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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.
    View publication on PubMedView publication on EuropePMC

Cloned(Commentary)

Cloned (Comment) Organism
expression of N-terminally His-tagged KDM4A in Escherichia coli Homo sapiens
expression of N-terminally His-tagged KDM4B in Escherichia coli Homo sapiens
expression of N-terminally His-tagged KDM4C in Escherichia coli Homo sapiens
expression of N-terminally His-tagged KDM4D in Escherichia coli Homo sapiens
expression of N-terminally His-tagged KDM4E in Escherichia coli Homo sapiens

Crystallization (Commentary)

Crystallization (Comment) Organism
purified recombinant KDM4C, sitting drop vapor diffusion method, mixing of 7 mg/ml protein with 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

Protein Variants

Protein Variants Comment Organism
I71L KDM4E mutant, no demethylation of H3K9me2, but the mutant demethylates H3K9me3 to H3K9me2 and H3K9me1 in a similar manner to wild-type KDM4A Homo sapiens
I87K KDM4E mutant, no demethylation of H3K9me2, but the mutant demethylates H3K9me3 to H3K9me2 and H3K9me1 in a similar manner to wild-type KDM4A Homo sapiens
N86H KDM4E mutant, no demethylation of H3K9me2, but the mutant demethylates H3K9me3 to H3K9me2 and H3K9me1 in a similar manner to wild-type KDM4A Homo sapiens
Q88K KDM4E mutant, the mutant shows demethylation of H3K9me2, and the mutant demethylates H3K9me3 to H3K9me2 and H3K9me1 in a similar manner to wild-type KDM4A Homo sapiens
R309G KDM4E mutant, poor demethylation of H3K9me2, but the mutant demethylates H3K9me3 to H3K9me2 and H3K9me1 in a similar manner to wild-type KDM4A Homo sapiens

KM Value [mM]

KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
0.023
-
histone H3 N6,N6,N6-trimethyl-L-lysine9 KDM4E, pH and temperature not specified in the publication Homo sapiens
0.025
-
histone H3 N6,N6-dimethyl-L-lysine9 KDM4E, pH and temperature not specified in the publication Homo sapiens
0.031
-
histone H3 N6,N6,N6-trimethyl-L-lysine9 KDM4B, pH and temperature not specified in the publication Homo sapiens
0.037
-
histone H3 N6,N6,N6-trimethyl-L-lysine9 KDM4D, pH and temperature not specified in the publication Homo sapiens
0.045
-
histone H3 N6,N6,N6-trimethyl-L-lysine9 KDM4A, pH and temperature not specified in the publication Homo sapiens
0.048
-
histone H3 N6,N6,N6-trimethyl-L-lysine9 KDM4C, pH and temperature not specified in the publication Homo sapiens
0.05
-
histone H3 N6,N6-dimethyl-L-lysine9 KDM4B, pH and temperature not specified in the publication Homo sapiens
0.066
-
histone H3 N6,N6-dimethyl-L-lysine9 KDM4C, pH and temperature not specified in the publication Homo sapiens
0.073
-
histone H3 N6,N6-dimethyl-L-lysine9 KDM4A, pH and temperature not specified in the publication Homo sapiens
0.074
-
histone H3 N6,N6-dimethyl-L-lysine9 KDM4D, pH and temperature not specified in the publication Homo sapiens

Localization

Localization Comment Organism GeneOntology No. Textmining
nucleus
-
Homo sapiens 5634
-

Metals/Ions

Metals/Ions Comment Organism Structure
Zn2+ structure of Zn2+ binding sites of the isozymes, overview Homo sapiens

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
histone H3 N6,N6,N6-trimethyl-L-lysine9 + 2-oxoglutarate + O2 Homo sapiens
-
histone H3 N6,N6-dimethyl-L-lysine9 + succinate + formaldehyde + CO2
-
?
histone H3 N6,N6-dimethyl-L-lysine9 + 2-oxoglutarate + O2 Homo sapiens
-
histone H3 N6-methyl-L-lysine9 + succinate + formaldehyde + CO2
-
?
additional information Homo sapiens KDM4D and -E only act on H3K9, with no evidence for demethylation of H3K36, while KDM4A/B/C act on both H3K9 and, less efficiently, on H3K36-methylated substrates. No activity by all isozymes with H3K4me3, H3K9me1, and H3K27me3 ?
-
?

Organism

Organism UniProt Comment Textmining
Homo sapiens B2RXH2 KDM4E
-
Homo sapiens O75164 KDM4A; KDM4A
-
Homo sapiens O94953 KDM4B
-
Homo sapiens Q6B0I6 KDM4D
-
Homo sapiens Q9H3R0 KDM4C
-

Purification (Commentary)

Purification (Comment) Organism
recombinant N-terminally His-tagged KDM4A from Escherichia coli by nickel affinity chromatography Homo sapiens
recombinant N-terminally His-tagged KDM4B from Escherichia coli by nickel affinity chromatography Homo sapiens
recombinant N-terminally His-tagged KDM4C from Escherichia coli by nickel affinity chromatography Homo sapiens
recombinant N-terminally His-tagged KDM4D from Escherichia coli by nickel affinity chromatography Homo sapiens
recombinant N-terminally His-tagged KDM4E from Escherichia coli by nickel affinity chromatography Homo sapiens

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
histone H3 N6,N6,N6-trimethyl-L-lysine9 + 2-oxoglutarate + O2
-
Homo sapiens histone H3 N6,N6-dimethyl-L-lysine9 + succinate + formaldehyde + CO2
-
?
histone H3 N6,N6-dimethyl-L-lysine9 + 2-oxoglutarate + O2
-
Homo sapiens histone H3 N6-methyl-L-lysine9 + succinate + formaldehyde + CO2
-
?
additional information KDM4D and -E only act on H3K9, with no evidence for demethylation of H3K36, while KDM4A/B/C act on both H3K9 and, less efficiently, on H3K36-methylated substrates. No activity by all isozymes with H3K4me3, H3K9me1, and H3K27me3 Homo sapiens ?
-
?

Synonyms

Synonyms Comment Organism
H3K9 demethylase
-
Homo sapiens
JMJD2
-
Homo sapiens
KDM4
-
Homo sapiens

Turnover Number [1/s]

Turnover Number Minimum [1/s] Turnover Number Maximum [1/s] Substrate Comment Organism Structure
0.0029
-
histone H3 N6,N6-dimethyl-L-lysine9 KDM4A, pH and temperature not specified in the publication Homo sapiens
0.005
-
histone H3 N6,N6-dimethyl-L-lysine9 KDM4B, pH and temperature not specified in the publication Homo sapiens
0.0072
-
histone H3 N6,N6-dimethyl-L-lysine9 KDM4C, pH and temperature not specified in the publication Homo sapiens
0.01
-
histone H3 N6,N6,N6-trimethyl-L-lysine9 KDM4A, pH and temperature not specified in the publication Homo sapiens
0.012
-
histone H3 N6,N6-dimethyl-L-lysine9 KDM4D, pH and temperature not specified in the publication Homo sapiens
0.015
-
histone H3 N6,N6,N6-trimethyl-L-lysine9 KDM4D, pH and temperature not specified in the publication Homo sapiens
0.028
-
histone H3 N6,N6,N6-trimethyl-L-lysine9 KDM4B, pH and temperature not specified in the publication Homo sapiens
0.029
-
histone H3 N6,N6,N6-trimethyl-L-lysine9 KDM4C, pH and temperature not specified in the publication Homo sapiens
0.065
-
histone H3 N6,N6-dimethyl-L-lysine9 KDM4E, pH and temperature not specified in the publication Homo sapiens
0.076
-
histone H3 N6,N6,N6-trimethyl-L-lysine9 KDM4E, pH and temperature not specified in the publication Homo sapiens

General Information

General Information Comment Organism
evolution human JMJD2 (KDM4) H3K9 and H3K36 demethylases can be divided into members that act on both H3K9 and H3K36 and H3K9 alone, structural and phylogenetic analysis, overview. KDM4D and -E only act on H3K9, with no evidence for demethylation of H3K36, while KDM4A/B/C act on both H3K9 and, less efficiently, on H3K36-methylated substrates, substrate selectivity of the human KDM4 histone demethylase subfamily, overview Homo sapiens
additional information substrate selectivity is determined by multiple interactions within the catalytic domain but outside the active site, structural basis of sequence celectivity between KDM4 members, overview. Ile71A, Asn86A, Ile87A, Gln88A, and Arg309A may not be required for binding of H3K9 substrate Homo sapiens

kcat/KM [mM/s]

kcat/KM Value [1/mMs-1] kcat/KM Value Maximum [1/mMs-1] Substrate Comment Organism Structure
4
-
histone H3 N6,N6-dimethyl-L-lysine9 KDM4A, pH and temperature not specified in the publication Homo sapiens
10
-
histone H3 N6,N6-dimethyl-L-lysine9 KDM4B, pH and temperature not specified in the publication Homo sapiens
11
-
histone H3 N6,N6-dimethyl-L-lysine9 KDM4C, pH and temperature not specified in the publication Homo sapiens
16
-
histone H3 N6,N6-dimethyl-L-lysine9 KDM4D, pH and temperature not specified in the publication Homo sapiens
22
-
histone H3 N6,N6,N6-trimethyl-L-lysine9 KDM4A, pH and temperature not specified in the publication Homo sapiens
41
-
histone H3 N6,N6,N6-trimethyl-L-lysine9 KDM4D, pH and temperature not specified in the publication Homo sapiens
60
-
histone H3 N6,N6,N6-trimethyl-L-lysine9 KDM4C, pH and temperature not specified in the publication Homo sapiens
90
-
histone H3 N6,N6,N6-trimethyl-L-lysine9 KDM4B, pH and temperature not specified in the publication Homo sapiens
260
-
histone H3 N6,N6-dimethyl-L-lysine9 KDM4E, pH and temperature not specified in the publication Homo sapiens
330
-
histone H3 N6,N6,N6-trimethyl-L-lysine9 KDM4E, pH and temperature not specified in the publication Homo sapiens