BRENDA - Enzyme Database show
show all sequences of 1.14.11.29

Biochemical characterization of human HIF hydroxylases using HIF protein substrates that contain all three hydroxylation sites

Pappalardi, M.B.; McNulty, D.E.; Martin, J.D.; Fisher, K.E.; Jiang, Y.; Burns, M.C.; Zhao, H.; Ho, T.; Sweitzer, S.; Schwartz, B.; Annan, R.S.; Copeland, R.A.; Tummino, P.J.; Luo, L.; Biochem. J. 436, 363-369 (2011)

Data extracted from this reference:

Activating Compound
Activating Compound
Commentary
Organism
Structure
ascorbate
-
Homo sapiens
Cloned(Commentary)
Commentary
Organism
expression of N-terminally MBP-tagged PHD3 in Escherichia coli strain BL21(DE3)pRR692; expression of PHD1-(1-407) in Spodoptera frugiperda Sf9 cells using the baculovirus expression vector, expression of His- and Strep-tagged tobacco etch virus-PHD1 in Escherichia coli strain BL21(DE3)pRR692; expression of PHD2-(1-426) in Spodoptera frugiperda Sf9 cells uing the baculovirus expression vector, expression of His- and Strep-tagged tobacco etch virus-PHD2 in Escherichia coli strain BL21(DE3)pRR692
Homo sapiens
KM Value [mM]
KM Value [mM]
KM Value Maximum [mM]
Substrate
Commentary
Organism
Structure
additional information
-
additional information
steady-state kinetic analysis and substrate selectivity for hypoxia-inducible factor and 2-oxoglutarate; steady-state kinetic analysis and substrate selectivity for hypoxia-inducible factor and 2-oxoglutarate; steady-state kinetic analysis and substrate selectivity for hypoxia-inducible factor and 2-oxoglutarate
Homo sapiens
0.000016
-
hypoxia-inducible factor1alpha C-terminal oxygen-dependent degradation domain-L-proline
pH 7.5, 25C, PHD3
Homo sapiens
0.00075
0.00094
hypoxia-inducible factor1alpha C-terminal oxygen-dependent degradation domain-L-proline
pH 7.5, 25C, PHD2
Homo sapiens
0.0047
0.023
hypoxia-inducible factor2alpha C-terminal oxygen-dependent degradation domain-L-proline
pH 7.5, 25C, PHD3
Homo sapiens
Metals/Ions
Metals/Ions
Commentary
Organism
Structure
Fe2+
dependent on; dependent on; dependent on
Homo sapiens
Natural Substrates/ Products (Substrates)
Natural Substrates
Organism
Commentary (Nat. Sub.)
Natural Products
Commentary (Nat. Pro.)
Organism (Nat. Pro.)
Reversibility
hypoxia-inducible factor-L-proline + 2-oxoglutarate + O2
Homo sapiens
-
hypoxia-inducible factor-trans-4-hydroxy-L-proline + succinate + CO2
-
-
?
hypoxia-inducible factor-L-proline + 2-oxoglutarate + O2
Homo sapiens
HIF1alpha is a better substrate than HIF2alpha for PHD2
hypoxia-inducible factor-trans-4-hydroxy-L-proline + succinate + CO2
-
-
?
Organism
Organism
Primary Accession No. (UniProt)
Commentary
Textmining
Homo sapiens
Q96KS0
isozyme PHD1
-
Homo sapiens
Q9GZT9
isozyme PHD2
-
Homo sapiens
Q9H6Z9
isozyme PHD3
-
Purification (Commentary)
Commentary
Organism
recombinant His- and Strep-tagged tobacco etch virus-PHD1 from Escherichia coli strain BL21(DE3)pRR692 by nickel affinity and avidin affinity chromatography; recombinant His- and Strep-tagged tobacco etch virus-PHD2 from Escherichia coli strain BL21(DE3)pRR692 by nickel affinity and avidin affinity chromatography; recombinant N-terminally MBP-tagged PHD3 from Escherichia coli strain BL21(DE3)pRR692 by amylosse affinity chromatography
Homo sapiens
Substrates and Products (Substrate)
Substrates
Commentary Substrates
Literature (Substrates)
Organism
Products
Commentary (Products)
Literature (Products)
Organism (Products)
Reversibility
hypoxia-inducible factor-L-proline + 2-oxoglutarate + O2
-
724225
Homo sapiens
hypoxia-inducible factor-trans-4-hydroxy-L-proline + succinate + CO2
-
-
-
?
