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FLASH GENE
Symbol PRTN3 contributors: mct - updated : 28-11-2017
HGNC name proteinase 3 (serine proteinase, neutrophil, Wegener granulomatosis autoantigen)
HGNC id 9495
Corresponding disease
WG Wegener's granulomatosis
Location 19p13.3      Physical location : 840.984 - 848.175
Synonym name
  • myeloblastin
  • azurophil granule protein 7
  • Synonym symbol(s) AGP7, PR3, MBN, MBT, ACPA, C-ANCA, CANCA, NP-4, NP4, P29, PR-3
    EC.number 3.4.21.76
    DNA
    TYPE functioning gene
    STRUCTURE 7.21 kb     5 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status confirmed
    Map see ELA2
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    5 - 1001 - 256 - 2017 28240246
    EXPRESSION
    Type restricted
       expressed in (based on citations)
    organ(s)
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Blood / hematopoieticbone marrow   
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Blood/Hematopoieticneutrophil
    cell lineage
    cell lines
    fluid/secretion blood
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
    a peptidase S1 domain
    HOMOLOGY
    interspecies homolog to murine Prtn3
    Homologene
    FAMILY peptidase family
    CATEGORY enzyme , antigen
    SUBCELLULAR LOCALIZATION extracellular
        plasma membrane
        intracellular
    intracellular,cytoplasm,cytosolic,granule
    basic FUNCTION
  • serine proteinase, inducing factor independent growth of hematopoietic cells
  • elastase-like protease, involved in proteolytic degradation of connective tissues
  • having intracellular specific protein substrates resulting in the involvement of PRTN3 in regulation of intracellular functions such as proliferation or apoptosis
  • is a major autoantigen in anti-neutrophil cytoplasmic antibodies (ANCA)-associated systemic vasculitis (AASV), and the proportion of neutrophils expressing PRTN3 on their membrane (mPR3+) is increased in AASV
  • ELANE and PRTN3 differ in intracellular localization, which may reflect different trafficking mechanisms of the precursor forms when synthesized at immature stages of neutrophils
  • collectively, membrane PRTN3 acts as a non-opsonic phagocytosis receptor for bacteria probably by activating F2RL1 in neutrophils
  • potential for neutrophil-derived PRTN3 to play a role in reestablishing vascular integrity after leukocyte transmigration and in protecting endothelial cells from NR1I2-induced permeability changes that occur during thrombotic and inflammatory events
  • neutrophil protease PRTN3 is a direct modulator of platelets and causes shape change through activation of the Rho/Rho kinase and Ca(2+) signaling pathways
  • on the surface of apoptotic neutrophils interferes with induction of antiinflammatory mechanisms following phagocytosis of these cells by macrophages
  • is involved in non-alcoholic fatty liver disease (NAFLD and insulin resistance
  • MPO and PRTN3 in neutrophils of Anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV) patients with active disease have a distinct pattern of histone modifications, which implicates epigenetic mechanisms in regulating expression of autoantigen genes
  • pathogenic properties of PRTN3 are not only a result of its enzymatic activity but also mediated by a particular structural element-the hydrophobic patch-which facilitates associations with various proteins and lipids and permits anchorage into the plasma membrane
  • might be key contributors to the systemic inflammation and to the immune dysregulation observed in granulomatosis with polyangiitis (GPA)
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • neutrophil-derived PRTN3 can proteolyze KNG1 and liberate PRTN3-kinin, thereby initiating kallikrein-independent activation of the kinin pathway
  • likely dual functions (activation/termination) of PRTN3 in IL33 biological activity
  • both ELANE and PRTN3 cleave the human NR1I2 N terminus at sites distinct from the thrombin cleavage site
  • CASP3 activation was mediated by serine protease proteinase 3 (PRTN3), which is present in the cytosol of aging neutrophils (PRTN3 cleaved procaspase-3 at a site upstream of the canonical CASP9 cleavage sit
  • is a phosphatidylserine-binding protein and this interaction is dependent on the hydrophobic patch responsible for membrane anchorage
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s) WG
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --over  
    in Wegener granulomatosis (OMIM608710)
    constitutional     --over  
    in patients with granulomatosis with polyangiitis
    constitutional     --over  
    increased mRNA levels of both PRTN3 and CD177 in ANCA)-associated systemic vasculitis (AASV)
    Susceptibility to Wegener granulomatosis
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    digestiveliver 
    inhibition of PRTN3 may have therapeutic potential in non-alcoholic fatty liver disease (NAFLD)
    ANIMAL & CELL MODELS