Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT4UG0KB)

DOT Name CD226 antigen (CD226)
Synonyms DNAX accessory molecule 1; DNAM-1; CD antigen CD226
Gene Name CD226
Related Disease
Advanced cancer ( )
Acute myelogenous leukaemia ( )
Alzheimer disease ( )
Anca-associated vasculitis ( )
Autoimmune disease, susceptibility to, 6 ( )
Breast cancer ( )
Breast carcinoma ( )
Breast neoplasm ( )
Colon carcinoma ( )
Colorectal carcinoma ( )
Colorectal neoplasm ( )
Epithelial ovarian cancer ( )
Graves disease ( )
Hepatitis C virus infection ( )
Hepatocellular carcinoma ( )
Hypothyroidism ( )
Inflammatory bowel disease ( )
Juvenile idiopathic arthritis ( )
Neoplasm ( )
Nervous system inflammation ( )
Plasma cell myeloma ( )
Primary sclerosing cholangitis ( )
Prostate cancer ( )
Prostate carcinoma ( )
Psoriasis ( )
Sclerosing cholangitis ( )
STAT3-related early-onset multisystem autoimmune disease ( )
Systemic lupus erythematosus ( )
Ankylosing spondylitis ( )
Gastric cancer ( )
Melanoma ( )
Stomach cancer ( )
Endometriosis ( )
Adult glioblastoma ( )
Carcinoma ( )
Crohn disease ( )
Deafness ( )
Glioblastoma multiforme ( )
leukaemia ( )
Leukemia ( )
Metastatic malignant neoplasm ( )
Multiple sclerosis ( )
Neuroblastoma ( )
Non-insulin dependent diabetes ( )
Type-1 diabetes ( )
Ulcerative colitis ( )
UniProt ID
CD226_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
PDB ID
6ISB; 6O3O
Pfam ID
PF07686
Sequence
MDYPTLLLALLHVYRALCEEVLWHTSVPFAENMSLECVYPSMGILTQVEWFKIGTQQDSI
AIFSPTHGMVIRKPYAERVYFLNSTMASNNMTLFFRNASEDDVGYYSCSLYTYPQGTWQK
VIQVVQSDSFEAAVPSNSHIVSEPGKNVTLTCQPQMTWPVQAVRWEKIQPRQIDLLTYCN
LVHGRNFTSKFPRQIVSNCSHGRWSVIVIPDVTVSDSGLYRCYLQASAGENETFVMRLTV
AEGKTDNQYTLFVAGGTVLLLLFVISITTIIVIFLNRRRRRERRDLFTESWDTQKAPNNY
RSPISTSQPTNQSMDDTREDIYVNYPTFSRRPKTRV
Function
Involved in intercellular adhesion, lymphocyte signaling, cytotoxicity and lymphokine secretion mediated by cytotoxic T-lymphocyte (CTL) and NK cell. 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.
Tissue Specificity Expressed by peripheral blood T-lymphocytes.
