Full text data of EPX
EPX
(EPER, EPO, EPP)
[Confidence: medium (present in either hRBCD or BSc_CH or PM22954596)]
Eosinophil peroxidase; EPO; 1.11.1.7; Eosinophil peroxidase light chain; Eosinophil peroxidase heavy chain; Flags: Precursor
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Eosinophil peroxidase; EPO; 1.11.1.7; Eosinophil peroxidase light chain; Eosinophil peroxidase heavy chain; Flags: Precursor
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
P11678
ID PERE_HUMAN Reviewed; 715 AA.
AC P11678; Q4TVP3;
DT 01-OCT-1989, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-FEB-1996, sequence version 2.
DT 22-JAN-2014, entry version 147.
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;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC TISSUE=Placenta;
RX PubMed=2550461;
RA Sakamaki K., Tomonaga M., Tsukui K., Nagata S.;
RT "Molecular cloning and characterization of a chromosomal gene for
RT human eosinophil peroxidase.";
RL J. Biol. Chem. 264:16828-16836(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS MET-40; HIS-122;
RP GLU-249; ARG-276; LEU-292; PRO-326; LEU-358; HIS-364; THR-441; GLN-496
RP 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
RP AND 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
RT the 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
RT Glu-241 in human eosinophil peroxidase. The ester with Asp-93 is only
RT partially 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
RT lysis 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.,
RA Acharya K.R., Schmid-Grendelmeier P., Simon H.-U., Schwarz H.,
RA Tsutsui M., Shimokawa H., Bellon G., Lee J.J., Przybylski M.,
RA 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 EPD 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
RT the 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
RT and 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
CC proteins in mature resting eosinophils. Shows significant
CC inhibitory activity towards Mycobacterium tuberculosis H37Rv by
CC inducing bacterial fragmentation and lysis.
CC -!- CATALYTIC ACTIVITY: 2 phenolic donor + H(2)O(2) = 2 phenoxyl
CC radical of the donor + 2 H(2)O.
CC -!- COFACTOR: Binds 1 calcium ion per heterodimer (By similarity).
CC -!- COFACTOR: Binds 1 heme B (iron-protoporphyrin IX) covalently
CC through ester linkages to hydroxylated methyl groups formed auto-
CC catalytically with hydrogen peroxide at the heme C-1 and C-5
CC positions. The ester linkage to Asp-232 was observed in 30% of the
CC chains.
CC -!- SUBUNIT: Tetramer of two light chains and two heavy chains.
CC -!- SUBCELLULAR LOCATION: Cytoplasmic granule. Note=Cytoplasmic
CC granules of eosinophils.
CC -!- POLYMORPHISM: Allelic variant in EPX is associated with Japanese
CC cedar pollinosis which is a type I allergic disease with ocular
CC and nasal symptoms that develop paroxysmally on contact with
CC Japanese cedar pollen. These symptoms, which occur seasonally each
CC year, are typical features of allergic rhinitis, such as sneezing,
CC excessive nasal secretion, nasal congestion, and conjunctival
CC itching.
CC -!- DISEASE: Eosinophil peroxidase deficiency (EPD) [MIM:261500]:
CC Autosomal recessive defect where anomalous eosinophils are
CC characterized by nuclear hypersegmentation, hypogranulation, and
CC negative peroxidase and phospholipid staining. Note=The disease is
CC caused by mutations affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the peroxidase family. XPO subfamily.
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/epx/";
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
CC -----------------------------------------------------------------------
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 PIR; A34408; A34408.
DR RefSeq; NP_000493.1; NM_000502.4.
DR UniGene; Hs.279259; -.
DR ProteinModelPortal; P11678; -.
DR SMR; P11678; 143-713.
DR IntAct; P11678; 3.
DR STRING; 9606.ENSP00000225371; -.
DR ChEMBL; CHEMBL2438; -.
DR PeroxiBase; 3317; HsEPO.
DR PhosphoSite; P11678; -.
DR DMDM; 1352738; -.
DR PaxDb; P11678; -.
DR PRIDE; P11678; -.
DR DNASU; 8288; -.
DR Ensembl; ENST00000225371; ENSP00000225371; ENSG00000121053.
DR GeneID; 8288; -.
DR KEGG; hsa:8288; -.
DR UCSC; uc002ivq.3; human.
DR CTD; 8288; -.
DR GeneCards; GC17P056270; -.
DR H-InvDB; HIX0202542; -.
DR HGNC; HGNC:3423; EPX.
DR HPA; HPA050507; -.
DR MIM; 131399; gene.
DR MIM; 261500; phenotype.
DR neXtProt; NX_P11678; -.
DR PharmGKB; PA27841; -.
DR eggNOG; NOG262194; -.
DR HOGENOM; HOG000016084; -.
DR HOVERGEN; HBG000071; -.
DR InParanoid; P11678; -.
DR KO; K10788; -.
DR OMA; MHVALGL; -.
DR OrthoDB; EOG7M0NQW; -.
DR PhylomeDB; P11678; -.
DR GeneWiki; Eosinophil_peroxidase; -.
DR GenomeRNAi; 8288; -.
DR NextBio; 31057; -.
DR PRO; PR:P11678; -.
DR Bgee; P11678; -.
DR CleanEx; HS_EPO; -.
DR CleanEx; HS_EPX; -.
DR Genevestigator; P11678; -.
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; TAS:ProtInc.
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:0032753; P:positive regulation of interleukin-4 production; IEA:Ensembl.
