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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
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