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Literature summary extracted from

  • Hancock, R.L.; Masson, N.; Dunne, K.; Flashman, E.; Kawamura, A.
    The activity of JmjC histone lysine demethylase KDM4A is highly sensitive to oxygen concentrations (2017), ACS Chem. Biol., 12, 1011-1019 .
    View publication on PubMedView publication on EuropePMC

Application

EC Number Application Comment Organism
1.14.11.66 analysis KDM4A possesses the potential to act as an oxygen sensor in the context of chromatin modifications, with possible implications for epigenetic regulation in hypoxic disease states Homo sapiens
1.14.11.66 pharmacology KDM4A possesses the potential to act as an oxygen sensor in the context of chromatin modifications, with possible implications for epigenetic regulation in hypoxic disease states Homo sapiens
1.14.11.69 analysis KDM4A possesses the potential to act as an oxygen sensor in the context of chromatin modifications, with possible implications for epigenetic regulation in hypoxic disease states Homo sapiens

Cloned(Commentary)

EC Number Cloned (Comment) Organism
1.14.11.66 gene KDM4A, recombinant expression of N-terminally FLAG-tagged wild-type KDM4A or KDM4A H188A variant in U2OS cells and in HeLa cells, quantitative RT-PCR enzyme expression analysis, recombinant expression of N-terminally His6-tagged truncated KDM4A1-359 in Escherichia coli BL21(DE3) Homo sapiens
1.14.11.66 gene KDM4A, recombinant overexpression in U2O2 cells, recombinant expression of N-terminally FLAG-tagged KDM4A or KDM4A mutant H188A in HeLa cells, recombinant expression of N-terminally His6-tagged truncated KDM4A1-359 in Escherichia coli strain BL21(DE3) Homo sapiens
1.14.11.69 gene KDM4A, recombinant overexpression in U2O2 cells, recombinant expression of N-terminally FLAG-tagged KDM4A or KDM4A mutant H188A in HeLa cells, recombinant expression of N-terminally His6-tagged truncated KDM4A1-359 in Escherichia coli strain BL21(DE3) Homo sapiens

Protein Variants

EC Number Protein Variants Comment Organism
1.14.11.66 additional information generation of the truncated enzyme variant KDM4A1?359 Homo sapiens

Inhibitors

EC Number Inhibitors Comment Organism Structure
1.14.11.66 H2O2 loss of KDM4A activity in hypoxia resulting in changes to global histone lysine methylation Homo sapiens
1.14.11.69 H2O2 loss of KDM4A activity in hypoxia resulting in changes to global histone lysine methylation Homo sapiens

KM Value [mM]

EC Number KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
1.14.11.66 additional information
-
 additional information steady-state kinetic analysis of KDM4A1-359 with respect to 2-oxoglutarate and a 15mer histone peptide substrate H31-15K9me3 Homo sapiens
1.14.11.66 additional information
-
 additional information steady-state kinetics for H3K9 demethylation activity of the enzyme, overview Homo sapiens
1.14.11.66 0.0232
-
 H31-15K9me3 pH 7.5, 37°C, recombinant enzyme Homo sapiens
1.14.11.66 0.0232
-
 H31-15K9me3 pH and temperature not specified in the publication Homo sapiens
1.14.11.66 0.0247
-
 2-oxoglutarate pH 7.5, 37°C, recombinant enzyme Homo sapiens
1.14.11.66 0.0247
-
 2-oxoglutarate pH and temperature not specified in the publication Homo sapiens
1.14.11.66 0.173
-
 O2 pH 7.5, 37°C, recombinant enzyme Homo sapiens
1.14.11.66 0.173
-
 O2 pH and temperature not specified in the publication Homo sapiens

Metals/Ions

EC Number Metals/Ions Comment Organism Structure
1.14.11.66 Fe2+ required for catalysis Homo sapiens
1.14.11.69 Fe2+ required for catalysis Homo sapiens

Natural Substrates/ Products (Substrates)

