KDM2A, KDM2B, KDM4A demethylate Me2K37-histone H3

Stable Identifier
Reaction [transition]
Homo sapiens
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All characterised lysine demethylases other than KDM1A belong to the jumonji C-domain (JmjC) containing family, members of the Cupin superfamily of mononuclear Fe (II)-dependent oxygenases. They require 2-oxoglutarate (2-OG) and molecular oxygen as co-substrates, producing succinate and carbon dioxide. This hydroxylation-based mechanism does not require a protonatable lysine epsilon-amine group and consequently JmjC-containing demethylases are able to demethylate tri-, di- and monomethylated lysines.

The first reported JmjC-containing demethylases were KDM2A and KDM2B (JHDM1A/B, FBXL11/10). These demethylate lysine-37 of histone H3 when mono- or di-methylated (H3K36Me1/2) (Tsukada et al. 2006). KDM4A (JHDM3A) can demethylate mono-, di and trimethylated lysine-37 of histone H3 (Klose et al. 2006).

KDM8 was initially thought to demethylate dimethylated lysine-37 of histone H3 (Hsia et al. 2010) but later work indicates that, consistent with its closer structural similarity to JmjC hydroxylases, the enzyme lacks histone demethylase activity and rather hydroxylates arginine residues of proteins RPS6 and RCCD1 (Wilkins et al. 2018).
Literature References
PubMed ID Title Journal Year
20457893 KDM8, a H3K36me2 histone demethylase that acts in the cyclin A1 coding region to regulate cancer cell proliferation

Izumiya, C, Kung, HJ, Hsia, EY, Huerta, SB, Wright, ME, Tepper, CG, Chen, HW, Izumiya, Y, Pochampalli, MR, Hsia, DA

Proc. Natl. Acad. Sci. U.S.A. 2010
16732292 The transcriptional repressor JHDM3A demethylates trimethyl histone H3 lysine 9 and lysine 36

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

Nature 2006
16362057 Histone demethylation by a family of JmjC domain-containing proteins

Tsukada, Y, Fang, J, Warren, ME, Zhang, Y, Borchers, CH, Tempst, P, Erdjument-Bromage, H

Nature 2006
29563586 JMJD5 is a human arginyl C-3 hydroxylase

Gannon, JM, Hopkinson, RJ, Chowdhury, R, Markolovic, S, Islam, MS, Schofield, CJ, Ge, W, Wilkins, SE

Nat Commun 2018
Catalyst Activity

histone demethylase activity of KDM2A, KDM2B, KDM4A [nucleoplasm]

Orthologous Events
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