EDN1 (endothelin 1)

Gene

• Entrez ID: 1906
• Gene name: Endothelin 1
• Gene symbol: EDN1
• Synonyms: ARCND3, ET1, HDLCQ7, PPET1, QME
• Chromosome: 6
• Chromosome location: 6p24.1
• Summary: This gene encodes a preproprotein that is proteolytically processed to generate a secreted peptide that belongs to the endothelin/sarafotoxin family. This peptide is a potent vasoconstrictor and its cognate receptors are therapeutic targets in the treatment of pulmonary arterial hypertension. Aberrant expression of this gene may promote tumorigenesis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2015]

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs587777231	A>G	Pathogenic	Missense variant, coding sequence variant
rs587777232	C>A	Pathogenic	Missense variant, coding sequence variant
rs587777233	T>A	Pathogenic	Missense variant, coding sequence variant
rs587777234	T>G	Pathogenic	Stop gained, coding sequence variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT004455	hsa-miR-155-5p	Luciferase reporter assay	19783678
MIRT005432	hsa-miR-199a-5p	Luciferase reporter assay	19783678
MIRT006855	hsa-miR-1-3p	Luciferase reporter assay	22963810
MIRT006855	hsa-miR-1-3p	Microarray	18668037
MIRT006855	hsa-miR-1-3p	Luciferase reporter assay, qRT-PCR	25394359
MIRT006855	hsa-miR-1-3p	Microarray, ELISA, qRT-PCR	24394957
MIRT006855	hsa-miR-1-3p	Luciferase reporter assay, qRT-PCR	28042875
MIRT006855	hsa-miR-1-3p	ELISA, Luciferase reporter assay, qRT-PCR, Western blot	28493075
MIRT022267	hsa-miR-124-3p	Microarray	18668037
MIRT244065	hsa-let-7a-5p	PAR-CLIP	23592263
MIRT244066	hsa-let-7b-5p	PAR-CLIP	23592263
MIRT244067	hsa-let-7c-5p	PAR-CLIP	23592263
MIRT244068	hsa-let-7d-5p	PAR-CLIP	23592263
MIRT244069	hsa-let-7e-5p	PAR-CLIP	23592263
MIRT244070	hsa-let-7f-5p	PAR-CLIP	23592263
MIRT244073	hsa-miR-98-5p	PAR-CLIP	23592263
MIRT244073	hsa-miR-98-5p	Luciferase reporter assay	26098770
MIRT244074	hsa-let-7g-5p	PAR-CLIP	23592263
MIRT244075	hsa-let-7i-5p	PAR-CLIP	23592263
MIRT244076	hsa-miR-130a-3p	PAR-CLIP	23592263
MIRT244077	hsa-miR-301a-3p	PAR-CLIP	23592263
MIRT244078	hsa-miR-130b-3p	PAR-CLIP	23592263
MIRT244079	hsa-miR-454-3p	PAR-CLIP	23592263
MIRT244080	hsa-miR-759	PAR-CLIP	23592263
MIRT244081	hsa-miR-301b-3p	PAR-CLIP	23592263
MIRT244082	hsa-miR-1294	PAR-CLIP	23592263
MIRT244083	hsa-miR-4295	PAR-CLIP	23592263
MIRT244085	hsa-miR-3666	PAR-CLIP	23592263
MIRT244086	hsa-miR-3927-3p	PAR-CLIP	23592263
MIRT244087	hsa-miR-4458	PAR-CLIP	23592263
MIRT244088	hsa-miR-4500	PAR-CLIP	23592263
MIRT244089	hsa-miR-4710	PAR-CLIP	23592263
MIRT244090	hsa-miR-6800-5p	PAR-CLIP	23592263
MIRT244091	hsa-miR-6831-5p	PAR-CLIP	23592263
MIRT378367	hsa-miR-4727-5p	PAR-CLIP	23592263
MIRT378368	hsa-miR-6738-3p	PAR-CLIP	23592263
MIRT477735	hsa-miR-670-3p	PAR-CLIP	23592263
MIRT477736	hsa-miR-5001-3p	PAR-CLIP	23592263
MIRT477737	hsa-miR-433-3p	PAR-CLIP	23592263
MIRT477738	hsa-miR-7154-5p	PAR-CLIP	23592263
MIRT477739	hsa-miR-202-3p	PAR-CLIP	23592263
MIRT477740	hsa-miR-6817-5p	PAR-CLIP	23592263
MIRT477741	hsa-miR-4769-3p	PAR-CLIP	23592263
MIRT477742	hsa-miR-8060	PAR-CLIP	23592263
MIRT477743	hsa-miR-1279	PAR-CLIP	23592263
MIRT477744	hsa-miR-664a-3p	PAR-CLIP	23592263
MIRT477745	hsa-miR-6074	PAR-CLIP	23592263
MIRT477746	hsa-miR-3529-5p	PAR-CLIP	23592263
MIRT477747	hsa-miR-379-5p	PAR-CLIP	23592263
MIRT615477	hsa-miR-3680-3p	HITS-CLIP	23824327
MIRT615478	hsa-miR-557	HITS-CLIP	23824327
MIRT615479	hsa-miR-507	HITS-CLIP	23824327
MIRT615480	hsa-miR-450b-5p	HITS-CLIP	23824327
MIRT615481	hsa-miR-33b-5p	HITS-CLIP	23824327
MIRT615482	hsa-miR-33a-5p	HITS-CLIP	23824327
MIRT615483	hsa-miR-1298-5p	HITS-CLIP	23824327
MIRT615484	hsa-miR-524-5p	HITS-CLIP	23824327
MIRT615485	hsa-miR-520d-5p	HITS-CLIP	23824327
MIRT615486	hsa-miR-19b-2-5p	HITS-CLIP	23824327
MIRT615487	hsa-miR-19b-1-5p	HITS-CLIP	23824327
MIRT615488	hsa-miR-19a-5p	HITS-CLIP	23824327
MIRT615489	hsa-miR-4328	HITS-CLIP	23824327
MIRT732169	hsa-miR-125a-5p	Luciferase reporter assay	27106952
MIRT732477	hsa-miR-648	qRT-PCR, Luciferase reporter assa, Northern blot, Western blot	25403488

Transcription factors

Transcription factor	Regulation	Reference
FOXO1	Unknown	19887561
HIF1A	Activation	19783678
JUN	Unknown	12208352
NFKB1	Unknown	21334436
NR1H4	Repression	16357303
RELA	Unknown	21334436
STAT1	Activation	20217138

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000122	Process	Negative regulation of transcription by RNA polymerase II	IDA	19767294
GO:0001516	Process	Prostaglandin biosynthetic process	IDA	9492062
GO:0001569	Process	Branching involved in blood vessel morphogenesis	IEA
GO:0001701	Process	In utero embryonic development	IEA
GO:0001821	Process	Histamine secretion	IEA
GO:0003100	Process	Regulation of systemic arterial blood pressure by endothelin	IBA	21873635
GO:0003100	Process	Regulation of systemic arterial blood pressure by endothelin	IDA	2649896
GO:0005125	Function	Cytokine activity	IDA	19767294
GO:0005179	Function	Hormone activity	IBA	21873635
GO:0005179	Function	Hormone activity	IDA	2649896, 10770212
GO:0005515	Function	Protein binding	IPI	23597562
GO:0005576	Component	Extracellular region	TAS
GO:0005615	Component	Extracellular space	IBA	21873635
GO:0005615	Component	Extracellular space	IDA	10770212, 15691296, 16820593
GO:0005737	Component	Cytoplasm	IDA	12379507
GO:0006874	Process	Cellular calcium ion homeostasis	IBA	21873635
GO:0006885	Process	Regulation of pH	IEA
GO:0007166	Process	Cell surface receptor signaling pathway	IDA	1713452
GO:0007186	Process	G protein-coupled receptor signaling pathway	IDA	17078114
GO:0007186	Process	G protein-coupled receptor signaling pathway	TAS
GO:0007193	Process	Adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway	IEA
GO:0007204	Process	Positive regulation of cytosolic calcium ion concentration	IDA	1917960
GO:0007205	Process	Protein kinase C-activating G protein-coupled receptor signaling pathway	IEA
GO:0007267	Process	Cell-cell signaling	IDA	12379507
GO:0007507	Process	Heart development	IEA
GO:0007585	Process	Respiratory gaseous exchange by respiratory system	IEA
GO:0007589	Process	Body fluid secretion	IEA
GO:0008284	Process	Positive regulation of cell population proliferation	IDA	1917960, 17078114
GO:0009953	Process	Dorsal/ventral pattern formation	IEA
GO:0010193	Process	Response to ozone	IEA
GO:0010259	Process	Multicellular organism aging	IEA
GO:0010460	Process	Positive regulation of heart rate	IDA	2649896
GO:0010595	Process	Positive regulation of endothelial cell migration	TAS	8999856
GO:0010613	Process	Positive regulation of cardiac muscle hypertrophy	IDA	12847114
GO:0010827	Process	Regulation of glucose transmembrane transport	IEA
GO:0014032	Process	Neural crest cell development	IEA
GO:0014065	Process	Phosphatidylinositol 3-kinase signaling	IDA	17078114
GO:0014823	Process	Response to activity	IEA
GO:0014824	Process	Artery smooth muscle contraction	IDA	8982507
GO:0014824	Process	Artery smooth muscle contraction	TAS	1725334
GO:0014826	Process	Vein smooth muscle contraction	IBA	21873635
GO:0014826	Process	Vein smooth muscle contraction	IDA	9422810
GO:0019229	Process	Regulation of vasoconstriction	IEA
GO:0019233	Process	Sensory perception of pain	IEA
GO:0019722	Process	Calcium-mediated signaling	IDA	1917960, 10770212
GO:0030072	Process	Peptide hormone secretion	IDA	10770212
GO:0030133	Component	Transport vesicle	TAS
GO:0030185	Process	Nitric oxide transport	IDA	16820593
GO:0030195	Process	Negative regulation of blood coagulation	TAS	16820593
GO:0030335	Process	Positive regulation of cell migration	IDA	9696419
GO:0030593	Process	Neutrophil chemotaxis	IDA	9696419
GO:0031583	Process	Phospholipase D-activating G protein-coupled receptor signaling pathway	IEA
GO:0031707	Function	Endothelin A receptor binding	IBA	21873635
GO:0031707	Function	Endothelin A receptor binding	IDA	10770212
GO:0031708	Function	Endothelin B receptor binding	IBA	21873635
GO:0031708	Function	Endothelin B receptor binding	IDA	10770212
GO:0031708	Function	Endothelin B receptor binding	IPI	1713452
GO:0032269	Process	Negative regulation of cellular protein metabolic process	IDA	19767294
GO:0032308	Process	Positive regulation of prostaglandin secretion	IEA
GO:0032496	Process	Response to lipopolysaccharide	IEA
GO:0033093	Component	Weibel-Palade body	IEA