hypoxia-inducible factor-L-proline + 2-oxoglutarate + O2
HIF1alpha is a better substrate than HIF2alpha for PHD2
724225
Homo sapiens
hypoxia-inducible factor-trans-4-hydroxy-L-proline + succinate + CO2
-
-
-
?
hypoxia-inducible factor-L-proline + 2-oxoglutarate + O2
differential regulation of HIF1alpha and HIF2alpha at the N-terminal oxygen-dependent degradation domain site by PHD2
724225
Homo sapiens
hypoxia-inducible factor-trans-4-hydroxy-L-proline + succinate + CO2
-
-
-
?
hypoxia-inducible factor-L-proline + 2-oxoglutarate + O2
the HIF1alpha C-terminal oxygen-dependent degradation domain is highly preferred for hydroxylation, no N-terminal oxygen-dependent degradation domain hydroxylation for both HIF2alpha and HIF1alpha
724225
Homo sapiens
hypoxia-inducible factor-trans-4-hydroxy-L-proline + succinate + CO2
-
-
-
?
hypoxia-inducible factor-L-proline + 2-oxoglutarate + O2
the PHD1 reaction at the N-terminal oxygen-dependent degradation domain site shows low level hydroxylation
724225
Homo sapiens
hypoxia-inducible factor-trans-4-hydroxy-L-proline + succinate + CO2
-
-
-
?
hypoxia-inducible factor1alpha C-terminal oxygen-dependent degradation domain-L-proline + 2-oxoglutarate + O2
-
724225
Homo sapiens
hypoxia-inducible factor1alpha C-terminal oxygen-dependent degradation domain-trans-4-hydroxy-L-proline + succinate + CO2
-
-
-
?
hypoxia-inducible factor1alpha C-terminal oxygen-dependent degradation domain-L-proline + 2-oxoglutarate + O2
low activity
724225
Homo sapiens
hypoxia-inducible factor1alpha C-terminal oxygen-dependent degradation domain-trans-4-hydroxy-L-proline + succinate + CO2
-
-
-
?
hypoxia-inducible factor1alpha N-terminal oxygen-dependent degradation domain-L-proline + 2-oxoglutarate + O2
-
724225
Homo sapiens
hypoxia-inducible factor1alpha N-terminal oxygen-dependent degradation domain-trans-4-hydroxy-L-proline + succinate + CO2
-
-
-
?
hypoxia-inducible factor1alpha N-terminal oxygen-dependent degradation domain-L-proline + 2-oxoglutarate + O2
low activity
724225
Homo sapiens
hypoxia-inducible factor1alpha N-terminal oxygen-dependent degradation domain-trans-4-hydroxy-L-proline + succinate + CO2
-
-
-
?
hypoxia-inducible factor2alpha C-terminal oxygen dependent degradation domain-L-proline + 2-oxoglutarate + O2
-
724225
Homo sapiens
hypoxia-inducible factor2alpha C-terminal oxygen dependent degradation domain-trans-4-hydroxy-L-proline + succinate + CO2
-
-
-
?
hypoxia-inducible factor2alpha C-terminal oxygen-dependent degradation domain-L-proline + 2-oxoglutarate + O2
-
724225
Homo sapiens
hypoxia-inducible factor2alpha C-terminal oxygen-dependent degradation domain-trans-4-hydroxy-L-proline + succinate + CO2
-
-
-
?
hypoxia-inducible factor2alpha N-terminal oxygen dependent degradation domain-L-proline + 2-oxoglutarate + O2
-
724225
Homo sapiens
hypoxia-inducible factor2alpha N-terminal oxygen dependent degradation domain-trans-4-hydroxy-L-proline + succinate + CO2
-
-
-
?
additional information
the substrate contains a C-terminal and a N-terminal oxygen-dependent degradation domain, as well as a C-terminal transactivation domain
724225
Homo sapiens
?
-
-
-
-
additional information
the subtrate contains a C-terminal and a N-terminal oxygen-dependent degradation domain, as well as a C-terminal transactivation domain
724225
Homo sapiens
?
