Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTF3UZS7)

DOT Name	CD151 antigen (CD151)
Synonyms	GP27; Membrane glycoprotein SFA-1; Platelet-endothelial tetraspan antigen 3; PETA-3; Tetraspanin-24; Tspan-24; CD antigen CD151
Gene Name	CD151
Related Disease	Ependymoma ( ) Glioma ( ) Adenocarcinoma ( ) Adult T-cell leukemia/lymphoma ( ) Advanced cancer ( ) Arteriosclerosis ( ) Bone osteosarcoma ( ) Breast neoplasm ( ) Clear cell renal carcinoma ( ) Colon cancer ( ) Colon carcinoma ( ) End-stage renal disease ( ) Epidermolysis bullosa simplex 7, with nephropathy and deafness ( ) Epithelial ovarian cancer ( ) Esophageal adenocarcinoma ( ) Gastric cancer ( ) Head and neck cancer ( ) Head and neck carcinoma ( ) Head-neck squamous cell carcinoma ( ) Hepatocellular carcinoma ( ) Liver cancer ( ) Lung adenocarcinoma ( ) Melanoma ( ) Osteosarcoma ( ) Ovarian cancer ( ) Ovarian neoplasm ( ) Pulmonary fibrosis ( ) Soft tissue sarcoma ( ) Squamous cell carcinoma ( ) Stomach cancer ( ) T-cell leukaemia ( ) Adult glioblastoma ( ) Carcinoma of liver and intrahepatic biliary tract ( ) Chronic renal failure ( ) Glioblastoma multiforme ( ) Matthew-Wood syndrome ( ) Myocardial infarction ( ) Pancreatic ductal carcinoma ( ) Renal cell carcinoma ( ) Childhood kidney Wilms tumor ( ) Wilms tumor ( ) Asthma ( ) Lung cancer ( ) Lung carcinoma ( ) Nephropathy ( ) Non-small-cell lung cancer ( )
UniProt ID	CD151_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
Pfam ID	PF00335
Sequence	MGEFNEKKTTCGTVCLKYLLFTYNCCFWLAGLAVMAVGIWTLALKSDYISLLASGTYLAT AYILVVAGTVVMVTGVLGCCATFKERRNLLRLYFILLLIIFLLEIIAGILAYAYYQQLNT ELKENLKDTMTKRYHQPGHEAVTSAVDQLQQEFHCCGSNNSQDWRDSEWIRSQEAGGRVV PDSCCKTVVALCGQRDHASNIYKVEGGCITKLETFIQEHLRVIGAVGIGIACVQVFGMIF TCCLYRSLKLEHY
Function	Essential for the proper assembly of the glomerular and tubular basement membranes in kidney; (Microbial infection) Plays a role in human papillomavirus 16/HPV-16 endocytosis upon binding to cell surface receptor.
Tissue Specificity	Expressed in a variety of tissues including vascular endothelium and epidermis. Expressed on erythroid cells, with a higher level of expression in erythroid precursors than on mature erythrocytes.
Reactome Pathway	Type I hemidesmosome assembly (R-HSA-446107 ) Assembly of collagen fibrils and other multimeric structures (R-HSA-2022090 )

