Endothelin-1

Details

Name
Endothelin-1
Synonyms
  • PPET1
  • Preproendothelin-1
Gene Name
EDN1
Organism
Humans
Amino acid sequence
>lcl|BSEQ0020676|Endothelin-1
MDYLLMIFSLLFVACQGAPETAVLGAELSAVGENGGEKPTPSPPWRLRRSKRCSCSSLMD
KECVYFCHLDIIWVNTPEHVVPYGLGSPRSKRALENLLPTKATDRENRCQCASQKDKKCW
NFCQAGKELRAEDIMEKDWNNHKKGKDCSKLGKKCIYQQLVRGRKIRRSSEEHLRQTRSE
TMRNSVKSSFHDPKLKGKPSRERYVTHNRAHW
Number of residues
212
Molecular Weight
24424.895
Theoretical pI
9.92
GO Classification
Functions
cytokine activity / endothelin A receptor binding / endothelin B receptor binding / hormone activity
Processes
artery smooth muscle contraction / body fluid secretion / calcium-mediated signaling / cartilage development / cell growth / cell surface receptor signaling pathway / cell-cell signaling / cellular response to calcium ion / cellular response to drug / cellular response to fatty acid / cellular response to glucocorticoid stimulus / cellular response to hypoxia / cellular response to interferon-gamma / cellular response to interleukin-1 / cellular response to mineralocorticoid stimulus / cellular response to peptide hormone stimulus / cellular response to transforming growth factor beta stimulus / cellular response to tumor necrosis factor / dorsal/ventral pattern formation / epithelial fluid transport / G-protein coupled receptor signaling pathway / glucose transport / heart development / histamine secretion / in utero embryonic development / inositol phosphate-mediated signaling / leukocyte activation / maternal process involved in parturition / membrane depolarization / middle ear morphogenesis / multicellular organismal aging / negative regulation of blood coagulation / negative regulation of cAMP biosynthetic process / negative regulation of cellular protein metabolic process / negative regulation of hormone secretion / negative regulation of nitric-oxide synthase biosynthetic process / negative regulation of smooth muscle cell apoptotic process / negative regulation of transcription from RNA polymerase II promoter / neural crest cell development / nitric oxide transport / patterning of blood vessels / peptide hormone secretion / phosphatidylinositol 3-kinase signaling / phospholipase D-activating G-protein coupled receptor signaling pathway / positive regulation of cardiac muscle hypertrophy / positive regulation of cell migration / positive regulation of cell proliferation / positive regulation of cell size / positive regulation of chemokine-mediated signaling pathway / positive regulation of cytosolic calcium ion concentration / positive regulation of cytosolic calcium ion concentration involved in phospholipase C-activating G-protein coupled signaling pathway / positive regulation of endothelial cell migration / positive regulation of heart rate / positive regulation of hormone secretion / positive regulation of JUN kinase activity / positive regulation of MAP kinase activity / positive regulation of mitotic nuclear division / positive regulation of neutrophil chemotaxis / positive regulation of nitric oxide biosynthetic process / positive regulation of odontogenesis / positive regulation of prostaglandin secretion / positive regulation of prostaglandin-endoperoxide synthase activity / positive regulation of receptor biosynthetic process / positive regulation of renal sodium excretion / positive regulation of sarcomere organization / positive regulation of smooth muscle cell proliferation / positive regulation of smooth muscle contraction / positive regulation of transcription from RNA polymerase II promoter / positive regulation of urine volume / prostaglandin biosynthetic process / protein kinase C deactivation / protein kinase C-activating G-protein coupled receptor signaling pathway / regulation of pH / regulation of sensory perception of pain / regulation of systemic arterial blood pressure by endothelin / regulation of vasoconstriction / respiratory gaseous exchange / response to activity / response to amino acid / response to dexamethasone / response to leptin / response to lipopolysaccharide / response to muscle stretch / response to nicotine / response to ozone / response to prostaglandin F / response to salt / response to testosterone / rhythmic excitation / sensory perception of pain / superoxide anion generation / vasoconstriction / vein smooth muscle contraction
Components
basal part of cell / cytoplasm / cytosol / extracellular region / extracellular space / rough endoplasmic reticulum lumen / Weibel-Palade body
General Function
Hormone activity
Specific Function
Endothelins are endothelium-derived vasoconstrictor peptides.