-
-
-
-
Temperature Optimum [C]
Temperature Optimum [C]
Temperature Optimum Maximum [C]
Commentary
Organism
25
-
assay at; assay at; assay at
Homo sapiens
Turnover Number [1/s]
Turnover Number Minimum [1/s]
Turnover Number Maximum [1/s]
Substrate
Commentary
Organism
Structure
0.0005
-
hypoxia-inducible factor2alpha C-terminal oxygen-dependent degradation domain-L-proline
pH 7.5, 25C, PHD3
Homo sapiens
0.0012
-
hypoxia-inducible factor1alpha C-terminal oxygen-dependent degradation domain-L-proline
pH 7.5, 25C, PHD3
Homo sapiens
0.0032
-
hypoxia-inducible factor1alpha C-terminal oxygen-dependent degradation domain-L-proline
pH 7.5, 25C, PHD2
Homo sapiens
pH Optimum
pH Optimum Minimum
pH Optimum Maximum
Commentary
Organism
7.5
-
assay at; assay at; assay at
Homo sapiens
Activating Compound (protein specific)
Activating Compound
Commentary
Organism
Structure
ascorbate
-
Homo sapiens
Cloned(Commentary) (protein specific)
Commentary
Organism
expression of N-terminally MBP-tagged PHD3 in Escherichia coli strain BL21(DE3)pRR692
Homo sapiens
expression of PHD2-(1-426) in Spodoptera frugiperda Sf9 cells uing the baculovirus expression vector, expression of His- and Strep-tagged tobacco etch virus-PHD2 in Escherichia coli strain BL21(DE3)pRR692
Homo sapiens
expression of PHD1-(1-407) in Spodoptera frugiperda Sf9 cells using the baculovirus expression vector, expression of His- and Strep-tagged tobacco etch virus-PHD1 in Escherichia coli strain BL21(DE3)pRR692
Homo sapiens
KM Value [mM] (protein specific)
KM Value [mM]
KM Value Maximum [mM]
Substrate
Commentary
Organism
Structure
additional information
-
additional information
steady-state kinetic analysis and substrate selectivity for hypoxia-inducible factor and 2-oxoglutarate
Homo sapiens
0.000016
-
hypoxia-inducible factor1alpha C-terminal oxygen-dependent degradation domain-L-proline
pH 7.5, 25C, PHD3
Homo sapiens
0.00075
0.00094
hypoxia-inducible factor1alpha C-terminal oxygen-dependent degradation domain-L-proline
pH 7.5, 25C, PHD2
Homo sapiens
0.0047
0.023
hypoxia-inducible factor2alpha C-terminal oxygen-dependent degradation domain-L-proline
pH 7.5, 25C, PHD3
Homo sapiens
Metals/Ions (protein specific)
Metals/Ions
Commentary
Organism
Structure
Fe2+
dependent on
Homo sapiens
Natural Substrates/ Products (Substrates) (protein specific)
Natural Substrates
Organism
Commentary (Nat. Sub.)
Natural Products
Commentary (Nat. Pro.)
Organism (Nat. Pro.)
Reversibility
hypoxia-inducible factor-L-proline + 2-oxoglutarate + O2
Homo sapiens
-
hypoxia-inducible factor-trans-4-hydroxy-L-proline + succinate + CO2
-
-
?
hypoxia-inducible factor-L-proline + 2-oxoglutarate + O2
Homo sapiens
HIF1alpha is a better substrate than HIF2alpha for PHD2
hypoxia-inducible factor-trans-4-hydroxy-L-proline + succinate + CO2
-
-
?
Purification (Commentary) (protein specific)
Commentary
Organism
recombinant His- and Strep-tagged tobacco etch virus-PHD1 from Escherichia coli strain BL21(DE3)pRR692 by nickel affinity and avidin affinity chromatography
Homo sapiens
recombinant His- and Strep-tagged tobacco etch virus-PHD2 from Escherichia coli strain BL21(DE3)pRR692 by nickel affinity and avidin affinity chromatography
Homo sapiens
recombinant N-terminally MBP-tagged PHD3 from Escherichia coli strain BL21(DE3)pRR692 by amylosse affinity chromatography
Homo sapiens
Substrates and Products (Substrate) (protein specific)
Substrates
Commentary Substrates
Literature (Substrates)
Organism
Products
Commentary (Products)
Literature (Products)
Organism (Products)
Reversibility
hypoxia-inducible factor-L-proline + 2-oxoglutarate + O2
-
724225
Homo sapiens
hypoxia-inducible factor-trans-4-hydroxy-L-proline + succinate + CO2
-
-
-
?
hypoxia-inducible factor-L-proline + 2-oxoglutarate + O2
HIF1alpha is a better substrate than HIF2alpha for PHD2
724225
Homo sapiens
hypoxia-inducible factor-trans-4-hydroxy-L-proline + succinate + CO2
-
-
-
?
