DNASE1

This gene encodes a member of the DNase family. This protein is stored in the zymogen granules of the nuclear envelope and functions by cleaving DNA in an endonucleolytic manner. At least six autosomal codominant alleles have been characterized, DNASE1*1 through DNASE1*6, and the sequence of DNASE1*2 represented in this record. Mutations in this gene have been associated with systemic lupus erythematosus (SLE), an autoimmune disease. A recombinant form of this protein is used to treat the one of the symptoms of cystic fibrosis by hydrolyzing the extracellular DNA in sputum and reducing its viscosity. Alternate transcriptional splice variants of this gene have been observed but have not been thoroughly characterized. [provided by RefSeq, Jul 2008]

Deoxyribonuclease 1

Serum endocuclease secreted into body fluids by a wide variety of exocrine and endocrine organs (PubMed:2251263, PubMed:11241278, PubMed:2277032).

Expressed by non-hematopoietic tissues and preferentially cleaves protein-free DNA (By similarity).

Among other functions, seems to be involved in cell death by apoptosis (PubMed:11241278).

Binds specifically to G-actin and blocks actin polymerization (By similarity).

Together with DNASE1L3, 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).

Apoptotic process Source: UniProtKB-KW
DNA catabolic process Source: GO_Central
DNA catabolic process, endonucleolytic Source: UniProtKB
Neutrophil activation involved in immune response Source: UniProtKB
Regulation of acute inflammatory response Source: UniProtKB
Regulation of neutrophil mediated cytotoxicity Source: UniProtKB

Secreted; Nucleus envelope; Zymogen granule. Secretory protein, stored in zymogen granules and found in the nuclear envelope.

Systemic lupus erythematosus (SLE):
Disease susceptibility is associated with variants affecting the gene represented in this entry. Neutrophil extracellular traps (NETs) are impaired in patients suffering from SLE (PubMed:20439745). NETs are mainly composed of DNA fibers and are released by neutrophils to bind pathogens during inflammation (PubMed:20439745). A chronic, relapsing, inflammatory, and often febrile multisystemic disorder of connective tissue, characterized principally by involvement of the skin, joints, kidneys and serosal membranes. It is of unknown etiology, but is thought to represent a failure of the regulatory mechanisms of the autoimmune system. 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.