Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

P14138 (EDN3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 152. 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·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Endothelin-3

Short name=ET-3
Alternative name(s):
Preproendothelin-3
Short name=PPET3
Gene names
Name:EDN3
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length238 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Endothelins are endothelium-derived vasoconstrictor peptides.

Subcellular location

Secreted.

Tissue specificity

Expressed in trophoblasts and placental stem villi vessels, but not in cultured placental smooth muscle cells. Ref.9

Involvement in disease

Hirschsprung disease 4 (HSCR4) [MIM:613712]: A disorder of neural crest development characterized by absence of enteric ganglia along a variable length of the intestine. It is the most common cause of congenital intestinal obstruction. Early symptoms range from complete acute neonatal obstruction, characterized by vomiting, abdominal distention and failure to pass stool, to chronic constipation in the older child.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.14

Congenital central hypoventilation syndrome (CCHS) [MIM:209880]: Rare disorder characterized by abnormal control of respiration in the absence of neuromuscular or lung disease, or an identifiable brain stem lesion. A deficiency in autonomic control of respiration results in inadequate or negligible ventilatory and arousal responses to hypercapnia and hypoxemia.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.13

Waardenburg syndrome 4B (WS4B) [MIM:613265]: A disorder characterized by the association of Waardenburg features (depigmentation and deafness) with the absence of enteric ganglia in the distal part of the intestine (Hirschsprung disease).
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.12 Ref.15 Ref.16

Sequence similarities

Belongs to the endothelin/sarafotoxin family.

Sequence caution

The sequence AAR16083.1 differs from that shown. Reason: Erroneous gene model prediction.

Ontologies

Keywords
   Cellular componentSecreted
   Coding sequence diversityAlternative splicing
   DiseaseDeafness
Disease mutation
Hirschsprung disease
Waardenburg syndrome
   DomainSignal
   Molecular functionVasoactive
Vasoconstrictor
   PTMCleavage on pair of basic residues
Disulfide bond
   Technical termComplete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processblood circulation

Traceable author statement PubMed 8298278. Source: ProtInc

cell surface receptor signaling pathway

Inferred from direct assay PubMed 1713452. Source: BHF-UCL

cell-cell signaling

Traceable author statement PubMed 8298278. Source: ProtInc

inositol phosphate-mediated signaling

Inferred from direct assay PubMed 1917960. Source: BHF-UCL

melanocyte differentiation

Inferred from electronic annotation. Source: Ensembl

multicellular organismal development

Traceable author statement PubMed 8630502. Source: ProtInc

neural crest cell migration

Inferred from electronic annotation. Source: Ensembl

neuron differentiation

Inferred from electronic annotation. Source: Ensembl

neutrophil chemotaxis

Inferred from direct assay PubMed 9696419. Source: BHF-UCL

peptide hormone secretion

Inferred from direct assay PubMed 10770212. Source: BHF-UCL

positive regulation of MAP kinase activity

Inferred from direct assay PubMed 10770212. Source: BHF-UCL

positive regulation of cell proliferation

Inferred from electronic annotation. Source: Ensembl

positive regulation of heart rate

Inferred from direct assay PubMed 2649896. Source: BHF-UCL

positive regulation of hormone secretion

Inferred from direct assay PubMed 10770212. Source: BHF-UCL

positive regulation of leukocyte chemotaxis

Inferred from direct assay PubMed 9696419. Source: BHF-UCL

positive regulation of mitosis

Inferred from direct assay PubMed 10770212. Source: BHF-UCL

regulation of developmental pigmentation

Inferred from electronic annotation. Source: Ensembl

regulation of systemic arterial blood pressure by endothelin

Inferred from direct assay PubMed 2649896. Source: BHF-UCL

regulation of vasoconstriction

Inferred from electronic annotation. Source: InterPro

signal transduction

Traceable author statement PubMed 8298278. Source: ProtInc

vasoconstriction

Inferred from direct assay PubMed 2649896PubMed 8982507. Source: BHF-UCL

vein smooth muscle contraction

Inferred from direct assay PubMed 8982507. Source: BHF-UCL

   Cellular_componentextracellular region

Traceable author statement. Source: Reactome

extracellular space

Inferred from direct assay PubMed 15691296. Source: BHF-UCL

   Molecular_functionhormone activity

Inferred from direct assay PubMed 10770212PubMed 2649896. Source: BHF-UCL

receptor binding

Traceable author statement PubMed 8298278. Source: ProtInc

Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform Long (identifier: P14138-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform Short (identifier: P14138-2)

The sequence of this isoform differs from the canonical sequence as follows:
     181-196: SNSRTAEKTDKEEEGK → RQ
Isoform 3 (identifier: P14138-3)

The sequence of this isoform differs from the canonical sequence as follows:
     198-238: EVKDQQSKQALDLHHPKLMPGSGLALAPSTCPRCLFQEGAP → RGANRGLCQRRLKSRTNKASRL

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 1616 Potential
Propeptide17 – 9478
PRO_0000008111
Peptide97 – 11721Endothelin-3
PRO_0000008112
Propeptide118 – 238121
PRO_0000008113

Regions

Region159 – 17315Endothelin-like

Sites

Site117 – 1182Cleavage; by KEL

Amino acid modifications

Disulfide bond97 ↔ 111
Disulfide bond99 ↔ 107

Natural variations

Alternative sequence181 – 19616SNSRT…EEEGK → RQ in isoform Short.
VSP_001445
Alternative sequence198 – 23841EVKDQ…QEGAP → RGANRGLCQRRLKSRTNKAS RL in isoform 3.
VSP_043139
Natural variant171A → T in HSCR4. Ref.4 Ref.14
Corresponds to variant rs11570255 [ dbSNP | Ensembl ].
VAR_009078
Natural variant1271Y → C in WS4B. Ref.16
VAR_015238
Natural variant1591C → F in WS4B. Ref.12
VAR_002353
Natural variant2241A → T in HSCR4. Ref.14
Corresponds to variant rs11570351 [ dbSNP | Ensembl ].
VAR_009079

Sequences

Sequence LengthMass (Da)Tools
Isoform Long [UniParc].

Last modified January 1, 1990. Version 1.
Checksum: 7D7E90BC7DE37273

FASTA23825,454
        10         20         30         40         50         60 
MEPGLWLLFG LTVTSAAGFV PCSQSGDAGR RGVSQAPTAA RSEGDCEETV AGPGEETVAG 

        70         80         90        100        110        120 
PGEGTVAPTA LQGPSPGSPG QEQAAEGAPE HHRSRRCTCF TYKDKECVYY CHLDIIWINT 

       130        140        150        160        170        180 
PEQTVPYGLS NYRGSFRGKR SAGPLPGNLQ LSHRPHLRCA CVGRYDKACL HFCTQTLDVS 

       190        200        210        220        230 
SNSRTAEKTD KEEEGKVEVK DQQSKQALDL HHPKLMPGSG LALAPSTCPR CLFQEGAP 

« Hide

Isoform Short [UniParc].

Checksum: 9A2295791A408FF3
Show »

FASTA22423,948
Isoform 3 [UniParc].

Checksum: D3CF0513D34705AC
Show »

