Elastase
From Wikipedia, the free encyclopedia
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elastase 1, pancreatic
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| Identifiers | |
| Symbol(s) | ELA1 |
| Entrez | 1990 |
| OMIM | 130120 |
| RefSeq | NM_001971 |
| UniProt | Q9UNI1 |
| Other data | |
| EC number | 3.4.21.36 |
| Locus | Chr. 12 [1] |
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elastase 2, neutrophil
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| Identifiers | |
| Symbol(s) | ELA2 |
| Entrez | 1991 |
| OMIM | 130130 |
| RefSeq | NM_001972 |
| UniProt | P08246 |
| Other data | |
| EC number | 3.4.21.37 |
| Locus | Chr. 19 p13.3 |
In molecular biology, elastase is an enzyme from the class of proteases (or better peptidases) that break down proteins.
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[edit] Forms and classification
There exist two human genes for elastase: pancreatic (ELA-1) and neutrophil (ELA-2) elastase. From recent research, it appears that of the two, ELA-1 is not transcribed into a protein [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.
Bacterial forms: Organisms such as P. aeruginosa also produce elastase, and is considered a virulence factor.
[edit] Function
Elastase breaks down elastin, an elastic fibre that—together with collagen—determines the mechanical properties of connective tissue. The neutrophil form also breaks down the Outer membrane protein A (OmpA) of E. coli and other Gram negative bacteria, and breaks down Shigella virulence factors. This is accomplished through the cleavage of peptide bonds in the target proteins. The specific peptide bonds cleaved are those on the carboxy side of small, hydrophobic amino acids such as glycine, alanine and valine. For more on how this is specifically accomplished see serine protease.
[edit] Genetics
The two ELA genes are located on different chromosomes:
- The gene for ELA-1 is located on chromosome 12q13.
- The gene for ELA-2 is located on chromosome 19p13.3. It consists of five exons.
[edit] The role of human elastase in disease
[edit] A1AD
Elastase is inhibited by the acute phase protein α1-antitryspin (A1AT), which binds almost irreversibly to the active site of elastase and trypsin. A1AT is normally secreted by the liver cells into the serum. α1-antitryspin deficiency (A1AD) leads to uninhibited destruction of elastic fibre by elastase; the main result is pulmonary emphysema.
[edit] Cyclic hematopoeiesis
The rare disease cyclic hematopoeiesis (also called "cyclic neutropenia") is an autosomal dominant genetic disorder characterised by fluctuating neutrophil granulocyte counts over 21-day periods. During neutropenia, patients are at risk for infections. In 1999, this disease was linked to disorders in the ELA-2 gene [3]. Other forms of congenital neutropenia also appear to be linked to ELA-2 mutations.
[edit] Other diseases
Neutrophil elastase is responsible for the blistering in bullous pemphigoid, a skin condition, in the presence of antibodies.
[edit] The role of bacterial elastase in disease
Elastase has been shown to disrupt tight junctions, cause proteolytic damage to tissue, break down cytokines and alpha proteinase inhibitor, cleave immunoglobuline A and G (IgA,IgG) and cleave both C3bi, a component of the complement system, and CR1, a receptor on neutrophils for another complement molecule involved in phagocytosis. The cleavage of IgA, IgG, C3bi and CR1 all contribute to a decrease of the ability of neutrophils to kill bacteria by phagocytosis. Together all these factors contribute to human pathology.