GO:0033574	Process	Response to testosterone	IEA
GO:0034392	Process	Negative regulation of smooth muscle cell apoptotic process	IEA
GO:0034696	Process	Response to prostaglandin F	IEA
GO:0035094	Process	Response to nicotine	IEA
GO:0035690	Process	Cellular response to drug	IEA
GO:0035810	Process	Positive regulation of urine volume	IEA
GO:0035815	Process	Positive regulation of renal sodium excretion	IEA
GO:0035994	Process	Response to muscle stretch	IEA
GO:0042045	Process	Epithelial fluid transport	IEA
GO:0042310	Process	Vasoconstriction	IDA	2649896, 11410113
GO:0042313	Process	Protein kinase C deactivation	IDA	16820593
GO:0042474	Process	Middle ear morphogenesis	IEA
GO:0042482	Process	Positive regulation of odontogenesis	IEA
GO:0042554	Process	Superoxide anion generation	IEA
GO:0043179	Process	Rhythmic excitation	IEA
GO:0043200	Process	Response to amino acid	IEA
GO:0043406	Process	Positive regulation of MAP kinase activity	IDA	10770212, 12847114
GO:0043507	Process	Positive regulation of JUN kinase activity	IDA	12847114
GO:0044321	Process	Response to leptin	IEA
GO:0045178	Component	Basal part of cell	IEA
GO:0045321	Process	Leukocyte activation	TAS	16820593
GO:0045429	Process	Positive regulation of nitric oxide biosynthetic process	TAS	8999856
GO:0045793	Process	Positive regulation of cell size	IDA	12847114
GO:0045840	Process	Positive regulation of mitotic nuclear division	IDA	10770212
GO:0045944	Process	Positive regulation of transcription by RNA polymerase II	IDA	24117217
GO:0045987	Process	Positive regulation of smooth muscle contraction	IEA
GO:0046887	Process	Positive regulation of hormone secretion	IDA	10770212
GO:0046888	Process	Negative regulation of hormone secretion	IEA
GO:0048016	Process	Inositol phosphate-mediated signaling	IDA	1917960
GO:0048237	Component	Rough endoplasmic reticulum lumen	IEA
GO:0048661	Process	Positive regulation of smooth muscle cell proliferation	IDA	10393673
GO:0051091	Process	Positive regulation of DNA-binding transcription factor activity	IDA	24117217
GO:0051216	Process	Cartilage development	IEA
GO:0051482	Process	Positive regulation of cytosolic calcium ion concentration involved in phospholipase C-activating G protein-coupled signaling pathway	IEA
GO:0051771	Process	Negative regulation of nitric-oxide synthase biosynthetic process	IDA	16820593
GO:0051899	Process	Membrane depolarization	IEA
GO:0051930	Process	Regulation of sensory perception of pain	IEA
GO:0060137	Process	Maternal process involved in parturition	IEA
GO:0060298	Process	Positive regulation of sarcomere organization	IMP	12847114
GO:0060585	Process	Positive regulation of prostaglandin-endoperoxide synthase activity	IBA	21873635
GO:0060585	Process	Positive regulation of prostaglandin-endoperoxide synthase activity	IMP	9492062
GO:0061051	Process	Positive regulation of cell growth involved in cardiac muscle cell development	IDA	24117217
GO:0061051	Process	Positive regulation of cell growth involved in cardiac muscle cell development	IGI	24117217
GO:0070101	Process	Positive regulation of chemokine-mediated signaling pathway	IDA	17178876
GO:0071277	Process	Cellular response to calcium ion	IEA
GO:0071346	Process	Cellular response to interferon-gamma	IEA
GO:0071347	Process	Cellular response to interleukin-1	IEA
GO:0071356	Process	Cellular response to tumor necrosis factor	IEA
GO:0071375	Process	Cellular response to peptide hormone stimulus	IEA
GO:0071385	Process	Cellular response to glucocorticoid stimulus	IEA
GO:0071389	Process	Cellular response to mineralocorticoid stimulus	IEA
GO:0071398	Process	Cellular response to fatty acid	IEA
GO:0071456	Process	Cellular response to hypoxia	IEA
GO:0071548	Process	Response to dexamethasone	IEA
GO:0071560	Process	Cellular response to transforming growth factor beta stimulus	IEA
GO:0086100	Process	Endothelin receptor signaling pathway	IMP	19086031
GO:0090023	Process	Positive regulation of neutrophil chemotaxis	IEA
GO:1901224	Process	Positive regulation of NIK/NF-kappaB signaling	IEA
GO:1902074	Process	Response to salt	IEA
GO:1904707	Process	Positive regulation of vascular associated smooth muscle cell proliferation	IEA
GO:2000273	Process	Positive regulation of signaling receptor activity	IDA	17178876

