TISIDB

Summary
Symbol	CDH5
Name	cadherin 5, type 2 (vascular endothelium)
Aliases	7B4; CD144; VE-cadherin; cadherin 5, type 2, VE-cadherin (vascular epithelium); 7B4 antigen; cd144 antigen; ......
Chromosomal Location	16q22.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Basic function annotation. > Subcellular Location, Domain and Function > Gene Ontology > KEGG and Reactome Pathway

> Subcellular Location, Domain and Function [ TOP ]
Subcellular Location	Cell junction Cell membrane Single-pass type I membrane protein Note=Found at cell-cell boundaries and probably at cell-matrix boundaries. KRIT1 and CDH5 reciprocally regulate their localization to endothelial cell-cell junctions.
Domain	PF00028 Cadherin domain PF01049 Cadherin cytoplasmic region
Function	Cadherins are calcium-dependent cell adhesion proteins. They preferentially interact with themselves in a homophilic manner in connecting cells; cadherins may thus contribute to the sorting of heterogeneous cell types. This cadherin may play a important role in endothelial cell biology through control of the cohesion and organization of the intercellular junctions. It associates with alpha-catenin forming a link to the cytoskeleton. Acts in concert with KRIT1 to establish and maintain correct endothelial cell polarity and vascular lumen. These effects are mediated by recruitment and activation of the Par polarity complex and RAP1B. Required for activation of PRKCZ and for the localization of phosphorylated PRKCZ, PARD3, TIAM1 and RAP1B to the cell junction.

> Gene Ontology [ TOP ]
Biological Process	GO:0001885 endothelial cell development GO:0001955 blood vessel maturation GO:0002064 epithelial cell development GO:0003158 endothelium development GO:0007043 cell-cell junction assembly GO:0007156 homophilic cell adhesion via plasma membrane adhesion molecules GO:0007163 establishment or maintenance of cell polarity GO:0007178 transmembrane receptor protein serine/threonine kinase signaling pathway GO:0007179 transforming growth factor beta receptor signaling pathway GO:0010720 positive regulation of cell development GO:0021700 developmental maturation GO:0030010 establishment of cell polarity GO:0030856 regulation of epithelial cell differentiation GO:0030858 positive regulation of epithelial cell differentiation GO:0032878 regulation of establishment or maintenance of cell polarity GO:0034329 cell junction assembly GO:0034330 cell junction organization GO:0034332 adherens junction organization GO:0045216 cell-cell junction organization GO:0045446 endothelial cell differentiation GO:0045601 regulation of endothelial cell differentiation GO:0045603 positive regulation of endothelial cell differentiation GO:0061028 establishment of endothelial barrier GO:0071559 response to transforming growth factor beta GO:0071560 cellular response to transforming growth factor beta stimulus GO:0071695 anatomical structure maturation GO:0098742 cell-cell adhesion via plasma-membrane adhesion molecules GO:1901550 regulation of endothelial cell development GO:1901552 positive regulation of endothelial cell development GO:1903140 regulation of establishment of endothelial barrier GO:1903142 positive regulation of establishment of endothelial barrier GO:2000114 regulation of establishment of cell polarity
Molecular Function	GO:0008013 beta-catenin binding GO:0019902 phosphatase binding GO:0019903 protein phosphatase binding GO:0044325 ion channel binding
Cellular Component	GO:0005923 bicellular tight junction GO:0009897 external side of plasma membrane GO:0043296 apical junction complex GO:0070160 occluding junction GO:0098552 side of membrane

> KEGG and Reactome Pathway [ TOP ]
KEGG	hsa04514 Cell adhesion molecules (CAMs) hsa04670 Leukocyte transendothelial migration
Reactome	R-HSA-418990: Adherens junctions interactions R-HSA-446728: Cell junction organization R-HSA-1500931: Cell-Cell communication R-HSA-421270: Cell-cell junction organization R-HSA-162582: Signal Transduction R-HSA-194138: Signaling by VEGF R-HSA-4420097: VEGFA-VEGFR2 Pathway R-HSA-5218920: VEGFR2 mediated vascular permeability

Summary
Symbol	CDH5
Name	cadherin 5, type 2 (vascular endothelium)
Aliases	7B4; CD144; VE-cadherin; cadherin 5, type 2, VE-cadherin (vascular epithelium); 7B4 antigen; cd144 antigen; ......
Chromosomal Location	16q22.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between CDH5 and anti-tumor immunity. The specific mechanism were also collected if the literature reports that a gene specifically promotes or inhibits the infiltration or function of T/NK cells.

