HOME
login
history
all enzymes
BRENDA home
History
Enzyme Nomenclature
Information on EC 1.14.11.29 - hypoxia-inducible factor-proline dioxygenase
for references in articles please use BRENDA:EC1.14.11.29
Word Map on EC 1.14.11.29
- 1.14.11.29
-
hypoxic
-
hydroxylases
- endothelial
-
angiogenesis
-
oxygen-dependent
-
erythropoietin
-
hippel-lindau
-
altitude
- tetrahydrobiopterin
- factor-1
-
ischemic
-
normoxia
-
oxygen-sensing
-
tibetan
- bh4
-
eglns
- erythrocytosis
-
cyclohydrolase
-
asparaginyl
-
high-altitude
-
hifalpha
-
hif-independent
-
hif-mediated
-
highland
-
2-oxoglutarate-dependent
-
hypoxia-responsive
- polycythemia
- paragangliomas
-
andeans
- dmog
-
gtp-cyclohydrolase
- drug development
Please wait a moment until all data is loaded. This message will disappear when all data is loaded.
Specify your search results
The enzyme appears in viruses and cellular organisms
topPlease wait a moment until the data is sorted. This message will disappear when the data is sorted.
EC NUMBER 
COMMENTARY 
1.14.11.29
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
RECOMMENDED NAME
GeneOntology No.
hypoxia-inducible factor-proline dioxygenase
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
hypoxia-inducible factor-L-proline + 2-oxoglutarate + O2 = hypoxia-inducible factor-trans-4-hydroxy-L-proline + succinate + CO2
-
-
-
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
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.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
evolution
malfunction
metabolism
physiological function
additional information
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
malfunction
-
silencing FIH, EC 1.14.11.30, under conditions where prolyl hydroxylase, is inhibited results in increased HIF-1alpha transcriptional activity, but paradoxically decreases HIF-1alpha stability
malfunction
-
isoform PHD3 silencing leads to downregulation of most glycolytic enzymes from glucose transport to lactate production supported by the reduction in extracellular acidification and lactate production and increase in cellular oxygen consumption rate
malfunction
-
inactivation of Phd2 in endothelial cells specifically results in severe pulmonary hypertension but not polycythemia and is associated with abnormal muscularization of peripheral pulmonary arteries and right ventricular hypertrophy
malfunction
-
hypoxia-inducible factor prolyl hydroxylase 2 knockdown leads to a less sustained activation of epidermal growth factor receptor and its downstream signaling pathways
metabolism
-
HIF protein stability is controlled by the oxygen sensing prolyl hydroxylase domain enzymes. Hypoxia-induced HIF signalling, mathematical modelling of the pathway, temporal dynamics of the HIF response to hypoxia, and molecular interaction map for the HIF network, overview. The hypoxia inducible factor is switched on and promotes adaptation to hypoxia by upregulatinggenes involved in angiogenesis, erythropoiesis and glycolysis
metabolism
-
hypoxia and oxidant stress can interact functionally as distinct regulators of HIF transcriptional output involving the enzyme. Oxidant stress activates hypoxia pathways through the inactivation of the oxygen-sensing hypoxia-inducible factor prolyl and asparaginyl hydroxylases
metabolism
-
optimal HIF-1alpha transcriptional activity requires sequential inhibition of both prolyl- and asparaginyl-hydroxylases
metabolism
-
isoforms PHD2 and 3 inhibit IkappaB kinase and decrease the activityof the nuclear factor-kappaB pathway. Isoform PHD2 also acts as a negative regulator of nuclear factor-kappaB during arteriogenesis
metabolism
-
isoforms PHD2 and 3 inhibit IkappaB kinase and decrease the activity of the nuclear factor-kappaB pathway. Isoform PHD2 also acts as a negative regulator of nuclear factor-kappaB during arteriogenesis
physiological function
-
HIF (hypoxia-inducible factor) is a transcription factor that plays a pivotal role in cellular adaptation to changes in oxygen availability. In the presence of oxygen, HIF is targeted for destruction by an E3 ubiquitin ligase containing the von Hippel-Lindau tumor suppressor protein (pVHL). Human pVHL binds to a short HIF-derived peptide when a conserved proline residue at the core of this peptide is hydroxylated. This protein modifiation may play a key role in mammalian oxygen sensing
physiological function
-
hypoxia-inducible factor (HIF) is a transcriptional complex that plays a central role in the regulation of gene expression by oxygen. In oxygenated and iron replete cells, HIF-alpha subunits are rapidly destroyed by a mechanism that involves ubiquitylation by the von Hippel-Lindau tumor suppressor (pVHL) E3 ligase complex. This process is suppressed by hypoxia and iron chelation, allowing transcriptional activation. The interaction between human pVHL and a specific domain of the HIF-1alpha subunit is regulated through hydroxylation of a proline residue (HIF-1alpha P564) by HIF-alpha prolyl-hydroxylase (HIF-PH). HIF-PH functions directly as a cellular oxygen sensor. Exposure of cells to dimethyl-oxalylglycine, that penetrates cells readily, results in rapid induction of HIF-1alpha
physiological function
