Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTI5C2DE)

DOT Name	Protein Mis18-beta (OIP5)
Synonyms	Cancer/testis antigen 86; CT86; Opa-interacting protein 5; OIP-5
Gene Name	OIP5
Related Disease	Acute myelogenous leukaemia ( ) Adult glioblastoma ( ) Bladder cancer ( ) Breast cancer ( ) Breast carcinoma ( ) Carcinoma of esophagus ( ) Carcinoma of liver and intrahepatic biliary tract ( ) Clear cell renal carcinoma ( ) Esophageal cancer ( ) Gastric cancer ( ) Glioblastoma multiforme ( ) Glioma ( ) Lentivirus infection ( ) Liver cancer ( ) Lung adenocarcinoma ( ) Lung cancer ( ) Neoplasm of esophagus ( ) Obesity ( ) Stomach cancer ( ) Urinary bladder cancer ( ) Urinary bladder neoplasm ( ) Advanced cancer ( ) Breast neoplasm ( ) Fetal growth restriction ( ) Hepatocellular carcinoma ( ) Nasopharyngeal carcinoma ( ) Neoplasm ( )
UniProt ID	MS18B_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
PDB ID	7SFY
Pfam ID	PF03226
Sequence	MAAQPLRHRSRCATPPRGDFCGGTERAIDQASFTTSMEWDTQVVKGSSPLGPAGLGAEEP AAGPQLPSWLQPERCAVFQCAQCHAVLADSVHLAWDLSRSLGAVVFSRVTNNVVLEAPFL VGIEGSLKGSTYNLLFCGSCGIPVGFHLYSTHAALAALRGHFCLSSDKMVCYLLKTKAIV NASEMDIQNVPLSEKIAELKEKIVLTHNRLKSLMKILSEVTPDQSKPEN
Function	Required for recruitment of CENPA to centromeres and normal chromosome segregation during mitosis.
Reactome Pathway	Deposition of new CENPA-containing nucleosomes at the centromere (R-HSA-606279 )

Molecular Interaction Atlas (MIA) of This DOT

27 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance
Acute myelogenous leukaemia	DISCSPTN	Definitive	Altered Expression	[1]
Adult glioblastoma	DISVP4LU	Strong	Altered Expression	[2]
Bladder cancer	DISUHNM0	Strong	Altered Expression	[3]
Breast cancer	DIS7DPX1	Strong	Biomarker	[4]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[4]
Carcinoma of esophagus	DISS6G4D	Strong	Altered Expression	[5]
Carcinoma of liver and intrahepatic biliary tract	DIS8WA0W	Strong	Altered Expression	[6]
Clear cell renal carcinoma	DISBXRFJ	Strong	Biomarker	[7]
Esophageal cancer	DISGB2VN	Strong	Altered Expression	[5]
Gastric cancer	DISXGOUK	Strong	Biomarker	[8]
Glioblastoma multiforme	DISK8246	Strong	Altered Expression	[2]
Glioma	DIS5RPEH	Strong	Posttranslational Modification	[9]
Lentivirus infection	DISX17PY	Strong	Altered Expression	[10]
Liver cancer	DISDE4BI	Strong	Altered Expression	[6]
Lung adenocarcinoma	DISD51WR	Strong	Biomarker	[11]
Lung cancer	DISCM4YA	Strong	Altered Expression	[5]
Neoplasm of esophagus	DISOLKAQ	Strong	Altered Expression	[5]
Obesity	DIS47Y1K	Strong	Biomarker	[12]
Stomach cancer	DISKIJSX	Strong	Biomarker	[8]
Urinary bladder cancer	DISDV4T7	Strong	Altered Expression	[3]
Urinary bladder neoplasm	DIS7HACE	Strong	Altered Expression	[3]
Advanced cancer	DISAT1Z9	moderate	Biomarker	[9]
Breast neoplasm	DISNGJLM	Limited	Altered Expression	[13]
Fetal growth restriction	DIS5WEJ5	Limited	Biomarker	[14]
Hepatocellular carcinoma	DIS0J828	Limited	Altered Expression	[6]
Nasopharyngeal carcinoma	DISAOTQ0	Limited	Altered Expression	[15]
Neoplasm	DISZKGEW	Limited	Biomarker	[15]
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⏷ Show the Full List of 27 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
Doxorubicin	DMVP5YE	Approved	Protein Mis18-beta (OIP5) affects the response to substance of Doxorubicin.	[37]
Vinblastine	DM5TVS3	Approved	Protein Mis18-beta (OIP5) affects the response to substance of Vinblastine.	[37]
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21 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Protein Mis18-beta (OIP5).	[16]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Protein Mis18-beta (OIP5).	[17]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Protein Mis18-beta (OIP5).	[18]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Protein Mis18-beta (OIP5).	[19]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Protein Mis18-beta (OIP5).	[20]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Protein Mis18-beta (OIP5).	[21]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Protein Mis18-beta (OIP5).	[22]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Protein Mis18-beta (OIP5).	[23]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Protein Mis18-beta (OIP5).	[24]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Protein Mis18-beta (OIP5).	[24]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Protein Mis18-beta (OIP5).	[25]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of Protein Mis18-beta (OIP5).	[26]
Azathioprine	DMMZSXQ	Approved	Azathioprine decreases the expression of Protein Mis18-beta (OIP5).	[27]
Palbociclib	DMD7L94	Approved	Palbociclib decreases the expression of Protein Mis18-beta (OIP5).	[28]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Protein Mis18-beta (OIP5).	[29]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Protein Mis18-beta (OIP5).	[30]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Protein Mis18-beta (OIP5).	[31]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN decreases the expression of Protein Mis18-beta (OIP5).	[33]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Protein Mis18-beta (OIP5).	[34]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Protein Mis18-beta (OIP5).	[35]
Deguelin	DMXT7WG	Investigative	Deguelin increases the expression of Protein Mis18-beta (OIP5).	[36]
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⏷ Show the Full List of 21 Drug(s)

