Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTRZQMU8)

• DOT Name: Trophinin (TRO)
• Synonyms: MAGE-D3 antigen
• Gene Name: TRO
• Related Disease:
  Advanced cancer
  Endometriosis
  Infertility
  Carcinoma of liver and intrahepatic biliary tract
  Colorectal neoplasm
  Hepatocellular carcinoma
  Liver cancer
  Lung cancer
  Lung carcinoma
  Neoplasm
  Ovarian neoplasm
  Testicular cancer
  Testicular germ cell tumor
  Breast cancer
  Breast carcinoma
  Gallbladder cancer
  Gallbladder carcinoma
• UniProt ID: TROP_HUMAN
• Pfam ID: PF01454
• Sequence:
  MDRRNDYGYRVPLFQGPLPPPGSLGLPFPPDIQTETTEEDSVLLMHTLLAATKDSLAMDP
  PVVNRPKKSKTKKAPIKTITKAAPAAPPVPAANEIATNKPKITWQALNLPVITQISQALP
  TTEVTNTQASSVTAQPKKANKMKRVTAKAAQGSQSPTGHEGGTIQLKSPLQVLKLPVISQ
  NIHAPIANESASSQALITSIKPKKASKAKKAANKAIASATEVSLAATATHTATTQGQITN
  ETASIHTTAASIRTKKASKARKTIAKVINTDTEHIEALNVTDAATRQIEASVVAIRPKKS
  KGKKAASRGPNSVSEISEAPLATQIVTNQALAATLRVKRGSRARKAATKARATESQTPNA
  DQGAQAKIASAQTNVSALETQVAAAVQALADDYLAQLSLEPTTRTRGKRNRKSKHLNGDE
  RSGSNYRRIPWGRRPAPPRDVAILQERANKLVKYLLVKDQTKIPIKRSDMLRDVIQEYDE
  YFPEIIERASYTLEKMFRVNLKEIDKQSSLYILISTQESSAGILGTTKDTPKLGLLMVIL
  SVIFMNGNKASEAVIWEVLRKLGLRPGVRHSLFGEVRKLITDEFVKQKYLEYKRVPNSRP
  PEYEFFWGLRSYHETSKMKVLKFACRVQKKDPKDWAVQYREAVEMEVQAAAVAVAEAEAR
  AEARAQMGIGEEAVAGPWNWDDMDIDCLTREELGDDAQAWSRFSFEIEARAQENADASTN
  VNFSRGASTRAGFSDGASISFNGAPSSSGGFSGGPGITFGVAPSTSASFSNTASISFGGT
  LSTSSSFSSAASISFGCAHSTSTSFSSEASISFGGMPCTSASFSGGVSSSFSGPLSTSAT
  FSGGASSGFGGTLSTTAGFSGVLSTSTSFGSAPTTSTVFSSALSTSTGFGGILSTSVCFG
  GSPSSSGSFGGTLSTSICFGGSPCTSTGFGGTLSTSVSFGGSSSTSANFGGTLSTSICFD
  GSPSTGAGFGGALNTSASFGSVLNTSTGFGGAMSTSADFGGTLSTSVCFGGSPGTSVSFG
  SALNTNAGYGGAVSTNTDFGGTLSTSVCFGGSPSTSAGFGGALNTNASFGCAVSTSASFS
  GAVSTSACFSGAPITNPGFGGAFSTSAGFGGALSTAADFGGTPSNSIGFGAAPSTSVSFG
  GAHGTSLCFGGAPSTSLCFGSASNTNLCFGGPPSTSACFSGATSPSFCDGPSTSTGFSFG
  NGLSTNAGFGGGLNTSAGFGGGLGTSAGFSGGLSTSSGFDGGLGTSAGFGGGPGTSTGFG
  GGLGTSAGFSGGLGTSAGFGGGLVTSDGFGGGLGTNASFGSTLGTSAGFSGGLSTSDGFG
  SRPNASFDRGLSTIIGFGSGSNTSTGFTGEPSTSTGFSSGPSSIVGFSGGPSTGVGFCSG
  PSTSGFSGGPSTGAGFGGGPNTGAGFGGGPSTSAGFGSGAASLGACGFSYG
• Function: Could be involved with bystin and tastin in a cell adhesion molecule complex that mediates an initial attachment of the blastocyst to uterine epithelial cells at the time of the embryo implantation. Directly responsible for homophilic cell adhesion.
• Tissue Specificity: Strong expression at implantation sites. Found in the placenta from the sixth week of pregnancy. Was localized in the cytoplasm of the syncytiotrophoblast in the chorionic villi and in endometrial decidual cells at the uteroplacental interface. After week 10, the level decreased and then disappeared from placental villi. Also found in macrophages.

