ECP_HUMAN
ID ECP_HUMAN Reviewed; 160 AA.
AC P12724; Q4VBC1; Q8WTP7; Q8WZ62; Q9GZN9;
DT 01-OCT-1989, integrated into UniProtKB/Swiss-Prot.
DT 15-MAY-2007, sequence version 2.
DT 03-AUG-2022, entry version 202.
DE RecName: Full=Eosinophil cationic protein;
DE Short=ECP;
DE EC=3.1.27.-;
DE AltName: Full=Ribonuclease 3;
DE Short=RNase 3;
DE Flags: Precursor;
GN Name=RNASE3; Synonyms=ECP, RNS3;
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 [MRNA], AND VARIANT ARG-124.
RC TISSUE=Peripheral blood granulocyte;
RX PubMed=2473157; DOI=10.1084/jem.170.1.163;
RA Rosenberg H.F., Ackerman S.J., Tenen D.G.;
RT "Human eosinophil cationic protein. Molecular cloning of a cytotoxin and
RT helminthotoxin with ribonuclease activity.";
RL J. Exp. Med. 170:163-176(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT ARG-124.
RC TISSUE=Fetal liver;
RX PubMed=2387583; DOI=10.1016/0888-7543(90)90197-3;
RA Hamann K.J., Ten R.M., Loegering D.A., Jenkins R.B., Heise M.T.,
RA Schad C.R., Pease L.R., Gleich G.J., Barker R.L.;
RT "Structure and chromosome localization of the human eosinophil-derived
RT neurotoxin and eosinophil cationic protein genes: evidence for intronless
RT coding sequences in the ribonuclease gene superfamily.";
RL Genomics 7:535-546(1990).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT ARG-124.
RX PubMed=2745977;
RA Barker R.L., Loegering D.A., Ten R.M., Hamann K.J., Pease L.R.,
RA Gleich G.J.;
RT "Eosinophil cationic protein cDNA. Comparison with other toxic cationic
RT proteins and ribonucleases.";
RL J. Immunol. 143:952-955(1989).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT ARG-124.
RC TISSUE=Colon;
RA Simonsen C.C., Kennedy J., Comstock L., Ashton N., McGrogan M.;
RL Submitted (OCT-1990) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT ARG-124.
RX PubMed=11102386; DOI=10.1093/genetics/156.4.1949;
RA Zhang J., Rosenberg H.F.;
RT "Sequence variation at two eosinophil-associated ribonuclease loci in
RT humans.";
RL Genetics 156:1949-1958(2000).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12508121; DOI=10.1038/nature01348;
RA Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C.,
RA Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A.,
RA Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S., Sun H.,
RA Du H., Pepin K., Artiguenave F., Robert C., Cruaud C., Bruels T.,
RA Jaillon O., Friedlander L., Samson G., Brottier P., Cure S., Segurens B.,
RA Aniere F., Samain S., Crespeau H., Abbasi N., Aiach N., Boscus D.,
RA Dickhoff R., Dors M., Dubois I., Friedman C., Gouyvenoux M., James R.,
RA Madan A., Mairey-Estrada B., Mangenot S., Martins N., Menard M., Oztas S.,
RA Ratcliffe A., Shaffer T., Trask B., Vacherie B., Bellemere C., Belser C.,
RA Besnard-Gonnet M., Bartol-Mavel D., Boutard M., Briez-Silla S.,
RA Combette S., Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C.,
RA Muselet D., Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P.,
RA Trybou A., Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M.,
RA Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V.,
RA Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L., Verdier J.,
RA Verdier-Discala C., Hillier L.W., Fulton L., McPherson J., Matsuda F.,
RA Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W., Quetier F.,
RA Waterston R., Hood L., Weissenbach J.;
RT "The DNA sequence and analysis of human chromosome 14.";
RL Nature 421:601-607(2003).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT ARG-124.
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [8]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 20-160, AND VARIANTS CYS-72 AND
RP ARG-124.
RA Bystrom J., Molin D., Jonsson U.B., Enblad G., Sundstrom C., Hogbom E.,
RA Venge P.;
RT "Identification of polymorphisms in the ECP gene. Relation to disease
RT activity in Hodgkins lymphoma.";
RL Submitted (OCT-2001) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP PROTEIN SEQUENCE OF 28-87.