> Text Mining

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Literatures describing the relation between CDH5 and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
28655790	Melanoma	Promote immunity	We developed an oligonucleotide-based inhibitor (CD5-2), which disrupted the interaction of VE-cadherin with its regulator miR-27a, resulting in increased VE-cadherin expression. Administration of CD5-2 in tumor-bearing mice enhanced expression of VE-cadherin in tumor endothelium, activating TIE-2 and tight junction pathways and normalizing vessel structure and function. Our work establishes a role for VE-cadherin in T-cell infiltration in tumors and offers a preclinical proof of concept for CD5-2 as a therapeutic modifier of cancer immunotherapy via effects on the tumor vasculature.

Summary
Symbol	CDH5
Name	cadherin 5, type 2 (vascular endothelium)
Aliases	7B4; CD144; VE-cadherin; cadherin 5, type 2, VE-cadherin (vascular epithelium); 7B4 antigen; cd144 antigen; ......
Chromosomal Location	16q22.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	High-throughput screening data (e.g. CRISPR-Cas9, shRNA and RNAi) for T cell-mediated killing. Genetic screen techniques can identify mechanisms of tumor cell resistance (e.g., PTPN2) and sensitivity (e.g., APLNR) to killing by cytotoxic T cells, the central effectors of anti-tumor immunity. After comprehensively searching, eight groups of screening data sets were collected in the current database. In this tab, users can check whether their selected genes cause resistance or increase sensitivity to T cell-mediated killing in various data sets.

> High-throughput Screening

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Statistical results of CDH5 in screening data sets for detecting immune reponses.

PMID	Screening System	Cancer Type	Cell Line	Data Set	Statistical Results	Relation to immunity
29301958	CRISPR-Cas9	melanoma	B16F10	Pmel-1 T cell	NA/NS	NA/NS
29301958	CRISPR-Cas9	melanoma	B16F10	OT-1 T cell	NA/NS	NA/NS
28783722	CRISPR-Cas9	melanoma	Mel624	2CT-CRISPR	NA/NS	NA/NS
28723893	CRISPR-Cas9	melanoma	B16	GVAX+Anti-PD1	NA/NS	NA/NS
28723893	CRISPR-Cas9	melanoma	B16	GVAX	NA/NS	NA/NS
25691366	RNAi	Breast cancer	MCF7	Luc-CTL assay	NA/NS	NA/NS
24476824	shRNA	melanoma	B16	Primary screen	NA/NS	NA/NS
24476824	shRNA	melanoma	B16	Secondary screen	NA/NS	NA/NS

Summary
Symbol	CDH5
Name	cadherin 5, type 2 (vascular endothelium)
Aliases	7B4; CD144; VE-cadherin; cadherin 5, type 2, VE-cadherin (vascular epithelium); 7B4 antigen; cd144 antigen; ......
Chromosomal Location	16q22.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Transcriptomic and genomic profiling of pre-treated tumor biopsies from responders and non-responders to immunotherapy. These data were used to identify signatures and mechanisms of response to checkpoint blockade (e.g., anti-PDL1 and anti-PD1). One example is that mutations in the gene PBRM1 benefit clinical survival of patients with clear cell renal cell carcinoma. After comprehensively searching, we collected 5 and 6 of transcriptomic and genomic data sets, respectively. In this tab, users can check whether their selected genes have significant difference of expression or mutation between responders and non-responders in various data sets. > Expression difference between responders and non-responders > Mutation difference between responders and non-responders

> Expression difference between responders and non-responders

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Points in the above scatter plot represent the expression difference of CDH5 in various data sets.

No	PMID	Cancer type	Group	Drug	# Res	# NRes	Log2 (Fold Change)	P value
1	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	14	12	-0.469	0.141
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	-0.526	0.716
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	-0.421	0.672
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	-0.262	0.546
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	-0.907	0.612
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0.552	0.808
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.483	0.287
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	0.662	0.621
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	0.257	0.866
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	1.152	0.496
11	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	2	0	0	1
12	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	2	8	2.434	0.292
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.2	0.091

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of CDH5 in various data sets.

