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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

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

EXPRESSION

Type

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol blood / hematopoietic thymus       highly Nervous brain       moderately Reproductive female system oviduct       Homo sapiens   female system breast mammary gland     Homo sapiens

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Epithelial barrier lining endometrium     Lymphoid

cells

System Cell Pubmed Species Stage Rna symbol Lymphoid/Immune macrophage Homo sapiens Reproductive epithelial cell Homo sapiens Skin/Tegument keratinocyte

cell lineage

cell lines

fluid/secretion

at STAGE

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)

Type Gene Modification Chromosome rearrangement Protein expression Protein 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
	System Type Disorder Pubmed cancer reproductive ovary therapeutic target in high-grade serous ovarian cancers and basal-like breast tumors respiratory lung   may be a new therapeutic target for preventing O2-induced lung injury in neonates

ANIMAL & CELL MODELS