P05305 (EDN1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Endothelin-1

Alternative name(s):
Preproendothelin-1
Short name=PPET1

Cleaved into the following 2 chains:

1. Endothelin-1
   Short name=ET-1
2. Big endothelin-1

Gene names

Name:

EDN1

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	212 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	Endothelins are endothelium-derived vasoconstrictor peptides.
Subcellular location	Secreted.
Tissue specificity	Expressed in lung, placental stem villi vessels and in cultured placental vascular smooth muscle cells. Ref.11
Sequence similarities	Belongs to the endothelin/sarafotoxin family.

Ontologies

Keywords
Cellular component	Secreted
Coding sequence diversity	Polymorphism
Domain	Signal
Molecular function	Vasoactive Vasoconstrictor
PTM	Cleavage on pair of basic residues Disulfide bond
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological process	artery smooth muscle contraction Inferred from direct assay. Source: BHF-UCL calcium-mediated signaling Inferred from direct assay. Source: BHF-UCL leukocyte activation Traceable author statement. Source: BHF-UCL negative regulation of blood coagulation Traceable author statement. Source: BHF-UCL negative regulation of cellular protein metabolic process Inferred from direct assay. Source: BHF-UCL negative regulation of nitric-oxide synthase biosynthetic process Inferred from direct assay. Source: BHF-UCL negative regulation of transcription from RNA polymerase II promoter Inferred from direct assay. Source: BHF-UCL nitric oxide transport Inferred from direct assay. Source: BHF-UCL peptide hormone secretion Inferred from direct assay. Source: BHF-UCL phosphatidylinositol 3-kinase cascade Inferred from direct assay. Source: BHF-UCL positive regulation of JUN kinase activity Inferred from direct assay. Source: BHF-UCL positive regulation of cardiac muscle hypertrophy Inferred from direct assay. Source: BHF-UCL positive regulation of cell size Inferred from direct assay. Source: BHF-UCL positive regulation of chemokine-mediated signaling pathway Inferred by curator. Source: BHF-UCL positive regulation of endothelial cell migration Traceable author statement. Source: BHF-UCL positive regulation of heart rate Inferred from direct assay Ref.8. Source: BHF-UCL positive regulation of hormone secretion Inferred from direct assay. Source: BHF-UCL positive regulation of mitosis Inferred from direct assay. Source: BHF-UCL positive regulation of nitric oxide biosynthetic process Traceable author statement. Source: BHF-UCL positive regulation of prostaglandin-endoperoxide synthase activity Inferred from mutant phenotype. Source: BHF-UCL positive regulation of receptor biosynthetic process Inferred from direct assay. Source: BHF-UCL positive regulation of sarcomere organization Inferred from mutant phenotype. Source: BHF-UCL positive regulation of smooth muscle cell proliferation Inferred from direct assay. Source: BHF-UCL prostaglandin biosynthetic process Inferred from direct assay. Source: BHF-UCL protein kinase C deactivation Inferred from direct assay. Source: BHF-UCL regulation of systemic arterial blood pressure by endothelin Inferred from direct assay Ref.8. Source: BHF-UCL regulation of vasoconstriction Inferred from electronic annotation. Source: InterPro vein smooth muscle contraction Inferred from direct assay. Source: BHF-UCL
Cellular component	cytoplasm Inferred from direct assay. Source: BHF-UCL extracellular space Inferred from direct assay. Source: BHF-UCL
Molecular function	cytokine activity Inferred from direct assay. Source: BHF-UCL endothelin A receptor binding Inferred from direct assay. Source: BHF-UCL endothelin B receptor binding Inferred from direct assay. Source: BHF-UCL hormone activity Inferred from direct assay Ref.8. Source: BHF-UCL
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 17

17

Propeptide

18 – 50

33

PRO_0000008058

Peptide

53 – 90

38

Big endothelin-1

PRO_0000008059

Peptide

53 – 73

21

Endothelin-1

PRO_0000008060

Propeptide

74 – 212

139

PRO_0000008061

Regions

Region

109 – 123

15

Endothelin-like

Sites

Site

73 – 74

2

Cleavage; by KEL

Amino acid modifications

Disulfide bond

53 ↔ 67

Ref.13

Disulfide bond

55 ↔ 63

Ref.13

Disulfide bond

109 ↔ 123

By similarity

Disulfide bond

111 ↔ 119

By similarity

Natural variations

Natural variant

186

1

V → I.
Corresponds to variant rs6413478 [ dbSNP | Ensembl ].

VAR_048933

Natural variant

198

1

K → N. Ref.5 Ref.7 Ref.19 Ref.20
Corresponds to variant rs5370 [ dbSNP | Ensembl ].

VAR_014188

Secondary structure

1

.

.

.

.

.

212

Helix Strand Turn

Details...

