Histone-lysine N-methyltransferase SETMAR (SETMAR)

Histone-lysine N-methyltransferase SETMAR (SETMAR, also known as Metnase) is a **primate-specific, chimeric protein** resulting from the fusion of a SET domain–containing histone methyltransferase and a *mariner* transposase domain[2][4][5][7]. The SET domain catalyzes methylation of histone H3 at lysines 4 and 36, marks associated with active chromatin and DNA repair[2][4][5][7]. The transposase domain, although inactive for transposition due to inactivating mutations, provides DNA binding (especially to remnants of the Hsmar1 transposon), looping, and limited nuclease activity, thereby targeting SETMAR’s activity across thousands of genomic loci[1][2][5]. **SETMAR plays a key role in DNA double-strand break repair**, particularly by enhancing non-homologous end joining (NHEJ), and contributes to other DNA transactions such as chromosome decatenation, regulation of gene expression, and alternative splicing[2][4][5]. SETMAR is dysregulated in several cancers, and altered expression or function may contribute to genomic instability and tumorigenesis[4][5][7]. Despite its implication in cancer and potential as a biomarker, there are currently no specific drugs targeting SETMAR[5][7]. Safety challenges for therapeutic targeting include the risk of compromising DNA repair and elevating genomic instability[5][7].

Other names

MetnaseSET domain and mariner transposase fusion proteinSET domain and mariner transposase fusion gene-containing proteinMar1Transposon Hsmar1 transposasehistone-lysine N-methyltransferase SETMARMETNASE

Inhibition of histone methyltransferase activity (hypothetical for undisclosed drugs); Interference with DNA end joining or chromatin modification (no specific approved drugs documented)