PKMTs methylate histone lysines

Some KMTs selectively methylate a particular lysine residue on a specific histone type. The extent of this methylation (mono-, di- or tri-methylation) also can be stringent. Many KMTs also have non-histone substrates, which are not discussed in this module.

The coordinates of post-translational modifications represented and described here follow UniProt standard practice whereby coordinates refer to the translated protein before any processing. Histone literature typically refers to specific residues by numbers which are determined after the initiating methionine has been removed. Therefore the coordinates of post-translated residues in the Reactome database and described here are frequently +1 when compared to the histone literature.

SET domain-containing proteins are classified in one of 7 families. First to be discovered were the SUV39 family named after founding member SUV39H1 (KMT1A), which selectively methylates lysine-10 of histone H3 (H3K9). Family member EHMT2 (KMT1C, G9A) is the predominant H3K9 methyltransferase in mammals. SETDB1 (KMT1E, ESET) also predominantly methylates H3K9, most effectively when complexed with ATF7IP (MCAF, hAM).

SETD2 (KMT3A, HYPB), a member of the SET2 family, specifically methylates histone H3 lysine-37 (H3K36). WHSC1 (KMT3G, NSD2, MMSET) a member of the same family, targets H3K36 when provided with nucleosome substrates but also can methylate histone H4 lysine-45 when octameric native or recombinant nucleosome substrates are provided; dimethylation of histone H3 at lysine-37 (H3K36me2) is thought to be the principal chromatin-regulatory activity of WHSC1. Relatives NSD1 (KMT3B) and WHSC1L1 (KMT3F, NSD3) also methylate nucleosomal H3K36. NSD1 is active on unmethylated or a mimetic monomethylated H3K36, but not di- or trimethylated H3K36 mimetics. Human SETD7 (KMT7, SET7/9), not classified within the 7 SET-domain containing families, mono-methylates lysine-5 of histone H3 (H3K4).