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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

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

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

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_002777 5 - 1001 NP_002768 - 256 - 2017 28240246

EXPRESSION

Type	restricted

expressed in	(based on citations)
organ(s)

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Blood / hematopoietic bone marrow

cells

System Cell Pubmed Species Stage Rna symbol Blood/Hematopoietic neutrophil

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)

Type Gene Modification Chromosome rearrangement Protein expression Protein 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
	System Type Disorder Pubmed digestive liver   inhibition of PRTN3 may have therapeutic potential in non-alcoholic fatty liver disease (NAFLD)

ANIMAL & CELL MODELS