Reviewed, UniProtKB/Swiss-Prot P11678 (PERE_HUMAN)

Names and originHide

Protein names

Recommended name:
Eosinophil peroxidase
Short name=EPO
EC=1.11.1.7

Cleaved into the following 2 chains:

1. Eosinophil peroxidase light chain
2. Eosinophil peroxidase heavy chain

Gene names

Name:	EPX
Synonyms:	EPER, EPO, EPP

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributesHide

Sequence length	715 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

General annotation (Comments)Hide

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	Donor + H2O2 = oxidized 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	Defects in EPX are the cause of eosinophil peroxidase deficiency (EPD) [MIM:261500]. EPD is an autosomal recessive defect where anomalous eosinophils are characterized by nuclear hypersegmentation, hypogranulation, and negative peroxidase and phospholipid staining. Ref.7
Sequence similarities	Belongs to the peroxidase family. XPO subfamily.

OntologiesHide

Keywords
Biological process	Hydrogen peroxide
Coding sequence diversity	Polymorphism
Disease	Disease mutation
Domain	Signal
Ligand	Calcium Heme Iron Metal-binding
Molecular function	Oxidoreductase Peroxidase
PTM	Disulfide bond Glycoprotein Nitration
Technical term	Complete proteome Direct protein sequencing
Gene Ontology (GO)
Biological process	hydrogen peroxide catabolic process Inferred from electronic annotation. Source: UniProtKB-KW oxidation reduction Inferred from electronic annotation. Source: UniProtKB-KW
Molecular function	heme binding Inferred from electronic annotation. Source: InterPro peroxidase activity Traceable author statement. Source: ProtInc protein binding Inferred from physical interaction. Source: IntAct
Complete GO annotation...

Binary interactionsHide

With	Entry	#Exp.	IntAct	Notes
NCK1	P16333	1	EBI-1761505,EBI-389883
PIK3R1	P27986	1	EBI-1761505,EBI-79464
PLCG1	P19174	1	EBI-1761505,EBI-79387

Sequence annotation (Features)Hide

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 17	17	Potential
	Propeptide	18 – 139	122			PRO_0000023639
	Chain	140 – 250	111	Eosinophil peroxidase light chain		PRO_0000023640
	Chain	251 – 715	465	Eosinophil peroxidase heavy chain		PRO_0000023641
Sites
	Active site	233	1	Proton acceptor By similarity
	Metal binding	234	1	Calcium By similarity
	Metal binding	306	1	Calcium By similarity
	Metal binding	308	1	Calcium; via carbonyl oxygen By similarity
	Metal binding	310	1	Calcium By similarity
	Metal binding	312	1	Calcium By similarity
	Metal binding	474	1	Iron (heme axial ligand) By similarity
	Binding site	232	1	Heme (covalent; via 2 links); partial
	Binding site	380	1	Heme (covalent; via 2 links)
	Site	377	1	Transition state stabilizer By similarity
Amino acid modifications
	Modified residue	488	1	Nitrated tyrosine Ref.6
	Glycosylation	52	1	N-linked (GlcNAc...) Potential
	Glycosylation	113	1	N-linked (GlcNAc...) Potential
	Glycosylation	327	1	N-linked (GlcNAc...) Potential
	Glycosylation	363	1	N-linked (GlcNAc...) Potential
	Glycosylation	700	1	N-linked (GlcNAc...) Potential
	Glycosylation	708	1	N-linked (GlcNAc...) Potential
	Disulfide bond	141 ↔ 152		By similarity
	Disulfide bond	253 ↔ 263		By similarity
	Disulfide bond	257 ↔ 281		By similarity
	Disulfide bond	359 ↔ 370		By similarity
	Disulfide bond	578 ↔ 635		By similarity
	Disulfide bond	676 ↔ 701		By similarity
Natural variations
	Natural variant	35	1	V → I. [dbSNP:rs34553736]		VAR_050485
	Natural variant	40	1	I → M. [dbSNP:rs11079339] Ref.2		VAR_025138
	Natural variant	122	1	Q → H. [dbSNP:rs11652709] Ref.2		VAR_025139
	Natural variant	249	1	A → E. [dbSNP:rs35896669] Ref.2		VAR_025140
	Natural variant	276	1	K → R. [dbSNP:rs35074452] Ref.2		VAR_025141
	Natural variant	286	1	R → H in EPD. Ref.7		VAR_015376
	Natural variant	292	1	P → L. [dbSNP:rs33971258] Ref.2		VAR_025142
	Natural variant	326	1	R → H		VAR_060197
	Natural variant	326	1	R → L		VAR_060198
	Natural variant	326	1	R → P. [dbSNP:rs35832094] Ref.2		VAR_025143
	Natural variant	358	1	P → L Associated with Japanese cedar pollinosis. [dbSNP:rs35135976] Ref.2 Ref.8		VAR_025144
	Natural variant	364	1	R → H. [dbSNP:rs35232062] Ref.2		VAR_025145
	Natural variant	441	1	K → T. [dbSNP:rs35750729] Ref.2		VAR_025146
	Natural variant	458	1	V → M. [dbSNP:rs34817773]		VAR_050486
	Natural variant	496	1	H → Q. [dbSNP:rs33955150] Ref.2		VAR_025147
	Natural variant	572	1	N → Y. [dbSNP:rs2302311] Ref.2		VAR_020031
Experimental info
	Sequence conflict	13 – 18	6	TLVLAQ → EFRGQD AA sequence Ref.3
	Sequence conflict	21	1	E → Q AA sequence Ref.3
	Sequence conflict	113	1	N → I in CAA32530. Ref.3
	Sequence conflict	163	1	S → C AA sequence Ref.3
	Sequence conflict	645 – 660	16	RDGDR…GVFTK → ETETGSGGRTRCFHQ AA sequence Ref.3

