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
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Genomic context

Location:: 6p24.1

Exon count:: 9

Annotation release	Status	Assembly	Chr	Location
109.20210514	current	GRCh38.p13 (GCF_000001405.39)	6	NC_000006.12 (12256463..12297194)
105.20201022	previous assembly	GRCh37.p13 (GCF_000001405.25)	6	NC_000006.11 (12290594..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?

Genetic dysregulation of endothelin-1 is implicated in coronary microvascular dysfunction.
Title: Genetic dysregulation of endothelin-1 is implicated in coronary microvascular dysfunction.
Priapism in sickle cell disease: Associations between NOS3 and EDN1 genetic polymorphisms and laboratory biomarkers.
Title: Priapism in sickle cell disease: Associations between NOS3 and EDN1 genetic polymorphisms and laboratory biomarkers.
Endothelin-1 induces lysyl oxidase expression in pulmonary artery smooth muscle cells.
Title: Endothelin-1 induces lysyl oxidase expression in pulmonary artery smooth muscle cells.
Diabetes-related sex differences in the brain endothelin system following ischemia in vivo and in human brain endothelial cells in vitro.
Title: Diabetes-related sex differences in the brain endothelin system following ischemia in vivo and in human brain endothelial cells in vitro.
Hyperglycemia Augments Endothelin-1-Induced Constriction of Human Retinal Venules.
Title: Hyperglycemia Augments Endothelin-1-Induced Constriction of Human Retinal Venules.
In vivo assessment of a single adenine mutation in 5'UTR of Endothelin-1 gene in paediatric cases with severe pulmonary hypertension: an observational study.
Title: In vivo assessment of a single adenine mutation in 5'UTR of Endothelin-1 gene in paediatric cases with severe pulmonary hypertension: an observational study.
The ratio of circulating endothelin-1 to endothelin-3 associated with TIMI risk and dynamic TIMI risk score in ST elevation acute myocardial infarction.
Title: The ratio of circulating endothelin-1 to endothelin-3 associated with TIMI risk and dynamic TIMI risk score in ST elevation acute myocardial infarction.
C-type natriuretic peptide (CNP)/guanylate cyclase B (GC-B) system and endothelin-1(ET-1)/ET receptor A and B system in human vasculature.
Title: C-type natriuretic peptide (CNP)/guanylate cyclase B (GC-B) system and endothelin-1(ET-1)/ET receptor A and B system in human vasculature.
Endothelin-1 (ET-1) promotes a proinflammatory microglia phenotype in diabetic conditions.
Title: Endothelin-1 (ET-1) promotes a proinflammatory microglia phenotype in diabetic conditions.
Correlations of endothelin-1 gene polymorphisms and hypertensive intracerebral hemorrhage.
Title: Correlations of endothelin-1 gene polymorphisms and hypertensive intracerebral hemorrhage.

Submit: New GeneRIF Correction See all GeneRIFs (739)

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: 396 organisms have orthologs with human gene EDN1
Orthologs

