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Information on EC 1.14.11.29 - hypoxia-inducible factor-proline dioxygenase and Organism(s) Homo sapiens and UniProt Accession Q9GZT9

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IUBMB Comments
Contains iron, and requires ascorbate. Specifically hydroxylates a proline residue in HIF-alpha, the alpha subunit of the transcriptional regulator HIF (hypoxia-inducible factor), which targets HIF for proteasomal destruction. The requirement of oxygen for the hydroxylation reaction enables animals to respond to hypoxia.
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This record set is specific for:
Homo sapiens
UNIPROT: Q9GZT9
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The taxonomic range for the selected organisms is: Homo sapiens
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria
Synonyms
egln1, prolyl hydroxylase domain, hph-1, egln2, hif prolyl, hif-ph, hif-prolyl hydroxylase, p4h-tm, prolyl hydroxylase-2, hif hydroxylase, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Egl nine homolog 1
-
HIF hydroxylase
-
HIF prolyl 4-hydroxylase
-
HIF prolyl hydroxylase
-
HIF-P4H-2
-
Hif-prolyl hydroxylase
-
hypoxia-inducible factor prolyl hydroxylase domain 2
-
prolyl hydroxylase domain
-
prolyl-4-hydroxylase 2
-
EGLN1
-
isoform
Egln2
EGLN3
factor inhibiting HIF
-
-
HIF hydroxylase
-
HIF prolyl
-
HIF prolyl 4-hydroxylase
-
-
HIF prolyl hydroxylase
HIF-1alpha PHD3
-
-
HIF-1alpha prolyl hydroxylase 3
-
-
HIF-alpha prolyl-hydroxylase
-
-
HIF-P4H-1
-
-
HIF-P4H-3
-
HIF-PH
-
-
Hif-prolyl hydroxylase
-
HIF-prolyl hydroxylase domain 2
-
-
HIF-prolyl hydroxylase-2
-
-
HPH-1
-
-
hypoxia-inducible factor prolyl hydroxylase 2
-
-
proline hydroxylase domain 2
-
-
prolyl hydroxylase
-
-
prolyl hydroxylase domain
prolyl hydroxylase domain protein
-
-
prolyl hydroxylase-2
-
-
transmembrane prolyl 4-hydroxylase
-
SYSTEMATIC NAME
IUBMB Comments
hypoxia-inducible factor-L-proline, 2-oxoglutarate:oxygen oxidoreductase (4-hydroxylating)
Contains iron, and requires ascorbate. Specifically hydroxylates a proline residue in HIF-alpha, the alpha subunit of the transcriptional regulator HIF (hypoxia-inducible factor), which targets HIF for proteasomal destruction. The requirement of oxygen for the hydroxylation reaction enables animals to respond to hypoxia.
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
DALDLEMLAPYISMDDDFQL + 2-oxoglutarate + O2
DALDLEMLA-((4R)-4-hydroxy-L-proline)-YISMDDDFQL + succinate + CO2
show the reaction diagram
a HIF-3alpha peptide. Vmax is 150% of the activity with DLDLEMLAPYIPMDDDFQL
-
-
?
DALTLLAPAAGDTIISLDF + 2-oxoglutarate + O2
DALTLLA-((4R)-4-hydroxy-L-proline)-AAGDTIISLDF + succinate + CO2
show the reaction diagram
hybrid substrate derived from C-terminal and N-terminal oxygen-dependent degradation domain
-
-
?
DALTLLAPAAGDTIISLDF + 2-oxoglutarate + O2
DLDLEMLA-((4R)-4-hydroxy-L-proline)-AAGDTIISLDF + succinate + CO2
show the reaction diagram
substrate derived from N-terminal oxygen-dependent degradation domain
-
-
?
DALTLLAPAAGDTIISLFG + 2-oxoglutarate + O2
DALTLLA-((4R)-4-hydroxy-L-proline)-AAGDTIISLFG + succinate + CO2
show the reaction diagram
N-terminal hydroxylation site of HIF-1alpha, Vmax is 100% of the activity with DLDLEMLAPYIPMDDDFQL
-
-
?
DLDLEALAPYIPADDDFQL + 2-oxoglutarate + O2
DLDLEALA-((4R)-4-hydroxy-L-proline)-YIPADDDFQL + succinate + CO2
show the reaction diagram
-
-
-
?
DLDLEMLAPAIPMDDDFQL + 2-oxoglutarate + O2
DLDLEMLA-((4R)-4-hydroxy-L-proline)-AIPMDDDFQL + succinate + CO2
show the reaction diagram
Vmax is 100% of the activity with DLDLEMLAPYIPMDDDFQL
-
-
?
DLDLEMLAPGIPMDDDFQL + 2-oxoglutarate + O2
DLDLEMLA-((4R)-4-hydroxy-L-proline)-GIPMDDDFQL + succinate + CO2
show the reaction diagram
Vmax is 100% of the activity with DLDLEMLAPYIPMDDDFQL
-
-
?
DLDLEMLAPYIPMD + 2-oxoglutarate + O2
DLDLEMLA-((4R)-4-hydroxy-L-proline)-YIPMD + succinate + CO2
show the reaction diagram
Vmax is 100% of the activity with DLDLEMLAPYIPMDDDFQL
-
-
?
DLDLEMLAPYIPMDD + 2-oxoglutarate + O2
DLDLEMLA-((4R)-4-hydroxy-L-proline)-YIPMDD + succinate + CO2
show the reaction diagram
Vmax is 100% of the activity with DLDLEMLAPYIPMDDDFQL
-
-
?
DLDLEMLAPYIPMDDDF + 2-oxoglutarate + O2
DLDLEMLA-((4R)-4-hydroxy-L-proline)-YIPMDDDF + succinate + CO2
show the reaction diagram
Vmax is 100% of the activity with DLDLEMLAPYIPMDDDFQL
-
-
?
DLDLEMLAPYIPMDDDFQL + 2-oxoglutarate + O2
?
show the reaction diagram
-
-
-
?
DLDLEMLAPYIPMDDDFQL + 2-oxoglutarate + O2
DLDLEMLA-((4R)-4-hydroxy-L-proline)-YIPMDDDFQL + succinate + CO2
show the reaction diagram
DLDLEMLAPYIPMDDDFQLRSFDQ + 2-oxoglutarate + O2
DLDLEMLA-((4R)-4-hydroxy-L-proline)-YIPMDDDFQLRSFDQ + succinate + CO2
show the reaction diagram
Vmax is 100% of the activity with DLDLEMLAPYIPMDDDFQL
-
-
?
DLDLEMLAPYIPTIISLDF + 2-oxoglutarate + O2
DLDLEMLA-((4R)-4-hydroxy-L-proline)-YIPTIISLDF + succinate + CO2
show the reaction diagram
hybrid substrate derived from C-terminal and N-terminal oxygen-dependent degradation domain
-
-
?
DLEMLAPYIPMDDDFQL + 2-oxoglutarate + O2
DLEMLA-((4R)-4-hydroxy-L-proline)-YIPMDDDFQL + succinate + CO2
show the reaction diagram
Vmax is 100% of the activity with DLDLEMLAPYIPMDDDFQL
-
-
?
ELDLETLAPYIPMDGEDFQ + 2-oxoglutarate + O2
?
show the reaction diagram
C-terminal hydroxylation site of HIF-2alpha. Vmax is 100% of the activity with DLDLEMLAPYIPMDDDFQL
-
-
?
EMLAPYIPMDDDFQL + 2-oxoglutarate + O2
EMLA-((4R)-4-hydroxy-L-proline)-YIPMDDDFQL + succinate + CO2
show the reaction diagram
Vmax is 100% of the activity with DLDLEMLAPYIPMDDDFQL
-
-
?
EPEELAQLAPTPGDAIISLD + 2-oxoglutarate + O2
?
show the reaction diagram
N-terminal hydroxylation site of HIF-2alpha. Vmax is 80% of the activity with DLDLEMLAPYIPMDDDFQL
-
-
?
hypoxia-inducible factor HIF1alpha-L-proline + 2-oxoglutarate + O2
hypoxia-inducible factor HIF1alpha-trans-4-hydroxy-L-proline + succinate + CO2
show the reaction diagram
-
-
-
?
hypoxia-inducible factor HIF2alpha-L-proline + 2-oxoglutarate + O2
hypoxia-inducible factor HIF2alpha-trans-4-hydroxy-L-proline + succinate + CO2
show the reaction diagram
-
-
-
?
hypoxia-inducible factor HIF3alpha-L-proline + 2-oxoglutarate + O2
hypoxia-inducible factor HIF3alpha-trans-4-hydroxy-L-proline + succinate + CO2
show the reaction diagram
-
-
-
?
hypoxia-inducible factor-alpha-L-proline + 2-oxoglutarate + O2
hypoxia-inducible factor-alpha-trans-4-hydroxy-L-proline + succinate + CO2
show the reaction diagram
hypoxia-inducible factor-L-proline + 2-oxoglutarate + O2
hypoxia-inducible factor-(4R)-4-hydroxy-L-proline + succinate + CO2
show the reaction diagram
hypoxia-inducible factor-L-proline + 2-oxoglutarate + O2
hypoxia-inducible factor-trans-4-hydroxy-L-proline + succinate + CO2
show the reaction diagram
hypoxia-inducible factor1alpha C-terminal oxygen-dependent degradation domain-L-proline + 2-oxoglutarate + O2
hypoxia-inducible factor1alpha C-terminal oxygen-dependent degradation domain-trans-4-hydroxy-L-proline + succinate + CO2
show the reaction diagram
-
-
-
?
hypoxia-inducible factor1alpha N-terminal oxygen-dependent degradation domain-L-proline + 2-oxoglutarate + O2
hypoxia-inducible factor1alpha N-terminal oxygen-dependent degradation domain-trans-4-hydroxy-L-proline + succinate + CO2
show the reaction diagram
-
-
-
?
hypoxia-inducible factor2alpha C-terminal oxygen dependent degradation domain-L-proline + 2-oxoglutarate + O2
hypoxia-inducible factor2alpha C-terminal oxygen dependent degradation domain-trans-4-hydroxy-L-proline + succinate + CO2
show the reaction diagram
-
-
-
?
hypoxia-inducible factor2alpha N-terminal oxygen dependent degradation domain-L-proline + 2-oxoglutarate + O2
hypoxia-inducible factor2alpha N-terminal oxygen dependent degradation domain-trans-4-hydroxy-L-proline + succinate + CO2
show the reaction diagram
-
-
-
?