FASTA21923,596

References

« Hide 'large scale' references
[1]"cDNA cloning and chromosomal assignment of the gene encoding endothelin 3."
Bloch K.D., Eddy R.L., Shows T.B., Quertermous T.
J. Biol. Chem. 264:18156-18161(1989) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]"One of the endothelin gene family, endothelin 3 gene, is expressed in the placenta."
Onda H., Ohkubo S., Ogi K., Kosaka T., Kimura C., Matsumoto H., Suzuki N., Fujino M.
FEBS Lett. 261:327-330(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM SHORT).
Tissue: Placenta.
[3]"Cloning of human full-length CDSs in BD Creator(TM) system donor vector."
Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A.
Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM LONG).
[4]NIEHS SNPs program
Submitted (OCT-2003) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT THR-17.
[5]"The DNA sequence and comparative analysis of human chromosome 20."
Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R., Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L., Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P., Bird C.P., Blakey S.E. expand/collapse author list , Bridgeman A.M., Brown A.J., Buck D., Burrill W.D., Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G., Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E., Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D., Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P., Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E., Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J., Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D., Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S., Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D., Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A., Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T., Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I., Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M., Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D., Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M., Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A., Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L., Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L., Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J.
Nature 414:865-871(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
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] (ISOFORMS LONG AND 3).
Tissue: Lung and Muscle.
[8]"Proteolytic processing of big endothelin-3 by the kell blood group protein."
Lee S., Lin M., Mele A., Cao Y., Farmar J., Russo D., Redman C.
Blood 94:1440-1450(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: PARTIAL PROTEIN SEQUENCE, CLEAVAGE BY KELL, IDENTIFICATION BY MASS SPECTROMETRY.
[9]"Endothelin-1 and ETA receptor expression in vascular smooth muscle cells from human placenta: a new ETA receptor messenger ribonucleic acid is generated by alternative splicing of exon 3."
Bourgeois C., Robert B., Rebourcet R., Mondon F., Mignot T.-M., Duc-Goiran P., Ferre F.
J. Clin. Endocrinol. Metab. 82:3116-3123(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY.
[10]"Solution structure of endothelin-3 determined using NMR spectroscopy."
Mills R.G., O'Donoghue S.I., Smith R., King G.F.
Biochemistry 31:5640-5645(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR OF ET-3.
[11]"Mutations in Hirschsprung disease: when does a mutation contribute to the phenotype."
Hofstra R.M.W., Osinga J., Buys C.H.C.M.
Eur. J. Hum. Genet. 5:180-185(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW ON VARIANTS.
[12]"A homozygous mutation in the endothelin-3 gene associated with a combined Waardenburg type 2 and Hirschsprung phenotype (Shah-Waardenburg syndrome)."
Hofstra R.M.W., Tan-Sindhunata G., Wu Y., Kamsteeg E.-J., Stulp R.P., van Ravenswaaij-Arts C., Majoor-Krakauer D., Angrist M., Chakravarti A., Meijers C., Buys C.H.C.M.
Nat. Genet. 12:445-447(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT WS4B PHE-159.
[13]"Endothelin-3 frameshift mutation in congenital central hypoventilation syndrome."
Bolk S., Angrist M., Xie J., Yanagisawa M., Silvestri J.M., Weese-Mayer D.E., Chakravarti A.
Nat. Genet. 13:395-396(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN CCHS.
[14]"Endothelin-3 gene mutations in isolated and syndromic Hirschsprung disease."
Bidaud C., Salomon R., Van Camp G., Pelet A., Attie T., Eng C., Bonduelle M., Amiel J., Nihoul-Fekete C., Willems P.J., Munnich A., Lyonnet S.
Eur. J. Hum. Genet. 5:247-251(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS HSCR4 THR-17 AND THR-224.
[15]"A heterozygous endothelin 3 mutation in Waardenburg-Hirschsprung disease: is there a dosage effect of EDN3/EDNRB gene mutations on neurocristopathy phenotypes?"
Pingault V., Bondurand N., Lemort N., Sancandi M., Ceccherini I., Hugot J.P., Jouk P.S., Goossens M.
J. Med. Genet. 38:205-209(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN WS4B.
[16]"SOX10 mutations in chronic intestinal pseudo-obstruction suggest a complex physiopathological mechanism."
Pingault V., Girard M., Bondurand N., Dorkins H., Van Maldergem L., Mowat D., Shimotake T., Verma I., Baumann C., Goossens M.
Hum. Genet. 111:198-206(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT WS4B CYS-127.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
J05081 mRNA. Translation: AAA52405.1.
X52001 mRNA. Translation: CAA36252.1.
BT007085 mRNA. Translation: AAP35748.1.
AY444503 Genomic DNA. Translation: AAR16083.1. Sequence problems.
AL035250 Genomic DNA. Translation: CAB65996.1.
AL035250 Genomic DNA. Translation: CAB65997.2.
AL035250 Genomic DNA. Translation: CAB65998.1.
CH471077 Genomic DNA. Translation: EAW75434.1.
CH471077 Genomic DNA. Translation: EAW75435.1.
CH471077 Genomic DNA. Translation: EAW75437.1.
BC008876 mRNA. Translation: AAH08876.1.
BC053866 mRNA. Translation: AAH53866.1.
PIRA34378.
RefSeqNP_000105.1. NM_000114.2.
NP_996915.1. NM_207032.1.
NP_996916.1. NM_207033.1.
NP_996917.1. NM_207034.1.
UniGeneHs.1408.