hypoxia-inducible factor-L-proline + 2-oxoglutarate + O2
differential regulation of HIF1alpha and HIF2alpha at the N-terminal oxygen-dependent degradation domain site by PHD2
724225
Homo sapiens
hypoxia-inducible factor-trans-4-hydroxy-L-proline + succinate + CO2
-
-
-
?
hypoxia-inducible factor-L-proline + 2-oxoglutarate + O2
the HIF1alpha C-terminal oxygen-dependent degradation domain is highly preferred for hydroxylation, no N-terminal oxygen-dependent degradation domain hydroxylation for both HIF2alpha and HIF1alpha
724225
Homo sapiens
hypoxia-inducible factor-trans-4-hydroxy-L-proline + succinate + CO2
-
-
-
?
hypoxia-inducible factor-L-proline + 2-oxoglutarate + O2
the PHD1 reaction at the N-terminal oxygen-dependent degradation domain site shows low level hydroxylation
724225
Homo sapiens
hypoxia-inducible factor-trans-4-hydroxy-L-proline + succinate + CO2
-
-
-
?
hypoxia-inducible factor1alpha C-terminal oxygen-dependent degradation domain-L-proline + 2-oxoglutarate + O2
-
724225
Homo sapiens
hypoxia-inducible factor1alpha C-terminal oxygen-dependent degradation domain-trans-4-hydroxy-L-proline + succinate + CO2
-
-
-
?
hypoxia-inducible factor1alpha C-terminal oxygen-dependent degradation domain-L-proline + 2-oxoglutarate + O2
low activity
724225
Homo sapiens
hypoxia-inducible factor1alpha C-terminal oxygen-dependent degradation domain-trans-4-hydroxy-L-proline + succinate + CO2
-
-
-
?
hypoxia-inducible factor1alpha N-terminal oxygen-dependent degradation domain-L-proline + 2-oxoglutarate + O2
-
724225
Homo sapiens
hypoxia-inducible factor1alpha N-terminal oxygen-dependent degradation domain-trans-4-hydroxy-L-proline + succinate + CO2
-
-
-
?
hypoxia-inducible factor1alpha N-terminal oxygen-dependent degradation domain-L-proline + 2-oxoglutarate + O2
low activity
724225
Homo sapiens
hypoxia-inducible factor1alpha N-terminal oxygen-dependent degradation domain-trans-4-hydroxy-L-proline + succinate + CO2
-
-
-
?
hypoxia-inducible factor2alpha C-terminal oxygen dependent degradation domain-L-proline + 2-oxoglutarate + O2
-
724225
Homo sapiens
hypoxia-inducible factor2alpha C-terminal oxygen dependent degradation domain-trans-4-hydroxy-L-proline + succinate + CO2
-
-
-
?
hypoxia-inducible factor2alpha C-terminal oxygen-dependent degradation domain-L-proline + 2-oxoglutarate + O2
-
724225
Homo sapiens
hypoxia-inducible factor2alpha C-terminal oxygen-dependent degradation domain-trans-4-hydroxy-L-proline + succinate + CO2
-
-
-
?
hypoxia-inducible factor2alpha N-terminal oxygen dependent degradation domain-L-proline + 2-oxoglutarate + O2
-
724225
Homo sapiens
hypoxia-inducible factor2alpha N-terminal oxygen dependent degradation domain-trans-4-hydroxy-L-proline + succinate + CO2
-
-
-
?
additional information
the substrate contains a C-terminal and a N-terminal oxygen-dependent degradation domain, as well as a C-terminal transactivation domain
724225
Homo sapiens
?
-
-
-
-
additional information
the subtrate contains a C-terminal and a N-terminal oxygen-dependent degradation domain, as well as a C-terminal transactivation domain
724225
Homo sapiens
?
