Reaction: protein N6,N6-dimethyl-L-lysine + 2 2-oxoglutarate + 2 O2 = protein L-lysine + 2 succinate + 2 formaldehyde + 2 CO2 (overall reaction)
(1a) protein-N6,N6-dimethyl-L-lysine + 2-oxoglutarate + O2 = protein-N6-methyl-L-lysine + succinate + formaldehyde + CO2
(1b) protein-N6-methyl-L-lysine + 2-oxoglutarate + O2 = protein-L-lysine + succinate + formaldehyde + CO2
Other name(s): JHDM1A; JmjC domain-containing histone demethylase 1A; H3-K36-specific demethylase; histone-lysine (H3-K36) demethylase; histone demethylase; protein-6-N,6-N-dimethyl-L-lysine,2-oxoglutarate:oxygen oxidoreductase
Systematic name: protein-N6,N6-dimethyl-L-lysine,2-oxoglutarate:oxygen oxidoreductase
Comments: Requires iron(II). Of the seven potential methylation sites in histones H3 (K4, K9, K27, K36, K79) and H4 (K20, R3) from HeLa cells, the enzyme is specific for Lys-36. Lysine residues exist in three methylation states (mono-, di- and trimethylated). The enzyme preferentially demethylates the dimethyl form of Lys-36 (K36me2), which is its natural substrate, to form the monomethyl and unmethylated forms of Lys-36. It can also demethylate the monomethyl- but not the trimethyl form of Lys-36.
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number:
1. Tsukada, Y., Fang, J., Erdjument-Bromage, H., Warren, M.E., Borchers, C.H., Tempst, P. and Zhang, Y. Histone demethylation by a family of JmjC domain-containing proteins. Nature 439 (2006) 811-816. [PMID: 16362057]