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Secreted
Gene sequence
>lcl|BSEQ0020677|Endothelin-1 (EDN1)
ATGGATTATTTGCTCATGATTTTCTCTCTGCTGTTTGTGGCTTGCCAAGGAGCTCCAGAA
ACAGTCTTAGGCGCTGAGCTCAGCGCGGTGGGTGAGAACGGCGGGGAGAAACCCACTCCC
AGTCCACCCTGGCGGCTCCGCCGGTCCAAGCGCTGCTCCTGCTCGTCCCTGATGGATAAA
GAGTGTGTCTACTTCTGCCACCTGGACATCATTTGGGTCAACACTCCCGAGCACGTTGTT
CCGTATGGACTTGGAAGCCCTAGGTCCAAGAGAGCCTTGGAGAATTTACTTCCCACAAAG
GCAACAGACCGTGAAAATAGATGCCAATGTGCTAGCCAAAAAGACAAGAAGTGCTGGAAT
TTTTGCCAAGCAGGAAAAGAACTCAGGGCTGAAGACATTATGGAGAAAGACTGGAATAAT
CATAAGAAAGGAAAAGACTGTTCCAAGCTTGGGAAAAAGTGTATTTATCAGCAGTTAGTG
AGAGGAAGAAAAATCAGAAGAAGTTCAGAGGAACACCTAAGACAAACCAGGTCGGAGACC
ATGAGAAACAGCGTCAAATCATCTTTTCATGATCCCAAGCTGAAAGGCAAGCCCTCCAGA
GAGCGTTATGTGACCCACAACCGAGCACATTGGTGA
Chromosome Location
6
Locus
6p24.1
External Identifiers
ResourceLink
UniProtKB IDP05305
UniProtKB Entry NameEDN1_HUMAN
GenBank Gene IDY00749
GenAtlas IDEDN1
HGNC IDHGNC:3176
General References
  1. Itoh Y, Yanagisawa M, Ohkubo S, Kimura C, Kosaka T, Inoue A, Ishida N, Mitsui Y, Onda H, Fujino M, et al.: Cloning and sequence analysis of cDNA encoding the precursor of a human endothelium-derived vasoconstrictor peptide, endothelin: identity of human and porcine endothelin. FEBS Lett. 1988 Apr 25;231(2):440-4. [Article]
  2. Inoue A, Yanagisawa M, Takuwa Y, Mitsui Y, Kobayashi M, Masaki T: The human preproendothelin-1 gene. Complete nucleotide sequence and regulation of expression. J Biol Chem. 1989 Sep 5;264(25):14954-9. [Article]
  3. Bloch KD, Friedrich SP, Lee ME, Eddy RL, Shows TB, Quertermous T: Structural organization and chromosomal assignment of the gene encoding endothelin. J Biol Chem. 1989 Jun 25;264(18):10851-7. [Article]
  4. Benatti L, Bonecchi L, Cozzi L, Sarmientos P: Two preproendothelin 1 mRNAs transcribed by alternative promoters. J Clin Invest. 1993 Mar;91(3):1149-56. [Article]
  5. Mungall AJ, Palmer SA, Sims SK, Edwards CA, Ashurst JL, Wilming L, Jones MC, Horton R, Hunt SE, Scott CE, Gilbert JG, Clamp ME, Bethel G, Milne S, Ainscough R, Almeida JP, Ambrose KD, Andrews TD, Ashwell RI, Babbage AK, Bagguley CL, Bailey J, Banerjee R, Barker DJ, Barlow KF, Bates K, Beare DM, Beasley H, Beasley O, Bird CP, Blakey S, Bray-Allen S, Brook J, Brown AJ, Brown JY, Burford DC, Burrill W, Burton J, Carder C, Carter NP, Chapman JC, Clark SY, Clark G, Clee CM, Clegg S, Cobley V, Collier RE, Collins JE, Colman LK, Corby NR, Coville GJ, Culley KM, Dhami P, Davies J, Dunn M, Earthrowl ME, Ellington AE, Evans KA, Faulkner L, Francis MD, Frankish A, Frankland J, French L, Garner P, Garnett J, Ghori MJ, Gilby LM, Gillson CJ, Glithero RJ, Grafham DV, Grant M, Gribble S, Griffiths C, Griffiths M, Hall R, Halls KS, Hammond S, Harley JL, Hart EA, Heath PD, Heathcott R, Holmes SJ, Howden PJ, Howe KL, Howell GR, Huckle E, Humphray SJ, Humphries MD, Hunt AR, Johnson CM, Joy AA, Kay M, Keenan SJ, Kimberley AM, King A, Laird GK, Langford C, Lawlor S, Leongamornlert DA, Leversha M, Lloyd CR, Lloyd DM, Loveland JE, Lovell J, Martin S, Mashreghi-Mohammadi M, Maslen GL, Matthews L, McCann OT, McLaren SJ, McLay K, McMurray A, Moore MJ, Mullikin JC, Niblett D, Nickerson T, Novik KL, Oliver K, Overton-Larty EK, Parker A, Patel R, Pearce AV, Peck AI, Phillimore B, Phillips S, Plumb RW, Porter KM, Ramsey Y, Ranby SA, Rice CM, Ross MT, Searle SM, Sehra HK, Sheridan E, Skuce CD, Smith S, Smith M, Spraggon L, Squares SL, Steward CA, Sycamore N, Tamlyn-Hall G, Tester J, Theaker AJ, Thomas DW, Thorpe A, Tracey A, Tromans A, Tubby B, Wall M, Wallis JM, West AP, White SS, Whitehead SL, Whittaker H, Wild A, Willey DJ, Wilmer TE, Wood JM, Wray PW, Wyatt JC, Young L, Younger RM, Bentley DR, Coulson A, Durbin R, Hubbard T, Sulston JE, Dunham I, Rogers J, Beck S: The DNA sequence and analysis of human chromosome 6. Nature. 2003 Oct 23;425(6960):805-11. [Article]
  6. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [Article]