-
-
-
-
Temperature Optimum [C] (protein specific)
Temperature Optimum [C]
Temperature Optimum Maximum [C]
Commentary
Organism
25
-
assay at
Homo sapiens
Turnover Number [1/s] (protein specific)
Turnover Number Minimum [1/s]
Turnover Number Maximum [1/s]
Substrate
Commentary
Organism
Structure
0.0005
-
hypoxia-inducible factor2alpha C-terminal oxygen-dependent degradation domain-L-proline
pH 7.5, 25C, PHD3
Homo sapiens
0.0012
-
hypoxia-inducible factor1alpha C-terminal oxygen-dependent degradation domain-L-proline
pH 7.5, 25C, PHD3
Homo sapiens
0.0032
-
hypoxia-inducible factor1alpha C-terminal oxygen-dependent degradation domain-L-proline
pH 7.5, 25C, PHD2
Homo sapiens
pH Optimum (protein specific)
pH Optimum Minimum
pH Optimum Maximum
Commentary
Organism
7.5
-
assay at
Homo sapiens
General Information
General Information
Commentary
Organism
evolution
the enzyme belongs to the of the 2-oxoglutarate- and iron-dependent dioxygenase family of enzymes; the enzyme belongs to the of the 2-oxoglutarate- and iron-dependent dioxygenase family of enzymes; the enzyme belongs to the of the 2-oxoglutarate- and iron-dependent dioxygenase family of enzymes
Homo sapiens
physiological function
the prolyl hydroxylases control the abundance of hypoxia-inducible factor through oxygen-dependent hydroxylation of specific proline residues in hypoxia-inducible factor proteins, triggering subsequent ubiquitination and proteasomal degradation; the prolyl hydroxylases control the abundance of hypoxia-inducible factor through oxygen-dependent hydroxylation of specific proline residues in hypoxia-inducible factor proteins, triggering subsequent ubiquitination and proteasomal degradation; the prolyl hydroxylases control the abundance of hypoxia-inducible factor through oxygen-dependent hydroxylation of specific proline residues in hypoxia-inducible factor proteins, triggering subsequent ubiquitination and proteasomal degradation. Differential regulation of HIF1alpha and HIF2alpha at the NODDD site by PHD2
Homo sapiens
General Information (protein specific)
General Information
Commentary
Organism
evolution
the enzyme belongs to the of the 2-oxoglutarate- and iron-dependent dioxygenase family of enzymes
Homo sapiens
physiological function
the prolyl hydroxylases control the abundance of hypoxia-inducible factor through oxygen-dependent hydroxylation of specific proline residues in hypoxia-inducible factor proteins, triggering subsequent ubiquitination and proteasomal degradation
Homo sapiens
physiological function
the prolyl hydroxylases control the abundance of hypoxia-inducible factor through oxygen-dependent hydroxylation of specific proline residues in hypoxia-inducible factor proteins, triggering subsequent ubiquitination and proteasomal degradation. Differential regulation of HIF1alpha and HIF2alpha at the NODDD site by PHD2
Homo sapiens
Other publictions for EC 1.14.11.29
No.
1st author
Pub Med
title
organims
journal
volume
pages
year
Activating Compound
Application
Cloned(Commentary)
Crystallization (Commentary)
Engineering
General Stability
Inhibitors
KM Value [mM]
Localization
Metals/Ions
Molecular Weight [Da]
Natural Substrates/ Products (Substrates)
Organic Solvent Stability
Organism
Oxidation Stability
Posttranslational Modification
Purification (Commentary)
Reaction
Renatured (Commentary)
Source Tissue
Specific Activity [micromol/min/mg]
Storage Stability
Substrates and Products (Substrate)
Subunits
Temperature Optimum [C]
Temperature Range [C]
Temperature Stability [C]
Turnover Number [1/s]
pH Optimum
pH Range
pH Stability
Cofactor
Ki Value [mM]
pI Value
IC50 Value
Activating Compound (protein specific)
Application (protein specific)
Cloned(Commentary) (protein specific)
Cofactor (protein specific)
Crystallization (Commentary) (protein specific)
Engineering (protein specific)
General Stability (protein specific)
IC50 Value (protein specific)
Inhibitors (protein specific)
Ki Value [mM] (protein specific)
KM Value [mM] (protein specific)
Localization (protein specific)
Metals/Ions (protein specific)
Molecular Weight [Da] (protein specific)
Natural Substrates/ Products (Substrates) (protein specific)
Organic Solvent Stability (protein specific)
Oxidation Stability (protein specific)
Posttranslational Modification (protein specific)
Purification (Commentary) (protein specific)
Renatured (Commentary) (protein specific)
Source Tissue (protein specific)
Specific Activity [micromol/min/mg] (protein specific)
Storage Stability (protein specific)
Substrates and Products (Substrate) (protein specific)
Subunits (protein specific)
Temperature Optimum [C] (protein specific)
Temperature Range [C] (protein specific)
Temperature Stability [C] (protein specific)
Turnover Number [1/s] (protein specific)
pH Optimum (protein specific)
pH Range (protein specific)
pH Stability (protein specific)
pI Value (protein specific)
Expression
General Information
General Information (protein specific)
Expression (protein specific)
KCat/KM [mM/s]
KCat/KM [mM/s] (protein specific)
741945
Osipyants
Enzymesubstrate reporters fo ...