L-ascorbate + 2-oxoglutarate + O2
? + succinate + CO2
show the reaction diagram
L-ascorbate is a co-substrate of HIF prolyl hydroxylase PHD that may compete for the binding site of 2-oxoglutarate in the enzyme active center
-
-
?
DALDLEMLAPYISMDDDFQL + 2-oxoglutarate + O2
?
show the reaction diagram
a HIF-3alpha peptide. Vmax is 120% of the activity with DLDLEMLAPYIPMDDDFQL
-
-
?
DALDLEMLAPYISMDDDFQL + 2-oxoglutarate + O2
DALDLEMLA-((4R)-4-hydroxy-L-proline)-YISMDDDFQL + succinate + CO2
show the reaction diagram
a HIF-3alpha peptide. Vmax is 120% of the activity with DLDLEMLAPYIPMDDDFQL
-
-
?
DALTLLAPAAGDTIISLFG + 2-oxoglutarate + O2
DALTLLA-((4R)-4-hydroxy-L-proline)-AAGDTIISLFG + succinate + CO2
show the reaction diagram
N-terminal hydroxylation site of HIF-1alpha, Vmax is 60% of the activity with DLDLEMLAPYIPMDDDFQL
-
-
?
DLDLEMLAPAIPMDDDFQL + 2-oxoglutarate + O2
DLDLEMLA-((4R)-4-hydroxy-L-proline)-AIPMDDDFQL + succinate + CO2
show the reaction diagram
Vmax is 100% of the activity with DLDLEMLAPYIPMDDDFQL
-
-
?
DLDLEMLAPGIPMDDDFQL + 2-oxoglutarate + O2
DLDLEMLA-((4R)-4-hydroxy-L-proline)-GIPMDDDFQL + succinate + CO2
show the reaction diagram
Vmax is 100% of the activity with DLDLEMLAPYIPMDDDFQL
-
-
?
DLDLEMLAPYIPMD + 2-oxoglutarate + O2
DLDLEMLA-((4R)-4-hydroxy-L-proline)-YIPMD + succinate + CO2
show the reaction diagram
Vmax is 100% of the activity with DLDLEMLAPYIPMDDDFQL
-
-
?
DLDLEMLAPYIPMDD + 2-oxoglutarate + O2
DLDLEMLA-((4R)-4-hydroxy-L-proline)-YIPMDD + succinate + CO2
show the reaction diagram
Vmax is 100% of the activity with DLDLEMLAPYIPMDDDFQL
-
-
?
DLDLEMLAPYIPMDDDF + 2-oxoglutarate + O2
DLDLEMLA-((4R)-4-hydroxy-L-proline)-YIPMDDDF + succinate + CO2
show the reaction diagram
Vmax is 100% of the activity with DLDLEMLAPYIPMDDDFQL
-
-
?
DLDLEMLAPYIPMDDDFQL + 2-oxoglutarate + O2
?
show the reaction diagram
-
-
-
?
DLDLEMLAPYIPMDDDFQL + 2-oxoglutarate + O2
DLDLEMLA-((4R)-4-hydroxy-L-proline)-YIPMDDDFQL + succinate + CO2
show the reaction diagram
-
-
-
?
DLDLEMLAPYIPMDDDFQLRSFDQ + 2-oxoglutarate + O2
DLDLEMLA-((4R)-4-hydroxy-L-proline)-YIPMDDDFQLRSFDQ + succinate + CO2
show the reaction diagram
Vmax is 100% of the activity with DLDLEMLAPYIPMDDDFQL
-
-
?
DLEMLAPYIPMDDDFQL + 2-oxoglutarate + O2
DLEMLA-((4R)-4-hydroxy-L-proline)-YIPMDDDFQL + succinate + CO2
show the reaction diagram
Vmax is 100% of the activity with DLDLEMLAPYIPMDDDFQL
-
-
?
EEPDLSCLAPFVDTYDMMQM + 2-oxoglutarate + O2
?
show the reaction diagram
ELDLETLAPYIPMDGEDFQ + 2-oxoglutarate + O2
?
show the reaction diagram
C-terminal hydroxylation site of HIF-2alpha. Vmax is 70% of the activity with DLDLEMLAPYIPMDDDFQL
-
-
?
ELDLETLAPYIPMDGEDFQ + 2-oxoglutarate + O2
ELDLETLA-((4R)-4-hydroxy-L-proline)-YIPMDGEDFQ + succinate + CO2
show the reaction diagram
C-terminal hydroxylation site of HIF-2alpha. Vmax is 80% of the activity with DLDLEMLAPYIPMDDDFQL
-
-
?
EMLAPYIPMDD + 2-oxoglutarate + O2
EMLA-((4R)-4-hydroxy-L-proline)-YIPMDD + succinate + CO2
show the reaction diagram
Vmax is 30% of the activity with DLDLEMLAPYIPMDDDFQL
-
-
?
EMLAPYIPMDDDFQL + 2-oxoglutarate + O2
EMLA-((4R)-4-hydroxy-L-proline)-YIPMDDDFQL + succinate + CO2
show the reaction diagram
EPEELAQLAPTPGDAIISLD + 2-oxoglutarate + O2
?
show the reaction diagram
hypoxia-inducible factor 1alpha-L-proline + 2-oxoglutarate + O2
hypoxia-inducible factor 1alpha-trans-4-hydroxy-L-proline + succinate + CO2
show the reaction diagram
-
-
-
-
?
hypoxia-inducible factor HIF1alpha-L-proline + 2-oxoglutarate + O2
hypoxia-inducible factor HIF1alpha-trans-4-hydroxy-L-proline + succinate + CO2
show the reaction diagram
-
-
-
?
hypoxia-inducible factor HIF2alpha-L-proline + 2-oxoglutarate + O2
hypoxia-inducible factor HIF2alpha-trans-4-hydroxy-L-proline + succinate + CO2
show the reaction diagram
-
-
-
?
hypoxia-inducible factor HIF3alpha-L-proline + 2-oxoglutarate + O2
hypoxia-inducible factor HIF3alpha-trans-4-hydroxy-L-proline + succinate + CO2
show the reaction diagram
-
-
-
?
hypoxia-inducible factor-L-proline + 2-oxoglutarate + O2
hypoxia-inducible factor-(4R)-4-hydroxy-L-proline + succinate + CO2
show the reaction diagram
hypoxia-inducible factor-L-proline + 2-oxoglutarate + O2
hypoxia-inducible factor-trans-4-hydroxy-L-proline + succinate + CO2
show the reaction diagram
hypoxia-inducible factor-L-proline peptide + 2-oxoglutarate + O2
hypoxia-inducible factor-trans-4-hydroxy-L-proline peptide + succinate + CO2
show the reaction diagram
-
peptide substrate is a peptide derived from the natural sequence of HIF-1alpha residues 556-574
hydroxylation at Pro564
-
?
hypoxia-inducible factor-proline + 2-oxoglutarate + O2
hypoxia-inducible factor-(3S)-3-hydroxy-proline + succinate + CO2
show the reaction diagram
-
HIF-1alpha
-
-
?
hypoxia-inducible factor1alpha C-terminal oxygen-dependent degradation domain-L-proline + 2-oxoglutarate + O2
hypoxia-inducible factor1alpha C-terminal oxygen-dependent degradation domain-trans-4-hydroxy-L-proline + succinate + CO2
show the reaction diagram
hypoxia-inducible factor1alpha N-terminal oxygen-dependent degradation domain-L-proline + 2-oxoglutarate + O2
hypoxia-inducible factor1alpha N-terminal oxygen-dependent degradation domain-trans-4-hydroxy-L-proline + succinate + CO2
show the reaction diagram
low activity
-
-
?
hypoxia-inducible factor2alpha C-terminal oxygen dependent degradation domain-L-proline + 2-oxoglutarate + O2
hypoxia-inducible factor2alpha C-terminal oxygen dependent degradation domain-trans-4-hydroxy-L-proline + succinate + CO2
show the reaction diagram
-
-
-
?
hypoxia-inducible factor2alpha C-terminal oxygen-dependent degradation domain-L-proline + 2-oxoglutarate + O2
hypoxia-inducible factor2alpha C-terminal oxygen-dependent degradation domain-trans-4-hydroxy-L-proline + succinate + CO2
show the reaction diagram
-
-
-
?
hypoxia-inducible factor2alpha N-terminal oxygen dependent degradation domain-L-proline + 2-oxoglutarate + O2
hypoxia-inducible factor2alpha N-terminal oxygen dependent degradation domain-trans-4-hydroxy-L-proline + succinate + CO2
show the reaction diagram
-
-
-
?
