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P11678 (PERE_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified February 19, 2014. Version 148. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Eosinophil peroxidase

Short name=EPO
EC=1.11.1.7
Gene names
Name:EPX
Synonyms:EPER, EPO, EPP
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length715 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

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 (EPXD) [MIM:261500]: A rare abnormality without clinical symptoms characterized by decreased or absent peroxidase activity and decreased volume of the granule matrix in eosinophils.
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.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 1717 Potential
Propeptide18 – 139122
PRO_0000023639
Chain140 – 250111Eosinophil peroxidase light chain
PRO_0000023640
Chain251 – 715465Eosinophil peroxidase heavy chain
PRO_0000023641

Sites

Active site2331Proton acceptor By similarity
Metal binding2341Calcium By similarity
Metal binding3061Calcium By similarity
Metal binding3081Calcium; via carbonyl oxygen By similarity
Metal binding3101Calcium By similarity
Metal binding3121Calcium By similarity
Metal binding4741Iron (heme axial ligand) By similarity
Binding site2321Heme (covalent; via 2 links); partial
Binding site3801Heme (covalent; via 2 links)
Site3771Transition state stabilizer By similarity

Amino acid modifications

Modified residue4881Nitrated tyrosine Ref.6
Glycosylation521N-linked (GlcNAc...) Potential
Glycosylation1131N-linked (GlcNAc...) Potential
Glycosylation3271N-linked (GlcNAc...) Potential
Glycosylation3631N-linked (GlcNAc...) Potential
Glycosylation7001N-linked (GlcNAc...) Potential
Glycosylation7081N-linked (GlcNAc...) Potential
Disulfide bond141 ↔ 152 By similarity
Disulfide bond253 ↔ 263 By similarity
Disulfide bond257 ↔ 281 By similarity
Disulfide bond359 ↔ 370 By similarity
Disulfide bond578 ↔ 635 By similarity
Disulfide bond676 ↔ 701 By similarity

Natural variations

Natural variant351V → I.
Corresponds to variant rs34553736 [ dbSNP | Ensembl ].
VAR_050485
Natural variant401I → M. Ref.2
Corresponds to variant rs11079339 [ dbSNP | Ensembl ].
VAR_025138
Natural variant1221Q → H. Ref.2
Corresponds to variant rs11652709 [ dbSNP | Ensembl ].
VAR_025139
Natural variant2491A → E. Ref.2
Corresponds to variant rs35896669 [ dbSNP | Ensembl ].
VAR_025140
Natural variant2761K → R. Ref.2
Corresponds to variant rs35074452 [ dbSNP | Ensembl ].
VAR_025141
Natural variant2861R → H in EPXD. Ref.7
Corresponds to variant rs121434566 [ dbSNP | Ensembl ].
VAR_015376
Natural variant2921P → L. Ref.2
Corresponds to variant rs33971258 [ dbSNP | Ensembl ].
VAR_025142
Natural variant3261R → H. Ref.8
Corresponds to variant rs35832094 [ dbSNP | Ensembl ].
VAR_060197
Natural variant3261R → L. Ref.8
VAR_060198
Natural variant3261R → P. Ref.2
Corresponds to variant rs35832094 [ dbSNP | Ensembl ].
VAR_025143
Natural variant3581P → L Associated with Japanese cedar pollinosis. Ref.2 Ref.8
Corresponds to variant rs35135976 [ dbSNP | Ensembl ].
VAR_025144
Natural variant3641R → H. Ref.2
Corresponds to variant rs35232062 [ dbSNP | Ensembl ].
VAR_025145
Natural variant4411K → T. Ref.2
Corresponds to variant rs35750729 [ dbSNP | Ensembl ].
VAR_025146
Natural variant4581V → M.
Corresponds to variant rs34817773 [ dbSNP | Ensembl ].
VAR_050486
Natural variant4961H → Q. Ref.2
Corresponds to variant rs33955150 [ dbSNP | Ensembl ].
VAR_025147
Natural variant5721N → Y. Ref.2
Corresponds to variant rs2302311 [ dbSNP | Ensembl ].
VAR_020031

Experimental info

Sequence conflict13 – 186TLVLAQ → EFRGQD AA sequence Ref.3
Sequence conflict211E → Q AA sequence Ref.3
Sequence conflict1131N → I in CAA32530. Ref.3
Sequence conflict1631S → C AA sequence Ref.3
Sequence conflict645 – 66016RDGDR…GVFTK → ETETGSGGRTRCFHQ AA sequence Ref.3

Sequences

Sequence LengthMass (Da)Tools
P11678 [UniParc].

