Neutrophil elastase

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Elastase, neutrophil expressed
Protein ELA2 PDB 1b0f.png
PDB rendering based on 1b0f.
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols ELANE ; ELA2; GE; HLE; HNE; NE; PMN-E; SCN1
External IDs OMIM130130 MGI2679229 HomoloGene20455 IUPHAR: 2358 ChEMBL: 248 GeneCards: ELANE Gene
EC number 3.4.21.37
RNA expression pattern
PBB GE ELA2 206871 at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 1991 50701
Ensembl ENSG00000197561 ENSMUSG00000020125
UniProt P08246 Q3UP87
RefSeq (mRNA) NM_001972 NM_015779
RefSeq (protein) NP_001963 NP_056594
Location (UCSC) Chr 19:
0.85 – 0.86 Mb
Chr 10:
79.89 – 79.89 Mb
PubMed search [1] [2]

Neutrophil elastase (EC 3.4.21.37, leukocyte elastase, ELANE, ELA2, elastase 2, neutrophil, elaszym, serine elastase) 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.[1] It also localizes to Neutrophil extracellular traps (NETs), via its high affinity for DNA, an unusual property for serine proteases.[2]

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.[2]

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[edit]

In humans, neutrophil elastase is encoded by the ELANE gene, which resides on chromosome 19.[3]

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.[4] 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.[5]

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 severe congenital neutropenia, which is a failure of neutrophils to mature.[6]

Interactions[edit]

Neutrophil elastase has been shown to interact with Alpha 2-antiplasmin.[7][8]

See also[edit]

References[edit]

  1. ^ 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. 
  2. ^ a b Thomas MP, Whangbo J, McCrossan G, Deutsch AJ, Martinod K, Walch M et al. (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. 
  3. ^ Takahashi H, Nukiwa T, Yoshimura K, Quick CD, States DJ, Holmes MD et al. (October 1988). "Structure of the human neutrophil elastase gene". J. Biol. Chem. 263 (29): 14739–47. PMID 2902087. 
  4. ^ 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. 
  5. ^ "Entrez Gene: ELA2 elastase 2, neutrophil". 
  6. ^ 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. 
  7. ^ 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. 
  8. ^ Shieh BH, Travis J (May 1987). "The reactive site of human alpha 2-antiplasmin". J. Biol. Chem. 262 (13): 6055–9. PMID 2437112. 

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): 208–10. doi:10.1097/00043426-200105000-00005. PMID 11846296. 
  • Horwitz M, Benson KF, Duan Z, Person RE, Wechsler J, Williams K et al. (2003). "Role of neutrophil elastase in bone marrow failure syndromes: molecular genetic revival of the chalone hypothesis". Curr. Opin. Hematol. 10 (1): 49–54. doi:10.1097/00062752-200301000-00008. PMID 12483111. 
  • Ancliff PJ, Gale RE, Linch DC (2003). "Neutrophil elastase mutations in congenital neutropenia". Hematology 8 (3): 165–71. doi:10.1080/1024533031000107497. PMID 12745650. 
  • Horwitz M, Benson KF, Duan Z, Li FQ, Person RE (2004). "Hereditary neutropenia: dogs explain human neutrophil elastase mutations". Trends Mol Med 10 (4): 163–70. doi:10.1016/j.molmed.2004.02.002. PMID 15059607. 

External links[edit]