  7. Inoue A, Yanagisawa M, Kimura S, Kasuya Y, Miyauchi T, Goto K, Masaki T: The human endothelin family: three structurally and pharmacologically distinct isopeptides predicted by three separate genes. Proc Natl Acad Sci U S A. 1989 Apr;86(8):2863-7. [Article]
  8. Lee S, Lin M, Mele A, Cao Y, Farmar J, Russo D, Redman C: Proteolytic processing of big endothelin-3 by the kell blood group protein. Blood. 1999 Aug 15;94(4):1440-50. [Article]
  9. Fabbrini MS, Valsasina B, Nitti G, Benatti L, Vitale A: The signal peptide of human preproendothelin-1. FEBS Lett. 1991 Jul 29;286(1-2):91-4. [Article]
  10. Bourgeois C, Robert B, Rebourcet R, Mondon F, Mignot TM, Duc-Goiran P, Ferre F: 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. J Clin Endocrinol Metab. 1997 Sep;82(9):3116-23. [Article]
  11. Pare G, Serre D, Brisson D, Anand SS, Montpetit A, Tremblay G, Engert JC, Hudson TJ, Gaudet D: Genetic analysis of 103 candidate genes for coronary artery disease and associated phenotypes in a founder population reveals a new association between endothelin-1 and high-density lipoprotein cholesterol. Am J Hum Genet. 2007 Apr;80(4):673-82. Epub 2007 Feb 21. [Article]
  12. Wiltshire S, Powell BL, Jennens M, McCaskie PA, Carter KW, Palmer LJ, Thompson PL, McQuillan BM, Hung J, Beilby JP: Investigating the association between K198N coding polymorphism in EDN1 and hypertension, lipoprotein levels, the metabolic syndrome and cardiovascular disease. Hum Genet. 2008 Apr;123(3):307-13. doi: 10.1007/s00439-008-0481-0. Epub 2008 Feb 21. [Article]
  13. Wolff M, Day J, Greenwood A, Larson S, McPherson A: Crystallization and preliminary X-ray analysis of human endothelin. Acta Crystallogr B. 1992 Apr 1;48 ( Pt 2):239-40. [Article]
  14. Janes RW, Peapus DH, Wallace BA: The crystal structure of human endothelin. Nat Struct Biol. 1994 May;1(5):311-9. [Article]
  15. Reily MD, Dunbar JB Jr: The conformation of endothelin-1 in aqueous solution: NMR-derived constraints combined with distance geometry and molecular dynamics calculations. Biochem Biophys Res Commun. 1991 Jul 31;178(2):570-7. [Article]
  16. Andersen NH, Chen CP, Marschner TM, Krystek SR Jr, Bassolino DA: Conformational isomerism of endothelin in acidic aqueous media: a quantitative NOESY analysis. Biochemistry. 1992 Feb 11;31(5):1280-95. [Article]
  17. Donlan ML, Brown FK, Jeffs PW: Solution conformation of human big endothelin-1. J Biomol NMR. 1992 Sep;2(5):407-20. [Article]
  18. Wallace BA, Janes RW, Bassolino DA, Krystek SR Jr: A comparison of X-ray and NMR structures for human endothelin-1. Protein Sci. 1995 Jan;4(1):75-83. [Article]
  19. Hewage CM, Jiang L, Parkinson JA, Ramage R, Sadler IH: 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. J Pept Res. 1999 Mar;53(3):223-33. [Article]
  20. Tiret L, Poirier O, Hallet V, McDonagh TA, Morrison C, McMurray JJ, Dargie HJ, Arveiler D, Ruidavets JB, Luc G, Evans A, Cambien F: The Lys198Asn polymorphism in the endothelin-1 gene is associated with blood pressure in overweight people. Hypertension. 1999 May;33(5):1169-74. [Article]
  21. Halushka MK, Fan JB, Bentley K, Hsie L, Shen N, Weder A, Cooper R, Lipshutz R, Chakravarti A: Patterns of single-nucleotide polymorphisms in candidate genes for blood-pressure homeostasis. Nat Genet. 1999 Jul;22(3):239-47. [Article]
  22. Gordon CT, Petit F, Kroisel PM, Jakobsen L, Zechi-Ceide RM, Oufadem M, Bole-Feysot C, Pruvost S, Masson C, Tores F, Hieu T, Nitschke P, Lindholm P, Pellerin P, Guion-Almeida ML, Kokitsu-Nakata NM, Vendramini-Pittoli S, Munnich A, Lyonnet S, Holder-Espinasse M, Amiel J: Mutations in endothelin 1 cause recessive auriculocondylar syndrome and dominant isolated question-mark ears. Am J Hum Genet. 2013 Dec 5;93(6):1118-25. doi: 10.1016/j.ajhg.2013.10.023. Epub 2013 Nov 21. [Article]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB05407TBC-3711investigationalunknownDetails