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Literature summary for 1.14.11.69 extracted from

  • Marmorstein, R.; Trievel, R.C.
    Histone modifying enzymes structures, mechanisms, and specificities (2009), Biochim. Biophys. Acta, 1789, 58-68 .
    View publication on PubMedView publication on EuropePMC
Search for more literature for 1.14.11.69

Crystallization (Commentary)

Crystallization (Comment) Organism
crystal structure determinations of JMJD2A in complex with histone H3 peptides bearing different methylated forms of K9 and K36 Homo sapiens

Protein Variants

Protein Variants Comment Organism
additional information introduction of a di-glycine motif at the +3 to +4 positions of the H3K27 sequence, a site which shares sequence homology with the H3K9 sequence, enables JMJD2A to efficiently demethylate H3K27me3, cf. EC 1.14.11.68 Homo sapiens

Inhibitors

Inhibitors Comment Organism Structure
N-oxalylglycine NOG, a nonreactive 2-OG analogue Homo sapiens
Ni2+ substitutes for Fe(II) and inhibits the hydroxylation reaction Homo sapiens

Metals/Ions

Metals/Ions Comment Organism Structure
Fe2+ required 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-lysine 36 + 2-oxoglutarate + O2 Homo sapiens
-
 [histone H3]-N6,N6-dimethyl-L-lysine 36 + succinate + formaldehyde + CO2
-
 ?
[histone H3]-N6,N6-dimethyl-L-lysine 36 + 2-oxoglutarate + O2 Homo sapiens
-
 [histone H3]-N6-methyl-L-lysine 36 + succinate + formaldehyde + CO2
-
 ?

Organism

Organism UniProt Comment Textmining
Homo sapiens O75164
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-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
additional information human JMJD2A exhibits dual specificity for the trimethylated and, to a lesser extent, the dimethylated forms of H3K9 and H3K36, with an approximately fivefold preference in specificity for the H3K9me3 substrate due to a higher KM value for the H3K36me3 peptide, suggesting that JMJD2A preferentially recognizes the H3K9me3 site Homo sapiens ?
-
 ?
[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
-
 ?
[histone H3]-N6,N6-dimethyl-L-lysine 36 + 2-oxoglutarate + O2
-
 Homo sapiens [histone H3]-N6-methyl-L-lysine 36 + succinate + formaldehyde + CO2
-
 ?

Synonyms

Synonyms Comment Organism
histone lysine demethylase
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 Homo sapiens
JMJD2A
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 Homo sapiens
KDM4A
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 Homo sapiens
More see also EC 1.14.11.66 Homo sapiens
trimethyllysine-specific JmjC HDM
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 Homo sapiens

General Information

General Information Comment Organism
metabolism many JmjC HDMs appear to function in the context of large multimeric complexes that govern their localization, transcriptional functions, and potentially their substrate specificity. In the case of certain JmjC enzymes, these complexes appear to be critical in conferring specificity for nucleosomal substrates Homo sapiens
additional information in H3K9me3- and H3K36me3-enzyme complexes, the peptides bind in the same directionality within the substrate binding cleft of JMJD2A, depositing the trimethyllysines into the active site. The majority of the interactions between the enzyme and H3 peptides involve hydrogen bond and van der Waals interactions with the backbone atoms in the substrates. The residues N-terminal to the trimethyllysines adopt a similar beta-strand-like conformation, while the C-terminal residues in the peptides adopt distinct binding modes. Mono-, di-, and trimethyllysines bind within a methylammonium binding pocket adjacent to the Fe(II) and 2-oxoglutarate binding sites in JMJD2A. This pocket is lined with an array of oxygen atoms that participate in direct contacts with zeta-methyl groups of the trimethylated substrate. Structure-activity analysis, overview Homo sapiens
physiological function JMJD2A is implicated in transcriptional silencing and is associated with the retinoblastoma protein, class I HDACs, and the nuclear corepressor N-CoR. JMJD2A and its paralogue JMJD2D associate with the androgen receptor (AR) to upregulate the expression of AR-dependent genes. The transcriptional functions of JMJD2 enzymes appear to be context-dependent Homo sapiens