LAPYIPMDDDFQL + 2-oxoglutarate + O2
LA-((4R)-4-hydroxy-L-proline)-YIPMDDDFQL + succinate + CO2
show the reaction diagram
Vmax is 90% of the activity with DLDLEMLAPYIPMDDDFQL
-
-
?
additional information
?
-
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
hypoxia-inducible factor-alpha-L-proline + 2-oxoglutarate + O2
hypoxia-inducible factor-alpha-trans-4-hydroxy-L-proline + succinate + CO2
show the reaction diagram
hypoxia-inducible factor-L-proline + 2-oxoglutarate + O2
hypoxia-inducible factor-(4R)-4-hydroxy-L-proline + succinate + CO2
show the reaction diagram
hypoxia-inducible factor-L-proline + 2-oxoglutarate + O2
hypoxia-inducible factor-trans-4-hydroxy-L-proline + succinate + CO2
show the reaction diagram
hypoxia-inducible factor 1alpha-L-proline + 2-oxoglutarate + O2
hypoxia-inducible factor 1alpha-trans-4-hydroxy-L-proline + succinate + CO2
show the reaction diagram
-
-
-
-
?
hypoxia-inducible factor-L-proline + 2-oxoglutarate + O2
hypoxia-inducible factor-(4R)-4-hydroxy-L-proline + succinate + CO2
show the reaction diagram
hypoxia-inducible factor-L-proline + 2-oxoglutarate + O2
hypoxia-inducible factor-trans-4-hydroxy-L-proline + succinate + CO2
show the reaction diagram
hypoxia-inducible factor-proline + 2-oxoglutarate + O2
hypoxia-inducible factor-(3S)-3-hydroxy-proline + succinate + CO2
show the reaction diagram
-
HIF-1alpha
-
-
?
additional information
?
-
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Ca2+
the crystal structure reveals an EF domain with two Ca2+-binding motifs inserted within the catalytic domain. The proximity of the EF domain to the active site suggests that Ca2+ binding is relevant to the catalytic activity. Functional analysis demonstrates that Ca2+-binding affinity of P4H-TM is within the range of physiological Ca2+ concentration in the endoplasmic reticulum. P4H-TM is found both as a monomer and a dimer in the solution, but the monomer-dimer equilibrium is not regulated by Ca2+
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
3-([1,1'-biphenyl]-4-yl)-8-[(3-methylpyridin-2-yl)methyl]-1-(pyrimidin-2-yl)-1,3,8-triazaspiro[4.5]decane-2,4-dione
compound stabilizes HIF-1alpha levels and is also active against lysine-specific demethylase KDM4A
-
3-carboxy-4-oxo-3,4-dihydro-1,10-phenanthroline
-
3-hydroxypyridine-2-carbonyl-glycine
-
3-[(1,3-benzoxazol-2-yl)carbamoyl]propanoic acid
-
-
3-[(5-chloro-1,3-benzoxazol-2-yl)carbamoyl]propanoic acid
-
-
4-hydroxy-2-(1H-pyrazol-1-yl)-N-[[4-(trifluoromethyl)phenyl]methyl]pyrimidine-5-carboxamide
-
-
4-hydroxy-N-[(1R)-2-hydroxy-1-phenylethyl]-2-(1H-pyrazol-1-yl)pyrimidine-5-carboxamide
-
-
4-hydroxy-N-[(4-phenoxyphenyl)methyl]-2-(1H-pyrazol-1-yl)pyrimidine-5-carboxamide
-
-
6-[5-oxo-4-(1H-1,2,3-triazol-1-yl)-2,5-dihydro-1H-pyrazol-1-yl]pyridine-3-carboxylic acid
-
7-[(4-chlorophenyl)[(3-hydroxypyridin-2-yl)amino]methyl]quinolin-8-ol
-
adaptaquin
-
-
ciclopirox
CO releasing molecule-2
i.e.CORM-2, [RuCl2(CO)3]2, in situ CO donor, reduces the hydroxylation of C-terminal and N-terminal oxygen-dependent degradation domains of HIF-1alpha
-
dimethyloxalyl glycine
mimicks 2-oxoglutarate binding mode
-
dimethyloxalylglycine
-
ethyl 3,4-dihydroxybenzoate
iron chelator that can fit inside the active center
FG-4592
IOX2
mimicks 2-oxoglutarate binding mode
-
N-((3,4-dimethoxyphenyl)(8-hydroxyquinolin-7-yl)methyl)-2-phenylacetamide
-
N-((3-hydroxy-6-chloroquinolin-2-yl)carbonyl)glycine
-
N-(1-[[6-(4-chlorophenoxy)pyridin-3-yl]methyl]-4-hydroxy-2-oxo-1,2,5,6-tetrahydropyridine-3-carbonyl)glycine
clinical candidate as PHD2 inhibitor, promotes the production of erythropoietin following oral administration in mice and rats. The predicted half-life in humans is 1.3-5.6 h
-
N-(4-hydroxy-1-[[4-(4-methylphenoxy)phenyl]methyl]-2-oxo-1,2,5,6-tetrahydropyridine-3-carbonyl)glycine
-
-
N-(4-hydroxy-1-[[5-(4-methylphenoxy)pyridin-2-yl]methyl]-2-oxo-1,2,5,6-tetrahydropyridine-3-carbonyl)glycine
-
-
N-(4-hydroxy-1-[[6-(4-methylphenoxy)pyridin-3-yl]methyl]-2-oxo-1,2,5,6-tetrahydropyridine-3-carbonyl)glycine
-
-
N-([1,1'-biphenyl]-4-yl)-4-hydroxy-2-(1H-pyrazol-1-yl)pyrimidine-5-carboxamide
compound stabilizes HIF-1alpha levels
-
N-oxalylglycine
-
N-[(1,3-dihydro-2-benzofuran-5-yl)methyl]-4-hydroxy-2-(1H-pyrazol-1-yl)pyrimidine-5-carboxamide
-
-
N-[([1,1'-biphenyl]-4-yl)methyl]-4-hydroxy-2-(1H-pyrazol-1-yl)pyrimidine-5-carboxamide
-
-
N-[1-[([1,1'-biphenyl]-4-yl)methyl]-4-hydroxy-2-oxo-1-azaspiro[5.5]undec-3-ene-3-carbonyl]glycine
lead compound for synthesis of orally administered agents for the treatment of renal anemia
-
oxalylglycine
-
Pyridine-2,4-dicarboxylate
-
RuCl3
inhibitor of PHD2 under the standard assay conditions in presence of 10 microM Fe(II). This effect can be alleviated by supplementing the enzymatic reaction mixture with excess Fe(II)
tert-butyl 6-(5-oxo-4-(1H-1,2,3-triazol-1-yl)-2,5-dihydro-1H-pyrazol-1-yl)nicotinate
potent and selective inhibitor of isoform PHD2
[(1-benzyl-4-hydroxy-2-oxo-1,2-dihydroquinoline-3-carbonyl)amino]acetic acid
-
[(1-chloro-4-hydroxyisoquinoline-3-carbonyl)amino]acetic acid
-
[(2E)-3-hydroxy-2-({[(naphthalen-2-yl)methanesulfonyl]acetyl}imino)-2,3-dihydro-1,3-thiazol-4-yl]acetic acid
-
[(4-hydroxy-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonyl)amino]acetic acid
-
(2R)-[2-[2-(5-cyano-3-hydroxypyridin-2-yl)-1,3-thiazol-4-yl]acetamido](phenyl)acetic acid
-
-
(2S)-[2-[2-(5-cyano-3-hydroxypyridin-2-yl)-1,3-thiazol-4-yl]acetamido](phenyl)acetic acid
-
-
1,1',1'',1'''-(1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrayl)tetrapropan-2-ol
1-(5-chloro-6-(trifluoromethoxy)-1H-benzoimidazol-2-yl)-1H-pyrazole-4-carboxylic acid
-
i.e. JNJ-42041935, 2-oxoglutarate analogue
-
2,2',2'',2'''-(1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrayl)tetraacetamide
-
chelates Fe2+ in a hexacoordinative mode through four nitrogens of the macrocycle and two oxygens in side arms
2,3-dihydroxypyridine
-
-
2-(2-(5-cyano-3-hydroxy-4-methylpyridin-2-yl)-5-methylthiazol-4-yl)-N-(2-(diethylamino)ethyl)acetamide
-
-
2-(2-(5-cyano-3-hydroxy-4-methylpyridin-2-yl)-5-phenylthiazol-4-yl)-N-(2-(pyridin-2-yl)ethyl)acetamide
-
-
2-(2-(5-cyano-3-hydroxypyridin-2-yl)-5-phenylthiazol-4-yl)-N-(2-(pyridin-2-yl)ethyl)acetamide
-
-
2-hydroxypyridine 1-oxide
-
-
2-[2-(5-cyano-3-hydroxy-4-methylpyridin-2-yl)-1,3-thiazol-4-yl]-N-[2-(diethylamino)ethyl]acetamide
-
-
2-[2-(5-cyano-3-hydroxy-4-methylpyridin-2-yl)-1,3-thiazol-4-yl]-N-[2-(pyridin-2-yl)ethyl]acetamide
-
-
2-[2-(5-cyano-3-hydroxy-4-methylpyridin-2-yl)-5-methyl-1,3-thiazol-4-yl]-N-propylacetamide
-
-
2-[2-(5-cyano-3-hydroxy-4-methylpyridin-2-yl)-5-methyl-1,3-thiazol-4-yl]-N-[2-(pyridin-2-yl)ethyl]acetamide
