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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

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

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

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_001795 12 - 4134 NP_001786 - 784 - 2008 18337748

EXPRESSION

Type

widely

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Endocrine thyroid       highly Reproductive female system placenta     highly Respiratory respiratory tract trachea     highly

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Epithelial barrier/lining

cells

System Cell Pubmed Species Stage Rna symbol Cardiovascular endothelial 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)

Type Gene Modification Chromosome rearrangement Protein expression Protein 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