Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTPQ7FPQ)

• DOT Name: Translation initiation factor IF-3, mitochondrial (MTIF3)
• Synonyms: IF-3(Mt); IF-3Mt; IF3(mt); IF3mt
• Gene Name: MTIF3
• Related Disease:
  Obesity
  Parkinson disease
• UniProt ID: IF3M_HUMAN
• PDB ID: 6NEQ; 6NF8; 6RW4; 6RW5; 7P2E
• Pfam ID: PF05198
• Sequence:
  MAALFLKRLTLQTVKSENSCIRCFGKHILQKTAPAQLSPIASAPRLSFLIHAKAFSTAED
  TQNEGKKTKKNKTAFSNVGRKISQRVIHLFDEKGNDLGNMHRANVIRLMDERDLRLVQRN
  TSTEPAEYQLMTGLQILQERQRLREMEKANPKTGPTLRKELILSSNIGQHDLDTKTKQIQ
  QWIKKKHLVQITIKKGKNVDVSENEMEEIFHQILQTMPGIATFSSRPQAVQGGKALMCVL
  RAFSKNEEKAYKETQETQERDTLNKDHGNDKESNVLHQ
• Function: IF-3 binds to the 28S ribosomal subunit and shifts the equilibrium between 55S ribosomes and their 39S and 28S subunits in favor of the free subunits, thus enhancing the availability of 28S subunits on which protein synthesis initiation begins.
• Reactome Pathway: Mitochondrial translation initiation (R-HSA-5368286)

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Obesity	DIS47Y1K	Strong	Genetic Variation	[1]
Parkinson disease	DISQVHKL	Strong	Biomarker	[2]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Josamycin	DMKJ8LB	Approved	Translation initiation factor IF-3, mitochondrial (MTIF3) decreases the response to substance of Josamycin.	[14]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate affects the expression of Translation initiation factor IF-3, mitochondrial (MTIF3).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Translation initiation factor IF-3, mitochondrial (MTIF3).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Translation initiation factor IF-3, mitochondrial (MTIF3).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Translation initiation factor IF-3, mitochondrial (MTIF3).	[6]
Cisplatin	DMRHGI9	Approved	Cisplatin affects the expression of Translation initiation factor IF-3, mitochondrial (MTIF3).	[7]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Translation initiation factor IF-3, mitochondrial (MTIF3).	[8]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Translation initiation factor IF-3, mitochondrial (MTIF3).	[9]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Translation initiation factor IF-3, mitochondrial (MTIF3).	[10]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Translation initiation factor IF-3, mitochondrial (MTIF3).	[11]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Translation initiation factor IF-3, mitochondrial (MTIF3).	[7]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Translation initiation factor IF-3, mitochondrial (MTIF3).	[13]

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 Translation initiation factor IF-3, mitochondrial (MTIF3).	[12]

References

• [1] Recapitulation of genome-wide association studies on body mass index in the Korean population.Int J Obes (Lond). 2012 Aug;36(8):1127-30. doi: 10.1038/ijo.2011.202. Epub 2011 Nov 1.
• [2] Mitochondrial translation initiation factor 3 polymorphism and Parkinson's disease.Neurosci Lett. 2010 Dec 17;486(3):228-30. doi: 10.1016/j.neulet.2010.09.059. Epub 2010 Sep 29.
• [3] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [4] Increased mitochondrial ROS formation by acetaminophen in human hepatic cells is associated with gene expression changes suggesting disruption of the mitochondrial electron transport chain. Toxicol Lett. 2015 Apr 16;234(2):139-50.
• [5] 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.
• [6] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [7] Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
• [8] Genistein and bisphenol A exposure cause estrogen receptor 1 to bind thousands of sites in a cell type-specific manner. Genome Res. 2012 Nov;22(11):2153-62.
• [9] 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.
• [10] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [11] Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
• [12] 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.
• [13] 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.
• [14] A genome-wide analysis of targets of macrolide antibiotics in mammalian cells. J Biol Chem. 2020 Feb 14;295(7):2057-2067. doi: 10.1074/jbc.RA119.010770. Epub 2020 Jan 8.