-
-
2-[2-(5-cyano-3-hydroxypyridin-2-yl)-1,3-thiazol-4-yl]-N-(2-phenylethyl)acetamide
-
-
2-[2-(5-cyano-3-hydroxypyridin-2-yl)-1,3-thiazol-4-yl]-N-[(1R)-2-hydroxy-1-phenylethyl]acetamide
-
-
2-[2-(5-cyano-3-hydroxypyridin-2-yl)-1,3-thiazol-4-yl]-N-[(1S)-2-hydroxy-1-phenylethyl]acetamide
-
-
2-[2-(5-cyano-3-hydroxypyridin-2-yl)-1,3-thiazol-4-yl]-N-[2-(pyridin-2-yl)ethyl]acetamide
-
-
2-[2-(5-cyano-3-hydroxypyridin-2-yl)-5-methyl-1,3-thiazol-4-yl]-N-[2-(pyridin-2-yl)ethyl]acetamide
-
-
2-[2-[2-(5-cyano-3-hydroxypyridin-2-yl)-1,3-thiazol-4-yl]acetamido]-2-methylpropanoic acid
-
-
3,3'-[(pyridin-2-ylmethyl)imino]dipropanenitrile
-
noncompetitive inhibition
3,3'-[(pyridin-4-ylimino)bis(propane-3,1-diyliminomethanediyl)]diphenol
-
noncompetitive inhibition
3,3'-[(pyridin-4-ylimino)bis[propane-3,1-diylnitrilo(Z)methylylidene]]diphenol
-
noncompetitive inhibition
3,4-dihydroxybenzoate
-
-
3,6,9-tris(naphthalen-1-ylmethyl)-3,6,9,15-tetraazabicyclo[9.3.1]pentadeca-1(15),11,13-triene
-
coordinates Fe2+ via triad or tetrad from nitrogen atoms of the parent ring, which leaves vacant position for other ligands binding
3-carboxy-4-oxo-3,4-dihydro-1,10-phenanthroline
-
3-cyano-6-methyl-2(H)-pyridinone
-
-
3-hydroxy-1,2-dimethyl-4(1H)-pyridinone
-
-
3-hydroxy-2-methyl-4-pyrone
-
-
3-hydroxypyridine-2-carbonyl-glycine
-
4-methylcatechol
-
-
4-nitrocatechol
-
-
4-tert-butylcatechol
-
-
5-hydroxy-2-hydroxymethyl-4-pyrone
-
-
5-hydroxy-4-oxo-4H-pyran-2-carboxylic acid
-
-
5-hydroxy-6-[4-[2-oxo-2-(pyrrolidin-1-yl)ethyl]-1,3-thiazol-2-yl]pyridine-3-carbonitrile
-
-
6-[5-oxo-4-(1H-1,2,3-triazol-1-yl)-2,5-dihydro-1H-pyrazol-1-yl]pyridine-3-carboxylic acid
-
7-[(4-chlorophenyl)[(3-hydroxypyridin-2-yl)amino]methyl]quinolin-8-ol
-
adaptaquin
-
EC50 of ca 2 mM in HIF1 ODD-luc fusion reporter assay
-
AKB-6548
-
-
BAY85-3934
-
-
ciclopirox olamine
-
-
cobalt chloride
-
-
deferoxamine
-
-
desferrioxamine
-
iron chelator
dimethyloxalylglycine
DLDLEALA-L-3,4-dehydroproline-YIPADDDFQLR
-
-
DLDLEALA-L-4-thioproline-YIPADDDFQLR
-
-
DLDLEALA-L-piperidine-2-carboxylic acid-YIPADDDFQLR
-
-
DLDLEALA-L-trans-4-fluoroproline-YIPADDDFQLR
-
-
DLDLEALA-L-trans-4-hydroxyproline-YIPADDDFQLR
-
-
FG-0041
-
-
FG-4497
-
-
-
FG-4592
FKBP38
-
-
-
GSK1278863
-
-
H2O2
-
poor inhibition. Prolyl hydroxylase is less sensitive to peroxide, preferential inhibition of N803-hydroxylation by FIH, EC 1.14.11.30, compared with inhibition of P402/P564 hydroxylation by PHDs
JNJ1935
-
a prolyl-hydroxylase selective inhibitor. Low concentrations of JNJ1935 selectively inhibit PHDs, whereas higher concentrations inhibit all hydroxylases, including FIH, EC 1.14.11.30, in vitro and in vivo inhibition
L-mimosine
-
-
Mn2+
-
-
Morg-1
-
-
-
N,N-dimethyl-5-[3,6,9,15-tetraazabicyclo[9.3.1]pentadeca-1(15),11,13-trien-6-ylsulfonyl]naphthalen-1-amine
-
coordinates Fe2+ via triad or tetrad from nitrogen atoms of the parent ring, which leaves vacant position for other ligands binding
N-((3,4-dimethoxyphenyl)(8-hydroxyquinolin-7-yl)methyl)-2-phenylacetamide
-
N-((3-hydroxy-6-chloroquinolin-2-yl)carbonyl)glycine
-
N-(methoxyoxoacetyl)-glycine methyl ester
-
a pan-hydroxylase inhibitor, in vitro and in vivo inhibition
N-benzyl-2-[2-(3-hydroxypyridin-2-yl)-1,3-thiazol-4-yl]acetamide
-
-
N-benzyl-2-[2-(5-cyano-3-hydroxypyridin-2-yl)-1,3-thiazol-4-yl]acetamide
-
-
N-oxalyl-(2S)-alanine
-
competed by 2-oxoglutarate, no inhibition by the enantiomer N-oxalyl-(2R)-alanine
N-oxalylglycine
N-[(3,4-dimethoxyphenyl)(8-hydroxyquinolin-7-yl)methyl]-2-phenylacetamide
-
optimized adaptaquin analog, shows no toxicity up to a 100fold increased range over EC50. The drug is ismetabolized by CYP3A4 and CYP2B6
-
oxalylglycine
-
oxygen
the transiently overexpressed HPH-1 enzyme is inhibited by a low-oxygen environment
PN-3602
-
-
-
Pyridine-2,4-dicarboxylate
-
TM6008
-
-
TM6089
-
-
Zn2+
-
-
[(1-benzyl-4-hydroxy-2-oxo-1,2-dihydroquinoline-3-carbonyl)amino]acetic acid
-
[(1-chloro-4-hydroxyisoquinoline-3-carbonyl)amino]acetic acid
-
[(2E)-3-hydroxy-2-({[(naphthalen-2-yl)methanesulfonyl]acetyl}imino)-2,3-dihydro-1,3-thiazol-4-yl]acetic acid
-
[(4-hydroxy-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonyl)amino]acetic acid
-
[2-(3-hydroxypyridin-2-yl)-1,3-thiazol-4-yl]acetic acid
-
-
[2-(3-hydroxypyridin-2-yl)-6-oxo-1,6-dihydropyrimidin-5-yl]acetic acid
-
-
[2-(5-cyano-3-hydroxypyridin-2-yl)-1,3-thiazol-4-yl]acetic acid
-
-
[2-(5-cyano-3-hydroxypyridin-2-yl)-6-oxo-1,6-dihydropyrimidin-5-yl]acetic acid
-
-
[2-[2-(5-cyano-3-hydroxypyridin-2-yl)-1,3-thiazol-4-yl]acetamido]acetic acid
-
-
additional information
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
ascorbate
ascorbate
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0007 - 0.06
2-oxoglutarate
0.015
DALDLEMLAPYISMDDDFQL
pH 7.8, 37°C
0.0366 - 0.1071
DALTLLAPAAGDTIISLDF
-
0.13
DALTLLAPAAGDTIISLFG
pH 7.8, 37°C
0.0008 - 0.0041
DLDLEALAPYIPADDDFQL
0.01
DLDLEMLAPAIPMDDDFQL
pH 7.8, 37°C
0.02
DLDLEMLAPGIPMDDDFQL
pH 7.8, 37°C
0.1
DLDLEMLAPYIPMD
pH 7.8, 37°C
0.06
DLDLEMLAPYIPMDD
pH 7.8, 37°C
0.05
DLDLEMLAPYIPMDDDF
pH 7.8, 37°C
0.0052 - 0.007
DLDLEMLAPYIPMDDDFQL
0.006
DLDLEMLAPYIPMDDDFQLRSFDQ
pH 7.8, 37°C
0.1306
DLDLEMLAPYIPTIISLDF
pH 7.5, 37°C
-
0.007
DLEMLAPYIPMDDDFQL
pH 7.8, 37°C
0.03
ELDLETLAPYIPMDGEDFQ
pH 7.8, 37°C
0.035
EMLAPYIPMDDDFQL
pH 7.8, 37°C
0.06
EPEELAQLAPTPGDAIISLD
pH 7.8, 37°C
0.00075 - 0.00094
hypoxia-inducible factor1alpha C-terminal oxygen-dependent degradation domain-L-proline
pH 7.5, 25°C, PHD2
-
0.1 - 0.76
O2
0.007 - 0.06
2-oxoglutarate
0.006 - 0.007
DALDLEMLAPYISMDDDFQL
0.38
DALTLLAPAAGDTIISLFG
pH 7.8, 37°C
0.01 - 0.02
DLDLEMLAPAIPMDDDFQL
0.02
DLDLEMLAPGIPMDDDFQL
pH 7.8, 37°C
0.03 - 0.1
DLDLEMLAPYIPMD
0.009 - 0.1
DLDLEMLAPYIPMDD
0.007 - 0.07
DLDLEMLAPYIPMDDDF
0.007 - 0.008
DLDLEMLAPYIPMDDDFQL
0.006 - 0.008
DLDLEMLAPYIPMDDDFQLRSFDQ
0.007 - 0.014
DLEMLAPYIPMDDDFQL
0.07 - 0.1
EEPDLSCLAPFVDTYDMMQM
0.011 - 0.03
ELDLETLAPYIPMDGEDFQ
0.05
EMLAPYIPMDD
pH 7.8, 37°C
0.007 - 0.08
EMLAPYIPMDDDFQL
0.1
EPEELAQLAPTPGDAIISLD
pH 7.8, 37°C
0.001 - 0.067
hypoxia-inducible factor-L-proline
0.000016
hypoxia-inducible factor1alpha C-terminal oxygen-dependent degradation domain-L-proline
pH 7.5, 25°C, PHD3
-
0.0047 - 0.023
hypoxia-inducible factor2alpha C-terminal oxygen-dependent degradation domain-L-proline
pH 7.5, 25°C, PHD3
-
0.015
LAPYIPMDDDFQL
pH 7.8, 37°C
0.23
O2
pH 7.8, 37°C
additional information
additional information
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.017 - 0.548
2-oxoglutarate
0.015 - 0.733
DLDLEALAPYIPADDDFQL
0.0032
hypoxia-inducible factor1alpha C-terminal oxygen-dependent degradation domain-L-proline
