EDN1_HUMAN
ID EDN1_HUMAN Reviewed; 212 AA.
AC P05305; Q96DA1;
DT 01-NOV-1988, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1988, sequence version 1.
DT 03-AUG-2022, entry version 222.
DE RecName: Full=Endothelin-1;
DE AltName: Full=Preproendothelin-1;
DE Short=PPET1;
DE Contains:
DE RecName: Full=Endothelin-1;
DE Short=ET-1;
DE Contains:
DE RecName: Full=Big endothelin-1;
DE Flags: Precursor;
GN Name=EDN1;
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].
RC TISSUE=Placenta;
RX PubMed=3282927; DOI=10.1016/0014-5793(88)80867-6;
RA Itoh Y., Yanagisawa M., Ohkubo S., Kimura C., Kosaka T., Inoue A.,
RA Ishida N., Mitsui Y., Onda H., Fujino M., Masaki T.;
RT "Cloning and sequence analysis of cDNA encoding the precursor of a human
RT endothelium-derived vasoconstrictor peptide, endothelin: identity of human
RT and porcine endothelin.";
RL FEBS Lett. 231:440-444(1988).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=2670930; DOI=10.1016/s0021-9258(18)63795-0;
RA Inoue A., Yanagisawa M., Takuwa Y., Mitsui Y., Kobayashi M., Masaki T.;
RT "The human preproendothelin-1 gene. Complete nucleotide sequence and
RT regulation of expression.";
RL J. Biol. Chem. 264:14954-14959(1989).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=2659594; DOI=10.1016/s0021-9258(18)81698-2;
RA Bloch K.D., Friedrich S.P., Lee M.E., Eddy R.L., Shows T.B.,
RA Quertermous T.;
RT "Structural organization and chromosomal assignment of the gene encoding
RT endothelin.";
RL J. Biol. Chem. 264:10851-10857(1989).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=8450044; DOI=10.1172/jci116274;
RA Benatti L., Bonecchi L., Cozzi L., Sarmientos P.;
RT "Two preproendothelin 1 mRNAs transcribed by alternative promoters.";
RL J. Clin. Invest. 91:1149-1156(1993).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT ASN-198.
RG NIEHS SNPs program;
RL Submitted (OCT-2003) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=14574404; DOI=10.1038/nature02055;
RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L.,
RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R.,
RA Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D.,
RA Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H.,
RA Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J.,
RA Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V.,
RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J.,
RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E.,
RA Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J.,
RA French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J.,
RA Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C.,
RA Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A.,
RA Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R.,
RA Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M.,
RA Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K.,
RA Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R.,
RA Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A.,
RA Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L.,
RA Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I.,
RA Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y.,
RA Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E.,
RA Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A.,
RA Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W.,
RA Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M.,
RA West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J.,
RA Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M.,
RA Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I.,
RA Rogers J., Beck S.;
RT "The DNA sequence and analysis of human chromosome 6.";
RL Nature 425:805-811(2003).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT ASN-198.
RC TISSUE=Pancreas;
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 27-67.
RX PubMed=2649896; DOI=10.1073/pnas.86.8.2863;
RA Inoue A., Yanagisawa M., Kimura S., Kasuya Y., Miyauchi T., Goto K.,
RA Masaki T.;
RT "The human endothelin family: three structurally and pharmacologically
RT distinct isopeptides predicted by three separate genes.";
RL Proc. Natl. Acad. Sci. U.S.A. 86:2863-2867(1989).
RN [9]
RP PARTIAL PROTEIN SEQUENCE, CLEAVAGE BY KEL, AND IDENTIFICATION BY MASS
RP SPECTROMETRY.
RX PubMed=10438732;
RA Lee S., Lin M., Mele A., Cao Y., Farmar J., Russo D., Redman C.;
RT "Proteolytic processing of big endothelin-3 by the kell blood group
RT protein.";
RL Blood 94:1440-1450(1999).
RN [10]
RP PROTEOLYTIC PROCESSING.
RX PubMed=1864385; DOI=10.1016/0014-5793(91)80948-3;
RA Fabbrini M.S., Valsasina B., Nitti G., Benatti L., Vitale A.;
RT "The signal peptide of human preproendothelin-1.";
RL FEBS Lett. 286:91-94(1991).
RN [11]
RP TISSUE SPECIFICITY.
RX PubMed=9284755; DOI=10.1210/jcem.82.9.4209;
RA Bourgeois C., Robert B., Rebourcet R., Mondon F., Mignot T.-M.,
RA Duc-Goiran P., Ferre F.;
RT "Endothelin-1 and ETA receptor expression in vascular smooth muscle cells
RT from human placenta: a new ETA receptor messenger ribonucleic acid is
RT generated by alternative splicing of exon 3.";
RL J. Clin. Endocrinol. Metab. 82:3116-3123(1997).