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

Drug Name	Drug ID	Highest Status	Interaction	REF
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the phosphorylation of Protein Mis18-beta (OIP5).	[32]
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of Protein Mis18-beta (OIP5).	[32]
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References

1	Expression analysis of four testis-specific genes AURKC, OIP5, PIWIL2 and TAF7L in acute myeloid leukemia: a gender-dependent expression pattern.Med Oncol. 2013 Mar;30(1):368. doi: 10.1007/s12032-012-0368-8. Epub 2013 Jan 6.
2	Cancer-testis specific gene OIP5: a downstream gene of E2F1 that promotes tumorigenesis and metastasis in glioblastoma by stabilizing E2F1 signaling.Neuro Oncol. 2018 Aug 2;20(9):1173-1184. doi: 10.1093/neuonc/noy037.
3	OIP5 Promotes Growth, Metastasis and Chemoresistance to Cisplatin in Bladder Cancer Cells.J Cancer. 2018 Nov 24;9(24):4684-4695. doi: 10.7150/jca.27381. eCollection 2018.
4	Downregulation of long non-coding RNA Opa interacting protein 5-antisense RNA 1 inhibits breast cancer progression by targeting sex-determining region Y-box 2 by microRNA-129-5p upregulation.Cancer Sci. 2019 Jan;110(1):289-302. doi: 10.1111/cas.13879. Epub 2018 Dec 13.
5	Characterization of an Opa interacting protein 5 involved in lung and esophageal carcinogenesis.Cancer Sci. 2012 Mar;103(3):577-86. doi: 10.1111/j.1349-7006.2011.02167.x. Epub 2012 Jan 9.
6	Overexpression of Opa interacting protein5 increases the progression of liver cancer via BMPR2/JUN/CHEK1/RAC1 dysregulation.Oncol Rep. 2019 Apr;41(4):2075-2088. doi: 10.3892/or.2019.7006. Epub 2019 Feb 11.
7	Expression of Opa interacting protein 5 (OIP5) is associated with tumor stage and prognosis of clear cell renal cell carcinoma.Acta Histochem. 2013 Oct;115(8):810-5. doi: 10.1016/j.acthis.2013.03.008. Epub 2013 May 10.
8	Opa interacting protein 5 (OIP5) is a novel cancer-testis specific gene in gastric cancer.Ann Surg Oncol. 2007 Feb;14(2):885-92. doi: 10.1245/s10434-006-9121-x. Epub 2006 Dec 7.
9	OIP5 Expression Sensitize Glioblastoma Cells to Lomustine Treatment.J Mol Neurosci. 2018 Nov;66(3):383-389. doi: 10.1007/s12031-018-1184-1. Epub 2018 Oct 3.
10	Opa interacting protein 5 acts as an oncogene in bladder cancer.J Cancer Res Clin Oncol. 2017 Nov;143(11):2221-2233. doi: 10.1007/s00432-017-2485-4. Epub 2017 Jul 27.
11	Identification of an eight-gene prognostic signature for lung adenocarcinoma.Cancer Manag Res. 2018 Sep 10;10:3383-3392. doi: 10.2147/CMAR.S173941. eCollection 2018.
12	Possible involvement of Opa-interacting protein 5 in adipose proliferation and obesity.PLoS One. 2014 Feb 6;9(2):e87661. doi: 10.1371/journal.pone.0087661. eCollection 2014.
13	Cancer/Testis OIP5 and TAF7L Genes are Up-Regulated in Breast Cancer.Asian Pac J Cancer Prev. 2015;16(11):4623-8. doi: 10.7314/apjcp.2015.16.11.4623.
14	Association between expression of long noncoding RNAs in placenta and pregnancy features.Per Med. 2019 Nov;16(6):457-466. doi: 10.2217/pme-2018-0078. Epub 2019 Nov 6.
15	Opa interacting protein 5 promotes metastasis of nasopharyngeal carcinoma cells by promoting EMT via modulation of JAK2/STAT3 signal.Eur Rev Med Pharmacol Sci. 2019 Jan;23(2):613-621. doi: 10.26355/eurrev_201901_16875.
16	Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
17	Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
18	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.
19	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.
20	Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
21	Global gene expression profiles induced by phytoestrogens in human breast cancer cells. Endocr Relat Cancer. 2008 Mar;15(1):161-73.
22	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.
23	Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
24	Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
25	Methotrexate modulates folate phenotype and inflammatory profile in EA.hy 926 cells. Eur J Pharmacol. 2014 Jun 5;732:60-7.
26	Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
27	A transcriptomics-based in vitro assay for predicting chemical genotoxicity in vivo. Carcinogenesis. 2012 Jul;33(7):1421-9.
28	Cdk4/6 inhibition induces epithelial-mesenchymal transition and enhances invasiveness in pancreatic cancer cells. Mol Cancer Ther. 2012 Oct;11(10):2138-48. doi: 10.1158/1535-7163.MCT-12-0562. Epub 2012 Aug 6.
29	Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
30	Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
31	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.
32	Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
33	Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.
34	Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
35	Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
36	Neurotoxicity and underlying cellular changes of 21 mitochondrial respiratory chain inhibitors. Arch Toxicol. 2021 Feb;95(2):591-615. doi: 10.1007/s00204-020-02970-5. Epub 2021 Jan 29.
37	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.