SETMAR (SET domain and mariner transposase fusion gene-containing protein), also known as METNASE or Hsmar1, is a ubiquitously expressed fusion protein with histone-lysine N-methyltransferase activity and DNA-binding, DNA-looping and DNA-cleavage activities. Localizing to the nucleus, SETMAR contains one N-terminal SET domain which facilitates the histone-lysine methyltransferase activity (at H3-Lys4 and H3-Lys36) and a C-terminal transposase domain which is responsible for the DNA-binding, -looping and -cleavage activities. Both domains are essential for the proper function of SETMAR. SETMAR specifically functions in DNA repair but, on its own, SETMAR can only bind to 5’-TIR (terminal inverted repeats) in DNA. For interactions with non-TIR DNA, SETMAR (via its SET domain) binds to and forms a stable complex with the pre-mRNA processing protein PRP19. Due to alternative splicing events, two isoforms exist.
