or three) they transfer. With just one exception, the HMTases belong to SET family that can be classified according to the sequences surrounding the SET domain. Structural studies on the human SET7/9, a mono-methylase, have revealed the molecular basis for the specificity of the enzyme for the histone-target and the roles of the invariant residues in the SET domain in determining the methylation specificities. Associated domains The N-terminal pre-SET domain (), as found in the SUV39 SET family, contains nine invariant cysteine residues that are grouped into two segments separated by a region of variable length. These 9 cysteines coordinate 3 zinc ions to form a triangular cluster, where each of the zinc ions is coordinated by 4 four cysteines to give a tetrahedral configuration. The function of this domain is structural, holding together 2 long segments of random coils. The C-terminal region including the post-SET domain () is disordered when not interacting with a histone tail and in the absence of zinc. The three conserved cysteines in the post-SET domain form a zinc-binding site when coupled to a fourth conserved cysteine in the knot-like structure close to the SET domain active site. The structured post-SET region brings in the C-terminal residues that participate in S-adenosyl-L-methionine-binding and histone tail interactions. The three conserved cysteine residues are essential for HMTase activity, as replacement with serine abolishes HMTase activity. Examples Human genes encoding proteins containing this domain include: ASH1L, also has an associated with SET domain (AWS) EHMT1 (FP13812), EHMT2 (BAT8), EZH1, EZH2 MLL, MLL2, MLL3, MLL5 NSD1 PRDM1, PRDM2, PRDM5 SETD1A, SETD2, SETD3, SETD4, SETD5, SETD6, SETD7, SETD8, SETDB1, SETDB2, SETMAR, SMYD1, SMYD3, SMYD4, SMYD5, SUV39H1, SUV39H2, KMT5B, SUV420H2, WBP7, WHSC1, WHSC1L1 References Protein families