Activating Compound | Comment | Organism | Structure |
---|---|---|---|
ascorbate | - |
Homo sapiens |
Cloned (Comment) | Organism |
---|---|
expression of N-terminally MBP-tagged PHD3 in Escherichia coli strain BL21(DE3)pRR692 | Homo sapiens |
expression of PHD1-(1-407) in Spodoptera frugiperda Sf9 cells using the baculovirus expression vector, expression of His- and Strep-tagged tobacco etch virus-PHD1 in Escherichia coli strain BL21(DE3)pRR692 | Homo sapiens |
expression of PHD2-(1-426) in Spodoptera frugiperda Sf9 cells uing the baculovirus expression vector, expression of His- and Strep-tagged tobacco etch virus-PHD2 in Escherichia coli strain BL21(DE3)pRR692 | Homo sapiens |
KM Value [mM] | KM Value Maximum [mM] | Substrate | Comment | Organism | Structure |
---|---|---|---|---|---|
additional information | - |
additional information | steady-state kinetic analysis and substrate selectivity for hypoxia-inducible factor and 2-oxoglutarate | Homo sapiens | |
0.000016 | - |
hypoxia-inducible factor1alpha C-terminal oxygen-dependent degradation domain-L-proline | pH 7.5, 25°C, PHD3 | Homo sapiens | |
0.00075 | 0.00094 | hypoxia-inducible factor1alpha C-terminal oxygen-dependent degradation domain-L-proline | pH 7.5, 25°C, PHD2 | Homo sapiens | |
0.0047 | 0.023 | hypoxia-inducible factor2alpha C-terminal oxygen-dependent degradation domain-L-proline | pH 7.5, 25°C, PHD3 | Homo sapiens |
Metals/Ions | Comment | Organism | Structure |
---|---|---|---|
Fe2+ | dependent on | Homo sapiens |
Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
---|---|---|---|---|---|---|
hypoxia-inducible factor-L-proline + 2-oxoglutarate + O2 | Homo sapiens | - |
hypoxia-inducible factor-trans-4-hydroxy-L-proline + succinate + CO2 | - |
? | |
hypoxia-inducible factor-L-proline + 2-oxoglutarate + O2 | Homo sapiens | HIF1alpha is a better substrate than HIF2alpha for PHD2 | hypoxia-inducible factor-trans-4-hydroxy-L-proline + succinate + CO2 | - |
? |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Homo sapiens | Q96KS0 | isozyme PHD1 | - |
Homo sapiens | Q9GZT9 | isozyme PHD2 | - |
Homo sapiens | Q9H6Z9 | isozyme PHD3 | - |
Purification (Comment) | Organism |
---|---|
recombinant His- and Strep-tagged tobacco etch virus-PHD1 from Escherichia coli strain BL21(DE3)pRR692 by nickel affinity and avidin affinity chromatography | Homo sapiens |
recombinant His- and Strep-tagged tobacco etch virus-PHD2 from Escherichia coli strain BL21(DE3)pRR692 by nickel affinity and avidin affinity chromatography | Homo sapiens |
recombinant N-terminally MBP-tagged PHD3 from Escherichia coli strain BL21(DE3)pRR692 by amylosse affinity chromatography | Homo sapiens |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
hypoxia-inducible factor-L-proline + 2-oxoglutarate + O2 | - |
Homo sapiens | hypoxia-inducible factor-trans-4-hydroxy-L-proline + succinate + CO2 | - |
? | |
hypoxia-inducible factor-L-proline + 2-oxoglutarate + O2 | HIF1alpha is a better substrate than HIF2alpha for PHD2 | Homo sapiens | hypoxia-inducible factor-trans-4-hydroxy-L-proline + succinate + CO2 | - |
? | |
hypoxia-inducible factor-L-proline + 2-oxoglutarate + O2 | differential regulation of HIF1alpha and HIF2alpha at the N-terminal oxygen-dependent degradation domain site by PHD2 | Homo sapiens | hypoxia-inducible factor-trans-4-hydroxy-L-proline + succinate + CO2 | - |
? | |
hypoxia-inducible factor-L-proline + 2-oxoglutarate + O2 | the HIF1alpha C-terminal oxygen-dependent degradation domain is highly preferred for hydroxylation, no N-terminal oxygen-dependent degradation domain hydroxylation for both HIF2alpha and HIF1alpha | Homo sapiens | hypoxia-inducible factor-trans-4-hydroxy-L-proline + succinate + CO2 | - |
? | |
hypoxia-inducible factor-L-proline + 2-oxoglutarate + O2 | the PHD1 reaction at the N-terminal oxygen-dependent degradation domain site shows low level hydroxylation | Homo sapiens | hypoxia-inducible factor-trans-4-hydroxy-L-proline + succinate + CO2 | - |
? | |