RN [12]
RP FUNCTION.
RX PubMed=17446437; DOI=10.1161/01.res.0000267716.96196.60;
RA Glorioso N., Herrera V.L., Bagamasbad P., Filigheddu F., Troffa C.,
RA Argiolas G., Bulla E., Decano J.L., Ruiz-Opazo N.;
RT "Association of ATP1A1 and dear single-nucleotide polymorphism haplotypes
RT with essential hypertension: sex-specific and haplotype-specific effects.";
RL Circ. Res. 100:1522-1529(2007).
RN [13]
RP VARIANT ASN-198, AND CHARACTERIZATION OF VARIANT ASN-198.
RX PubMed=17357073; DOI=10.1086/513286;
RA Pare G., Serre D., Brisson D., Anand S.S., Montpetit A., Tremblay G.,
RA Engert J.C., Hudson T.J., Gaudet D.;
RT "Genetic analysis of 103 candidate genes for coronary artery disease and
RT associated phenotypes in a founder population reveals a new association
RT between endothelin-1 and high-density lipoprotein cholesterol.";
RL Am. J. Hum. Genet. 80:673-682(2007).
RN [14]
RP VARIANT ASN-198.
RX PubMed=18288492; DOI=10.1007/s00439-008-0481-0;
RA Wiltshire S., Powell B.L., Jennens M., McCaskie P.A., Carter K.W.,
RA Palmer L.J., Thompson P.L., McQuillan B.M., Hung J., Beilby J.P.;
RT "Investigating the association between K198N coding polymorphism in EDN1
RT and hypertension, lipoprotein levels, the metabolic syndrome and
RT cardiovascular disease.";
RL Hum. Genet. 123:307-313(2008).
RN [15]
RP FUNCTION.
RX PubMed=19086031; DOI=10.1002/jcp.21649;
RA Rufanova V.A., Alexanian A., Wakatsuki T., Lerner A., Sorokin A.;
RT "Pyk2 mediates endothelin-1 signaling via p130Cas/BCAR3 cascade and
RT regulates human glomerular mesangial cell adhesion and spreading.";
RL J. Cell. Physiol. 219:45-56(2009).
RN [16]
RP X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF ET-1.
RX PubMed=1515112; DOI=10.1107/s0108768191010625;
RA Wolff M., Day J., Greenwood A., Larson S., McPherson A.;
RT "Crystallization and preliminary X-ray analysis of human endothelin.";
RL Acta Crystallogr. B 48:239-240(1992).
RN [17]
RP X-RAY CRYSTALLOGRAPHY (2.18 ANGSTROMS) OF ET-1, AND DISULFIDE BONDS.
RX PubMed=7664037; DOI=10.1038/nsb0594-311;
RA Janes R.W., Peapus D.H., Wallace B.A.;
RT "The crystal structure of human endothelin.";
RL Nat. Struct. Biol. 1:311-319(1994).
RN [18]
RP STRUCTURE BY NMR OF ET-1.
RX PubMed=1859417; DOI=10.1016/0006-291x(91)90146-x;
RA Reily M.D., Dunbar J.B. Jr.;
RT "The conformation of endothelin-1 in aqueous solution: NMR-derived
RT constraints combined with distance geometry and molecular dynamics
RT calculations.";
RL Biochem. Biophys. Res. Commun. 178:570-577(1991).
RN [19]
RP STRUCTURE BY NMR OF ET-1.
RX PubMed=1736987; DOI=10.1021/bi00120a003;
RA Andersen N.H., Chen C., Marschner T.M., Krystek S.R. Jr., Bassolino D.A.;
RT "Conformational isomerism of endothelin in acidic aqueous media: a
RT quantitative NOESY analysis.";
RL Biochemistry 31:1280-1295(1992).
RN [20]
RP STRUCTURE BY NMR OF 53-90.
RX PubMed=1422154; DOI=10.1007/bf02192805;
RA Donlan M.L., Brown F.K., Jeffs P.W.;
RT "Solution conformation of human big endothelin-1.";
RL J. Biomol. NMR 2:407-420(1992).
RN [21]
RP COMPARISON OF NMR STRUCTURE WITH X-RAY STRUCTURE.