Last modified February 1, 1996. Version 2.
Checksum: CEB4E689A6C46374

FASTA71581,040
        10         20         30         40         50         60 
MHLLPALAGV LATLVLAQPC EGTDPASPGA VETSVLRDCI AEAKLLVDAA YNWTQKSIKQ 

        70         80         90        100        110        120 
RLRSGSASPM DLLSYFKQPV AATRTVVRAA DYMHVALGLL EEKLQPQRSG PFNVTDVLTE 

       130        140        150        160        170        180 
PQLRLLSQAS GCALRDQAER CSDKYRTITG RCNNKRRPLL GASNQALARW LPAEYEDGLS 

       190        200        210        220        230        240 
LPFGWTPSRR RNGFLLPLVR AVSNQIVRFP NERLTSDRGR ALMFMQWGQF IDHDLDFSPE 

       250        260        270        280        290        300 
SPARVAFTAG VDCERTCAQL PPCFPIKIPP NDPRIKNQRD CIPFFRSAPS CPQNKNRVRN 

       310        320        330        340        350        360 
QINALTSFVD ASMVYGSEVS LSLRLRNRTN YLGLLAINQR FQDNGRALLP FDNLHDDPCL 

       370        380        390        400        410        420 
LTNRSARIPC FLAGDTRSTE TPKLAAMHTL FMREHNRLAT ELRRLNPRWN GDKLYNEARK 

       430        440        450        460        470        480 
IMGAMVQIIT YRDFLPLVLG KARARRTLGH YRGYCSNVDP RVANVFTLAF RFGHTMLQPF 

       490        500        510        520        530        540 
MFRLDSQYRA SAPNSHVPLS SAFFASWRIV YEGGIDPILR GLMATPAKLN RQDAMLVDEL 

       550        560        570        580        590        600 
RDRLFRQVRR IGLDLAALNM QRSRDHGLPG YNAWRRFCGL SQPRNLAQLS RVLKNQDLAR 

       610        620        630        640        650        660 
KFLNLYGTPD NIDIWIGAIA EPLLPGARVG PLLACLFENQ FRRARDGDRF WWQKRGVFTK 

       670        680        690        700        710 
RQRKALSRIS LSRIICDNTG ITTVSRDIFR ANIYPRGFVN CSRIPRLNLS AWRGT 

« Hide

References

[1]"Molecular cloning and characterization of a chromosomal gene for human eosinophil peroxidase."
Sakamaki K., Tomonaga M., Tsukui K., Nagata S.
J. Biol. Chem. 264:16828-16836(1989) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
Tissue: Placenta.
[2]NIEHS SNPs program
Submitted (MAY-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS MET-40; HIS-122; GLU-249; ARG-276; LEU-292; PRO-326; LEU-358; HIS-364; THR-441; GLN-496 AND TYR-572.
[3]"Molecular cloning of the human eosinophil peroxidase. Evidence for the existence of a peroxidase multigene family."
Ten R.M., Pease L.R., McKean D.J., Bell M.P., Gleich G.J.
J. Exp. Med. 169:1757-1769(1989) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 13-715, PROTEIN SEQUENCE OF 140-187 AND 251-288.
Tissue: Blood.
[4]"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."
Oxvig C., Thomsen A.R., Overgaard M.T., Sorensen E.S., Hoejrup P., Bjerrum M.J., Gleich G.J., Sottrup-Jensen L.
J. Biol. Chem. 274:16953-16958(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: COVALENT HEME ATTACHMENT, PARTIAL PROTEIN SEQUENCE.
Tissue: Blood.
[5]"Human eosinophil peroxidase induces surface alteration, killing, and lysis of Mycobacterium tuberculosis."
Borelli V., Vita F., Shankar S., Soranzo M.R., Banfi E., Scialino G., Brochetta C., Zabucchi G.
Infect. Immun. 71:605-613(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[6]"Post-translational tyrosine nitration of eosinophil granule toxins mediated by eosinophil peroxidase."
Ulrich M., Petre A., Youhnovski N., Proemm F., Schirle M., Schumm M., Pero R.S., Doyle A., Checkel J., Kita H., Thiyagarajan N., Acharya K.R., Schmid-Grendelmeier P., Simon H.-U., Schwarz H., Tsutsui M., Shimokawa H., Bellon G. expand/collapse author list , Lee J.J., Przybylski M., Doering G.
J. Biol. Chem. 283:28629-28640(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, NITRATION AT TYR-488.
[7]"Hereditary eosinophil peroxidase deficiency: immunochemical and spectroscopic studies and evidence for a compound heterozygosity of the defect."
Romano M., Patriarca P., Melo C., Baralle F.E., Dri P.
Proc. Natl. Acad. Sci. U.S.A. 91:12496-12500(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT EPXD HIS-286.
[8]"High contribution contrast between the genes of eosinophil peroxidase and IL-4 receptor alpha-chain in Japanese cedar pollinosis."
Nakamura H., Miyagawa K., Ogino K., Endo T., Imai T., Ozasa K., Motohashi Y., Matsuzaki I., Sasahara S., Hatta K., Eboshida A.
J. Allergy Clin. Immunol. 112:1127-1131(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS HIS-326; LEU-326 AND LEU-358, POLYMORPHISM.
+Additional computationally mapped references.

