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Symbol PI3 contributors: mct - updated : 27-11-2017
HGNC name protease inhibitor 3, skin-derived (SKALP)
HGNC id 8947
Location 20q13.12      Physical location : 43.803.539 - 43.805.184
Synonym name
  • skin derived antileuko-proteinase (elafin),(SKALP)
  • WAP four-disulfide core domain 14
  • WAP four-disulfide core domain protein 14
  • elastase-specific inhibitor
  • peptidase inhibitor 3, skin-derived
  • trappin-2
  • Synonym symbol(s) SKALP, ESI, ELAFIN, ELAF, WAP3, C4A4, WFDC14, cementoin
    TYPE functioning gene
    STRUCTURE 1.65 kb     3 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Promoter
    Binding site
    text structure
  • FOXA2 binding site in the elafin promoter was critical for the activation of the promoter
  • MAPPING cloned Y linked N status confirmed
    Physical map
    RPL37AP1 20q12 ribosomal protein L37a pseudogene 1 C20orf121 20q13.11 chromosome 20 open reading frame 121 TDE1 20q13.1-q13.3 tumor differentially expressed 1 PKIG 20q13.2-q13.13 protein kinase (cAMP-dependent, catalytic) inhibitor gamma ADA 20q12 adenosine deaminase MGC5566 20q13.12 hypothetical protein MGC5566 WISP2 20q12-q13.1 WNT1 inducible signaling pathway protein 2 KCNK15 20q12-q13 potassium channel, subfamily K, member 15 RIMS4 20 regulating synaptic membrane exocytosis 4 LOC391252 20 similar to piggyBac transposable element derived 4 YWHAB 20q13.1 tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, beta polypeptide LOC200226 20q13.12 similar to Polyadenylate-binding protein 2 (Poly(A)-binding protein 2) (PABP 2) TOMM34 20q12-q13.11 translocase of outer mitochondrial membrane 34 STK4 20q11.2-q13.2 serine/threonine kinase 4 KCNS1 20q12 potassium voltage-gated channel, delayed-rectifier, subfamily S, member 1 WFDC5 20q13.11 WAP four-disulfide core domain 5 WFDC12 20q12-q13.1 WAP four-disulfide core domain 12 PI3 20q12-q13 protease inhibitor 3, skin-derived (SKALP) SEMG1 20q13.1 semenogelin I SEMG2 20q13.1 semenogelin II LOC149709 20q13.12 similar to RIKEN cDNA 1700049M11 SLPI 20q12-q13.2 secretory leukocyte protease inhibitor (antileukoproteinase) MATN4 20q13.1-q13.2 matrilin 4 RBPSUHL 20q12-q13.1 recombining binding protein suppressor of hairless (Drosophila)-like SDC4 20q13.1 syndecan 4 (amphiglycan, ryudocan) C20orf35 20q13.12 chromosome 20 open reading frame 35 C20orf10 20q12-13.12 chromosome 20 open reading frame 10 PIGT 20q12-q13.1 phosphatidyl inositol glycan class T LOC149710 20q13.12 hypothetical LOC149710 WFDC2 20q12-q13.2 WAP four-disulfide core domain 2 WFDC6 20q13.12 WAP four-disulfide core domain 6 SPINLW1 20q12-q13.2 serine protease inhibitor-like, with Kunitz and WAP domains 1 (eppin) WFDC8 20q13.12 WAP four-disulfide core domain 8 WFDC9 20q12-q13.1 WAP four-disulfide core domain 9 WFDC10A 20q13.12 WAP four-disulfide core domain 10A RPS2L1 20q13.11 ribosomal protein S2-like 1 WFDC11 20q12-q13.1 WAP four-disulfide core domain 11 WFDC10B 20 WAP four-disulfide core domain 10B WFDC13 20q13.12 WAP four-disulfide core domain 13 LOC391253 20 similar to dJ601O1.1 (novel protein with Kunitz/Bovine pancreatic trypsin inhibitor domain)
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    3 - 579 - 117 - 2009 19906197
       expressed in (based on citations)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    blood / hematopoieticthymus   highly
    Nervousbrain   moderately
    Reproductivefemale systemoviduct    Homo sapiens
     female systembreastmammary gland   Homo sapiens
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Epithelialbarrier liningendometrium  
    SystemCellPubmedSpeciesStageRna symbol
    Lymphoid/Immunemacrophage Homo sapiens
    Reproductiveepithelial cell Homo sapiens
    cell lineage
    cell lines
    at STAGE
  • 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
    FAMILY member of the trappin family
    CATEGORY enzyme , immunity/defense
    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
    a component
    small molecule
  • 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
    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
    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
  • 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
    therapeutic target in high-grade serous ovarian cancers and basal-like breast tumors
    may be a new therapeutic target for preventing O2-induced lung injury in neonates