Literature summary for 1.14.11.66 extracted from

Hillringhaus, L.; Yue, W.W.; Rose, N.R.; Ng, S.S.; Gileadi, C.; Loenarz, C.; Bello, S.H.; Bray, J.E.; Schofield, C.J.; Oppermann, U.
Structural and evolutionary basis for the dual substrate selectivity of human KDM4 histone demethylase family (2011), J. Biol. Chem., 286, 41616-41625 .

Search for more literature for 1.14.11.66

Cloned(Commentary)

Cloned (Comment)	Organism
gene KDM4A, phylogenetic analysis, recombinant expression of N-terminally His-tagged KDM4A catalytic domain in Escherichia coli	Homo sapiens
gene KDM4B, phylogenetic analysis, recombinant expression of N-terminally His-tagged KDM4B catalytic domain in Escherichia coli	Homo sapiens
gene KDM4C, phylogenetic analysis, recombinant expression of N-terminally His-tagged KDM4C catalytic domain in Escherichia coli	Homo sapiens
gene KDM4D, phylogenetic analysis, recombinant expression of N-terminally His-tagged KDM4D catalytic domain in Escherichia coli	Homo sapiens
gene KDM4E, phylogenetic analysis, recombinant expression of N-terminally His-tagged KDM4E catalytic domain in Escherichia coli	Homo sapiens

Crystallization (Commentary)

Crystallization (Comment)	Organism
purified recombinant enzyme in complex with inhibitor, sitting drop vapor diffusion method, mixing of 10 mg/ml protein and 2.5 mM 2,4-pyridinedicarboxylic acid with well solution, containing 20% v/v PEG 3350, 0.1 M sodium citrate, pH 5.5, and 2 mM NiCl2, in a 2:1 ratio, 4°C, X-ray diffraction structure determination and analysis at 2.1 A resolution. The zinc-binding site in KDM4E is disordered possibly due to loss of zinc in the crystallization process	Homo sapiens
purified recombinant enzyme in complex with inhibitor, sitting drop vapor diffusion method, mixing of 7 mg/ml protein and 2 mM N-oxalylglycine with well solution, containing 25% v/v PEG 3350, 0.2 M sodium nitrate, 0.1 M bis-tris propane, pH 6.5, 5% v/v ethylene glycol, 0.01 M NiCl2, in a 2:1 ratio, 4°C, X-ray diffraction structure determination and analysis at 2.55 A resolution	Homo sapiens

Crystallization (Comment)

Organism

purified recombinant enzyme in complex with inhibitor, sitting drop vapor diffusion method, mixing of 10 mg/ml protein and 2.5 mM 2,4-pyridinedicarboxylic acid with well solution, containing 20% v/v PEG 3350, 0.1 M sodium citrate, pH 5.5, and 2 mM NiCl2, in a 2:1 ratio, 4°C, X-ray diffraction structure determination and analysis at 2.1 A resolution. The zinc-binding site in KDM4E is disordered possibly due to loss of zinc in the crystallization process

Homo sapiens

purified recombinant enzyme in complex with inhibitor, sitting drop vapor diffusion method, mixing of 7 mg/ml protein and 2 mM N-oxalylglycine with well solution, containing 25% v/v PEG 3350, 0.2 M sodium nitrate, 0.1 M bis-tris propane, pH 6.5, 5% v/v ethylene glycol, 0.01 M NiCl2, in a 2:1 ratio, 4°C, X-ray diffraction structure determination and analysis at 2.55 A resolution

Homo sapiens

KM Value [mM]

KM Value [mM]	KM Value Maximum [mM]	Substrate	Comment	Organism
0.023	-	[histone H3]-N6,N6,N6-trimethyl-L-lysine 9	pH and temperature not specified in the publication, recombinant isozyme KDM4E	Homo sapiens
0.025	-	[histone H3]-N6,N6-dimethyl-L-lysine 9	pH and temperature not specified in the publication, recombinant isozyme KDM4E	Homo sapiens
0.031	-	[histone H3]-N6,N6,N6-trimethyl-L-lysine 9	pH and temperature not specified in the publication, recombinant isozyme KDM4B	Homo sapiens
0.037	-	[histone H3]-N6,N6,N6-trimethyl-L-lysine 9	pH and temperature not specified in the publication, recombinant isozyme KDM4D	Homo sapiens
0.045	-	[histone H3]-N6,N6,N6-trimethyl-L-lysine 9	pH and temperature not specified in the publication, recombinant isozyme KDM4A	Homo sapiens
0.048	-	[histone H3]-N6,N6,N6-trimethyl-L-lysine 9	pH and temperature not specified in the publication, recombinant isozyme KDM4C	Homo sapiens
0.05	-	[histone H3]-N6,N6-dimethyl-L-lysine 9	pH and temperature not specified in the publication, recombinant isozyme KDM4B	Homo sapiens
0.066	-	[histone H3]-N6,N6-dimethyl-L-lysine 9	pH and temperature not specified in the publication, recombinant isozyme KDM4C	Homo sapiens
0.073	-	[histone H3]-N6,N6-dimethyl-L-lysine 9	pH and temperature not specified in the publication, recombinant isozyme KDM4A	Homo sapiens
0.074	-	[histone H3]-N6,N6-dimethyl-L-lysine 9	pH and temperature not specified in the publication, recombinant isozyme KDM4D	Homo sapiens