DR Gene3D; 1.10.640.10; -; 1.
DR InterPro; IPR010255; Haem_peroxidase.
DR InterPro; IPR002007; Haem_peroxidase_animal.
DR InterPro; IPR019791; Haem_peroxidase_animal_subgr.
DR Pfam; PF03098; An_peroxidase; 1.
DR PRINTS; PR00457; ANPEROXIDASE.
DR SUPFAM; SSF48113; SSF48113; 1.
DR PROSITE; PS00435; PEROXIDASE_1; 1.
DR PROSITE; PS00436; PEROXIDASE_2; FALSE_NEG.
DR PROSITE; PS50292; PEROXIDASE_3; 1.
PE 1: Evidence at protein level;
KW Calcium; Complete proteome; Direct protein sequencing;
KW Disease mutation; Disulfide bond; Glycoprotein; Heme;
KW Hydrogen peroxide; Iron; Metal-binding; Nitration; Oxidoreductase;
KW Peroxidase; Polymorphism; Reference proteome; Signal.
FT SIGNAL 1 17 Potential.
FT PROPEP 18 139
FT /FTId=PRO_0000023639.
FT CHAIN 140 250 Eosinophil peroxidase light chain.
FT /FTId=PRO_0000023640.
FT CHAIN 251 715 Eosinophil peroxidase heavy chain.
FT /FTId=PRO_0000023641.
FT ACT_SITE 233 233 Proton acceptor (By similarity).
FT METAL 234 234 Calcium (By similarity).
FT METAL 306 306 Calcium (By similarity).
FT METAL 308 308 Calcium; via carbonyl oxygen (By
FT similarity).
FT METAL 310 310 Calcium (By similarity).
FT METAL 312 312 Calcium (By similarity).
FT METAL 474 474 Iron (heme axial ligand) (By similarity).
FT BINDING 232 232 Heme (covalent; via 2 links); partial.
FT BINDING 380 380 Heme (covalent; via 2 links).
FT SITE 377 377 Transition state stabilizer (By
FT similarity).
FT MOD_RES 488 488 Nitrated tyrosine.
FT CARBOHYD 52 52 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 113 113 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 327 327 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 363 363 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 700 700 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 708 708 N-linked (GlcNAc...) (Potential).
FT DISULFID 141 152 By similarity.
FT DISULFID 253 263 By similarity.
FT DISULFID 257 281 By similarity.
FT DISULFID 359 370 By similarity.
FT DISULFID 578 635 By similarity.
FT DISULFID 676 701 By similarity.
FT VARIANT 35 35 V -> I (in dbSNP:rs34553736).
FT /FTId=VAR_050485.
FT VARIANT 40 40 I -> M (in dbSNP:rs11079339).
FT /FTId=VAR_025138.
FT VARIANT 122 122 Q -> H (in dbSNP:rs11652709).
FT /FTId=VAR_025139.
FT VARIANT 249 249 A -> E (in dbSNP:rs35896669).
FT /FTId=VAR_025140.
FT VARIANT 276 276 K -> R (in dbSNP:rs35074452).
FT /FTId=VAR_025141.
FT VARIANT 286 286 R -> H (in EPD; dbSNP:rs121434566).
FT /FTId=VAR_015376.
FT VARIANT 292 292 P -> L (in dbSNP:rs33971258).
FT /FTId=VAR_025142.
FT VARIANT 326 326 R -> H (in dbSNP:rs35832094).
FT /FTId=VAR_060197.
FT VARIANT 326 326 R -> L.
FT /FTId=VAR_060198.
FT VARIANT 326 326 R -> P (in dbSNP:rs35832094).
FT /FTId=VAR_025143.
FT VARIANT 358 358 P -> L (associated with Japanese cedar
FT pollinosis; dbSNP:rs35135976).
FT /FTId=VAR_025144.
FT VARIANT 364 364 R -> H (in dbSNP:rs35232062).
FT /FTId=VAR_025145.
FT VARIANT 441 441 K -> T (in dbSNP:rs35750729).
FT /FTId=VAR_025146.
FT VARIANT 458 458 V -> M (in dbSNP:rs34817773).
FT /FTId=VAR_050486.
FT VARIANT 496 496 H -> Q (in dbSNP:rs33955150).
FT /FTId=VAR_025147.
FT VARIANT 572 572 N -> Y (in dbSNP:rs2302311).
FT /FTId=VAR_020031.
FT CONFLICT 13 18 TLVLAQ -> EFRGQD (in Ref. 3; AA
FT sequence).
FT CONFLICT 21 21 E -> Q (in Ref. 3; AA sequence).
FT CONFLICT 113 113 N -> I (in Ref. 3; CAA32530).
FT CONFLICT 163 163 S -> C (in Ref. 3; AA sequence).
FT CONFLICT 645 660 RDGDRFWWQKRGVFTK -> ETETGSGGRTRCFHQ (in
FT Ref. 3; AA sequence).
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
//
ID PERE_HUMAN Reviewed; 715 AA.
AC P11678; Q4TVP3;
DT 01-OCT-1989, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-FEB-1996, sequence version 2.
DT 22-JAN-2014, entry version 147.