in cultured mammalian cells, inappropriate accumulation of hypoxia-inducible factor caused by forced expression of the hypoxia-inducible factor-1alpha subunit under normoxic conditions is attenuated by coexpression of HIF prolyl hydroxylase. Suppression of HIF prolyl hydroxylase in cultured Drosophila melanogaster cells by RNA interference results in elevated expression of a hypoxia-inducible gene (LDH, encoding lactate dehydrogenase) under normoxic conditions. HIF prolyl hydroxylase is an essential component of the pathway through which cells sense oxygen; in cultured mammalian cells, inappropriate accumulation of hypoxia-inducible factor caused by forced expression of the hypoxia-inducible factor-1alpha subunit under normoxic conditions is attenuated by coexpression of HIF prolyl hydroxylase. Suppression of HIF prolyl hydroxylase in cultured Drosophila melanogaster cells by RNA interference results in elevated expression of a hypoxia-inducible gene (LDH, encoding lactate dehydrogenase) under normoxic conditions. HIF prolyl hydroxylase is an essential component of the pathway through which cells sense oxygen; in cultured mammalian cells, inappropriate accumulation of hypoxia-inducible factor caused by forced expression of the hypoxia-inducible factor-1alpha subunit under normoxic conditions is attenuated by coexpression of HIF prolyl. Suppression of HIF prolyl in cultured Drosophila melanogaster cells by RNA interference results in elevated expression of a hypoxia-inducible gene (LDH, encoding lactate dehydrogenase) under normoxic conditions. HIF prolyl is an essential component of the pathway through which cells sense oxygen
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
physiological function
-
HIF transcriptional activity is controlled by the asparaginyl hydroxylase factor inhibiting HIF-1, FIH
physiological function
-
key enzyme in activation of the hypoxia-inducible factor (HIF) pathway, a critical step in the transcriptional response to hypoxia. The enzyme is involved in the HIF-1alpha signalling network, overview
physiological function
-
prolyl hydroxylases inactivate hypoxia-inducible factor-1alpha by hydroxylation, PHD isozymes play an integral role in oxygen homeostasis. HIF-1alpha is an important regulation factor in the histiocyte under hypoxia conditions
physiological function
-
HIF prolyl-4-hydroxylase 2 regulates the hypoxia inducible transcription factor by hydroxylating two conserved prolyl residues in N-terminal oxygen degradation domain and C-terminal oxygen degradation domain of HIF-1alpha, the enzyme PHD2 prefers the C-terminal oxygen degradation domain by 20fold over the N-terminal, loop closure is the dominant contributor to substrate selectivity in PHD2
physiological function
isoform PHD3 plays important roles in hypoxia response and early embryo development of Megalobrama amblycephala
physiological function
-
isoform PHD3 is involved in the maintenance of key cellular functions including glycolysis and protein synthesis in clear cell renal cell carcinoma. The enzyme regulates ribosomal subunits and protein translation in clear cell renal cell carcinoma
physiological function
-
hypoxia-inducible factor prolyl hydroxylase 2 is a direct regulator of epidermal growth factor receptor signaling in breast cancer
additional information
-
PHD has a higher affinity for oxygen than FIH, EC 1.14.11.30
additional information
-
HIF asparaginyl hydroxylase, EC 1.14.11.30, is strikingly more sensitive to peroxide than the HIF prolyl hydroxylases
additional information
-
modeling of the dynamic regulation of HIF-1alpha transcriptional activity by the hydroxylase. HIF-1alpha stabilisation and transcriptional activity is dependent on oxygen tension
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
DALDLEMLAPYISMDDDFQL + 2-oxoglutarate + O2
?
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
DALTLLAPAAGDTIISLFG + 2-oxoglutarate + O2
DALTLLA-((4R)-4-hydroxy-L-proline)-AAGDTIISLFG + succinate + CO2
DLDLEALAPYIPADDDFQL + 2-oxoglutarate + O2
hydroxylated DLDLEALA-((4R)-4-hydroxy-L-proline)-YIPADDDFQL+ succinate + CO2
-
-
-
-
?
DLDLEMLAPAIPMDDDFQL + 2-oxoglutarate + O2
DLDLEMLA-((4R)-4-hydroxy-L-proline)-AIPMDDDFQL + succinate + CO2
Vmax is 100% of the activity with DLDLEMLAPYIPMDDDFQL
-
-
?
DLDLEMLAPAIPMDDDFQL + 2-oxoglutarate + O2
DLDLEMLA-((4R)-4-hydroxy-L-proline)-AIPMDDDFQL succinate + CO2
Vmax is 100% of the activity with DLDLEMLAPYIPMDDDFQL
-
-
?
DLDLEMLAPGIPMDDDFQL + 2-oxoglutarate + O2
DLDLEMLA-((4R)-4-hydroxy-L-proline)-GIPMDDDFQL + succinate + CO2
Vmax is 100% of the activity with DLDLEMLAPYIPMDDDFQL
-
-
?
DLDLEMLAPYIPMD + 2-oxoglutarate + O2
DLDLEMLA-((4R)-4-hydroxy-L-proline)-YIPMD + succinate + CO2
Vmax is 100% of the activity with DLDLEMLAPYIPMDDDFQL
-
-
?
DLDLEMLAPYIPMDD + 2-oxoglutarate + O2
DLDLEMLA-((4R)-4-hydroxy-L-proline)-YIPMDD + succinate + CO2
Vmax is 100% of the activity with DLDLEMLAPYIPMDDDFQL
-
-
?
DLDLEMLAPYIPMDDDF + 2-oxoglutarate + O2
DLDLEMLA-((4R)-4-hydroxy-L-proline)-YIPMDDDF + succinate + CO2
Vmax is 100% of the activity with DLDLEMLAPYIPMDDDFQL
-
-
?
DLDLEMLAPYIPMDDDFQL + 2-oxoglutarate + O2
DLDLEMLA-((4R)-4-hydroxy-L-proline)-YIPMDDDFQL + succinate + CO2
-
-
-
?
DLDLEMLAPYIPMDDDFQLRSFDQ + 2-oxoglutarate + O2
DLDLEMLA-((4R)-4-hydroxy-L-proline)-YIPMDDDFQLRSFDQ + succinate + CO2
Vmax is 100% of the activity with DLDLEMLAPYIPMDDDFQL
-
-
?
DLEMLAPYIPMDDDFQL + 2-oxoglutarate + O2
DLDLEMLA-((4R)-4-hydroxy-L-proline)-YIPMDDDFQL + succinate + CO2
Vmax is 100% of the activity with DLDLEMLAPYIPMDDDFQL
-
-
?
DLEMLAPYIPMDDDFQL + 2-oxoglutarate + O2
DLEMLA-((4R)-4-hydroxy-L-proline)-YIPMDDDFQL + succinate + CO2
Vmax is 100% of the activity with DLDLEMLAPYIPMDDDFQL
-
-
?