EC Number Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
1.14.11.66 histone H3 N6,N6,N6-trimethyl-L-lysine9 + 2-oxoglutarate + O2 Homo sapiens
-
 histone H3 N6,N6-dimethyl-L-lysine9 + succinate + formaldehyde + CO2
-
 ?
1.14.11.66 [histone H3]-N6,N6,N6-trimethyl-L-lysine 9 + 2-oxoglutarate + O2 Homo sapiens
-
 [histone H3]-N6,N6-dimethyl-L-lysine 9 + succinate + formaldehyde + CO2
-
 ?
1.14.11.66 [histone H3]-N6,N6-dimethyl-L-lysine 9 + 2-oxoglutarate + O2 Homo sapiens
-
 [histone H3]-N6-methyl-L-lysine 9 + succinate + formaldehyde + CO2
-
 ?
1.14.11.69 [histone H3]-N6,N6,N6-trimethyl-L-lysine 36 + 2-oxoglutarate + O2 Homo sapiens
-
 [histone H3]-N6,N6-dimethyl-L-lysine 36 + succinate + formaldehyde + CO2
-
 ?
1.14.11.69 [histone H3]-N6,N6-dimethyl-L-lysine 36 + 2-oxoglutarate + O2 Homo sapiens
-
 [histone H3]-N6-methyl-L-lysine 36 + succinate + formaldehyde + CO2
-
 ?

Organism

EC Number Organism UniProt Comment Textmining
1.14.11.66 Homo sapiens O75164
-
-
1.14.11.69 Homo sapiens O75164
-
-

Purification (Commentary)

EC Number Purification (Comment) Organism
1.14.11.66 recombinant N-terminally His6-tagged truncated KDM4A1-359 from Escherichia coli BL21(DE3) by nickel affinity chromatography and gel filtration Homo sapiens
1.14.11.66 recombinant N-terminally His6-tagged truncated KDM4A1-359 from Escherichia coli strain BL21(DE3) by nickel affinity chromatography Homo sapiens
1.14.11.69 recombinant N-terminally His6-tagged truncated KDM4A1-359 from Escherichia coli strain BL21(DE3) by nickel affinity chromatography Homo sapiens

Source Tissue

EC Number Source Tissue Comment Organism Textmining
1.14.11.66 U2-OS cell
-
 Homo sapiens
-
1.14.11.69 U2-OS cell
-
 Homo sapiens
-

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
1.14.11.66 H31-15K9me3 + 2-oxoglutarate + O2
-
 Homo sapiens H31-15K9me2 + succinate + formaldehyde + CO2
-
 ?
1.14.11.66 H31-15K9me3 + 2-oxoglutarate + O2 a 15mer histone peptide substrate H31-15K9me3 Homo sapiens H31-15K9me2 + succinate + formaldehyde + CO2
-
 ?
1.14.11.66 histone H3 N6,N6,N6-trimethyl-L-lysine9 + 2-oxoglutarate + O2
-
 Homo sapiens histone H3 N6,N6-dimethyl-L-lysine9 + succinate + formaldehyde + CO2
-
 ?
1.14.11.66 additional information the enzyme KDM4A also seems to be active with histone H3 N6,N6,N6-trimethyl-L-lysine27 and histone H3 N6,N6,N6-trimethyl-L-lysine36 (EC 1.14.11.27), overview Homo sapiens ?
-
 ?
1.14.11.66 additional information the bifunctional enzyme is active on H3K9me3/me2 and H3K36me3/me2 substrates. The cellular activity of recombinant KDM4A against its primary substrate, H3K9me3, displays a graded response to depleting oxygen concentrations in line with the data obtained using isolated protein Homo sapiens ?
-
 ?
1.14.11.66 [histone H3]-N6,N6,N6-trimethyl-L-lysine 9 + 2-oxoglutarate + O2
-
 Homo sapiens [histone H3]-N6,N6-dimethyl-L-lysine 9 + succinate + formaldehyde + CO2
-
 ?
1.14.11.66 [histone H3]-N6,N6-dimethyl-L-lysine 9 + 2-oxoglutarate + O2
-
 Homo sapiens [histone H3]-N6-methyl-L-lysine 9 + succinate + formaldehyde + CO2
-
 ?
1.14.11.69 additional information the bifunctional enzyme is active on H3K9me3/me2 and H3K36me3/me2 substrates. The cellular activity of recombinant KDM4A against its primary substrate, H3K9me3, displays a graded response to depleting oxygen concentrations in line with the data obtained using isolated protein Homo sapiens ?
-
 ?
1.14.11.69 [histone H3]-N6,N6,N6-trimethyl-L-lysine 36 + 2-oxoglutarate + O2
-
 Homo sapiens [histone H3]-N6,N6-dimethyl-L-lysine 36 + succinate + formaldehyde + CO2
-
 ?
1.14.11.69 [histone H3]-N6,N6-dimethyl-L-lysine 36 + 2-oxoglutarate + O2
-
 Homo sapiens [histone H3]-N6-methyl-L-lysine 36 + succinate + formaldehyde + CO2
-
 ?