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;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC TISSUE=Placenta;
RX PubMed=2550461;
RA Sakamaki K., Tomonaga M., Tsukui K., Nagata S.;
RT "Molecular cloning and characterization of a chromosomal gene for
RT human eosinophil peroxidase.";
RL J. Biol. Chem. 264:16828-16836(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS MET-40; HIS-122;
RP GLU-249; ARG-276; LEU-292; PRO-326; LEU-358; HIS-364; THR-441; GLN-496
RP 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
RP AND 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
RT the 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
RT Glu-241 in human eosinophil peroxidase. The ester with Asp-93 is only
RT partially 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
RT lysis 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.,
RA Acharya K.R., Schmid-Grendelmeier P., Simon H.-U., Schwarz H.,
RA Tsutsui M., Shimokawa H., Bellon G., Lee J.J., Przybylski M.,
RA 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 EPD 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
RT the 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
RT and 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
CC proteins in mature resting eosinophils. Shows significant
CC inhibitory activity towards Mycobacterium tuberculosis H37Rv by
CC inducing bacterial fragmentation and lysis.
CC -!- CATALYTIC ACTIVITY: 2 phenolic donor + H(2)O(2) = 2 phenoxyl
CC radical of the donor + 2 H(2)O.
CC -!- COFACTOR: Binds 1 calcium ion per heterodimer (By similarity).
CC -!- COFACTOR: Binds 1 heme B (iron-protoporphyrin IX) covalently
CC through ester linkages to hydroxylated methyl groups formed auto-
CC catalytically with hydrogen peroxide at the heme C-1 and C-5
CC positions. The ester linkage to Asp-232 was observed in 30% of the
CC chains.
CC -!- SUBUNIT: Tetramer of two light chains and two heavy chains.
CC -!- SUBCELLULAR LOCATION: Cytoplasmic granule. Note=Cytoplasmic
CC granules of eosinophils.
CC -!- POLYMORPHISM: Allelic variant in EPX is associated with Japanese
CC cedar pollinosis which is a type I allergic disease with ocular
CC and nasal symptoms that develop paroxysmally on contact with
CC Japanese cedar pollen. These symptoms, which occur seasonally each
CC year, are typical features of allergic rhinitis, such as sneezing,
CC excessive nasal secretion, nasal congestion, and conjunctival
CC itching.
CC -!- DISEASE: Eosinophil peroxidase deficiency (EPD) [MIM:261500]:
CC Autosomal recessive defect where anomalous eosinophils are
CC characterized by nuclear hypersegmentation, hypogranulation, and
CC negative peroxidase and phospholipid staining. Note=The disease is
CC caused by mutations affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the peroxidase family. XPO subfamily.
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/epx/";
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
CC -----------------------------------------------------------------------
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 PIR; A34408; A34408.
DR RefSeq; NP_000493.1; NM_000502.4.
DR UniGene; Hs.279259; -.
DR ProteinModelPortal; P11678; -.
DR SMR; P11678; 143-713.
DR IntAct; P11678; 3.
DR STRING; 9606.ENSP00000225371; -.
DR ChEMBL; CHEMBL2438; -.
DR PeroxiBase; 3317; HsEPO.
DR PhosphoSite; P11678; -.
DR DMDM; 1352738; -.
DR PaxDb; P11678; -.
DR PRIDE; P11678; -.
DR DNASU; 8288; -.
DR Ensembl; ENST00000225371; ENSP00000225371; ENSG00000121053.
DR GeneID; 8288; -.
DR KEGG; hsa:8288; -.
DR UCSC; uc002ivq.3; human.
DR CTD; 8288; -.
DR GeneCards; GC17P056270; -.
DR H-InvDB; HIX0202542; -.
DR HGNC; HGNC:3423; EPX.
DR HPA; HPA050507; -.
DR MIM; 131399; gene.
DR MIM; 261500; phenotype.
DR neXtProt; NX_P11678; -.
DR PharmGKB; PA27841; -.
DR eggNOG; NOG262194; -.
DR HOGENOM; HOG000016084; -.
DR HOVERGEN; HBG000071; -.
DR InParanoid; P11678; -.
DR KO; K10788; -.
DR OMA; MHVALGL; -.
DR OrthoDB; EOG7M0NQW; -.
DR PhylomeDB; P11678; -.
DR GeneWiki; Eosinophil_peroxidase; -.
DR GenomeRNAi; 8288; -.
DR NextBio; 31057; -.
DR PRO; PR:P11678; -.
DR Bgee; P11678; -.
DR CleanEx; HS_EPO; -.
DR CleanEx; HS_EPX; -.
DR Genevestigator; P11678; -.
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; TAS:ProtInc.
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:0032753; P:positive regulation of interleukin-4 production; IEA:Ensembl.
DR Gene3D; 1.10.640.10; -; 1.
DR InterPro; IPR010255; Haem_peroxidase.
DR InterPro; IPR002007; Haem_peroxidase_animal.
DR InterPro; IPR019791; Haem_peroxidase_animal_subgr.
DR Pfam; PF03098; An_peroxidase; 1.
DR PRINTS; PR00457; ANPEROXIDASE.
DR SUPFAM; SSF48113; SSF48113; 1.
DR PROSITE; PS00435; PEROXIDASE_1; 1.
DR PROSITE; PS00436; PEROXIDASE_2; FALSE_NEG.
DR PROSITE; PS50292; PEROXIDASE_3; 1.
PE 1: Evidence at protein level;
KW Calcium; Complete proteome; Direct protein sequencing;
KW Disease mutation; Disulfide bond; Glycoprotein; Heme;
KW Hydrogen peroxide; Iron; Metal-binding; Nitration; Oxidoreductase;
KW Peroxidase; Polymorphism; Reference proteome; Signal.