RX PubMed=3458170; DOI=10.1073/pnas.83.10.3146;
RA Gleich G.J., Loegering D.A., Bell M.P., Checkel J.L., Ackerman S.J.,
RA McKean D.J.;
RT "Biochemical and functional similarities between human eosinophil-derived
RT neurotoxin and eosinophil cationic protein: homology with ribonuclease.";
RL Proc. Natl. Acad. Sci. U.S.A. 83:3146-3150(1986).
RN [10]
RP PROTEIN SEQUENCE OF 28-47, AND FUNCTION AS AN ANTIMICROBIAL PROTEIN.
RX PubMed=2501794; DOI=10.1073/pnas.86.14.5610;
RA Gabay J.E., Scott R.W., Campanelli D., Griffith J., Wilde C., Marra M.N.,
RA Seeger M., Nathan C.F.;
RT "Antibiotic proteins of human polymorphonuclear leukocytes.";
RL Proc. Natl. Acad. Sci. U.S.A. 86:5610-5614(1989).
RN [11]
RP NITRATION AT TYR-60.
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 [12]
RP FUNCTION, AND INTERACTION WITH LPS; LTA AND LIPID BILAYERS.
RX PubMed=19450231; DOI=10.1042/bj20082330;
RA Torrent M., de la Torre B.G., Nogues V.M., Andreu D., Boix E.;
RT "Bactericidal and membrane disruption activities of the eosinophil cationic
RT protein are largely retained in an N-terminal fragment.";
RL Biochem. J. 421:425-434(2009).
RN [13]
RP IN VITRO FORMATION OF AMYLOID-LIKE AGGREGATES, AND MUTAGENESIS OF ILE-40.
RX PubMed=20690710; DOI=10.1021/bm100334u;
RA Torrent M., Odorizzi F., Nogues M.V., Boix E.;
RT "Eosinophil cationic protein aggregation: identification of an N-terminus
RT amyloid prone region.";
RL Biomacromolecules 11:1983-1990(2010).
RN [14]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [15]
RP X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 28-160.
RX PubMed=10606511; DOI=10.1021/bi9919145;
RA Boix E., Leonidas D.D., Nikolovski Z., Nogues M.V., Cuchillo C.M.,
RA Acharya K.R.;
RT "Crystal structure of eosinophil cationic protein at 2.4 A resolution.";
RL Biochemistry 38:16794-16801(1999).
RN [16]
RP X-RAY CRYSTALLOGRAPHY (1.75 ANGSTROMS) OF 28-160.
RX PubMed=10903870; DOI=10.1006/jmbi.2000.3939;
RA Mallorqui-Fernandez G., Pous J., Peracaula R., Aymami J., Maeda T.,
RA Tada H., Yamada H., Seno M., de Llorens R., Gomis-Rueth F.-X., Coll M.;
RT "Three-dimensional crystal structure of human eosinophil cationic protein
RT (RNase 3) at 1.75 A resolution.";
RL J. Mol. Biol. 300:1297-1307(2000).
RN [17]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 28-160.
RX PubMed=12356310; DOI=10.1021/bi0264521;
RA Mohan C.G., Boix E., Evans H.R., Nikolovski Z., Nogues M.V., Cuchillo C.M.,
RA Acharya K.R.;
RT "The crystal structure of eosinophil cationic protein in complex with
RT 2',5'-ADP at 2.0 A resolution reveals the details of the ribonucleolytic
RT active site.";
RL Biochemistry 41:12100-12106(2002).
CC -!- FUNCTION: Cytotoxin and helminthotoxin with low-efficiency ribonuclease
CC activity. Possesses a wide variety of biological activities. Exhibits
CC antibacterial activity, including cytoplasmic membrane depolarization
CC of preferentially Gram-negative, but also Gram-positive strains.
CC Promotes E.coli outer membrane detachment, alteration of the overall
CC cell shape and partial loss of cell content.
CC {ECO:0000269|PubMed:19450231, ECO:0000269|PubMed:2501794}.
