Selected-GenAtlas references SOURCE GeneCards NCBI Gene Swiss-Prot Orphanet Ensembl
HGNC UniGene Nucleotide OMIM UCSC
Home Page
FLASH GENE
Symbol EDN3 contributors: mct - updated : 26-05-2015
HGNC name endothelin 3
HGNC id 3178
Corresponding disease
CCHS2 congenital central hypoventilation syndrome 2
HSCR4 Hirschsprung disease 4
WS4B Waardenburg syndrome, type 4B
Location 20q13.32      Physical location : 57.875.498 - 57.901.046
Synonym name
  • truncated endothelin 3
  • preproendothelin-3
    • Synonym symbol(s) ET3, MGC15067, MGC61498, ET-3, PPET3, HSCR4, WS4B
    DNA
    TYPE functioning gene
    STRUCTURE 25.55 kb     6 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status confirmed
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    6 splicing 2438 25 238 - 1997 9284755
  • variant 1
  • encoding the same isoform than variant 4
    • 5 splicing 2694 23 219 - 1997 9284755
  • variant 2
  • using an alternative splice site in the coding region
  • lacking a segment in the 3' UTR compared to variant 1
    • 4 splicing 2617 23 224 - 1997 9284755
  • variant 3
  • lacking an exon
  • using an alternative splice site in the coding region compared to variant 1
  • the translation frame remains the same
    • 5 splicing 2659 25 238 - 1997 9284755
  • variant 4
  • containing an additional fragment within the 3' UTR compared to variant 1
  • encoding the same isoform than variant 1
    		•
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart   highly
    Digestiveintestine    
     mouthtongue  moderately
     pancreas exocrine   highly
    Reproductivefemale systemovary  moderately
    Respiratoryrespiratory tractlarynx  highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Muscular    
    Nervousperipherous   
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a preproendothelin giving proendothelin from the N terminus
  • a C terminal region containing an endothelin-like peptide
  • the preendothelin gives EDN3 (21AA with two SH bounds) after cleavage by endothelin conversion enzyme (ECE1) and/or KELL group protein (KEL)
  • prepro Vic cleaved to Big VIC including a VIC-like peptide, then releasing mature VIC (EDN3)
    • HOMOLOGY
    interspecies ortholog to murine Edn3
    ortholog to rattus Edn3
    Homologene
    FAMILY
  • endothelin/sarafotoxin family
    • CATEGORY regulatory , signaling
    SUBCELLULAR LOCALIZATION extracellular
        intracellular
    text soluble fraction
    basic FUNCTION
  • endothelin 3, vaso-constrictor/pressor peptide
  • inducing several cellular responses, including the production of second messengers, diacylglycerol and inositol-triphosphate
  • playing an essential in development of neural crest-derived cell lineages, such as melanocytes and enteric neurons
  • essential paracrine factor for the proliferation, migration, and survival of embryonic melanocytes during fetal development
  • is involved in regulating colonic epithelial cell proliferation and survival, particularly for goblet cells, and may be an important component of colonic homeostasis
  • induces cortical neurite elongation through the endothelin A receptor (Uesugi 2009)
  • at low concentrations may attenuate inflammatory responses via EDNRB activation and NO production
    • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling signal transduction , sensory transduction/hearing
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • endothelin receptor type B (EDNRB)
  • interactions between SOX10, EDN3 and EDNRB during enteric nervous system and melanocyte development
  • BMP4 induces MITF expression in pluripotent stem cells and EDN3 subsequently promotes differentiation of these MITF expressing cells along the melanocyte lineage
    • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s) CCHS2 , HSCR4 , WS4B
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --low  
    reduction may be important in the transition from normal to cancerous cervical epithelium (Sun 2007)
    tumoral     --low  
    in cervical cancer compared with normal cervical epithelial cells (Sun 2007)
    tumoral       loss of function
    occurs frequently in colon cancers
    constitutional     --low  
    not only affects development and function of the enteric nervous system, but also specific classes of spinal rectal mechanoreceptors, which are required for visceral nociception from the colorectum
    Susceptibility to sporadic Hirschsprung disease
    Variant & Polymorphism other
  • common susceptibility gene for sporadic Hirschsprung disease in a low-penetrance fashion
    • Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
  • mice with deletions of the endothelin-3 gene (lethal spotted mice, ls/ls) develop congenital aganglionosis