FT SIGNAL 1 17 Potential.
FT PROPEP 18 139
FT /FTId=PRO_0000023639.
FT CHAIN 140 250 Eosinophil peroxidase light chain.
FT /FTId=PRO_0000023640.
FT CHAIN 251 715 Eosinophil peroxidase heavy chain.
FT /FTId=PRO_0000023641.
FT ACT_SITE 233 233 Proton acceptor (By similarity).
FT METAL 234 234 Calcium (By similarity).
FT METAL 306 306 Calcium (By similarity).
FT METAL 308 308 Calcium; via carbonyl oxygen (By
FT similarity).
FT METAL 310 310 Calcium (By similarity).
FT METAL 312 312 Calcium (By similarity).
FT METAL 474 474 Iron (heme axial ligand) (By similarity).
FT BINDING 232 232 Heme (covalent; via 2 links); partial.
FT BINDING 380 380 Heme (covalent; via 2 links).
FT SITE 377 377 Transition state stabilizer (By
FT similarity).
FT MOD_RES 488 488 Nitrated tyrosine.
FT CARBOHYD 52 52 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 113 113 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 327 327 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 363 363 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 700 700 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 708 708 N-linked (GlcNAc...) (Potential).
FT DISULFID 141 152 By similarity.
FT DISULFID 253 263 By similarity.
FT DISULFID 257 281 By similarity.
FT DISULFID 359 370 By similarity.
FT DISULFID 578 635 By similarity.
FT DISULFID 676 701 By similarity.
FT VARIANT 35 35 V -> I (in dbSNP:rs34553736).
FT /FTId=VAR_050485.
FT VARIANT 40 40 I -> M (in dbSNP:rs11079339).
FT /FTId=VAR_025138.
FT VARIANT 122 122 Q -> H (in dbSNP:rs11652709).
FT /FTId=VAR_025139.
FT VARIANT 249 249 A -> E (in dbSNP:rs35896669).
FT /FTId=VAR_025140.
FT VARIANT 276 276 K -> R (in dbSNP:rs35074452).
FT /FTId=VAR_025141.
FT VARIANT 286 286 R -> H (in EPD; dbSNP:rs121434566).
FT /FTId=VAR_015376.
FT VARIANT 292 292 P -> L (in dbSNP:rs33971258).
FT /FTId=VAR_025142.
FT VARIANT 326 326 R -> H (in dbSNP:rs35832094).
FT /FTId=VAR_060197.
FT VARIANT 326 326 R -> L.
FT /FTId=VAR_060198.
FT VARIANT 326 326 R -> P (in dbSNP:rs35832094).
FT /FTId=VAR_025143.
FT VARIANT 358 358 P -> L (associated with Japanese cedar
FT pollinosis; dbSNP:rs35135976).
FT /FTId=VAR_025144.
FT VARIANT 364 364 R -> H (in dbSNP:rs35232062).
FT /FTId=VAR_025145.
FT VARIANT 441 441 K -> T (in dbSNP:rs35750729).
FT /FTId=VAR_025146.
FT VARIANT 458 458 V -> M (in dbSNP:rs34817773).
FT /FTId=VAR_050486.
FT VARIANT 496 496 H -> Q (in dbSNP:rs33955150).
FT /FTId=VAR_025147.
FT VARIANT 572 572 N -> Y (in dbSNP:rs2302311).
FT /FTId=VAR_020031.
FT CONFLICT 13 18 TLVLAQ -> EFRGQD (in Ref. 3; AA
FT sequence).
FT CONFLICT 21 21 E -> Q (in Ref. 3; AA sequence).
FT CONFLICT 113 113 N -> I (in Ref. 3; CAA32530).
FT CONFLICT 163 163 S -> C (in Ref. 3; AA sequence).
FT CONFLICT 645 660 RDGDRFWWQKRGVFTK -> ETETGSGGRTRCFHQ (in
FT Ref. 3; AA sequence).
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
//
MIM
131399
*RECORD*
*FIELD* NO
131399
*FIELD* TI
*131399 EOSINOPHIL PEROXIDASE; EPX
*FIELD* TX
DESCRIPTION
Human eosinophil peroxidase (EC 1.11.1.7) is a heme-containing
read moreglycoprotein that is present in lysosomes of eosinophilic granulocytes.
EPX has been purified from human eosinophils and from eosinophilic
leukemia cells. The purified enzyme has been shown to have a molecular
mass of about 70 kD and to be composed of 1 heavy chain and 1 light
chain. In contrast to myeloperoxidase (MPO; 606989), eosinophil
peroxidase uses bromide instead of chloride to generate a halogenating
oxidant. Myeloperoxidase is more sensitive to cyanide than eosinophil
peroxidase; antibodies directed against human eosinophil peroxidase do
not neutralize myeloperoxidase and vice versa (summary by Sakamaki et
al., 1989).
CLONING
Sakamaki et al. (1989) used human myeloperoxidase cDNA as a probe to
isolate a gene which, from its sequence, was concluded to encode human
eosinophil peroxidase. EPX encodes a deduced 715-amino acid protein. The
heavy chain and the light chain of eosinophil peroxidase were located on
the COOH and NH2 terminus of the protein, respectively, both chains
being coded by a single mRNA, as is the case with myeloperoxidase. The
coding sequences of eosinophil peroxidase and myeloperoxidase showed
homologies of 72.4% at the nucleotide and 69.8% at the amino acid level,
while little homology was found in the 5-prime flanking region.
