PERE_HUMAN
ID PERE_HUMAN Reviewed; 715 AA.
AC P11678; Q4TVP3;
DT 01-OCT-1989, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1996, sequence version 2.
DT 03-AUG-2022, entry version 205.
DE RecName: Full=Eosinophil peroxidase;
DE Short=EPO;
DE EC=1.11.1.7;
DE Contains:
DE RecName: Full=Eosinophil peroxidase light chain;
DE Contains:
DE RecName: Full=Eosinophil peroxidase heavy chain;
DE Flags: Precursor;
GN Name=EPX; Synonyms=EPER, EPO, EPP;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC TISSUE=Placenta;
RX PubMed=2550461; DOI=10.1016/s0021-9258(19)84781-6;
RA Sakamaki K., Tomonaga M., Tsukui K., Nagata S.;
RT "Molecular cloning and characterization of a chromosomal gene for human
RT eosinophil peroxidase.";
RL J. Biol. Chem. 264:16828-16836(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS MET-40; HIS-122; GLU-249;
RP ARG-276; LEU-292; PRO-326; LEU-358; HIS-364; THR-441; GLN-496 AND TYR-572.
RG NIEHS SNPs program;
RL Submitted (MAY-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 13-715, AND PROTEIN SEQUENCE OF 140-187 AND
RP 251-288.
RC TISSUE=Blood;
RX PubMed=2541222; DOI=10.1084/jem.169.5.1757;
RA Ten R.M., Pease L.R., McKean D.J., Bell M.P., Gleich G.J.;
RT "Molecular cloning of the human eosinophil peroxidase. Evidence for the
RT existence of a peroxidase multigene family.";
RL J. Exp. Med. 169:1757-1769(1989).
RN [4]
RP COVALENT HEME ATTACHMENT, AND PARTIAL PROTEIN SEQUENCE.
RC TISSUE=Blood;
RX PubMed=10358043; DOI=10.1074/jbc.274.24.16953;
RA Oxvig C., Thomsen A.R., Overgaard M.T., Sorensen E.S., Hoejrup P.,
RA Bjerrum M.J., Gleich G.J., Sottrup-Jensen L.;
RT "Biochemical evidence for heme linkage through esters with Asp-93 and Glu-
RT 241 in human eosinophil peroxidase. The ester with Asp-93 is only partially
RT formed in vivo.";
RL J. Biol. Chem. 274:16953-16958(1999).
RN [5]
RP FUNCTION.
RX PubMed=12540536; DOI=10.1128/iai.71.2.605-613.2003;
RA Borelli V., Vita F., Shankar S., Soranzo M.R., Banfi E., Scialino G.,
RA Brochetta C., Zabucchi G.;
RT "Human eosinophil peroxidase induces surface alteration, killing, and lysis
RT of Mycobacterium tuberculosis.";
RL Infect. Immun. 71:605-613(2003).
RN [6]
RP FUNCTION, AND NITRATION AT TYR-488.
RX PubMed=18694936; DOI=10.1074/jbc.m801196200;
RA Ulrich M., Petre A., Youhnovski N., Proemm F., Schirle M., Schumm M.,
RA Pero R.S., Doyle A., Checkel J., Kita H., Thiyagarajan N., Acharya K.R.,
RA Schmid-Grendelmeier P., Simon H.-U., Schwarz H., Tsutsui M., Shimokawa H.,
RA Bellon G., Lee J.J., Przybylski M., Doering G.;
RT "Post-translational tyrosine nitration of eosinophil granule toxins
RT mediated by eosinophil peroxidase.";
RL J. Biol. Chem. 283:28629-28640(2008).
RN [7]
RP VARIANT EPXD HIS-286.
RX PubMed=7809065; DOI=10.1073/pnas.91.26.12496;
RA Romano M., Patriarca P., Melo C., Baralle F.E., Dri P.;
RT "Hereditary eosinophil peroxidase deficiency: immunochemical and
RT spectroscopic studies and evidence for a compound heterozygosity of the
RT defect.";
RL Proc. Natl. Acad. Sci. U.S.A. 91:12496-12500(1994).
RN [8]
RP VARIANTS HIS-326; LEU-326 AND LEU-358, AND POLYMORPHISM.
RX PubMed=14657871; DOI=10.1016/j.jaci.2003.08.051;
RA Nakamura H., Miyagawa K., Ogino K., Endo T., Imai T., Ozasa K.,
RA Motohashi Y., Matsuzaki I., Sasahara S., Hatta K., Eboshida A.;
RT "High contribution contrast between the genes of eosinophil peroxidase and
RT IL-4 receptor alpha-chain in Japanese cedar pollinosis.";
RL J. Allergy Clin. Immunol. 112:1127-1131(2003).
