Details for: EPX

Gene ID: 8288

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: EPX

Ensembl ID: ENSG00000121053

Description: eosinophil peroxidase

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • granulocyte CL0000094
    CSI 10.94
    rCSI 16.71%
    PRS 99.48
  • basophil mast progenitor cell CL0002028
    CSI 10.55
    rCSI 56.32%
    PRS 99.47
  • conventional dendritic cell CL0000990
    CSI 7.68
    rCSI 6.41%
    PRS 96.81
  • eosinophil CL0000771
    CSI 4.22
    rCSI 27.67%
    PRS 99.59
  • melanocyte of skin CL1000458
    CSI 3.49
    rCSI 4.75%
    PRS 92.33
  • basal cell of epidermis CL0002187
    CSI 3.2
    rCSI 5.67%
    PRS 90.84
  • CD8-positive, alpha-beta memory T cell, CD45RO-positive CL0001203
    CSI 1.42
    rCSI 1.72%
    PRS 93.39

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
Network Configuration

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  • Node Color (Target Cell CSI, relative to current network):
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    • High
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  • Node Size: Proportional to Target Cell CSI magnitude
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  • Shared Pathway Edge (ONTOLOGY)

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Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary Eosinophil peroxidase, encoded by the [EPX](/details-gene/8288) gene, is a heme-containing enzyme primarily located in the secretory granules of eosinophils. It is a key component of the innate immune system, playing a critical role in host defense by catalyzing the production of reactive oxygen species to combat pathogens, particularly bacteria and nematodes. Expression data highlights its profound significance in [granulocytes](/details-cell/CL0000094), especially [eosinophils](/details-cell/CL0000771), and their progenitors, underscoring its role as a defining marker for this lineage. Clinically, variations in [EPX](/details-gene/8288) are associated with hereditary eosinophil peroxidase deficiency ([261500](https://omim.org/entry/261500)) and have been linked to allergic conditions such as pollinosis ([Link](https://pubmed.ncbi.nlm.nih.gov/14657871)). ## Cellular Roles and Expression Landscape The expression profile of [EPX](/details-gene/8288) firmly establishes its identity as a central effector molecule within the myeloid compartment of the immune system. **Overall**, the gene shows the highest significance in [granulocytes](/details-cell/CL0000094) (CSI: 10.94) and their precursors, [basophil mast progenitor cells](/details-cell/CL0002028) (CSI: 10.55), indicating its early and sustained expression during granulopoiesis. As its name implies, it is a hallmark of [eosinophils](/details-cell/CL0000771) (CSI: 4.22), where it is a major component of the crystalline core of their specific granules ([Link](https://pubmed.ncbi.nlm.nih.gov/2550461)). Its significant expression in [conventional dendritic cells](/details-cell/CL0000990) (CSI: 7.68) suggests a potential role in modulating antigen presentation or the broader innate immune response. Interestingly, [EPX](/details-gene/8288) also shows moderate significance in non-immune cells of the skin, including [melanocytes of skin](/details-cell/CL1000458) and [basal cells of the epidermis](/details-cell/CL0002187), which may point to a role in cutaneous host defense or inflammatory skin conditions. In contrast, its relatively low significance in the lymphoid lineage, such as in [CD8-positive, alpha-beta memory T cells, CD45RO-positive](/details-cell/CL0001203), highlights its specialized function within the innate, rather than the adaptive, immune system. ## Pathways and Molecular Function The functional annotations for [EPX](/details-gene/8288) are highly consistent with its role as a secreted antimicrobial enzyme. Its primary molecular functions include [peroxidase activity](/details-term/GO:0004601) and [heme binding](/details-term/GO:0020037), which are essential for its enzymatic action ([Link](https://pubmed.ncbi.nlm.nih.gov/10358043)). Biologically, [EPX](/details-gene/8288) is integral to the [Innate immune