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

Summary

Official Symbol: EDN1provided by HGNC
Official Full Name: endothelin 1provided by HGNC
Primary source: HGNC:HGNC:3176
See related: Ensembl:ENSG00000078401 MIM:131240
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; QME; PPET1; ARCND3; HDLCQ7
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]
Expression: Broad expression in lung (RPKM 13.6), fat (RPKM 10.9) and 23 other tissues See more
Orthologs: mouse all

Genomic context

Location:: 6p24.1

Exon count:: 9

Annotation release	Status	Assembly	Chr	Location
109.20201120	current	GRCh38.p13 (GCF_000001405.39)	6	NC_000006.12 (12256463..12297194)
105	previous assembly	GRCh37.p13 (GCF_000001405.25)	6	NC_000006.11 (12290529..12297427)

Chromosome 6 - NC_000006.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Interaction between PGI2 and ET-1 pathways in vascular smooth muscle from Group-III pulmonary hypertension patients.
Title: Interaction between PGI<sub>2</sub> and ET-1 pathways in vascular smooth muscle from Group-III pulmonary hypertension patients.
IL-17A Induces Endothelin-1 Expression through p38 Pathway in Prurigo Nodularis.
Title: IL-17A Induces Endothelin-1 Expression through p38 Pathway in Prurigo Nodularis.
Endothelins and their receptors in embryo implantation.
Title: Endothelins and their receptors in embryo implantation.
Influence of LYS198ASN polymorphism of endothelin-1 gene on ischemic atherothrombotic stroke characteristics.
Title: Influence of LYS198ASN polymorphism of endothelin-1 gene on ischemic atherothrombotic stroke characteristics.
ET-1 accelerates atherogenesis by promoting the expression of adhesion molecules and chemokines, as well as subsequent macrophage activation.
Title: PKC-Mediated Endothelin-1 Expression in Endothelial Cell Promotes Macrophage Activation in Atherogenesis.
findings are consistent with the hypothesis that elevated endothelin-1 levels contribute to subepithelial thickening and highlight this factor as a possible therapeutic target for difficult-to-treat fungal-induced asthma.
Title: Endothelin-1 mediates Aspergillus fumigatus-induced airway inflammation and remodelling.
was determined that in patients-carriers of Asn198Asn genotype of endothelin-1, Left ventricular mass (LVMI) and hypertrophy left ventricular indexes (LVMMI) were higher compared to patients-carriers of Lys198Lys and Lys198Asn type, both in men and women
Title: Indicators of left ventricle hypertrophy in patients with arterial hypertension combined with obesity and their interconnection with polymorphism of lys198asn genе of endothelin-1.
Downregulation of endothelial nitric oxide synthase (eNOS) and endothelin-1 (ET-1) in a co-culture system with human stimulated X-linked CGD neutrophils
Title: Downregulation of endothelial nitric oxide synthase (eNOS) and endothelin-1 (ET-1) in a co-culture system with human stimulated X-linked CGD neutrophils.
Lys198Asn polymorphism of EDN1 gene is associated with an increased risk for Ischemic Stroke.
Title: Association between Lys198Asn polymorphism of endothelin-1 gene and ischemic stroke: A meta-analysis.
Plasma levels of endothelin-1 is associated with increased coronary microvascular resistance.
Title: Plasma endothelin-1 and adrenomedullin are associated with coronary artery function and cardiovascular outcomes in humans.

Submit: New GeneRIF Correction See all GeneRIFs (713)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Auriculocondylar syndrome 3 MedGen: C3810332 OMIM: 615706 GeneReviews: Not available	Compare labs
Genome-wide association study on plasma levels of midregional-proadrenomedullin and C-terminal-pro-endothelin-1. GeneReviews: Not available
Question mark ears, isolated MedGen: C2748545 OMIM: 612798 GeneReviews: Not available	Compare labs

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Protein interactions

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	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	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
matrix	gag	HIV-1 MA-induced capillary-like structure formation is partially mediated by the ET-1/ETB receptor axis in human primary lymph node-derived lymphatic endothelial cells	PubMed
	gag	Exposure of human primary lymph node-derived lymphatic endothelial cells with HIV-1 MA induces release of ET-1	PubMed
	gag	Treatment of human stellate cells with HIV-1 MA upregulates the expression of CXCR2, syndecan-2, collagen-I, alpha-SMA, vimentin, and endothelin-1	PubMed