ELDLETLAPYIPMDGEDFQ + 2-oxoglutarate + O2
ELDLETLA-((4R)-4-hydroxy-L-proline)-YIPMDGEDFQ + succinate + CO2
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
Vmax is 30% of the activity with DLDLEMLAPYIPMDDDFQL
-
-
?
EMLAPYIPMDDDFQL + 2-oxoglutarate + O2
EMLA-((4R)-4-hydroxy-L-proline)-YIPMDDDFQL + succinate + CO2
hypoxia-inducible factor 1 alpha-L-proline + 2-oxoglutarate + O2
hypoxia-inducible factor 1alpha-trans-4-hydroxy-L-proline + succinate + CO2
-
-
-
?
hypoxia-inducible factor 1alpha-L-proline + 2-oxoglutarate + O2
hypoxia-inducible factor 1alpha-trans-4-hydroxy-L-proline + succinate + CO2
-
-
-
-
?
hypoxia-inducible factor-L-proline + 2-oxoglutarate + O2
hypoxia-inducible factor-(4R)-4-hydroxy-L-proline + succinate + CO2
hypoxia-inducible factor-L-proline + 2-oxoglutarate + O2
hypoxia-inducible factor-trans-4-hydroxy-L-proline + succinate + CO2
hypoxia-inducible factor-L-proline peptide + 2-oxoglutarate + O2
hypoxia-inducible factor-trans-4-hydroxy-L-proline peptide + succinate + CO2
-
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
-
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
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
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
-
-
-
?
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
-
-
-
?
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
-
-
-
?
LAPYIPMDDDFQL + 2-oxoglutarate + O2
LA-((4R)-4-hydroxy-L-proline)-YIPMDDDFQL + succinate + CO2
Vmax is 90% of the activity with DLDLEMLAPYIPMDDDFQL
-
-
?
DALDLEMLAPYISMDDDFQL + 2-oxoglutarate + O2
DALDLEMLA-((4R)-4-hydroxy-L-proline)-YISMDDDFQL + succinate + CO2
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
a HIF-3alpha peptide. Vmax is 150% of the activity with DLDLEMLAPYIPMDDDFQL
-
-
?
DALTLLAPAAGDTIISLFG + 2-oxoglutarate + O2
DALTLLA-((4R)-4-hydroxy-L-proline)-AAGDTIISLFG + succinate + CO2
N-terminal hydroxylation site of HIF-1alpha, Vmax is 100% of the activity with DLDLEMLAPYIPMDDDFQL
-
-
?
DALTLLAPAAGDTIISLFG + 2-oxoglutarate + O2
DALTLLA-((4R)-4-hydroxy-L-proline)-AAGDTIISLFG + succinate + CO2
N-terminal hydroxylation site of HIF-1alpha, Vmax is 60% of the activity with DLDLEMLAPYIPMDDDFQL
-
-
?
EEPDLSCLAPFVDTYDMMQM + 2-oxoglutarate + O2
?
hydroxylation site of Caenorhabditis elegans HIF-alpha. Vmax is 60% of the activity with DLDLEMLAPYIPMDDDFQL
-
-
?
EEPDLSCLAPFVDTYDMMQM + 2-oxoglutarate + O2
?
hydroxylation site of Caenorhabditis elegans HIF-alpha. Vmax is 80% of the activity with DLDLEMLAPYIPMDDDFQL
-
-
?
ELDLETLAPYIPMDGEDFQ + 2-oxoglutarate + O2
?
C-terminal hydroxylation site of HIF-2alpha. Vmax is 100% of the activity with DLDLEMLAPYIPMDDDFQL
-
-
?
ELDLETLAPYIPMDGEDFQ + 2-oxoglutarate + O2
?
C-terminal hydroxylation site of HIF-2alpha. Vmax is 70% of the activity with DLDLEMLAPYIPMDDDFQL
-
-
?
EMLAPYIPMDDDFQL + 2-oxoglutarate + O2
EMLA-((4R)-4-hydroxy-L-proline)-YIPMDDDFQL + succinate + CO2
Vmax is 100% of the activity with DLDLEMLAPYIPMDDDFQL
-
-
?
EMLAPYIPMDDDFQL + 2-oxoglutarate + O2
EMLA-((4R)-4-hydroxy-L-proline)-YIPMDDDFQL + succinate + CO2
Vmax is 80% of the activity with DLDLEMLAPYIPMDDDFQL
-
-
?
EPEELAQLAPTPGDAIISLD + 2-oxoglutarate + O2
?
N-terminal hydroxylation site of HIF-2alpha. Vmax is 30% of the activity with DLDLEMLAPYIPMDDDFQL
-
-
?
EPEELAQLAPTPGDAIISLD + 2-oxoglutarate + O2
?
N-terminal hydroxylation site of HIF-2alpha. Vmax is 70% of the activity with DLDLEMLAPYIPMDDDFQL
-
-
?
EPEELAQLAPTPGDAIISLD + 2-oxoglutarate + O2
?
N-terminal hydroxylation site of HIF-2alpha. Vmax is 80% of the activity with DLDLEMLAPYIPMDDDFQL
-
-
?
hypoxia-inducible factor-L-proline + 2-oxoglutarate + O2
hypoxia-inducible factor-(4R)-4-hydroxy-L-proline + succinate + CO2
-
-
-
?
hypoxia-inducible factor-L-proline + 2-oxoglutarate + O2
hypoxia-inducible factor-(4R)-4-hydroxy-L-proline + succinate + CO2
-
-
-
-
?
hypoxia-inducible factor-L-proline + 2-oxoglutarate + O2
hypoxia-inducible factor-(4R)-4-hydroxy-L-proline + succinate + CO2
-
HIF (hypoxia-inducible factor) is a transcription factor that plays a pivotal role in cellular adaptation to changes in oxygen availability. In the presence of oxygen, HIF is targeted for destruction by an E3 ubiquitin ligase containing the von Hippel-Lindau tumor suppressor protein (pVHL). Human pVHL binds to a short HIF-derived peptide when a conserved proline residue at the core of this peptide is hydroxylated. This protein modifiation may play a key role in mammalian oxygen sensing
-
-
?
