Browse CD226

Summary
SymbolCD226
NameCD226 molecule
Aliases DNAM-1; DNAM1; PTA1; TLiSA1; CD226 antigen; DNAX accessory molecule 1; DNAX accessory molecule-1; T lineage- ......
Chromosomal Location18q22.3
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
 
Subcellular Location Cell membrane Single-pass type I membrane protein
Domain PF07686 Immunoglobulin V-set domain
Function

Involved in intercellular adhesion, lymphocyte signaling, cytotoxicity and lymphokine secretion mediated by cytotoxic T-lymphocyte (CTL) and NK cell (PubMed:8673704). Cell surface receptor for NECTIN2. Upon ligand binding, stimulates T-cell proliferation and cytokine production, including that of IL2, IL5, IL10, IL13, and IFNG. Competes with PVRIG for NECTIN2-binding (PubMed:26755705).

> Gene Ontology
 
Biological Process GO:0001819 positive regulation of cytokine production
GO:0001906 cell killing
GO:0001909 leukocyte mediated cytotoxicity
GO:0001910 regulation of leukocyte mediated cytotoxicity
GO:0001912 positive regulation of leukocyte mediated cytotoxicity
GO:0002228 natural killer cell mediated immunity
GO:0002250 adaptive immune response
GO:0002274 myeloid leukocyte activation
GO:0002347 response to tumor cell
GO:0002367 cytokine production involved in immune response
GO:0002370 natural killer cell cytokine production
GO:0002418 immune response to tumor cell
GO:0002420 natural killer cell mediated cytotoxicity directed against tumor cell target
GO:0002423 natural killer cell mediated immune response to tumor cell
GO:0002429 immune response-activating cell surface receptor signaling pathway
GO:0002431 Fc receptor mediated stimulatory signaling pathway
GO:0002440 production of molecular mediator of immune response
GO:0002443 leukocyte mediated immunity
GO:0002449 lymphocyte mediated immunity
GO:0002460 adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains
GO:0002694 regulation of leukocyte activation
GO:0002696 positive regulation of leukocyte activation
GO:0002697 regulation of immune effector process
GO:0002699 positive regulation of immune effector process
GO:0002700 regulation of production of molecular mediator of immune response
GO:0002702 positive regulation of production of molecular mediator of immune response
GO:0002703 regulation of leukocyte mediated immunity
GO:0002705 positive regulation of leukocyte mediated immunity
GO:0002706 regulation of lymphocyte mediated immunity
GO:0002708 positive regulation of lymphocyte mediated immunity
GO:0002712 regulation of B cell mediated immunity
GO:0002714 positive regulation of B cell mediated immunity
GO:0002715 regulation of natural killer cell mediated immunity
GO:0002717 positive regulation of natural killer cell mediated immunity
GO:0002718 regulation of cytokine production involved in immune response
GO:0002720 positive regulation of cytokine production involved in immune response
GO:0002727 regulation of natural killer cell cytokine production
GO:0002729 positive regulation of natural killer cell cytokine production
GO:0002757 immune response-activating signal transduction
GO:0002764 immune response-regulating signaling pathway
GO:0002768 immune response-regulating cell surface receptor signaling pathway
GO:0002819 regulation of adaptive immune response
GO:0002821 positive regulation of adaptive immune response
GO:0002822 regulation of adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains
GO:0002824 positive regulation of adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains
GO:0002831 regulation of response to biotic stimulus
GO:0002833 positive regulation of response to biotic stimulus
GO:0002834 regulation of response to tumor cell
GO:0002836 positive regulation of response to tumor cell
GO:0002837 regulation of immune response to tumor cell
GO:0002839 positive regulation of immune response to tumor cell
GO:0002855 regulation of natural killer cell mediated immune response to tumor cell
GO:0002857 positive regulation of natural killer cell mediated immune response to tumor cell
GO:0002858 regulation of natural killer cell mediated cytotoxicity directed against tumor cell target
GO:0002860 positive regulation of natural killer cell mediated cytotoxicity directed against tumor cell target
GO:0002889 regulation of immunoglobulin mediated immune response
GO:0002891 positive regulation of immunoglobulin mediated immune response
GO:0007156 homophilic cell adhesion via plasma membrane adhesion molecules
GO:0007157 heterophilic cell-cell adhesion via plasma membrane cell adhesion molecules
GO:0008037 cell recognition
GO:0016064 immunoglobulin mediated immune response
GO:0019724 B cell mediated immunity
GO:0031341 regulation of cell killing
GO:0031343 positive regulation of cell killing
GO:0031349 positive regulation of defense response
GO:0032609 interferon-gamma production
GO:0032649 regulation of interferon-gamma production
GO:0032729 positive regulation of interferon-gamma production
GO:0033003 regulation of mast cell activation
GO:0033005 positive regulation of mast cell activation
GO:0042267 natural killer cell mediated cytotoxicity
GO:0042269 regulation of natural killer cell mediated cytotoxicity
GO:0045088 regulation of innate immune response
GO:0045089 positive regulation of innate immune response
GO:0045576 mast cell activation
GO:0045954 positive regulation of natural killer cell mediated cytotoxicity
GO:0050865 regulation of cell activation
GO:0050867 positive regulation of cell activation
GO:0060368 regulation of Fc receptor mediated stimulatory signaling pathway
GO:0060369 positive regulation of Fc receptor mediated stimulatory signaling pathway
GO:0098742 cell-cell adhesion via plasma-membrane adhesion molecules
Molecular Function GO:0005178 integrin binding
GO:0050839 cell adhesion molecule binding
Cellular Component GO:0005913 cell-cell adherens junction
GO:0009897 external side of plasma membrane
GO:0045121 membrane raft
GO:0098552 side of membrane
GO:0098589 membrane region
GO:0098857 membrane microdomain
> KEGG and Reactome Pathway
 
