Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTQGJWI0)

• DOT Name: Non-homologous end joining factor IFFO1 (IFFO1)
• Synonyms: NHEJ factor IFFO1; Intermediate filament family orphan 1; Tumor antigen HOM-TES-103
• Gene Name: IFFO1
• Related Disease:
  Epithelial ovarian cancer
  Ovarian cancer
  Ovarian neoplasm
• UniProt ID: IFFO1_HUMAN
• PDB ID: 6ABO
• Sequence:
  MNPLFGPNLFLLQQEQQGLAGPLGDSLGGDHFAGGGDLPPAPLSPAGPAAYSPPGPGPAP
  PAAMALRNDLGSNINVLKTLNLRFRCFLAKVHELERRNRLLEKQLQQALEEGKQGRRGLG
  RRDQAVQTGFVSPIRPLGLQLGARPAAVCSPSARVLGSPARSPAGPLAPSAASLSSSSTS
  TSTTYSSSARFMPGTIWSFSHARRLGPGLEPTLVQGPGLSWVHPDGVGVQIDTITPEIRA
  LYNVLAKVKRERDEYKRRWEEEYTVRIQLQDRVNELQEEAQEADACQEELALKVEQLKAE
  LVVFKGLMSNNLSELDTKIQEKAMKVDMDICRRIDITAKLCDVAQQRNCEDMIQMFQVPS
  MGGRKRERKAAVEEDTSLSESEGPRQPDGDEEESTALSINEEMQRMLNQLREYDFEDDCD
  SLTWEETEETLLLWEDFSGYAMAAAEAQGEQEDSLEKVIKDTESLFKTREKEYQETIDQI
  ELELATAKNDMNRHLHEYMEMCSMKRGLDVQMETCRRLITQSGDRKSPAFTAVPLSDPPP
  PPSEAEDSDRDVSSDSSMR
• Function: Nuclear matrix protein involved in the immobilization of broken DNA ends and the suppression of chromosome translocation during DNA double-strand breaks (DSBs). Interacts with the nuclear lamina component LMNA, resulting in the formation of a nucleoskeleton that relocalizes to the DSB sites in a XRCC4-dependent manner and promotes the immobilization of the broken ends, thereby preventing chromosome translocation. Acts as a scaffold that allows the DNA repair protein XRCC4 and LMNA to assemble into a complex at the DSB sites.
• Tissue Specificity: Ubiquitously expressed.

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Epithelial ovarian cancer	DIS56MH2	Limited	Biomarker	[1]
Ovarian cancer	DISZJHAP	Limited	Biomarker	[1]
Ovarian neoplasm	DISEAFTY	Limited	Biomarker	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Non-homologous end joining factor IFFO1 (IFFO1).	[2]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Non-homologous end joining factor IFFO1 (IFFO1).	[3]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Non-homologous end joining factor IFFO1 (IFFO1).	[4]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Non-homologous end joining factor IFFO1 (IFFO1).	[5]

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 decreases the methylation of Non-homologous end joining factor IFFO1 (IFFO1).	[6]

References

• [1] Genome-scale screen for DNA methylation-based detection markers for ovarian cancer.PLoS One. 2011;6(12):e28141. doi: 10.1371/journal.pone.0028141. Epub 2011 Dec 7.
• [2] 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.
• [3] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [4] Identification of vitamin D3 target genes in human breast cancer tissue. J Steroid Biochem Mol Biol. 2016 Nov;164:90-97.
• [5] 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.
• [6] 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.