pH 7.5, 25°C, PHD2
-
0.063 - 0.483
O2
0.0101 - 0.02
hypoxia-inducible factor-L-proline
0.0012
hypoxia-inducible factor1alpha C-terminal oxygen-dependent degradation domain-L-proline
pH 7.5, 25°C, PHD3
-
0.0005
hypoxia-inducible factor2alpha C-terminal oxygen-dependent degradation domain-L-proline
pH 7.5, 25°C, PHD3
-
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
25 - 45
2-oxoglutarate
11.7 - 183
DLDLEALAPYIPADDDFQL
0.0083 - 5
O2
0.72 - 18.8
hypoxia-inducible factor-L-proline
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.01
3-carboxy-4-oxo-3,4-dihydro-1,10-phenanthroline
pH 7.8, 37°C
0.002
3-hydroxypyridine-2-carbonyl-glycine
pH 7.8, 37°C
0.0002
N-((3-hydroxy-6-chloroquinolin-2-yl)carbonyl)glycine
pH 7.8, 37°C
0.008
oxalylglycine
pH 7.8, 37°C
0.007
Pyridine-2,4-dicarboxylate
pH 7.8, 37°C
0.00628 - 0.067
1,1',1'',1'''-(1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrayl)tetrapropan-2-ol
0.00998
2,2',2'',2'''-(1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrayl)tetraacetamide
-
recombinant enzyme, pH 7.0, 37°C
0.0821
3,3'-[(pyridin-2-ylmethyl)imino]dipropanenitrile
-
recombinant enzyme, pH 7.0, 37°C
0.0673
3,3'-[(pyridin-4-ylimino)bis(propane-3,1-diyliminomethanediyl)]diphenol
-
recombinant enzyme, pH 7.0, 37°C
0.0253
3,3'-[(pyridin-4-ylimino)bis[propane-3,1-diylnitrilo(Z)methylylidene]]diphenol
-
recombinant enzyme, pH 7.0, 37°C
0.00191
3,6,9-tris(naphthalen-1-ylmethyl)-3,6,9,15-tetraazabicyclo[9.3.1]pentadeca-1(15),11,13-triene
-
recombinant enzyme, pH 7.0, 37°C
0.01 - 0.03
3-carboxy-4-oxo-3,4-dihydro-1,10-phenanthroline
0.001 - 0.015
3-hydroxypyridine-2-carbonyl-glycine
0.00249
N,N-dimethyl-5-[3,6,9,15-tetraazabicyclo[9.3.1]pentadeca-1(15),11,13-trien-6-ylsulfonyl]naphthalen-1-amine
-
recombinant enzyme, pH 7.0, 37°C
0.0002 - 0.0008
N-((3-hydroxy-6-chloroquinolin-2-yl)carbonyl)glycine
0.01 - 0.05
oxalylglycine
0.008 - 0.04
Pyridine-2,4-dicarboxylate
additional information
additional information
-
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.000253
3-([1,1'-biphenyl]-4-yl)-8-[(3-methylpyridin-2-yl)methyl]-1-(pyrimidin-2-yl)-1,3,8-triazaspiro[4.5]decane-2,4-dione
Homo sapiens
pH not specified in the publication, temperature not specified in the publication
-
0.00224
3-[(1,3-benzoxazol-2-yl)carbamoyl]propanoic acid
Homo sapiens
pH 7.8, temperature not specified in the publication
-
0.00132
3-[(5-chloro-1,3-benzoxazol-2-yl)carbamoyl]propanoic acid
Homo sapiens
pH 7.8, temperature not specified in the publication
-
0.000153
4-hydroxy-2-(1H-pyrazol-1-yl)-N-[[4-(trifluoromethyl)phenyl]methyl]pyrimidine-5-carboxamide
Homo sapiens
pH not specified in the publication, temperature not specified in the publication
-
0.000093
4-hydroxy-N-[(1R)-2-hydroxy-1-phenylethyl]-2-(1H-pyrazol-1-yl)pyrimidine-5-carboxamide
Homo sapiens
pH not specified in the publication, temperature not specified in the publication
-
0.000256
4-hydroxy-N-[(4-phenoxyphenyl)methyl]-2-(1H-pyrazol-1-yl)pyrimidine-5-carboxamide
Homo sapiens
pH not specified in the publication, temperature not specified in the publication
-
0.0000048
6-[5-oxo-4-(1H-1,2,3-triazol-1-yl)-2,5-dihydro-1H-pyrazol-1-yl]pyridine-3-carboxylic acid
Homo sapiens
isoform PHD2, pH and temperature not specified in the publication
0.0244 - 0.1425
CO releasing molecule-2
-
0.00221
FG-4592
Homo sapiens
pH 7.8, temperature not specified in the publication
0.000013
N-(1-[[6-(4-chlorophenoxy)pyridin-3-yl]methyl]-4-hydroxy-2-oxo-1,2,5,6-tetrahydropyridine-3-carbonyl)glycine
Homo sapiens
pH not specified in the publication, temperature not specified in the publication
-
0.000049
N-(4-hydroxy-1-[[4-(4-methylphenoxy)phenyl]methyl]-2-oxo-1,2,5,6-tetrahydropyridine-3-carbonyl)glycine
Homo sapiens
pH not specified in the publication, temperature not specified in the publication
-
0.000069
N-(4-hydroxy-1-[[5-(4-methylphenoxy)pyridin-2-yl]methyl]-2-oxo-1,2,5,6-tetrahydropyridine-3-carbonyl)glycine
Homo sapiens
pH not specified in the publication, temperature not specified in the publication
-
0.000039
N-(4-hydroxy-1-[[6-(4-methylphenoxy)pyridin-3-yl]methyl]-2-oxo-1,2,5,6-tetrahydropyridine-3-carbonyl)glycine
Homo sapiens
pH not specified in the publication, temperature not specified in the publication
-
0.000213
N-([1,1'-biphenyl]-4-yl)-4-hydroxy-2-(1H-pyrazol-1-yl)pyrimidine-5-carboxamide
Homo sapiens
pH not specified in the publication, temperature not specified in the publication
-
0.0000022
N-oxalylglycine
Homo sapiens
isoform PHD2, pH and temperature not specified in the publication
0.000261
N-[(1,3-dihydro-2-benzofuran-5-yl)methyl]-4-hydroxy-2-(1H-pyrazol-1-yl)pyrimidine-5-carboxamide
Homo sapiens
pH not specified in the publication, temperature not specified in the publication
-
0.00021
N-[([1,1'-biphenyl]-4-yl)methyl]-4-hydroxy-2-(1H-pyrazol-1-yl)pyrimidine-5-carboxamide
Homo sapiens
pH not specified in the publication, temperature not specified in the publication
-
0.0000016
tert-butyl 6-(5-oxo-4-(1H-1,2,3-triazol-1-yl)-2,5-dihydro-1H-pyrazol-1-yl)nicotinate
Homo sapiens
isoform PHD2, pH and temperature not specified in the publication
0.000022
[(1-benzyl-4-hydroxy-2-oxo-1,2-dihydroquinoline-3-carbonyl)amino]acetic acid
Homo sapiens
isoform PHD2, pH and temperature not specified in the publication
0.0026
(2R)-[2-[2-(5-cyano-3-hydroxypyridin-2-yl)-1,3-thiazol-4-yl]acetamido](phenyl)acetic acid
Homo sapiens
-
pH and temperature not specified in the publication
0.0028
(2S)-[2-[2-(5-cyano-3-hydroxypyridin-2-yl)-1,3-thiazol-4-yl]acetamido](phenyl)acetic acid
Homo sapiens
-
pH and temperature not specified in the publication
0.0295 - 0.0397
1,1',1'',1'''-(1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrayl)tetrapropan-2-ol
0.0309
2,2',2'',2'''-(1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrayl)tetraacetamide
Homo sapiens
-
recombinant enzyme, pH 7.0, 37°C
0.005
2,3-dihydroxypyridine
Homo sapiens
-
pH 7.0, 37°C
0.0004
2-(2-(5-cyano-3-hydroxy-4-methylpyridin-2-yl)-5-methylthiazol-4-yl)-N-(2-(diethylamino)ethyl)acetamide
Homo sapiens
-
pH and temperature not specified in the publication
0.0057
2-(2-(5-cyano-3-hydroxy-4-methylpyridin-2-yl)-5-phenylthiazol-4-yl)-N-(2-(pyridin-2-yl)ethyl)acetamide
Homo sapiens
-
pH and temperature not specified in the publication
0.024
2-(2-(5-cyano-3-hydroxypyridin-2-yl)-5-phenylthiazol-4-yl)-N-(2-(pyridin-2-yl)ethyl)acetamide
Homo sapiens
-
pH and temperature not specified in the publication
0.003
2-hydroxypyridine 1-oxide
Homo sapiens
-
pH 7.0, 37°C
0.0038
2-[2-(5-cyano-3-hydroxy-4-methylpyridin-2-yl)-1,3-thiazol-4-yl]-N-[2-(diethylamino)ethyl]acetamide
Homo sapiens
-
