P12724 (ECP_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Eosinophil cationic protein
Short name=ECP
EC=3.1.27.-

Alternative name(s):
Ribonuclease 3
Short name=RNase 3

Gene names

Name:	RNASE3
Synonyms:	ECP, RNS3

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	160 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)

Function	Cytotoxin and helminthotoxin with low-efficiency ribonuclease activity. Possesses a wide variety of biological activities. Exhibits antibacterial activity, including cytoplasmic membrane depolarization of preferentially Gram-negative, but also Gram-positive strains. Promotes E.coli outer membrane detachment, alteration of the overall cell shape and partial loss of cell content. Ref.10 Ref.12
Subunit structure	Interacts with bacterial lipopolysaccharide (LPS) and lipoteichoic acid (LTA). In vitro interacts with and insert into lipid bilayers composed of dioleoyl phosphatidylcholine and dioleoyl phosphatidylglycerol. In vitro, tends to form amyloid-like aggregates at pH 3, but not at pH 5, nor 7. Ref.12
Subcellular location	Secreted. Note: Located in the matrix of eosinophil large specific granule, which are released following activation by an immune stimulus.
Sequence similarities	Belongs to the pancreatic ribonuclease family.

Ontologies

Keywords
Cellular component	Secreted
Coding sequence diversity	Polymorphism
Domain	Signal
Molecular function	Antibiotic Antimicrobial Endonuclease Hydrolase Nuclease
PTM	Disulfide bond Glycoprotein Nitration
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	RNA catabolic process Traceable author statement Ref.3. Source: ProtInc defense response to bacterium Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	extracellular region Traceable author statement PubMed 10706854. Source: ProtInc
Molecular_function	nucleic acid binding Inferred from electronic annotation. Source: InterPro pancreatic ribonuclease activity Inferred from electronic annotation. Source: InterPro ribonuclease activity Traceable author statement Ref.3. Source: ProtInc
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 27

27

Ref.9 Ref.10

Chain

28 – 160

133

Eosinophil cationic protein

PRO_0000030862

Regions

Region

28 – 72

45

Required for nearly all of the bactericidal activity; partially involved in LPS-binding and bacterial membrane depolarization

Region

65 – 69

5

Substrate binding

Sites

Active site

42

1

Proton acceptor

Active site

155

1

Proton donor

Site

60

1

May be involved in LPS-binding

Site

62

1

May be involved in LPS- and LTA-binding

Amino acid modifications

Modified residue

60

1

Nitrated tyrosine Ref.11

Glycosylation

84

1

N-linked (GlcNAc...) Potential

Glycosylation

92

1

N-linked (GlcNAc...) Potential

Glycosylation

119

1

N-linked (GlcNAc...) Potential

Disulfide bond

50 ↔ 110

Disulfide bond

64 ↔ 123

Disulfide bond

82 ↔ 138

Disulfide bond

89 ↔ 98

Natural variations

Natural variant

72

1

R → C. Ref.8

VAR_014109

Natural variant

124

1

T → R. Ref.1 Ref.2 Ref.3 Ref.4 Ref.5 Ref.7 Ref.8
Corresponds to variant rs2073342 [ dbSNP | Ensembl ].

VAR_013149

Natural variant

130

1

G → R.
Corresponds to variant rs12147890 [ dbSNP | Ensembl ].

VAR_029017

Experimental info

Mutagenesis

40

1

I → A: Loss of in vitro formation of amyloid-like aggregates. Ref.13

Secondary structure

1

.

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160

Helix Strand Turn

Details...

Beta strand

30 – 32

3

Helix

34 – 42

9

Helix

50 – 53

4

Helix

55 – 58

4

Beta strand

61 – 63

3

Beta strand

66 – 73

8

Helix

75 – 81

7

Beta strand

98 – 100

3

Beta strand

105 – 113

9

Helix

120 – 122

3

Beta strand

125 – 132

8

Beta strand

134 – 140

7

Turn

143 – 145

3

Beta strand

150 – 159

10

Sequences

	Sequence		Length	Mass (Da)
	P12724 [UniParc]. Last modified May 15, 2007. Version 2. Checksum: D7BED24F67B23FA9	FASTA	160	18,385
	10 20 30 40 50 60 MVPKLFTSQI CLLLLLGLMG VEGSLHARPP QFTRAQWFAI QHISLNPPRC TIAMRAINNY 70 80 90 100 110 120 RWRCKNQNTF LRTTFANVVN VCGNQSIRCP HNRTLNNCHR SRFRVPLLHC DLINPGAQNI 130 140 150 160 SNCTYADRPG RRFYVVACDN RDPRDSPRYP VVPVHLDTTI

