Eosinophil peroxidase
| Eosinophil peroxidase | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Identifiers | |||||||||||
| Symbols | EPX ; EPO; EPP; EPX-PEN | ||||||||||
| External IDs | OMIM: 131399 MGI: 107569 HomoloGene: 20144 ChEMBL: 2438 GeneCards: EPX Gene | ||||||||||
| EC number | 1.11.1.7 | ||||||||||
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| Orthologs | |||||||||||
| Species | Human | Mouse | |||||||||
| Entrez | 8288 | 13861 | |||||||||
| Ensembl | ENSG00000121053 | ENSMUSG00000052234 | |||||||||
| UniProt | P11678 | P49290 | |||||||||
| RefSeq (mRNA) | NM_000502 | NM_007946 | |||||||||
| RefSeq (protein) | NP_000493 | NP_031972 | |||||||||
| Location (UCSC) | Chr 17: 56.27 – 56.28 Mb | Chr 11: 87.86 – 87.88 Mb | |||||||||
| PubMed search | |||||||||||
Eosinophil peroxidase is a haloperoxidase enzyme that in humans is encoded by the EPX gene.[1][2] The enzyme is a heterodimeric 71-77 kD peroxidase consisting of a heavier glycosylated chain and a lighter nonglycosylated chain. This enzyme prefers bromide over chloride as a substrate, converting it to cytotoxic hypobromite.
Function
In the presence of H2O2 formed by the eosinophil, and either chloride or bromide ions, eosinophil peroxidase provides a potent mechanism by which eosinophils kill multicellular parasites (such as, for example, the nematode worms involved in filariasis); and also certain bacteria (such as tuberculosis bacteria). Eosinophil peroxidase is a haloperoxidase that preferentially uses bromide over chloride for this purpose, generating hypobromite (hypobromous acid).[3] The enzyme is also capable of oxidizing thiocyanate (SCN−) and uses it as a co-substrate, with optimal concentrations occurring at about normal plasma levels.[4]
Eosinophil peroxidase is also partly responsible for tissue remodeling.
Role in pathology
The oxidizing compounds produced by eosinophil peroxidase have been implicated in the inflammatory pathology of several disease states, including asthma.[5]
See also
- Eosinophil
- Major basic protein
References
- ↑ Sakamaki K, Tomonaga M, Tsukui K, Nagata S (October 1989). "Molecular cloning and characterization of a chromosomal gene for human eosinophil peroxidase". J. Biol. Chem. 264 (28): 16828–36. PMID 2550461.
- ↑ Ten RM, Pease LR, McKean DJ, Bell MP, Gleich GJ (May 1989). "Molecular cloning of the human eosinophil peroxidase. Evidence for the existence of a peroxidase multigene family". J. Exp. Med. 169 (5): 1757–69. doi:10.1084/jem.169.5.1757. PMC 2189302. PMID 2541222.
- ↑ Mayeno AN, Curran AJ, Roberts RL, Foote CS (April 1989). "Eosinophils preferentially use bromide to generate halogenating agents". J. Biol. Chem. 264 (10): 5660–8. PMID 2538427.
- ↑ Tahboub YR, Galijasevic S, Diamond MP, Abu-Soud HM (2005). "Thiocyanate modulates the catalytic activity of mammalian peroxidases". J. Biol. Chem. 280 (28): 26129–36. doi:10.1074/jbc.M503027200. PMID 15894800.
- ↑ van Dalen CJ, Kettle AJ (August 2001). "Substrates and products of eosinophil peroxidase". Biochem. J. 358 (Pt 1): 233–9. doi:10.1042/0264-6021:3580233. PMC 1222052. PMID 11485572.
Further reading
- Romano M, Patriarca P, Melo C, Baralle FE, Dri P (1994). "Hereditary eosinophil peroxidase deficiency: immunochemical and spectroscopic studies and evidence for a compound heterozygosity of the defect". Proc. Natl. Acad. Sci. U.S.A. 91 (26): 12496–500. doi:10.1073/pnas.91.26.12496. PMC 45465. PMID 7809065.
- Ten RM, Pease LR, McKean DJ, Bell MP, Gleich GJ (1989). "Molecular cloning of the human eosinophil peroxidase. Evidence for the existence of a peroxidase multigene family". J. Exp. Med. 169 (5): 1757–69. doi:10.1084/jem.169.5.1757. PMC 2189302. PMID 2541222.
- Ulrich M, Petre A, Youhnovski N, Prömm F, Schirle M, Schumm M et al. (2008). "Post-translational tyrosine nitration of eosinophil granule toxins mediated by eosinophil peroxidase". J. Biol. Chem. 283 (42): 28629–40. doi:10.1074/jbc.M801196200. PMC 2661412. PMID 18694936.