Beta strand

53 – 56

4

Helix

61 – 67

7

Sequences

	Sequence		Length	Mass (Da)
	P05305 [UniParc]. Last modified November 1, 1988. Version 1. Checksum: E2DA0EB86755BC3D	FASTA	212	24,425
	10 20 30 40 50 60 MDYLLMIFSL LFVACQGAPE TAVLGAELSA VGENGGEKPT PSPPWRLRRS KRCSCSSLMD 70 80 90 100 110 120 KECVYFCHLD IIWVNTPEHV VPYGLGSPRS KRALENLLPT KATDRENRCQ CASQKDKKCW 130 140 150 160 170 180 NFCQAGKELR AEDIMEKDWN NHKKGKDCSK LGKKCIYQQL VRGRKIRRSS EEHLRQTRSE 190 200 210 TMRNSVKSSF HDPKLKGKPS RERYVTHNRA HW

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning and sequence analysis of cDNA encoding the precursor of a human endothelium-derived vasoconstrictor peptide, endothelin: identity of human and porcine endothelin." Itoh Y., Yanagisawa M., Ohkubo S., Kimura C., Kosaka T., Inoue A., Ishida N., Mitsui Y., Onda H., Fujino M., Masaki T. FEBS Lett. 231:440-444(1988) [PubMed: 3282927] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Placenta.
[2]	"The human preproendothelin-1 gene. Complete nucleotide sequence and regulation of expression." Inoue A., Yanagisawa M., Takuwa Y., Mitsui Y., Kobayashi M., Masaki T. J. Biol. Chem. 264:14954-14959(1989) [PubMed: 2670930] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]	"Structural organization and chromosomal assignment of the gene encoding endothelin." Bloch K.D., Friedrich S.P., Lee M.E., Eddy R.L., Shows T.B., Quertermous T. J. Biol. Chem. 264:10851-10857(1989) [PubMed: 2659594] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]	"Two preproendothelin 1 mRNAs transcribed by alternative promoters." Benatti L., Bonecchi L., Cozzi L., Sarmientos P. J. Clin. Invest. 91:1149-1156(1993) [PubMed: 8450044] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[5]	NIEHS SNPs program Submitted (OCT-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT ASN-198.
[6]	"The DNA sequence and analysis of human chromosome 6." Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D., Andrews T.D. , Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V., Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J., Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J., French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I., Rogers J., Beck S. Nature 425:805-811(2003) [PubMed: 14574404] [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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT ASN-198. Tissue: Pancreas.
[8]	"The human endothelin family: three structurally and pharmacologically distinct isopeptides predicted by three separate genes." Inoue A., Yanagisawa M., Kimura S., Kasuya Y., Miyauchi T., Goto K., Masaki T. Proc. Natl. Acad. Sci. U.S.A. 86:2863-2867(1989) [PubMed: 2649896] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 27-67.
[9]	"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: 10438732] [Abstract] Cited for: PARTIAL PROTEIN SEQUENCE, CLEAVAGE BY KELL, MASS SPECTROMETRY.
[10]	"The signal peptide of human preproendothelin-1." Fabbrini M.S., Valsasina B., Nitti G., Benatti L., Vitale A. FEBS Lett. 286:91-94(1991) [PubMed: 1864385] [Abstract] Cited for: PROTEOLYTIC PROCESSING.
[11]	"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: 9284755] [Abstract] Cited for: TISSUE SPECIFICITY.
[12]	"Crystallization and preliminary X-ray analysis of human endothelin." Wolff M., Day J., Greenwood A., Larson S., McPherson A. Acta Crystallogr. B 48:239-240(1992) [PubMed: 1515112] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF ET-1.
[13]	"The crystal structure of human endothelin." Janes R.W., Peapus D.H., Wallace B.A. Nat. Struct. Biol. 1:311-319(1994) [PubMed: 7664037] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.18 ANGSTROMS) OF ET-1, DISULFIDE BONDS.
[14]	"The conformation of endothelin-1 in aqueous solution: NMR-derived constraints combined with distance geometry and molecular dynamics calculations." Reily M.D., Dunbar J.B. Jr. Biochem. Biophys. Res. Commun. 178:570-577(1991) [PubMed: 1859417] [Abstract] Cited for: STRUCTURE BY NMR OF ET-1.
[15]	"Conformational isomerism of endothelin in acidic aqueous media: a quantitative NOESY analysis." Andersen N.H., Chen C., Marschner T.M., Krystek S.R. Jr., Bassolino D.A. Biochemistry 31:1280-1295(1992) [PubMed: 1736987] [Abstract] Cited for: STRUCTURE BY NMR OF ET-1.
[16]	"Solution conformation of human big endothelin-1." Donlan M.L., Brown F.K., Jeffs P.W. J. Biomol. NMR 2:407-420(1992) [PubMed: 1422154] [Abstract] Cited for: STRUCTURE BY NMR OF 53-90.
[17]	"A comparison of X-ray and NMR structures for human endothelin-1." Wallace B.A., Janes R.W., Bassolino D.A., Krystek S.R. Jr. Protein Sci. 4:75-83(1995) [PubMed: 7773179] [Abstract] Cited for: COMPARISON OF NMR STRUCTURE WITH X-RAY STRUCTURE.
[18]	"Solution structure of a novel ETB receptor selective agonist ET1-21 [Cys(Acm)1,15, Aib3,11, Leu7] by nuclear magnetic resonance spectroscopy and molecular modelling." Hewage C.M., Jiang L., Parkinson J.A., Ramage R., Sadler I.H. J. Pept. Res. 53:223-233(1999) [PubMed: 10231710] [Abstract] Cited for: STRUCTURE BY NMR OF ET1 AGONIST.
[19]	"The Lys198Asn polymorphism in the endothelin-1 gene is associated with blood pressure in overweight people." Tiret L., Poirier O., Hallet V., McDonagh T.A., Morrison C., McMurray J.J., Dargie H.J., Arveiler D., Ruidavets J.B., Luc G., Evans A., Cambien F. Hypertension 33:1169-1174(1999) [PubMed: 10334806] [Abstract] Cited for: VARIANT ASN-198.
[20]	"Patterns of single-nucleotide polymorphisms in candidate genes for blood-pressure homeostasis." Halushka M.K., Fan J.-B., Bentley K., Hsie L., Shen N., Weder A., Cooper R., Lipshutz R., Chakravarti A. Nat. Genet. 22:239-247(1999) [PubMed: 10391210] [Abstract] Cited for: VARIANT ASN-198.
+	Additional computationally mapped references.

