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FLASH GENE
Symbol EPHB4 contributors: mct - updated : 27-01-2016
HGNC name EPH receptor B4
HGNC id 3395
Location 7q22.1      Physical location : 100.400.186 - 100.425.143
Synonym name
  • hepatome transmembrane kinase
  • EPH-related tyrosine kinase receptor B4
  • tyrosine-protein kinase TYRO11
  • soluble EPHB4 variants (1, 2, 3)
  • Synonym symbol(s) HTK, TYRO11, MYK1
    EC.number 2.7.10.1
    DNA
    TYPE functioning gene
    STRUCTURE 24.96 kb     17 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status provisional
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    17 - 4369 - 987 - 2008 18593464
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularvesselartery    Homo sapiens
     vesselvein    Homo sapiens
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Nervousneuron
    Skeletonosteoblast Homo sapiens
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period pregnancy
    Text placenta
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a vestigial Ig-I domain
  • a single cysteine rich region
  • two FNIII domains in the extracellular region
  • HOMOLOGY
    Homologene
    FAMILY
  • protein kinase superfamily
  • Tyr protein kinase family
  • ephrin receptor subfamily
  • CATEGORY enzyme
    SUBCELLULAR LOCALIZATION extracellular
        plasma membrane
        intracellular
    intracellular,cytoplasm,cytosolic
    basic FUNCTION
  • receptor tyrosine kinase, involved in short-range contact-mediated axonal guidance
  • involved in angiogenesis by marking venous but not arterial endothelial cells
  • plays critical roles in axonal pathfinding and blood vessel maturation
  • can affect cancer cell behaviour in an ephrin-independent manner
  • adhesive EPHB4/EFNB2 interactions between tumor cells and endothelial cells is a mechanism for the site-specific metastatic dissemination of tumor cells
  • plays an important role in the progression of papillary thyroid carcinoma by stimulating cell migration
  • EPHB4 remains active in adult venous endothelial cells and loss of EPHB4 plays a role in vein graft adaptation
  • EPHB4 and EPHB2 play important roles in neovascularization and arteriovenous differentiation/plasticity
  • plays an essential role in regulating small artery contractility and blood pressure
  • is a critical mediator of erythropoietin-induced tumor progression and further provide clinically significant dimension to the biology of erythropoietin
  • EFNB2 and EPHB4 are likely involved in the regulation of spiral artery remodeling in pregnancy
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
  • EFNB2/EPHB4 signaling plays an important role in physiological and pathological angiogenesis
  • EPHB4/RASA1/MTOR signaling in endothelial cells promotes vascular malformation
  • a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • ephrins B4 binding
  • interacts with its EFNB2 ligand to act as a bidirectional signaling system that mediates adhesion, migration, and guidance by controlling attractive and repulsive activities
  • VEGFA inhibits EPHB4 and stimulates DLL4 expression in adult endothelial cells
  • EPHB4 can promote osteogenic differentiation of mesenchymal stem cells (MSCs) via upregulation of POSTN expression
  • cell & other
    REGULATION
    activated by EFNB2 in osteoarthritis subchondral bone that could affect abnormal metabolism in this tissue by inhibiting resorption factors and their activities
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --other  
    expressed in ovarian cancers and significantly associated with advanced stage of disease and the presence of ascite
    tumoral     --over  
    in a variety of different epithelial cancers including prostate where it has been shown to be involved in survival, migration and angiogenesis
    tumoral     --over  
    in transitional cell carcinoma of the bladder
    tumoral     --over  
    in papillary thyroid carcinoma cell lines
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancerurinary 
    therapeutic compounds targeting EPHB4 have potential for diagnosing and treating transitional cell carcinoma of the bladder
    cancerreproductiveovary
    inhibition of EPHB4 may hence have prognostic and therapeutic utility in ovarian carcinoma
    cancerendocrinethyroid
    might be a potential therapeutic target in papillary thyroid carcinoma
    ANIMAL & CELL MODELS
    deletions of the gene reveal its essential roles for conduit vessel development in mice, suggesting similar functions during human vascular development and deregulation in vascular malformations