VE-cadherin

Cadherin-5, or VE-cadherin (vascular endothelial cadherin), also known as CD144 (Cluster of Differentiation 144), is a type of cadherin. It is encoded by the human gene CDH5.^[5]

CDH5
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2KOH
Identifiers
Aliases	CDH5, 7B4, CD144, VE-cadherin, cadherin 5
External IDs	OMIM: 601120; MGI: 105057; HomoloGene: 1359; GeneCards: CDH5; OMA:CDH5 - orthologs
Gene location (Human) Chr. Chromosome 16 (human)[1] Band 16q21 Start 66,366,622 bp[1] End 66,404,784 bp[1]
Gene location (Mouse) Chr. Chromosome 8 (mouse)[2] Band 8 D3|8 53.04 cM Start 104,828,257 bp[2] End 104,871,143 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in right lung upper lobe of left lung apex of heart lower lobe of lung subcutaneous adipose tissue placenta pericardium vena cava left ventricle right lobe of thyroid gland Top expressed in gastrula cardiac muscle tissue of left ventricle decidua left lung interventricular septum left lung lobe lactiferous gland right lung right lung lobe extensor digitorum longus muscle More reference expression data BioGPS More reference expression data
Gene ontology Molecular function calcium ion binding beta-catenin binding transmembrane transporter binding metal ion binding protein binding protein phosphatase binding signaling receptor binding cytoskeletal protein binding protein homodimerization activity cadherin binding vascular endothelial growth factor receptor 2 binding Cellular component integral component of membrane membrane cell-cell junction bicellular tight junction adherens junction cell surface cell junction external side of plasma membrane cell periphery plasma membrane catenin complex Biological process positive regulation of establishment of endothelial barrier cell adhesion cell-cell junction assembly adherens junction organization transforming growth factor beta receptor signaling pathway regulation of establishment of cell polarity negative regulation of cell population proliferation homophilic cell adhesion via plasma membrane adhesion molecules blood vessel maturation cell-cell adhesion negative regulation of inflammatory response positive regulation of angiogenesis calcium-dependent cell-cell adhesion via plasma membrane cell adhesion molecules cell-cell adhesion mediated by cadherin cell morphogenesis Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 1003 12562 Ensembl ENSG00000179776 ENSMUSG00000031871 UniProt P33151 P55284 RefSeq (mRNA) NM_001114117 NM_001795 NM_009868 RefSeq (protein) NP_001786 NP_033998 Location (UCSC) Chr 16: 66.37 – 66.4 Mb Chr 8: 104.83 – 104.87 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Function

VE-cadherin is a classical cadherin from the cadherin superfamily and the gene is located in a six-cadherin cluster in a region on the long arm of chromosome 16 that is involved in loss of heterozygosity events in breast and prostate cancer. The encoded protein is a calcium-dependent cell–cell adhesion glycoprotein composed of five extracellular cadherin repeats, a transmembrane region and a highly conserved cytoplasmic tail. Functioning as a classic cadherin by imparting to cells the ability to adhere in a homophilic manner, the protein may play an important role in endothelial cell biology through control of the cohesion and organization of the intercellular junctions.^[6]

Integrity of intercellular junctions is a major determinant of permeability of the endothelium, and the VE-cadherin-based adherens junction is thought to be particularly important. VE-cadherin is known to be required for maintaining a restrictive endothelial barrier – early studies using blocking antibodies to VE-cadherin increased monolayer permeability in cultured cells^[7] and resulted in interstitial edema and hemorrhage in vivo.^[8] A recent study has shown that TNFAIP3 (A20, a dual-ubiquitin editing enzyme) is essential for stability and expression of VE-cadherin. Deubiquitinase function of A20 was shown to remove ubiquitin chains from VE-cadherin, thereby prevented loss of VE-cadherin expression at the endothelial adherens junctions.^[9]

VE-cadherin is indispensable for proper vascular development – there have been two transgenic mouse models of VE-cadherin deficiency, both embryonic lethal due to vascular defects.^[10][11] Further studies using one of these models revealed that although vasculogenesis occurred, nascent vessels collapsed or disassembled in the absence of VE-cadherin.^[12] Therefore, it was concluded that VE-cadherin serves the purpose of maintaining newly formed vessels.

Interactions

VE-cadherin has been shown to interact with:

• Beta-catenin^[13][14]
• Plakoglobin^[13][14]
• PTPRB^[15]
• Catenin (cadherin-associated protein), alpha 1^[13][14]
• CTNND1^[16][17]
• PTPmu (PTPRM)^[18]
• PTPrho (PTPRT)^[19]

As a biomarker

VE-cadherin may serve as a biomarker for radiation exposure.^[20]

See also

• Vasculogenic Mimicry