EDN1 endothelin 1 [Homo sapiens (human)] - Gene

Summary

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Official Symbol: EDN1provided by HGNC
Official Full Name: endothelin 1provided by HGNC
Primary source: HGNC:3176
See related: Ensembl:ENSG00000078401; HPRD:07030; MIM:131240; Vega:OTTHUMG00000014266
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: ET1; PPET1; HDLCQ7
Summary: The protein encoded by this gene is proteolytically processed to release a secreted peptide termed endothelin 1. This peptide is a potent vasoconstrictor and is produced by vascular endothelial cells. Endothelin 1 also can affect the central nervous system. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2009]

Genomic context

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Location :: 6p24.1

Sequence :: Chromosome: 6; NC_000006.11 (12290529..12297427)

See EDN1 in Epigenomics, MapViewer

Chromosome 6 - NC_000006.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence

Go to nucleotideGraphics FASTA GenBank

Go to reference sequence details

Bibliography

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GeneRIFs: Gene References Into Functions What's a GeneRIF?

The plasma ET-1 level may be a predictor of all-cause death in a healthy population.
Title: Plasma endothelin-1 level is a predictor of 10-year mortality in a general population: the Tanushimaru study.
Under physiological conditions, leptin stimulates both ET-1 and NO activity in the human circulation.
Title: Leptin stimulates both endothelin-1 and nitric oxide activity in lean subjects but not in patients with obesity-related metabolic syndrome.
Activation of LXR reduced the binding of the transcriptional factors AP-1 and NF-kappaB to the ET-1 gene promoter region, thereby regulating gene expression.
Title: Activation of liver X receptor attenuates endothelin-1 expression in vascular endothelial cells.
Fenofibrate decreases ET-1 expression by PPARalpha-dependent/independent pathways in endothelial cells.
Title: Fenofibrate inhibits endothelin-1 expression by peroxisome proliferator-activated receptor α-dependent and independent mechanisms in human endothelial cells.
The discovery of genetic variants in the kallikrein-kinin system and in the genes encoding pre-pro-endothelin-1 and pre-pro-adrenomedullin provides novel insights into the (co-)regulation of these vasoactive peptides in the vascular system.
Title: Genome-wide association study on plasma levels of midregional-proadrenomedullin and C-terminal-pro-endothelin-1.
This study found that the -3a/-4a ET-1 gene polymorphism is associated with HAPH in highlanders.
Title: Bosentan reduces pulmonary artery pressure in high altitude residents.
Higher levels of ET-1 were associated with higher pulmonary artery pressure and possibly higher pulmonary vascular resistance in patients with idiopathic pulmonary fibrosis. In some, ET-1 may contribute to pulmonary vascular disease burden in IPF.
Title: Plasma endothelin-1 and vascular endothelial growth factor levels and their relationship to hemodynamics in idiopathic pulmonary fibrosis.
Plasma ET-1 increases 2 days following aortic valve replacement (AVR) and myocardial ET-1 protein levels are increased in patients with aortic stenosis (AS) before AVR. Peroperatively, no plasma ET-1 augmentation or release from the heart was observed in AS patients.
Title: Endothelin-1 in the human myocardium and circulating plasma: evaluation before, during and after correction of aortic stenosis with aortic valve replacement.
Endothelin-1 levels are increased in right ventricular hypertrophy compared with the level in nonhypertrophied right ventricle.
Title: Endothelin axis is upregulated in human and rat right ventricular hypertrophy.
Therefore, this review summarizes recent clinical trials on the role of ET-1 receptor blockers with respect to the modulation of liver function. [review]
Title: The role of endothelin-1 and its receptor blockers on the liver function.

Submit: New GeneRIF Correction See all (433)

Phenotypes

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Review eQTL and phenotype association data in this region using PheGenI

HIV-1 protein interactions

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Protein	Gene	Interaction	Pubs
Envelope surface glycoprotein gp120	env	HIV-1 gp120 stimulates the secretion of endothelin-1, as well as TNF-alpha, from human cells in a concentration-dependent manner	PubMed
Nef, p27	nef	The activation of extracellular signal-regulated kinase (ERK) by endothelin-1 (ET-1) is inhibited by HIV-1 Nef in human astrocytes; a similar inhibitory action of Nef on ERK activation was observed after direct stimulation of G proteins	PubMed
Tat, p14	tat	HIV-1 Tat-linked intracellular third loop of the endothelin-1 type B receptor markedly enhances the endothelin-1 activation of ERK in the bone morphogenetic protein-2 receptor human pulmonary artery smooth muscle cells	PubMed
	tat	In HIV-1 Tat-expressing and HIV-infected astrocytes, endothelin-1 (ET-1) is significantly elevated through NF-kappaB (NF-kappaB)-responsive sites in the ET-1 promoter	PubMed

