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FLASH GENE
Symbol DNASE1L3 contributors: mct - updated : 25-02-2020
HGNC name deoxyribonuclease I-like 3
HGNC id 2959
Corresponding disease
SLEB3P systemic lupus erythematosus on 3p
Location 3p14.3      Physical location : 58.178.353 - 58.200.398
Synonym name
  • DNase I homolog protein 2
  • Liver and spleen DNase
  • DNase gamma
    • Synonym symbol(s) DHP2, DNAS1L3, LSD, SLEB16, DHP2
    EC.number 3.1.21.
    DNA
    TYPE functioning gene
    STRUCTURE 22.04 kb     10 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked   status provisional
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    10 - 1463 - 305 - 2004 15167901
    7 - 986 - 275 - 2004 15167901
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveliver   highly
     pharynx   highly
    Lymphoid/Immunespleen   highly
    Urinarykidney   highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
          Homo sapiens
    Lymphoid    
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Lymphoid/Immunedendritic cell Homo sapiens
    Lymphoid/Immunemacrophage Homo sapiens
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
    HOMOLOGY
    Homologene
    FAMILY DNase I family
    CATEGORY enzyme
    SUBCELLULAR LOCALIZATION extracellular
        intracellular
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,organelle,endoplasmic reticulum
    intracellular,nucleus
    basic FUNCTION
  • hydrolyzes DNA, is not inhibited by actin, and mediates the breakdown of DNA during apoptosis
  • potentially involved in naturally occurring apoptosis in developing nervous systems
  • plays an active role in lymphoma cell sensitization to VP-16 and its deficiency may constitute a novel mechanism of drug resistance in these cells
  • DNASE1L3 is uniquely capable of digesting chromatin in microparticles released from apoptotic cells
  • is an endonuclease to degrade the chromatin of apoptotic or necrotic cells
  • plays a role in circulating plasma DNA homeostasis by enhancing fragmentation and influencing end-motif frequencies
  • distinct role of DNASE1L3 as a regulator of the physical form and availability of cell-free DNA and may have important implications for the mechanism whereby this enzyme prevents autoimmunity
  • DNASE1L3 was the endonuclease responsible for generating cell-free DNA in acetaminophen-induced hepatocyte necrosis
  • DNASE1L3 digestion within the plasma might be a subsequent step that would result in the typical homeostatic cell-free DNA
  • DNASE1L3 plays a role in the fragmentation of plasma DNA
  • is an important player in the fragmentation of plasma DNA, which appears to act in a cell-extrinsic manner to regulate plasma DNA size and motif frequency
  • DNASE1L3 has a strong preference for cutting DNA sequences adjacent to the CC dinucleotides regardless of the presence of nucleosomal structural proteins
  • is an important component of the mechanism for maintaining plasma DNA homeostasis
    • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • interacting with DFFB (providing an alternative mechanism for inducing nuclear changes when the working apoptotic cascade is unsuitable for DFFB activation)
  • in its role as an apoptotic intracellular endonuclease, DNASE1L3 cooperates with DFFB in DNA fragmentation
    • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s) SLEB3P
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --low  
    in dermatomyositis/polymyositis and systemic lupus erythematosus
    constitutional germinal mutation      
    in hypocomplementemic urticarial vasculitis syndrome (HUVS)
    tumoral     --low  
    in late stage of clear cell renal cell carcinoma (ccRCC)
    Susceptibility
  • to autoimmune disease
  • to scleroderma
    • Variant & Polymorphism SNP
  • G82R and R206C in DNASE1L3 might be potential risk factors for autoimmune disease
  • missense polymorphism rs35677470 in DNASE1L3, influencing scleroderma susceptibility
    • Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
  • deletion of Dnase1l3 in mice resulted in aberrations in the fragmentation of plasma DNA