同: ELA2 deficiency

WordNet

the chief phagocytic leukocyte; stains with either basic or acid dyes (同)neutrophile
a pancreatic enzyme that catalyzes the hydrolysis of elastin

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2016/11/16 22:21:54」(JST)

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Neutrophil 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. Secreted by neutrophils and macrophages during inflammation, it destroys bacteria and host tissue.^[4] It also localizes to Neutrophil extracellular traps (NETs), via its high affinity for DNA, an unusual property for serine proteases.^[5]

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.^[5]

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.

Gene

In humans, neutrophil elastase is encoded by the ELANE gene, which resides on chromosome 19.^[6]

Function

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.^[7] Mutations in this gene are associated with cyclic neutropenia and severe congenital neutropenia (SCN). 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.^[8]

Clinical significance

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 severe congenital neutropenia, which is a failure of neutrophils to mature.^[9]

Interactions

Neutrophil elastase has been shown to interact with Alpha 2-antiplasmin.^[10]^[11]

References

^ "Drugs that physically interact with Neutrophil elastase view/edit references on wikidata".
^ "Human PubMed Reference:".
^ "Mouse PubMed Reference:".
^ Belaaouaj A, Kim KS, Shapiro SD (August 2000). "Degradation of outer membrane protein A in Escherichia coli killing by neutrophil elastase". Science. 289 (5482): 1185–8. doi:10.1126/science.289.5482.1185. PMID 10947984.
^ ^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): 5390–7. doi:10.4049/jimmunol.1303296. PMC 4041364. PMID 24771851.
^ 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): 14739–47. PMID 2902087.
^ Weinrauch Y, Drujan D, Shapiro SD, Weiss J, Zychlinsky A (May 2002). "Neutrophil elastase targets virulence factors of enterobacteria". Nature. 417 (6884): 91–4. doi:10.1038/417091a. PMID 12018205.
^ "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): 3–5. doi:10.1056/NEJMp0806821. PMC 4162527. PMID 19118300.
^ 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): 9849–54. PMID 6980881.
^ Shieh BH, Travis J (May 1987). "The reactive site of human alpha 2-antiplasmin". J. Biol. Chem. 262 (13): 6055–9. PMID 2437112.

External links

GeneReviews/NCBI/NIH/UW entry on ELANE-Related Neutropenias
Neutrophil Elastase at the US National Library of Medicine Medical Subject Headings (MeSH)

UpToDate Contents

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1. 急性呼吸窮迫症候群：成人を対象にした臨床試験中の薬物療法あるいは成人にとって無効な薬物療法 acute respiratory distress syndrome investigational or ineffective pharmacotherapy in adults
2. 先天性好中球減少症 congenital neutropenia
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4. α-1アンチトリプシン欠乏症の臨床症状、診断、および自然経過 clinical manifestations diagnosis and natural history of alpha 1 antitrypsin deficiency
5. α-1アンチトリプシン欠乏の治療 treatment of alpha 1 antitrypsin deficiency

English Journal

Participation of dectin-1 receptor on NETs release against Paracoccidioides brasiliensis: Role on extracellular killing.

Bachiega TF1, Dias-Melicio LA2, Fernandes RK1, de Almeida Balderramas H1, Rodrigues DR1, Ximenes VF3, de Campos Soares ÂM4.
Immunobiology.Immunobiology.2016 Feb;221(2):228-35. doi: 10.1016/j.imbio.2015.09.003. Epub 2015 Sep 14.
Paracoccidioides brasiliensis is a dimorphic fungus from the Paracoccidioides genus, which is the causative agent of paracoccidioidomycosis, a chronic, subacute or acute mycosis, with visceral and cutaneous involvement. This disease that is acquired through inhalation primarily attacks the lungs but
PMID 26416210

Corticosteroid-binding globulin cleavage is paradoxically reduced in alpha-1 antitrypsin deficiency: Implications for cortisol homeostasis.

