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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-[histone] = S-adenosyl-L-homocysteine + N(6)-methyl-L-lysine-[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
General
ankyrin repeat domain protein (ANKRD)
histone N-methyltransferase
phosphoprotein
Properties
SIZE: entity length = 1298 aa
MW = 141 kD
COMPARTMENT: cell nucleus
MOTIF: glutamate-rich region {406-409}
MOTIF: glutamate residue (SEVERAL)
arginine-rich region {442-449}
MOTIF: arginine residue (SEVERAL)
Ser phosphorylation site {S497}
ankyrin repeat
NAME: ankyrin repeat
SITE: 737-766
ankyrin repeat
NAME: ankyrin repeat
SITE: 772-801
ankyrin repeat
NAME: ankyrin repeat
SITE: 805-834
ankyrin repeat
NAME: ankyrin repeat
SITE: 838-868
ankyrin repeat
NAME: ankyrin repeat
SITE: 872-901
ankyrin repeat
NAME: ankyrin repeat
SITE: 905-934
MOTIF: H3K9me binding {905-907}
ankyrin repeat
NAME: ankyrin repeat
SITE: 938-967
ankyrin repeat
NAME: ankyrin repeat
SITE: 971-1004
pre-SET domain {1060-1123}
MOTIF: Zn+2-binding site
SITE: 1062-1062
Zn+2-binding site
SITE: 1064-1064
Zn+2-binding site
SITE: 1068-1068
Zn+2-binding site
SITE: 1073-1073
Zn+2-binding site
SITE: 1075-1075
Zn+2-binding site
SITE: 1105-1105
Zn+2-binding site
SITE: 1109-1109
Zn+2-binding site
SITE: 1111-1111
Zn+2-binding site
SITE: 1115-1115
SET domain {1125-1247}
MOTIF: SAM binding {1136-1138}
binding site
SITE: 1155-1155
FOR-BINDING-OF: Histone H3K9me
H3 interaction {1162-1181}
binding site
SITE: 1173-1173
FOR-BINDING-OF: S-adenosylmethionine
SAM binding {1200-1201}
Zn+2-binding site
SITE: 1203-1203
H3 interaction {1242-1245}
Zn+2-binding site
SITE: 1256-1256
binding site
SITE: 1257-1257
FOR-BINDING-OF: S-adenosylmethionine
Zn+2-binding site
SITE: 1258-1258
Zn+2-binding site
SITE: 1263-1263
alanine-rich region {1292-1295}
MOTIF: alanine residue (SEVERAL)
Database Correlations
OMIM correlations
MORBIDMAP 607001
UniProt Q9H9B1
PFAM correlations
Entrez Gene 79813
Kegg hsa:79813
ENZYME correlations
References
UniProt :accession Q9H9B1