TASP1 (Threonine aspartase 1), a threonine-type endopeptidase that localizes to the light membrane and cytosolic subcellular fractions, cleaves KMT2A (also known as MLL or MLL1) between an aspartate residue at position 2718 and a glycine residue at position 2719 (Hsieh, Cheng and Korsmeyer 2003; Yokoyama et al. 2002; Hsieh, Ernst et al. 2003). An additional upstream cleavage site exists, but the 2718-2719 cleavage site is preferentially used (Yokoyama et al. 2002; Hsieh, Cheng and Korsmeyer 2003; Hsieh, Ernst et al. 2003). The cleavage produces two fragments commonly known as N320 and C180, which dimerize through their FY-rich N-terminal (FYRN) and FY-rich C-terminal (FYRC) domains, respectively (Yokoyama et al. 2002; Hsieh, Ernst et al. 2003). The cleavage and dimerization are required for KMT2A's proper subnuclear localization and catalytic activity (Hsieh, Ernst et al. 2003; Hsieh, Cheng and Korsmeyer 2003; Takeda et al. 2006).

Yokoyama et al. 2002: Recombinant human KMT2A was used.

Hsieh, Ernst et al. 2003, and Hsieh, Cheng, and Korsmeyer 2003: Recombinant and endogenous human TASP1 and KMT2A proteins were used, and experiments were performed in human embryonic kidney cell line HEK293.

Takeda et al. 2006: endogenous mouse Kmt2a purified from wild type or Tasp1 null mouse embryonic fibroblasts (MEFs) was used in an in vitro methyltransferase assay; H3K4 methylation of Kmt2a-target genes was compared between wild type or Tasp1 null mouse embryonic fibroblasts (MEFs) using chromatin immunoprecipitation (ChIP).