[{"@context":"http:\/\/schema.org\/","@type":"BlogPosting","@id":"https:\/\/wiki.edu.vn\/en\/wiki24\/neutrophil-elastase-wikipedia\/#BlogPosting","mainEntityOfPage":"https:\/\/wiki.edu.vn\/en\/wiki24\/neutrophil-elastase-wikipedia\/","headline":"Neutrophil elastase – Wikipedia","name":"Neutrophil elastase – Wikipedia","description":"before-content-x4 From Wikipedia, the free encyclopedia after-content-x4 Protein-coding gene in the species Homo sapiens ELANE Available structures PDB Ortholog search:","datePublished":"2019-11-16","dateModified":"2019-11-16","author":{"@type":"Person","@id":"https:\/\/wiki.edu.vn\/en\/wiki24\/author\/lordneo\/#Person","name":"lordneo","url":"https:\/\/wiki.edu.vn\/en\/wiki24\/author\/lordneo\/","image":{"@type":"ImageObject","@id":"https:\/\/secure.gravatar.com\/avatar\/c9645c498c9701c88b89b8537773dd7c?s=96&d=mm&r=g","url":"https:\/\/secure.gravatar.com\/avatar\/c9645c498c9701c88b89b8537773dd7c?s=96&d=mm&r=g","height":96,"width":96}},"publisher":{"@type":"Organization","name":"Enzyklop\u00e4die","logo":{"@type":"ImageObject","@id":"https:\/\/wiki.edu.vn\/wiki4\/wp-content\/uploads\/2023\/08\/download.jpg","url":"https:\/\/wiki.edu.vn\/wiki4\/wp-content\/uploads\/2023\/08\/download.jpg","width":600,"height":60}},"image":{"@type":"ImageObject","@id":"https:\/\/upload.wikimedia.org\/wikipedia\/commons\/thumb\/1\/1d\/Protein_ELA2_PDB_1b0f.png\/250px-Protein_ELA2_PDB_1b0f.png","url":"https:\/\/upload.wikimedia.org\/wikipedia\/commons\/thumb\/1\/1d\/Protein_ELA2_PDB_1b0f.png\/250px-Protein_ELA2_PDB_1b0f.png","height":"218","width":"250"},"url":"https:\/\/wiki.edu.vn\/en\/wiki24\/neutrophil-elastase-wikipedia\/","wordCount":6155,"articleBody":"     (adsbygoogle = window.adsbygoogle || []).push({});before-content-x4From Wikipedia, the free encyclopedia       (adsbygoogle = window.adsbygoogle || []).push({});after-content-x4Protein-coding gene in the species Homo sapiensELANEAvailable structuresPDBOrtholog search: PDBe RCSB List of PDB id codes1B0F, 1H1B, 1HNE, 1PPF, 1PPG, 2RG3, 2Z7F, 3Q76, 3Q77, 4NZL, 4WVP, 5A09, 5A0A, 5A0B, 5A0C, 5ABW       (adsbygoogle = window.adsbygoogle || []).push({});after-content-x4IdentifiersAliasesELANE, ELA2, GE, HLE, HNE, NE, PMN-E, SCN1, elastase, neutrophil expressedExternal IDsOMIM: 130130 MGI: 2679229 HomoloGene: 20455 GeneCards: ELANE WikidataNeutrophil elastase (EC 3.4.21.37, leukocyte elastase, ELANE, ELA2, elastase 2, neutrophil, elaszym, serine elastase, subtype human leukocyte elastase (HLE)) is a serine proteinase in the same family as chymotrypsin and has broad substrate specificity. Neutrophil elastase is secreted by neutrophils during inflammation, and destroys bacteria and host tissue.[5] It also localizes to neutrophil extracellular traps (NETs), via its high affinity for DNA, an unusual property for serine proteases.[6]As with other serine proteinases it contains a charge relay system composed of the catalytic triad of histidine, aspartate, and serine residues that are dispersed throughout the primary sequence of the polypeptide but that are brought together in the three dimensional conformation of the folded protein. The gene encoding neutrophil elastase, ELA2, consists of five exons. Neutrophil elastase is closely related to other cytotoxic immune serine proteases, such as the granzymes and cathepsin G. It is more distantly related to the digestive CELA1.[6]The neutrophil form of elastase (EC 3.4.21.37) is 218 amino acids long, with two asparagine-linked carbohydrate chains (see glycosylation). It is present in azurophil granules in the neutrophil cytoplasm. There appear to be two forms of neutrophil elastase, termed IIa and IIb.       (adsbygoogle = window.adsbygoogle || []).push({});after-content-x4In humans, neutrophil elastase is encoded by the ELANE gene, which resides on chromosome 19.[7]Table of ContentsFunction[edit]Clinical significance[edit]Inhibitors[edit]See also[edit]References[edit]Further reading[edit]External links[edit]Function[edit]Elastases form a subfamily of serine proteases that hydrolyze many proteins in addition to elastin. Humans have six elastase genes that encode the structurally similar proteins elastase 1, 2, 2A, 2B, 3A, and 3B. Neutrophil elastase hydrolyzes proteins within specialized neutrophil lysosomes, called azurophil granules, as well as proteins of the extracellular matrix following the protein’s release from activated neutrophils. Neutrophil elastase may play a role in degenerative and inflammatory diseases by its proteolysis of collagen-IV and elastin of the extracellular matrix. This protein degrades the outer membrane protein A (OmpA) of E. coli as well as the virulence factors of such bacteria as Shigella, Salmonella and Yersinia.[8] Mutations in this gene are associated with cyclic neutropenia (CyN) and severe congenital neutropenia (SCN). At least 95 disease-causing mutations in this gene have been discovered.[9] This gene is clustered with other serine protease gene family members, azurocidin 1 and proteinase 3 genes, at chromosome 19pter. All 3 genes are expressed coordinately and their protein products are packaged together into azurophil granules during neutrophil differentiation.[10]Clinical significance[edit]Neutrophil elastase is an important protease enzyme that when expressed aberrantly can cause emphysema or emphysematous changes.  This involves breakdown of the lung structure and increased airspaces. Mutations of the ELANE gene cause cyclic and severe congenital neutropenia, which is a failure of neutrophils to mature.[11] In 2019 study was confirmed that ELANE deletion does not cause neutropenia.[12]Inhibitors[edit]In order to minimize damage to tissues, there are few inhibitors of neutrophil elastase. One group of inhibitors are the Serpins (Serine Protease Inhibitors).[13] Neutrophil elastase has been shown to interact with Alpha 2-antiplasmin, which belongs to the Serpin family of proteins.[14][15]See also[edit]References[edit]^ a b c ENSG00000197561 GRCh38: Ensembl release 89: ENSG00000277571, ENSG00000197561 – Ensembl, May 2017^ a b c GRCm38: Ensembl release 89: ENSMUSG00000020125 – Ensembl, May 2017^ “Human PubMed Reference:”. National Center for Biotechnology Information, U.S. National Library of Medicine.^ “Mouse PubMed Reference:”. National Center for Biotechnology Information, U.S. National Library of Medicine.^ Belaaouaj A, Kim KS, Shapiro SD (August 2000). “Degradation of outer membrane protein A in Escherichia coli killing by neutrophil elastase”. Science. 289 (5482): 1185\u20138. Bibcode:2000Sci…289.1185B. doi:10.1126\/science.289.5482.1185. PMID\u00a010947984.^ a b Thomas MP, Whangbo J, McCrossan G, Deutsch AJ, Martinod K, Walch M, Lieberman J (June 2014). “Leukocyte protease binding to nucleic acids promotes nuclear localization and cleavage of nucleic acid binding proteins”. J. Immunol. 192 (11): 5390\u20137. doi:10.4049\/jimmunol.1303296. PMC\u00a04041364. PMID\u00a024771851.^ Takahashi H, Nukiwa T, Yoshimura K, Quick CD, States DJ, Holmes MD, Whang-Peng J, Knutsen T, Crystal RG (October 1988). “Structure of the human neutrophil elastase gene”. J. Biol. Chem. 263 (29): 14739\u201347. doi:10.1016\/S0021-9258(18)68099-8. PMID\u00a02902087.^ Weinrauch Y, Drujan D, Shapiro SD, Weiss J, Zychlinsky A (May 2002). “Neutrophil elastase targets virulence factors of enterobacteria”. Nature. 