Synonyms

EC Number Synonyms Comment Organism
1.14.11.66 JmjC histone lysine demethylase
-
 Homo sapiens
1.14.11.66 JMJD2A
-
 Homo sapiens
1.14.11.66 KDM4A
-
 Homo sapiens
1.14.11.66 More see also EC 1.14.11.69 Homo sapiens
1.14.11.69 JmjC histone lysine demethylase
-
 Homo sapiens
1.14.11.69 JMJD2A
-
 Homo sapiens
1.14.11.69 KDM4A
-
 Homo sapiens
1.14.11.69 More see also EC 1.14.11.66 Homo sapiens

Temperature Optimum [°C]

EC Number Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
1.14.11.66 37
-
 assay at Homo sapiens
1.14.11.69 37
-
 assay at Homo sapiens

pH Optimum

EC Number pH Optimum Minimum pH Optimum Maximum Comment Organism
1.14.11.66 7.5
-
 assay at Homo sapiens
1.14.11.69 7.5
-
 assay at Homo sapiens

Cofactor

EC Number Cofactor Comment Organism Structure
1.14.11.66 additional information alteration of multiple H3 methylation marks by KDM4A at different oxygen concentrations, overview Homo sapiens
1.14.11.69 additional information alteration of multiple H3 methylation marks by KDM4A at different oxygen concentrations, overview Homo sapiens

General Information

EC Number General Information Comment Organism
1.14.11.66 malfunction the percentage loss of H3K9me3 in KDM4A-induced U2OS cells at 1% O2 is relatively consistent with loss of H3K9me3 found in HeLa cells transiently transfected with KDM4A (50% compared with 40%, respectively), indicating a similar effect of hypoxia on KDM4A activity in different cell lines Homo sapiens
1.14.11.66 metabolism KDM4A possesses the potential to act as an oxygen sensor in the context of epigenetic regulation Homo sapiens
1.14.11.66 additional information cellular demethylase activity of KDM4A demonstrates a graded response to oxygen concentration in U2OS cells. Analysis of the H3K27me3 (cf. EC 1.14.11.68) mark shows loss of this mark upon overexpression of KDM4A in normoxia, with a graded response to oxygen similar to that seen for H3K9me3, although less-pronounced. H3K27me3 is not a canonical substrate for KDM4A, hence, loss of this mark cannot be directly attributed to catalytic KDM4A activity. Effect of oxygen availability on the activity of the KDM4 subfamily member KDM4A, overview. A high level of O2 sensitivity both with isolated protein and in cells is observed Homo sapiens
1.14.11.66 physiological function the JmjC histone lysine demethylases (KDMs) are epigenetic regulators involved in the removal of methyl groups from post-translationally modified lysyl residues within histone tails, modulating gene transcription. The activity of some KDMs, including the pseudogene-encoded KDM4E, may be sensitive to changing oxygen concentrations, U2OS cells conditionally overexpressing KDM4A show that the cellular activity of KDM4A against its primary substrate, H3K9me3, displays a graded response to depleting oxygen concentrations in line with the data obtained using isolated protein. KDM4A possesses the potential to act as an oxygen sensor in the context of chromatin modifications, with possible implications for epigenetic regulation in hypoxic disease states Homo sapiens
1.14.11.66 physiological function the JmjC histone lysine demethylases (KDMs) are epigenetic regulators involved in the removal of methyl groups from post-translationally modified lysyl residues within histone tails, modulating gene transcription Homo sapiens
1.14.11.69 metabolism KDM4A possesses the potential to act as an oxygen sensor in the context of epigenetic regulation Homo sapiens
1.14.11.69 additional information cellular demethylase activity of KDM4A demonstrates a graded response to oxygen concentration in U2OS cells. Analysis of the H3K27me3 (cf. EC 1.14.11.68) mark shows loss of this mark upon overexpression of KDM4A in normoxia, with a graded response to oxygen similar to that seen for H3K9me3, although less-pronounced. H3K27me3 is not a canonical substrate for KDM4A, hence, loss of this mark cannot be directly attributed to catalytic KDM4A activity. Effect of oxygen availability on the activity of the KDM4 subfamily member KDM4A, overview. A high level of O2 sensitivity both with isolated protein and in cells is observed Homo sapiens
1.14.11.69 physiological function the JmjC histone lysine demethylases (KDMs) are epigenetic regulators involved in the removal of methyl groups from post-translationally modified lysyl residues within histone tails, modulating gene transcription Homo sapiens