Molecular Interaction Atlas (MIA) of This DOT

46 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance
Ependymoma	DISUMRNZ	Definitive	Genetic Variation	[1]
Glioma	DIS5RPEH	Definitive	Biomarker	[2]
Adenocarcinoma	DIS3IHTY	Strong	Altered Expression	[3]
Adult T-cell leukemia/lymphoma	DIS882XU	Strong	Altered Expression	[4]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[5]
Arteriosclerosis	DISK5QGC	Strong	Biomarker	[6]
Bone osteosarcoma	DIST1004	Strong	Biomarker	[7]
Breast neoplasm	DISNGJLM	Strong	Altered Expression	[8]
Clear cell renal carcinoma	DISBXRFJ	Strong	Biomarker	[9]
Colon cancer	DISVC52G	Strong	Altered Expression	[10]
Colon carcinoma	DISJYKUO	Strong	Altered Expression	[10]
End-stage renal disease	DISXA7GG	Strong	Biomarker	[11]
Epidermolysis bullosa simplex 7, with nephropathy and deafness	DISD5EYR	Strong	Autosomal recessive	[12]
Epithelial ovarian cancer	DIS56MH2	Strong	Altered Expression	[13]
Esophageal adenocarcinoma	DISODWFP	Strong	Biomarker	[3]
Gastric cancer	DISXGOUK	Strong	Altered Expression	[14]
Head and neck cancer	DISBPSQZ	Strong	Altered Expression	[15]
Head and neck carcinoma	DISOU1DS	Strong	Altered Expression	[15]
Head-neck squamous cell carcinoma	DISF7P24	Strong	Altered Expression	[15]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[16]
Liver cancer	DISDE4BI	Strong	Altered Expression	[17]
Lung adenocarcinoma	DISD51WR	Strong	Altered Expression	[18]
Melanoma	DIS1RRCY	Strong	Biomarker	[19]
Osteosarcoma	DISLQ7E2	Strong	Biomarker	[7]
Ovarian cancer	DISZJHAP	Strong	Altered Expression	[13]
Ovarian neoplasm	DISEAFTY	Strong	Altered Expression	[13]
Pulmonary fibrosis	DISQKVLA	Strong	Biomarker	[20]
Soft tissue sarcoma	DISSN8XB	Strong	Biomarker	[21]
Squamous cell carcinoma	DISQVIFL	Strong	Altered Expression	[22]
Stomach cancer	DISKIJSX	Strong	Altered Expression	[14]
T-cell leukaemia	DISJ6YIF	Strong	Altered Expression	[4]
Adult glioblastoma	DISVP4LU	moderate	Biomarker	[2]
Carcinoma of liver and intrahepatic biliary tract	DIS8WA0W	moderate	Biomarker	[23]
Chronic renal failure	DISGG7K6	moderate	Biomarker	[11]
Glioblastoma multiforme	DISK8246	moderate	Biomarker	[2]
Matthew-Wood syndrome	DISA7HR7	moderate	Biomarker	[24]
Myocardial infarction	DIS655KI	moderate	Biomarker	[25]
Pancreatic ductal carcinoma	DIS26F9Q	moderate	Biomarker	[24]
Renal cell carcinoma	DISQZ2X8	moderate	Biomarker	[9]
Childhood kidney Wilms tumor	DIS0NMK3	Disputed	Biomarker	[26]
Wilms tumor	DISB6T16	Disputed	Biomarker	[26]
Asthma	DISW9QNS	Limited	Biomarker	[27]
Lung cancer	DISCM4YA	Limited	Biomarker	[28]
Lung carcinoma	DISTR26C	Limited	Biomarker	[28]
Nephropathy	DISXWP4P	Limited	Genetic Variation	[29]
Non-small-cell lung cancer	DIS5Y6R9	Limited	Altered Expression	[28]
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⏷ Show the Full List of 46 Disease(s)

Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This DOT

This DOT Affected the Drug Response of 2 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Cisplatin	DMRHGI9	Approved	CD151 antigen (CD151) decreases the response to substance of Cisplatin.	[44]
Methotrexate	DM2TEOL	Approved	CD151 antigen (CD151) affects the response to substance of Methotrexate.	[45]
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4 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 CD151 antigen (CD151).	[30]
Arsenic	DMTL2Y1	Approved	Arsenic increases the methylation of CD151 antigen (CD151).	[35]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of CD151 antigen (CD151).	[41]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of CD151 antigen (CD151).	[43]
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10 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 CD151 antigen (CD151).	[31]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of CD151 antigen (CD151).	[32]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of CD151 antigen (CD151).	[33]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of CD151 antigen (CD151).	[34]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of CD151 antigen (CD151).	[36]
Cannabidiol	DM0659E	Approved	Cannabidiol decreases the expression of CD151 antigen (CD151).	[37]
Aspirin	DM672AH	Approved	Aspirin decreases the expression of CD151 antigen (CD151).	[38]
Testosterone enanthate	DMB6871	Approved	Testosterone enanthate affects the expression of CD151 antigen (CD151).	[39]
DTI-015	DMXZRW0	Approved	DTI-015 decreases the expression of CD151 antigen (CD151).	[40]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of CD151 antigen (CD151).	[42]
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⏷ Show the Full List of 10 Drug(s)