KEGG Pathway
Cell adhesion molecules (hsa04514 )
Reactome Pathway
Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell (R-HSA-198933 )

Molecular Interaction Atlas (MIA) of This DOT

46 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Advanced cancer DISAT1Z9 Definitive Biomarker [1]
Acute myelogenous leukaemia DISCSPTN Strong Biomarker [2]
Alzheimer disease DISF8S70 Strong Altered Expression [3]
Anca-associated vasculitis DISU3CNU Strong Genetic Variation [4]
Autoimmune disease, susceptibility to, 6 DISHNUXI Strong Genetic Variation [5]
Breast cancer DIS7DPX1 Strong Altered Expression [6]
Breast carcinoma DIS2UE88 Strong Altered Expression [6]
Breast neoplasm DISNGJLM Strong Biomarker [7]
Colon carcinoma DISJYKUO Strong Biomarker [8]
Colorectal carcinoma DIS5PYL0 Strong Biomarker [9]
Colorectal neoplasm DISR1UCN Strong Genetic Variation [9]
Epithelial ovarian cancer DIS56MH2 Strong Altered Expression [10]
Graves disease DISU4KOQ Strong Genetic Variation [4]
Hepatitis C virus infection DISQ0M8R Strong Biomarker [11]
Hepatocellular carcinoma DIS0J828 Strong Biomarker [12]
Hypothyroidism DISR0H6D Strong Genetic Variation [5]
Inflammatory bowel disease DISGN23E Strong Biomarker [13]
Juvenile idiopathic arthritis DISQZGBV Strong Genetic Variation [14]
Neoplasm DISZKGEW Strong Altered Expression [15]
Nervous system inflammation DISB3X5A Strong Biomarker [16]
Plasma cell myeloma DIS0DFZ0 Strong Altered Expression [17]
Primary sclerosing cholangitis DISTH5WJ Strong Genetic Variation [18]
Prostate cancer DISF190Y Strong Biomarker [19]
Prostate carcinoma DISMJPLE Strong Biomarker [19]
Psoriasis DIS59VMN Strong Genetic Variation [20]
Sclerosing cholangitis DIS7GZNB Strong Genetic Variation [21]
STAT3-related early-onset multisystem autoimmune disease DISAXTN7 Strong Genetic Variation [5]
Systemic lupus erythematosus DISI1SZ7 Strong Biomarker [22]
Ankylosing spondylitis DISRC6IR moderate Genetic Variation [20]
Gastric cancer DISXGOUK moderate Biomarker [23]
Melanoma DIS1RRCY moderate Biomarker [24]
Stomach cancer DISKIJSX moderate Biomarker [23]
Endometriosis DISX1AG8 Disputed Biomarker [25]
Adult glioblastoma DISVP4LU Limited Altered Expression [26]
Carcinoma DISH9F1N Limited Biomarker [27]
Crohn disease DIS2C5Q8 Limited Genetic Variation [20]
Deafness DISKCLH4 Limited Genetic Variation [28]
Glioblastoma multiforme DISK8246 Limited Altered Expression [26]
leukaemia DISS7D1V Limited Altered Expression [29]
Leukemia DISNAKFL Limited Altered Expression [29]
Metastatic malignant neoplasm DIS86UK6 Limited Biomarker [29]
Multiple sclerosis DISB2WZI Limited Genetic Variation [30]
Neuroblastoma DISVZBI4 Limited Altered Expression [31]
Non-insulin dependent diabetes DISK1O5Z Limited Altered Expression [32]
Type-1 diabetes DIS7HLUB Limited Genetic Variation [33]
Ulcerative colitis DIS8K27O Limited Genetic Variation [20]
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⏷ Show the Full List of 46 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
4 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Progesterone DMUY35B Approved Progesterone increases the expression of CD226 antigen (CD226). [25]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the expression of CD226 antigen (CD226). [35]
(+)-JQ1 DM1CZSJ Phase 1 (+)-JQ1 decreases the expression of CD226 antigen (CD226). [36]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 increases the expression of CD226 antigen (CD226). [37]
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1 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Bisphenol A DM2ZLD7 Investigative Bisphenol A affects the methylation of CD226 antigen (CD226). [38]
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References

1 Interaction of PVR/PVRL2 with TIGIT/DNAM-1 as a novel immune checkpoint axis and therapeutic target in cancer.Mamm Genome. 2018 Dec;29(11-12):694-702. doi: 10.1007/s00335-018-9770-7. Epub 2018 Aug 21.
2 Monitoring TIGIT/DNAM-1 and PVR/PVRL2 Immune Checkpoint Expression Levels in Allogeneic Stem Cell Transplantation for Acute Myeloid Leukemia.Biol Blood Marrow Transplant. 2019 May;25(5):861-867. doi: 10.1016/j.bbmt.2019.01.013. Epub 2019 Jan 11.
3 Hippocampal expression of cell-adhesion glycoprotein neuroplastin is altered in Alzheimer's disease.J Cell Mol Med. 2019 Feb;23(2):1602-1607. doi: 10.1111/jcmm.13998. Epub 2018 Nov 28.