RX PubMed=7773179; DOI=10.1002/pro.5560040110;
RA Wallace B.A., Janes R.W., Bassolino D.A., Krystek S.R. Jr.;
RT "A comparison of X-ray and NMR structures for human endothelin-1.";
RL Protein Sci. 4:75-83(1995).
RN [22]
RP STRUCTURE BY NMR OF ET1 AGONIST.
RX PubMed=10231710; DOI=10.1034/j.1399-3011.1999.00001.x;
RA Hewage C.M., Jiang L., Parkinson J.A., Ramage R., Sadler I.H.;
RT "Solution structure of a novel ETB receptor selective agonist ET1-21
RT [Cys(Acm)1,15, Aib3,11, Leu7] by nuclear magnetic resonance spectroscopy
RT and molecular modelling.";
RL J. Pept. Res. 53:223-233(1999).
RN [23]
RP VARIANT ASN-198.
RX PubMed=10334806; DOI=10.1161/01.hyp.33.5.1169;
RA Tiret L., Poirier O., Hallet V., McDonagh T.A., Morrison C., McMurray J.J.,
RA Dargie H.J., Arveiler D., Ruidavets J.B., Luc G., Evans A., Cambien F.;
RT "The Lys198Asn polymorphism in the endothelin-1 gene is associated with
RT blood pressure in overweight people.";
RL Hypertension 33:1169-1174(1999).
RN [24]
RP VARIANT ASN-198.
RX PubMed=10391210; DOI=10.1038/10297;
RA Halushka M.K., Fan J.-B., Bentley K., Hsie L., Shen N., Weder A.,
RA Cooper R., Lipshutz R., Chakravarti A.;
RT "Patterns of single-nucleotide polymorphisms in candidate genes for blood-
RT pressure homeostasis.";
RL Nat. Genet. 22:239-247(1999).
RN [25]
RP VARIANT QME ASP-64, AND VARIANTS ARCND3 HIS-77 AND GLU-91.
RX PubMed=24268655; DOI=10.1016/j.ajhg.2013.10.023;
RA Gordon C.T., Petit F., Kroisel P.M., Jakobsen L., Zechi-Ceide R.M.,
RA Oufadem M., Bole-Feysot C., Pruvost S., Masson C., Tores F., Hieu T.,
RA Nitschke P., Lindholm P., Pellerin P., Guion-Almeida M.L.,
RA Kokitsu-Nakata N.M., Vendramini-Pittoli S., Munnich A., Lyonnet S.,
RA Holder-Espinasse M., Amiel J.;
RT "Mutations in endothelin 1 cause recessive auriculocondylar syndrome and
RT dominant isolated question-mark ears.";
RL Am. J. Hum. Genet. 93:1118-1125(2013).
CC -!- FUNCTION: Endothelins are endothelium-derived vasoconstrictor peptides
CC (By similarity). Probable ligand for G-protein coupled receptors EDNRA
CC and EDNRB which activates PTK2B, BCAR1, BCAR3 and, GTPases RAP1 and
CC RHOA cascade in glomerular mesangial cells (PubMed:19086031). Also
CC binds the DEAR/FBXW7-AS1 receptor (PubMed:17446437).
CC {ECO:0000250|UniProtKB:P09558, ECO:0000269|PubMed:17446437,
CC ECO:0000269|PubMed:19086031}.
CC -!- INTERACTION:
CC P05305; P25101: EDNRA; NbExp=2; IntAct=EBI-715181, EBI-6624559;
CC P05305; P24530: EDNRB; NbExp=2; IntAct=EBI-715181, EBI-6624656;
CC -!- SUBCELLULAR LOCATION: Secreted.
CC -!- TISSUE SPECIFICITY: Expressed in lung, placental stem villi vessels and
CC in cultured placental vascular smooth muscle cells.
CC {ECO:0000269|PubMed:9284755}.
CC -!- POLYMORPHISM: EDN1 genetic variants may influence high density
CC lipoprotein cholesterol (HDLC) levels in some populations and in a sex-
CC specific manner, defining the high density lipoprotein cholesterol
CC level quantitative trait locus 7 (HDLCQ7) [MIM:618979].
CC {ECO:0000269|PubMed:17357073}.
CC -!- DISEASE: Question mark ears, isolated (QME) [MIM:612798]: An auricular
CC abnormality characterized by a cleft between the lobule and the lower
CC part of the helix, sometimes accompanied by a prominent or deficient
CC upper part of the helix, shallow skin dimple on the posterior surface
CC of the ear, or transposition of the ear lobe/antitragus.