References

1	Novel fusion genes and chimeric transcripts in ependymal tumors.Genes Chromosomes Cancer. 2016 Dec;55(12):944-953. doi: 10.1002/gcc.22392. Epub 2016 Jul 28.
2	Regulation of Glioblastoma Tumor-Propagating Cells by the Integrin Partner Tetraspanin CD151.Neoplasia. 2016 Mar;18(3):185-98. doi: 10.1016/j.neo.2016.02.003.
3	CD151 Gene and Protein Expression Provides Independent Prognostic Information for Patients with Adenocarcinoma of the Esophagus and Gastroesophageal Junction Treated by Esophagectomy.Ann Surg Oncol. 2016 Dec;23(Suppl 5):746-754. doi: 10.1245/s10434-016-5504-9. Epub 2016 Aug 30.
4	SFA-1/PETA-3 (CD151), a member of the transmembrane 4 superfamily, associates preferentially with alpha 5 beta 1 integrin and regulates adhesion of human T cell leukemia virus type 1-infected T cells to fibronectin.J Immunol. 1998 Sep 15;161(6):3087-95.
5	Integrin-independent support of cancer drug resistance by tetraspanin CD151.Cell Mol Life Sci. 2019 Apr;76(8):1595-1604. doi: 10.1007/s00018-019-03014-7. Epub 2019 Feb 18.
6	Distorted leukocyte migration, angiogenesis, wound repair and metastasis in Tspan8 and Tspan8/CD151 double knockout mice indicate complementary activities of Tspan8 and CD51.Biochim Biophys Acta Mol Cell Res. 2018 Feb;1865(2):379-391. doi: 10.1016/j.bbamcr.2017.11.007. Epub 2017 Nov 11.
7	CD151 knockdown inhibits osteosarcoma metastasis through the GSK-3/-catenin/MMP9 pathway.Oncol Rep. 2016 Mar;35(3):1764-70. doi: 10.3892/or.2015.4517. Epub 2015 Dec 24.
8	Expression of tetraspanins NET-6 and CD151 in breast cancer as a potential tumor biomarker.Clin Exp Med. 2019 Aug;19(3):377-384. doi: 10.1007/s10238-019-00554-x. Epub 2019 Apr 20.
9	CD151 promotes cell metastasis via activating TGF-1/Smad signaling in renal cell carcinoma.Oncotarget. 2018 Jan 8;9(17):13313-13323. doi: 10.18632/oncotarget.24028. eCollection 2018 Mar 2.
10	Clinical significance of transmembrane 4 superfamily in colon cancer.Br J Cancer. 2003 Jul 7;89(1):158-67. doi: 10.1038/sj.bjc.6601015.
11	Blood pressure influences end-stage renal disease of Cd151 knockout mice.J Clin Invest. 2012 Jan;122(1):348-58. doi: 10.1172/JCI58878. Epub 2011 Dec 27.
12	CD151, the first member of the tetraspanin (TM4) superfamily detected on erythrocytes, is essential for the correct assembly of human basement membranes in kidney and skin. Blood. 2004 Oct 15;104(8):2217-23. doi: 10.1182/blood-2004-04-1512. Epub 2004 Jul 20.
13	Interrogation of Functional Cell-Surface Markers Identifies CD151 Dependency in High-Grade Serous Ovarian Cancer.Cell Rep. 2017 Mar 7;18(10):2343-2358. doi: 10.1016/j.celrep.2017.02.028.
14	Long Noncoding RNA PVT1 Acts as a "Sponge" to Inhibit microRNA-152 in Gastric Cancer Cells.Dig Dis Sci. 2017 Nov;62(11):3021-3028. doi: 10.1007/s10620-017-4508-z. Epub 2017 Mar 3.
15	CD151 expression is frequent but unrelated to clinical outcome in head and neck cancer.Clin Oral Investig. 2017 Jun;21(5):1503-1508. doi: 10.1007/s00784-016-1911-3. Epub 2016 Jul 21.
16	LncRNA SNHG3 induces EMT and sorafenib resistance by modulating the miR-128/CD151 pathway in hepatocellular carcinoma.J Cell Physiol. 2019 Mar;234(3):2788-2794. doi: 10.1002/jcp.27095. Epub 2018 Aug 21.
17	CD151 supports VCAM-1-mediated lymphocyte adhesion to liver endothelium and is upregulated in chronic liver disease and hepatocellular carcinoma.Am J Physiol Gastrointest Liver Physiol. 2017 Aug 1;313(2):G138-G149. doi: 10.1152/ajpgi.00411.2016. Epub 2017 May 4.
18	Effects of tetraspanin CD151 inhibition on A549 human lung adenocarcinoma cells.Mol Med Rep. 2015 Feb;11(2):1258-65. doi: 10.3892/mmr.2014.2774. Epub 2014 Oct 27.
19	Homophilic interactions of Tetraspanin CD151 up-regulate motility and matrix metalloproteinase-9 expression of human melanoma cells through adhesion-dependent c-Jun activation signaling pathways.J Biol Chem. 2006 Aug 25;281(34):24279-92. doi: 10.1074/jbc.M601209200. Epub 2006 Jun 23.
20	Tetraspanin CD151 protects against pulmonary fibrosis by maintaining epithelial integrity.Am J Respir Crit Care Med. 2012 Jul 15;186(2):170-80. doi: 10.1164/rccm.201201-0117OC. Epub 2012 May 16.
21	CD151 confers metastatic potential to clear cell sarcoma of the soft tissue in animal model.Oncol Lett. 2019 Jun;17(6):4811-4818. doi: 10.3892/ol.2019.10164. Epub 2019 Mar 19.
22	Critical role of peroxisome proliferator-activated receptor gamma on anoikis and invasion of squamous cell carcinoma.Clin Cancer Res. 2005 Jun 1;11(11):4012-21. doi: 10.1158/1078-0432.CCR-05-0087.
23	SP1 is required for basal activation and chromatin accessibility of CD151 promoter in liver cancer cells.Biochem Biophys Res Commun. 2010 Mar 5;393(2):291-6. doi: 10.1016/j.bbrc.2010.01.127. Epub 2010 Feb 10.
24	Expression and prognostic significance of CD151, c-Met, and integrin alpha3/alpha6 in pancreatic ductal adenocarcinoma.Dig Dis Sci. 2011 Apr;56(4):1090-8. doi: 10.1007/s10620-010-1416-x. Epub 2010 Oct 7.
25	Adeno associated viral vector-delivered and hypoxia response element-regulated CD151 expression in ischemic rat heart.Acta Pharmacol Sin. 2011 Feb;32(2):201-8. doi: 10.1038/aps.2010.205. Epub 2011 Jan 17.
26	CD151 promotes proliferation and migration of SK-NEP-1 cells via the GSK-3/P21/cyclinD signaling pathway.Pathol Res Pract. 2019 Feb;215(2):329-334. doi: 10.1016/j.prp.2018.11.007. Epub 2018 Nov 10.
27	CD151, a laminin receptor showing increased expression in asthmatic patients, contributes to airway hyperresponsiveness through calcium signaling.J Allergy Clin Immunol. 2017 Jan;139(1):82-92.e5. doi: 10.1016/j.jaci.2016.03.029. Epub 2016 Apr 27.
28	Clinical significance of CD151 gene expression in non-small cell lung cancer.Clin Cancer Res. 2001 Dec;7(12):4109-14.
29	Recessive mutation in tetraspanin CD151 causes Kindler syndrome-like epidermolysis bullosa with multi-systemic manifestations including nephropathy.Matrix Biol. 2018 Mar;66:22-33. doi: 10.1016/j.matbio.2017.11.003. Epub 2017 Nov 11.
30	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.
31	Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
32	Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
33	Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
34	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.
35	Effect of prenatal arsenic exposure on DNA methylation and leukocyte subpopulations in cord blood. Epigenetics. 2014 May;9(5):774-82. doi: 10.4161/epi.28153. Epub 2014 Feb 13.
36	Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
37	Cannabidiol Modulates the Immunophenotype and Inhibits the Activation of the Inflammasome in Human Gingival Mesenchymal Stem Cells. Front Physiol. 2016 Nov 24;7:559. doi: 10.3389/fphys.2016.00559. eCollection 2016.
38	Magnitude and time course of platelet inhibition with Aggrenox and Aspirin in patients after ischemic stroke: the AGgrenox versus Aspirin Therapy Evaluation (AGATE) trial. Eur J Pharmacol. 2004 Sep 24;499(3):315-24. doi: 10.1016/j.ejphar.2004.07.114.
39	Transcriptional profiling of testosterone-regulated genes in the skeletal muscle of human immunodeficiency virus-infected men experiencing weight loss. J Clin Endocrinol Metab. 2007 Jul;92(7):2793-802. doi: 10.1210/jc.2006-2722. Epub 2007 Apr 17.
40	Gene expression profile induced by BCNU in human glioma cell lines with differential MGMT expression. J Neurooncol. 2005 Jul;73(3):189-98.
41	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.
42	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.
43	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.
44	Gene expression analysis using human cancer xenografts to identify novel predictive marker genes for the efficacy of 5-fluorouracil-based drugs. Cancer Sci. 2006 Jun;97(6):510-22. doi: 10.1111/j.1349-7006.2006.00204.x.
45	Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.