hypoxia-inducible factor-L-proline + 2-oxoglutarate + O2
hypoxia-inducible factor-(4R)-4-hydroxy-L-proline + succinate + CO2
-
hypoxia-inducible factor (HIF) is a transcriptional complex that plays a central role in the regulation of gene expression by oxygen. In oxygenated and iron replete cells, HIF-alpha subunits are rapidly destroyed by a mechanism that involves ubiquitylation by the von Hippel-Lindau tumor suppressor (pVHL) E3 ligase complex. This process is suppressed by hypoxia and iron chelation, allowing transcriptional activation. The interaction between human pVHL and a specific domain of the HIF-1alpha subunit is regulated through hydroxylation of a proline residue (HIF-1alpha P564) by HIF-alpha prolyl-hydroxylase (HIF-PH). HIF-PH functions directly as a cellular oxygen sensor
-
-
?
hypoxia-inducible factor-L-proline + 2-oxoglutarate + O2
hypoxia-inducible factor-(4R)-4-hydroxy-L-proline + succinate + CO2
mammalian cells respond to changes in oxygen availability through a conserved pathway that is regulated by the hypoxia-inducible factor (HIF). The alpha subunit of the hypoxia-inducible factor is targeted for degradation under normoxic conditions by a ubiquitin-ligase complex that recognizes a hydroxylated proline residue in hypoxia-inducible factor. HIF prolyl hydroxylase is responsible for this posttranslational modification
-
-
?
hypoxia-inducible factor-L-proline + 2-oxoglutarate + O2
hypoxia-inducible factor-(4R)-4-hydroxy-L-proline + succinate + CO2
mammalian cells respond to changes in oxygen availability through a conserved pathway that is regulated by the hypoxia-inducible factor (HIF). The alpha subunit of the hypoxia-inducible factor is targeted for degradation under normoxic conditions by a ubiquitin-ligase complex that recognizes a hydroxylated proline residue in hypoxia-inducible factor. HIF prolyl is responsible for this posttranslational modification
-
-
?
hypoxia-inducible factor-L-proline + 2-oxoglutarate + O2
hypoxia-inducible factor-(4R)-4-hydroxy-L-proline + succinate + CO2
target proline residue: Pro564 in human HIF-alpha. A control peptide in which the target proline residue is replaced by alanine is not modified
-
-
?
hypoxia-inducible factor-L-proline + 2-oxoglutarate + O2
hypoxia-inducible factor-(4R)-4-hydroxy-L-proline + succinate + CO2
target proline residue: Pro564 in human HIF-alpha. A control peptide in which the target proline residue is replaced by alanine is not modified. The endogenous HIF prolyl hydroxylase, HPH-1 generates by in vitro transcription/translation does not modify peptides containing the L562A, A563G, or Y565A mutations. However, a peptide containing the Pro567 to Gly mutation is an equal, if not better, substrate for the human HPH enzymes
-
-
?
hypoxia-inducible factor-L-proline + 2-oxoglutarate + O2
hypoxia-inducible factor-(4R)-4-hydroxy-L-proline + succinate + CO2
target proline residue: Pro564 in human HIF-alpha. A control peptide in which the target proline residue is replaced by alanine is not modified. The recombinant HPH-2 purified from Escherichia coli does not modify peptides containing the L562A, A563G, or Y565A mutations. However, a peptide containing the Pro567 to Gly mutation is an equal, if not better, substrate for the human HPH enzymes
-
-
?
hypoxia-inducible factor-L-proline + 2-oxoglutarate + O2
hypoxia-inducible factor-trans-4-hydroxy-L-proline + succinate + CO2
-
hypoxia-inducible factor 1alpha is hydroxylated at Pro402 and Pro564
-
-
?
hypoxia-inducible factor-L-proline + 2-oxoglutarate + O2
hypoxia-inducible factor-trans-4-hydroxy-L-proline + succinate + CO2
-
hypoxia-inducible factor 1alpha is hydroxylated at Pro402 and Pro564
-
-
?
hypoxia-inducible factor-L-proline + 2-oxoglutarate + O2
hypoxia-inducible factor-trans-4-hydroxy-L-proline + succinate + CO2
-
-
-
-
?
hypoxia-inducible factor-L-proline + 2-oxoglutarate + O2
hypoxia-inducible factor-trans-4-hydroxy-L-proline + succinate + CO2
-
-
-
?
hypoxia-inducible factor-L-proline + 2-oxoglutarate + O2
hypoxia-inducible factor-trans-4-hydroxy-L-proline + succinate + CO2
-
-
-
?
hypoxia-inducible factor-L-proline + 2-oxoglutarate + O2
hypoxia-inducible factor-trans-4-hydroxy-L-proline + succinate + CO2
-
-
-
-
?
hypoxia-inducible factor-L-proline + 2-oxoglutarate + O2
hypoxia-inducible factor-trans-4-hydroxy-L-proline + succinate + CO2
-
-
-
?
hypoxia-inducible factor-L-proline + 2-oxoglutarate + O2
hypoxia-inducible factor-trans-4-hydroxy-L-proline + succinate + CO2
-
-
-
-
?
hypoxia-inducible factor-L-proline + 2-oxoglutarate + O2
hypoxia-inducible factor-trans-4-hydroxy-L-proline + succinate + CO2
HIF1alpha is a better substrate than HIF2alpha for PHD2
-
-
?
hypoxia-inducible factor-L-proline + 2-oxoglutarate + O2
hypoxia-inducible factor-trans-4-hydroxy-L-proline + succinate + CO2
-
PHD enzymes hydroxylates HIF-alpha at prolyl residues present in the transcriptional activation domain N-TAD
-
-
?
hypoxia-inducible factor-L-proline + 2-oxoglutarate + O2
hypoxia-inducible factor-trans-4-hydroxy-L-proline + succinate + CO2
-
PHD2 hydroxylates Pro402 and/or Pro564 of HIF-1alpha
-
-
?
hypoxia-inducible factor-L-proline + 2-oxoglutarate + O2
hypoxia-inducible factor-trans-4-hydroxy-L-proline + succinate + CO2
differential regulation of HIF1alpha and HIF2alpha at the N-terminal oxygen-dependent degradation domain site by PHD2
-
-
?
