TASP1 cleaves KMT2B

Stable Identifier
Reaction [transition]
Homo sapiens
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Based on experiments performed in wild-type and Tasp1 null mouse embryonic fibroblasts (MEFs), KMT2B (also known as MLL2) undergoes TASP1 (Threonine aspartase 1)-mediated proteolysis at a cleavage site conserved between KMT2B and KMT2A (also known as MLL or MLL1) (Takeda et al. 2006). TASP1 is a threonine-type endopeptidase that localizes to the light membrane and cytosolic subcellular fractions (Hsieh, Cheng and Korsmeyer 2003). TASP1 cleaves KMT2A at two sites, of which the site between an aspartate residue at position 2718 and a glycine residue at position 2719 is preferred (Hsieh, Ernst et al. 2003, Hsieh, Cheng and Korsmeyer 2003). The KMT2B is predicted to have a single TASP1 cleavage site between aspartate residue at position 2062 and glycine residue at position 2063, corresponding to the 2718-2719 cleavage site of KMT2A (Yokoyama et al. 2002; Hsieh, Cheng and Korsmeyer 2003), and the cleavage products of KMT2B of predicted size are detectable in lysates of human embryonic kidney HEK293 cell line (Hughes et al. 2004). Based on sequence conservation between KMT2B and KMT2A, the two cleavage products of KMT2B are expected to dimerize through their FY-rich N-terminal (FYRN) and FY-rich C-terminal (FYRC) domains. The cleavage and dimerization of KMT2A are required for its proper subnuclear localization (Hsieh, Ernst et al. 2003; Hsieh, Cheng and Korsmeyer 2003) and catalytic activity (Takeda et al. 2006), and the cleavage of the mouse orthologue of KMT2B was shown to be required for it to promote cellular proliferation.

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 HEK293 cells.

Takeda et al. 2006: endogenous mouse Kmt2b and a recombinant non-cleavable mutant of Kmt2b were studied in wild type or Tasp1 null mouse embryonic fibroblasts (MEFs), and Tasp1 null MEFs in which recombinant Tasp1 was exogenously expressed.
Catalyst Activity

threonine-type endopeptidase activity of TASP1 [cytosol]

Inferred From
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