GENE STRUCTURE
The EPX gene contains 12 exons and spans about 12 kb (Sakamaki et al.,
1989).
MAPPING
By somatic cell hybrid analysis and in situ hybridization, Sakamaki et
al. (2000) mapped the EPX gene to 17q23.1 in a cluster with
lactoperoxidase (LPO; 150205) and myeloperoxidase.
MOLECULAR GENETICS
Romano et al. (1994) reported the molecular characterization of
eosinophil peroxidase in a man with deficiency of this enzyme (261500)
and his family members. His eosinophils contained EPX-related material
as determined immunochemically using either monoclonal or polyclonal
anti-EPX antibodies but had no spectroscopic evidence of the enzyme.
Eosinophil precursors from the proband contained normal-sized EPX mRNA,
which was reverse transcribed into the corresponding cDNA encompassing
the whole gene. Sequence of the cDNA disclosed 2 mutations, a G-to-A
transition causing a nonconservative replacement of an arginine residue
with a histidine (R286H; 131399.0001) and an insertion causing a shift
in the reading frame with appearance of a premature stop codon
(131399.0002). Both the son and the daughter of the proband inherited
the G-to-A transition and their eosinophils contained a peroxidase
activity intermediate between that of control subjects and the proband,
suggesting that the transition is a deficiency-causing mutation.
Eosinophil precursors from the proband were found to synthesize actively
a peroxidase that was apparently normal in terms of cytochemical
reaction and immunoreactivity, but spectroscopically abnormal. The
cytochemical reaction for peroxidase tended to decrease or disappear in
the eosinophil precursors of the proband but not in those of a normal
subject, suggesting that the R286H substitution results in the synthesis
of an unstable EPX that undergoes progressive degradation as the cells
mature.
*FIELD* AV
.0001
EOSINOPHIL PEROXIDASE DEFICIENCY
EPX, ARG286HIS
In a blood donor at the blood bank of Trieste Hospital, Romano et al.
(1994) identified a man with eosinophil peroxidase deficiency (261500)
who was found to be compound heterozygous for 2 mutations in the EPX
gene. One was a G-to-A transition at position 857 that predicted the
nonconservative substitution of histidine for arginine at codon 286
(R286H). Both his son and his daughter had inherited this mutation in
heterozygous state. The other chromosome carried an insertion of a G
within the G tract 1537-1541 at the intron-exon 10 junction
(131399.0002). This caused a shift in the reading frame with the
generation of a stop codon after codon 538, leading to a truncated EPX
precursor that lacked 177 amino acids and had a completely subverted
sequence of the 24-amino acid carboxyl-terminal tail downstream of the
insertion. To establish that the 2 mutations were located on different
chromosomes, a cDNA fragment corresponding to a region including both
mutations (nucleotides 659-1608) was amplified by PCR, cloned, and
sequenced. Each clone was found to contain only 1 of the 2 mutations,
indicating the compound heterozygosity.
.0002
EOSINOPHIL PEROXIDASE DEFICIENCY
EPX, 1-BP INS, 1537G
See 131399.0001 and Romano et al. (1994).
*FIELD* RF
1. Romano, M.; Patriarca, P.; Melo, C.; Baralle, F. E.; Dri, P.:
Hereditary eosinophil peroxidase deficiency: immunochemical and spectroscopic
studies and evidence for a compound heterozygosity of the defect. Proc.
Nat. Acad. Sci. 91: 12496-12500, 1994.
2. Sakamaki, K.; Kanda, N.; Ueda, T.; Aikawa, E.; Nagata, S.: The
eosinophil peroxidase gene forms a cluster with the genes for myeloperoxidase
and lactoperoxidase on human chromosome 17. Cytogenet. Cell Genet. 88:
246-248, 2000.
3. Sakamaki, K.; Tomonaga, M.; Tsukui, K.; Nagata, S.: Molecular
cloning and characterization of a chromosomal gene for human eosinophil
peroxidase. J. Biol. Chem. 264: 16828-16836, 1989.
*FIELD* CN
Joanna S. Amberger - updated: 3/9/2001
*FIELD* CD
Victor A. McKusick: 12/12/1989
*FIELD* ED
carol: 11/12/2013
ckniffin: 5/29/2002
mcapotos: 3/15/2001
joanna: 3/9/2001
carol: 1/13/1995
supermim: 3/16/1992
supermim: 3/20/1990
carol: 12/12/1989
*RECORD*
*FIELD* NO
131399
*FIELD* TI
*131399 EOSINOPHIL PEROXIDASE; EPX
*FIELD* TX
DESCRIPTION
Human eosinophil peroxidase (EC 1.11.1.7) is a heme-containing
read moreglycoprotein that is present in lysosomes of eosinophilic granulocytes.
EPX has been purified from human eosinophils and from eosinophilic
leukemia cells. The purified enzyme has been shown to have a molecular
mass of about 70 kD and to be composed of 1 heavy chain and 1 light
chain. In contrast to myeloperoxidase (MPO; 606989), eosinophil
peroxidase uses bromide instead of chloride to generate a halogenating
oxidant. Myeloperoxidase is more sensitive to cyanide than eosinophil
peroxidase; antibodies directed against human eosinophil peroxidase do
not neutralize myeloperoxidase and vice versa (summary by Sakamaki et
al., 1989).
CLONING
Sakamaki et al. (1989) used human myeloperoxidase cDNA as a probe to
isolate a gene which, from its sequence, was concluded to encode human
eosinophil peroxidase. EPX encodes a deduced 715-amino acid protein. The
heavy chain and the light chain of eosinophil peroxidase were located on
the COOH and NH2 terminus of the protein, respectively, both chains
being coded by a single mRNA, as is the case with myeloperoxidase. The
coding sequences of eosinophil peroxidase and myeloperoxidase showed
homologies of 72.4% at the nucleotide and 69.8% at the amino acid level,
while little homology was found in the 5-prime flanking region.
GENE STRUCTURE
The EPX gene contains 12 exons and spans about 12 kb (Sakamaki et al.,
1989).
MAPPING
By somatic cell hybrid analysis and in situ hybridization, Sakamaki et
al. (2000) mapped the EPX gene to 17q23.1 in a cluster with
lactoperoxidase (LPO; 150205) and myeloperoxidase.
MOLECULAR GENETICS
Romano et al. (1994) reported the molecular characterization of
eosinophil peroxidase in a man with deficiency of this enzyme (261500)
and his family members. His eosinophils contained EPX-related material
as determined immunochemically using either monoclonal or polyclonal
anti-EPX antibodies but had no spectroscopic evidence of the enzyme.
Eosinophil precursors from the proband contained normal-sized EPX mRNA,
which was reverse transcribed into the corresponding cDNA encompassing
the whole gene. Sequence of the cDNA disclosed 2 mutations, a G-to-A
transition causing a nonconservative replacement of an arginine residue
with a histidine (R286H; 131399.0001) and an insertion causing a shift
in the reading frame with appearance of a premature stop codon
(131399.0002). Both the son and the daughter of the proband inherited
the G-to-A transition and their eosinophils contained a peroxidase
activity intermediate between that of control subjects and the proband,
suggesting that the transition is a deficiency-causing mutation.
Eosinophil precursors from the proband were found to synthesize actively
a peroxidase that was apparently normal in terms of cytochemical
reaction and immunoreactivity, but spectroscopically abnormal. The
cytochemical reaction for peroxidase tended to decrease or disappear in
the eosinophil precursors of the proband but not in those of a normal
subject, suggesting that the R286H substitution results in the synthesis
of an unstable EPX that undergoes progressive degradation as the cells
mature.
*FIELD* AV
.0001
EOSINOPHIL PEROXIDASE DEFICIENCY
EPX, ARG286HIS
In a blood donor at the blood bank of Trieste Hospital, Romano et al.
(1994) identified a man with eosinophil peroxidase deficiency (261500)
who was found to be compound heterozygous for 2 mutations in the EPX
gene. One was a G-to-A transition at position 857 that predicted the
nonconservative substitution of histidine for arginine at codon 286
(R286H). Both his son and his daughter had inherited this mutation in
heterozygous state. The other chromosome carried an insertion of a G
within the G tract 1537-1541 at the intron-exon 10 junction
(131399.0002). This caused a shift in the reading frame with the
generation of a stop codon after codon 538, leading to a truncated EPX
precursor that lacked 177 amino acids and had a completely subverted
sequence of the 24-amino acid carboxyl-terminal tail downstream of the
insertion. To establish that the 2 mutations were located on different
chromosomes, a cDNA fragment corresponding to a region including both
mutations (nucleotides 659-1608) was amplified by PCR, cloned, and
sequenced. Each clone was found to contain only 1 of the 2 mutations,
indicating the compound heterozygosity.
.0002
EOSINOPHIL PEROXIDASE DEFICIENCY
EPX, 1-BP INS, 1537G
See 131399.0001 and Romano et al. (1994).
*FIELD* RF
1. Romano, M.; Patriarca, P.; Melo, C.; Baralle, F. E.; Dri, P.:
Hereditary eosinophil peroxidase deficiency: immunochemical and spectroscopic
studies and evidence for a compound heterozygosity of the defect. Proc.
Nat. Acad. Sci. 91: 12496-12500, 1994.
2. Sakamaki, K.; Kanda, N.; Ueda, T.; Aikawa, E.; Nagata, S.: The
eosinophil peroxidase gene forms a cluster with the genes for myeloperoxidase
and lactoperoxidase on human chromosome 17. Cytogenet. Cell Genet. 88:
246-248, 2000.
3. Sakamaki, K.; Tomonaga, M.; Tsukui, K.; Nagata, S.: Molecular
cloning and characterization of a chromosomal gene for human eosinophil
peroxidase. J. Biol. Chem. 264: 16828-16836, 1989.
*FIELD* CN
Joanna S. Amberger - updated: 3/9/2001
*FIELD* CD
Victor A. McKusick: 12/12/1989
*FIELD* ED
carol: 11/12/2013
ckniffin: 5/29/2002
mcapotos: 3/15/2001
joanna: 3/9/2001
carol: 1/13/1995
supermim: 3/16/1992
supermim: 3/20/1990
carol: 12/12/1989
MIM
261500
*RECORD*
*FIELD* NO
261500
*FIELD* TI
#261500 EOSINOPHIL PEROXIDASE DEFICIENCY; EPXD
;;EOSINOPHIL PEROXIDASE DEFICIENCY, PARTIAL;;
read morePEROXIDASE AND PHOSPHOLIPID DEFICIENCY IN EOSINOPHILS;;
PRESENTEY ANOMALY
*FIELD* TX
A number sign (#) is used with this entry because of evidence that
eosinophil peroxidase deficiency (EXPD) is caused by compound
heterozygous mutation in the EPXD gene (131399) on chromosome 17q22.
DESCRIPTION
Eosinophil peroxidase deficiency is a rare abnormality of eosinophil
granulocytes characterized by decreased or absent peroxidase activity
and decreased volume of the granule matrix (summary by Romano et al.,
1994).
CLINICAL FEATURES
In Yemenite Jews in Israel, Presentey (1969) and Presentey and Szapiro
(1969) described a 'new' anomaly of eosinophils characterized by nuclear
hypersegmentation, hypogranulation, and negative peroxidase and
phospholipid staining.
Lepelley et al. (1987) described the Presentey anomaly in twin sisters;
one had refractory anemia, which may have been coincidental and merely
the symptom that brought the twins to attention.
In contrast to myeloperoxidase deficiency (254600), in which all
neutrophils and monocytes are affected, isolated deficiency of
eosinophil peroxidase is very rare (Presentey, 1970, 1984; Presentey and
Joshua, 1982; Schaeffer et al., 1977).
Hoffmann and Tielens (1987) reported the case of an affected 4-year-old
boy of Turkish ancestry whose parents were 'consanguineous in the second
degree.' Hoffmann and Tielens (1987) commented on the fact that the use
of automated flow-cytochemical analyzers in the hematology laboratory
had stimulated interest in peroxidase activity of granulocytes and
brought many cases of hereditary and acquired deficiency to attention.
It was in this way that their case was detected. Valdes and Calero
(1987) described a patient with deficiency of eosinophil peroxidase
detected by flow cytochemistry.
Electron microscopic analyses of peroxidase-deficient eosinophils showed
an increase in the ratio between the size of the matrix and the core of
the specific granules (Lepelley et al., 1987; Lejeune et al., 1988).
Zabucchi et al. (1992) found 5 eosinophil peroxidase-deficient subjects
among 131,000 peripheral blood samples examined by routine automated
methods. All met the main criteria: absent or strongly decreased
reaction for peroxidase, absent or strongly decreased staining with
Sudan Black, and an increased ratio of the granule core volume to the
total granule volume. Zabucchi et al. (1992) demonstrated that the
increased core-matrix ratio was caused mainly by a decrease of the
volume of the matrix and that 2 other matrix proteins, eosinophil
cationic protein (131398) and eosinophil-derived neurotoxin (131410),
appeared to be present in normal amounts.
INHERITANCE
In the patients with eosinophil peroxidase deficiency reported by
Presentey (1969) and Presentey and Szapiro (1969), recessive inheritance
seemed quite clear.
MOLECULAR GENETICS
In a man with eosinophil peroxidase deficiency, Romano et al. (1994)
identified compound heterozygosity for mutations in the EPX gene
(131399.0001-131399.0002).
*FIELD* RF
1. Hoffmann, J. J.; Tielens, A. G.: Partial deficiency of eosinophil
peroxidase. Blut 54: 165-169, 1987.
2. Lejeune, F.; Dournovo, M.; Turpin, F.; Saula, H.; Lortholary, P.
: Deficit en peroxidase des eosinophiles: etude cytologique en microscopie
optique et electronique a propos d'un cas. Nouv. Rev. Franc. Hemat. 30:
177-182, 1988.
3. Lepelley, P.; Zandecky, M.; Parquet, S.; Lerche, B.; Estienne,
M. H.; Fenaux, P.; Torpier, G.; Cosson, A.: Total peroxidase deficiency
in eosinophils: a report on twin sisters, one with a refractory anaemia. Europ.
J. Haemat. 39: 77-81, 1987.
4. Presentey, B.: Partial and severe peroxidase and phospholipid
deficiency in eosinophils: cytochemical and genetic considerations. Acta
Haemat. 44: 345-354, 1970.
5. Presentey, B.: Ultrastructure of human eosinophils genetically
lacking peroxidase. Acta Haemat. 71: 334-340, 1984.
6. Presentey, B.; Joshua, H.: Peroxidase and phospholipid deficiency
in human eosinophilic granulocytes: a marker in population genetics. Experientia 38:
628-629, 1982.
7. Presentey, B. Z.: Morphologic observations and genetic follow-up
of a familial anomaly of eosinophils. Am. J. Clin. Path. 51: 458-462,
1969.
8. Presentey, B. Z.; Szapiro, L.: Hereditary deficiency of peroxidase
and phospholipids in eosinophilic granulocytes. Acta Haemat. 41:
359-362, 1969.
9. Romano, M.; Patriarca, P.; Melo, C.; Baralle, F. E.; Dri, P.:
Hereditary eosinophil peroxidase deficiency: immunochemical and spectroscopic
studies and evidence for a compound heterozygosity of the defect. Proc.
Nat. Acad. Sci. 91: 12496-12500, 1994.
10. Schaeffer, H. E.; Hellriegel, K. P.; Fischer, R.: Zytochemischer
Nachweis der Eosinophilen-Peroxidase (EPOX) unter besonderer Berucksichtigung
des isolierten Peroxidase-Defektes in Eosinophilen. Acta Histochem. Suppl.
XVIII: 195-201, 1977.
11. Valdes, M. D.; Calero, M. A.: Deficiency of eosinophil peroxidase
detected by automated cytochemistry. Acta Haemat. 78: 265 only,
1987.
12. Zabucchi, G.; Soranzo, M. R.; Menegazzi, R.; Vecchio, M.; Knowles,
A.; Piccinini, C.; Spessotto, P.; Patriarca, P.: Eosinophil peroxidase
deficiency: morphological and immunocytochemical studies of the eosinophil-specific
granules. Blood 80: 2903-2910, 1992.
