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FLASH GENE
Symbol EDN1 contributors: mct/npt/pgu - updated : 18-06-2015
HGNC name endothelin 1
HGNC id 3176
RNA
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
5 - 2117 24.2 212 - 2000 10708518
EXPRESSION
Type widely
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Cardiovascularheart   highly
Digestiveesophagus   highly
 liver   highly
Nervousbrain   moderately Homo sapiens
Respiratorylung   moderately
Urinarykidney   moderately
tissue
SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
Connectiveadipose  highly
Muscularstriatumskeletal  
Nervouscentral    Homo sapiens
cells
SystemCellPubmedSpeciesStageRna symbol
Cardiovascularendothelial cell
cell lineage
cell lines
fluid/secretion
at STAGE
physiological period pregnancy
Text placenta
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
isoforms Precursor prepro ET1 cleaved to Big ET1 including a ET1-like peptide, then releasing mature ET1 (EDN1)
HOMOLOGY
interspecies homolog to rattus Edn1 (72.14 pc)
homolog to murine Edn1 (73.63 pc)
Homologene
FAMILY
  • endothelin/sarafotoxin family
  • CATEGORY signaling hormone growth factor
    SUBCELLULAR LOCALIZATION extracellular
        intracellular
    intracellular,cytoplasm
    basic FUNCTION
  • endothelin 1, vaso-constrictor/pressor peptide
  • phospholipase C activator, playing a role in airways, including bronchoconstriction, airway mucus secretion, cell proliferation, and inflammation
  • playing a role on epithelial ion transport in airways
  • playing a direct role in HDL metabolism
  • endothelial cell-derived vasoconstrictor and growth factor
  • potent vasoactive peptide that is synthesized and released by the vascular endothelium and is a marker of endothelial function
  • induces cortical neurite elongation through the endothelin A receptor
  • may exert its vasoconstrictive effects in part by targeting KCNK3
  • induces mRNA and protein secretion of CCL2 and IL6, forming an autocrine signaling pathway that stimulates collagen accumulation in the extracellular matrix
  • increases collagen deposition in the extracellular matrix by inducing an autocrine signaling loop involving secretion of CCL2 and IL6
  • increases CCL2 and IL6 mRNAs and peptide secretion in mesangial cells
  • role of EDN1 in linking TLR7 inflammatory signaling to subsequent fibrosis
  • TGFbeta-induced EDN1 expression in dermal fibroblasts and showed that the TGFB1-induced expression of profibrotic genes was dependent on EDN1
  • in part because it induces the unfolded protein response in pulmonary artery smooth muscle cells, triggers proinflammatory processes that likely contribute to vascular remodeling in pulmonary hypertension
  • BMPs act upstream and in parallel to EDN1 to promote ventral fates in the arches during early dorsal-ventral patterning
  • would act in a cooperative manner with EDN2, giving to the villus the straight enough to withstand mechanical stress
  • potent vasoconstrictor, the production of which is mainly catalyzed by endothelin-converting enzymes (
  • is a potent lymphangiogenic factor that relies on the interplay with hypoxic microenvironment and with VEGFA, VEGFC, and FIGF
  • induces positive inotropy (enhanced contractility) in cardiac muscle
  • EDN1 affects systolic Ca2+, and myofilament Ca2+ sensitivity and PRKCE is the upstream kinase involved in all of these intracellular regulatory processes
  • integral role for ectoderm-derived EDN1 in early arch morphogenesis, particularly in the intermediate domain (
  • essential role of endothelin 1 (EDN1) signaling through the endothelin receptor type A (EDNRA) in patterning the mandibular portion of the first pharyngeal arch
  • RETN and EDN1 have been reported to inhibit adipogenesis and regulate adipocyte insulin resistance, respectively
  • EDN1 activation of EDNRA signalled through ARF6, which is crucial for lipolysis
  • CELLULAR PROCESS cell life, proliferation/growth
    cell communication
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling signal transduction
    a component
  • components of the endothelin system, are EDN1, EDNRB and ECE1
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • interacting with CHGA (variation in expression of the CHGA gene influences endothelial EDN1 secretion, explained by a CHGA stimulus/EDN1 secretion coupling in endothelial cells)
  • EDNRB is involved in the regulation of the growth of and in the formation of functional vessels upon activation by EDN1
  • interacting with ZNF260 (ZNF260 is an obligatory effector of EDN1 signaling in cardiomyocytes)
  • interacting with IL6, and CCL2 (an autocrine signaling loop involving CCL2 and IL6 contributes to EDN1-induced collagen accumulation)
  • link between EDN1 and EDNRA and myelination during oligodendrocyte differentiation
  • decreases ABCG1 possibly due to the enhancement of the proteosome/calpain pathway-dependent degradation of ABCG1
  • PRKCA, PRKCB, stimulates collecting duct EDN1 synthesis via transcriptional activation of the EDN1 promoter (
  • GDF2 induced EDN1 release is involved in both inhibition of endothelial cell migration and promotion of tubule formation
  • mediates the autocrine effect of endothelin-1 (EDN1) on endothelial cell survival
  • CDC42 plays an important role in trophoblast migration and is obligatory for EDN1 action
  • ARRB1 is a nuclear transcriptional regulator of EDN1-induced CTNNB1 signaling
  • EDN1 regulates neural crest deployment and fate to form great vessels through DLX5/DLX6-independent mechanisms
  • EDN1 stimulates RETN gene expression
  • ARF6 plays a role in EDN1 promoted endothelial cell migration, and acts upstream of ERK in EDN1-induced lipolysis
  • NR4A1 is a novel negative regulator of EDN1 expression in vascular ECs through an inhibitory interaction with the JUN pathway
  • sarcolemmal and nuclear membrane CACNA1E in vascular smooth muscle cells are involved in EDN1 modulation of vascular tone in physiology and pathology
  • cell & other
    REGULATION
    induced by GATA2 in endothelial cells
    repressed by GPER (endogenous GPER inhibits EDN1-induced vasoconstriction, an effect that may be associated with reduced VSMC Ca(2+) sensitivity)
    Other regulated by hypoxia in non endothelial cells (through overexpression of GATA2 and HIF1A)
    up-regulated by leptin
    ASSOCIATED DISORDERS
    corresponding disease(s) ACDS3
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in clear cell renal tumor patients and hypertension
    tumoral     --low  
    in papillary renal tumor
    constitutional   deletion    
    ectodermal deletion of EDN1 results in craniofacial defects with concomitant changes in the expression of early mandibular arch patterning genes (
    constitutional     --over  
    higher expressed in Alzheimer disease than in control tissue
    Susceptibility
  • to coronary heart disease
  • to developing cardiac hypertrophy
  • Variant & Polymorphism SNP , other
  • decreasing HDL level and increasing coronary heart disease
  • homozygosity for the -1224A/198K haplotype, is associated with the risk of developing cardiac hypertrophy
  • Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS