Deoxyribonuclease II, lysosomal (DNASE2)

Deoxyribonuclease II, lysosomal (DNASE2), is an acid-active lysosomal endonuclease critical for intracellular DNA degradation. It cleaves DNA in the lysosomal compartment under acidic conditions, producing 3'-phosphate termini. DNASE2 operates independently of divalent metal ions and is required for the final degradation of nuclear DNA from apoptotic cells and extruded nuclei during erythropoiesis. This enzyme helps remove DNA waste and prevents immune activation caused by DNA accumulation, playing an essential role in both normal development and immune homeostasis. Deficiencies of DNASE2 result in the failure to properly clear self-DNA, leading to pathologies such as severe neonatal anemia, chronic inflammation, and autoimmunity due to excess interferon production. Molecularly, DNASE2 is synthesized as a precursor that is processed in the lysosome (with forms of ~45 kDa, later processed to 30 and 23 kDa), involving a pseudodimeric structure and PLD-family signature motifs in its active site. No approved drugs currently target DNASE2 directly.

Other names

Deoxyribonuclease-2-alphaDNASE2ADNL2DNase II alphaAcid DNaseDeoxyribonuclease II alphaLysosomal DNase IIR31240_2AIPCSDNLdeoxyribonuclease II, lysosomal