Web resources

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M29913 expand/collapse EMBL AC list , M29904, M29905, M29906, M29907, M29908, M29909, M29910, M29911, M29912 Genomic DNA. Translation: AAA58458.1.
DQ054598 Genomic DNA. Translation: AAY43126.1.
X14346 mRNA. Translation: CAA32530.1.
PIRA34408.
RefSeqNP_000493.1. NM_000502.4.
UniGeneHs.279259.

3D structure databases

ProteinModelPortalP11678.
SMRP11678. Positions 143-713.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

IntActP11678. 3 interactions.
STRING9606.ENSP00000225371.

Chemistry

ChEMBLCHEMBL2438.

Protein family/group databases

PeroxiBase3317. HsEPO.

PTM databases

PhosphoSiteP11678.

Polymorphism databases

DMDM1352738.

Proteomic databases

PaxDbP11678.
PRIDEP11678.

Protocols and materials databases

DNASU8288.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000225371; ENSP00000225371; ENSG00000121053.
GeneID8288.
KEGGhsa:8288.
UCSCuc002ivq.3. human.

Organism-specific databases

CTD8288.
GeneCardsGC17P056270.
H-InvDBHIX0202542.
HGNCHGNC:3423. EPX.
HPAHPA050507.
MIM131399. gene.
261500. phenotype.
neXtProtNX_P11678.
PharmGKBPA27841.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG262194.
HOGENOMHOG000016084.
HOVERGENHBG000071.
InParanoidP11678.
KOK10788.
OMAMHVALGL.
OrthoDBEOG7M0NQW.
PhylomeDBP11678.
TreeFamTF314316.

Gene expression databases

BgeeP11678.
CleanExHS_EPO.
HS_EPX.
GenevestigatorP11678.

Family and domain databases

Gene3D1.10.640.10. 1 hit.
InterProIPR010255. Haem_peroxidase.
IPR002007. Haem_peroxidase_animal.
IPR019791. Haem_peroxidase_animal_subgr.
[Graphical view]
PfamPF03098. An_peroxidase. 1 hit.
[Graphical view]
PRINTSPR00457. ANPEROXIDASE.
SUPFAMSSF48113. SSF48113. 1 hit.
PROSITEPS00435. PEROXIDASE_1. 1 hit.
PS50292. PEROXIDASE_3. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiEosinophil_peroxidase.
GenomeRNAi8288.
NextBio31057.
PROP11678.
SOURCESearch...

Entry information

Entry namePERE_HUMAN
AccessionPrimary (citable) accession number: P11678
Secondary accession number(s): Q4TVP3
Entry history
Integrated into UniProtKB/Swiss-Prot: October 1, 1989
Last sequence update: February 1, 1996
Last modified: February 19, 2014
This is version 148 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 17

Human chromosome 17: entries, gene names and cross-references to MIM