Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTPYXV64)

• DOT Name: Fetal and adult testis-expressed transcript protein (FATE1)
• Synonyms: Cancer/testis antigen 43; CT43; Tumor antigen BJ-HCC-2
• Gene Name: FATE1
• Related Disease:
  Ewing sarcoma
  Irritable bowel syndrome
  Niemann-Pick disease type C
  Pancreatic cancer
  Adrenocortical carcinoma
  Aplasia cutis congenita
  Corpus callosum, agenesis of
  Hepatocellular carcinoma
  Neoplasm
• UniProt ID: FATE1_HUMAN
• Pfam ID: PF05644
• Sequence:
  MAGGPPNTKAEMEMSLAEELNHGRQGENQEHLVIAEMMELGSRSRGASQKKQKLEQKAAG
  SASAKRVWNMTATRPKKMGSQLPKPRMLRESGHGDAHLQEYAGNFQGIRFHYDRNPGTDA
  VAQTSLEEFNVLEMEVMRRQLYAVNRRLRALEEQGATWRHRETLIIAVLVSASIANLWLW
  MNQ
• Function: Involved in the regulation of endoplasmic reticulum (ER)-mitochondria coupling. Negatively regulates the ER-mitochondria distance and Ca(2+) transfer from ER to mitochondria possibly implicating it in the regulation of apoptosis. May collaborate with RNF183 to restrain BIK protein levels thus regulating apoptotic signaling.
• Tissue Specificity: Testis-specific in fetus (aged from 6 to 11 weeks). In adult, expressed predominantly in testis, with some expression in lung, heart, kidney, adrenal gland and whole brain . Highly expressed in certain types of cancer tissues such as hepatocellular carcinoma, colon and gastric cancer. Weakly expressed in normal pancreas .

Molecular Interaction Atlas (MIA) of This DOT

9 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Ewing sarcoma	DISQYLV3	Strong	Biomarker	[1]
Irritable bowel syndrome	DIS27206	Strong	Genetic Variation	[2]
Niemann-Pick disease type C	DIS492ZO	moderate	Biomarker	[3]
Pancreatic cancer	DISJC981	moderate	Posttranslational Modification	[4]
Adrenocortical carcinoma	DISZF4HX	Limited	Altered Expression	[5]
Aplasia cutis congenita	DISMDAYM	Limited	Altered Expression	[5]
Corpus callosum, agenesis of	DISO9P40	Limited	Altered Expression	[5]
Hepatocellular carcinoma	DIS0J828	Limited	Biomarker	[6]
Neoplasm	DISZKGEW	Limited	Altered Expression	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Fetal and adult testis-expressed transcript protein (FATE1).	[7]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Fetal and adult testis-expressed transcript protein (FATE1).	[9]

1 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Decitabine	DMQL8XJ	Approved	Decitabine increases the expression of Fetal and adult testis-expressed transcript protein (FATE1).	[8]

References

• [1] EWSR1-FLI1 Activation of the Cancer/Testis Antigen FATE1 Promotes Ewing Sarcoma Survival.Mol Cell Biol. 2019 Jun 27;39(14):e00138-19. doi: 10.1128/MCB.00138-19. Print 2019 Jul 15.
• [2] Lactase persistence/non-persistence genetic variants in irritable bowel syndrome in an endemic area for lactose malabsorption.J Gastroenterol Hepatol. 2012 Dec;27(12):1825-30. doi: 10.1111/j.1440-1746.2012.07259.x.
• [3] Automated microscopy screening for compounds that partially revert cholesterol accumulation in Niemann-Pick C cells.J Lipid Res. 2006 Feb;47(2):284-301. doi: 10.1194/jlr.M500388-JLR200. Epub 2005 Nov 15.
• [4] Ring1b-dependent epigenetic remodelling is an essential prerequisite for pancreatic carcinogenesis.Gut. 2019 Nov;68(11):2007-2018. doi: 10.1136/gutjnl-2018-317208. Epub 2019 Apr 6.
• [5] FATE1 antagonizes calcium- and drug-induced apoptosis by uncoupling ER and mitochondria.EMBO Rep. 2016 Sep;17(9):1264-80. doi: 10.15252/embr.201541504. Epub 2016 Jul 11.
• [6] Immunohistochemical analysis of the expression of FATE/BJ-HCC-2 antigen in normal and malignant tissues.Lab Invest. 2005 Feb;85(2):205-13. doi: 10.1038/labinvest.3700220.
• [7] 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.
• [8] Treatment of chronic lymphocytic leukemia with a hypomethylating agent induces expression of NXF2, an immunogenic cancer testis antigen. Clin Cancer Res. 2009 May 15;15(10):3406-15. doi: 10.1158/1078-0432.CCR-08-2099. Epub 2009 Apr 28.
• [9] 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.