Metals/Ions

Metals/Ions	Comment	Organism	Structure
Fe2+	required	Homo sapiens
Zn2+	comparison of the Zn(II)-binding site	Homo sapiens

Natural Substrates/ Products (Substrates)

Natural Substrates	Organism	Comment (Nat. Sub.)	Natural Products	Comment (Nat. Pro.)	Rev.
additional information	Homo sapiens	the enzyme acts on H3K9me3/me2, but not on H3K36 substrates	?	-	?
[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	-	?
[histone H3]-N6,N6-dimethyl-L-lysine 9 + 2-oxoglutarate + O2	Homo sapiens	-	[histone H3]-N6-methyl-L-lysine 9 + succinate + formaldehyde + CO2	-	?

Organism

Organism	UniProt	Comment	Textmining
Homo sapiens	B2RXH2	-	-
Homo sapiens	O75164	-	-
Homo sapiens	O94953	-	-
Homo sapiens	Q6B0I6	-	-
Homo sapiens	Q9H3R0	-	-

Purification (Commentary)

Purification (Comment)	Organism
recombinant N-terminally His-tagged KDM4A catalytic domain from Escherichia coli	Homo sapiens

Substrates and Products (Substrate)

Substrates	Comment Substrates	Organism	Products	Comment (Products)	Rev.
additional information	the enzyme acts on H3K9me3/me2, but not on H3K36 substrates	Homo sapiens	?	-	?
additional information	bifunctional KDM4A catalyzes demethylation of tri- and di-methylated forms of both histone H3 lysine 9 (H3K9me3/me2) and lysine 36 (H3K36me3/me2). Enzyme KDM4A preferentially catalyzes demethylation at Lys9 rather than Lys36 under identical conditions. Demethylation of H3K9me3 to H3K9me0 is observed on prolonged incubation of 15-residue H3K9me3 peptides	Homo sapiens	?	-	?
additional information	bifunctional KDM4A catalyzes demethylation of tri- and di-methylated forms of both histone H3 lysine 9 (H3K9me3/me2) and lysine 36 (H3K36me3/me2). Enzyme KDM4B preferentially catalyzes demethylation at Lys9 rather than Lys36 under identical conditions. Demethylation of H3K9me3 to H3K9me0 is observed on prolonged incubation of 15-residue H3K9me3 peptides	Homo sapiens	?	-	?
additional information	bifunctional KDM4A catalyzes demethylation of tri- and di-methylated forms of both histone H3 lysine 9 (H3K9me3/me2) and lysine 36 (H3K36me3/me2). Enzyme KDM4C preferentially catalyzes demethylation at Lys9 rather than Lys36 under identical conditions. Demethylation of H3K9me3 to H3K9me0 is observed on prolonged incubation of 15-residue H3K9me3 peptides	Homo sapiens	?	-	?
additional information	the enzyme acts on tri- and di-methylated forms of H3K9, but not on H3K36 substrates. Demethylation of H3K9me3 to H3K9me0 is observed on prolonged incubation of 15-residue H3K9me3 peptides	Homo sapiens	?	-	?
[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	-	?
[histone H3]-N6,N6-dimethyl-L-lysine 9 + 2-oxoglutarate + O2	-	Homo sapiens	[histone H3]-N6-methyl-L-lysine 9 + succinate + formaldehyde + CO2	-	?

Synonyms

Synonyms	Comment	Organism
JMJD2A	-	Homo sapiens
JMJD2B	-	Homo sapiens
JMJD2C	-	Homo sapiens
KDM4A	-	Homo sapiens
KDM4B	-	Homo sapiens
Kdm4c	-	Homo sapiens
KDM4D	-	Homo sapiens
KDM4E	-	Homo sapiens
More	see also EC 1.14.11.69	Homo sapiens

Turnover Number [1/s]

