Identification of the three non-identical subunits constituting human deoxyribonuclease II

We purified DNase II from human liver to apparent homogeneity. The N-terminal amino acid sequences of each of three components constituting the purified mature enzyme were then separately determined by automatic Edman degradation. A combination of this chemical information and the previously reported nucleotide sequence of the cDNA encoding human DNase II [Yasuda et al. (1998) J. Biol. Chem. 273, 2610-2626] allowed detailed elucidation of the enzyme's subunit structure: human DNase II was composed of three non-identical subunits, a propeptide, proprotein and mature protein, following a signal peptide. Expression analysis of a series of deletion mutants derived from the cDNA of DNase II in COS-7 cells suggested that although a single large precursor protein may not be necessary for proteolytic maturation, the propeptide region L17-Q46 may play an essential role in generating the active form of the enzyme.