CC {ECO:0000269|PubMed:24268655}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Auriculocondylar syndrome 3 (ARCND3) [MIM:615706]: A
CC craniofacial malformation syndrome characterized by variable mandibular
CC anomalies, including mild to severe micrognathia, temporomandibular
CC joint ankylosis, cleft palate, and a characteristic ear malformation
CC that consists of separation of the lobule from the external ear, giving
CC the appearance of a question mark (question-mark ear). Other frequently
CC described features include prominent cheeks, cupped and posteriorly
CC rotated ears, preauricular tags, and microstomia.
CC {ECO:0000269|PubMed:24268655}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the endothelin/sarafotoxin family.
CC {ECO:0000305}.
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/edn1/";
CC -!- WEB RESOURCE: Name=Wikipedia; Note=Endothelin entry;
CC URL="https://en.wikipedia.org/wiki/Endothelin";
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DR EMBL; Y00749; CAA68718.1; -; mRNA.
DR EMBL; M25380; AAA52407.1; -; Genomic_DNA.
DR EMBL; M25377; AAA52407.1; JOINED; Genomic_DNA.
DR EMBL; M25378; AAA52407.1; JOINED; Genomic_DNA.
DR EMBL; M25379; AAA52407.1; JOINED; Genomic_DNA.
DR EMBL; J05008; AAA52339.1; -; Genomic_DNA.
DR EMBL; S56805; AAB25760.1; -; mRNA.
DR EMBL; AY434104; AAQ96600.1; -; Genomic_DNA.
DR EMBL; Z98050; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC009720; AAH09720.1; -; mRNA.
DR EMBL; M25549; AAA52338.1; -; Genomic_DNA.
DR CCDS; CCDS4522.1; -.
DR PIR; A36517; ANHU1.
DR RefSeq; NP_001161791.1; NM_001168319.1.
DR RefSeq; NP_001946.3; NM_001955.4.
DR RefSeq; XP_011512632.1; XM_011514330.2.
DR RefSeq; XP_011512633.1; XM_011514331.2.
DR RefSeq; XP_016865820.1; XM_017010331.1.
DR PDB; 1EDN; X-ray; 2.18 A; A=53-73.
DR PDB; 1EDP; NMR; -; A=53-69.
DR PDB; 1T7H; X-ray; 1.13 A; A/B=51-68.
DR PDB; 1V6R; NMR; -; A=53-73.
DR PDB; 5GLH; X-ray; 2.80 A; B=53-73.
DR PDB; 6DK5; X-ray; 1.85 A; A/B=53-73.
DR PDBsum; 1EDN; -.
DR PDBsum; 1EDP; -.
DR PDBsum; 1T7H; -.
DR PDBsum; 1V6R; -.
DR PDBsum; 5GLH; -.
DR PDBsum; 6DK5; -.
DR AlphaFoldDB; P05305; -.
DR BMRB; P05305; -.
DR SMR; P05305; -.
DR BioGRID; 108228; 5.
DR CORUM; P05305; -.
DR IntAct; P05305; 7.
DR STRING; 9606.ENSP00000368683; -.
DR BindingDB; P05305; -.
DR DrugBank; DB05407; TBC-3711.
DR iPTMnet; P05305; -.
DR PhosphoSitePlus; P05305; -.
DR BioMuta; EDN1; -.
DR DMDM; 119610; -.
DR MassIVE; P05305; -.
DR PaxDb; P05305; -.
DR PeptideAtlas; P05305; -.
DR PRIDE; P05305; -.
DR ProteomicsDB; 51829; -.
DR TopDownProteomics; P05305; -.
DR Antibodypedia; 10136; 802 antibodies from 38 providers.
DR DNASU; 1906; -.
DR Ensembl; ENST00000379375.6; ENSP00000368683.5; ENSG00000078401.7.
DR GeneID; 1906; -.
DR KEGG; hsa:1906; -.
DR MANE-Select; ENST00000379375.6; ENSP00000368683.5; NM_001955.5; NP_001946.3.
DR CTD; 1906; -.
DR DisGeNET; 1906; -.
DR GeneCards; EDN1; -.
DR HGNC; HGNC:3176; EDN1.
DR HPA; ENSG00000078401; Low tissue specificity.
DR MalaCards; EDN1; -.
DR MIM; 131240; gene.
DR MIM; 612798; phenotype.
DR MIM; 615706; phenotype.
DR MIM; 618979; phenotype.
DR neXtProt; NX_P05305; -.
DR OpenTargets; ENSG00000078401; -.
DR Orphanet; 137888; Auriculocondylar syndrome.
DR PharmGKB; PA27614; -.