Web resources

NIEHS-SNPs

R&D Systems' cytokine source book: Endothelin-1

Wikipedia

Endothelin entry

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

Y00749 mRNA. Translation: CAA68718.1.
M25380 , M25377, M25378, M25379 Genomic DNA. Translation: AAA52407.1.
J05008 Genomic DNA. Translation: AAA52339.1.
S56805 mRNA. Translation: AAB25760.1.
AY434104 Genomic DNA. Translation: AAQ96600.1.
Z98050 Genomic DNA. Translation: CAB10846.1.
BC009720 mRNA. Translation: AAH09720.1.
M25549 Genomic DNA. Translation: AAA52338.1.

IPI

IPI00008327.

PIR

ANHU1. A36517.

RefSeq

NP_001161791.1. NM_001168319.1.
NP_001946.3. NM_001955.4.

UniGene

Hs.511899.
Hs.713645.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1EDN	X-ray	2.18	A	53-73	[»]
1EDP	NMR	-	A	53-69	[»]
1T7H	X-ray	1.13	A/B	51-68	[»]
1V6R	NMR	-	A	53-73	[»]

ProteinModelPortal

P05305.

ModBase

Search...

Protein-protein interaction databases

IntAct

P05305. 3 interactions.

MINT

MINT-1387120.

STRING

P05305.

Polymorphism databases

DMDM

119610.

Proteomic databases

PRIDE

P05305.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000379375; ENSP00000368683; ENSG00000078401.

GeneID

1906.

KEGG

hsa:1906.

UCSC

uc003nae.2. human.

Organism-specific databases

CTD

1906.

GeneCards

GC06P012290.

H-InvDB

HIX0005582.
HIX0033211.

HGNC

HGNC:3176. EDN1.

HPA

CAB032500.
HPA031976.

MIM

131240. gene.

neXtProt

NX_P05305.

PharmGKB

PA27614.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG19729.

HOGENOM

HBG279519.

HOVERGEN

HBG051441.

InParanoid

P05305.

OMA

QKDKKCW.

OrthoDB

EOG4QZ7N8.

PhylomeDB

P05305.

Enzyme and pathway databases

Pathway_Interaction_DB

endothelinpathway. Endothelins.
hif1_tfpathway. HIF-1-alpha transcription factor network.

Reactome

REACT_111102. Signal Transduction.

Gene expression databases

ArrayExpress

P05305.

Bgee

P05305.

CleanEx

HS_EDN1.

Genevestigator

P05305.

GermOnline

ENSG00000078401. Homo sapiens.

Family and domain databases

InterPro

IPR020475. Bibrotoxin/Sarafotoxin-D.
IPR019764. Endothelin_toxin_CS.
IPR001928. Endothln-like_toxin.
[Graphical view]

KO

K05227.

Pfam

PF00322. Endothelin. 1 hit.
[Graphical view]

PRINTS

PR00365. ENDOTHELIN.

SMART

SM00272. END. 2 hits.
[Graphical view]

PROSITE

PS00270. ENDOTHELIN. 2 hits.
[Graphical view]

ProtoNet

Search...

Other

NextBio

7757.

PMAP-CutDB

P05305.

SOURCE

Search...

Entry information

Entry name

EDN1_HUMAN

Accession

Primary (citable) accession number: P05305
Secondary accession number(s): Q96DA1

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1988
Last sequence update:	November 1, 1988
Last modified:	December 14, 2011
This is version 140 of the entry and version 1 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.