Oxidoreductases;
Acting on paired donors, with incorporation or reduction of molecular oxygen;
With 2-oxoglutarate as one donor, and incorporation of one atom of oxygen into each donor
BRITE hierarchy

[histone H3]-N6,N6,N6-trimethyl-L-lysine36,2-oxoglutarate:oxygen oxidoreductase

a [histone H3]-N6,N6,N6-trimethyl-L-lysine36 + 2 2-oxoglutarate + 2 O2 = a [histone H3]-N6-methyl-L-lysine36 + 2 succinate + 2 formaldehyde + 2 CO2 (overall reaction) [RN:R12459];
(1a) a [histone H3]-N6,N6,N6-trimethyl-L-lysine36 + 2-oxoglutarate + O2 = a [histone H3]-N6,N6-dimethyl-L-lysine36 + succinate + formaldehyde + CO2 [RN:R12460];
(1b) a [histone H3]-N6,N6-dimethyl-L-lysine36 + 2-oxoglutarate + O2 = a [histone H3]-N6-methyl-L-lysine36 + succinate + formaldehyde + CO2 [RN:R09510]

R09510 R12459 R12460
Reaction

[histone H3]-N6,N6,N6-trimethyl-L-lysine36;
2-oxoglutarate [CPD:C00026];
O2 [CPD:C00007];
[histone H3]-N6,N6-dimethyl-L-lysine36

Requires iron(II). This entry describes a group of enzymes that demethylate N-methylated Lys36 residues in the tail of the histone protein H3 (H3K36). This lysine residue can exist in three methylation states (mono-, di- and trimethylated), but this group of enzymes only act on the the tri- and di-methylated forms. The enzymes are dioxygenases and act by hydroxylating the methyl group, forming an unstable hemiaminal that leaves as formaldehyde. Since trimethylation of H3K36 enhances transcription, this enzyme acts as a transcription repressor. The enzymes that possess this activity often also catalyse the activity of EC 1.14.11.66, [histone H3]-trimethyl-L-lysine9 demethylase. cf. EC 1.14.11.27, [histone H3]-dimethyl-L-lysine36 demethylase.

EC 1.14.11.69 created 2019

1  [PMID:16603238]

Whetstine JR, Nottke A, Lan F, Huarte M, Smolikov S, Chen Z, Spooner E, Li E, Zhang G, Colaiacovo M, Shi Y

Reversal of histone lysine trimethylation by the JMJD2 family of histone demethylases.

Cell 125:467-81 (2006)
DOI:10.1016/j.cell.2006.03.028

[hsa:9682] [cel:CELE_Y48B6A.11]

2  [PMID:16732292]

Klose RJ, Yamane K, Bae Y, Zhang D, Erdjument-Bromage H, Tempst P, Wong J, Zhang Y

The transcriptional repressor JHDM3A demethylates trimethyl histone H3 lysine 9 and lysine 36.

Nature 442:312-6 (2006)
DOI:10.1038/nature04853

[hsa:9682]

3  [PMID:17525156]

Kim T, Buratowski S

Two Saccharomyces cerevisiae JmjC domain proteins demethylate histone H3 Lys36 in transcribed regions to promote elongation.

J Biol Chem 282:20827-35 (2007)
DOI:10.1074/jbc.M703034200

[sce:YER169W]

4  [PMID:17589523]

Couture JF, Collazo E, Ortiz-Tello PA, Brunzelle JS, Trievel RC

Specificity and mechanism of JMJD2A, a trimethyllysine-specific histone demethylase.

Nat Struct Mol Biol 14:689-95 (2007)
DOI:10.1038/nsmb1273

[hsa:9682]

5  [PMID:19061644]

Lin CH, Li B, Swanson S, Zhang Y, Florens L, Washburn MP, Abmayr SM, Workman JL

Heterochromatin protein 1a stimulates histone H3 lysine 36 demethylation by the Drosophila KDM4A demethylase.

Mol Cell 32:696-706 (2008)
DOI:10.1016/j.molcel.2008.11.008

[dme:Dmel_CG15835 Dmel_CG33182]

6  [PMID:28743002]

Colmenares SU, Swenson JM, Langley SA, Kennedy C, Costes SV, Karpen GH

Drosophila Histone Demethylase KDM4A Has Enzymatic and Non-enzymatic Roles in Controlling Heterochromatin Integrity.

Dev Cell 42:156-169.e5 (2017)
DOI:10.1016/j.devcel.2017.06.014

[dme:Dmel_CG15835]