- van Dalen CJ, Winterbourn CC, Kettle AJ (2006). "Mechanism of nitrite oxidation by eosinophil peroxidase: implications for oxidant production and nitration by eosinophils". Biochem. J. 394 (Pt 3): 707–13. doi:10.1042/BJ20051470. PMC 1383721. PMID 16336215.
- Parwez Q, Stemmler S, Epplen JT, Hoffjan S (2008). "Variation in genes encoding eosinophil granule proteins in atopic dermatitis patients from Germany". J Negat Results Biomed 7: 9. doi:10.1186/1477-5751-7-9. PMC 2596079. PMID 19014520.
- Yamaguchi E, Nishihira J, Shimizu T, Takahashi T, Kitashiro N, Hizawa N et al. (2000). "Macrophage migration inhibitory factor (MIF) in bronchial asthma". Clin. Exp. Allergy 30 (9): 1244–9. doi:10.1046/j.1365-2222.2000.00888.x. PMID 10971470.
- Sakamaki K, Tomonaga M, Tsukui K, Nagata S (1989). "Molecular cloning and characterization of a chromosomal gene for human eosinophil peroxidase". J. Biol. Chem. 264 (28): 16828–36. PMID 2550461.
- Nakamura H, Miyagawa K, Ogino K, Endo T, Imai T, Ozasa K et al. (2003). "High contribution contrast between the genes of eosinophil peroxidase and IL-4 receptor alpha-chain in Japanese cedar pollinosis". J. Allergy Clin. Immunol. 112 (6): 1127–31. doi:10.1016/j.jaci.2003.08.051. PMID 14657871.
- Hrdlickova B, Izakovicova-Holla L (2009). "Association of single nucleotide polymorphisms in the eosinophil peroxidase gene with allergic rhinitis in the Czech population". Int. Arch. Allergy Immunol. 150 (2): 184–91. doi:10.1159/000218122. PMID 19439985.
- Nakamura H, Higashikawa F, Miyagawa K, Nobukuni Y, Endo T, Imai T et al. (2004). "Association of single nucleotide polymorphisms in the eosinophil peroxidase gene with Japanese cedar pollinosis". Int. Arch. Allergy Immunol. 135 (1): 40–3. doi:10.1159/000080222. PMID 15316147.
- Keyhani E, Zarei MA, Lashgarblooki-Livani T (1999). "Kinetics of peroxidases in guinea pig bone marrow under immunostimulation". FEBS Lett. 452 (3): 233–6. doi:10.1016/S0014-5793(99)00665-1. PMID 10386597.
- Hartley JL, Temple GF, Brasch MA (2000). "DNA cloning using in vitro site-specific recombination". Genome Res. 10 (11): 1788–95. doi:10.1101/gr.143000. PMC 310948. PMID 11076863.
- Sakamaki K, Kanda N, Ueda T, Aikawa E, Nagata S (2000). "The eosinophil peroxidase gene forms a cluster with the genes for myeloperoxidase and lactoperoxidase on human chromosome 17". Cytogenet. Cell Genet. 88 (3-4): 246–8. doi:10.1159/000015529. PMID 10828600.
- Strausberg RL, Feingold EA, Grouse LH, Derge JG, Klausner RD, Collins FS et al. (2002). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
- Borelli V, Vita F, Shankar S, Soranzo MR, Banfi E, Scialino G et al. (2003). "Human eosinophil peroxidase induces surface alteration, killing, and lysis of Mycobacterium tuberculosis". Infect. Immun. 71 (2): 605–13. doi:10.1128/IAI.71.2.605-613.2003. PMC 145361. PMID 12540536.
- Wu C, Ma MH, Brown KR, Geisler M, Li L, Tzeng E et al. (2007). "Systematic identification of SH3 domain-mediated human protein-protein interactions by peptide array target screening". Proteomics 7 (11): 1775–85. doi:10.1002/pmic.200601006. PMID 17474147.
- Oxvig C, Thomsen AR, Overgaard MT, Sorensen ES, Højrup P, Bjerrum MJ et al. (1999). "Biochemical evidence for heme linkage through esters with Asp-93 and Glu-241 in human eosinophil peroxidase. The ester with Asp-93 is only partially formed in vivo". J. Biol. Chem. 274 (24): 16953–8. doi:10.1074/jbc.274.24.16953. PMID 10358043.
External links
- Eosinophil peroxidase at the US National Library of Medicine Medical Subject Headings (MeSH)
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From JC Segen Dictionary of Modern Medicine database