Go to the HIV-1, Human Protein Interaction Database

Interactions

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Products	Interactant	Other Gene	Source	Pubs	Description
P05305	P35318	ADM	HPRD	PubMed
P05305	P46379	BAG6	HPRD	PubMed
P05305	P23946	CMA1	HPRD	PubMed
P05305	Q7L5N1	COPS6	HPRD	PubMed
P05305	P42892	ECE1	HPRD	PubMed
P05305	P25101	EDNRA	HPRD	PubMed
P05305	P24530	EDNRB	HPRD	PubMed
P05305	P23276	KEL	HPRD	PubMed
P05305	P08473	MME	HPRD	PubMed
P05305	Q9NRR5	UBQLN4	HPRD	PubMed
BioGRID:108228	BioGRID:113647	BAG6	BioGRID	PubMed	Two-hybrid
BioGRID:108228	BioGRID:116176	COPS6	BioGRID	PubMed	Two-hybrid
BioGRID:108228	BioGRID:121223	UBQLN4	BioGRID	PubMed	Two-hybrid

Pathways from BioSystems

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Class A/1 (Rhodopsin-like receptors), organism-specific biosystem (from REACTOME)
Class A/1 (Rhodopsin-like receptors), organism-specific biosystemRhodopsin-like receptors (class A/1) are the largest group of GPCRs and are the best studied group from a functional and structural point of view. They show great diversity at the sequence level and ...
EGFR-dependent Endothelin signaling events, organism-specific biosystem (from Pathway Interaction Database)
EGFR-dependent Endothelin signaling events, organism-specific biosystem
EGFR-dependent Endothelin signaling events
Endothelin, organism-specific biosystem (from WikiPathways)
Endothelin, organism-specific biosystemEndothelin-1 is a bicyclic 21 amino acid peptide, produced primarily in the endothelium. It is a potent stimulus of long-lasting and persistent vasoconstriction. It also has a role as a stimulus of i...
Endothelins, organism-specific biosystem (from Pathway Interaction Database)
Endothelins, organism-specific biosystem
Endothelins
G alpha (q) signalling events, organism-specific biosystem (from REACTOME)
G alpha (q) signalling events, organism-specific biosystemThe classic signalling route for G alpha (q) is activation of phospholipase C beta thereby triggering phosphoinositide hydrolysis, calcium mobilization and protein kinase C activation. This provides ...
GPCR downstream signaling, organism-specific biosystem (from REACTOME)
GPCR downstream signaling, organism-specific biosystemG protein-coupled receptors (GPCRs) are classically defined as the receptor, G-protein and downstream effectors, the alpha subunit of the G-protein being the primary signaling molecule. However, it h...
GPCR ligand binding, organism-specific biosystem (from REACTOME)
GPCR ligand binding, organism-specific biosystemThere are more than 800 G-protein coupled receptor (GPCRs) in the human genome, making it the largest receptor superfamily. GPCRs are also the largest class of drug targets, involved in virtually all...
Gastrin-CREB signalling pathway via PKC and MAPK, organism-specific biosystem (from REACTOME)
Gastrin-CREB signalling pathway via PKC and MAPK, organism-specific biosystemGastrin is a hormone whose main function is to stimulate secretion of hydrochloric acid by the gastric mucosa, which results in gastrin formation inhibition. This hormone also acts as a mitogenic fac...
HIF-1 signaling pathway, organism-specific biosystem (from KEGG)
HIF-1 signaling pathway, organism-specific biosystemHypoxia-inducible factor 1 (HIF-1) is a transcription factor that functions as a master regulator of oxygen homeostasis. It consists of two subunits: an inducibly-expressed HIF-1alpha subunit and a c...
HIF-1-alpha transcription factor network, organism-specific biosystem (from Pathway Interaction Database)
HIF-1-alpha transcription factor network, organism-specific biosystem
HIF-1-alpha transcription factor network
Melanogenesis, organism-specific biosystem (from KEGG)
Melanogenesis, organism-specific biosystemCutaneous melanin pigment plays a critical role in camouflage, mimicry, social communication, and protection against harmful effects of solar radiation. Melanogenesis is under complex regulatory cont...
Melanogenesis, conserved biosystem (from KEGG)
Melanogenesis, conserved biosystemCutaneous melanin pigment plays a critical role in camouflage, mimicry, social communication, and protection against harmful effects of solar radiation. Melanogenesis is under complex regulatory cont...
MicroRNAs in cardiomyocyte hypertrophy, organism-specific biosystem (from WikiPathways)
MicroRNAs in cardiomyocyte hypertrophy, organism-specific biosystemThis pathway shows the role of microRNAs in the process of cardiac hypertrophy. MicroRNA targets were predicted by the TargetScan algorithm, and the predicted interactions are shown in red dashed lin...
Peptide ligand-binding receptors, organism-specific biosystem (from REACTOME)
Peptide ligand-binding receptors, organism-specific biosystemThese receptors, a subset of the Class A/1 (Rhodopsin-like) family, all bind peptide ligands which include the chemokines, opioids and somatostatins.
Prostaglandin Synthesis and Regulation, organism-specific biosystem (from WikiPathways)
Prostaglandin Synthesis and Regulation, organism-specific biosystem
Prostaglandin Synthesis and Regulation
Signal Transduction, organism-specific biosystem (from REACTOME)
Signal Transduction, organism-specific biosystemSignal transduction is a process in which extracellular signals elicit changes in cell state and activity. Transmembrane receptors sense changes in the cellular environment by binding ligands, such a...
Signaling by GPCR, organism-specific biosystem (from REACTOME)
Signaling by GPCR, organism-specific biosystemG protein-coupled receptors (GPCRs; 7TM receptors; seven transmembrane domain receptors; heptahelical receptors; G protein-linked receptors [GPLR]) are the largest family of transmembrane receptors i...