Homo sapiens
Biochemistry
82
1207-1214
2017
-
-
-
-
-
-
4
-
-
-
-
3
-
3
-
-
-
-
-
1
-
-
3
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
12
-
-
-
-
-
3
-
-
-
-
-
3
-
-
3
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
742225
Miikkulainen
HIF prolyl hydroxylase PHD3 r ...
Homo sapiens
Cancer Metab.
5
5-5
2017
-
-
-
-
-
-
-
-
-
-
-
1
-
1
-
-
-
-
-
2
-
-
1
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
1
-
-
-
-
-
2
-
-
1
-
-
-
-
-
-
-
-
-
-
2
2
-
-
-
742585
Badawi
Relative contribution of prol ...
Homo sapiens
Front. Neurosci.
11
239
2017
-
-
-
-
-
-
1
-
-
-
-
1
-
1
-
-
-
-
-
2
-
-
1
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
1
-
-
-
-
-
1
-
-
-
-
-
2
-
-
1
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
743380
Kozlova
Hypoxia-inducible factor prol ...
Homo sapiens
Oncotarget
8
9885-9898
2017
-
-
-
-
-
-
-
-
-
-
-
1
-
2
-
-
-
-
-
2
-
-
1
1
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
1
-
-
-
-
-
2
-
-
1
1
-
-
-
-
-
-
-
-
-
2
2
-
-
-
741826
Chen
Alternative splicing transcri ...
Megalobrama amblycephala
Biochem. Biophys. Res. Commun.
469
737-742
2016
-
-
-
-
-
-
-
-
-
-
-
1
-
1
-
-
-
-
-
10
-
-
1
1
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
1
-
-
-
-
-
10
-
-
1
1
-
-
-
-
-
-
-
-
1
1
1
1
-
-
743284
Kapitsinou
The endothelial prolyl-4-hydr ...
Mus musculus
Mol. Cell. Biol.
36
1584-1594
2016
-
-
-
-
-
-
-
-
-
-
-
1
-
1
-
-
-
-
-
1
-
-
1
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
1
-
-
-
-
-
1
-
-
1
-
-
-
-
-
-
-
-
-
-
1
1
-
-
-
743285
Arsenault
The zinc finger of prolyl hyd ...
Mus musculus
Mol. Cell. Biol.
36
2328-2343
2016
-
-
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-
-
-
-
-
-
1
-
1
-
3
-
-
-
-
-
2
-
-
1
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
1
-
1
-
-
-
-
-
2
-
-
1
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
741910
Pektas
Increased turnover at limitin ...
Homo sapiens
Biochemistry
54
2851-2857
2015
-
-
1
-
2
-
-
9
-
-
-
1
-
2
-
-
1
-
-
-
-
-
2
1
-
-
-
9
-
-
-
-
-
-
-
-
-
1
-
-
2
-
-
-
-
9
-
-
-
1
-
-
-
1
-
-
-
-
2
1
-
-
-
9
-
-
-
-
-
-
-
-
8
8
742307
Bishop
HIF hydroxylase pathways in c ...
Homo sapiens
Circ. Res.
117
65-79
2015
-
-
-
-
-
-
2
-
-
-
-
1
-
1
-
-
-
-
-
-
-
-
1
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
2
-
-
-
-
-
1
-
-
-
-
-
-
-
-
1
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
742656
Wang
Current advances in the novel ...
Caenorhabditis elegans, Drosophila melanogaster
Insect Mol. Biol.
24
634-648
2015
-
-
-
-
-
-
-
-
-
-
-
2
-
7
-
-
-
-
-
-
-
-
2
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
2
-
-
-
-
-
-
-
-
2
-
-
-
-
-
-
-
-
-
-
2
2
-
-
-
743203
Giannetto
Hypoxia-inducible factor alph ...
Mytilus galloprovincialis
Mar. Biotechnol.
17
768-781
2015
-
-
-
-
-
-
-
-
-
-
-
1
-
7
-
-
-
-
-
1
-
-
1
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
1
-
-
-
-
-
1
-
-
1
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
743581
Chan
Potent and selective triazole ...
Homo sapiens, Mus musculus
PLoS ONE
10
e0132004
2015
-
-
-
2
-
-
16
-
-
-
-
-
-
6
-
-
-
-
-
7
-
-
6
-
-
-
-
-
-
-
-
-
-
-
6
-
-
-
-
3
-
-
6
37
-
-
-
-
-
-
-
-
-
-
-
21
-
-
6
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
744664
Sun
Prolyl-4-hydroxylase 2 potent ...
Homo sapiens
Cell. Physiol. Biochem.