pH and temperature not specified in the publication
0.0007
2-[2-(5-cyano-3-hydroxy-4-methylpyridin-2-yl)-1,3-thiazol-4-yl]-N-[2-(pyridin-2-yl)ethyl]acetamide
Homo sapiens
-
pH and temperature not specified in the publication
0.0014
2-[2-(5-cyano-3-hydroxy-4-methylpyridin-2-yl)-5-methyl-1,3-thiazol-4-yl]-N-propylacetamide
Homo sapiens
-
pH and temperature not specified in the publication
0.0008
2-[2-(5-cyano-3-hydroxy-4-methylpyridin-2-yl)-5-methyl-1,3-thiazol-4-yl]-N-[2-(pyridin-2-yl)ethyl]acetamide
Homo sapiens
-
pH and temperature not specified in the publication
0.0034
2-[2-(5-cyano-3-hydroxypyridin-2-yl)-1,3-thiazol-4-yl]-N-(2-phenylethyl)acetamide
Homo sapiens
-
pH and temperature not specified in the publication
0.0021
2-[2-(5-cyano-3-hydroxypyridin-2-yl)-1,3-thiazol-4-yl]-N-[(1R)-2-hydroxy-1-phenylethyl]acetamide
Homo sapiens
-
pH and temperature not specified in the publication
0.0024
2-[2-(5-cyano-3-hydroxypyridin-2-yl)-1,3-thiazol-4-yl]-N-[(1S)-2-hydroxy-1-phenylethyl]acetamide
Homo sapiens
-
pH and temperature not specified in the publication
0.003
2-[2-(5-cyano-3-hydroxypyridin-2-yl)-1,3-thiazol-4-yl]-N-[2-(pyridin-2-yl)ethyl]acetamide
Homo sapiens
-
pH and temperature not specified in the publication
0.0012
2-[2-(5-cyano-3-hydroxypyridin-2-yl)-5-methyl-1,3-thiazol-4-yl]-N-[2-(pyridin-2-yl)ethyl]acetamide
Homo sapiens
-
pH and temperature not specified in the publication
0.0073
2-[2-[2-(5-cyano-3-hydroxypyridin-2-yl)-1,3-thiazol-4-yl]acetamido]-2-methylpropanoic acid
Homo sapiens
-
pH and temperature not specified in the publication
0.0604
3,3'-[(pyridin-2-ylmethyl)imino]dipropanenitrile
Homo sapiens
-
recombinant enzyme, pH 7.0, 37°C
0.0128
3,3'-[(pyridin-4-ylimino)bis(propane-3,1-diyliminomethanediyl)]diphenol
Homo sapiens
-
recombinant enzyme, pH 7.0, 37°C
0.016
3,3'-[(pyridin-4-ylimino)bis[propane-3,1-diylnitrilo(Z)methylylidene]]diphenol
Homo sapiens
-
recombinant enzyme, pH 7.0, 37°C
0.0103
3,6,9-tris(naphthalen-1-ylmethyl)-3,6,9,15-tetraazabicyclo[9.3.1]pentadeca-1(15),11,13-triene
Homo sapiens
-
recombinant enzyme, pH 7.0, 37°C
1
3-cyano-6-methyl-2(H)-pyridinone
Homo sapiens
-
above, pH 7.0, 37°C
0.04
3-hydroxy-1,2-dimethyl-4(1H)-pyridinone
Homo sapiens
-
pH 7.0, 37°C
1
3-hydroxy-2-methyl-4-pyrone
Homo sapiens
-
above, pH 7.0, 37°C
0.004
4-methylcatechol
Homo sapiens
-
pH 7.0, 37°C
0.006
4-nitrocatechol
Homo sapiens
-
pH 7.0, 37°C
0.03
4-tert-butylcatechol
Homo sapiens
-
pH 7.0, 37°C
0.4
5-hydroxy-2-hydroxymethyl-4-pyrone
Homo sapiens
-
pH 7.0, 37°C
0.03
5-hydroxy-4-oxo-4H-pyran-2-carboxylic acid
Homo sapiens
-
pH 7.0, 37°C
0.002
5-hydroxy-6-[4-[2-oxo-2-(pyrrolidin-1-yl)ethyl]-1,3-thiazol-2-yl]pyridine-3-carbonitrile
Homo sapiens
-
pH and temperature not specified in the publication
0.0039
FG-2216
Homo sapiens
-
pH and temperature not specified in the publication
0.0207
N,N-dimethyl-5-[3,6,9,15-tetraazabicyclo[9.3.1]pentadeca-1(15),11,13-trien-6-ylsulfonyl]naphthalen-1-amine
Homo sapiens
-
recombinant enzyme, pH 7.0, 37°C
0.081
N-benzyl-2-[2-(3-hydroxypyridin-2-yl)-1,3-thiazol-4-yl]acetamide
Homo sapiens
-
pH and temperature not specified in the publication
0.0054
N-benzyl-2-[2-(5-cyano-3-hydroxypyridin-2-yl)-1,3-thiazol-4-yl]acetamide
Homo sapiens
-
pH and temperature not specified in the publication
0.195
[2-(3-hydroxypyridin-2-yl)-1,3-thiazol-4-yl]acetic acid
Homo sapiens
-
pH and temperature not specified in the publication
0.0275
[2-(3-hydroxypyridin-2-yl)-6-oxo-1,6-dihydropyrimidin-5-yl]acetic acid
Homo sapiens
-
pH and temperature not specified in the publication
0.006
[2-(5-cyano-3-hydroxypyridin-2-yl)-1,3-thiazol-4-yl]acetic acid
Homo sapiens
-
pH and temperature not specified in the publication
0.0135
[2-(5-cyano-3-hydroxypyridin-2-yl)-6-oxo-1,6-dihydropyrimidin-5-yl]acetic acid
Homo sapiens
-
pH and temperature not specified in the publication
0.0022
[2-[2-(5-cyano-3-hydroxypyridin-2-yl)-1,3-thiazol-4-yl]acetamido]acetic acid
Homo sapiens
-
pH and temperature not specified in the publication
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
30
-
assay at
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
the levels of HIF-P4H-2 mRNA expression is highest in the adult heart, brain, lung, and liver and in the fetal brain, heart, spleen, and skeletal muscle
Manually annotated by BRENDA team
the levels of HIF-P4H-2 mRNA expression is highest in the adult heart, brain, lung, and liver and in the fetal brain, heart, spleen, and skeletal muscle
Manually annotated by BRENDA team
the levels of HIF-P4H-2 mRNA expression is highest in the adult heart, brain, lung, and liver and in the fetal brain, heart, spleen, and skeletal muscle
Manually annotated by BRENDA team
the levels of HIF-P4H-2 mRNA expression is highest in the adult heart, brain, lung, and liver and in the fetal brain, heart, spleen, and skeletal muscle
Manually annotated by BRENDA team
the levels of HIF-P4H-2 mRNA expression is highest in the adult heart, brain, lung, and liver and in the fetal brain, heart, spleen, and skeletal muscle
Manually annotated by BRENDA team
the levels of HIF-P4H-2 mRNA expression is highest in the adult heart, brain, lung, and liver and in the fetal brain, heart, spleen, and skeletal muscle
Manually annotated by BRENDA team
-
C-terminal domain and N-terminal domain of PDH2
Manually annotated by BRENDA team
expression level of of HIF-P4H-3 mRNA is highest in the adult heart, brain, placenta, lung, and skeletal muscle and in the fetal heart, spleen, and skeletal muscle
Manually annotated by BRENDA team
the level of HIF-P4H-1 mRNA expression is highest in the adult brain, placenta, lung, and kidney
Manually annotated by BRENDA team
expression level of of HIF-P4H-3 mRNA is highest in the adult heart, brain, placenta, lung, and skeletal muscle and in the fetal heart, spleen, and skeletal muscle
Manually annotated by BRENDA team
expression level of of HIF-P4H-3 mRNA is highest in the adult heart, brain, placenta, lung, and skeletal muscle and in the fetal heart, spleen, and skeletal muscle
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
the enzyme is composed of an N-terminal cytoplasmic tail, a membrane-anchoring transmembrane helix, and a unique combination of a Ca2+-binding EF domain and a catalytic domain that is located within the ER lumen membrane
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
evolution
the enzyme belongs to the of the 2-oxoglutarate- and iron-dependent dioxygenase family of enzymes
malfunction
metabolism
physiological function
evolution
malfunction
metabolism
physiological function
additional information
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION?