No	PMID	Cancer type	Group	Drug	# Res	# NRes	% Mut/Res	% Mut/NRes	% Diff (R vs NR)	Pval
1	25765070	Non-small cell lung cancer (NSCLC)	all	Anti-PD-1 (pembrolizumab)	14	17	0	0	0	1
2	25765070	Non-small cell lung cancer (NSCLC)	smoking	Anti-PD-1 (pembrolizumab)	10	3	0	0	0	1
3	25765070	Non-small cell lung cancer (NSCLC)	non-smoking	Anti-PD-1 (pembrolizumab)	4	14	0	0	0	1
4	26359337	Melanoma	all	Anti-CTLA-4 (ipilimumab)	27	73	3.7	1.4	2.3	0.469
5	26359337	Melanoma	BRAFi	Anti-CTLA-4 (ipilimumab)	0	14	0	0	0	1
6	26359337	Melanoma	non-BRAFi	Anti-CTLA-4 (ipilimumab)	27	59	3.7	1.7	2	0.532
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	0	0	0	1
8	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	6	0	0	0	1
9	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	13	11	0	0	0	1
10	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0	6.2	-6.2	1
11	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0	11.1	-11.1	1
12	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0	0	0	1
13	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	38	27	2.6	0	2.6	1
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	4.5	0	4.5	1
15	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	16	14	0	0	0	1
16	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	11	13	0	7.7	-7.7	1
17	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	6	1	0	0	0	1
18	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	5	12	0	8.3	-8.3	1

Summary
Symbol	CDH5
Name	cadherin 5, type 2 (vascular endothelium)
Aliases	7B4; CD144; VE-cadherin; cadherin 5, type 2, VE-cadherin (vascular epithelium); 7B4 antigen; cd144 antigen; ......
Chromosomal Location	16q22.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of CDH5. The immune-related signatures of 28 TIL types from Charoentong's study, which can be viewed in the download page. For each cancer type, the relative abundance of TILs were inferred by using gene set variation analysis (GSVA) based on gene expression profile. In this tab, users can examine which kinds of TILs might be regulated by the current gene.

> Lymphocyte [ TOP ]

Summary
Symbol	CDH5
Name	cadherin 5, type 2 (vascular endothelium)
Aliases	7B4; CD144; VE-cadherin; cadherin 5, type 2, VE-cadherin (vascular epithelium); 7B4 antigen; cd144 antigen; ......
Chromosomal Location	16q22.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of CDH5. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by CDH5. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	CDH5
Name	cadherin 5, type 2 (vascular endothelium)
Aliases	7B4; CD144; VE-cadherin; cadherin 5, type 2, VE-cadherin (vascular epithelium); 7B4 antigen; cd144 antigen; ......
Chromosomal Location	16q22.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of CDH5. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene. > Chemokine > Receptor

> Chemokine [ TOP ]

> Receptor [ TOP ]

Summary
Symbol	CDH5
Name	cadherin 5, type 2 (vascular endothelium)
Aliases	7B4; CD144; VE-cadherin; cadherin 5, type 2, VE-cadherin (vascular epithelium); 7B4 antigen; cd144 antigen; ......
Chromosomal Location	16q22.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of CDH5 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	CDH5
Name	cadherin 5, type 2 (vascular endothelium)
Aliases	7B4; CD144; VE-cadherin; cadherin 5, type 2, VE-cadherin (vascular epithelium); 7B4 antigen; cd144 antigen; ......
Chromosomal Location	16q22.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between CDH5 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	CDH5
Name	cadherin 5, type 2 (vascular endothelium)
Aliases	7B4; CD144; VE-cadherin; cadherin 5, type 2, VE-cadherin (vascular epithelium); 7B4 antigen; cd144 antigen; ......
Chromosomal Location	16q22.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting CDH5 collected from DrugBank database.

> Drugs from DrugBank database

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Details on drugs targeting CDH5.

ID	Name	Drug Type	Targets	#Targets
DB00480	Lenalidomide	Small Molecule	CDH5, CRBN, PTGS2, TNFSF11	4
DB05685	FX06	Biotech	CDH5	1

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