Recombinant Human Deoxyribonuclease gamma (DNASE1L3)

Function

Has DNA hydrolytic activity. Is capable of both single- and double-stranded DNA cleavage, producing DNA fragments with 3'-OH ends (By similarity). Can cleave chromatin to nucleosomal units and cleaves nucleosomal and liposome-coated DNA (PubMed:10807908, PubMed:14646506, PubMed:27293190, PubMed:9070308, PubMed:9714828). Acts in internucleosomal DNA fragmentation (INDF) during apoptosis and necrosis (PubMed:23229555, PubMed:24312463). The role in apoptosis includes myogenic and neuronal differentiation, and BCR-mediated clonal deletion of self-reactive B cells (By similarity). Is active on chromatin in apoptotic cell-derived membrane-coated microparticles and thus suppresses anti-DNA autoimmunity (PubMed:27293190). Together with DNASE1, plays a key role in degrading neutrophil extracellular traps (NETs) (By similarity). NETs are mainly composed of DNA fibers and are released by neutrophils to bind pathogens during inflammation (By similarity). Degradation of intravascular NETs by DNASE1 and DNASE1L3 is required to prevent formation of clots that obstruct blood vessels and cause organ damage following inflammation (By similarity)

Subcellular Location

Nucleus; Endoplasmic reticulum; Secreted

Disease Association

Systemic lupus erythematosus 16 (SLEB16) : A rare autosomal recessive form of systemic lupus erythematosus with childhood onset, characterized by high frequency of anti-neutrophil cytoplasmic antibodies and lupus nephritis. Systemic lupus erythematosus is a chronic, relapsing, inflammatory, and often febrile multisystemic disorder of connective tissue, characterized principally by involvement of the skin, joints, kidneys and serosal membranes. The disease is marked by a wide range of system dysfunctions, an elevated erythrocyte sedimentation rate, and the formation of LE cells in the blood or bone marrow. [The disease is caused by variants affecting the gene represented in this entry]

Tissue Specificity

Liver and spleen

• Rodriguez A.M. et al. Identification, localization, and expression of two novel human genes similar to deoxyribonuclease I. — Genomics (1997)
• Zeng Z. et al. Cloning and characterization of a novel human DNase. — Biochem. Biophys. Res. Commun. (1997)
• Baron W.F. et al. Cloning and characterization of an actin-resistant DNase I-like endonuclease secreted by macrophages. — Gene (1998)
• Shiokawa D. et al. cDNA cloning of human DNase gamma: chromosomal localization of its gene and enzymatic properties of recombinant protein. — Apoptosis (1998)
• Ota T. et al. Complete sequencing and characterization of 21,243 full-length human cDNAs. — Nat. Genet. (2004)
• Muzny D.M. et al. The DNA sequence, annotation and analysis of human chromosome 3. — Nature (2006)
• Mural R.J. et al. PubMed: CI-5GBDQ6B103N1E (JUL-)
• The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). — Genome Res. (2004)