CC -!- SUBUNIT: Interacts with bacterial lipopolysaccharide (LPS) and
CC lipoteichoic acid (LTA). In vitro interacts with and insert into lipid
CC bilayers composed of dioleoyl phosphatidylcholine and dioleoyl
CC phosphatidylglycerol. In vitro, tends to form amyloid-like aggregates
CC at pH 3, but not at pH 5, nor 7. {ECO:0000269|PubMed:19450231}.
CC -!- SUBCELLULAR LOCATION: Secreted. Note=Located in the matrix of
CC eosinophil large specific granule, which are released following
CC activation by an immune stimulus.
CC -!- SIMILARITY: Belongs to the pancreatic ribonuclease family.
CC {ECO:0000305}.
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DR EMBL; X15161; CAA33251.1; -; mRNA.
DR EMBL; M28128; AAA50283.1; -; mRNA.
DR EMBL; X16545; CAA34545.1; -; Genomic_DNA.
DR EMBL; X55990; CAA39462.1; -; Genomic_DNA.
DR EMBL; AF294019; AAG31589.1; -; Genomic_DNA.
DR EMBL; AF294020; AAG31590.1; -; Genomic_DNA.
DR EMBL; AF294021; AAG31591.1; -; Genomic_DNA.
DR EMBL; AF294022; AAG31592.1; -; Genomic_DNA.
DR EMBL; AF294023; AAG31593.1; -; Genomic_DNA.
DR EMBL; AF294024; AAG31594.1; -; Genomic_DNA.
DR EMBL; AF294025; AAG31595.1; -; Genomic_DNA.
DR EMBL; AF294026; AAG31596.1; -; Genomic_DNA.
DR EMBL; AL133371; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC096060; AAH96060.1; -; mRNA.
DR EMBL; BC096061; AAH96061.1; -; mRNA.
DR EMBL; BC096062; AAH96062.1; -; mRNA.
DR EMBL; AF441204; AAL35279.1; -; Genomic_DNA.
DR EMBL; AF441205; AAL35280.1; -; Genomic_DNA.
DR EMBL; AF441206; AAL35281.1; -; Genomic_DNA.
DR CCDS; CCDS9560.1; -.
DR PIR; B35328; JL0106.
DR RefSeq; NP_002926.2; NM_002935.2.
DR PDB; 1DYT; X-ray; 1.75 A; A/B=28-160.
DR PDB; 1H1H; X-ray; 2.00 A; A=28-160.
DR PDB; 1QMT; X-ray; 2.40 A; A=28-160.
DR PDB; 2KB5; NMR; -; A=28-160.
DR PDB; 2LVZ; NMR; -; A=28-160.
DR PDB; 4A2O; X-ray; 1.69 A; A/B=28-160.
DR PDB; 4A2Y; X-ray; 1.70 A; A/B=28-160.
DR PDB; 4OWZ; X-ray; 1.47 A; A/B=28-160.
DR PDB; 4OXB; X-ray; 1.50 A; A/B=28-160.
DR PDB; 4OXF; X-ray; 1.50 A; A/B=28-160.
DR PDB; 4X08; X-ray; 1.34 A; A/B=28-160.
DR PDBsum; 1DYT; -.
DR PDBsum; 1H1H; -.
DR PDBsum; 1QMT; -.
DR PDBsum; 2KB5; -.
DR PDBsum; 2LVZ; -.
DR PDBsum; 4A2O; -.
DR PDBsum; 4A2Y; -.
DR PDBsum; 4OWZ; -.
DR PDBsum; 4OXB; -.
DR PDBsum; 4OXF; -.
DR PDBsum; 4X08; -.
DR AlphaFoldDB; P12724; -.
DR BMRB; P12724; -.
DR SMR; P12724; -.
DR BioGRID; 111966; 16.
DR IntAct; P12724; 13.
DR STRING; 9606.ENSP00000302324; -.
DR DrugBank; DB02098; Adenosine-2'-5'-Diphosphate.
DR DrugBank; DB04272; Citric acid.
DR DrugBank; DB01411; Pranlukast.
DR GlyGen; P12724; 3 sites.
DR iPTMnet; P12724; -.
DR PhosphoSitePlus; P12724; -.
DR BioMuta; RNASE3; -.
DR DMDM; 147744558; -.
DR EPD; P12724; -.
DR jPOST; P12724; -.
DR MassIVE; P12724; -.
