSYDCEVNAPIQGSRNLLQGEELLRAL) Homo sapiens ?
-
?
1.14.11.30 DESGLPQLTSYDCEVNAPIQGSRNLLQGEELLRAL + 2-oxoglutarate + O2 hypoxia-inducible factor-1alpha peptide 788-822 Homo sapiens ?
-
?
1.14.11.30 ESYLLPELTRYDCEVNVPVLGSSTLLQGGDLLRAL + 2-oxoglutarate + O2 hypoxia-inducible factor-2alpha peptide 832-857. 7% of the activity obtained with the 35-amino-acid HIF-1alpha peptide DES35 (DESGLPQLTSYDCEVNAPIQGSRNLLQGEELLRAL) Homo sapiens ?
-
?
1.14.11.30 hypoxia-inducible factor-L-asparagine + 2-oxoglutarate + O2 the activity of hypoxia-inducible transcription factor HIF, an alphabeta heterodimer that has an essential role in adaptation to low oxygen availability, is regulated by two oxygen-dependent hydroxylation events. Hydroxylation of specific proline residues by HIF prolyl 4-hydroxylases targets the HIF-alpha subunit for proteasomal destruction, whereas hydroxylation of an asparagine in the C-terminal transactivation domain prevents its interaction with the transcriptional coactivator p300 Homo sapiens hypoxia-inducible factor-(3S)-3-hydroxy-L-asparagine + succinate + CO2
-
?
1.14.11.30 hypoxia-inducible factor-L-asparagine + 2-oxoglutarate + O2 the enzyme requires particularly long peptide substrates, so that omission of only a few residues from the N or C terminus of a 35-residue HIF-1alpha sequence markedly reduces its substrate activity. Hydroxylation of two HIF-2alpha peptides is far less efficient than that of the corresponding HIF-1alpha peptides Homo sapiens hypoxia-inducible factor-(3S)-3-hydroxy-L-asparagine + succinate + CO2
-
?
1.14.11.30 LTRYDCEVNVPVLGSSTLL + O2 hypoxia-inducible factor-2alpha peptide 839-866. 1% of the activity obtained with the 35-amino-acid HIF-1alpha peptide DES35 (DESGLPQLTSYDCEVNAPIQGSRNLLQGEELLRAL) Homo sapiens ?
-
?
1.14.11.30 LTSYDCEVNAPIQGSRNLL + 2-oxoglutarate + O2 hypoxia-inducible factor-1alpha peptide 795-813. 4% of the activity obtained with the 35-amino-acid HIF-1alpha peptide DES35 (DESGLPQLTSYDCEVNAPIQGSRNLLQGEELLRAL) Homo sapiens ?
-
?
1.14.11.30 PSDLACRLLGQSMDESGLPQLTSYDCEVNAPIQGSRNLLQGEELLRALDQVN + 2-oxoglutarate + O2 hypoxia-inducible factor-1alpha peptide 775-826. 120% of the activity obtained with the 35-amino-acid HIF-1alpha peptide DES35 (DESGLPQLTSYDCEVNAPIQGSRNLLQGEELLRAL) Homo sapiens ?
-
?

Subunits

EC Number Subunits Comment Organism
1.14.11.16 dimer homodimer Homo sapiens
1.14.11.30 dimer
-
Homo sapiens

Synonyms

EC Number Synonyms Comment Organism
1.14.11.16 factor inhibiting hypoxia-inducible transcription factor (HIF)
-
Homo sapiens
1.14.11.16 FIH
-
Homo sapiens
1.14.11.30 FIH
-
Homo sapiens
1.14.11.30 HIF asparaginyl hydroxylase
-
Homo sapiens

Temperature Optimum [°C]

EC Number Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
1.14.11.30 37
-
assay at Homo sapiens

Turnover Number [1/s]

EC Number Turnover Number Minimum [1/s] Turnover Number Maximum [1/s] Substrate Comment Organism Structure
1.14.11.30 additional information
-
additional information the catalytic center activities obtained for the enzyme purified by two alternative procedures are 85-135 and 70-120 mol/mol/min, respectively Homo sapiens

pH Optimum

EC Number pH Optimum Minimum pH Optimum Maximum Comment Organism
1.14.11.30 7.8
-
assay at Homo sapiens

Ki Value [mM]

EC Number Ki Value [mM] Ki Value maximum [mM] Inhibitor Comment Organism Structure
1.14.11.30 additional information
-
additional information the Ki-value for 3-hydroxypyridine-2-carbonylglycine and N-((3-Hydroxy-6-chloroquinolin-2-yl)carbonyl)glycine are above 0.3 mM Homo sapiens
1.14.11.30 0.002
-
oxalylglycine pH 7.8, 37°C, Ki-value is determined using soluble extracts of cells expressing enzyme-FLAGHis Homo sapiens
1.14.11.30 0.01
-
3,4-dihydroxybenzoate pH 7.8, 37°C, Ki-value is determined using soluble extracts of cells expressing enzyme-FLAGHis Homo sapiens
1.14.11.30 0.03
-
Pyridine-2,4-dicarboxylate pH 7.8, 37°C, Ki-value is determined using soluble extracts of cells expressing enzyme-FLAGHis Homo sapiens
1.14.11.30 0.05
-
Pyridine-2,5-dicarboxylate pH 7.8, 37°C, Ki-value is determined using soluble extracts of cells expressing enzyme-FLAGHis Homo sapiens
1.14.11.30 0.1
-
PSDLACRLLGQSMDESGLPQLTSYDCEVNAPIQGSRNLLQGEELLRALDQVN pH 7.8, 37°C, Ki-value is determined using soluble extracts of cells expressing enzyme-FLAGHis Homo sapiens
1.14.11.30 0.1
-
DESGLPQLTSYDCEVNAPIQGSRNLLQGEELLRAL pH 7.8, 37°C, Ki-value is determined using soluble extracts of cells expressing enzyme-FLAGHis Homo sapiens
1.14.11.30 0.16
-
ESYLLPELTRYDCEVNVPVLGSSTLLQGGDLLRAL pH 7.8, 37°C, Ki-value is determined using soluble extracts of cells expressing enzyme-FLAGHis Homo sapiens