Gene Ontology Provided by GOA

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

Process	Evidence Code	Pubs
involved_in G protein-coupled receptor signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in artery smooth muscle contraction	IDA Inferred from Direct Assay more info	PubMed
involved_in artery smooth muscle contraction	TAS Traceable Author Statement more info	PubMed
involved_in body fluid secretion	IEA Inferred from Electronic Annotation more info
involved_in branching involved in blood vessel morphogenesis	IEA Inferred from Electronic Annotation more info
involved_in calcium-mediated signaling	IDA Inferred from Direct Assay more info	PubMed
involved_in cartilage development	IEA Inferred from Electronic Annotation more info
involved_in cell surface receptor signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in cell-cell signaling	IDA Inferred from Direct Assay more info	PubMed
involved_in cellular calcium ion homeostasis	IBA Inferred from Biological aspect of Ancestor more info	PubMed
involved_in cellular response to calcium ion	IEA Inferred from Electronic Annotation more info
involved_in cellular response to fatty acid	IEA Inferred from Electronic Annotation more info
involved_in cellular response to glucocorticoid stimulus	IEA Inferred from Electronic Annotation more info
involved_in cellular response to hypoxia	IEA Inferred from Electronic Annotation more info
involved_in cellular response to interferon-gamma	IEA Inferred from Electronic Annotation more info
involved_in cellular response to interleukin-1	IEA Inferred from Electronic Annotation more info
involved_in cellular response to mineralocorticoid stimulus	IEA Inferred from Electronic Annotation more info
involved_in cellular response to peptide hormone stimulus	IEA Inferred from Electronic Annotation more info
involved_in cellular response to transforming growth factor beta stimulus	IEA Inferred from Electronic Annotation more info
involved_in cellular response to tumor necrosis factor	IEA Inferred from Electronic Annotation more info
involved_in cellular response to xenobiotic stimulus	IEA Inferred from Electronic Annotation more info
involved_in dorsal/ventral pattern formation	IEA Inferred from Electronic Annotation more info
involved_in endothelin receptor signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in epithelial fluid transport	IEA Inferred from Electronic Annotation more info
involved_in heart development	IEA Inferred from Electronic Annotation more info
involved_in histamine secretion	IEA Inferred from Electronic Annotation more info
involved_in in utero embryonic development	IEA Inferred from Electronic Annotation more info
involved_in inositol phosphate-mediated signaling	IDA Inferred from Direct Assay more info	PubMed
involved_in leukocyte activation	TAS Traceable Author Statement more info	PubMed
involved_in maternal process involved in parturition	IEA Inferred from Electronic Annotation more info
involved_in membrane depolarization	IEA Inferred from Electronic Annotation more info
involved_in middle ear morphogenesis	IEA Inferred from Electronic Annotation more info
involved_in multicellular organism aging	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of blood coagulation	TAS Traceable Author Statement more info	PubMed
involved_in negative regulation of cellular protein metabolic process	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of gene expression	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of hormone secretion	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of nitric-oxide synthase biosynthetic process	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of smooth muscle cell apoptotic process	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of transcription by RNA polymerase II	IDA Inferred from Direct Assay more info	PubMed
involved_in neural crest cell development	IEA Inferred from Electronic Annotation more info
NOT involved_in neutrophil chemotaxis	IDA Inferred from Direct Assay more info	PubMed
involved_in nitric oxide transport	IDA Inferred from Direct Assay more info	PubMed
involved_in peptide hormone secretion	IDA Inferred from Direct Assay more info	PubMed
involved_in phosphatidylinositol 3-kinase signaling	IDA Inferred from Direct Assay more info	PubMed
involved_in phospholipase D-activating G protein-coupled receptor signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of DNA-binding transcription factor activity	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of JUN kinase activity	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of MAP kinase activity	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of NIK/NF-kappaB signaling	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of cardiac muscle hypertrophy	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of cell growth involved in cardiac muscle cell development	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of cell growth involved in cardiac muscle cell development	IGI Inferred from Genetic Interaction more info	PubMed
involved_in positive regulation of cell migration	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of cell population proliferation	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of cell size	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of positive regulation of chemokine-mediated signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of cytosolic calcium ion concentration	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of cytosolic calcium ion concentration involved in phospholipase C-activating G protein-coupled signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of endothelial cell migration	TAS Traceable Author Statement more info	PubMed
involved_in positive regulation of heart rate	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of hormone secretion	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of mitotic nuclear division	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of neutrophil chemotaxis	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of nitric oxide biosynthetic process	TAS Traceable Author Statement more info	PubMed
involved_in positive regulation of odontogenesis	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of prostaglandin secretion	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of prostaglandin-endoperoxide synthase activity	IBA Inferred from Biological aspect of Ancestor more info	PubMed
involved_in positive regulation of prostaglandin-endoperoxide synthase activity	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of renal sodium excretion	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of sarcomere organization	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of positive regulation of signaling receptor activity	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of smooth muscle cell proliferation	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of smooth muscle contraction	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of transcription by RNA polymerase II	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of urine volume	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of vascular associated smooth muscle cell proliferation	IEA Inferred from Electronic Annotation more info
involved_in prostaglandin biosynthetic process	IDA Inferred from Direct Assay more info	PubMed
involved_in protein kinase C deactivation	IDA Inferred from Direct Assay more info	PubMed
involved_in protein kinase C-activating G protein-coupled receptor signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in regulation of glucose transmembrane transport	IEA Inferred from Electronic Annotation more info
involved_in regulation of pH	IEA Inferred from Electronic Annotation more info
involved_in regulation of sensory perception of pain	IEA Inferred from Electronic Annotation more info
involved_in regulation of systemic arterial blood pressure by endothelin	IBA Inferred from Biological aspect of Ancestor more info	PubMed
involved_in regulation of systemic arterial blood pressure by endothelin	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of vasoconstriction	IEA Inferred from Electronic Annotation more info
involved_in respiratory gaseous exchange by respiratory system	IEA Inferred from Electronic Annotation more info
involved_in response to activity	IEA Inferred from Electronic Annotation more info
involved_in response to amino acid	IEA Inferred from Electronic Annotation more info
involved_in response to dexamethasone	IEA Inferred from Electronic Annotation more info
involved_in response to leptin	IEA Inferred from Electronic Annotation more info
involved_in response to lipopolysaccharide	IEA Inferred from Electronic Annotation more info
involved_in response to muscle stretch	IEA Inferred from Electronic Annotation more info
involved_in response to nicotine	IEA Inferred from Electronic Annotation more info
involved_in response to ozone	IEA Inferred from Electronic Annotation more info
involved_in response to prostaglandin F	IEA Inferred from Electronic Annotation more info
involved_in response to salt	IEA Inferred from Electronic Annotation more info
involved_in response to testosterone	IEA Inferred from Electronic Annotation more info
involved_in rhythmic excitation	IEA Inferred from Electronic Annotation more info
involved_in sensory perception of pain	IEA Inferred from Electronic Annotation more info
involved_in superoxide anion generation	IEA Inferred from Electronic Annotation more info
involved_in vasoconstriction	IDA Inferred from Direct Assay more info	PubMed
involved_in vein smooth muscle contraction	IBA Inferred from Biological aspect of Ancestor more info	PubMed
involved_in vein smooth muscle contraction	IDA Inferred from Direct Assay more info	PubMed

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

Download

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 109.20210514

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