EHMT1

Domain

The ANK repeats recognize and bind RELA subunit of NF-kappa-B, when RELA is monomethylated at 'Lys-310' (By similarity). They also specifically recognize and bind H3K9me1 and H3K9me2.

The SET domain mediates interaction with WIZ.

In the pre-SET domain, Cys residues bind 3 zinc ions that are arranged in a triangular cluster; some of these Cys residues contribute to the binding of two zinc ions within the cluster.

Function

Histone methyltransferase that specifically mono- and dimethylates 'Lys-9' of histone H3 (H3K9me1 and H3K9me2, respectively) in euchromatin. H3K9me represents a specific tag for epigenetic transcriptional repression by recruiting HP1 proteins to methylated histones. Also 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 and/or DP1. During G0 phase, it probably contributes to silencing of MYC- and E2F-responsive genes, suggesting a role in G0/G1 transition in cell cycle. In addition to the histone methyltransferase activity, also methylates non-histone proteins: mediates dimethylation of 'Lys-373' of p53/TP53. Represses the expression of mitochondrial function-related genes, perhaps by occupying their promoter regions, working in concert with probable chromatin reader BAZ2B (By similarity).

Involvement in disease

Kleefstra syndrome 1

KLEFS1

A form of Kleefstra syndrome, an autosomal dominant disease characterized by variable intellectual disability, psychomotor developmental delay, seizures, behavioral abnormalities, and facial dysmorphisms. KLEFS1 patients additionally manifest brachy(micro)cephaly, congenital heart defects, and urogenital defects.

None

The disease is caused by variants affecting the gene represented in this entry. The syndrome can be either caused by intragenic EHMT1 mutations leading to haploinsufficiency of the EHMT1 gene or by a submicroscopic 9q34.3 deletion. Although it is not known if and to what extent other genes in the 9q34.3 region contribute to the syndrome observed in deletion cases, EHMT1 seems to be the major determinant of the core disease phenotype (PubMed:19264732).

Sequence Similarities

Belongs to the class V-like SAM-binding methyltransferase superfamily.

Tissue Specificity

Widely expressed.

Cellular localization

• Nucleus
• Chromosome
• Associates with euchromatic regions.

Alternative names

EUHMTASE1, GLP, KIAA1876, KMT1D, EHMT1, Histone-lysine N-methyltransferase EHMT1, Euchromatic histone-lysine N-methyltransferase 1, G9a-like protein 1, Histone H3-K9 methyltransferase 5, Lysine N-methyltransferase 1D, Eu-HMTase1, GLP1, H3-K9-HMTase 5

Database links

swissprot:Q9H9B1 entrezGene:79813 entrezGene:10919 swissprot:Q96KQ7 omim:607001 omim:604599