General gene information

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Markers

A006R11 (e-PCR)
- UniSTS:39263

WI-7563 (e-PCR)
- UniSTS:73697

Genotypes

See EDN1 SNP Geneview Report
See EDN1 SNP Genotype Report
See EDN1 SNP Variation Viewer Report

Homology

Homologs of the EDN1 gene: The EDN1 gene is conserved in chimpanzee, Rhesus monkey, dog, cow, mouse, rat, chicken, and zebrafish.
Map Viewer (Mouse, Rat)
OrthoDB: The Hierarchical Catalog of Eukaryotic Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
cytokine activity	IDA Inferred from Direct Assay more info	PubMed
endothelin A receptor binding	IDA Inferred from Direct Assay more info	PubMed
endothelin B receptor binding	IDA Inferred from Direct Assay more info	PubMed
hormone activity	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
G-protein coupled receptor signaling pathway	IDA Inferred from Direct Assay more info	PubMed
artery smooth muscle contraction	IDA Inferred from Direct Assay more info	PubMed
artery smooth muscle contraction	TAS Traceable Author Statement more info	PubMed
body fluid secretion	IEA Inferred from Electronic Annotation more info
calcium-mediated signaling	IDA Inferred from Direct Assay more info	PubMed
cartilage development	IEA Inferred from Electronic Annotation more info
cell growth	IEA Inferred from Electronic Annotation more info
cell surface receptor signaling pathway	IDA Inferred from Direct Assay more info	PubMed
cell-cell signaling	IDA Inferred from Direct Assay more info	PubMed
cellular response to interleukin-1	IEA Inferred from Electronic Annotation more info
cellular response to tumor necrosis factor	IEA Inferred from Electronic Annotation more info
dorsal/ventral pattern formation	IEA Inferred from Electronic Annotation more info
elevation of cytosolic calcium ion concentration	IDA Inferred from Direct Assay more info	PubMed
elevation of cytosolic calcium ion concentration involved in phospholipase C-activating G-protein coupled signaling pathway	IEA Inferred from Electronic Annotation more info
epithelial fluid transport	IEA Inferred from Electronic Annotation more info
glucose transport	IEA Inferred from Electronic Annotation more info
heart development	IEA Inferred from Electronic Annotation more info
histamine secretion	IEA Inferred from Electronic Annotation more info
in utero embryonic development	IEA Inferred from Electronic Annotation more info
inositol phosphate-mediated signaling	IDA Inferred from Direct Assay more info	PubMed
intracellular protein kinase cascade	IEA Inferred from Electronic Annotation more info
leukocyte activation	TAS Traceable Author Statement more info	PubMed
maternal process involved in parturition	IEA Inferred from Electronic Annotation more info
membrane depolarization	IEA Inferred from Electronic Annotation more info
middle ear morphogenesis	IEA Inferred from Electronic Annotation more info
multicellular organismal aging	IEA Inferred from Electronic Annotation more info
negative regulation of blood coagulation	TAS Traceable Author Statement more info	PubMed
negative regulation of cAMP biosynthetic process	IEA Inferred from Electronic Annotation more info
negative regulation of cellular protein metabolic process	IDA Inferred from Direct Assay more info	PubMed
negative regulation of hormone secretion	IEA Inferred from Electronic Annotation more info
negative regulation of nitric-oxide synthase biosynthetic process	IDA Inferred from Direct Assay more info	PubMed
negative regulation of smooth muscle cell apoptotic process	IEA Inferred from Electronic Annotation more info
negative regulation of transcription from RNA polymerase II promoter	IDA Inferred from Direct Assay more info	PubMed
neural crest cell development	IEA Inferred from Electronic Annotation more info
NOT neutrophil chemotaxis	IDA Inferred from Direct Assay more info	PubMed