hypoxia-inducible factor-L-proline + 2-oxoglutarate + O2
hypoxia-inducible factor-trans-4-hydroxy-L-proline + succinate + CO2
-
hydroxylation at P402 and P564
-
-
?
hypoxia-inducible factor-L-proline + 2-oxoglutarate + O2
hypoxia-inducible factor-trans-4-hydroxy-L-proline + succinate + CO2
-
hydroxylation of the proline residue in the HIF-1alpha (556-574) peptide substrate, sequence of residues 556-574: DLDLEMLAPYIPMDDDFQL
-
-
?
hypoxia-inducible factor-L-proline + 2-oxoglutarate + O2
hypoxia-inducible factor-trans-4-hydroxy-L-proline + succinate + CO2
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
-
-
?
hypoxia-inducible factor-L-proline + 2-oxoglutarate + O2
hypoxia-inducible factor-trans-4-hydroxy-L-proline + succinate + CO2
the PHD1 reaction at the N-terminal oxygen-dependent degradation domain site shows low level hydroxylation
-
-
?
hypoxia-inducible factor-L-proline + 2-oxoglutarate + O2
hypoxia-inducible factor-trans-4-hydroxy-L-proline + succinate + CO2
-
-
-
?
hypoxia-inducible factor-L-proline + 2-oxoglutarate + O2
hypoxia-inducible factor-trans-4-hydroxy-L-proline + succinate + CO2
-
-
-
-
?
hypoxia-inducible factor-L-proline + 2-oxoglutarate + O2
hypoxia-inducible factor-trans-4-hydroxy-L-proline + succinate + CO2
-
-
-
?
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
-
-
-
?
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
low activity
-
-
?
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
-
-
-
?
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
low activity
-
-
?
additional information
?
-
-
the enzyme requires long peptide substrates. No hydroxylation of: Leu-Ala-Pro, Leu-Ala-Pro-Tyr, Leu-Glu-Met-Leu-Ala-Pro, and Leu-Glu-Met-Leu-Ala-Pro-Tyr
-
-
-
additional information
?
-
the enzyme requires long peptide substrates. No hydroxylation of: Leu-Ala-Pro, Leu-Ala-Pro-Tyr, Leu-Glu-Met-Leu-Ala-Pro, and Leu-Glu-Met-Leu-Ala-Pro-Tyr
-
-
-
additional information
?
-
the enzyme requires long peptide substrates. No hydroxylation of: Leu-Ala-Pro, Leu-Ala-Pro-Tyr, Leu-Glu-Met-Leu-Ala-Pro, and Leu-Glu-Met-Leu-Ala-Pro-Tyr
-
-
-
additional information
?
-
-
HIF prolyl-4-hydroxylase 2 substrate binding analysis using isolated sequences of the C-terminal oxygen degradation domain DLDLEALAP564YIPADDDFQL mutant M561A/M568A, and the N-terminal oxygen degradation domain DALTLLAP402AAGDTIISLDYG mutant F413Y, overview
-
-
-
additional information
?
-
-
substrate selectivity of PHD2 by kinetic competition assays, varied ionic strength, and global protein flexibility using amide H/D exchange, overview
-
-
-
additional information
?
-
the substrate contains a C-terminal and a N-terminal oxygen-dependent degradation domain, as well as a C-terminal transactivation domain
-
-
-
additional information
?
-
the substrate contains a C-terminal and a N-terminal oxygen-dependent degradation domain, as well as a C-terminal transactivation domain
-
-
-
additional information
?
-
the substrate contains a C-terminal and a N-terminal oxygen-dependent degradation domain, as well as a C-terminal transactivation domain
-
-
-
additional information
?
-
the subtrate contains a C-terminal and a N-terminal oxygen-dependent degradation domain, as well as a C-terminal transactivation domain
-
-
-
additional information
?
-
the subtrate contains a C-terminal and a N-terminal oxygen-dependent degradation domain, as well as a C-terminal transactivation domain
-
-
-
additional information
?
-
the subtrate contains a C-terminal and a N-terminal oxygen-dependent degradation domain, as well as a C-terminal transactivation domain
-
-
-
additional information
?
-
-
isozyme PHD2 is more active on hypoxia-inducible factor-1alpha than on hypoxia-inducible factor-2alpha, whereas PHD1 and PHD3 hydroxylate hypoxia-inducible factor-2alpha more efficiently
-
-
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
hypoxia-inducible factor 1 alpha-L-proline + 2-oxoglutarate + O2
hypoxia-inducible factor 1alpha-trans-4-hydroxy-L-proline + succinate + CO2
Q91YE2
-
-
-
?
hypoxia-inducible factor 1alpha-L-proline + 2-oxoglutarate + O2
hypoxia-inducible factor 1alpha-trans-4-hydroxy-L-proline + succinate + CO2
-
-
-
-
?
hypoxia-inducible factor-L-proline + 2-oxoglutarate + O2
hypoxia-inducible factor-(4R)-4-hydroxy-L-proline + succinate + CO2
hypoxia-inducible factor-L-proline + 2-oxoglutarate + O2
hypoxia-inducible factor-trans-4-hydroxy-L-proline + succinate + CO2
hypoxia-inducible factor-proline + 2-oxoglutarate + O2
hypoxia-inducible factor-(3S)-3-hydroxy-proline + succinate + CO2
-
HIF-1alpha
-
-
?
hypoxia-inducible factor-L-proline + 2-oxoglutarate + O2
hypoxia-inducible factor-(4R)-4-hydroxy-L-proline + succinate + CO2
Q9GZT9, Q9H6Z9
-
-
-
?
hypoxia-inducible factor-L-proline + 2-oxoglutarate + O2
hypoxia-inducible factor-(4R)-4-hydroxy-L-proline + succinate + CO2
-
HIF (hypoxia-inducible factor) is a transcription factor that plays a pivotal role in cellular adaptation to changes in oxygen availability. In the presence of oxygen, HIF is targeted for destruction by an E3 ubiquitin ligase containing the von Hippel-Lindau tumor suppressor protein (pVHL). Human pVHL binds to a short HIF-derived peptide when a conserved proline residue at the core of this peptide is hydroxylated. This protein modifiation may play a key role in mammalian oxygen sensing
-
-
?