Other IDs

• MIM: 131240
• HGNC: 3176
• e!Ensembl: ENSG00000078401

Protein

• UniProt ID: P05305
• Protein name: Endothelin-1 (Preproendothelin-1) (PPET1) [Cleaved into: Endothelin-1 (ET-1); Big endothelin-1]
• Protein function: Endothelins are endothelium-derived vasoconstrictor peptides (By similarity). Probable ligand for G-protein coupled receptors EDNRA and EDNRB which activates PTK2B, BCAR1, BCAR3 and, GTPases RAP1 and RHOA cascade in glomerular mesangial cells (PubMed:19086031).
• PDB: 1EDN, 1EDP, 1T7H, 1V6R, 5GLH, 6DK5
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00322	Endothelin	49 → 77	Endothelin family	Repeat

• Sequence:

  MDYLLMIFSLLFVACQGAPETAVLGAELSAVGENGGEKPTPSPPWRLRRSKRCSCSSLMD
  KECVYFCHLDIIWVNTPEHVVPYGLGSPRSKRALENLLPTKATDRENRCQCASQKDKKCW
  NFCQAGKELRAEDIMEKDWNNHKKGKDCSKLGKKCIYQQLVRGRKIRRSSEEHLRQTRSE
  TMRNSVKSSFHDPKLKGKPSRERYVTHNRAHW

• Sequence length: 212