37
2257-2264
2015
-
1
1
-
1
-
-
-
-
-
-
1
-
2
-
-
-
-
-
2
-
-
1
-
-
-
-
-
-
-
-
-
-
-
-
-
1
1
-
-
1
-
-
-
-
-
-
-
-
1
-
-
-
-
-
2
-
-
1
-
-
-
-
-
-
-
-
-
-
3
3
-
-
-
745336
Li
Prolyl-4-hydroxylase domain p ...
Homo sapiens, Rattus norvegicus
J. Biol. Chem.
290
7195-7207
2015
-
1
2
-
1
-
-
-
-
-
-
2
-
2
-
-
-
-
-
4
-
-
2
-
-
-
-
-
-
-
-
-
-
-
-
-
1
2
-
-
1
-
-
-
-
-
-
-
-
2
-
-
-
-
-
4
-
-
2
-
-
-
-
-
-
-
-
-
-
4
4
-
-
-
741852
Tarhonskaya
Investigating the contributio ...
Homo sapiens
Biochem. J.
463
363-372
2014
-
-
-
-
2
-
-
-
-
1
-
1
-
2
-
-
-
-
-
-
-
-
1
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
2
-
-
-
-
-
-
1
-
1
-
-
-
-
-
-
-
-
1
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
742048
Fan
The hypoxia-inducible factor ...
Homo sapiens
BioMed Res. Int.
2014
239356
2014
-
-
-
-
-
-
17
-
-
-
-
2
-
1
-
-
-
-
-
1
-
-
2
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
17
-
-
-
-
-
2
-
-
-
-
-
1
-
-
2
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
742072
Hong
Discovery of novel 2-[2-(3-hy ...
Homo sapiens
Bioorg. Med. Chem. Lett.
24
3142-3145
2014
-
-
-
-
-
-
33
-
-
-
-
1
-
1
-
-
-
-
-
1
-
-
1
-
-
-
-
-
-
-
-
-
-
-
24
-
-
-
-
-
-
-
24
33
-
-
-
-
-
1
-
-
-
-
-
1
-
-
1
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
744649
Sun
Prolyl-4-hydroxylase 2 enhanc ...
Homo sapiens
Cell Death Dis.
5
e1322
2014
-
1
1
-
1
-
-
-
-
-
-
1
-
1
-
-
-
-
-
4
-
-
1
-
-
-
-
-
-
-
-
-
-
-
-
-
1
1
-
-
1
-
-
-
-
-
-
-
-
1
-
-
-
-
-
4
-
-
1
-
-
-
-
-
-
-
-
-
-
2
2
-
-
-
745510
Taylor
A PHD in macrophage survival ...
Mus musculus
J. Leukoc. Biol.
96
365-375
2014
-
-
-
-
-
-
-
-
-
-
-
1
-
1
-
-
-
-
-
1
-
-
1
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
1
-
-
-
-
-
1
-
-
1
-
-
-
-
-
-
-
-
-
1
4
4
1
-
-
724696
Cavadas
Hypoxia-inducible factor (HIF) ...
Homo sapiens
Cell Commun. Signal.
11
42
2013
-
-
-
-
-
-
-
-
-
-
-
1
-
1
-
-
-
-
-
-
-
-
2
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
1
-
-
-
-
-
-
-
-
2
-
-
-
-
-
-
-
-
-
-
3
3
-
-
-
725596
Nguyen
A dynamic model of the hypoxia ...
Homo sapiens
J. Cell Sci.
126
1454-1463
2013
-
-
-
-
-
-
3
-
-
1
-
1
-
1
-
-
-
-
-
2
-
-
1
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
3
-
-
-
1
-
1
-
-
-
-
-
2
-
-
1
-
-
-
-
-
-
-
-
-
-
4
4
-
-
-
725653
Pektas
Substrate preference of the HI ...
Homo sapiens
J. Inorg. Biochem.
126
55-60
2013
1
-
1
-
-
-
-
4
-
1
-
2
-
1
-
-
1
-
-
1
-
-
3
-
1
-
-
4
1
-
-
-
-
-
-
1
-
1
-
-
-
-
-
-
-
4
-
1
-
2
-
-
-
1
-
1
-
-
3
-
1
-
-
4
1
-
-
-
-
1
1
-
4
4
724847
Masson
The FIH hydroxylase is a cellu ...
Homo sapiens
EMBO Rep.
