SET and MYND domain-containing protein 4 (SMYD4)

SMYD4 (SET and MYND domain-containing protein 4) is a protein-lysine N-methyltransferase that belongs to the SMYD family of lysine methyltransferases, which includes five members (SMYD1–5)[1][3][5]. SMYD4 contains a catalytic SET domain (split by a MYND-type zinc finger domain), allowing it to methylate lysine residues on histone and non-histone proteins, thereby modulating chromatin structure and gene expression[1][2][5]. SMYD4 also interacts with and negatively regulates histone deacetylase HDAC1, linking methylation and acetylation marks[2][6]. SMYD4 is critical for cardiac development—as shown by severe cardiac malformations upon its loss in animal models—and is implicated in congenital heart disease, cancer, and other developmental disorders[2][3][4][6]. Due to its essential roles in epigenetic regulation, especially in the heart, SMYD4 is under study as a potential therapeutic target and disease biomarker, although specific drugs are not yet available.

Other names

Protein-lysine N-methyltransferase SMYD4KIAA1936ZMYND21SET and MYND domain containing 4SMYD4

Inhibition or modulation of SMYD4 would theoretically affect lysine methylation status of histone and non-histone proteins, thereby altering gene expression and epigenetic state; also, modulation may affect histone acetylation via HDAC1 interaction[2][3][5][6]. No specific drugs or inhibitors are established or in clinical use for SMYD4.