Histone-lysine N-methyltransferase SMYD1 (SMYD1)

Histone-lysine N-methyltransferase SMYD1 (SMYD1) is a muscle- and heart-specific enzyme belonging to the SET and MYND domain-containing (SMYD) family of protein lysine methyltransferases[1][4][5]. It catalyzes the mono-, di-, and trimethylation of histone H3 at lysine 4 (H3K4), functioning as both a transcriptional activator and repressor in a context-dependent manner[2][3][4][5]. Its “split” SET domain catalyzes methyl transfer using S-adenosylmethionine as a cofactor, while its MYND zinc finger domain mediates protein–protein interactions, notably with muscle-specific transcription factor skNAC, which directs SMYD1 to specific genomic loci[1][3][5]. SMYD1 is required for normal heart development and skeletal muscle differentiation, with essential roles in myofibril organization and the activation of muscle-specific genes such as myoglobin[3][5][6][8]. Disruption or dysregulation of SMYD1 leads to congenital heart defects and other muscle pathologies, and it may be involved in certain cancers where epigenetic regulation is altered[1][3][6]. Although it is an emerging therapeutic target for cardiovascular and possibly oncological indications, no direct SMYD1-targeting drugs are currently approved[1].

Other names

BOPZMYND22KMT3DSET and MYND domain-containing protein 1ZMYND18CD8 beta oppositezinc finger MYND domain containing 18SMYD1aSMYD1b

Inhibition or modulation of histone methyltransferase activity leading to altered chromatin state and gene expression