histone-lysine N-methyltransferase EHMT1; Euchromatic histone-lysine N-methyltransferase 1; Eu-HMTase1; G9a-like protein 1; GLP; GLP1; histone H3-K9 methyltransferase 5; H3-K9-HMTase 5; lysine N-methyltransferase 1D (EHMT1 EUHMTASE1 GLP KIAA1876 KMT1D)

Function

• histone methyltransferase
• specifically mono- & dimethylates Lys-9 of histone H3 (H3K9me1 & H3K9me2, respectively) in euchromatin
• H3K9me represents a specific tag for epigenetic transcriptional repression by recruiting HP1 proteins to methylated histones
• weakly methylates Lys-27 of histone H3 (H3K27me)
• also required for DNA methylation
• the histone methyltransferase activity is not required for DNA methylation, suggesting that these 2 activities function independently probably targeted to histone H3 by different DNA-binding proteins like E2F6, MGA, MAX &/or DP1
• during G0 phase, probably contributes to silencing of MYC- & E2F-responsive genes, suggesting a role in G0/G1 transition in cell cycle.
• in addition to histone methyltransferase activity, also methylates non-histone proteins:
  • mediates dimethylation of Lys-373 of p53/TP53
• phosphorylated upon DNA damage, probably by ATM or ATR
• heterodimer; heterodimerizes with EHMT2/G9a
• interacts with WIZ & EHMT2. part of the E2F6.com-1 complex in G0 phase
• interacts (via ANK repeats) with RELA (when monomethylated at Lys-310)

S-adenosyl-L-methionine + L-lysine-[[[A137031|histone]]] = S-adenosyl-L-homocysteine + N(6)-methyl-L-lysine-[[[A137031|histone]]]

Inhibition:

• methyltransferase activity is inhibited by BIX-01294
• efficiently inhibited by compound E72, a BIX-01294 derivative

Structure

• the ANK repeats recognize & bind RELA subunit of NF-kappa-B, when RELA is monomethylated at Lys-310 (putative)
  • they also specifically recognize & bind H3K9me1 & H3K9me2
• the SET domain mediates interaction with WIZ
• belongs to the histone-lysine methyltransferase family
• contains 8 ANK repeats
• contains 1 pre-SET domain
• contains 1 SET domain

Compartment

• nucleus, chromosome
• associates with euchromatic regions

Alternative splicing

named isoforms=4

Expression

widely expressed

Pathology

• defects in EHMT1 are the cause of chromosome 9q subtelomeric deletion syndrome

More general terms

• histone N-methyltransferase
• ankyrin repeat domain protein (ANKRD)
• phosphoprotein

Component of

• E2F6.com-1 complex

Database

• Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=79813
• Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:79813
• OMIM: https://mirror.omim.org/entry/607001
• OMIM: https://mirror.omim.org/entry/610253
• UniProt: http://www.uniprot.org/uniprot/Q9H9B1.html