Nenke MA1, Holmes M2, Rankin W3, Lewis JG4, Torpy DJ5.
Clinica chimica acta; international journal of clinical chemistry.Clin Chim Acta.2016 Jan 15;452:27-31. doi: 10.1016/j.cca.2015.10.028. Epub 2015 Oct 29.
High-affinity corticosteroid-binding globulin (haCBG) is cleaved by neutrophil elastase (NE) resulting in permanent transition to the low cortisol-binding affinity form (laCBG), thereby increasing cortisol availability at inflammatory sites. Alpha-1 antitrypsin (AAT) is the major inhibitor of NE. AA
PMID 26522656

NETosis delays diabetic wound healing in mice and humans.

Fadini GP1, Menegazzo L2, Rigato M3, Scattolini V2, Poncina N2, Bruttocao A3, Ciciliot S2, Mammano F4, Ciubotaru CD5, Brocco E6, Marescotti MC3, Cappellari R3, Arrigoni G7, Millioni R8, Vigili de Kreutzenberg S3, Albiero M2, Avogaro A2.
Diabetes.Diabetes.2016 Jan 6. pii: db150863. [Epub ahead of print]
Upon activation, neutrophils undergo histone citrullination by protein arginine deiminase-4 (PAD4), exocytosis of chromatin and enzymes as neutrophil extracellular traps (NETs), and death. In diabetes, neutrophils are primed to release NETs and die by NETosis. Although this process is a defense agai
PMID 26740598

Japanese Journal

セレウス菌感染を契機に急性呼吸促迫症候群を発症した摂食障害の一例

町田貴胤,遠藤由香,福土審
心身医学 54(12), 1118-1123, 2014-12-01
37歳,女性.16年前から自己誘発性嘔吐や下剤使用を開始,著明な低カリウム血症により入院した.体重29.2kg,全身状態不良で末梢補液を開始したが入院1週間後に発熱・呼吸苦が出現,胸部X線・胸部CTで両肺浸潤影と胸水を認め,血液培養でBacillus cereusを検出した.セレウス菌敗血症に急性呼吸促迫症候群(ARDS)を合併したと診断しICUで人工呼吸器管理を開始,好中球エラスターゼ阻害薬・抗 …
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NAID 40020188441

Neutrophil elastase inhibitor suppresses IL-17 based inflammation of murine experimental colitis

Shioya Yasuo,Katakura Kyoko,Ohira Hiromasa
Fukushima Journal of Medical Science 60(1), 14-21, 2014-08-08
… [Background] Neutrophil elastase (NE) is a proteinase in granulocytes and plays an important role in the pathogenesis of inflammatory disorders. …
NAID 120005473477

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★リンクテーブル★

リンク元	「好中球エラスターゼ」「leukocyte elastase」

「好中球エラスターゼ」

ELANE
Available structures
PDB	Ortholog search: PDBe RCSB
List of PDB id codes
	1B0F, 1H1B, 1HNE, 1PPF, 1PPG, 2RG3, 2Z7F, 3Q76, 3Q77, 4NZL, 4WVP, 5A09, 5A0A, 5A0B, 5A0C, 5ABW
Identifiers
Aliases	ELANE, ELA2, GE, HLE, HNE, NE, PMN-E, SCN1, elastase, neutrophil expressed
External IDs	OMIM: 130130 MGI: 2679229 HomoloGene: 20455 GeneCards: ELANE
Targeted by Drug
	sivelestat
Gene ontology
Molecular function	• RNA polymerase II transcription corepressor activity; • heparin binding; • endopeptidase activity; • protease binding; • peptidase activity; • protein binding; • serine-type peptidase activity; • hydrolase activity; • cytokine binding; • serine-type endopeptidase activity;
Cellular component	• cytoplasm; • transcriptional repressor complex; • secretory granule; • extracellular space; • extracellular region; • cell surface; • extracellular exosome;
Biological process	• response to yeast; • positive regulation of MAP kinase activity; • negative regulation of growth of symbiont in host; • negative regulation of chemotaxis; • cellular calcium ion homeostasis; • extracellular matrix disassembly; • acute inflammatory response to antigenic stimulus; • negative regulation of transcription from RNA polymerase II promoter; • negative regulation of interleukin-8 biosynthetic process; • defense response to fungus; • proteolysis; • response to lipopolysaccharide; • positive regulation of immune response; • protein catabolic process; • defense response to bacterium; • phagocytosis; • neutrophil mediated killing of fungus; • negative regulation of chemokine biosynthetic process; • positive regulation of interleukin-8 biosynthetic process; • negative regulation of inflammatory response; • response to UV; • leukocyte migration; • positive regulation of smooth muscle cell proliferation; • leukocyte migration involved in inflammatory response; • positive regulation of leukocyte tethering or rolling;
	Sources:Amigo / QuickGO
RNA expression pattern
	More reference expression data
Orthologs
	1991
	50701
	n/a
	ENSMUSG00000020125
	P08246
	Q3UP87
	NM_001972
	NM_015779
	NP_001963.1
	NP_056594.2
	Wikidata
View/Edit Human	View/Edit Mouse