4 CD226 Gly307Ser association with multiple autoimmune diseases: a meta-analysis.Hum Immunol. 2013 Feb;74(2):249-55. doi: 10.1016/j.humimm.2012.10.009. Epub 2012 Oct 13.
5 Leveraging Polygenic Functional Enrichment to Improve GWAS Power.Am J Hum Genet. 2019 Jan 3;104(1):65-75. doi: 10.1016/j.ajhg.2018.11.008. Epub 2018 Dec 27.
6 CD155 expression in human breast cancer: Clinical significance and relevance to natural killer cell infiltration.Life Sci. 2019 Aug 15;231:116543. doi: 10.1016/j.lfs.2019.116543. Epub 2019 Jun 6.
7 E-Cadherin/ROS1 Inhibitor Synthetic Lethality in Breast Cancer.Cancer Discov. 2018 Apr;8(4):498-515. doi: 10.1158/2159-8290.CD-17-0603.
8 Enhanced therapeutic effects against murine colon carcinoma induced by a Colon 26/Ag85A-CD226 tumor cell vaccine.Oncol Rep. 2015 Oct;34(4):1795-804. doi: 10.3892/or.2015.4137. Epub 2015 Jul 20.
9 Prognostic and predictive relevance of DNAM-1, SOCS6 and CADH-7 genes on chromosome 18q in colorectal cancer.Oncology. 2005;68(2-3):246-55. doi: 10.1159/000086781. Epub 2005 Jul 7.
10 Differential expression of ligands for NKG2D and DNAM-1 receptors by epithelial ovarian cancer-derived exosomes and its influence on NK cell cytotoxicity.Tumour Biol. 2016 Apr;37(4):5455-66. doi: 10.1007/s13277-015-4313-2. Epub 2015 Nov 13.
11 DNAM-1 Activating Receptor and Its Ligands: How Do Viruses Affect the NK Cell-Mediated Immune Surveillance during the Various Phases of Infection?.Int J Mol Sci. 2019 Jul 30;20(15):3715. doi: 10.3390/ijms20153715.
12 Human CD96 Correlates to Natural Killer Cell Exhaustion and Predicts the Prognosis of Human Hepatocellular Carcinoma.Hepatology. 2019 Jul;70(1):168-183. doi: 10.1002/hep.30347. Epub 2019 Mar 5.
13 Fine tuning of the DNAM-1/TIGIT/ligand axis in mucosal T cells and its dysregulation in pediatric inflammatory bowel diseases (IBD).Mucosal Immunol. 2019 Nov;12(6):1358-1369. doi: 10.1038/s41385-019-0208-7. Epub 2019 Oct 3.
14 CD226 (DNAM-1) is associated with susceptibility to juvenile idiopathic arthritis.Ann Rheum Dis. 2015 Dec;74(12):2193-8. doi: 10.1136/annrheumdis-2013-205138. Epub 2014 Jul 23.
15 High expression of soluble CD155 in estrogen receptor-negative breast cancer.Breast Cancer. 2020 Jan;27(1):92-99. doi: 10.1007/s12282-019-00999-8. Epub 2019 Aug 1.
16 CD226 ligation protects against EAE by promoting IL-10 expression via regulation of CD4+ T cell differentiation.Oncotarget. 2016 Apr 12;7(15):19251-64. doi: 10.18632/oncotarget.7834.
17 Key Role of the CD56(low)CD16(low) Natural Killer Cell Subset in the Recognition and Killing of Multiple Myeloma Cells.Cancers (Basel). 2018 Nov 29;10(12):473. doi: 10.3390/cancers10120473.
18 Dense genotyping of immune-related disease regions identifies nine new risk loci for primary sclerosing cholangitis.Nat Genet. 2013 Jun;45(6):670-5. doi: 10.1038/ng.2616. Epub 2013 Apr 21.
19 Identification of targets for prostate cancer immunotherapy.Prostate. 2019 Apr;79(5):498-505. doi: 10.1002/pros.23756. Epub 2019 Jan 6.