KEGG hsa04514 Cell adhesion molecules (CAMs)
Reactome R-HSA-1280218: Adaptive Immune System
R-HSA-168256: Immune System
R-HSA-198933: Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell
Summary
SymbolCD226
NameCD226 molecule
Aliases DNAM-1; DNAM1; PTA1; TLiSA1; CD226 antigen; DNAX accessory molecule 1; DNAX accessory molecule-1; T lineage- ......
Chromosomal Location18q22.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Literatures that report relations between CD226 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
 
  Literatures describing the relation between CD226 and anti-tumor immunity in human cancer.
PMID Cancer type Relation to immunity Evidence sentences
25893601Plasma Cell MyelomaPromote immunity (T cell function)In this study using this unique mouse model of multiple myeloma (MM), we demonstrate the importance of NK and CD8+ T cells in MM immunosurveillance and response to treatment in vivo through CD226 and CD155 interactions.
27777574Colorectal carcinomaPromote immunityCRC-NK cells displayed underexpression of CD16, NKG2D, DNAM-1, CD161, NKp46, and NKp30 activating receptors, while inhibitory receptors CD85j and NKG2A were overexpressed. This inhibited phenotype affected cytotoxic functionality against CRC cells and interferon-γ production.
24510590Ovarian CarcinomaPromote immunity (T and NK cell function)Most tumor-associated NK cells displayed a CD56(bright) , CD16(neg) or CD56(bright) , CD16(dim) phenotype, and very poor cytolytic activities, despite an increased expression of the activation marker CD69. They also showed downregulation of DNAM-1, 2B4, and NTB-A activating receptors, and an altered chemokine receptor repertoire.
23192659Mesothelioma and lung carcinoma; breast carcinoma; colon carcinoma; gastric carcinoma; bladder carcinoma; uterus carcinomaPromote immunityTumor cell lysis was primarily mediated by NKG2D and NKp30 and partially by NKp46 and DNAM-1, in agreement with the expression of the corresponding ligands on tumor cells.
19404979Hepatocellular carcinomaPromote immunityFinally, we showed by combined mAb-mediated blockade that DNAM-1 and NKG2D could cooperate in the cell lysis of HCC.
19349689MelanomaPromote immunity (NK cell function)Here we show that human melanoma cell lines derived from LN metastases express ligands for natural cytotoxicity receptors (NCRs) and DNAX accessory molecule-1 (DNAM-1), two emerging NK cell receptors key for cancer cell recognition, but not NK group 2 member D (NKG2D).
23440424NeuroblastomaPromote immunityThe final products contained more than 90% CD56(+) cells and could kill neuroblastoma cells effectively that were originally highly resistant to nonprocessed NK cells. Mechanistically, cytolysis of neuroblastoma was mediated through natural cytotoxicity receptor (NCR), DNAX accessory molecule-1 (DNAM-1; CD226), perforin, and granzyme B.
21224372MelanomaPromote immunity (T cell function)A dynamic label free assay was used to determine the pathways involved in the lysis of melanoma cells by IL-2-activated NK cells. NKG2D, NCR (natural cytotoxicity receptor), and DNAM-1 are involved in the NK-mediated lysis of melanoma cells.
22419581MyelomaPromote immunity (NK cell function)Expanded natural killer cells killed both allogeneic and autologous primary myeloma cells avidly via a perforin-mediated mechanism in which the activating receptor NKG2D, natural cytotoxicity receptors, and DNAX-accessory molecule-1 played a central role. The transferred, expanded natural killer cells proliferated in vivo in an interleukin-2 dose-dependent fashion, persisted up to 4 weeks, were readily detectable in the human bone, inhibited myeloma growth and protected bone from myeloma-induced osteolysis.