CC -!- FUNCTION: Mediates tyrosine nitration of secondary granule proteins in
CC mature resting eosinophils. Shows significant inhibitory activity
CC towards Mycobacterium tuberculosis H37Rv by inducing bacterial
CC fragmentation and lysis. {ECO:0000269|PubMed:12540536,
CC ECO:0000269|PubMed:18694936}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2 a phenolic donor + H2O2 = 2 a phenolic radical donor + 2
CC H2O; Xref=Rhea:RHEA:56136, ChEBI:CHEBI:15377, ChEBI:CHEBI:16240,
CC ChEBI:CHEBI:139520, ChEBI:CHEBI:139521; EC=1.11.1.7;
CC -!- COFACTOR:
CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU00298};
CC Note=Binds 1 Ca(2+) ion per heterodimer. {ECO:0000255|PROSITE-
CC ProRule:PRU00298};
CC -!- COFACTOR:
CC Name=heme b; Xref=ChEBI:CHEBI:60344;
CC Note=Binds 1 heme b (iron(II)-protoporphyrin IX) covalently through
CC ester linkages to hydroxylated methyl groups formed auto-catalytically
CC with hydrogen peroxide at the heme C-1 and C-5 positions. The ester
CC linkage to Asp-232 was observed in 30% of the chains.;
CC -!- SUBUNIT: Tetramer of two light chains and two heavy chains.
CC -!- SUBCELLULAR LOCATION: Cytoplasmic granule. Note=Cytoplasmic granules of
CC eosinophils.
CC -!- POLYMORPHISM: Allelic variant in EPX is associated with Japanese cedar
CC pollinosis which is a type I allergic disease with ocular and nasal
CC symptoms that develop paroxysmally on contact with Japanese cedar
CC pollen. These symptoms, which occur seasonally each year, are typical
CC features of allergic rhinitis, such as sneezing, excessive nasal
CC secretion, nasal congestion, and conjunctival itching.
CC -!- DISEASE: Eosinophil peroxidase deficiency (EPXD) [MIM:261500]: A rare
CC abnormality without clinical symptoms characterized by decreased or
CC absent peroxidase activity and decreased volume of the granule matrix
CC in eosinophils. {ECO:0000269|PubMed:7809065}. Note=The disease is
CC caused by variants affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the peroxidase family. XPO subfamily.
CC {ECO:0000255|PROSITE-ProRule:PRU00298}.
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/epx/";
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DR EMBL; M29913; AAA58458.1; -; Genomic_DNA.
DR EMBL; M29904; AAA58458.1; JOINED; Genomic_DNA.
DR EMBL; M29905; AAA58458.1; JOINED; Genomic_DNA.
DR EMBL; M29906; AAA58458.1; JOINED; Genomic_DNA.
DR EMBL; M29907; AAA58458.1; JOINED; Genomic_DNA.
DR EMBL; M29908; AAA58458.1; JOINED; Genomic_DNA.
DR EMBL; M29909; AAA58458.1; JOINED; Genomic_DNA.
DR EMBL; M29910; AAA58458.1; JOINED; Genomic_DNA.
DR EMBL; M29911; AAA58458.1; JOINED; Genomic_DNA.
DR EMBL; M29912; AAA58458.1; JOINED; Genomic_DNA.
DR EMBL; DQ054598; AAY43126.1; -; Genomic_DNA.
DR EMBL; X14346; CAA32530.1; -; mRNA.
DR CCDS; CCDS11602.1; -.
DR PIR; A34408; A34408.
DR RefSeq; NP_000493.1; NM_000502.5.
DR AlphaFoldDB; P11678; -.
DR SMR; P11678; -.
DR BioGRID; 113893; 14.
DR IntAct; P11678; 4.
DR STRING; 9606.ENSP00000225371; -.
DR BindingDB; P11678; -.
DR ChEMBL; CHEMBL2438; -.
DR DrugBank; DB01065; Melatonin.
DR PeroxiBase; 3317; HsEPO.
DR GlyConnect; 1208; 4 N-Linked glycans (1 site).
DR GlyGen; P11678; 6 sites, 4 N-linked glycans (1 site).
DR iPTMnet; P11678; -.
DR PhosphoSitePlus; P11678; -.
DR BioMuta; EPX; -.
DR DMDM; 1352738; -.
DR EPD; P11678; -.
DR jPOST; P11678; -.
DR MassIVE; P11678; -.
DR PaxDb; P11678; -.
DR PeptideAtlas; P11678; -.
DR PRIDE; P11678; -.
DR ProteomicsDB; 52797; -.
DR TopDownProteomics; P11678; -.