417 (6884): 91\u20134. Bibcode:2002Natur.417…91W. doi:10.1038\/417091a. PMID\u00a012018205. S2CID\u00a04341470.^ \u0160im\u010d\u00edkov\u00e1 D, Heneberg P (December 2019). “Refinement of evolutionary medicine predictions based on clinical evidence for the manifestations of Mendelian diseases”. Scientific Reports. 9 (1): 18577. Bibcode:2019NatSR…918577S. doi:10.1038\/s41598-019-54976-4. PMC\u00a06901466. PMID\u00a031819097.^ “Entrez Gene: ELA2 elastase 2, neutrophil”.^ Dale DC, Link DC (January 2009). “The many causes of severe congenital neutropenia”. N. Engl. J. Med. 360 (1): 3\u20135. doi:10.1056\/NEJMp0806821. PMC\u00a04162527. PMID\u00a019118300.^ Horwitz MS, Laurino MY, Keel SB (August 2019). “ELANE whole gene deletion mutation”. Blood Advances. 3 (16): 2470\u20132473. doi:10.1182\/bloodadvances.2019000498. PMC\u00a06712528. PMID\u00a031427279.^ Korkmaz B, Horwitz MS, Jenne DE, Gauthier F (December 2010). “Neutrophil elastase, proteinase 3, and cathepsin G as therapeutic targets in human diseases”. Pharmacol. Rev. 4 (62): 726\u201359. doi:10.1124\/pr.110.002733. PMC\u00a02993259. PMID\u00a021079042.^ Brower MS, Harpel PC (August 1982). “Proteolytic cleavage and inactivation of alpha 2-plasmin inhibitor and C1 inactivator by human polymorphonuclear leukocyte elastase”. J. Biol. Chem. 257 (16): 9849\u201354. doi:10.1016\/S0021-9258(18)34149-8. PMID\u00a06980881.^ Shieh BH, Travis J (May 1987). “The reactive site of human alpha 2-antiplasmin”. J. Biol. Chem. 262 (13): 6055\u20139. doi:10.1016\/S0021-9258(18)45536-6. PMID\u00a02437112.Further reading[edit]Dale DC, Liles WC, Garwicz D, Aprikyan AG (2001). “Clinical implications of mutations of neutrophil elastase in congenital and cyclic neutropenia”. J. Pediatr. Hematol. Oncol. 23 (4): 208\u201310. doi:10.1097\/00043426-200105000-00005. PMID\u00a011846296.Horwitz M, Benson KF, Duan Z, Person RE, Wechsler J, Williams K, Albani D, Li FQ (2003). “Role of neutrophil elastase in bone marrow failure syndromes: molecular genetic revival of the chalone hypothesis”. Curr. Opin. Hematol. 10 (1): 49\u201354. doi:10.1097\/00062752-200301000-00008. PMID\u00a012483111. S2CID\u00a022277675.Ancliff PJ, Gale RE, Linch DC (2003). “Neutrophil elastase mutations in congenital neutropenia”. Hematology. 8 (3): 165\u201371. doi:10.1080\/1024533031000107497. PMID\u00a012745650. S2CID\u00a019283939.Horwitz M, Benson KF, Duan Z, Li FQ, Person RE (2004). “Hereditary neutropenia: dogs explain human neutrophil elastase mutations”. Trends Mol Med. 10 (4): 163\u201370. doi:10.1016\/j.molmed.2004.02.002. PMID\u00a015059607.External links[edit]PDB gallery1b0f: CRYSTAL STRUCTURE OF HUMAN NEUTROPHIL ELASTASE WITH MDL 101, 1461h1b: CRYSTAL STRUCTURE OF HUMAN NEUTROPHIL ELASTASE COMPLEXED WITH AN INHIBITOR (GW475151)1hne: STRUCTURE OF HUMAN NEUTROPHIL ELASTASE IN COMPLEX WITH A PEPTIDE CHLOROMETHYL KETONE INHIBITOR AT 1.84-ANGSTROMS RESOLUTION1ppf: X-RAY CRYSTAL STRUCTURE OF THE COMPLEX OF HUMAN LEUKOCYTE ELASTASE (PMN ELASTASE) AND THE THIRD DOMAIN OF THE TURKEY OVOMUCOID INHIBITOR1ppg: THE REFINED 2.3 ANGSTROMS CRYSTAL STRUCTURE OF HUMAN LEUKOCYTE ELASTASE IN A COMPLEX WITH A VALINE CHLOROMETHYL KETONE INHIBITOR       (adsbygoogle = window.adsbygoogle || []).push({});after-content-x4"},{"@context":"http:\/\/schema.org\/","@type":"BreadcrumbList","itemListElement":[{"@type":"ListItem","position":1,"item":{"@id":"https:\/\/wiki.edu.vn\/en\/wiki24\/#breadcrumbitem","name":"Enzyklop\u00e4die"}},{"@type":"ListItem","position":2,"item":{"@id":"https:\/\/wiki.edu.vn\/en\/wiki24\/neutrophil-elastase-wikipedia\/#breadcrumbitem","name":"Neutrophil elastase – Wikipedia"}}]}]