Neutrophil elastase

Function

Serine protease that modifies the functions of natural killer cells, monocytes and granulocytes. Shows microbicidal activity in neutrophils by mediating cleavage and degradation of bacterial proteins. Capable of killing E.coli but not S.aureus in vitro; digests outer membrane protein A (ompA) in E.coli and K.pneumoniae. Involved for the formation of neutrophil extracellular traps (NETs): translocates into the nucleus downstream of MPO and mediates degadation of histone H4, thereby participating to chromatin decondensation. NETs are mainly composed of DNA fibers and are released by neutrophils to trap pathogens during inflammation. Inhibits C5a-dependent neutrophil enzyme release and chemotaxis. Promotes cleavage of GSDMB, thereby inhibiting pyroptosis. Promotes blood coagulation. Through the activation of the platelet fibrinogen receptor integrin alpha-IIb/beta-3, potentiates platelet aggregation induced by a threshold concentration of cathepsin G (CTSG). Cleaves and thus inactivates tissue factor pathway inhibitor (TFPI).

Classification

Family (Pfam)

PF00089 Trypsin

InterPro

Peptidase_S1_Elastase_sf, Peptidase_S1_PA, Peptidase_S1_PA_chymotrypsin, Peptidase_S1A, Trypsin_dom, TRYPSIN_HIS, TRYPSIN_SER

Functional cluster

Venom Serine Proteases & Phospholipase A2

Experimental structures · PDB · 38

• 1B0F X-ray 3.00A
• 1H1B X-ray 2.00A
• 1HNE X-ray 1.84A
• 1PPF X-ray 1.80A
• 1PPG X-ray 2.30A
• 2RG3 X-ray 1.80A
• 2Z7F X-ray 1.70A
• 3Q76 X-ray 1.86A
• 3Q77 X-ray 2.00A
• 4NZL X-ray 1.85A
• 4WVP X-ray 1.63A
• 5A09 X-ray 1.81A
• … and 26 more

A predicted model is available from AlphaFold.

Gene Ontology · 47

• GO:0042582 azurophil granule
• GO:0035578 azurophil granule lumen
• GO:0009986 cell surface
• GO:0005737 cytoplasm
• GO:0005829 cytosol
• GO:0070062 extracellular exosome
• GO:0031012 extracellular matrix
• GO:0005576 extracellular region
• GO:0005615 extracellular space
• GO:0140644 neutrophil extracellular trap
• GO:0005634 nucleus
• GO:0045335 phagocytic vesicle
• GO:0030141 secretory granule
• GO:0035580 specific granule lumen
• GO:0017053 transcription repressor complex
• GO:0019955 cytokine binding
• GO:0004175 endopeptidase activity
• GO:0008201 heparin binding
• GO:0008233 peptidase activity
• GO:0002020 protease binding
• GO:0004252 serine-type endopeptidase activity
• GO:0003714 transcription corepressor activity
• GO:0002438 acute inflammatory response to antigenic stimulus
• GO:0002812 biosynthetic process of antibacterial peptides active against Gram-negative bacteria
• GO:0042742 defense response to bacterium
• GO:0022617 extracellular matrix disassembly
• GO:0006874 intracellular calcium ion homeostasis
• GO:0002523 leukocyte migration involved in inflammatory response
• GO:0032682 negative regulation of chemokine production
• GO:0050922 negative regulation of chemotaxis
• GO:0031452 negative regulation of heterochromatin formation
• GO:0050728 negative regulation of inflammatory response
• GO:0032717 negative regulation of interleukin-8 production
• GO:0000122 negative regulation of transcription by RNA polymerase II
• GO:0140645 neutrophil extracellular trap formation
• GO:0070944 neutrophil-mediated killing of bacterium
• GO:0070947 neutrophil-mediated killing of fungus
• GO:0070945 neutrophil-mediated killing of gram-negative bacterium
• GO:0006909 phagocytosis
• GO:0032757 positive regulation of interleukin-8 production
• GO:1903238 positive regulation of leukocyte tethering or rolling
• GO:0043406 positive regulation of MAP kinase activity
• GO:0048661 positive regulation of smooth muscle cell proliferation
• GO:0030163 protein catabolic process
• GO:0006508 proteolysis
• GO:0070269 pyroptotic inflammatory response
• GO:0009411 response to UV

Disease associations

• cyclic hematopoiesis MONDO:0008090
• neutropenia, severe congenital, 1, autosomal dominant MONDO:0042490

Drugs targeting this protein · 2

• ALVELESTAT inhibitor
• SIVELESTAT inhibitor

Related proteins · sequence + function similarity

• Neutrophil elastase 0.96
• Azurocidin 0.85
• Cathepsin G 0.83
• Azurocidin 0.82
• Cathepsin G 0.81
• Cathepsin G 0.81
• Thrombin-like enzyme 1 0.79
• Protein C activator 0.78
• Snake venom serine protease BPA 0.78
• Thrombin-like enzyme chitribrisin 0.78
• Kallikrein-14 0.78
• Myeloblastin 0.78

Co-cited proteins · studied together in the literature

• Neutrophil elastase 3 shared papers
• Myeloperoxidase 4 shared papers
• Cathepsin G 9 shared papers
• Serine protease inhibitor Eap 3 shared papers
• Notch homolog 2 N-terminal-like protein A 1 shared papers
• Tissue factor pathway inhibitor 1 shared papers
• Agaphelin 1 shared papers
• Glucose-6-phosphatase 3 1 shared papers
• Azurocidin 2 shared papers
• Serine protease inhibitor EapH2 2 shared papers
• Myeloblastin 2 shared papers
• Protein-arginine deiminase type-4 1 shared papers

Literature · 48 cited papers

• S. aureus Eap is a polyvalent inhibitor of neutrophil serine proteases. J. Biol. Chem. · 2024
• Simultaneous inhibition of two neutrophil serine proteases by the S. aureus innate immune evasion protein EapH2. J. Biol. Chem. · 2023
• Distinct GSDMB protein isoforms and protease cleavage processes differentially control pyroptotic cell death and mitochondrial damage in cancer cells. Cell Death Differ. · 2023
• Characterization of two distinct neutrophil serine protease-binding modes within a Staphylococcus aureus innate immune evasion protein family. J. Biol. Chem. · 2023
• Thrombus NET content is associated with clinical outcome in stroke and myocardial infarction. Neurology · 2020
• Diverse stimuli engage different neutrophil extracellular trap pathways. Elife · 2017
• Complementary LC-MS/MS-Based N-Glycan, N-Glycopeptide, and Intact N-Glycoprotein Profiling Reveals Unconventional Asn71-Glycosylation of Human Neutrophil Cathepsin G. Biomolecules · 2015
• N-terminome analysis of the human mitochondrial proteome. Proteomics · 2015
• Plasmodium falciparum infection induces expression of a mosquito salivary protein (Agaphelin) that targets neutrophil function and inhibits thrombosis without impairing hemostasis. PLoS Pathog. · 2014
• Staphylococcus aureus secretes a unique class of neutrophil serine protease inhibitors. Proc. Natl. Acad. Sci. U.S.A. · 2014
• A myeloperoxidase-containing complex regulates neutrophil elastase release and actin dynamics during NETosis. Cell Rep. · 2014
• The spectrum of ELANE mutations and their implications in severe congenital and cyclic neutropenia. Hum. Mutat. · 2013
• … and 36 more in the literature graph