DR VEuPathDB; HostDB:ENSG00000078401; -.
DR eggNOG; ENOG502S1NV; Eukaryota.
DR GeneTree; ENSGT00950000183053; -.
DR HOGENOM; CLU_090013_1_0_1; -.
DR InParanoid; P05305; -.
DR OMA; RCQCANQ; -.
DR OrthoDB; 1264335at2759; -.
DR PhylomeDB; P05305; -.
DR TreeFam; TF333184; -.
DR PathwayCommons; P05305; -.
DR Reactome; R-HSA-375276; Peptide ligand-binding receptors.
DR Reactome; R-HSA-416476; G alpha (q) signalling events.
DR SignaLink; P05305; -.
DR SIGNOR; P05305; -.
DR BioGRID-ORCS; 1906; 9 hits in 1072 CRISPR screens.
DR EvolutionaryTrace; P05305; -.
DR GeneWiki; Endothelin_1; -.
DR GenomeRNAi; 1906; -.
DR Pharos; P05305; Tbio.
DR PRO; PR:P05305; -.
DR Proteomes; UP000005640; Chromosome 6.
DR RNAct; P05305; protein.
DR Bgee; ENSG00000078401; Expressed in lower lobe of lung and 172 other tissues.
DR ExpressionAtlas; P05305; baseline and differential.
DR Genevisible; P05305; HS.
DR GO; GO:0045178; C:basal part of cell; IEA:Ensembl.
DR GO; GO:0005737; C:cytoplasm; IDA:BHF-UCL.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0005615; C:extracellular space; IDA:BHF-UCL.
DR GO; GO:0048237; C:rough endoplasmic reticulum lumen; IEA:Ensembl.
DR GO; GO:0030133; C:transport vesicle; TAS:Reactome.
DR GO; GO:0033093; C:Weibel-Palade body; IEA:Ensembl.
DR GO; GO:0005125; F:cytokine activity; IDA:BHF-UCL.
DR GO; GO:0031707; F:endothelin A receptor binding; IDA:BHF-UCL.
DR GO; GO:0031708; F:endothelin B receptor binding; IDA:BHF-UCL.
DR GO; GO:0005179; F:hormone activity; IDA:BHF-UCL.
DR GO; GO:0007193; P:adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway; IEA:Ensembl.
DR GO; GO:0014824; P:artery smooth muscle contraction; IDA:BHF-UCL.
DR GO; GO:0048675; P:axon extension; IEA:Ensembl.
DR GO; GO:0060385; P:axonogenesis involved in innervation; IEA:Ensembl.
DR GO; GO:0007589; P:body fluid secretion; IEA:Ensembl.
DR GO; GO:0001569; P:branching involved in blood vessel morphogenesis; IEA:Ensembl.
DR GO; GO:0070588; P:calcium ion transmembrane transport; IEA:Ensembl.
DR GO; GO:0019722; P:calcium-mediated signaling; IDA:BHF-UCL.
DR GO; GO:0060070; P:canonical Wnt signaling pathway; IEA:Ensembl.
DR GO; GO:0003253; P:cardiac neural crest cell migration involved in outflow tract morphogenesis; IEA:Ensembl.
DR GO; GO:0051216; P:cartilage development; IEA:Ensembl.
DR GO; GO:0007166; P:cell surface receptor signaling pathway; IDA:BHF-UCL.
DR GO; GO:0007267; P:cell-cell signaling; IDA:BHF-UCL.
DR GO; GO:0006874; P:cellular calcium ion homeostasis; IDA:MGI.
DR GO; GO:0071277; P:cellular response to calcium ion; IEA:Ensembl.
DR GO; GO:0071398; P:cellular response to fatty acid; IEA:Ensembl.
DR GO; GO:0071372; P:cellular response to follicle-stimulating hormone stimulus; IEA:Ensembl.
DR GO; GO:0071385; P:cellular response to glucocorticoid stimulus; IEA:Ensembl.
DR GO; GO:0044751; P:cellular response to human chorionic gonadotropin stimulus; IEA:Ensembl.
DR GO; GO:0070301; P:cellular response to hydrogen peroxide; IDA:MGI.
DR GO; GO:0071456; P:cellular response to hypoxia; IEA:Ensembl.
DR GO; GO:0071346; P:cellular response to interferon-gamma; IEA:Ensembl.
DR GO; GO:0071347; P:cellular response to interleukin-1; IEA:Ensembl.
DR GO; GO:0071373; P:cellular response to luteinizing hormone stimulus; IEA:Ensembl.
