Neutrophil elastase

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[1]
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 fluid • 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
Species	Human	Mouse
Entrez	1991	50701
Ensembl	n/a	ENSMUSG00000020125
UniProt	P08246	Q3UP87
RefSeq (mRNA)	NM_001972	NM_015779
RefSeq (protein)	NP_001963.1	NP_056594.2
Location (UCSC)	Chr 19: 0.85 – 0.86 Mb	Chr 10: 79.89 – 79.89 Mb
PubMed search	[2]	[3]
Wikidata

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]

See also

• Elastase

References

Further reading

External links

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

PDB gallery
1b0f: CRYSTAL STRUCTURE OF HUMAN NEUTROPHIL ELASTASE WITH MDL 101, 146  1h1b: 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 RESOLUTION  1ppf: X-RAY CRYSTAL STRUCTURE OF THE COMPLEX OF HUMAN LEUKOCYTE ELASTASE (PMN ELASTASE) AND THE THIRD DOMAIN OF THE TURKEY OVOMUCOID INHIBITOR  1ppg: THE REFINED 2.3 ANGSTROMS CRYSTAL STRUCTURE OF HUMAN LEUKOCYTE ELASTASE IN A COMPLEX WITH A VALINE CHLOROMETHYL KETONE INHIBITOR