EGLN1_HUMAN
426
0
46021
Swiss-Prot
other Location (Reliability: 2)
PDB
SCOP
CATH
UNIPROT
ORGANISM
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
45000
-
x * 45642, recombinant N-terminally Trx- and C-terminally His-tagged enzyme, mass spectrometry, x * 45651, recombinant His-tagged enzyme, mass spectrometry, x * 45000, recombinant His-tagged enzyme, SDS-PAGE
45642
-
x * 45642, recombinant N-terminally Trx- and C-terminally His-tagged enzyme, mass spectrometry, x * 45651, recombinant His-tagged enzyme, mass spectrometry, x * 45000, recombinant His-tagged enzyme, SDS-PAGE
45651
-
x * 45642, recombinant N-terminally Trx- and C-terminally His-tagged enzyme, mass spectrometry, x * 45651, recombinant His-tagged enzyme, mass spectrometry, x * 45000, recombinant His-tagged enzyme, SDS-PAGE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
isoform PHD2 in complex with Mn2+, sitting drop vapor diffusion method, using 1.6 M sodium citrate/citric acid pH 6.5
L-ascorbic acid can be docked in the binding site of 2-oxoglutarate and may chelate the iron ion, D-ascorbate cannot be docked
structure of a truncated domain of PHD2 with MnII substituting for FeII and complexed with inhibitor 4-hydroxy-N-[(4-phenoxyphenyl)methyl]-2-(1H-pyrazol-1-yl)pyrimidine-5-carboxamide reveals a binding mode involving chelation of the active site metal via nitrogen atoms of the pyrazolo and a pyrimidyl rings which adopt a coplanar conformation. The pyrazole ring of the inhibitor occupies the entrance of the active site pocket that is occupied by the CH2CO2H group of 2-oxoglutarate during catalysis
isoform PHD2 in complex with Mn2+, sitting drop vapor diffusion method, using 1.6 M sodium citrate/citric acid pH 6.5
sitting-drop vapor-diffusion method, the crystal structure reveals an EF domain with two Ca2+-binding motifs inserted within the catalytic domain. A substrate-binding groove is formed between the EF domain and the conserved core of the catalytic domain
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
D315E
substitution of the Fe(II)-binding aspartate for a glutamate residue manifests significantly reduced Fe(II) binding, yet maintains catalytic activity with a 5fold faster reaction with O2
R383K
disruption of 2OG binding in this variant does not accelerate O2 activation
T387A
the mutant shows 15fold increased turnover at limiting O2 concentrations compared to the wild type enzyme
T387N
the mutant shows about 2fold reduced turnover at limiting O2 concentrations compared to the wild type enzyme
D137A
mutation eliminates prolyl hydroxylase activity of HPH-1
H135A
mutation eliminates prolyl hydroxylase activity of HPH-1
H196A
mutation eliminates prolyl hydroxylase activity of HPH-1
R367K
inactive mutant of HIF-P4H-1
additional information
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
GSTrap column chromatography and Hitrap benzamidine column 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 GST-tagged PHD2 by glutathione affinity chromatography
-
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-tagged enzyme from Escherichia coli strain BL21(DE3) by nickel affinity chromatography
-
recombinant N-terminally GST-tagged PHD2 residues 178-426 from Escherichia coli strain L21(DE3) by glutathione affinity chromatography
-
recombinant N-terminally MBP-tagged PHD3 from Escherichia coli strain BL21(DE3)pRR692 by amylosse affinity chromatography
recombinant Trx- and His-tagged enzyme from Escherichia coli strain BL21(DE3)pLysS by nickel affinity chromatography to over 94% purity
-
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
expressed in Escherichia coli BL21(DE3) cells
expression in Escherichia coli
expression in H5 insect cells
expression in Spodoptera frugiperda Sf9 cells and Escherichia coli
expression of catalytic domain, residues 181-426
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
gene EGLN1
gene EGLN1, recombinant expression in HEK 293T cells from vector pRL-TK containing Renilla reniformis luciferase gene, real-time RT-PCR enzyme expression analysis
expression in Escherichia coli
expression in H5 insect cells
expression in Spodoptera frugiperda Sf9 cells and Escherichia coli
expression of His-tagged human PHD3 in Escherichia coli strain BL21(DE3)
-
expression of N-terminally GST-tagged PHD2 residues 178-426 in Escherichia coli strain L21(DE3)
-
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 catalytic domain residues 177-426, expression of N-terminally GST-tagged PHD2 in Escherichia coli strain BL21(DE3)
-
recombinant expression of GST-tagged PHD2
-
the coding region of human PHD3 DNA is optimized by using synonymous codons according to the code bias of Escherichia coli, expression of soluble and active N-terminally Trx- and C-terminally His-tagged human PHD3 in Escherichia coli strain BL21(DE3)pLysS at lower induction temperature of 25°C
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
analysis
assay for measuring the substrate hydroxylation-coupled decarboxylation of radioactive 2-oxoglutarate to radioactive carbon dioxide as a fast, efficient, and diverse method
medicine
pharmacology
modulation of PHD2 activity might be considered as a new way to inhibit glioblastoma progression
analysis
-
specific protocols for the knockdown and inhibition of the HIF prolyl hydroxylases 1-3 and the asparagine hydroxylase factor-inhibiting HIF using RNA interference and hydroxylase inhibitors, respectively
drug development
-
the unique function of PHD2 makes it a prime target for selective inhibition leading to regulatory control of diseases such as cancer and stroke
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Hirsila, M.; Koivunen, P.; Gunzler, V.; Kivirikko, K.I.; Myllyharju, J.
Characterization of the human prolyl 4-hydroxylases that modify the hypoxia-inducible factor
J. Biol. Chem.
278
30772-30780
2003
Homo sapiens, Homo sapiens (Q9GZT9), Homo sapiens (Q9H6Z9)
Manually annotated by BRENDA team
Ivan, M.; Kondo, K.; Yang, H.F.; Kim, W.; Valiando, J.; Ohh, M.; Salic, A.; Asara, J.M.; Lane, W.S.; Kaelin, W.G.
HIF alpha targeted for VHL-mediated destruction by proline hydroxylation: Implications for O2 sensing
Science
292
464-468
2001
Homo sapiens
Manually annotated by BRENDA team
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
Science
292
468-472
2001
Homo sapiens
Manually annotated by BRENDA team
Bruick, R.K.; McKnight, S.L.
A conserved family of prolyl-4-hydroxylases that modify HIF
Science
294
1337-1340
2001
Drosophila melanogaster, Homo sapiens, Homo sapiens (Q96KS0), Homo sapiens (Q9GZT9)
Manually annotated by BRENDA team
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.
Biochemical characterization of human HIF hydroxylases using HIF protein substrates that contain all three hydroxylation sites
Biochem. J.
436
363-369
2011
Homo sapiens (Q96KS0), Homo sapiens (Q9GZT9), Homo sapiens (Q9H6Z9)
Manually annotated by BRENDA team
Kwon, H.S.; Choi, Y.K.; Kim, J.W.; Park, Y.K.; Yang, E.G.; Ahn, D.R.
Inhibition of a prolyl hydroxylase domain (PHD) by substrate analog peptides
Bioorg. Med. Chem. Lett.
21
4325-4328
2011
Homo sapiens
Manually annotated by BRENDA team
Cavadas, M.A.; Nguyen, L.K.; Cheong, A.
Hypoxia-inducible factor (HIF) network: insights from mathematical models
Cell Commun. Signal.
11
42
2013
Homo sapiens
Manually annotated by BRENDA team
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
EMBO Rep.
13
251-257
2012
Homo sapiens
Manually annotated by BRENDA team
Nguyen, L.K.; Cavadas, M.A.; Scholz, C.C.; Fitzpatrick, S.F.; Bruning, U.; Cummins, E.P.; Tambuwala, M.M.; Manresa, M.C.; Kholodenko, B.N.; Taylor, C.T.; Cheong, A.
A dynamic model of the hypoxia-inducible factor 1alpha (HIF-1alpha) network
J. Cell Sci.
126
1454-1463
2013
Homo sapiens
Manually annotated by BRENDA team
Geng, Z.; Zhu, J.; Cao, J.; Geng, J.; Song, X.; Zhang, Z.; Bian, N.; Wang, Z.
Effects of polynitrogen compounds on the activity of recombinant human HIF-1alpha prolyl hydroxylase 3 in E. coli
J. Inorg. Biochem.
105
391-399
2011
Homo sapiens
Manually annotated by BRENDA team
Flagg, S.C.; Martin, C.B.; Taabazuing, C.Y.; Holmes, B.E.; Knapp, M.J.
Screening chelating inhibitors of HIF-prolyl hydroxylase domain 2 (PHD2) and factor inhibiting HIF (FIH)
J. Inorg. Biochem.
113
25-30
2012
Homo sapiens
Manually annotated by BRENDA team
Pektas, S.; Knapp, M.J.
Substrate preference of the HIF-prolyl hydroxylase-2 (PHD2) and substrate-induced conformational change
J. Inorg. Biochem.
126
55-60
2013
Homo sapiens
Manually annotated by BRENDA team
Cao, J.; Geng, Z.; Ma, X.; Wen, J.; Yin, Y.; Wang, Z.
Evidence for inhibition of HIF-1alpha prolyl hydroxylase 3 activity by four biologically active tetraazamacrocycles
Org. Biomol. Chem.
10
3913-3923
2012
Homo sapiens
Manually annotated by BRENDA team
Tarhonskaya, H.; Chowdhury, R.; Leung, I.K.; Loik, N.D.; McCullagh, J.S.; Claridge, T.D.; Schofield, C.J.; Flashman, E.
Investigating the contribution of the active site environment to the slow reaction of hypoxia-inducible factor prolyl hydroxylase domain 2 with oxygen
Biochem. J.
463
363-372
2014
Homo sapiens (Q9GZT9), Homo sapiens
Manually annotated by BRENDA team
Pektas, S.; Taabazuing, C.Y.; Knapp, M.J.
Increased turnover at limiting O2 concentrations by the Thr387 -> Ala variant of HIF-prolyl hydroxylase PHD2
Biochemistry
54
2851-2857
2015
Homo sapiens (Q9GZT9), Homo sapiens
Manually annotated by BRENDA team
Osipyants, A.; Smirnova, N.; Khristichenko, A.; Hushpulian, D.; Nikulin, S.; Chubar, T.; Zakhariants, A.; Tishkov, V.; Gazaryan, I.; Poloznikov, A.
Enzymesubstrate reporters for evaluation of substrate specificity of HIF prolyl hydroxylase isoforms
Biochemistry
82
1207-1214
2017
Homo sapiens (Q96KS0), Homo sapiens (Q9GZT9), Homo sapiens (Q9H6Z9)
Manually annotated by BRENDA team
Fan, L.; Li, J.; Yu, Z.; Dang, X.; Wang, K.
The hypoxia-inducible factor pathway, prolyl hydroxylase domain protein inhibitors, and their roles in bone repair and regeneration
BioMed Res. Int.
2014
239356
2014
Homo sapiens
Manually annotated by BRENDA team
Hong, Y.R.; Kim, H.T.; Ro, S.; Cho, J.M.; Lee, S.H.; Kim, I.S.; Jung, Y.H.
Discovery of novel 2-[2-(3-hydroxy-pyridin-2-yl)-thiazol-4-yl]-acetamide derivatives as HIF prolyl 4-hydroxylase inhibitors; SAR, synthesis and modeling evaluation
Bioorg. Med. Chem. Lett.
24
3142-3145
2014
Homo sapiens
Manually annotated by BRENDA team
Miikkulainen, P.; Hoegel, H.; Rantanen, K.; Suomi, T.; Kouvonen, P.; Elo, L.L.; Jaakkola, P.M.
HIF prolyl hydroxylase PHD3 regulates translational machinery and glucose metabolism in clear cell renal cell carcinoma
Cancer Metab.
5
5-5
2017
Homo sapiens (Q9H6Z9)
Manually annotated by BRENDA team
Bishop, T.; Ratcliffe, P.J.
HIF hydroxylase pathways in cardiovascular physiology and medicine
Circ. Res.
117
65-79
2015
Homo sapiens
Manually annotated by BRENDA team
Badawi, Y.; Shi, H.
Relative contribution of prolyl hydroxylase-dependent and -independent degradation of HIF-1alpha by proteasomal pathways in cerebral ischemia
Front. Neurosci.
11
239
2017
Homo sapiens
Manually annotated by BRENDA team
Kozlova, N.; Wottawa, M.; Katschinski, D.M.; Kristiansen, G.; Kietzmann, T.
Hypoxia-inducible factor prolyl hydroxylase 2 (PHD2) is a direct regulator of epidermal growth factor receptor (EGFR) signaling in breast cancer
Oncotarget
8
9885-9898
2017
Homo sapiens
Manually annotated by BRENDA team
Chan, M.C.; Atasoylu, O.; Hodson, E.; Tumber, A.; Leung, I.K.; Chowdhury, R.; Gomez-Perez, V.; Demetriades, M.; Rydzik, A.M.; Holt-Martyn, J.; Tian, Y.M.; Bishop, T.; Claridge, T.D.; Kawamura, A.; Pugh, C.W.; Ratcliffe, P.J.; Schofield, C.J.
Potent and selective triazole-based inhibitors of the hypoxia-inducible factor prolyl-hydroxylases with activity in the murine brain
PLoS ONE
10
e0132004
2015
Mus musculus (Q91UZ4), Mus musculus (Q91YE2), Mus musculus (Q91YE3), Homo sapiens (Q96KS0), Homo sapiens (Q9GZT9), Homo sapiens (Q9H6Z9)
Manually annotated by BRENDA team
Sun, W.; Jelkmann, W.; Depping, R.
Prolyl-4-hydroxylase 2 enhances hypoxia-induced glioblastoma cell death by regulating the gene expression of hypoxia-inducible factor-alpha
Cell Death Dis.
5
e1322
2014
Homo sapiens (Q9GZT9)
Manually annotated by BRENDA team
Sun, W.; Kosyna, F.K.; Jelkmann, W.; Depping, R.
Prolyl-4-hydroxylase 2 potentially contributes to hepatocellular carcinoma-associated erythrocytosis by maintaining hepatocyte nuclear factor-4alpha expression
Cell. Physiol. Biochem.
37
2257-2264
2015
Homo sapiens (Q9GZT9), Homo sapiens
Manually annotated by BRENDA team
Li, J.; Yuan, W.; Jiang, S.; Ye, W.; Yang, H.; Shapiro, I.M.; Risbud, M.V.
Prolyl-4-hydroxylase domain protein 2 controls NF-kappaB/p65 transactivation and enhances the catabolic effects of inflammatory cytokines on cells of the nucleus pulposus
J. Biol. Chem.
290
7195-7207
2015
Rattus norvegicus (P59722), Homo sapiens (Q9GZT9)
Manually annotated by BRENDA team
Osipyants, A.I.; Poloznikov, A.A.; Smirnova, N.A.; Hushpulian, D.M.; Khristichenko, A.Y.; Chubar, T.A.; Zakhariants, A.A.; Ahuja, M.; Gaisina, I.N.; Thomas, B.; Brown, A.M.; Gazaryan, I.G.; Tishkov, V.I.
L-ascorbic acid A true substrate for HIF prolyl hydroxylase?
Biochimie
147
46-54
2018
Homo sapiens (Q9GZT9)
Manually annotated by BRENDA team
Hamada, M.; Takayama, T.; Shibata, T.; Hiratate, A.; Takahashi, M.; Yashiro, M.; Takayama, N.; Okumura-Kitajima, L.; Koretsune, H.; Kajiyama, H.; Naruse, T.; Kato, S.; Takano, H.; Kakinuma, H.
Discovery of novel 2-[(4-hydroxy-6-oxo-2,3-dihydro-1H-pyridine-5-carbonyl)amino]acetic acid derivatives as HIF prolyl hydroxylase inhibitors for treatment of renal anemia
Bioorg. Med. Chem. Lett.
28
1725-1730
2018
Homo sapiens (Q9GZT9)
Manually annotated by BRENDA team
Mbenza, N.M.; Nasarudin, N.; Vadakkedath, P.G.; Patel, K.; Ismail, A.Z.; Hanif, M.; Wright, L.J.; Sarojini, V.; Hartinger, C.G.; Leung, I.K.H.
Carbon monoxide is an inhibitor of HIF prolyl hydroxylase domain 2
ChemBioChem
22
2521-2525
2021
Homo sapiens (Q9GZT9)
Manually annotated by BRENDA team
Holt-Martyn, J.P.; Chowdhury, R.; Tumber, A.; Yeh, T.L.; Abboud, M.I.; Lippl, K.; Lohans, C.T.; Langley, G.W.; Figg, W.; McDonough, M.A.; Pugh, C.W.; Ratcliffe, P.J.; Schofield, C.J.
Structure-activity relationship and crystallographic studies on 4-hydroxypyrimidine HIF prolyl hydroxylase domain inhibitors
ChemMedChem
15
270-273
2020
Homo sapiens (Q9GZT9)
Manually annotated by BRENDA team
Poloznikov, A.A.; Nikulin, S.V.; Zakhariants, A.A.; Khristichenko, A.Y.; Hushpulian, D.M.; Gazizov, I.N.; Tishkov, V.I.; Gazaryan, I.G.
''Branched Tail'' oxyquinoline inhibitors of HIF prolyl hydroxylase early evaluation of toxicity and metabolism using liver-on-a-chip
Drug Metab. Lett.
13
45-52
2019
Homo sapiens
Manually annotated by BRENDA team
Cockman, M.E.; Lippl, K.; Tian, Y.M.; Pegg, H.B.; Figg, W.D.; Abboud, M.I.; Heilig, R.; Fischer, R.; Myllyharju, J.; Schofield, C.J.; Ratcliffe, P.J.
Lack of activity of recombinant HIF prolyl hydroxylases (PHDs) on reported non-HIF substrates
eLife
8
e46490
2019
Homo sapiens (Q96KS0), Homo sapiens (Q9GZT9), Homo sapiens (Q9H6Z9), Homo sapiens
Manually annotated by BRENDA team
Myllykoski, M.; Sutinen, A.; Koski, M.; Kallio, J.; Raasakka, A.; Myllyharju, J.; Wierenga, R.; Koivunen, P.
Structure of transmembrane prolyl 4-hydroxylase reveals unique organization of EF and dioxygenase domains
J. Biol. Chem.
296
100197
2021
Homo sapiens (Q9NXG6), Homo sapiens
Manually annotated by BRENDA team
Chong, M.; Toh, L.; Tumber, A.; Chan, Y.; Chan, M.; Abboud, M.; Schofield, C.; Yeoh, K.
Evaluation of 3-carbamoylpropanoic acid analogs as inhibitors of human hypoxia-inducible factor (HIF) prolyl hydroxylase domain enzymes
Med. Chem. Res.
30
977-986
2021
Homo sapiens (Q9GZT9)
-
Manually annotated by BRENDA team
Pickel, C.; Taylor, C.; Scholz, C.
Genetic knockdown and pharmacologic inhibition of hypoxia-inducible factor (HIF) hydroxylases
Methods Mol. Biol.
1742
1-14
2018
Homo sapiens
Manually annotated by BRENDA team
Koivunen, P.; Myllyharju, J.
Kinetic analysis of HIF prolyl hydroxylases
Methods Mol. Biol.
1742
15-25
2018
Homo sapiens (Q9GZT9)
Manually annotated by BRENDA team