DR GO; GO:0071389; P:cellular response to mineralocorticoid stimulus; IEA:Ensembl.
DR GO; GO:0071310; P:cellular response to organic substance; IDA:MGI.
DR GO; GO:0071560; P:cellular response to transforming growth factor beta stimulus; IEA:Ensembl.
DR GO; GO:0071356; P:cellular response to tumor necrosis factor; IEA:Ensembl.
DR GO; GO:0071466; P:cellular response to xenobiotic stimulus; IEA:Ensembl.
DR GO; GO:0009953; P:dorsal/ventral pattern formation; IEA:Ensembl.
DR GO; GO:0035050; P:embryonic heart tube development; IEA:Ensembl.
DR GO; GO:0086100; P:endothelin receptor signaling pathway; IMP:UniProtKB.
DR GO; GO:0086101; P:endothelin receptor signaling pathway involved in heart process; IEA:Ensembl.
DR GO; GO:0042045; P:epithelial fluid transport; IEA:Ensembl.
DR GO; GO:0070371; P:ERK1 and ERK2 cascade; IEA:Ensembl.
DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; IDA:BHF-UCL.
DR GO; GO:0001821; P:histamine secretion; IEA:Ensembl.
DR GO; GO:0007249; P:I-kappaB kinase/NF-kappaB signaling; IEA:Ensembl.
DR GO; GO:0001701; P:in utero embryonic development; IEA:Ensembl.
DR GO; GO:0048016; P:inositol phosphate-mediated signaling; IDA:BHF-UCL.
DR GO; GO:0045321; P:leukocyte activation; TAS:BHF-UCL.
DR GO; GO:0060137; P:maternal process involved in parturition; IEA:Ensembl.
DR GO; GO:1903537; P:meiotic cell cycle process involved in oocyte maturation; IEA:Ensembl.
DR GO; GO:0051899; P:membrane depolarization; IEA:Ensembl.
DR GO; GO:0042474; P:middle ear morphogenesis; IEA:Ensembl.
DR GO; GO:0007005; P:mitochondrion organization; IEA:Ensembl.
DR GO; GO:0010259; P:multicellular organism aging; IEA:Ensembl.
DR GO; GO:0030195; P:negative regulation of blood coagulation; TAS:BHF-UCL.
DR GO; GO:0010629; P:negative regulation of gene expression; IEA:Ensembl.
DR GO; GO:0046888; P:negative regulation of hormone secretion; IEA:Ensembl.
DR GO; GO:0051771; P:negative regulation of nitric-oxide synthase biosynthetic process; IDA:BHF-UCL.
DR GO; GO:0051248; P:negative regulation of protein metabolic process; IDA:BHF-UCL.
DR GO; GO:0034392; P:negative regulation of smooth muscle cell apoptotic process; IEA:Ensembl.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:BHF-UCL.
DR GO; GO:0014034; P:neural crest cell fate commitment; IEA:Ensembl.
DR GO; GO:0030185; P:nitric oxide transport; IDA:BHF-UCL.
DR GO; GO:0003357; P:noradrenergic neuron differentiation; IEA:Ensembl.
DR GO; GO:0030072; P:peptide hormone secretion; IDA:BHF-UCL.
DR GO; GO:0061626; P:pharyngeal arch artery morphogenesis; IEA:Ensembl.
DR GO; GO:0014065; P:phosphatidylinositol 3-kinase signaling; IDA:BHF-UCL.
DR GO; GO:0031583; P:phospholipase D-activating G protein-coupled receptor signaling pathway; IEA:Ensembl.
DR GO; GO:0010613; P:positive regulation of cardiac muscle hypertrophy; IDA:BHF-UCL.
DR GO; GO:2001259; P:positive regulation of cation channel activity; IDA:MGI.
DR GO; GO:0061051; P:positive regulation of cell growth involved in cardiac muscle cell development; IDA:BHF-UCL.
DR GO; GO:0030335; P:positive regulation of cell migration; IDA:BHF-UCL.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; IDA:BHF-UCL.
DR GO; GO:0045793; P:positive regulation of cell size; IDA:BHF-UCL.
DR GO; GO:0070101; P:positive regulation of chemokine-mediated signaling pathway; IDA:BHF-UCL.
DR GO; GO:0007204; P:positive regulation of cytosolic calcium ion concentration; IDA:BHF-UCL.
DR GO; GO:0051482; P:positive regulation of cytosolic calcium ion concentration involved in phospholipase C-activating G protein-coupled signaling pathway; IEA:Ensembl.
