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FLASH GENE
Symbol PI3 contributors: mct - updated : 27-11-2017
HGNC name protease inhibitor 3, skin-derived (SKALP)
HGNC id 8947
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • a N terminal domain consisting of a variable number of repeats (Gly - Glu - Asp - Pro - Val - Lys)
  • a C terminal four disulphide core or whey acidic protein domain, involed in binding of proteinase (or other proteins)
  • one transglutaminase substrate domain
    • HOMOLOGY
    Homologene
    FAMILY member of the trappin family
    CATEGORY enzyme , immunity/defense
    SUBCELLULAR LOCALIZATION extracellular
        intracellular
    intracellular,cytoplasm,cytosolic
    basic FUNCTION
  • involved in the regulation of inflammation and in protection against tissue damage
  • is a component of cervicovaginal secretions in pregnancy, and levels are diminished in bacterial vaginosis; may be an important component of innate immunity in the lower genital tract
  • is a potent serine protease inhibitor which prevents excessive damage under inflammatory status
  • possess anti-microbial properties against different classes of pathogens including viruses, fungi and bacteria
  • is an elastase-specific inhibitor with increased transcription in normal mammary epithelial cells compared to mammary carcinoma cells
  • plays a direct role in the suppression of tumors through inhibition of elastase
  • regulating proteolytic enzymes during menstruation and contributing to the innate defense against uterine infection
  • is a critical component of the epithelial barrier against ELANE
  • arrests luminal breast cancer cells, perhaps suggesting a role in tumor dormancy
  • constitutive expression of PI3 and SLPI in cervical cells during pregnancy suggests their essential roles in local tissue homeostasis and immune defense
    • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS inflammation
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • TNFA1 (inducer of SKALP (PI3), expression in keratinocytes)
  • binds to elastic fibers by transglutaminase-mediated cross-linking and protects against proteolytic breakdown
  • IL1B
  • PI3-expression is modulated via epigenetically regulated expression of the transcription factor FOXA2
  • ELANE is largely contributed by activated neutrophils in the tumor microenvironment, and may be negatively regulating the ability of PI3 to arrest cells in G0
  • the actions of KLK7 are tightly controlled by PI3 and SPINK5, which also inhibits KLK5, localizing protease activity to the stratum corneum
  • prevented the elastin degradation, neutrophil influx, activation of TGFB1 and apoptosis caused by 85p100 O2 exposure in lung
    • cell & other
    REGULATION
    activated by activation of elafin in keratinocytes by IL1B and TNFA1 (in dermal neutrophilic infiltration)
    induced by induced in epidermis by cellular stress
    Other regulated by neutrophil elastase in type II alveolar epithelial cells
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --over  
    higher PI3 expression in preterm prelabor rupture of membranes (PPROM fetal membranes suggests a host response to an inflammatory pathology
    tumoral     --low  
    in the majority of breast cancer cell lines compared with normal human mammary epithelial cells
    constitutional     --low  
    in tubal epithelium of women with hydrosalpinx with, likely, a lower expression of elafin, an elastase inhibitor and a natural antimicrobial molecule, compared to normal tubes
    Susceptibility to acute respiratory distress syndrome (ARDS)
    Variant & Polymorphism SNP
  • association between SNP rs2664581 in the PI3 gene, increased risk of acute respiratory distress syndrome (ARDS) and pre-elafin circulating levels
    • Candidate gene
    Marker
  • may serve as a biomarker in high-grade serous ovarian cancers and basal-like breast tumors
  • Elafin predicts poor outcome in breast and ovarian cancer patients
  • serves as a prognostic indicator for breast cancer patients
  • elafin has significant diagnostic and prognostic value as a biomarker of skin Graft-versus-host disease (GVHD)
    • Therapy target
    SystemTypeDisorderPubmed
    cancerreproductiveovary
    therapeutic target in high-grade serous ovarian cancers and basal-like breast tumors
    respiratorylung 
    may be a new therapeutic target for preventing O2-induced lung injury in neonates
    ANIMAL & CELL MODELS