SequencesHide

	Sequence		Length	Mass (Da)
	P11678-1 [UniParc]. Last modified February 1, 1996. Version 2. Checksum: CEB4E689A6C46374	FASTA	715	81,040
	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

ReferencesHide

[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: 2550461] [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: 2541222] [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: 10358043] [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: 12540536] [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. , Lee J.J., Przybylski M., Doering G. J. Biol. Chem. 283:28629-28640(2008) [PubMed: 18694936] [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: 7809065] [Abstract] Cited for: VARIANT EPD 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: 14657871] [Abstract] Cited for: VARIANTS HIS-326; LEU-326 AND LEU-358, POLYMORPHISM.
+	Additional computationally mapped references.

Web resourcesHide

NIEHS-SNPs

Cross-referencesHide

Sequence databases
EMBL GenBank DDBJ	M29913 , 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.
IPI	IPI00006690.
PIR	A34408.
RefSeq	NP_000493.1.
UniGene	Hs.279259
3D structure databases
SMR	P11678. Positions 129-714.
ModBase	Search...
Protein-protein interaction databases
IntAct	P11678. 3 interactions.
MINT	MINT-7242336.
STRING	P11678.
Protein family/group databases
PeroxiBase	3317. HsEPO.
PTM databases
PhosphoSite	P11678.
Proteomic databases
PRIDE	P11678.
Genome annotation databases
Ensembl	ENST00000225371; ENSP00000225371; ENSG00000121053; Homo sapiens. [Genome view]
GeneID	8288.
KEGG	hsa:8288.
UCSC	uc002ivq.2. human.
Organism-specific databases
CTD	8288.
GeneCards	GC17P053625.
HGNC	HGNC:3423. EPX.
MIM	131399. gene. 261500. phenotype.
PharmGKB	PA27841.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG09805.
HOGENOM	HBG357654.
HOVERGEN	HBG000071.
InParanoid	P11678.
OMA	DSQYRAS.
OrthoDB	EOG97DD1D.
PhylomeDB	P11678.
Enzyme and pathway databases
BRENDA	1.11.1.7. 247.
Gene expression databases
ArrayExpress	P11678.
Bgee	P11678.
CleanEx	HS_EPO. HS_EPX.
Genevestigator	P11678.
GermOnline	ENSG00000121053. Homo sapiens.
Family and domain databases
InterPro	IPR010255. Haem_peroxidase. IPR002007. Haem_peroxidase_animal. IPR019791. Haem_peroxidase_animal_sg. [Graphical view]
Gene3D	G3DSA:1.10.640.10. Haem_peroxidase_animal. 1 hit.
Pfam	PF03098. An_peroxidase. 1 hit. [Graphical view]
PRINTS	PR00457. ANPEROXIDASE.
SUPFAM	SSF48113. Peroxidase_super. 1 hit.
PROSITE	PS00435. PEROXIDASE_1. 1 hit. PS00436. PEROXIDASE_2. False negative. PS50292. PEROXIDASE_3. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	31057.
SOURCE	Search...

Entry informationHide

Entry name

PERE_HUMAN

Accession

Primary (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:	July 13, 2010
This is version 115 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

Disclaimer

Any 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.