nitric oxide transport	IDA Inferred from Direct Assay more info	PubMed
patterning of blood vessels	IEA Inferred from Electronic Annotation more info
peptide hormone secretion	IDA Inferred from Direct Assay more info	PubMed
phosphatidylinositol 3-kinase cascade	IDA Inferred from Direct Assay more info	PubMed
phospholipase D-activating G-protein coupled receptor signaling pathway	IEA Inferred from Electronic Annotation more info
positive regulation of JUN kinase activity	IDA Inferred from Direct Assay more info	PubMed
positive regulation of MAP kinase activity	IDA Inferred from Direct Assay more info	PubMed
positive regulation of cardiac muscle hypertrophy	IDA Inferred from Direct Assay more info	PubMed
positive regulation of cell migration	IDA Inferred from Direct Assay more info	PubMed
positive regulation of cell proliferation	IDA Inferred from Direct Assay more info	PubMed
positive regulation of cell size	IDA Inferred from Direct Assay more info	PubMed
positive regulation of chemokine-mediated signaling pathway	IC Inferred by Curator more info	PubMed
positive regulation of endothelial cell migration	TAS Traceable Author Statement more info	PubMed
positive regulation of heart rate	IDA Inferred from Direct Assay more info	PubMed
positive regulation of hormone secretion	IDA Inferred from Direct Assay more info	PubMed
positive regulation of mitosis	IDA Inferred from Direct Assay more info	PubMed
positive regulation of neutrophil chemotaxis	IEA Inferred from Electronic Annotation more info
positive regulation of nitric oxide biosynthetic process	TAS Traceable Author Statement more info	PubMed
positive regulation of odontogenesis	IEA Inferred from Electronic Annotation more info
positive regulation of prostaglandin-endoperoxide synthase activity	IMP Inferred from Mutant Phenotype more info	PubMed
positive regulation of receptor biosynthetic process	IDA Inferred from Direct Assay more info	PubMed
positive regulation of renal sodium excretion	IEA Inferred from Electronic Annotation more info
positive regulation of sarcomere organization	IMP Inferred from Mutant Phenotype more info	PubMed
positive regulation of smooth muscle cell proliferation	IDA Inferred from Direct Assay more info	PubMed
positive regulation of smooth muscle contraction	IEA Inferred from Electronic Annotation more info
positive regulation of urine volume	IEA Inferred from Electronic Annotation more info
prostaglandin biosynthetic process	IDA Inferred from Direct Assay more info	PubMed
protein kinase C deactivation	IDA Inferred from Direct Assay more info	PubMed
protein kinase C-activating G-protein coupled receptor signaling pathway	IEA Inferred from Electronic Annotation more info
regulation of pH	IEA Inferred from Electronic Annotation more info
regulation of sensory perception of pain	IEA Inferred from Electronic Annotation more info
regulation of systemic arterial blood pressure by endothelin	IDA Inferred from Direct Assay more info	PubMed
regulation of vasoconstriction	IEA Inferred from Electronic Annotation more info
respiratory gaseous exchange	IEA Inferred from Electronic Annotation more info
response to amino acid stimulus	IEA Inferred from Electronic Annotation more info
response to hypoxia	IEA Inferred from Electronic Annotation more info
response to lipopolysaccharide	IEA Inferred from Electronic Annotation more info
response to nicotine	IEA Inferred from Electronic Annotation more info
response to testosterone stimulus	IEA Inferred from Electronic Annotation more info
rhythmic excitation	IEA Inferred from Electronic Annotation more info
sensory perception of pain	IEA Inferred from Electronic Annotation more info
superoxide anion generation	IEA Inferred from Electronic Annotation more info
vasoconstriction	IDA Inferred from Direct Assay more info	PubMed
vein smooth muscle contraction	IDA Inferred from Direct Assay more info	PubMed