DR GO; GO:0051091; P:positive regulation of DNA-binding transcription factor activity; IDA:BHF-UCL.
DR GO; GO:0010595; P:positive regulation of endothelial cell migration; TAS:BHF-UCL.
DR GO; GO:0010460; P:positive regulation of heart rate; IDA:BHF-UCL.
DR GO; GO:0046887; P:positive regulation of hormone secretion; IDA:BHF-UCL.
DR GO; GO:0043507; P:positive regulation of JUN kinase activity; IDA:BHF-UCL.
DR GO; GO:0043406; P:positive regulation of MAP kinase activity; IDA:BHF-UCL.
DR GO; GO:0045840; P:positive regulation of mitotic nuclear division; IDA:BHF-UCL.
DR GO; GO:0090023; P:positive regulation of neutrophil chemotaxis; IEA:Ensembl.
DR GO; GO:1901224; P:positive regulation of NIK/NF-kappaB signaling; IEA:Ensembl.
DR GO; GO:0045429; P:positive regulation of nitric oxide biosynthetic process; TAS:BHF-UCL.
DR GO; GO:0042482; P:positive regulation of odontogenesis; IEA:Ensembl.
DR GO; GO:0032308; P:positive regulation of prostaglandin secretion; IEA:Ensembl.
DR GO; GO:0060585; P:positive regulation of prostaglandin-endoperoxide synthase activity; IMP:BHF-UCL.
DR GO; GO:0035815; P:positive regulation of renal sodium excretion; IEA:Ensembl.
DR GO; GO:0060298; P:positive regulation of sarcomere organization; IMP:BHF-UCL.
DR GO; GO:2000273; P:positive regulation of signaling receptor activity; IDA:BHF-UCL.
DR GO; GO:0048661; P:positive regulation of smooth muscle cell proliferation; IDA:BHF-UCL.
DR GO; GO:0045987; P:positive regulation of smooth muscle contraction; IEA:Ensembl.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:BHF-UCL.
DR GO; GO:0035810; P:positive regulation of urine volume; IEA:Ensembl.
DR GO; GO:1904707; P:positive regulation of vascular associated smooth muscle cell proliferation; IEA:Ensembl.
DR GO; GO:0001516; P:prostaglandin biosynthetic process; IDA:BHF-UCL.
DR GO; GO:0010737; P:protein kinase A signaling; IDA:MGI.
DR GO; GO:0042313; P:protein kinase C deactivation; IDA:BHF-UCL.
DR GO; GO:0007205; P:protein kinase C-activating G protein-coupled receptor signaling pathway; IEA:Ensembl.
DR GO; GO:0006468; P:protein phosphorylation; IEA:Ensembl.
DR GO; GO:0010827; P:regulation of glucose transmembrane transport; IEA:Ensembl.
DR GO; GO:0006885; P:regulation of pH; IEA:Ensembl.
DR GO; GO:0051930; P:regulation of sensory perception of pain; IEA:Ensembl.
DR GO; GO:0003100; P:regulation of systemic arterial blood pressure by endothelin; IDA:BHF-UCL.
DR GO; GO:0019229; P:regulation of vasoconstriction; IEA:InterPro.
DR GO; GO:0070294; P:renal sodium ion absorption; IEA:Ensembl.
DR GO; GO:0007585; P:respiratory gaseous exchange by respiratory system; IEA:Ensembl.
DR GO; GO:0014823; P:response to activity; IEA:Ensembl.
DR GO; GO:0043200; P:response to amino acid; IEA:Ensembl.
DR GO; GO:0001975; P:response to amphetamine; IEA:Ensembl.
DR GO; GO:0071548; P:response to dexamethasone; IEA:Ensembl.
DR GO; GO:0044321; P:response to leptin; IEA:Ensembl.
DR GO; GO:0032496; P:response to lipopolysaccharide; IEA:Ensembl.
DR GO; GO:0035994; P:response to muscle stretch; IEA:Ensembl.
DR GO; GO:0035094; P:response to nicotine; IEA:Ensembl.
DR GO; GO:0010193; P:response to ozone; IEA:Ensembl.
DR GO; GO:0034696; P:response to prostaglandin F; IEA:Ensembl.
DR GO; GO:1902074; P:response to salt; IEA:Ensembl.
DR GO; GO:0033574; P:response to testosterone; IEA:Ensembl.
DR GO; GO:0043179; P:rhythmic excitation; IEA:Ensembl.
DR GO; GO:1902287; P:semaphorin-plexin signaling pathway involved in axon guidance; IEA:Ensembl.
DR GO; GO:0019233; P:sensory perception of pain; IEA:Ensembl.
DR GO; GO:0042554; P:superoxide anion generation; IEA:Ensembl.
DR GO; GO:0097492; P:sympathetic neuron axon guidance; IEA:Ensembl.
DR GO; GO:0030878; P:thyroid gland development; IEA:Ensembl.
DR GO; GO:0006366; P:transcription by RNA polymerase II; IEA:Ensembl.
DR GO; GO:0042310; P:vasoconstriction; IDA:BHF-UCL.
DR GO; GO:0014826; P:vein smooth muscle contraction; IDA:BHF-UCL.
DR InterPro; IPR020475; Endothelin.
DR InterPro; IPR019764; Endothelin_toxin_CS.
DR InterPro; IPR001928; Endothln-like_toxin.
DR PANTHER; PTHR13874; PTHR13874; 1.
DR Pfam; PF00322; Endothelin; 1.
DR PRINTS; PR00365; ENDOTHELIN.
DR SMART; SM00272; END; 2.
DR PROSITE; PS00270; ENDOTHELIN; 2.
PE 1: Evidence at protein level;
KW 3D-structure; Cleavage on pair of basic residues;
KW Direct protein sequencing; Disease variant; Disulfide bond;
KW Reference proteome; Secreted; Signal; Vasoactive; Vasoconstrictor.
FT SIGNAL 1..17
FT /evidence="ECO:0000269|PubMed:1864385"
FT PROPEP 18..50
FT /id="PRO_0000008058"
FT PEPTIDE 53..90
FT /note="Big endothelin-1"
FT /evidence="ECO:0000269|PubMed:10438732"
FT /id="PRO_0000008059"
FT PEPTIDE 53..73
FT /note="Endothelin-1"
FT /evidence="ECO:0000269|PubMed:10438732"
FT /id="PRO_0000008060"
FT PROPEP 74..212
FT /id="PRO_0000008061"
FT REGION 109..123
FT /note="Endothelin-like"
FT REGION 168..212
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 73..74
FT /note="Cleavage; by KEL"
FT /evidence="ECO:0000269|PubMed:10438732"
FT DISULFID 53..67
FT /evidence="ECO:0000269|PubMed:7664037"
FT DISULFID 55..63
FT /evidence="ECO:0000269|PubMed:7664037"
FT VARIANT 64
FT /note="V -> D (in QME; dbSNP:rs587777233)"
FT /evidence="ECO:0000269|PubMed:24268655"
FT /id="VAR_071152"
FT VARIANT 77
FT /note="P -> H (in ARCND3; dbSNP:rs587777232)"
FT /evidence="ECO:0000269|PubMed:24268655"
FT /id="VAR_071153"
FT VARIANT 91
FT /note="K -> E (in ARCND3; dbSNP:rs587777231)"
FT /evidence="ECO:0000269|PubMed:24268655"
FT /id="VAR_071154"
FT VARIANT 186
FT /note="V -> I (in dbSNP:rs6413478)"
FT /id="VAR_048933"
FT VARIANT 198
FT /note="K -> N (associated with HDL cholesterol levels is
FT some populations and in a sex-specific manner;
FT dbSNP:rs5370)"
FT /evidence="ECO:0000269|PubMed:10334806,
FT ECO:0000269|PubMed:10391210, ECO:0000269|PubMed:15489334,
FT ECO:0000269|PubMed:17357073, ECO:0000269|PubMed:18288492,
FT ECO:0000269|Ref.5"
FT /id="VAR_014188"
FT STRAND 53..56
FT /evidence="ECO:0007829|PDB:1T7H"
FT STRAND 57..59
FT /evidence="ECO:0007829|PDB:1EDN"
FT HELIX 61..67
FT /evidence="ECO:0007829|PDB:1T7H"
FT TURN 68..70
FT /evidence="ECO:0007829|PDB:1EDN"
SQ SEQUENCE 212 AA; 24425 MW; E2DA0EB86755BC3D CRC64;
MDYLLMIFSL LFVACQGAPE TAVLGAELSA VGENGGEKPT PSPPWRLRRS KRCSCSSLMD
KECVYFCHLD IIWVNTPEHV VPYGLGSPRS KRALENLLPT KATDRENRCQ CASQKDKKCW
NFCQAGKELR AEDIMEKDWN NHKKGKDCSK LGKKCIYQQL VRGRKIRRSS EEHLRQTRSE
TMRNSVKSSF HDPKLKGKPS RERYVTHNRA HW