　　[★]

英: neutrophil elastase
関: 白血球エラスターゼ

「leukocyte elastase」

　　[★]

白血球エラスターゼ

関: neutrophil elastase

[1] "Drugs that physically interact with Neutrophil elastase view/edit references on wikidata".

[2] "Human PubMed Reference:".

[3] "Mouse PubMed Reference:".

[pmid10947984-4] Belaaouaj A, Kim KS, Shapiro SD (August 2000). "Degradation of outer membrane protein A in Escherichia coli killing by neutrophil elastase". Science. 289 (5482): 1185–8. doi:10.1126/science.289.5482.1185. PMID 10947984.

[Thomas-5] 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): 5390–7. doi:10.4049/jimmunol.1303296. PMC 4041364. PMID 24771851.

[pmid2902087-6] 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): 14739–47. PMID 2902087.

[pmid12018205-7] Weinrauch Y, Drujan D, Shapiro SD, Weiss J, Zychlinsky A (May 2002). "Neutrophil elastase targets virulence factors of enterobacteria". Nature. 417 (6884): 91–4. doi:10.1038/417091a. PMID 12018205.

[8] "Entrez Gene: ELA2 elastase 2, neutrophil".

[pmid19118300-9] Dale DC, Link DC (January 2009). "The many causes of severe congenital neutropenia". N. Engl. J. Med. 360 (1): 3–5. doi:10.1056/NEJMp0806821. PMC 4162527. PMID 19118300.

[pmid6980881-10] 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): 9849–54. PMID 6980881.

[pmid2437112-11] Shieh BH, Travis J (May 1987). "The reactive site of human alpha 2-antiplasmin". J. Biol. Chem. 262 (13): 6055–9. PMID 2437112.

v t e Endopeptidases: serine proteases/serine endopeptidases (EC 3.4.21)

Digestive enzymes	Enteropeptidase Trypsin Chymotrypsin Elastase Neutrophil Pancreatic

Coagulation	factors: Thrombin Factor VIIa Factor IXa Factor Xa Factor XIa Factor XIIa Kallikrein PSA KLK1 KLK2 KLK3 KLK4 KLK5 KLK6 KLK7 KLK8 KLK9 KLK10 KLK11 KLK12 KLK13 KLK14 KLK15 fibrinolysis: Plasmin Plasminogen activator Tissue plasminogen activator Urinary plasminogen activator

Complement system	Factor B Factor D Factor I MASP MASP1 MASP2 C3-convertase

Other immune system	Chymase Granzyme Tryptase Proteinase 3/Myeloblastin

Venombin	Ancrod Batroxobin

Other	Acrosin Prolyl endopeptidase Pronase Proprotein convertases 1 2 Prostasin Reelin Subtilisin/Furin Streptokinase S1P Cathepsin A G

v t e Enzymes

Activity	Active site Binding site Catalytic triad Oxyanion hole Enzyme promiscuity Catalytically perfect enzyme Coenzyme Cofactor Enzyme catalysis Enzyme kinetics Lineweaver–Burk plot Michaelis–Menten kinetics

Regulation	Allosteric regulation Cooperativity Enzyme inhibitor

Classification	EC number Enzyme superfamily Enzyme family List of enzymes

Types	EC1 Oxidoreductases (list) EC2 Transferases (list) EC3 Hydrolases (list) EC4 Lyases (list) EC5 Isomerases (list) EC6 Ligases (list)

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案内

neutrophil elastase