SET2: The founding member of this subfamily is the domain from the Saccharomyces cerevisiae SET2 protein (ySET2). This protein has intrinsic histone methyltransferase activity specific for H3 K36. Members of the mammalian nuclear receptor-binding SET-domain-containing (NSD) family contain a SET domain that is highly related to that of ySET2, leading to the suggestion that NSD proteins might be involved in chromatin regulation. However, NSD proteins have yet to be shown to possess methyltransferase activity, probably because of inappropriate assay conditions and/or addition of the incorrect substrate. In any case, based on the presence of a SET domain that is highly homologous to ySET2, we suggest that these proteins will eventually be shown to possess methyltransferase activity. (1)

Reference
1. Schneider R, Bannister AJ, Kouzarides T.Unsafe SETs: histone lysine methyltransferases and cancer. Trends Biochem Sci.2002;27(8):396-402. PMID: 12151224.