Component	Evidence Code	Pubs
cytoplasm	IDA Inferred from Direct Assay more info	PubMed
extracellular region	TAS Traceable Author Statement more info
extracellular space	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: endothelin-1

Names: endothelin-1; preproendothelin-1

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_016196.1 RefSeqGene

Range

5001..11899

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001168319.1 → NP_001161791.1 endothelin-1 isoform 2 preproprotein

Status: REVIEWED

Description

Transcript Variant: This variant (2) uses an alternate in-frame splice site at the 5' end of an exon compared to variant 1. The resulting isoform (2) has the same N- and C-termini but is 1 aa shorter compared to isoform 1.

Source sequence(s)

AL548191, AW044634, BQ009676, BX439515, S56805, Z98050

UniProtKB/Swiss-Prot

P05305

Conserved Domains (2) summary

smart00272
Location:107 – 128
Blast Score: 100

END; Endothelin

cl15291
Location:59 – 77
Blast Score: 116

Endothelin; Endothelin family
NM_001955.4 → NP_001946.3 endothelin-1 isoform 1 preproprotein

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1).

Source sequence(s)

AL548191, AW044634, BQ009676, S56805, Z98050

Consensus CDS

CCDS4522.1

UniProtKB/Swiss-Prot

P05305

UniProtKB/TrEMBL

Q6FH53

Related

ENSP00000368683, OTTHUMP00000016038, ENST00000379375, OTTHUMT00000039872

Conserved Domains (2) summary

smart00272
Location:108 – 129
Blast Score: 100

END; Endothelin

cl15291
Location:60 – 78
Blast Score: 116

Endothelin; Endothelin family

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 104

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh37.p10 Primary Assembly

Genomic

NC_000006.11 Reference GRCh37.p10 Primary Assembly

Range

12290529..12297427

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate HuRef

Genomic

AC_000138.1 Alternate HuRef

Range

12222160..12229052

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate CHM1_1.0

Genomic

NC_018917.1 Alternate CHM1_1.0

Range

12213196..12220096

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Nucleotide		Protein
Heading	Accession and Version	Protein
genomic	ABBA01022112.1 (243331..250223)	None
genomic	AMYH01016087.1 (277630..284530)	None
genomic	AY434104.1	AAQ96600.1
genomic	CH471087.1	EAW55313.1
		EAW55314.1
		EAW55315.1
		EAW55316.1
genomic	J05008.1	AAA52339.1
genomic	M25380.1	AAA52407.1
genomic	M25549.1	AAA52338.1
genomic	Z98050.1 (154182..161080)	None
mRNA	AK226096.1	None
mRNA	AK291838.1	BAF84527.1
mRNA	AK307089.1	None
mRNA	AK313914.1	None
mRNA	AL548191.3	None
mRNA	AW044634.1	None
mRNA	BC009720.1	AAH09720.1
mRNA	BC036851.1	None
mRNA	BG540968.1	None
mRNA	BM680754.1	None
mRNA	BQ009676.1	None
mRNA	BX439515.2	None
mRNA	CA306604.1	None
mRNA	CR541903.1	CAG46701.1
mRNA	S56805.1	AAB25760.1
mRNA	Y00749.1	CAA68718.1
other-genetic	DQ890981.2	ABM81907.1
other-genetic	DQ894155.2	ABM85081.1