Endothelin 1

Endothelin 1 (ET-1), also known as preproendothelin-1 (PPET1), is a potent vasoconstrictor that in humans is encoded by the EDN1 gene and produced by vascular endothelial cells. The protein encoded by this gene is proteolytically processed to release a secreted peptide termed endothelin 1. Endothelin 1 is one of three isoforms of human endothelin.

EDN1
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1EDN, 1EDP, 1T7H, 1V6R, 6DK5, 5GLH
Identifiers
Aliases	EDN1, ARCND3, ET1, HDLCQ7, QME, endothelin 1, PPET1
External IDs	MGI: 95283 HomoloGene: 1476 GeneCards: EDN1
Gene location (Human) Chr. Chromosome 6 (human)[1] Band 6p24.1 Start 12,290,361 bp[1] End 12,297,194 bp[1]
Gene location (Mouse) Chr. Chromosome 13 (mouse)[2] Band 13 A4|13 20.82 cM Start 42,301,476 bp[2] End 42,307,990 bp[2]
RNA expression pattern More reference expression data
Gene ontology Molecular function • hormone activity • receptor binding • cytokine activity • endothelin B receptor binding • GO:0001948 protein binding • endothelin A receptor binding Cellular component • cytoplasm • Weibel-Palade body • basal part of cell • extracellular region • rough endoplasmic reticulum lumen • extracellular • transport vesicle Biological process • skeletal system development • response to amino acid • positive regulation of cytosolic calcium ion concentration involved in phospholipase C-activating G-protein coupled signaling pathway • negative regulation of cellular protein metabolic process • positive regulation of MAP kinase activity • regulation of sensory perception of pain • vasoconstriction • body fluid secretion • positive regulation of sarcomere organization • positive regulation of cardiac muscle hypertrophy • cell surface receptor signaling pathway • cellular response to drug • multicellular organism aging • artery smooth muscle contraction • cellular response to interferon-gamma • positive regulation of chemokine-mediated signaling pathway • phosphatidylinositol 3-kinase signaling • response to leptin • positive regulation of mitotic nuclear division • cellular response to hypoxia • response to muscle stretch • cellular response to calcium ion • cellular response to transforming growth factor beta stimulus • positive regulation of renal sodium excretion • blood vessel morphogenesis • negative regulation of blood coagulation • response to nicotine • in utero embryonic development • neutrophil chemotaxis • heart development • positive regulation of prostaglandin secretion • vein smooth muscle contraction • cartilage development • rhythmic excitation • protein kinase C-activating G-protein coupled receptor signaling pathway • cellular response to glucocorticoid stimulus • branching involved in blood vessel morphogenesis • negative regulation of hormone secretion • positive regulation of smooth muscle contraction • negative regulation of nitric-oxide synthase biosynthetic process • positive regulation of prostaglandin-endoperoxide synthase activity • positive regulation of urine volume • positive regulation of JUN kinase activity • leukocyte activation • positive regulation of receptor biosynthetic process • membrane depolarization • negative regulation of transcription from RNA polymerase II promoter • response to ozone • respiratory gaseous exchange • positive regulation of heart rate • regulation of blood pressure • response to lipopolysaccharide • response to prostaglandin F • regulation of vasoconstriction • cellular response to interleukin-1 • response to salt • positive regulation of cell size • middle ear morphogenesis • nociception • prostaglandin biosynthetic process • dorsal/ventral pattern formation • phospholipase D-activating G-protein coupled receptor signaling pathway • positive regulation of odontogenesis • regulation of pH • positive regulation of smooth muscle cell proliferation • protein kinase C deactivation • histamine secretion • maternal process involved in parturition • GO:0007243 intracellular signal transduction • response to hypoxia • neural crest cell development • regulation of systemic arterial blood pressure by endothelin • nitric oxide transport • positive regulation of cell migration • response to testosterone • positive regulation of cytosolic calcium ion concentration • epithelial fluid transport • positive regulation of nitric oxide biosynthetic process • cell-cell signaling • cellular response to tumor necrosis factor • response to activity • response to dexamethasone • superoxide anion generation • positive regulation of endothelial cell migration • cellular response to peptide hormone stimulus • cellular response to fatty acid • peptide hormone secretion • cellular response to mineralocorticoid stimulus • positive regulation of cell proliferation • inositol phosphate-mediated signaling • positive regulation of hormone secretion • negative regulation of smooth muscle cell apoptotic process • response to drug • calcium-mediated signaling • response to transforming growth factor beta • positive regulation of transcription from RNA polymerase II promoter • positive regulation of sequence-specific DNA binding transcription factor activity • positive regulation of cell growth involved in cardiac muscle cell development • positive regulation of neutrophil chemotaxis • regulation of receptor activity • G-protein coupled receptor signaling pathway • adenylate cyclase-inhibiting G-protein coupled receptor signaling pathway • regulation of glucose transport • negative regulation of gene expression • positive regulation of NIK/NF-kappaB signaling • positive regulation of vascular smooth muscle cell proliferation Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	1906	13614
Ensembl	ENSG00000078401	ENSMUSG00000021367
UniProt	P05305	P22387
RefSeq (mRNA)	NM_001168319 NM_001955	NM_010104
RefSeq (protein)	NP_001161791 NP_001946 NP_001161791 NP_001946	NP_034234
Location (UCSC)	Chr 6: 12.29 – 12.3 Mb	Chr 13: 42.3 – 42.31 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