3D structure databases

ProteinModelPortalP14138.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid108230. 1 interaction.
STRING9606.ENSP00000337128.

Polymorphism databases

DMDM119618.

Proteomic databases

PaxDbP14138.
PRIDEP14138.

Protocols and materials databases

DNASU1908.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000311585; ENSP00000311854; ENSG00000124205. [P14138-3]
ENST00000337938; ENSP00000337128; ENSG00000124205. [P14138-1]
ENST00000371028; ENSP00000360067; ENSG00000124205. [P14138-1]
ENST00000395654; ENSP00000379015; ENSG00000124205. [P14138-2]
GeneID1908.
KEGGhsa:1908.
UCSCuc002yap.3. human. [P14138-1]
uc002yar.3. human. [P14138-3]
uc002yas.3. human. [P14138-2]

Organism-specific databases

CTD1908.
GeneCardsGC20P057875.
HGNCHGNC:3178. EDN3.
HPAHPA057987.
MIM131242. gene.
209880. phenotype.
613265. phenotype.
613712. phenotype.
neXtProtNX_P14138.
Orphanet388. Hirschsprung disease.
661. Ondine syndrome.
897. Waardenburg-Shah syndrome.
PharmGKBPA27616.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG41573.
HOGENOMHOG000231110.
HOVERGENHBG051442.
InParanoidP14138.
KOK05227.
OMAHHRSRRC.
OrthoDBEOG7PCJHP.
PhylomeDBP14138.
TreeFamTF333184.

Enzyme and pathway databases

ReactomeREACT_111102. Signal Transduction.

Gene expression databases

ArrayExpressP14138.
BgeeP14138.
CleanExHS_EDN3.
GenevestigatorP14138.

Family and domain databases

InterProIPR020475. Bibrotoxin/Sarafotoxin-D.
IPR019764. Endothelin_toxin_CS.
IPR001928. Endothln-like_toxin.
[Graphical view]
PfamPF00322. Endothelin. 1 hit.
[Graphical view]
PRINTSPR00365. ENDOTHELIN.
SMARTSM00272. END. 2 hits.
[Graphical view]
PROSITEPS00270. ENDOTHELIN. 2 hits.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiEndothelin_3.
GenomeRNAi1908.
NextBio7765.
PMAP-CutDBP14138.
PROP14138.
SOURCESearch...

Entry information

Entry nameEDN3_HUMAN
AccessionPrimary (citable) accession number: P14138
Secondary accession number(s): E1P5I5 expand/collapse secondary AC list , Q03229, Q7Z6D2, Q9UGT7
Entry history
Integrated into UniProtKB/Swiss-Prot: January 1, 1990
Last sequence update: January 1, 1990
Last modified: April 16, 2014
This is version 152 of the entry and version 1 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 20

Human chromosome 20: entries, gene names and cross-references to MIM