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Deoxyribonuclease 1 and related proteins This family includes Deoxyribonuclease 1 (DNase1, EC 3.1.21.1) and related proteins. DNase1, also known as DNase I, is a Ca2+, Mg2+/Mn2+-dependent secretory endonuclease, first isolated from bovine pancreas extracts. It cleaves DNA preferentially at phosphodiester linkages next to a pyrimidine nucleotide, producing 5'-phosphate terminated polynucleotides with a free hydroxyl group on position 3'. It generally produces tetranucleotides. DNase1 substrates include single-stranded DNA, double-stranded DNA, and chromatin. This enzyme may be responsible for apoptotic DNA fragmentation. Other deoxyribonucleases in this subfamily include human DNL1L (human DNase I lysosomal-like, also known as DNASE1L1, Xib and DNase X ), human DNASE1L2 (also known as DNAS1L2), and DNASE1L3 (also known as DNAS1L3, nhDNase, LS-DNase, DNase Y, and DNase gamma). DNASE1L3 is also implicated in apoptotic DNA fragmentation. DNase1 is also a cytoskeletal protein which binds actin. A recombinant form of human DNase1 is used as a mucoactive therapy in patients with cystic fibrosis; it hydrolyzes the extracellular DNA in sputum and reduces its viscosity. Mutations in the gene encoding DNase1 have been associated with Systemic Lupus Erythematosus, a multifactorial autoimmune disease. This family also includes a subfamily of mostly uncharacterized proteins, which includes Mycoplasma pulmonis MnuA, a membrane-associated nuclease. The in vivo role of MnuA is as yet undetermined. This family belongs to the large EEP (exonuclease/endonuclease/phosphatase) superfamily that contains functionally diverse enzymes that share a common catalytic mechanism of cleaving phosphodiester bonds. |
Jiyao W et al.(2023). "The conserved domain database in 2023.",