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Human eosinophil cationic protein. Molecular cloning of a cytotoxin and helminthotoxin with ribonuclease activity." Rosenberg H.F., Ackerman S.J., Tenen D.G. J. Exp. Med. 170:163-176(1989) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT ARG-124. Tissue: Peripheral blood granulocyte.
[2]	"Structure and chromosome localization of the human eosinophil-derived neurotoxin and eosinophil cationic protein genes: evidence for intronless coding sequences in the ribonuclease gene superfamily." Hamann K.J., Ten R.M., Loegering D.A., Jenkins R.B., Heise M.T., Schad C.R., Pease L.R., Gleich G.J., Barker R.L. Genomics 7:535-546(1990) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT ARG-124. Tissue: Fetal liver.
[3]	"Eosinophil cationic protein cDNA. Comparison with other toxic cationic proteins and ribonucleases." Barker R.L., Loegering D.A., Ten R.M., Hamann K.J., Pease L.R., Gleich G.J. J. Immunol. 143:952-955(1989) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT ARG-124.
[4]	Simonsen C.C., Kennedy J., Comstock L., Ashton N., McGrogan M. Submitted (OCT-1990) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT ARG-124. Tissue: Colon.
[5]	"Sequence variation at two eosinophil-associated ribonuclease loci in humans." Zhang J., Rosenberg H.F. Genetics 156:1949-1958(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT ARG-124.
[6]	"The DNA sequence and analysis of human chromosome 14." Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C., Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A., Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S., Sun H., Du H. , Pepin K., Artiguenave F., Robert C., Cruaud C., Bruels T., Jaillon O., Friedlander L., Samson G., Brottier P., Cure S., Segurens B., Aniere F., Samain S., Crespeau H., Abbasi N., Aiach N., Boscus D., Dickhoff R., Dors M., Dubois I., Friedman C., Gouyvenoux M., James R., Madan A., Mairey-Estrada B., Mangenot S., Martins N., Menard M., Oztas S., Ratcliffe A., Shaffer T., Trask B., Vacherie B., Bellemere C., Belser C., Besnard-Gonnet M., Bartol-Mavel D., Boutard M., Briez-Silla S., Combette S., Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C., Muselet D., Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P., Trybou A., Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M., Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V., Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L., Verdier J., Verdier-Discala C., Hillier L.W., Fulton L., McPherson J., Matsuda F., Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W., Quetier F., Waterston R., Hood L., Weissenbach J. Nature 421:601-607(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT ARG-124.
[8]	"Identification of polymorphisms in the ECP gene. Relation to disease activity in Hodgkins lymphoma." Bystrom J., Molin D., Jonsson U.B., Enblad G., Sundstrom C., Hogbom E., Venge P. Submitted (OCT-2001) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 20-160, VARIANTS CYS-72 AND ARG-124.
[9]	"Biochemical and functional similarities between human eosinophil-derived neurotoxin and eosinophil cationic protein: homology with ribonuclease." Gleich G.J., Loegering D.A., Bell M.P., Checkel J.L., Ackerman S.J., McKean D.J. Proc. Natl. Acad. Sci. U.S.A. 83:3146-3150(1986) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 28-87.
[10]	"Antibiotic proteins of human polymorphonuclear leukocytes." Gabay J.E., Scott R.W., Campanelli D., Griffith J., Wilde C., Marra M.N., Seeger M., Nathan C.F. Proc. Natl. Acad. Sci. U.S.A. 86:5610-5614(1989) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 28-47, FUNCTION AS AN ANTIMICROBIAL PROTEIN.
[11]	"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] [Europe PMC] [Abstract] Cited for: NITRATION AT TYR-60.
[12]	"Bactericidal and membrane disruption activities of the eosinophil cationic protein are largely retained in an N-terminal fragment." Torrent M., de la Torre B.G., Nogues V.M., Andreu D., Boix E. Biochem. J. 421:425-434(2009) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH LPS; LTA AND LIPID BILAYERS.
[13]	"Eosinophil cationic protein aggregation: identification of an N-terminus amyloid prone region." Torrent M., Odorizzi F., Nogues M.V., Boix E. Biomacromolecules 11:1983-1990(2010) [PubMed] [Europe PMC] [Abstract] Cited for: IN VITRO FORMATION OF AMYLOID-LIKE AGGREGATES, MUTAGENESIS OF ILE-40.
[14]	"Crystal structure of eosinophil cationic protein at 2.4 A resolution." Boix E., Leonidas D.D., Nikolovski Z., Nogues M.V., Cuchillo C.M., Acharya K.R. Biochemistry 38:16794-16801(1999) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 28-160.
[15]	"Three-dimensional crystal structure of human eosinophil cationic protein (RNase 3) at 1.75 A resolution." Mallorqui-Fernandez G., Pous J., Peracaula R., Aymami J., Maeda T., Tada H., Yamada H., Seno M., de Llorens R., Gomis-Rueth F.-X., Coll M. J. Mol. Biol. 300:1297-1307(2000) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.75 ANGSTROMS) OF 28-160.
[16]	"The crystal structure of eosinophil cationic protein in complex with 2',5'-ADP at 2.0 A resolution reveals the details of the ribonucleolytic active site." Mohan C.G., Boix E., Evans H.R., Nikolovski Z., Nogues M.V., Cuchillo C.M., Acharya K.R. Biochemistry 41:12100-12106(2002) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 28-160.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

X15161 mRNA. Translation: CAA33251.1.
M28128 mRNA. Translation: AAA50283.1.
X16545 Genomic DNA. Translation: CAA34545.1.
X55990 Genomic DNA. Translation: CAA39462.1.
AF294019 Genomic DNA. Translation: AAG31589.1.
AF294020 Genomic DNA. Translation: AAG31590.1.
AF294021 Genomic DNA. Translation: AAG31591.1.
AF294022 Genomic DNA. Translation: AAG31592.1.
AF294023 Genomic DNA. Translation: AAG31593.1.
AF294024 Genomic DNA. Translation: AAG31594.1.
AF294025 Genomic DNA. Translation: AAG31595.1.
AF294026 Genomic DNA. Translation: AAG31596.1.
AL133371 Genomic DNA. No translation available.
BC096060 mRNA. Translation: AAH96060.1.
BC096061 mRNA. Translation: AAH96061.1.
BC096062 mRNA. Translation: AAH96062.1.
AF441204 Genomic DNA. Translation: AAL35279.1.
AF441205 Genomic DNA. Translation: AAL35280.1.
AF441206 Genomic DNA. Translation: AAL35281.1.

IPI

IPI00025427.

PIR

JL0106. B35328.

RefSeq

NP_002926.2. NM_002935.2.

UniGene

Hs.73839.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1DYT	X-ray	1.75	A/B	28-160	[»]
1H1H	X-ray	2.00	A	28-160	[»]
1QMT	X-ray	2.40	A	28-160	[»]
2KB5	NMR	-	A	28-160	[»]
4A2O	X-ray	1.69	A/B	28-160	[»]
4A2Y	X-ray	1.70	A/B	28-160	[»]

ProteinModelPortal

P12724.

ModBase

Search...

Protein-protein interaction databases

STRING

9606.ENSP00000302324.

PTM databases

PhosphoSite

P12724.

Polymorphism databases

DMDM

147744558.

Proteomic databases

PaxDb

P12724.

PRIDE

P12724.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000304639; ENSP00000302324; ENSG00000169397.

GeneID

6037.

KEGG

hsa:6037.

UCSC

uc001vyj.3. human.

Organism-specific databases

CTD

6037.

GeneCards

GC14P021359.

H-InvDB

HIX0037784.

HGNC

HGNC:10046. RNASE3.

MIM

131398. gene.

neXtProt

NX_P12724.

PharmGKB

PA34414.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG118739.

HOGENOM

HOG000276882.

HOVERGEN

HBG008396.

InParanoid

P12724.

KO

K10787.

OMA

PRCDDAM.

OrthoDB

EOG42V8HJ.

PhylomeDB

P12724.

Gene expression databases

Bgee

P12724.

CleanEx

HS_RNASE3.

Genevestigator

P12724.

GermOnline

ENSG00000169397. Homo sapiens.

Family and domain databases

Gene3D

3.10.130.10. 1 hit.

InterPro

IPR001427. RNaseA.
IPR023411. RNaseA_AS.
IPR023412. RNaseA_domain.
[Graphical view]

PANTHER

PTHR11437. PTHR11437. 1 hit.

Pfam

PF00074. RnaseA. 1 hit.
[Graphical view]

PRINTS

PR00794. RIBONUCLEASE.

ProDom

PD000535. RNaseA. 1 hit.
[Graphical view] [Entries sharing at least one domain]

SMART

SM00092. RNAse_Pc. 1 hit.
[Graphical view]

SUPFAM

SSF54076. RNaseA. 1 hit.

PROSITE

PS00127. RNASE_PANCREATIC. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

DrugBank

DB01411. Pranlukast.

EvolutionaryTrace

P12724.

GenomeRNAi

6037.

NextBio

23529.

SOURCE

Search...

Entry information

Entry name

ECP_HUMAN

Accession

Primary (citable) accession number: P12724
Secondary accession number(s): Q4VBC1 , Q8WTP7, Q8WZ62, Q9GZN9

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1989
Last sequence update:	May 15, 2007
Last modified:	May 1, 2013
This is version 136 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

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.