Eosinophil Peroxidase (EPX) Enzyme

This gene is a member of the peroxidase gene family and is expressed in eosinophils. The encoded precursor protein is processed into covalently attached heavy and light chains to form the mature enzyme, which functions as an oxidant. The enzyme is released at sites of parasitic infection or allergen stimulation to mediate lysis of protozoa or parasitic worms. The gene is found in a cluster of three peroxidase genes at chromosome 17q23. Mutations in this gene result in eosinophil peroxidase deficiency. [provided by RefSeq, Sep 2009]

Function: Mediates tyrosine nitration of secondary granule proteins in mature resting eosinophils. Shows significant inhibitory activity towards Mycobacterium tuberculosis H37Rv by inducing bacterial fragmentation and lysis. Ref.5 Ref.6

Catalytic activity: 2 phenolic donor + H2O2 = 2 phenoxyl radical of the donor + 2 H2O.

Cofactor: Binds 1 calcium ion per heterodimer

By similarity.Binds 1 heme B (iron-protoporphyrin IX) covalently through ester linkages to hydroxylated methyl groups formed auto-catalytically with hydrogen peroxide at the heme C-1 and C-5 positions. The ester linkage to Asp-232 was observed in 30% of the chains.

Subunit structure: Tetramer of two light chains and two heavy chains.

Subcellular location: Cytoplasmic granule. Note: Cytoplasmic granules of eosinophils.

Polymorphism: Allelic variant in EPX is associated with Japanese cedar pollinosis which is a type I allergic disease with ocular and nasal symptoms that develop paroxysmally on contact with Japanese cedar pollen. These symptoms, which occur seasonally each year, are typical features of allergic rhinitis, such as sneezing, excessive nasal secretion, nasal congestion, and conjunctival itching.

Involvement in disease: Eosinophil peroxidase deficiency (EPD) [MIM:261500]: Autosomal recessive defect where anomalous eosinophils are characterized by nuclear hypersegmentation, hypogranulation, and negative peroxidase and phospholipid staining.Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.7

Sequence similarities: Belongs to the peroxidase family. XPO subfamily.