Molecular Interaction Atlas (MIA) of This DOT

17 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Definitive	Altered Expression	[1]
Endometriosis	DISX1AG8	Definitive	Altered Expression	[2]
Infertility	DISAMOWP	Definitive	Altered Expression	[2]
Carcinoma of liver and intrahepatic biliary tract	DIS8WA0W	Strong	Biomarker	[3]
Colorectal neoplasm	DISR1UCN	Strong	Biomarker	[4]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[3]
Liver cancer	DISDE4BI	Strong	Biomarker	[3]
Lung cancer	DISCM4YA	Strong	Altered Expression	[5]
Lung carcinoma	DISTR26C	Strong	Altered Expression	[5]
Neoplasm	DISZKGEW	Strong	Biomarker	[6]
Ovarian neoplasm	DISEAFTY	Strong	Altered Expression	[7]
Testicular cancer	DIS6HNYO	Strong	Altered Expression	[6]
Testicular germ cell tumor	DIS5RN24	Strong	Biomarker	[6]
Breast cancer	DIS7DPX1	moderate	Biomarker	[8]
Breast carcinoma	DIS2UE88	moderate	Biomarker	[8]
Gallbladder cancer	DISXJUAF	Limited	Altered Expression	[9]
Gallbladder carcinoma	DISD6ACL	Limited	Altered Expression	[9]

12 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 Trophinin (TRO).	[10]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Trophinin (TRO).	[11]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Trophinin (TRO).	[12]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Trophinin (TRO).	[13]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Trophinin (TRO).	[14]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Trophinin (TRO).	[15]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Trophinin (TRO).	[16]
Selenium	DM25CGV	Approved	Selenium increases the expression of Trophinin (TRO).	[17]
Dexamethasone	DMMWZET	Approved	Dexamethasone decreases the expression of Trophinin (TRO).	[18]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Trophinin (TRO).	[17]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Trophinin (TRO).	[20]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of Trophinin (TRO).	[21]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Trophinin (TRO).	[19]

References

• [1] Influence of novel supramolecular substance, [2] rotaxane, on the caspase signaling pathway in melanoma and colon cancer cells in vitro.J Pharmacol Sci. 2013;122(2):153-7. doi: 10.1254/jphs.12244sc. Epub 2013 Jun 5.
• [2] Expression of trophinin in the cycling endometrium and its association with infertility.Di Yi Jun Yi Da Xue Xue Bao. 2002 Jun;22(6):539-41.
• [3] KIAA1114, a full-length protein encoded by the trophinin gene, is a novel surface marker for isolating tumor-initiating cells of multiple hepatocellular carcinoma subtypes.Oncotarget. 2014 Mar 15;5(5):1226-40. doi: 10.18632/oncotarget.1677.
• [4] The role of trophinin, an adhesion molecule unique to human trophoblasts, in progression of colorectal cancer.Int J Cancer. 2007 Sep 1;121(5):1072-8. doi: 10.1002/ijc.22821.
• [5] Identification of trophinin as an enhancer for cell invasion and a prognostic factor for early stage lung cancer.Eur J Cancer. 2007 Mar;43(4):782-90. doi: 10.1016/j.ejca.2006.09.029. Epub 2007 Jan 24.
• [6] Functional correlation of trophinin expression with the malignancy of testicular germ cell tumor.Cancer Res. 2004 Jun 15;64(12):4257-62. doi: 10.1158/0008-5472.CAN-04-0732.
• [7] Trophinin is a potent prognostic marker of ovarian cancer involved in platinum sensitivity.Biochem Biophys Res Commun. 2007 Aug 24;360(2):363-9. doi: 10.1016/j.bbrc.2007.06.070. Epub 2007 Jun 19.
• [8] Prognostic roles of MAGE family members in breast cancer based on KM-Plotter Data.Oncol Lett. 2019 Oct;18(4):3501-3516. doi: 10.3892/ol.2019.10722. Epub 2019 Aug 6.
• [9] Enhanced expression of trophinin promotes invasive and metastatic potential of human gallbladder cancer cells.J Cancer Res Clin Oncol. 2009 Apr;135(4):581-90. doi: 10.1007/s00432-008-0492-1. Epub 2008 Oct 10.
• [10] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [11] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [12] Retinoic acid receptor alpha amplifications and retinoic acid sensitivity in breast cancers. Clin Breast Cancer. 2013 Oct;13(5):401-8.
• [13] 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.
• [14] 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.
• [15] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [16] Minimal peroxide exposure of neuronal cells induces multifaceted adaptive responses. PLoS One. 2010 Dec 17;5(12):e14352. doi: 10.1371/journal.pone.0014352.
• [17] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [18] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
• [19] 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.
• [20] 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.
• [21] Transcriptome profile analysis of saturated aliphatic aldehydes reveals carbon number-specific molecules involved in pulmonary toxicity. Chem Res Toxicol. 2014 Aug 18;27(8):1362-70.