system](/pathway-details/R-HSA-168249) and participates in processes like [Neutrophil degranulation](/pathway-details/R-HSA-6798695), a pathway it shares with related peroxidases. It contributes to host protection through [defense response to bacterium](/details-term/GO:0042742) and [defense response to nematode](/details-term/GO:0002215). This is achieved via its ability to generate hypohalous acids, a process central to [cellular oxidant detoxification](/details-term/GO:0098869) and the [response to oxidative stress](/details-term/GO:0006979). For example, research has demonstrated that [EPX](/details-gene/8288) can directly kill *Mycobacterium tuberculosis* ([Link](https://doi.org/10.1128/iai.71.2.605-613.2003)). Beyond direct pathogen killing, [EPX](/details-gene/8288) appears to have immunomodulatory functions. It is annotated with the [negative regulation of interleukin-10 production](/details-term/GO:0032693) and [positive regulation of interleukin-4 production](/details-term/GO:0032753), suggesting it can influence the cytokine environment to shape the character of an immune response, potentially polarizing it towards a type 2 profile. Its localization to the [secretory granule lumen](/details-term/GO:0034774) and the [extracellular space](/details-term/GO:0005615) confirms its role as an effector molecule released at sites of inflammation. ## Research Directions The function of [EPX](/details-gene/8288) as a primary eosinophil effector is well-established, but its broader immunomodulatory roles, particularly in the context of allergic disease and interactions with other immune cells, warrant further investigation. **Testable Hypotheses:** 1. Given its significant expression in [conventional dendritic cells](/details-cell/CL0000990) and its function in modifying proteins via nitration ([Link](https://doi.org/10.1074/jbc.m801196200)), we hypothesize that **[EPX](/details-gene/8288) released during allergic inflammation post-translationally modifies self-proteins, creating neoantigens that are subsequently processed and presented by dendritic cells, thereby perpetuating chronic inflammation.** 2. Based on its annotated role in regulating cytokine production (e.g., IL-4, IL-10), we hypothesize that **enzymatically active [EPX](/details-gene/8288) directly modulates the function of bystander immune cells, such as macrophages and T cells, by altering the local redox environment, which in turn influences their transcriptional programs for cytokine secretion.** **Key Experimental Approach:** To test the first hypothesis, one could incubate a model allergen (e.g., ovalbumin) with purified, active [EPX](/details-gene/8288) *in vitro* in the presence of hydrogen peroxide and nitrite. The modified allergen would then be used to pulse human monocyte-derived dendritic cells. The impact on DC activation could be assessed by measuring the upregulation of co-stimulatory molecules (CD80/CD86) via flow cytometry. Subsequently, these pulsed DCs would be co-cultured with autologous naive T cells to determine their ability to drive allergen-specific T cell proliferation and differentiation into Th2 cells (measured by IL-4 and IL-5 production). A comparison with DCs pulsed with unmodified allergen would reveal the specific contribution of [EPX](/details-gene/8288)-mediated modifications to the adaptive immune response. **Therapeutic Potential:** As a central mediator of eosinophil-driven pathology in diseases like severe asthma, eosinophilic esophagitis, and hypereosinophilic syndromes, [EPX](/details-gene/8288) is a compelling therapeutic target. Its enzymatic nature makes it amenable to small-molecule inhibition. The development of a highly specific inhibitor of [EPX](/details-gene/8288) peroxidase activity could represent a targeted therapeutic strategy. Such an approach would aim to dampen the tissue-damaging effects of eosinophil degranulation without requiring the complete depletion of eosinophils, potentially offering a more nuanced and safer alternative to current biologics that target the IL-5 pathway. Therefore, **inhibition** of [EPX](/details-gene/8288) is the most viable therapeutic strategy.