DR Antibodypedia; 30927; 380 antibodies from 27 providers.
DR DNASU; 8288; -.
DR Ensembl; ENST00000225371.6; ENSP00000225371.5; ENSG00000121053.6.
DR GeneID; 8288; -.
DR KEGG; hsa:8288; -.
DR MANE-Select; ENST00000225371.6; ENSP00000225371.5; NM_000502.6; NP_000493.1.
DR UCSC; uc002ivq.4; human.
DR CTD; 8288; -.
DR DisGeNET; 8288; -.
DR GeneCards; EPX; -.
DR HGNC; HGNC:3423; EPX.
DR HPA; ENSG00000121053; Tissue enriched (bone).
DR MalaCards; EPX; -.
DR MIM; 131399; gene.
DR MIM; 261500; phenotype.
DR neXtProt; NX_P11678; -.
DR OpenTargets; ENSG00000121053; -.
DR PharmGKB; PA27841; -.
DR VEuPathDB; HostDB:ENSG00000121053; -.
DR eggNOG; KOG2408; Eukaryota.
DR GeneTree; ENSGT00940000156009; -.
DR HOGENOM; CLU_006087_1_1_1; -.
DR InParanoid; P11678; -.
DR OMA; CEGTDTD; -.
DR OrthoDB; 276568at2759; -.
DR PhylomeDB; P11678; -.
DR TreeFam; TF314316; -.
DR PathwayCommons; P11678; -.
DR Reactome; R-HSA-6798695; Neutrophil degranulation.
DR SignaLink; P11678; -.
DR SIGNOR; P11678; -.
DR BioGRID-ORCS; 8288; 30 hits in 1071 CRISPR screens.
DR ChiTaRS; EPX; human.
DR GeneWiki; Eosinophil_peroxidase; -.
DR GenomeRNAi; 8288; -.
DR Pharos; P11678; Tchem.
DR PRO; PR:P11678; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; P11678; protein.
DR Bgee; ENSG00000121053; Expressed in trabecular bone tissue and 76 other tissues.
DR Genevisible; P11678; HS.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR GO; GO:0034774; C:secretory granule lumen; TAS:Reactome.
DR GO; GO:0020037; F:heme binding; IEA:InterPro.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004601; F:peroxidase activity; IBA:GO_Central.
DR GO; GO:0042742; P:defense response to bacterium; IBA:GO_Central.
DR GO; GO:0002215; P:defense response to nematode; IEA:Ensembl.
DR GO; GO:0072677; P:eosinophil migration; IEA:Ensembl.
DR GO; GO:0042744; P:hydrogen peroxide catabolic process; IEA:UniProtKB-KW.
DR GO; GO:0032693; P:negative regulation of interleukin-10 production; IEA:Ensembl.
DR GO; GO:0032714; P:negative regulation of interleukin-5 production; IEA:Ensembl.
DR GO; GO:0010936; P:negative regulation of macrophage cytokine production; IEA:Ensembl.
DR GO; GO:0032753; P:positive regulation of interleukin-4 production; IEA:Ensembl.
DR GO; GO:0006979; P:response to oxidative stress; IEA:InterPro.
DR Gene3D; 1.10.640.10; -; 1.
DR InterPro; IPR029599; EPX/EPO.
DR InterPro; IPR019791; Haem_peroxidase_animal.
DR InterPro; IPR010255; Haem_peroxidase_sf.
DR InterPro; IPR037120; Haem_peroxidase_sf_animal.
DR PANTHER; PTHR11475:SF63; PTHR11475:SF63; 1.
DR Pfam; PF03098; An_peroxidase; 1.
DR PRINTS; PR00457; ANPEROXIDASE.
DR SUPFAM; SSF48113; SSF48113; 1.
DR PROSITE; PS00435; PEROXIDASE_1; 1.
DR PROSITE; PS50292; PEROXIDASE_3; 1.
PE 1: Evidence at protein level;
KW Calcium; Direct protein sequencing; Disease variant; Disulfide bond;
KW Glycoprotein; Heme; Hydrogen peroxide; Iron; Metal-binding; Nitration;
KW Oxidoreductase; Peroxidase; Reference proteome; Signal.