hypoxia-inducible factor1alpha C-terminal oxygen-dependent degradation domain-L-proline + 2-oxoglutarate + O2 | - |
Homo sapiens | hypoxia-inducible factor1alpha C-terminal oxygen-dependent degradation domain-trans-4-hydroxy-L-proline + succinate + CO2 | - |
? | |
hypoxia-inducible factor1alpha C-terminal oxygen-dependent degradation domain-L-proline + 2-oxoglutarate + O2 | low activity | Homo sapiens | hypoxia-inducible factor1alpha C-terminal oxygen-dependent degradation domain-trans-4-hydroxy-L-proline + succinate + CO2 | - |
? | |
hypoxia-inducible factor1alpha N-terminal oxygen-dependent degradation domain-L-proline + 2-oxoglutarate + O2 | - |
Homo sapiens | hypoxia-inducible factor1alpha N-terminal oxygen-dependent degradation domain-trans-4-hydroxy-L-proline + succinate + CO2 | - |
? | |
hypoxia-inducible factor1alpha N-terminal oxygen-dependent degradation domain-L-proline + 2-oxoglutarate + O2 | low activity | Homo sapiens | hypoxia-inducible factor1alpha N-terminal oxygen-dependent degradation domain-trans-4-hydroxy-L-proline + succinate + CO2 | - |
? | |
hypoxia-inducible factor2alpha C-terminal oxygen dependent degradation domain-L-proline + 2-oxoglutarate + O2 | - |
Homo sapiens | hypoxia-inducible factor2alpha C-terminal oxygen dependent degradation domain-trans-4-hydroxy-L-proline + succinate + CO2 | - |
? | |
hypoxia-inducible factor2alpha C-terminal oxygen-dependent degradation domain-L-proline + 2-oxoglutarate + O2 | - |
Homo sapiens | hypoxia-inducible factor2alpha C-terminal oxygen-dependent degradation domain-trans-4-hydroxy-L-proline + succinate + CO2 | - |
? | |
hypoxia-inducible factor2alpha N-terminal oxygen dependent degradation domain-L-proline + 2-oxoglutarate + O2 | - |
Homo sapiens | hypoxia-inducible factor2alpha N-terminal oxygen dependent degradation domain-trans-4-hydroxy-L-proline + succinate + CO2 | - |
? | |
additional information | the substrate contains a C-terminal and a N-terminal oxygen-dependent degradation domain, as well as a C-terminal transactivation domain | Homo sapiens | ? | - |
? | |
additional information | the subtrate contains a C-terminal and a N-terminal oxygen-dependent degradation domain, as well as a C-terminal transactivation domain | Homo sapiens | ? | - |
? |
Synonyms | Comment | Organism |
---|---|---|
HIF hydroxylase | - |
Homo sapiens |
PHD1 | - |
Homo sapiens |
PHD2 | - |
Homo sapiens |
PHD3 | - |
Homo sapiens |
prolyl hydroxylase domain | - |
Homo sapiens |
Temperature Optimum [°C] | Temperature Optimum Maximum [°C] | Comment | Organism |
---|---|---|---|
25 | - |
assay at | Homo sapiens |
Turnover Number Minimum [1/s] | Turnover Number Maximum [1/s] | Substrate | Comment | Organism | Structure |
---|---|---|---|---|---|
0.0005 | - |
hypoxia-inducible factor2alpha C-terminal oxygen-dependent degradation domain-L-proline | pH 7.5, 25°C, PHD3 | Homo sapiens | |
0.0012 | - |
hypoxia-inducible factor1alpha C-terminal oxygen-dependent degradation domain-L-proline | pH 7.5, 25°C, PHD3 | Homo sapiens | |
0.0032 | - |
hypoxia-inducible factor1alpha C-terminal oxygen-dependent degradation domain-L-proline | pH 7.5, 25°C, PHD2 | Homo sapiens |
pH Optimum Minimum | pH Optimum Maximum | Comment | Organism |
---|---|---|---|
7.5 | - |
assay at | Homo sapiens |
General Information | Comment | Organism |
---|---|---|
evolution | the enzyme belongs to the of the 2-oxoglutarate- and iron-dependent dioxygenase family of enzymes | Homo sapiens |
physiological function | the prolyl hydroxylases control the abundance of hypoxia-inducible factor through oxygen-dependent hydroxylation of specific proline residues in hypoxia-inducible factor proteins, triggering subsequent ubiquitination and proteasomal degradation | Homo sapiens |
physiological function | the prolyl hydroxylases control the abundance of hypoxia-inducible factor through oxygen-dependent hydroxylation of specific proline residues in hypoxia-inducible factor proteins, triggering subsequent ubiquitination and proteasomal degradation. Differential regulation of HIF1alpha and HIF2alpha at the NODDD site by PHD2 | Homo sapiens |