hypoxia-inducible factor-L-proline + 2-oxoglutarate + O2
hypoxia-inducible factor-(4R)-4-hydroxy-L-proline + succinate + CO2
-
hypoxia-inducible factor (HIF) is a transcriptional complex that plays a central role in the regulation of gene expression by oxygen. In oxygenated and iron replete cells, HIF-alpha subunits are rapidly destroyed by a mechanism that involves ubiquitylation by the von Hippel-Lindau tumor suppressor (pVHL) E3 ligase complex. This process is suppressed by hypoxia and iron chelation, allowing transcriptional activation. The interaction between human pVHL and a specific domain of the HIF-1alpha subunit is regulated through hydroxylation of a proline residue (HIF-1alpha P564) by HIF-alpha prolyl-hydroxylase (HIF-PH). HIF-PH functions directly as a cellular oxygen sensor
-
-
?
hypoxia-inducible factor-L-proline + 2-oxoglutarate + O2
hypoxia-inducible factor-(4R)-4-hydroxy-L-proline + succinate + CO2
Q96KS0, Q9GZT9
mammalian cells respond to changes in oxygen availability through a conserved pathway that is regulated by the hypoxia-inducible factor (HIF). The alpha subunit of the hypoxia-inducible factor is targeted for degradation under normoxic conditions by a ubiquitin-ligase complex that recognizes a hydroxylated proline residue in hypoxia-inducible factor. HIF prolyl hydroxylase is responsible for this posttranslational modification
-
-
?
hypoxia-inducible factor-L-proline + 2-oxoglutarate + O2
hypoxia-inducible factor-(4R)-4-hydroxy-L-proline + succinate + CO2
Q96KS0, Q9GZT9
mammalian cells respond to changes in oxygen availability through a conserved pathway that is regulated by the hypoxia-inducible factor (HIF). The alpha subunit of the hypoxia-inducible factor is targeted for degradation under normoxic conditions by a ubiquitin-ligase complex that recognizes a hydroxylated proline residue in hypoxia-inducible factor. HIF prolyl is responsible for this posttranslational modification
-
-
?
hypoxia-inducible factor-L-proline + 2-oxoglutarate + O2
hypoxia-inducible factor-trans-4-hydroxy-L-proline + succinate + CO2
-
hypoxia-inducible factor 1alpha is hydroxylated at Pro402 and Pro564
-
-
?
hypoxia-inducible factor-L-proline + 2-oxoglutarate + O2
hypoxia-inducible factor-trans-4-hydroxy-L-proline + succinate + CO2
-
hypoxia-inducible factor 1alpha is hydroxylated at Pro402 and Pro564
-
-
?
hypoxia-inducible factor-L-proline + 2-oxoglutarate + O2
hypoxia-inducible factor-trans-4-hydroxy-L-proline + succinate + CO2
-
-
-
-
?
hypoxia-inducible factor-L-proline + 2-oxoglutarate + O2
hypoxia-inducible factor-trans-4-hydroxy-L-proline + succinate + CO2
Q96KS0, Q9GZT9, Q9H6Z9
-
-
-
?
hypoxia-inducible factor-L-proline + 2-oxoglutarate + O2
hypoxia-inducible factor-trans-4-hydroxy-L-proline + succinate + CO2
Q96KS0, Q9H6Z9
-
-
-
?
hypoxia-inducible factor-L-proline + 2-oxoglutarate + O2
hypoxia-inducible factor-trans-4-hydroxy-L-proline + succinate + CO2
-
-
-
-
?
hypoxia-inducible factor-L-proline + 2-oxoglutarate + O2
hypoxia-inducible factor-trans-4-hydroxy-L-proline + succinate + CO2
Q9GZT9
-
-
-
?
hypoxia-inducible factor-L-proline + 2-oxoglutarate + O2
hypoxia-inducible factor-trans-4-hydroxy-L-proline + succinate + CO2
-
-
-
-
?
hypoxia-inducible factor-L-proline + 2-oxoglutarate + O2
hypoxia-inducible factor-trans-4-hydroxy-L-proline + succinate + CO2
Q96KS0, Q9GZT9, Q9H6Z9
HIF1alpha is a better substrate than HIF2alpha for PHD2
-
-
?
hypoxia-inducible factor-L-proline + 2-oxoglutarate + O2
hypoxia-inducible factor-trans-4-hydroxy-L-proline + succinate + CO2
-
PHD enzymes hydroxylates HIF-alpha at prolyl residues present in the transcriptional activation domain N-TAD
-
-
?
hypoxia-inducible factor-L-proline + 2-oxoglutarate + O2
hypoxia-inducible factor-trans-4-hydroxy-L-proline + succinate + CO2
-
PHD2 hydroxylates Pro402 and/or Pro564 of HIF-1alpha
-
-
?
hypoxia-inducible factor-L-proline + 2-oxoglutarate + O2
hypoxia-inducible factor-trans-4-hydroxy-L-proline + succinate + CO2
A0A140EDB6
-
-
-
?
hypoxia-inducible factor-L-proline + 2-oxoglutarate + O2
hypoxia-inducible factor-trans-4-hydroxy-L-proline + succinate + CO2
-
-
-
-
?
hypoxia-inducible factor-L-proline + 2-oxoglutarate + O2
hypoxia-inducible factor-trans-4-hydroxy-L-proline + succinate + CO2
A0A0K0M9M3
-
-
-
?
additional information
?
-
-
HIF prolyl-4-hydroxylase 2 substrate binding analysis using isolated sequences of the C-terminal oxygen degradation domain DLDLEALAP564YIPADDDFQL mutant M561A/M568A, and the N-terminal oxygen degradation domain DALTLLAP402AAGDTIISLDYG mutant F413Y, overview
-
-
-
additional information
?
-
-
isozyme PHD2 is more active on hypoxia-inducible factor-1alpha than on hypoxia-inducible factor-2alpha, whereas PHD1 and PHD3 hydroxylate hypoxia-inducible factor-2alpha more efficiently
-
-
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Fe2+
Fe2+
-
required. the enzyme activity is inhibited by substitution of Fe2+ with Co2+ or Ni2+
Fe2+
the enzyme contains Fe2+; the enzyme contains Fe2+; the enzyme contains Fe2+
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
(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
-
-
-
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-(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-[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-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
3,6,9-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
5-hydroxy-6-[4-[2-oxo-2-(pyrrolidin-1-yl)ethyl]-1,3-thiazol-2-yl]pyridine-3-carbonitrile
-
-
-
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
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-(methoxyoxoacetyl)-glycine methyl ester
-
a pan-hydroxylase inhibitor, in vitro and in vivo inhibition
N-oxalyl-(2S)-alanine
-
competed by 2-oxoglutarate, no inhibition by the enantiomer N-oxalyl-(2R)-alanine
oxygen
the transiently overexpressed HPH-1 enzyme is inhibited by a low-oxygen environment
[(2E)-3-hydroxy-2-({[(naphthalen-2-yl)methanesulfonyl]acetyl}imino)-2,3-dihydro-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
-
-
-
1,1',1'',1'''-(1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrayl)tetrapropan-2-ol
-
noncompetitive inhibition
1,1',1'',1'''-(1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrayl)tetrapropan-2-ol
-
chelates Fe2+ in a hexacoordinative mode through four nitrogens of the macrocycle and two oxygens in side arms
6-[5-oxo-4-(1H-1,2,3-triazol-1-yl)-2,5-dihydro-1H-pyrazol-1-yl]pyridine-3-carboxylic acid
-
-
6-[5-oxo-4-(1H-1,2,3-triazol-1-yl)-2,5-dihydro-1H-pyrazol-1-yl]pyridine-3-carboxylic acid
;
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
-
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-benzyl-4-hydroxy-2-oxo-1,2-dihydroquinoline-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
-
-
[(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
-
-
[(4-hydroxy-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonyl)amino]acetic acid
;
additional information
-
the peptide inhibitors consist of amino acids identical to those in the CODD556-575 except the 564 proline residue, and target the C-terminal oxygen-dependent degradation domain binding site in the PHD2 active pocket. Specific inhibition of PHD2, no inhibition of FIH, EC 1.14.11.30
-
additional information
-
temporal dynamics of hydroxylase inhibition, overview
-
additional information
-
polynitrogen compound as HIF-1alpha PHD3 inhibitors, the metal complexes of these polynitrogen compounds cannot inhibit the catalytical activity of PHD3, overview. The inhibitory mechanism of PHD3 activity by polynitrogen compounds is due to their binding to iron to form stable coordination complexes
-
additional information
-
screening of iron chelators pyridines, hydroxypyrones/hydroxypyridinones, and catechols as inhibitors for PHD2, analysis of selectivity of the inhibitors for PHD2 compared to FIH, EC 1.14.11.30. Ligand binding kinetics and structural analysis, overview. Representative inhibitors bind to the metal center in PHD2 as an 2-oxoglutarate mimic
-
additional information
-
inhibition of the recombinant human PHD3 activity by tetraazamacrocycles, overview
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
ascorbate
activates, Km: 0.14 mM; activates, Km: 0.17 mM; activates, Km: 0.18 mM
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.000016 - 0.00094
hypoxia-inducible factor1alpha C-terminal oxygen-dependent degradation domain-L-proline
-
0.0047 - 0.023
hypoxia-inducible factor2alpha C-terminal oxygen-dependent degradation domain-L-proline
pH 7.5, 25°C, PHD3
-
0.001
hypoxia-inducible factor-L-proline
-
C-terminal oxygen degradation domain DLDLEALAP564YIPADDDFQL mutant M561A/M568A in absence of NaCl, pH 7.0, 37°C
0.0042
hypoxia-inducible factor-L-proline
-
C-terminal oxygen degradation domain DLDLEALAP564YIPADDDFQL mutant M561A/M568A in presence of 100 mM NaCl, pH 7.0, 37°C
0.011
hypoxia-inducible factor-L-proline
-
N-terminal oxygen degradation domain DALTLLAP402AAGDTIISLDYG mutant F413Y in presence of 100 mM NaCl, pH 7.0, 37°C
0.014
hypoxia-inducible factor-L-proline
-
N-terminal oxygen degradation domain DALTLLAP402AAGDTIISLDYG mutant F413Y in absence of NaCl, pH 7.0, 37°C
0.000016
hypoxia-inducible factor1alpha C-terminal oxygen-dependent degradation domain-L-proline
pH 7.5, 25°C, PHD3
-
0.00075 - 0.00094
hypoxia-inducible factor1alpha C-terminal oxygen-dependent degradation domain-L-proline
pH 7.5, 25°C, PHD2
-
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
-
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
-
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
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0012 - 0.0032
hypoxia-inducible factor1alpha C-terminal oxygen-dependent degradation domain-L-proline
-
0.0005
hypoxia-inducible factor2alpha C-terminal oxygen-dependent degradation domain-L-proline
pH 7.5, 25°C, PHD3
-
0.0101
hypoxia-inducible factor-L-proline
-
N-terminal oxygen degradation domain DALTLLAP402AAGDTIISLDYG mutant F413Y in absence of NaCl, pH 7.0, 37°C
0.0103
hypoxia-inducible factor-L-proline
-
N-terminal oxygen degradation domain DALTLLAP402AAGDTIISLDYG mutant F413Y in presence of 100 mM NaCl, pH 7.0, 37°C
0.0188
hypoxia-inducible factor-L-proline
-
C-terminal oxygen degradation domain DLDLEALAP564YIPADDDFQL mutant M561A/M568A in absence of NaCl, pH 7.0, 37°C
0.02
hypoxia-inducible factor-L-proline
-
C-terminal oxygen degradation domain DLDLEALAP564YIPADDDFQL mutant M561A/M568A in presence of 100 mM NaCl, pH 7.0, 37°C
0.0012
hypoxia-inducible factor1alpha C-terminal oxygen-dependent degradation domain-L-proline
pH 7.5, 25°C, PHD3
-
0.0032
hypoxia-inducible factor1alpha C-terminal oxygen-dependent degradation domain-L-proline
pH 7.5, 25°C, PHD2
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
45
2-oxoglutarate
-
mutant enzyme T387A, at pH 7.0 and 37°C; wild type isoform PHD2, at pH 7.0 and 37°C
0.72
hypoxia-inducible factor-L-proline
-
N-terminal oxygen degradation domain DALTLLAP402AAGDTIISLDYG mutant F413Y in absence of NaCl, pH 7.0, 37°C
