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FLASH GENE
Symbol EDN1 contributors: mct/npt/pgu - updated : 18-06-2015
HGNC name endothelin 1
HGNC id 3176
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