Go to the HIV-1, Human Interaction Database

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

A006R11 (e-PCR)
- UniSTS:39263

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

Homology

Homologs of the EDN1 gene: The EDN1 gene is conserved in chimpanzee, Rhesus monkey, dog, cow, mouse, rat, chicken, zebrafish, and frog.
Orthologs from Annotation Pipeline: 328 organisms have orthologs with human gene EDN1
Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
cytokine activity	IDA Inferred from Direct Assay more info	PubMed
endothelin A receptor binding	IBA Inferred from Biological aspect of Ancestor more info	PubMed
endothelin A receptor binding	IDA Inferred from Direct Assay more info	PubMed
endothelin B receptor binding	IBA Inferred from Biological aspect of Ancestor more info	PubMed
endothelin B receptor binding	IDA Inferred from Direct Assay more info	PubMed
endothelin B receptor binding	IPI Inferred from Physical Interaction more info	PubMed
hormone activity	IBA Inferred from Biological aspect of Ancestor more info	PubMed
hormone activity	IDA Inferred from Direct Assay more info	PubMed
protein binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
G protein-coupled receptor signaling pathway	IDA Inferred from Direct Assay more info	PubMed
G protein-coupled receptor signaling pathway	TAS Traceable Author Statement more info
adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway	IEA Inferred from Electronic Annotation more info
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
branching involved in blood vessel morphogenesis	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 surface receptor signaling pathway	IDA Inferred from Direct Assay more info	PubMed
cell-cell signaling	IDA Inferred from Direct Assay more info	PubMed
cellular calcium ion homeostasis	IBA Inferred from Biological aspect of Ancestor more info	PubMed
cellular response to calcium ion	IEA Inferred from Electronic Annotation more info
cellular response to drug	IEA Inferred from Electronic Annotation more info
cellular response to fatty acid	IEA Inferred from Electronic Annotation more info
cellular response to glucocorticoid stimulus	IEA Inferred from Electronic Annotation more info
cellular response to hypoxia	IEA Inferred from Electronic Annotation more info
cellular response to interferon-gamma	IEA Inferred from Electronic Annotation more info
cellular response to interleukin-1	IEA Inferred from Electronic Annotation more info
cellular response to mineralocorticoid stimulus	IEA Inferred from Electronic Annotation more info
cellular response to peptide hormone stimulus	IEA Inferred from Electronic Annotation more info
cellular response to transforming growth factor beta stimulus	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
endothelin receptor signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
epithelial fluid 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
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 organism aging	IEA Inferred from Electronic Annotation more info
negative regulation of blood coagulation	TAS Traceable Author Statement more info	PubMed
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 by RNA polymerase II	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
peptide hormone secretion	IDA Inferred from Direct Assay more info	PubMed
phosphatidylinositol 3-kinase signaling	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 DNA-binding transcription factor activity	IDA Inferred from Direct Assay more info	PubMed
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 NIK/NF-kappaB signaling	IEA Inferred from Electronic Annotation more info
positive regulation of cardiac muscle hypertrophy	IDA Inferred from Direct Assay more info	PubMed
positive regulation of cell growth involved in cardiac muscle cell development	IDA Inferred from Direct Assay more info	PubMed
positive regulation of cell growth involved in cardiac muscle cell development	IGI Inferred from Genetic Interaction more info	PubMed
positive regulation of cell migration	IDA Inferred from Direct Assay more info	PubMed
positive regulation of cell population 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 cytosolic calcium ion concentration	IDA Inferred from Direct Assay more info	PubMed
positive regulation of cytosolic calcium ion concentration involved in phospholipase C-activating G protein-coupled signaling pathway	IEA Inferred from Electronic Annotation more info
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 mitotic nuclear division	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 secretion	IEA Inferred from Electronic Annotation more info
positive regulation of prostaglandin-endoperoxide synthase activity	IBA Inferred from Biological aspect of Ancestor more info	PubMed
positive regulation of prostaglandin-endoperoxide synthase activity	IMP Inferred from Mutant Phenotype 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 transcription by RNA polymerase II	IDA Inferred from Direct Assay more info	PubMed
positive regulation of urine volume	IEA Inferred from Electronic Annotation more info
positive regulation of vascular associated smooth muscle cell proliferation	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 glucose transmembrane transport	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	IBA Inferred from Biological aspect of Ancestor more info	PubMed
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 by respiratory system	IEA Inferred from Electronic Annotation more info
response to activity	IEA Inferred from Electronic Annotation more info
response to amino acid	IEA Inferred from Electronic Annotation more info
response to dexamethasone	IEA Inferred from Electronic Annotation more info
response to leptin	IEA Inferred from Electronic Annotation more info
response to lipopolysaccharide	IEA Inferred from Electronic Annotation more info
response to muscle stretch	IEA Inferred from Electronic Annotation more info
response to nicotine	IEA Inferred from Electronic Annotation more info
response to ozone	IEA Inferred from Electronic Annotation more info
response to prostaglandin F	IEA Inferred from Electronic Annotation more info
response to salt	IEA Inferred from Electronic Annotation more info
response to testosterone	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	IBA Inferred from Biological aspect of Ancestor more info	PubMed
vein smooth muscle contraction	IDA Inferred from Direct Assay more info	PubMed

Component	Evidence Code	Pubs
Weibel-Palade body	IEA Inferred from Electronic Annotation more info
basal part of cell	IEA Inferred from Electronic Annotation more info
cytoplasm	IDA Inferred from Direct Assay more info	PubMed
extracellular region	TAS Traceable Author Statement more info
extracellular space	IBA Inferred from Biological aspect of Ancestor more info	PubMed
extracellular space	IDA Inferred from Direct Assay more info	PubMed
rough endoplasmic reticulum lumen	IEA Inferred from Electronic Annotation more info
transport vesicle	TAS Traceable Author Statement more info

General protein information

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Preferred Names: endothelin-1

Names: 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

5066..11899

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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

See identical proteins and their annotated locations for NP_001161791.1

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 (3) summary

PHA02659
Location:4 → 72

PHA02659; endothelin precursor; Provisional

smart00272
Location:107 → 128

END; Endothelin

pfam00322
Location:48 → 76

Endothelin; Endothelin family
NM_001955.5 → NP_001946.3 endothelin-1 isoform 1 preproprotein

See identical proteins and their annotated locations for NP_001946.3

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

ENSP00000368683.5, ENST00000379375.6

Conserved Domains (2) summary

smart00272
Location:108 → 129

END; Endothelin

pfam00322
Location:49 → 77

Endothelin; Endothelin family

RefSeqs of Annotated Genomes: Homo sapiens Updated Annotation Release 109.20201120

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

Reference GRCh38.p13 Primary Assembly

Genomic

NC_000006.12 Reference GRCh38.p13 Primary Assembly

Range

12256463..12297194

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_011514331.3 → XP_011512633.1 endothelin-1 isoform X1

See identical proteins and their annotated locations for XP_011512633.1

UniProtKB/Swiss-Prot

P05305

UniProtKB/TrEMBL

Q6FH53

Conserved Domains (2) summary

smart00272
Location:108 → 129

END; Endothelin

pfam00322
Location:49 → 77

Endothelin; Endothelin family
XM_011514332.2 → XP_011512634.1 endothelin-1 isoform X2

See identical proteins and their annotated locations for XP_011512634.1

Conserved Domains (3) summary

PHA02659
Location:4 → 72

PHA02659; endothelin precursor; Provisional

smart00272
Location:107 → 128

END; Endothelin

pfam00322
Location:48 → 76

Endothelin; Endothelin family
XM_011514330.2 → XP_011512632.1 endothelin-1 isoform X1

See identical proteins and their annotated locations for XP_011512632.1

UniProtKB/Swiss-Prot

P05305

UniProtKB/TrEMBL

Q6FH53

Conserved Domains (2) summary

smart00272
Location:108 → 129

END; Endothelin

pfam00322
Location:49 → 77

Endothelin; Endothelin family
XM_017010331.1 → XP_016865820.1 endothelin-1 isoform X1

UniProtKB/Swiss-Prot

P05305

UniProtKB/TrEMBL

Q6FH53

Conserved Domains (2) summary

smart00272
Location:108 → 129

END; Endothelin

pfam00322
Location:49 → 77

Endothelin; Endothelin family