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FLASH GENE
Symbol CDH5 contributors: mct - updated : 10-09-2015
HGNC name cadherin 5, type 2, VE-cadherin (vascular epithelium)
HGNC id 1764
Location 16q21      Physical location : 66.400.524 - 66.438.688
Synonym name
  • major adhesive protein of interendothelial adherens junctions
  • 7B4 antigen
  • VE-cadherin
  • cd144 antigen
  • vascular endothelial cadherin
  • Synonym symbol(s) 7B4, CD144, FLJ17376, VE-cadherin
    DNA
    TYPE functioning gene
    STRUCTURE 38.16 kb     12 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status provisional
    Map see TSG16H
    Physical map
    CDH5 16q22.1 cadherin 5, type 2, VE-cadherin (vascular epithelium) LOC390736 16 similar to Spermatogenesis associated protein 2 (Spermatogenesis associated protein PD1) TK2 16q22 thymidine kinase 2, mitochondrial FLJ20006 16q22.1 hypothetical protein FLJ20006 CKLF 16q22.1 chemokine-like factor CKLFSF1 16q22.1 chemokine-like factor super family 1 CKLFSF2 16q22.1 chemokine-like factor super family 2 CKLFSF3 16q22.1 chemokine-like factor super family 3 CKLFSF4 16q22.1 chemokine-like factor super family 4 DNCLI2 16q22.1 dynein, cytoplasmic, light intermediate polypeptide 2 FLJ35894 16q22.1 hypothetical protein FLJ35894 APPBP1 16q22 amyloid beta precursor protein binding protein 1, 59kDa CA7 16q22.1 carbonic anhydrase VII KIAA1348 CDH16 16q22.1 cadherin 16, KSP-cadherin RRAD 16q22 Ras-related associated with diabetes CGI-128 16q22.1-q22.3 CGI-128 protein CES2 16q22.1 carboxylesterase 2 (intestine, liver) FLJ21736 16q22.1 esterase 31 FLJ37464 16q22.1 hypothetical protein FLJ37464 CBFB 16q22.1 core-binding factor, beta subunit
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    12 - 4134 - 784 - 2008 18337748
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Endocrinethyroid   highly
    Reproductivefemale systemplacenta  highly
    Respiratoryrespiratory tracttrachea  highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Epithelialbarrier/lining   
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Cardiovascularendothelial cell
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a N terminal hydrophobic domain
  • five extracellular cadherin repeats with four cysteines in the most proximal (MPED)
  • a transmembrane segment and a highly conserved cytoplasmic tail required for interactions
  • conjugated GlycoP
    HOMOLOGY
    Homologene
    FAMILY cadherin superfamily of calcium dependent cell-cell adhesion glycoproteins
    CATEGORY adhesion
    SUBCELLULAR LOCALIZATION     plasma membrane,junction,tight
    basic FUNCTION
  • transmembrane glycoprotein component of adherens junction
  • involved in cell-cell or cell-ECM interactions
  • having a function in tumor progression
  • mediates contact inhibition of cell growth in quiescent endothelial cell layers
  • playing a role in modulating c-Src activation in VEGF signaling, thus providing new insights into the importance of CDH5 in VEGF signaling and vascular function
  • positive and endothelial cells -specific regulator of TGF-beta signaling
  • required for efficient ALK-dependent Smad phosphorylation as shown by faster and more potent activation of Smad1/5 and SMAD2/3 signaling
  • endothelial specific cell-cell adhesion molecule, plays a pivotal role in the formation, maturation and remodeling of the vascular wall
  • antagonizes VEGFR2 signaling, and consequently, inhibition of CDH5, Rho-kinase, or actomyosin contractility leads to VEGF-driven, RAC1-dependent sprouting
  • CDH5 and PECAM1 enhance acute lymphoblastic leukemia migration across brain microvascular endothelial cell monolayers
  • plasticity of the CDH5-CTNNA1 complex is central for the leukocyte diapedesis mechanism
  • controls potentially vascular permeability and limits fibrogenesis after Unilateral ureteral obstruction
  • vinculin-dependent cadherin mechanosensing in endothelial processes such as leukocyte extravasation and angiogenesis
  • major adherens junction adhesion molecule in endothelial cells
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • hemophilic, calcium dependent interactions
  • interacting by its C terminus with the cytoskeleton via beta-catenin
  • interacting with CSK (CSK binds via its SH2 domain to the phosphorylated tyrosine 685 of CDH5)
  • directly or indirectly associates with many other signaling molecules, including vascular endothelial cell growth factor receptor 2 (KDR)
  • interacting with KLF4 (key role of KLF4 in the regulation of CDH5 expression at the level of the adherens junctions and in the acquisition of CDH5-mediated endothelial barrier function)
  • PECAM1 is associated with CDH5 and may similarly regulate its signaling via recruitment of PTPN6/PTPN11
  • interacting with JCAD (JCAD is not essential for CDH5-mediated cell–cell adhesion)
  • SOX7 binds and activates the promoter of CDH5, demonstrating that this gene is a novel downstream transcriptional target of SOX7
  • PTPN11 controls the recovery of endothelial barrier function by dephosphorylating CTNNB1 and promoting the mobility of CDH5 at the plasma membrane
  • interacts with CTNND1and CTNNB1 through its cytoplasmic tail
  • regulates transendothelial permeability in synergy with RRAS and CDH5 in an endothelial monolayer
  • importance of spatio-temporal regulation of the actin cytoskeleton through TRIO and RAC1 at CDH5-based cell-cell junctions in the maintenance of the endothelial barrier
  • endothelial TSPAN5- and TSPAN17-ADAM10 complexes may regulate inflammation by maintaining normal CDH5 expression and promoting T lymphocyte transmigration
  • CGNL1 regulates vascular growth by promoting CDH5 association with the actin cytoskeleton, thereby stabilizing adherens junctions
  • cell & other
    REGULATION
    Other phosphorylation of CDH5 controls endothelial phenotypes via CTNND1 coupling and RAC1 activation
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --other  
    aberrantly expressed in invasive breast carcinomas
    constitutional     --over  
    in late onset preeclampsia significantly more expressed compared to late controls (differential expression of CDH5 and VEGFR2 in placental syncytiotrophoblast during preeclampsia)
    constitutional     --over  
    of circulating CDH5 and FABP1 in association with drug-induced liver injury
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS