Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT3N91T7)

DOT Name	Poliovirus receptor (PVR)
Synonyms	Nectin-like protein 5; NECL-5; CD antigen CD155
Gene Name	PVR
Related Disease	Acute myelogenous leukaemia ( ) Adenocarcinoma ( ) Adult glioblastoma ( ) Alzheimer disease ( ) Atherosclerosis ( ) Breast cancer ( ) Breast carcinoma ( ) Breast neoplasm ( ) Colon cancer ( ) Colon carcinoma ( ) Colonic neoplasm ( ) Colorectal carcinoma ( ) Epithelial ovarian cancer ( ) Glioblastoma multiforme ( ) Hepatocellular carcinoma ( ) Leukemia ( ) Malignant glioma ( ) Metastatic malignant neoplasm ( ) Pancreatic cancer ( ) Plasma cell myeloma ( ) Poliomyelitis ( ) Polycythemia vera ( ) Proliferative vitreoretinopathy ( ) Prostate cancer ( ) Prostate neoplasm ( ) Schizophrenia ( ) Stroke ( ) Type-1/2 diabetes ( ) Gastric cancer ( ) Glioma ( ) Neuroblastoma ( ) Prostate carcinoma ( ) Squamous cell carcinoma ( ) Stomach cancer ( ) Triple negative breast cancer ( ) Advanced cancer ( ) Bone osteosarcoma ( ) Lung adenocarcinoma ( ) Lung cancer ( ) Lung carcinoma ( ) Melanoma ( ) Osteosarcoma ( ) Tetralogy of fallot ( )
UniProt ID	PVR_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
PDB ID	1DGI; 1NN8; 3EPC; 3EPD; 3EPF; 3J8F; 3J9F; 3UDW; 3URO; 4FQP; 6ARQ; 6ISC; 6O3O
Pfam ID	PF08205 ; PF07686
Sequence	MARAMAAAWPLLLVALLVLSWPPPGTGDVVVQAPTQVPGFLGDSVTLPCYLQVPNMEVTH VSQLTWARHGESGSMAVFHQTQGPSYSESKRLEFVAARLGAELRNASLRMFGLRVEDEGN YTCLFVTFPQGSRSVDIWLRVLAKPQNTAEVQKVQLTGEPVPMARCVSTGGRPPAQITWH SDLGGMPNTSQVPGFLSGTVTVTSLWILVPSSQVDGKNVTCKVEHESFEKPQLLTVNLTV YYPPEVSISGYDNNWYLGQNEATLTCDARSNPEPTGYNWSTTMGPLPPFAVAQGAQLLIR PVDKPINTTLICNVTNALGARQAELTVQVKEGPPSEHSGISRNAIIFLVLGILVFLILLG IGIYFYWSKCSREVLWHCHLCPSSTEHASASANGHVSYSAVSRENSSSQDPQTEGTR
Function	Mediates NK cell adhesion and triggers NK cell effector functions. Binds two different NK cell receptors: CD96 and CD226. These interactions accumulates at the cell-cell contact site, leading to the formation of a mature immunological synapse between NK cell and target cell. This may trigger adhesion and secretion of lytic granules and IFN-gamma and activate cytotoxicity of activated NK cells. May also promote NK cell-target cell modular exchange, and PVR transfer to the NK cell. This transfer is more important in some tumor cells expressing a lot of PVR, and may trigger fratricide NK cell activation, providing tumors with a mechanism of immunoevasion. Plays a role in mediating tumor cell invasion and migration; (Microbial infection) Acts as a receptor for poliovirus. May play a role in axonal transport of poliovirus, by targeting virion-PVR-containing endocytic vesicles to the microtubular network through interaction with DYNLT1. This interaction would drive the virus-containing vesicle to the axonal retrograde transport; (Microbial infection) Acts as a receptor for Pseudorabies virus; (Microbial infection) Is prevented to reach cell surface upon infection by Human cytomegalovirus /HHV-5, presumably to escape immune recognition of infected cell by NK cells.
KEGG Pathway	Cell adhesion molecules (hsa04514 )
Reactome Pathway	Nectin/Necl trans heterodimerization (R-HSA-420597 ) Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell (R-HSA-198933 )

Molecular Interaction Atlas (MIA) of This DOT

43 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance
Acute myelogenous leukaemia	DISCSPTN	Strong	Biomarker	[1]
Adenocarcinoma	DIS3IHTY	Strong	Altered Expression	[2]
Adult glioblastoma	DISVP4LU	Strong	Altered Expression	[3]
Alzheimer disease	DISF8S70	Strong	Genetic Variation	[4]
Atherosclerosis	DISMN9J3	Strong	Biomarker	[5]
Breast cancer	DIS7DPX1	Strong	Altered Expression	[6]
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[6]
Breast neoplasm	DISNGJLM	Strong	Biomarker	[7]
Colon cancer	DISVC52G	Strong	Altered Expression	[8]
Colon carcinoma	DISJYKUO	Strong	Altered Expression	[8]
Colonic neoplasm	DISSZ04P	Strong	Altered Expression	[9]
Colorectal carcinoma	DIS5PYL0	Strong	Altered Expression	[2]
Epithelial ovarian cancer	DIS56MH2	Strong	Biomarker	[10]
Glioblastoma multiforme	DISK8246	Strong	Altered Expression	[3]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[11]
Leukemia	DISNAKFL	Strong	Biomarker	[12]
Malignant glioma	DISFXKOV	Strong	Biomarker	[13]
Metastatic malignant neoplasm	DIS86UK6	Strong	Altered Expression	[14]
Pancreatic cancer	DISJC981	Strong	Altered Expression	[15]
Plasma cell myeloma	DIS0DFZ0	Strong	Biomarker	[16]
Poliomyelitis	DISANFJN	Strong	Biomarker	[17]
Polycythemia vera	DISB5FPO	Strong	Biomarker	[18]
Proliferative vitreoretinopathy	DISZTEK1	Strong	Biomarker	[19]
Prostate cancer	DISF190Y	Strong	Biomarker	[14]
Prostate neoplasm	DISHDKGQ	Strong	Biomarker	[20]
Schizophrenia	DISSRV2N	Strong	Genetic Variation	[21]
Stroke	DISX6UHX	Strong	Genetic Variation	[22]
Type-1/2 diabetes	DISIUHAP	Strong	Genetic Variation	[23]
Gastric cancer	DISXGOUK	moderate	Biomarker	[24]
Glioma	DIS5RPEH	moderate	Biomarker	[3]
Neuroblastoma	DISVZBI4	moderate	Altered Expression	[25]
Prostate carcinoma	DISMJPLE	moderate	Biomarker	[14]
Squamous cell carcinoma	DISQVIFL	moderate	Altered Expression	[26]
Stomach cancer	DISKIJSX	moderate	Biomarker	[24]
Triple negative breast cancer	DISAMG6N	moderate	Biomarker	[27]
Advanced cancer	DISAT1Z9	Limited	Altered Expression	[2]
Bone osteosarcoma	DIST1004	Limited	Biomarker	[28]
Lung adenocarcinoma	DISD51WR	Limited	Biomarker	[29]
Lung cancer	DISCM4YA	Limited	Altered Expression	[29]
Lung carcinoma	DISTR26C	Limited	Altered Expression	[29]
Melanoma	DIS1RRCY	Limited	Biomarker	[30]
Osteosarcoma	DISLQ7E2	Limited	Biomarker	[28]
Tetralogy of fallot	DISMHFNW	Limited	Biomarker	[31]
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Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This DOT

2 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Poliovirus receptor (PVR).	[32]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Poliovirus receptor (PVR).	[40]
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11 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Poliovirus receptor (PVR).	[33]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Poliovirus receptor (PVR).	[34]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Poliovirus receptor (PVR).	[35]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Poliovirus receptor (PVR).	[36]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Poliovirus receptor (PVR).	[37]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Poliovirus receptor (PVR).	[38]
Folic acid	DMEMBJC	Approved	Folic acid decreases the expression of Poliovirus receptor (PVR).	[39]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Poliovirus receptor (PVR).	[41]
Torcetrapib	DMDHYM7	Discontinued in Phase 2	Torcetrapib increases the expression of Poliovirus receptor (PVR).	[42]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Poliovirus receptor (PVR).	[43]
Manganese	DMKT129	Investigative	Manganese decreases the expression of Poliovirus receptor (PVR).	[44]
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⏷ Show the Full List of 11 Drug(s)

References

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2	Analysis of poliovirus receptor, CD155 expression in different human colorectal cancer cell lines: Implications for poliovirus virotherapy.J Cancer Res Ther. 2019 Jan-Mar;15(1):61-67. doi: 10.4103/jcrt.JCRT_13_17.
