Neutrophil elastase (ELANE)
The protein contains 267 amino acids for an estimated molecular weight of 28518 Da.
Modifies the functions of natural killer cells, monocytes and granulocytes. Inhibits C5a-dependent neutrophil enzyme release and chemotaxis (PubMed:15140022). Capable of killing E.coli but not S.aureus in vitro; digests outer membrane protein A (ompA) in E.coli and K.pneumoniae (PubMed:10947984). (updated: June 5, 2019)
Protein identification was indicated in the following studies:
- Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
- Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
This protein is predicted to be membranous by TOPCONS.
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Biological Process
Acute inflammatory response to antigenic stimulus
Antimicrobial humoral response
Biosynthetic process of antibacterial peptides active against Gram-negative bacteria
Cellular calcium ion homeostasis
Collagen catabolic process
Defense response to bacterium
Extracellular matrix disassembly
Extracellular matrix organization
Leukocyte migration
Leukocyte migration involved in inflammatory response
Negative regulation of chemokine biosynthetic process
Negative regulation of chemokine production
Negative regulation of chemotaxis
Negative regulation of inflammatory response
Negative regulation of interleukin-8 biosynthetic process
Negative regulation of interleukin-8 production
Negative regulation of transcription by RNA polymerase II
Neutrophil degranulation
Neutrophil-mediated killing of fungus
Neutrophil-mediated killing of gram-negative bacterium
Obsolete negative regulation of growth of symbiont in host
Phagocytosis
Positive regulation of immune response
Positive regulation of interleukin-8 biosynthetic process
Positive regulation of interleukin-8 production
Positive regulation of leukocyte tethering or rolling
Positive regulation of MAP kinase activity
Positive regulation of smooth muscle cell proliferation
Protein catabolic process
Proteolysis
Response to lipopolysaccharide
Response to UV
Response to yeast
The reference OMIM entry for this protein is 130130
Elastase, neutrophil-expressed; elane
Elastase 2; ela2
Elastase, neutrophil; ne
Hne
Elastase, leukocyte
Hle
Medullasin
Protease, serine, bone marrow
DESCRIPTION
Neutrophil elastase (EC 3.4.21.37) is a serine protease of neutrophil and monocyte granules (Horwitz et al., 1999). Its key physiologic role is in innate host defense, but it can also participate in tissue remodeling and possesses secretagogue actions important to local inflammatory responses (Chua and Laurent, 2006).CLONING
Aoki (1978) purified a 31-kD serine protease from human bone marrow cell mitochondria. Both granulocytes and erythroblasts were found to contain the protease medullasin, but it was not detected in lymphocytes or thrombocytes. It was shown to be located on the inner membrane of mitochondria. Nakamura et al. (1987) reported the complete genomic sequence and deduced the amino acid sequence of the medullasin precursor. It contains 267 amino acids, including a possible leader sequence of 29 amino acids. Fletcher et al. (1987) cloned a cDNA encoding elastase-2 from a human pancreatic cDNA library. Similarities to and differences from elastase-1 (130120) and the chymotrypsins (e.g., 118890) were described. Kawashima et al. (1987) isolated cDNAs from a human pancreatic cDNA library, which indicated that at least 2 elastase II messages are expressed in pancreas. The 2 human elastases II have been designated IIA and IIB. There is 90% overall homology between the amino acid sequences of these 2 classes of elastase II, which is synthesized as a preproenzyme of 269 amino acids. Sinha et al. (1987) determined the complete amino acid sequence of human neutrophil elastase. The protein consists of 218 amino acid residues, contains 2 asparagine-linked carbohydrate side chains, and is joined together by 2 disulfide bonds. There is only moderate homology with porcine pancreatic elastase (43%). Okano et al. (1987) showed that the 218-amino acid sequence of human neutrophil elastase is identical to that of medullasin.GENE FUNCTION
Belaaouaj et al. (2000) determined the mechanism of neutrophil elastase-mediated killing of E. coli. They found that neutrophil elastase degraded outer membrane protein A (OmpA), localized on the surface of gram-negative bacteria. Weinrauch et al. (2002) identified human neutrophil elastase as a key host defense protein in preventing the escape of Shigella from phagocytic vacuoles in neutrophils. Neutrophil elastase degrades Shigella virulence factors at a 1,000-fold lower concentration than that needed to degrade other bacterial proteins. In neutrophils in which neutrophil elastase is inactivated pharmacologically or genetically, Shigella escapes from phagosomes, increasing bacterial survival. Neutrophil elastase also preferentially cleaves virulence factors of Salmonella and Yersinia. Weinrauch et al. (2002) concluded that their findings established neutrophil elastase as the first neutrophil factor that targets bacterial virulence proteins. Increased leukocyte elastase activity in mice lacking secretory leukocyte protease inhibitor (SLPI; 107285) leads to impaired wound healing due to enhanced activity of transforming growth factor-beta (190180) and perhaps additional mechanisms (Ashcroft et al., 2000). Proepithelin (PEPI; 138945), also known as progranulin, an epithelial growth factor, can be converted to epithelins (EPIs) in vivo. Zhu et al. (2002) found that PEPI and EPIs exert opposing activities. EPIs inhibited the growth of epithelial cells but induced them to secrete the neutrophil attractant interleukin-8 (IL8; 146930), while PEPI blocked neutrophil acti ... More on the omim web site
June 7, 2019: Protein entry updated
Automatic update: Entry updated from uniprot information.
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 130130 was added.
Jan. 28, 2016: Protein entry updated
Automatic update: model status changed
Jan. 24, 2016: Protein entry updated
Automatic update: model status changed