Turnover Number Minimum [1/s]	Turnover Number Maximum [1/s]	Substrate	Comment	Organism
0.0029	-	[histone H3]-N6,N6-dimethyl-L-lysine 9	pH and temperature not specified in the publication, recombinant isozyme KDM4A	Homo sapiens
0.01	-	[histone H3]-N6,N6,N6-trimethyl-L-lysine 9	pH and temperature not specified in the publication, recombinant isozyme KDM4A	Homo sapiens
0.012	-	[histone H3]-N6,N6-dimethyl-L-lysine 9	pH and temperature not specified in the publication, recombinant isozyme KDM4D	Homo sapiens
0.015	-	[histone H3]-N6,N6,N6-trimethyl-L-lysine 9	pH and temperature not specified in the publication, recombinant isozyme KDM4D	Homo sapiens
0.028	-	[histone H3]-N6,N6,N6-trimethyl-L-lysine 9	pH and temperature not specified in the publication, recombinant isozyme KDM4B	Homo sapiens
0.029	-	[histone H3]-N6,N6,N6-trimethyl-L-lysine 9	pH and temperature not specified in the publication, recombinant isozyme KDM4C	Homo sapiens
0.05	-	[histone H3]-N6,N6-dimethyl-L-lysine 9	pH and temperature not specified in the publication, recombinant isozyme KDM4B	Homo sapiens
0.065	-	[histone H3]-N6,N6-dimethyl-L-lysine 9	pH and temperature not specified in the publication, recombinant isozyme KDM4E	Homo sapiens
0.072	-	[histone H3]-N6,N6-dimethyl-L-lysine 9	pH and temperature not specified in the publication, recombinant isozyme KDM4C	Homo sapiens
0.076	-	[histone H3]-N6,N6,N6-trimethyl-L-lysine 9	pH and temperature not specified in the publication, recombinant isozyme KDM4E	Homo sapiens

General Information

General Information	Comment	Organism
evolution	the enzyme belongs to the KDM4/JmjC demethylase histone demethylase family. KDM4F is very similar to KDM4E sharing 94% identity over 369 residues. The selectivity of KDM4 enzymes is determined by multiple interactions within the catalytic domain but outside the active site. Evolutionary analysis of the KDM4 demethylase subfamily	Homo sapiens
evolution	the enzyme belongs to the KDM4/JmjC demethylase histone demethylase family. The selectivity of KDM4 enzymes is determined by multiple interactions within the catalytic domain but outside the active site. All KDM4 subfamily members have highly conserved residues lining the methylammonium-binding pocket. The exceptions are Ser288A/Ser-289B/Ser290C and Thr289A/Thr290B/Thr291C in KDM4A, B, and C, which are substituted by Ala287D/Ala289E/Ala286F and Ile288D/Ile290E/Ile287F in KDM4D-F, respectively. Evolutionary analysis of the KDM4 demethylase subfamily	Homo sapiens
evolution	the enzyme belongs to the KDM4/JmjC demethylase histone demethylase family. The selectivity of KDM4 enzymes is determined by multiple interactions within the catalytic domain but outside the active site. Evolutionary analysis of the KDM4 demethylase subfamily	Homo sapiens
evolution	the enzyme belongs to the KDM4/JmjC demethylase histone demethylase family. The selectivity of KDM4 enzymes is determined by multiple interactions within the catalytic domain but outside the active site. Evolutionary analysis of the KDM4 demethylase subfamily, a KDM4D type activity is important in eutherian biology	Homo sapiens
additional information	enzyme structure-function relationships and substrate selectivity, comparisons of KDM4 enzymes, overview	Homo sapiens

kcat/KM [mM/s]

kcat/KM Value [1/mMs^-1]	kcat/KM Value Maximum [1/mMs^-1]	Substrate	Comment	Organism
0.0397	-	[histone H3]-N6,N6-dimethyl-L-lysine 9	pH and temperature not specified in the publication, recombinant isozyme KDM4A	Homo sapiens
0.162	-	[histone H3]-N6,N6-dimethyl-L-lysine 9	pH and temperature not specified in the publication, recombinant isozyme KDM4D	Homo sapiens
0.222	-	[histone H3]-N6,N6,N6-trimethyl-L-lysine 9	pH and temperature not specified in the publication, recombinant isozyme KDM4A	Homo sapiens
0.405	-	[histone H3]-N6,N6,N6-trimethyl-L-lysine 9	pH and temperature not specified in the publication, recombinant isozyme KDM4D	Homo sapiens
0.604	-	[histone H3]-N6,N6,N6-trimethyl-L-lysine 9	pH and temperature not specified in the publication, recombinant isozyme KDM4C	Homo sapiens
0.903	-	[histone H3]-N6,N6,N6-trimethyl-L-lysine 9	pH and temperature not specified in the publication, recombinant isozyme KDM4B	Homo sapiens
1	-	[histone H3]-N6,N6-dimethyl-L-lysine 9	pH and temperature not specified in the publication, recombinant isozyme KDM4B	Homo sapiens
1.09	-	[histone H3]-N6,N6-dimethyl-L-lysine 9	pH and temperature not specified in the publication, recombinant isozyme KDM4C	Homo sapiens
2.6	-	[histone H3]-N6,N6-dimethyl-L-lysine 9	pH and temperature not specified in the publication, recombinant isozyme KDM4E	Homo sapiens
3.304	-	[histone H3]-N6,N6,N6-trimethyl-L-lysine 9	pH and temperature not specified in the publication, recombinant isozyme KDM4E	Homo sapiens