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FLASH GENE
Symbol CDH5 contributors: mct - updated : 11-07-2019
HGNC name cadherin 5, type 2, VE-cadherin (vascular epithelium)
HGNC id 1764
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
  • CDH5-homophilic adhesion controls endothelial barrier permeability through assembly of adherens junctions (AJs)
  • major adherens junction adhesion molecule in endothelial cells
  • CDH5, NECTIN2, and CLDN5 are involved in the regulation of vascular permeability in a mutually interacting manner, which indicates their prominent role for the functionality of the human corpus luteum
  • its phosphorylation and binding partner status are important indicators of endothelial permeability
  • CDH5 organizes junctional and cortical actin cytoskeletons
  • chiefly organizes the opening and closing of the endothelial barrier, and is central in permeability changes
  • RNA-binding protein quaking maintains endothelial barrier function and affects CDH5 and CTNNB1 protein expression
  • novel junction protective mechanism during polarized trafficking of CDH5, which supports barrier maintenance within dynamic endothelial tissue
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • AMOTL2/CDH5 complex is responsible for transmitting mechanical force between endothelial cells for the coordination of cellular morphogenesis consistent with aortic lumen expansion and function
  • 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
  • CDH5-mediated adhesion modulates steady-state microtubules (MT) dynamics by suppressing MT growth
  • CDH5 outside-in signaling regulates cytosolic Ca2+ homeostasis and MAPRE3 phosphorylation, which are required for assembly of adherens junctions (AJs)
  • CHRM3 facilitates interaction of the CDH5-based adherens junctional complex and the actin-based cytoskeleton by maintaining RAC1 activity, which regulates the interaction between IQGAP1/RAC1 and IQGAP1/CTNNB1, and may contribute to endothelial barrier function under physiological conditions
  • AMOTL2 associates to the CDH5 adhesion complex where it couples adherens junctions to contractile actin fibres
  • 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
  • EPS8, a signaling adapter regulating actin dynamics, is a novel partner of CDH5 and is able to modulate YAP1 activity 7)
  • new role for PACSIN2 in the control of CDH5-based endothelial adhesion
  • biological activity of CDH5 in regulating endothelial polarity and vascular lumen formation is mediated through its interaction with the two cell polarity proteins PALS1 and PARD3
  • CMTM3 is involved in CDH5 turnover and is a regulator of the cell surface pool of CDH5
  • endothelial TSPAN5- and TSPAN17-ADAM10 complexes may regulate inflammation by maintaining normal CDH5 expression and promoting T lymphocyte transmigration
  • endothelial cell PTPN11 negatively regulates neutrophil adhesion and promotes transmigration by enhancing ICAM1-CDH5 interaction
  • endothelial flow mechanotransduction through the junctional complex is mediated by a specific pool of CDH5 that is phosphorylated on Y658 and bound to GPSM2
  • CGNL1 regulates vascular growth by promoting CDH5 association with the actin cytoskeleton, thereby stabilizing adherens junctions
  • functional interaction of CDH5 with the cell polarity protein PALS1
  • 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