3	Large-scale analysis reveals the specific clinical and immune features of CD155 in glioma.Aging (Albany NY). 2019 Aug 4;11(15):5463-5482. doi: 10.18632/aging.102131. Epub 2019 Aug 4.
4	Shared genetic architecture between metabolic traits and Alzheimer's disease: a large-scale genome-wide cross-trait analysis.Hum Genet. 2019 Mar;138(3):271-285. doi: 10.1007/s00439-019-01988-9. Epub 2019 Feb 25.
5	Poliovirus Receptor-Related 2: A Cholesterol-Responsive Gene Affecting Atherosclerosis Development by Modulating Leukocyte Migration.Arterioscler Thromb Vasc Biol. 2017 Mar;37(3):534-542. doi: 10.1161/ATVBAHA.116.308715. Epub 2017 Jan 5.
6	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.
7	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.
8	CD155 knockdown promotes apoptosis via AKT/Bcl-2/Bax in colon cancer cells.J Cell Mol Med. 2018 Jan;22(1):131-140. doi: 10.1111/jcmm.13301. Epub 2017 Aug 16.
9	Overexpression of the CD155 gene in human colorectal carcinoma.Gut. 2001 Aug;49(2):236-40. doi: 10.1136/gut.49.2.236.
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	Expression of TIGIT/CD155 and correlations with clinical pathological features in human hepatocellular carcinoma.Mol Med Rep. 2019 Oct;20(4):3773-3781. doi: 10.3892/mmr.2019.10641. Epub 2019 Sep 2.
12	Human NUP98-HOXA9 promotes hyperplastic growth of hematopoietic tissues in Drosophila.Dev Biol. 2017 Jan 1;421(1):16-26. doi: 10.1016/j.ydbio.2016.11.003. Epub 2016 Nov 10.
13	Validation of an Immunohistochemistry Assay for Detection of CD155, the Poliovirus Receptor, in Malignant Gliomas.Arch Pathol Lab Med. 2017 Dec;141(12):1697-1704. doi: 10.5858/arpa.2016-0580-OA. Epub 2017 Aug 22.
14	The bispecific anti-CD3anti-CD155 antibody mediates T cell immunotherapy for human prostate cancer.Invest New Drugs. 2019 Oct;37(5):810-817. doi: 10.1007/s10637-018-0683-9. Epub 2018 Oct 29.
15	Clinical significance of CD155 expression in human pancreatic cancer.Anticancer Res. 2015 Apr;35(4):2287-97.
16	NK cells and multiple myeloma-associated endothelial cells: molecular interactions and influence of IL-27.Oncotarget. 2017 May 23;8(21):35088-35102. doi: 10.18632/oncotarget.17070.
17	CRISPR/Cas9-mediated gene knockout screens and target identification via whole-genome sequencing uncover host genes required for picornavirus infection. J Biol Chem. 2017 Jun 23;292(25):10664-10671. doi: 10.1074/jbc.M117.782425. Epub 2017 Apr 26.
18	Poliomyelitis in transgenic mice expressing CD155 under the control of the Tage4 promoter after oral and parenteral poliovirus inoculation.J Gen Virol. 2014 Aug;95(Pt 8):1668-1676. doi: 10.1099/vir.0.064535-0. Epub 2014 Apr 30.
19	Comparison of Chemokine CXCL-1 and Interleukin-6 Concentrations in the Subretinal Fluid and Vitreous in Rhegmatogenous Retinal Detachment.Ocul Immunol Inflamm. 2021 Feb 17;29(2):355-361. doi: 10.1080/09273948.2019.1672197. Epub 2019 Oct 29.
20	Identification of targets for prostate cancer immunotherapy.Prostate. 2019 Apr;79(5):498-505. doi: 10.1002/pros.23756. Epub 2019 Jan 6.
21	How a poliovirus might cause schizophrenia: a commentary on Eagles' hypothesis.Neurochem Res. 1997 May;22(5):647-56. doi: 10.1023/a:1022486423238.
22	Clinical Significance of Magnetic Resonance Imaging Markers of Vascular Brain Injury: A Systematic Review and Meta-analysis.JAMA Neurol. 2019 Jan 1;76(1):81-94. doi: 10.1001/jamaneurol.2018.3122.
23	Perivascular spaces in the centrum semiovale at the beginning of the 8th decade of life: effect on cognition and associations with mineral deposition.Brain Imaging Behav. 2020 Oct;14(5):1865-1875. doi: 10.1007/s11682-019-00128-1.
24	CD155T/TIGIT Signaling Regulates CD8(+) T-cell Metabolism and Promotes Tumor Progression in Human Gastric Cancer.Cancer Res. 2017 Nov 15;77(22):6375-6388. doi: 10.1158/0008-5472.CAN-17-0381. Epub 2017 Sep 7.
25	Oncolytic virotherapy for human bone and soft tissue sarcomas using live attenuated poliovirus.Int J Oncol. 2012 Sep;41(3):893-902. doi: 10.3892/ijo.2012.1514. Epub 2012 Jun 12.
26	Aberrant DNA Methylation in Keratoacanthoma.PLoS One. 2016 Oct 27;11(10):e0165370. doi: 10.1371/journal.pone.0165370. eCollection 2016.
27	CD155 contributes to the mesenchymal phenotype of triple-negative breast cancer.Cancer Sci. 2020 Feb;111(2):383-394. doi: 10.1111/cas.14276. Epub 2020 Jan 2.
28	Overexpression of CD155 relates to metastasis and invasion in osteosarcoma.Oncol Lett. 2018 May;15(5):7312-7318. doi: 10.3892/ol.2018.8228. Epub 2018 Mar 9.
29	The role of Necl-5 in the invasive activity of lung adenocarcinoma.Exp Mol Pathol. 2013 Apr;94(2):330-5. doi: 10.1016/j.yexmp.2012.12.003. Epub 2012 Dec 28.
30	A Multikinase and DNA-PK Inhibitor Combination Immunomodulates Melanomas, Suppresses Tumor Progression, and Enhances Immunotherapies.Cancer Immunol Res. 2017 Sep;5(9):790-803. doi: 10.1158/2326-6066.CIR-17-0009. Epub 2017 Aug 3.
31	Whether Pulmonary Valve Replacement in Asymptomatic Patients With Moderate or Severe Regurgitation After Tetralogy of Fallot Repair Is Appropriate: A Case-Control Study.J Am Heart Assoc. 2019 Jan 8;8(1):e010689. doi: 10.1161/JAHA.118.010689.
32	Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
33	Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
34	Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
35	Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
36	Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
37	Genistein and bisphenol A exposure cause estrogen receptor 1 to bind thousands of sites in a cell type-specific manner. Genome Res. 2012 Nov;22(11):2153-62.
38	Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
39	Folic acid supplementation dysregulates gene expression in lymphoblastoid cells--implications in nutrition. Biochem Biophys Res Commun. 2011 Sep 9;412(4):688-92. doi: 10.1016/j.bbrc.2011.08.027. Epub 2011 Aug 16.
40	Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
41	Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
42	Clarifying off-target effects for torcetrapib using network pharmacology and reverse docking approach. BMC Syst Biol. 2012 Dec 10;6:152.
43	Bisphenolic compounds alter gene expression in MCF-7 cells through interaction with estrogen receptor . Toxicol Appl Pharmacol. 2020 Jul 15;399:115030. doi: 10.1016/j.taap.2020.115030. Epub 2020 May 6.
44	Gene expression profiling of human primary astrocytes exposed to manganese chloride indicates selective effects on several functions of the cells. Neurotoxicology. 2007 May;28(3):478-89.