19029379FibrosarcomaPromote immunity (T cell function)DNAM-1-deficient cytotoxic T lymphocyte (CTL) and NK cells showed significantly less cytotoxic activity against DNAM-1 ligand-expressing tumors in vitro than wild-type (WT) cells. The methylcholanthrene (MCA)-induced fibrosarcoma cell line Meth A expressed the DNAM-1 ligand CD155, and DNAM-1-deficient mice showed increased tumor development and mortality after transplantation of Meth A cells. Moreover, the DNAM-1-deficient mice developed significantly more DNAM-1 ligand-expressing fibrosarcoma and papilloma cells in response to the chemical carcinogens MCA and 7,12-dimethylbenz[a]anthracene (DMBA), respectively, than did WT mice.
19934056MelanomaPromote immunity (NK cell function)Thus, both the IL-2-induced up-regulation of the surface expression of NKp44, NKp30, and DNAM-1 triggering receptors and the acquisition of cytolytic granules were inhibited in NK cells. This resulted in an impairment of the NK cell-mediated killing of melanoma target cells.
29308322MelanomaPromote immunity (NK cell function)We demonstrate that BRAFV600E mutant melanoma cells cultured in the presence of vemurafenib, strongly decreased surface expression of ligands for NK activating receptors including the NKG2D-ligand, MICA, and the DNAM-1 ligand, CD155, and became significantly less susceptible to NK cell attack.
25209846Hepatocellular CarcinomaPromote immunity(NK cell function)Here, we demonstrated that activated unfolded protein response (UPR) attenuated the sensitivity of human hepatocellular carcinoma cell (HCC) to NK-cell cytotoxicity by decreasing the expression level of CD226 ligand CD155 in HCC
21937679Breast CarcinomaPromote immunityFunctional experiments in breast cancer subtypes expressing various levels of NK cell ligands showed that NK-mediated cytotoxicity is mainly HLA, NKG2D, and DNAM dependent
21900395colon carcinomaPromote immunityMechanistic investigations revealed that IRF-1-induced NK cell cytotoxicity was independent of perforin and granzyme B but dependent on the NK cell activating receptor DNAM-1. Taken together, our findings establish IRF-1 as an essential mediator of the cross-talk between tumor cells and NK cells that mediate immune surveillance in the metastatic niche
21841316Breast CarcinomaPromote immunityWith disease progression, we found that expression of activating NK cell receptors (such as NKp30, NKG2D, DNAM-1, and CD16) decreased while expression of inhibitory receptors (such as NKG2A) increased and that this correlated with decreased NK cell function, most notably cytotoxicity
Summary
SymbolCD226
NameCD226 molecule
Aliases DNAM-1; DNAM1; PTA1; TLiSA1; CD226 antigen; DNAX accessory molecule 1; DNAX accessory molecule-1; T lineage- ......
Chromosomal Location18q22.3
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
  Statistical results of CD226 in screening data sets for detecting immune reponses.
PMID Screening System Cancer Type Cell Line Data Set Statistical Results Relation to immunity
29301958CRISPR-Cas9 melanomaB16F10Pmel-1 T cell NA/NSNA/NS
29301958CRISPR-Cas9 melanomaB16F10OT-1 T cell NA/NSNA/NS
28783722CRISPR-Cas9 melanomaMel6242CT-CRISPR NA/NSNA/NS
28723893CRISPR-Cas9 melanomaB16GVAX+Anti-PD1 NA/NSNA/NS
28723893CRISPR-Cas9 melanomaB16GVAX NA/NSNA/NS
25691366RNAiBreast cancerMCF7Luc-CTL assay NA/NSNA/NS
24476824shRNAmelanomaB16Primary screen NA/NSNA/NS
24476824shRNAmelanomaB16Secondary screen NA/NSNA/NS
Summary
SymbolCD226
NameCD226 molecule
Aliases DNAM-1; DNAM1; PTA1; TLiSA1; CD226 antigen; DNAX accessory molecule 1; DNAX accessory molecule-1; T lineage- ......
Chromosomal Location18q22.3
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
 