Genular Protein ID: 642215863

Symbol: PERE_HUMAN

Name: Eosinophil peroxidase

UniProtKB Accession Codes:

P11678 Q4TVP3

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BindingDB 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 1 CTD 1 ChEBI 15 ChEMBL 1 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 DrugBank 1 EC 2 EMBL 12 Ensembl 1 GO 17 Gene3D 1 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 GlyConnect 1 GlyCosmos 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 4 KEGG 1 MANE-Select 1 MIM 3 MalaCards 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PIR 1 PRINTS 1 PRO 1 PROSITE 2 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 PeroxiBase 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 Pumba 1 RNAct 1 Reactome 1 RefSeq 1 Rhea 1 SIGNOR 1 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 TopDownProteomics 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 2550461

Title: Molecular cloning and characterization of a chromosomal gene for human eosinophil peroxidase.

PubMed ID: 2550461

DOI: 10.1016/s0021-9258(19)84781-6

PubMed ID: 2541222

Title: Molecular cloning of the human eosinophil peroxidase. Evidence for the existence of a peroxidase multigene family.

PubMed ID: 2541222

DOI: 10.1084/jem.169.5.1757

PubMed ID: 10358043

Title: 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.

PubMed ID: 10358043

DOI: 10.1074/jbc.274.24.16953

PubMed ID: 12540536

Title: Human eosinophil peroxidase induces surface alteration, killing, and lysis of Mycobacterium tuberculosis.

PubMed ID: 12540536

DOI: 10.1128/iai.71.2.605-613.2003

PubMed ID: 18694936

Title: Post-translational tyrosine nitration of eosinophil granule toxins mediated by eosinophil peroxidase.

PubMed ID: 18694936

DOI: 10.1074/jbc.m801196200

PubMed ID: 7809065

Title: Hereditary eosinophil peroxidase deficiency: immunochemical and spectroscopic studies and evidence for a compound heterozygosity of the defect.

PubMed ID: 7809065

DOI: 10.1073/pnas.91.26.12496

PubMed ID: 14657871

Title: High contribution contrast between the genes of eosinophil peroxidase and IL-4 receptor alpha-chain in Japanese cedar pollinosis.

PubMed ID: 14657871

DOI: 10.1016/j.jaci.2003.08.051

Sequence Information:

  • Length: 715
  • Mass: 81040
  • Checksum: CEB4E689A6C46374
  • Sequence:
    • MHLLPALAGV LATLVLAQPC EGTDPASPGA VETSVLRDCI AEAKLLVDAA YNWTQKSIKQ 
RLRSGSASPM DLLSYFKQPV AATRTVVRAA DYMHVALGLL EEKLQPQRSG PFNVTDVLTE 
PQLRLLSQAS GCALRDQAER CSDKYRTITG RCNNKRRPLL GASNQALARW LPAEYEDGLS 
LPFGWTPSRR RNGFLLPLVR AVSNQIVRFP NERLTSDRGR ALMFMQWGQF IDHDLDFSPE 
SPARVAFTAG VDCERTCAQL PPCFPIKIPP NDPRIKNQRD CIPFFRSAPS CPQNKNRVRN 
QINALTSFVD ASMVYGSEVS LSLRLRNRTN YLGLLAINQR FQDNGRALLP FDNLHDDPCL 
LTNRSARIPC FLAGDTRSTE TPKLAAMHTL FMREHNRLAT ELRRLNPRWN GDKLYNEARK 
IMGAMVQIIT YRDFLPLVLG KARARRTLGH YRGYCSNVDP RVANVFTLAF RFGHTMLQPF 
MFRLDSQYRA SAPNSHVPLS SAFFASWRIV YEGGIDPILR GLMATPAKLN RQDAMLVDEL 
RDRLFRQVRR IGLDLAALNM QRSRDHGLPG YNAWRRFCGL SQPRNLAQLS RVLKNQDLAR 
KFLNLYGTPD NIDIWIGAIA EPLLPGARVG PLLACLFENQ FRRARDGDRF WWQKRGVFTK 
RQRKALSRIS LSRIICDNTG ITTVSRDIFR ANIYPRGFVN CSRIPRLNLS AWRGT