0.94
hypoxia-inducible factor-L-proline
-
N-terminal oxygen degradation domain DALTLLAP402AAGDTIISLDYG mutant F413Y in presence of 100 mM NaCl, pH 7.0, 37°C
4.76
hypoxia-inducible factor-L-proline
-
C-terminal oxygen degradation domain DLDLEALAP564YIPADDDFQL mutant M561A/M568A in presence of 100 mM NaCl, pH 7.0, 37°C
18.8
hypoxia-inducible factor-L-proline
-
C-terminal oxygen degradation domain DLDLEALAP564YIPADDDFQL mutant M561A/M568A in absence of NaCl, pH 7.0, 37°C
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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
0.00249
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
0.00628
1,1',1'',1'''-(1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrayl)tetrapropan-2-ol
-
recombinant enzyme, pH 7.0, 37°C
0.067
1,1',1'',1'''-(1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrayl)tetrapropan-2-ol
-
recombinant enzyme, pH 7.0, 37°C
0.01
3-carboxy-4-oxo-3,4-dihydro-1,10-phenanthroline
pH 7.8, 37°C; pH 7.8, 37°C
0.0002
N-((3-hydroxy-6-chloroquinolin-2-yl)carbonyl)glycine
pH 7.8, 37°C; pH 7.8, 37°C
0.0008
N-((3-hydroxy-6-chloroquinolin-2-yl)carbonyl)glycine
pH 7.8, 37°C
additional information
additional information
Ki-values above 0.3 mM: pyridine-2,5-dicarboxylate and 3,4-dihydroxybenzoic acid; Ki-values above 0.3 mM: pyridine-2,5-dicarboxylate and 3,4-dihydroxybenzoic acid; Ki-values above 0.3 mM: pyridine-2,5-dicarboxylate and 3,4-dihydroxybenzoic acid
-
additional information
additional information
Ki-values above 0.3 mM: pyridine-2,5-dicarboxylate and 3,4-dihydroxybenzoic acid; Ki-values above 0.3 mM: pyridine-2,5-dicarboxylate and 3,4-dihydroxybenzoic acid; Ki-values above 0.3 mM: pyridine-2,5-dicarboxylate and 3,4-dihydroxybenzoic acid
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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
0.0004
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
0.0038
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
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
-
0.0000048
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
0.0207
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
0.0000016
tert-butyl 6-(5-oxo-4-(1H-1,2,3-triazol-1-yl)-2,5-dihydro-1H-pyrazol-1-yl)nicotinate
-
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
0.195
[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
-
0.0295
1,1',1'',1'''-(1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrayl)tetrapropan-2-ol
Homo sapiens
-
recombinant enzyme, pH 7.0, 37°C
0.0397
1,1',1'',1'''-(1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrayl)tetrapropan-2-ol
Homo sapiens
-
recombinant enzyme, pH 7.0, 37°C
0.0000022
N-oxalylglycine
Homo sapiens
-
isoform PHD2, pH and temperature not specified in the publication
0.0000022
N-oxalylglycine
Mus musculus
Q91UZ4, Q91YE3
isoform PHD2, pH and 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
-
0.0000016
tert-butyl 6-(5-oxo-4-(1H-1,2,3-triazol-1-yl)-2,5-dihydro-1H-pyrazol-1-yl)nicotinate
Mus musculus
Q91UZ4, Q91YE3
isoform PHD2, pH and temperature not specified in the publication
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
37
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
detected only in the initial stages of embryo development
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; the level of HIF-P4H-1 mRNA expression is highest in the adult brain, placenta, lung, and kidney; 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
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; the level of HIF-P4H-1 mRNA expression is highest in the adult brain, placenta, lung, and kidney
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; 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
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; the level of HIF-P4H-1 mRNA expression is highest in the adult brain, placenta, lung, and kidney; 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
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; 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
the level of HIF-P4H-1 mRNA expression is highest in the adult brain, placenta, lung, and kidney
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
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; 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
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
PDB
SCOP
CATH
ORGANISM
UNIPROT
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
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
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
?
-
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
?
-
x * 27785, QStar-XL hybrid quadrupole-TOF mass spectrometry; x * 27787, calculated from amino acid sequence
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
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; isoform PHD2 in complex with Mn2+, sitting drop vapor diffusion method, using 1.6 M sodium citrate/citric acid pH 6.5
-
isoform PHD2 in complex with Mn2+, sitting drop vapor diffusion method, using 1.6 M sodium citrate/citric acid pH 6.5
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
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
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 Trx- and His-tagged enzyme from Escherichia coli strain BL21(DE3)pLysS by nickel affinity chromatography to over 94% purity
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
expression in Spodoptera frugiperda Sf9 cells and Escherichia coli; expression in Spodoptera frugiperda Sf9 cells and Escherichia coli; expression in Spodoptera frugiperda Sf9 cells and Escherichia coli
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-(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
expression of PHD2 catalytic domain residues 177-426, expression of N-terminally GST-tagged PHD2 in Escherichia coli strain BL21(DE3)
-
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
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
after hypoxia treatment the enzyme expression is significantly increased in all analyzed tissues
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY
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
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
LINKS TO OTHER DATABASES (specific for EC-Number 1.14.11.29)
html completed
Use of this online version of BRENDA is free but requires a license. See terms of use.
Information