DR PaxDb; P12724; -.
DR PeptideAtlas; P12724; -.
DR PRIDE; P12724; -.
DR ProteomicsDB; 52864; -.
DR Antibodypedia; 57757; 320 antibodies from 29 providers.
DR DNASU; 6037; -.
DR Ensembl; ENST00000304639.4; ENSP00000302324.3; ENSG00000169397.4.
DR GeneID; 6037; -.
DR KEGG; hsa:6037; -.
DR MANE-Select; ENST00000304639.4; ENSP00000302324.3; NM_002935.3; NP_002926.2.
DR UCSC; uc001vyj.4; human.
DR CTD; 6037; -.
DR DisGeNET; 6037; -.
DR GeneCards; RNASE3; -.
DR HGNC; HGNC:10046; RNASE3.
DR HPA; ENSG00000169397; Tissue enriched (bone).
DR MIM; 131398; gene.
DR neXtProt; NX_P12724; -.
DR OpenTargets; ENSG00000169397; -.
DR PharmGKB; PA34414; -.
DR VEuPathDB; HostDB:ENSG00000169397; -.
DR eggNOG; ENOG502TF52; Eukaryota.
DR GeneTree; ENSGT00940000162253; -.
DR HOGENOM; CLU_117006_0_1_1; -.
DR InParanoid; P12724; -.
DR OMA; NQSIRCP; -.
DR OrthoDB; 1482425at2759; -.
DR PhylomeDB; P12724; -.
DR TreeFam; TF333393; -.
DR PathwayCommons; P12724; -.
DR Reactome; R-HSA-6798695; Neutrophil degranulation.
DR Reactome; R-HSA-6803157; Antimicrobial peptides.
DR SignaLink; P12724; -.
DR SIGNOR; P12724; -.
DR BioGRID-ORCS; 6037; 11 hits in 1069 CRISPR screens.
DR EvolutionaryTrace; P12724; -.
DR GeneWiki; Eosinophil_cationic_protein; -.
DR GenomeRNAi; 6037; -.
DR Pharos; P12724; Tbio.
DR PRO; PR:P12724; -.
DR Proteomes; UP000005640; Chromosome 14.
DR RNAct; P12724; protein.
DR Bgee; ENSG00000169397; Expressed in trabecular bone tissue and 123 other tissues.
DR Genevisible; P12724; HS.
DR GO; GO:0035578; C:azurophil granule lumen; TAS:Reactome.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0005615; C:extracellular space; IDA:UniProtKB.
DR GO; GO:0004519; F:endonuclease activity; IEA:UniProtKB-KW.
DR GO; GO:0001530; F:lipopolysaccharide binding; IDA:UniProtKB.
DR GO; GO:0003676; F:nucleic acid binding; IEA:InterPro.
DR GO; GO:0004540; F:ribonuclease activity; IBA:GO_Central.
DR GO; GO:0019731; P:antibacterial humoral response; IDA:UniProtKB.
DR GO; GO:0061844; P:antimicrobial humoral immune response mediated by antimicrobial peptide; IDA:UniProtKB.
DR GO; GO:0006935; P:chemotaxis; IBA:GO_Central.
DR GO; GO:0050829; P:defense response to Gram-negative bacterium; IDA:UniProtKB.
DR GO; GO:0050830; P:defense response to Gram-positive bacterium; IDA:UniProtKB.
DR GO; GO:0043152; P:induction of bacterial agglutination; IDA:UniProtKB.
DR GO; GO:0045087; P:innate immune response; IDA:UniProtKB.
DR GO; GO:0002227; P:innate immune response in mucosa; IDA:UniProtKB.
DR GO; GO:0006401; P:RNA catabolic process; TAS:ProtInc.
DR Gene3D; 3.10.130.10; -; 1.
DR InterPro; IPR001427; RNaseA.
DR InterPro; IPR036816; RNaseA-like_dom_sf.
DR InterPro; IPR023411; RNaseA_AS.
DR InterPro; IPR023412; RNaseA_domain.
DR PANTHER; PTHR11437; PTHR11437; 1.
DR Pfam; PF00074; RnaseA; 1.
DR PRINTS; PR00794; RIBONUCLEASE.
DR SMART; SM00092; RNAse_Pc; 1.
DR SUPFAM; SSF54076; SSF54076; 1.
DR PROSITE; PS00127; RNASE_PANCREATIC; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Antibiotic; Antimicrobial; Direct protein sequencing;
KW Disulfide bond; Endonuclease; Glycoprotein; Hydrolase; Nitration; Nuclease;
KW Reference proteome; Secreted; Signal.
FT SIGNAL 1..27
FT /evidence="ECO:0000269|PubMed:2501794,
FT ECO:0000269|PubMed:3458170"
FT CHAIN 28..160
FT /note="Eosinophil cationic protein"
FT /id="PRO_0000030862"
FT REGION 28..72
FT /note="Required for nearly all of the bactericidal
FT activity; partially involved in LPS-binding and bacterial
FT membrane depolarization"
FT ACT_SITE 42
FT /note="Proton acceptor"
FT ACT_SITE 155
FT /note="Proton donor"
FT BINDING 65..69
FT /ligand="substrate"
FT SITE 60
FT /note="May be involved in LPS-binding"
FT SITE 62
FT /note="May be involved in LPS- and LTA-binding"
FT MOD_RES 60
FT /note="3'-nitrotyrosine"
FT /evidence="ECO:0000269|PubMed:18694936"
FT CARBOHYD 84
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 92
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 119
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 50..110
FT DISULFID 64..123
FT DISULFID 82..138
FT DISULFID 89..98
FT VARIANT 72
FT /note="R -> C (in dbSNP:rs151169198)"
FT /evidence="ECO:0000269|Ref.8"
FT /id="VAR_014109"
FT VARIANT 124
FT /note="T -> R (in dbSNP:rs2073342)"
FT /evidence="ECO:0000269|PubMed:11102386,
FT ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:2387583,
FT ECO:0000269|PubMed:2473157, ECO:0000269|PubMed:2745977,
FT ECO:0000269|Ref.4, ECO:0000269|Ref.8"
FT /id="VAR_013149"
FT VARIANT 130
FT /note="G -> R (in dbSNP:rs12147890)"
FT /id="VAR_029017"
FT MUTAGEN 40
FT /note="I->A: Loss of in vitro formation of amyloid-like
FT aggregates."
FT /evidence="ECO:0000269|PubMed:20690710"
FT STRAND 30..32
FT /evidence="ECO:0007829|PDB:2KB5"
FT HELIX 34..42
FT /evidence="ECO:0007829|PDB:4X08"
FT HELIX 50..53
FT /evidence="ECO:0007829|PDB:4X08"
FT HELIX 55..58
FT /evidence="ECO:0007829|PDB:4X08"
FT STRAND 61..63
FT /evidence="ECO:0007829|PDB:4OWZ"
FT STRAND 66..73
FT /evidence="ECO:0007829|PDB:4X08"
FT HELIX 75..81
FT /evidence="ECO:0007829|PDB:4X08"
FT STRAND 90..92
FT /evidence="ECO:0007829|PDB:4X08"
FT TURN 93..95
FT /evidence="ECO:0007829|PDB:2LVZ"
FT STRAND 98..100
FT /evidence="ECO:0007829|PDB:4X08"
FT STRAND 105..113
FT /evidence="ECO:0007829|PDB:4X08"
FT HELIX 120..122
FT /evidence="ECO:0007829|PDB:4X08"
FT STRAND 125..132
FT /evidence="ECO:0007829|PDB:4X08"
FT STRAND 134..140
FT /evidence="ECO:0007829|PDB:4X08"
FT TURN 143..145
FT /evidence="ECO:0007829|PDB:2KB5"
FT STRAND 150..159
FT /evidence="ECO:0007829|PDB:4X08"
SQ SEQUENCE 160 AA; 18385 MW; D7BED24F67B23FA9 CRC64;
MVPKLFTSQI CLLLLLGLMG VEGSLHARPP QFTRAQWFAI QHISLNPPRC TIAMRAINNY
RWRCKNQNTF LRTTFANVVN VCGNQSIRCP HNRTLNNCHR SRFRVPLLHC DLINPGAQNI
SNCTYADRPG RRFYVVACDN RDPRDSPRYP VVPVHLDTTI