Points in the above scatter plot represent the expression difference of CD226 in various data sets.
No PMID Cancer type Group Drug # Res # NRes Log2 (Fold Change) P value Anno
126997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)1412-0.1320.647
226997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)65-0.1950.694
326997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)87-0.090.833
428552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 916-0.6390.164
528552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 59-0.8630.353
628552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 47-0.3510.763
729033130MelanomaallAnti-PD-1 (nivolumab) 26230.3270.433
829033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 15110.6810.352
929033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 1112-0.1840.837
1029301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 480.1020.893
1129301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 2001
1229301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 280.4350.666
1329443960Urothelial cancerallAnti-PD-L1 (atezolizumab) 682300.1760.352
> Mutation difference between responders and non-responders
 
Points in the above scatter plot represent the mutation difference of CD226 in various data sets.
No PMID Cancer type Group Drug # Res # NRes % Mut/Res % Mut/NRes % Diff (R vs NR) Pval Anno
125765070Non-small cell lung cancer (NSCLC)allAnti-PD-1 (pembrolizumab) 14170001
225765070Non-small cell lung cancer (NSCLC)smokingAnti-PD-1 (pembrolizumab) 1030001
325765070Non-small cell lung cancer (NSCLC)non-smokingAnti-PD-1 (pembrolizumab) 4140001
426359337MelanomaallAnti-CTLA-4 (ipilimumab) 27733.71.42.30.469
526359337MelanomaBRAFiAnti-CTLA-4 (ipilimumab) 0140001
626359337Melanomanon-BRAFiAnti-CTLA-4 (ipilimumab) 27593.71.720.532
726997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)21174.804.81
826997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)8612.5012.51
926997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)13110001
1028552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 9160001
1128552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 590001
1228552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 470001
1329033130MelanomaallAnti-PD-1 (nivolumab) 38270001
1429033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 22130001
1529033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 16140001
1629301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 11130001
1729301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 610001
1829301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 5120001
Summary
SymbolCD226
NameCD226 molecule
Aliases DNAM-1; DNAM1; PTA1; TLiSA1; CD226 antigen; DNAX accessory molecule 1; DNAX accessory molecule-1; T lineage- ......
Chromosomal Location18q22.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of CD226. 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
 
Summary
SymbolCD226
NameCD226 molecule
Aliases DNAM-1; DNAM1; PTA1; TLiSA1; CD226 antigen; DNAX accessory molecule 1; DNAX accessory molecule-1; T lineage- ......
Chromosomal Location18q22.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of CD226. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by CD226.
> Immunoinhibitor
> Immunostimulator
> MHC molecule
> Immunoinhibitor
 
> Immunostimulator
 
> MHC molecule
 
Summary
SymbolCD226
NameCD226 molecule
Aliases DNAM-1; DNAM1; PTA1; TLiSA1; CD226 antigen; DNAX accessory molecule 1; DNAX accessory molecule-1; T lineage- ......
Chromosomal Location18q22.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of CD226. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene.
> Chemokine
> Receptor
> Chemokine
 
> Receptor
 
Summary
SymbolCD226
NameCD226 molecule
Aliases DNAM-1; DNAM1; PTA1; TLiSA1; CD226 antigen; DNAX accessory molecule 1; DNAX accessory molecule-1; T lineage- ......
Chromosomal Location18q22.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Distribution of CD226 expression across immune and molecular subtypes.
> Immune subtype
> Molecular subtype
> Immune subtype
 
> Molecular subtype
 
Summary
SymbolCD226
NameCD226 molecule
Aliases DNAM-1; DNAM1; PTA1; TLiSA1; CD226 antigen; DNAX accessory molecule 1; DNAX accessory molecule-1; T lineage- ......
Chromosomal Location18q22.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Associations between CD226 and clinical features.
> Overall survival analysis
> Cancer stage
> Tumor grade
> Overall survival
 
> Stage
 
> Grade
 
Summary
SymbolCD226
NameCD226 molecule
Aliases DNAM-1; DNAM1; PTA1; TLiSA1; CD226 antigen; DNAX accessory molecule 1; DNAX accessory molecule-1; T lineage- ......
Chromosomal Location18q22.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Drugs targeting CD226 collected from DrugBank database.
> Drugs from DrugBank database
 

There is no record.