This entry represents the SET domain of SET and MYND domain-containing protein 2 (SMYD2). SMYD2 functions as a histone methyltransferase that methylates both histones and non-histone proteins, including p53/TP53 and RB1 [, ]. It specifically methylates histone H3 'Lys-4' (H3K4me) and dimethylates histone H3 'Lys-36' (H3K36me2). It plays a role in myofilament organisation in both skeletal and cardiac muscles via Hsp90 methylation []. SMYD2 overexpression is associated with tumour cell proliferation and a worse outcome in human papillomavirus-unrelated nonmultiple head and neck carcinomas []. It regulates leukemia cell growth such that diminished SMYD2 expression upregulates SET7/9, thereby possibly shifting leukemia cells from growth to quiescence state associated with resistance to DNA damage associated with Acute Myeloid Leukemia (AML) [].The SMYD family consists of five members including SMYD1/2/3/4/5. They contain two highly conserved structural and functional domains, the SET and MYND domains. The SET domain is involved in lysine methylation, while the MYND domain is involved in protein-protein interaction. They are essential in several mammalian developmental pathways [, , , ].