13
251-257
2012
1
-
-
-
-
-
1
-
-
1
-
1
-
1
-
-
-
-
-
1
-
-
2
-
-
-
-
-
-
-
-
-
-
-
-
1
-
-
-
-
-
-
-
1
-
-
-
1
-
1
-
-
-
-
-
1
-
-
2
-
-
-
-
-
-
-
-
-
-
2
2
-
-
-
725647
Flagg
Screening chelating inhibitors ...
Homo sapiens
J. Inorg. Biochem.
113
25-30
2012
1
1
1
-
-
-
12
1
-
1
-
1
-
2
-
-
-
-
-
-
-
-
2
-
1
-
-
-
1
-
-
-
-
-
10
1
1
1
-
-
-
-
10
12
-
1
-
1
-
1
-
-
-
-
-
-
-
-
2
-
1
-
-
-
1
-
-
-
-
-
-
-
-
-
726084
Cao
Evidence for inhibition of HIF ...
Homo sapiens
Org. Biomol. Chem.
10
3913-3923
2012
1
-
1
-
-
-
5
2
-
1
-
1
-
1
-
-
1
-
-
-
-
-
1
-
-
-
-
-
-
-
-
-
4
-
4
1
-
1
-
-
-
-
4
5
4
2
-
1
-
1
-
-
-
1
-
-
-
-
1
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
724225
Pappalardi
Biochemical characterization o ...
Homo sapiens
Biochem. J.
436
363-369
2011
1
-
1
-
-
-
-
4
-
1
-
3
-
3
-
-
1
-
-
-
-
-
19
-
1
-
-
3
1
-
-
-
-
-
-
3
-
3
-
-
-
-
-
-
-
6
-
3
-
3
-
-
-
3
-
-
-
-
19
-
3
-
-
3
3
-
-
-
-
2
6
-
-
-
724523
Kwon
Inhibition of a prolyl hydroxy ...
Homo sapiens
Bioorg. Med. Chem. Lett.
21
4325-4328
2011
-
-
1
-
-
-
6
-
-
1
-
1
-
1
-
-
1
-
-
-
-
-
1
-
-
-
-
-
-
-
-
-
-
-
-
-
-
1
-
-
-
-
-
6
-
-
-
1
-
1
-
-
-
1
-
-
-
-
1
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
725644
Geng
Effects of polynitrogen compou ...
Homo sapiens
J. Inorg. Biochem.
105
391-399
2011
1
-
1
-
-
-
5
-
-
-
3
1
-
1
-
-
1
-
-
-
-
-
2
1
1
-
-
-
1
-
-
-
5
-
4
1
-
1
-
-
-
-
4
5
5
-
-
-
3
1
-
-
-
1
-
-
-
-
2
1
1
-
-
-
1
-
-
-
-
2
2
-
-
-
659235
Hirsila
Characterization of the human ...
Homo sapiens
J. Biol. Chem.
278
30772-30780
2003
1
-
1
-
1
-
5
37
-
-
-
3
-
3
-
-
1
-
-
8
-
-
48
-
1
-
-
-
1
-
-
-
14
-
-
3
-
3
-
-
1
-
-
15
18
48
-
-
-
3
-
-
-
2
-
16
-
-
48
-
3
-
-
-
3
-
-
-
-
-
-
-
-
-
701217
Ivan
HIF alpha targeted for VHL-med ...
Homo sapiens
Science
292
464-468
2001
-
-
-
-
-
-
-
-
-
1
-
1
-
1
-
-
-
-
-
-
-
-
1
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
1
-
1
-
-
-
-
-
-
-
-
1
-
-
-
-
-
-
-
-
-
-
1
1
-
-
-
701218
Jaakkola
Targeting of HIF-alpha to the ...
Homo sapiens
Science
292
468-472
2001
1
-
-
-
-
-
2
-
-
1
-
1
-
2
-
-
-
-
-
-
-
-
2
-
-
-
-
-
-
-
-
-
-
-
-
1
-
-
-
-
-
-
-
2
-
-
-
1
-
1
-
-
-
-
-
-
-
-
2
-
-
-
-
-
-
-
-
-
-
1
1
-
-
-
701219
Bruick
A conserved family of prolyl-4 ...
Drosophila melanogaster, Homo sapiens
Science
294
1337-1340
2001
-
-
1
-
3
-
1
-
-
1
-
3
-
5
-
-
1
-
-
-
-
-
6
-
-
-
-
-
-
-
-
-
-
-
-
-
-
3
-
-
3
-
-
1
-
-
-
3
-
3
-
-
-
3
-
-
-
-
6
-
-
-
-
-
-
-
-
-
-
1
3
-
-
-