Source

Preproendothelin is precursor of the peptide ET-1. Endothelial cells convert preproendothelin to proendothelin and subsequently to mature endothelin, which the cells release.[5]

Clinical significance

Long term ET-1 exposure has been associated with hypertrophic cardiomyopathy.[6]

Endothelin-1 receptor antagonists (Bosentan) are used in the treatment of pulmonary hypertension. Inhibition of these receptors prevents pulmonary vasculature constriction and thus decreases pulmonary vascular resistance.

References

1. GRCh38: Ensembl release 89: ENSG00000078401 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000021367 - Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Boulpaep EL, Boron WF (2009). Medical physiology: a cellular and molecular approach. Saunders/Elsevier. ISBN 978-1-4160-3115-4.
6. Archer CR, Robinson EL, Drawnel FM, Roderick HL (August 2017). "Endothelin-1 promotes hypertrophic remodelling of cardiac myocytes by activating sustained signalling and transcription downstream of endothelin type A receptors". Cellular Signalling. 36: 240–254. doi:10.1016/j.cellsig.2017.04.010. PMC 5486433. PMID 28412414.

Further reading

• Bruno CM, Neri S, Di Prima P, Sciacca C (June 2003). "Pathophysiology of endothelin and medical emergencies". Panminerva Medica. 45 (2): 151–4. PMID 12855940.
• Doggrell SA (June 2004). "The endothelin system and its role in acute myocardial infarction". Expert Opinion on Therapeutic Targets. 8 (3): 191–201. doi:10.1517/14728222.8.3.191. PMID 15161426.
• Beghetti M, Black SM, Fineman JR (May 2005). "Endothelin-1 in congenital heart disease". Pediatric Research. 57 (5 Pt 2): 16R–20R. doi:10.1203/01.PDR.0000160447.83332.13. PMID 15817494.
• Cazaubon S, Deshayes F, Couraud PO, Nahmias C (April 2006). "[Endothelin-1, angiotensin II and cancer]". Médicine/Sciences. 22 (4): 416–22. doi:10.1051/medsci/2006224416. PMID 16597412.
• Ariza AC, Bobadilla NA, Halhali A (2007). "[Endothelin 1 and angiotensin II in preeeclampsia]". Revista de Investigacion Clinica. 59 (1): 48–56. PMID 17569300.
• Davenport AP, Hyndman KA, Dhaun N, Southan C, Kohan DE, Pollock JS, et al. (April 2016). "Endothelin". Pharmacological Reviews. 68 (2): 357–418. doi:10.1124/pr.115.011833. PMC 4815360. PMID 26956245.
• Han SG, Ko S, Lee WK, Jung ST, Yu YG (August 2017). "Determination of the endothelin-1 recognition sites of endothelin receptor type A by the directed-degeneration method". Scientific Reports. 7 (1): 7577. Bibcode:2017NatSR...7.7577H. doi:10.1038/s41598-017-08096-6. PMC 5548930. PMID 28790412.

External links

• Overview of all the structural information available in the PDB for UniProt: P05305 (Endothelin-1) at the PDBe-KB.

This article incorporates text from the United States National Library of Medicine, which is in the public domain.