20 Analysis of five chronic inflammatory diseases identifies 27 new associations and highlights disease-specific patterns at shared loci.Nat Genet. 2016 May;48(5):510-8. doi: 10.1038/ng.3528. Epub 2016 Mar 14.
21 Genome-wide association study of primary sclerosing cholangitis identifies new risk loci and quantifies the genetic relationship with inflammatory bowel disease.Nat Genet. 2017 Feb;49(2):269-273. doi: 10.1038/ng.3745. Epub 2016 Dec 19.
22 High-density genotyping of immune-related loci identifies new SLE risk variants in individuals with Asian ancestry.Nat Genet. 2016 Mar;48(3):323-30. doi: 10.1038/ng.3496. Epub 2016 Jan 25.
23 Altered NKp30, NKp46, NKG2D, and DNAM-1 Expression on Circulating NK Cells Is Associated with Tumor Progression in Human Gastric Cancer.J Immunol Res. 2018 Sep 3;2018:6248590. doi: 10.1155/2018/6248590. eCollection 2018.
24 DNAM-1-based chimeric antigen receptors enhance T cell effector function and exhibit in vivo efficacy against melanoma.Cancer Immunol Immunother. 2015 Apr;64(4):409-18. doi: 10.1007/s00262-014-1648-2. Epub 2014 Dec 31.
25 Unique transcriptome, pathways, and networks in the human endometrial fibroblast response to progesterone in endometriosis. Biol Reprod. 2011 Apr;84(4):801-15.
26 Cord blood natural killer cells expressing a dominant negative TGF- receptor: Implications for adoptive immunotherapy for glioblastoma.Cytotherapy. 2017 Mar;19(3):408-418. doi: 10.1016/j.jcyt.2016.12.005. Epub 2017 Jan 19.
27 Loss of p21Waf1 expression is a strong predictor of reduced survival in primary superficial bladder cancers.Clin Cancer Res. 2000 Aug;6(8):3131-8.
28 Clinical aspects of an autosomal dominantly inherited hearing impairment linked to the DFNA60 locus on chromosome 2q23.1-2q23.3.Hear Res. 2013 Jun;300:10-7. doi: 10.1016/j.heares.2013.03.007. Epub 2013 Mar 26.
29 DNAM-1 and the TIGIT/PVRIG/TACTILE Axis: Novel Immune Checkpoints for Natural Killer Cell-Based Cancer Immunotherapy.Cancers (Basel). 2019 Jun 23;11(6):877. doi: 10.3390/cancers11060877.
30 High-resolution melting curve analysis of polymorphisms within CD58, CD226, HLA-G genes and association with multiple sclerosis susceptibility in a subset of Iranian population: a case-control study.Acta Neurol Belg. 2020 Jun;120(3):645-652. doi: 10.1007/s13760-018-0992-y. Epub 2018 Aug 20.
31 Diminished cytolytic activity of T cells with reduced DNAM-1 expression in neuroblastoma patients.Clin Immunol. 2019 Jun;203:63-71. doi: 10.1016/j.clim.2019.04.006. Epub 2019 Apr 15.
32 CD226 reduces endothelial cell glucose uptake under hyperglycemic conditions with inflammation in type 2 diabetes mellitus.Oncotarget. 2016 Mar 15;7(11):12010-23. doi: 10.18632/oncotarget.7505.
33 Fine mapping of type 1 diabetes susceptibility loci and evidence for colocalization of causal variants with lymphoid gene enhancers.Nat Genet. 2015 Apr;47(4):381-6. doi: 10.1038/ng.3245. Epub 2015 Mar 9.
34 Unique transcriptome, pathways, and networks in the human endometrial fibroblast response to progesterone in endometriosis. Biol Reprod. 2011 Apr;84(4):801-15.
35 Genome-wide transcriptional and functional analysis of human T lymphocytes treated with benzo[alpha]pyrene. Int J Mol Sci. 2018 Nov 17;19(11).
36 Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem. 2012 Dec 14;287(51):43137-55.
37 Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
38 DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.