Reaction: a [histone H3]-N6,N6,N6-trimethyl-L-lysine4 + 3 2-oxoglutarate + 3 O2 = a [histone H3]-L-lysine4 + 3 succinate + 3 formaldehyde + 3 CO2 (overall reaction)
(1a) a [histone H3]-N6,N6,N6-trimethyl-L-lysine4 + 2-oxoglutarate + O2 = a [histone H3]-N6,N6-dimethyl-L-lysine4 + succinate + formaldehyde + CO2
(1b) a [histone H3]-N6,N6-dimethyl-L-lysine4 + 2-oxoglutarate + O2 = a [histone H3]-N6-methyl-L-lysine4 + succinate + formaldehyde + CO2
(1c) a [histone H3]-N6-methyl-L-lysine4 + 2-oxoglutarate + O2 = a [histone H3]-L-lysine4 + succinate + formaldehyde + CO2
Other name(s): KDM5A (gene name); KDM5B (gene name); KDM5C (gene name); KDM5D (gene name); JARID1A (gene name)
Systematic name: [histone H3]-N6,N6,N6-trimethyl-L-lysine-4,2-oxoglutarate:oxygen oxidoreductase
Comments: Requires iron(II). This entry describes a group of enzymes that demethylate N-methylated L-lysine residues at position 4 of histone H3 (H3K4). The enzymes are dioxygenases and act by hydroxylating the methyl group, forming an unstable hemiaminal that leaves as formaldehyde. They can act on tri-, di-, and mono-methylated forms.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:
References:
1. Seward, D.J., Cubberley, G., Kim, S., Schonewald, M., Zhang, L., Tripet, B. and Bentley, D.L. Demethylation of trimethylated histone H3 Lys4 in vivo by JARID1 JmjC proteins. Nat. Struct. Mol. Biol. 14 (2007) 240-242. [PMID: 17310255]
2. Klose, R.J., Yan, Q., Tothova, Z., Yamane, K., Erdjument-Bromage, H., Tempst, P., Gilliland, D.G., Zhang, Y. and Kaelin, W.G., Jr. The retinoblastoma binding protein RBP2 is an H3K4 demethylase. Cell 128 (2007) 889-900. [PMID: 17320163]
3. Iwase, S., Lan, F., Bayliss, P., de la Torre-Ubieta, L., Huarte, M., Qi, H.H., Whetstine, J.R., Bonni, A., Roberts, T.M. and Shi, Y. The X-linked mental retardation gene SMCX/JARID1C defines a family of histone H3 lysine 4 demethylases. Cell 128 (2007) 1077-1088. [PMID: 17320160]
4. Christensen, J., Agger, K., Cloos, P.A., Pasini, D., Rose, S., Sennels, L., Rappsilber, J., Hansen, K.H., Salcini, A.E. and Helin, K. RBP2 belongs to a family of demethylases, specific for tri-and dimethylated lysine 4 on histone 3. Cell 128 (2007) 1063-1076. [PMID: 17320161]