*FIELD* CS
Misc:
No proved associated illness
Lab:
Eosinophil nuclear hypersegmentation, hypogranulation, and negative
peroxidase and phospholipid staining;
Increased ratio of eosinophil granule core volume to total volume
Inheritance:
Autosomal recessive
*FIELD* CD
Victor A. McKusick: 6/4/1986
*FIELD* ED
carol: 11/13/2013
carol: 11/12/2013
carol: 1/13/1995
terry: 4/18/1994
mimadm: 3/29/1994
warfield: 3/22/1994
carol: 2/11/1993
carol: 1/28/1993
*RECORD*
*FIELD* NO
261500
*FIELD* TI
#261500 EOSINOPHIL PEROXIDASE DEFICIENCY; EPXD
;;EOSINOPHIL PEROXIDASE DEFICIENCY, PARTIAL;;
read morePEROXIDASE AND PHOSPHOLIPID DEFICIENCY IN EOSINOPHILS;;
PRESENTEY ANOMALY
*FIELD* TX
A number sign (#) is used with this entry because of evidence that
eosinophil peroxidase deficiency (EXPD) is caused by compound
heterozygous mutation in the EPXD gene (131399) on chromosome 17q22.
DESCRIPTION
Eosinophil peroxidase deficiency is a rare abnormality of eosinophil
granulocytes characterized by decreased or absent peroxidase activity
and decreased volume of the granule matrix (summary by Romano et al.,
1994).
CLINICAL FEATURES
In Yemenite Jews in Israel, Presentey (1969) and Presentey and Szapiro
(1969) described a 'new' anomaly of eosinophils characterized by nuclear
hypersegmentation, hypogranulation, and negative peroxidase and
phospholipid staining.
Lepelley et al. (1987) described the Presentey anomaly in twin sisters;
one had refractory anemia, which may have been coincidental and merely
the symptom that brought the twins to attention.
In contrast to myeloperoxidase deficiency (254600), in which all
neutrophils and monocytes are affected, isolated deficiency of
eosinophil peroxidase is very rare (Presentey, 1970, 1984; Presentey and
Joshua, 1982; Schaeffer et al., 1977).
Hoffmann and Tielens (1987) reported the case of an affected 4-year-old
boy of Turkish ancestry whose parents were 'consanguineous in the second
degree.' Hoffmann and Tielens (1987) commented on the fact that the use
of automated flow-cytochemical analyzers in the hematology laboratory
had stimulated interest in peroxidase activity of granulocytes and
brought many cases of hereditary and acquired deficiency to attention.
It was in this way that their case was detected. Valdes and Calero
(1987) described a patient with deficiency of eosinophil peroxidase
detected by flow cytochemistry.
Electron microscopic analyses of peroxidase-deficient eosinophils showed
an increase in the ratio between the size of the matrix and the core of
the specific granules (Lepelley et al., 1987; Lejeune et al., 1988).
Zabucchi et al. (1992) found 5 eosinophil peroxidase-deficient subjects
among 131,000 peripheral blood samples examined by routine automated
methods. All met the main criteria: absent or strongly decreased
reaction for peroxidase, absent or strongly decreased staining with
Sudan Black, and an increased ratio of the granule core volume to the
total granule volume. Zabucchi et al. (1992) demonstrated that the
increased core-matrix ratio was caused mainly by a decrease of the
volume of the matrix and that 2 other matrix proteins, eosinophil
cationic protein (131398) and eosinophil-derived neurotoxin (131410),
appeared to be present in normal amounts.
INHERITANCE
In the patients with eosinophil peroxidase deficiency reported by
Presentey (1969) and Presentey and Szapiro (1969), recessive inheritance
seemed quite clear.
MOLECULAR GENETICS
In a man with eosinophil peroxidase deficiency, Romano et al. (1994)
identified compound heterozygosity for mutations in the EPX gene
(131399.0001-131399.0002).
*FIELD* RF
1. Hoffmann, J. J.; Tielens, A. G.: Partial deficiency of eosinophil
peroxidase. Blut 54: 165-169, 1987.
2. Lejeune, F.; Dournovo, M.; Turpin, F.; Saula, H.; Lortholary, P.
: Deficit en peroxidase des eosinophiles: etude cytologique en microscopie
optique et electronique a propos d'un cas. Nouv. Rev. Franc. Hemat. 30:
177-182, 1988.
3. Lepelley, P.; Zandecky, M.; Parquet, S.; Lerche, B.; Estienne,
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lacking peroxidase. Acta Haemat. 71: 334-340, 1984.
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in human eosinophilic granulocytes: a marker in population genetics. Experientia 38:
628-629, 1982.
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Hereditary eosinophil peroxidase deficiency: immunochemical and spectroscopic
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granules. Blood 80: 2903-2910, 1992.
*FIELD* CS
Misc:
No proved associated illness
Lab:
Eosinophil nuclear hypersegmentation, hypogranulation, and negative
peroxidase and phospholipid staining;
Increased ratio of eosinophil granule core volume to total volume
Inheritance:
Autosomal recessive
*FIELD* CD
Victor A. McKusick: 6/4/1986
*FIELD* ED
carol: 11/13/2013
carol: 11/12/2013
carol: 1/13/1995
terry: 4/18/1994
mimadm: 3/29/1994
warfield: 3/22/1994
carol: 2/11/1993
carol: 1/28/1993