FT SIGNAL 1..17
FT /evidence="ECO:0000255"
FT PROPEP 18..139
FT /evidence="ECO:0000269|PubMed:2541222"
FT /id="PRO_0000023639"
FT CHAIN 140..250
FT /note="Eosinophil peroxidase light chain"
FT /id="PRO_0000023640"
FT CHAIN 251..715
FT /note="Eosinophil peroxidase heavy chain"
FT /id="PRO_0000023641"
FT ACT_SITE 233
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00298"
FT BINDING 232
FT /ligand="heme b"
FT /ligand_id="ChEBI:CHEBI:60344"
FT /note="covalent; partial"
FT BINDING 234
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00298"
FT BINDING 306
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00298"
FT BINDING 308
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00298"
FT BINDING 310
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00298"
FT BINDING 312
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00298"
FT BINDING 380
FT /ligand="heme b"
FT /ligand_id="ChEBI:CHEBI:60344"
FT /note="covalent"
FT BINDING 474
FT /ligand="heme b"
FT /ligand_id="ChEBI:CHEBI:60344"
FT /ligand_part="Fe"
FT /ligand_part_id="ChEBI:CHEBI:18248"
FT /note="axial binding residue"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00298"
FT SITE 377
FT /note="Transition state stabilizer"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00298"
FT MOD_RES 488
FT /note="3'-nitrotyrosine"
FT /evidence="ECO:0000269|PubMed:18694936"
FT CARBOHYD 52
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 113
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 327
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 363
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 700
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 708
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 141..152
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00298"
FT DISULFID 253..263
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00298"
FT DISULFID 257..281
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00298"
FT DISULFID 359..370
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00298"
FT DISULFID 578..635
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00298"
FT DISULFID 676..701
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00298"
FT VARIANT 35
FT /note="V -> I (in dbSNP:rs34553736)"
FT /id="VAR_050485"
FT VARIANT 40
FT /note="I -> M (in dbSNP:rs11079339)"
FT /evidence="ECO:0000269|Ref.2"
FT /id="VAR_025138"
FT VARIANT 122
FT /note="Q -> H (in dbSNP:rs11652709)"
FT /evidence="ECO:0000269|Ref.2"
FT /id="VAR_025139"
FT VARIANT 249
FT /note="A -> E (in dbSNP:rs35896669)"
FT /evidence="ECO:0000269|Ref.2"
FT /id="VAR_025140"
FT VARIANT 276
FT /note="K -> R (in dbSNP:rs35074452)"
FT /evidence="ECO:0000269|Ref.2"
FT /id="VAR_025141"
FT VARIANT 286
FT /note="R -> H (in EPXD; dbSNP:rs121434566)"
FT /evidence="ECO:0000269|PubMed:7809065"
FT /id="VAR_015376"
FT VARIANT 292
FT /note="P -> L (in dbSNP:rs33971258)"
FT /evidence="ECO:0000269|Ref.2"
FT /id="VAR_025142"
FT VARIANT 326
FT /note="R -> H (in dbSNP:rs35832094)"
FT /evidence="ECO:0000269|PubMed:14657871"
FT /id="VAR_060197"
FT VARIANT 326
FT /note="R -> L"
FT /evidence="ECO:0000269|PubMed:14657871"
FT /id="VAR_060198"
FT VARIANT 326
FT /note="R -> P (in dbSNP:rs35832094)"
FT /evidence="ECO:0000269|Ref.2"
FT /id="VAR_025143"
FT VARIANT 358
FT /note="P -> L (associated with Japanese cedar pollinosis;
FT dbSNP:rs35135976)"
FT /evidence="ECO:0000269|PubMed:14657871, ECO:0000269|Ref.2"
FT /id="VAR_025144"
FT VARIANT 364
FT /note="R -> H (in dbSNP:rs35232062)"
FT /evidence="ECO:0000269|Ref.2"
FT /id="VAR_025145"
FT VARIANT 441
FT /note="K -> T (in dbSNP:rs35750729)"
FT /evidence="ECO:0000269|Ref.2"
FT /id="VAR_025146"
FT VARIANT 458
FT /note="V -> M (in dbSNP:rs34817773)"
FT /id="VAR_050486"
FT VARIANT 496
FT /note="H -> Q (in dbSNP:rs33955150)"
FT /evidence="ECO:0000269|Ref.2"
FT /id="VAR_025147"
FT VARIANT 572
FT /note="N -> Y (in dbSNP:rs2302311)"
FT /evidence="ECO:0000269|Ref.2"
FT /id="VAR_020031"
FT CONFLICT 13..18
FT /note="TLVLAQ -> EFRGQD (in Ref. 3; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 21
FT /note="E -> Q (in Ref. 3; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 113
FT /note="N -> I (in Ref. 3; CAA32530)"
FT /evidence="ECO:0000305"
FT CONFLICT 163
FT /note="S -> C (in Ref. 3; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 645..660
FT /note="RDGDRFWWQKRGVFTK -> ETETGSGGRTRCFHQ (in Ref. 3; AA
FT sequence)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 715 AA; 81040 MW; CEB4E689A6C46374 CRC64;
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
