Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTAIOZ0J)

• DOT Name: Translation initiation factor IF-2, mitochondrial (MTIF2)
• Synonyms: IF-2(Mt); IF-2Mt; IF2(mt)
• Gene Name: MTIF2
• UniProt ID: IF2M_HUMAN
• PDB ID: 6GAW; 6GAZ; 6GB2; 6RW5; 7PO2
• Pfam ID: PF00009 ; PF11987
• Sequence:
  MNQKLLKLENLLRFHTIYRQLHSLCQRRALRQWRHGFSSAYPVWTAQLCAWPWPTDVLTG
  AALSQYRLLVTKKEEGPWKSQLSSTKSKKVVEVWIGMTIEELARAMEKNTDYVYEALLNT
  DIDIDSLEADSHLDEVWIKEVITKAGMKLKWSKLKQDKVRKNKDAVRRPQADPALLTPRS
  PVVTIMGHVDHGKTTLLDKFRKTQVAAVETGGITQHIGAFLVSLPSGEKITFLDTPGHAA
  FSAMRARGAQVTDIVVLVVAADDGVMKQTVESIQHAKDAQVPIILAVNKCDKAEADPEKV
  KKELLAYDVVCEDYGGDVQAVPVSALTGDNLMALAEATVALAEMLELKADPNGPVEGTVI
  ESFTDKGRGLVTTAIIQRGTLRKGSVLVAGKCWAKVRLMFDENGKTIDEAYPSMPVGITG
  WRDLPSAGEEILEVESEPRAREVVDWRKYEQEQEKGQEDLKIIEEKRKEHKEAHQKAREK
  YGHLLWKKRSILRFLERKEQIPLKPKEKRERDSNVLSVIIKGDVDGSVEAILNIIDTYDA
  SHECELELVHFGVGDVSANDVNLAETFDGVIYGFNVNAGNVIQQSAAKKGVKIKLHKIIY
  RLVEDLQEELSSRLPCAVEEHPVGEASILATFSVTEGKKKVPVAGCRVQKGQLEKQKKFK
  LTRNGHVIWKGSLTSLKHHKDDISIVKTGMDCGLSLDEDNMEFQVGDRIVCYEEKQIQAK
  TSWDPGF
• Function: One of the essential components for the initiation of protein synthesis. Protects formylmethionyl-tRNA from spontaneous hydrolysis and promotes its binding to the 30S ribosomal subunits. Also involved in the hydrolysis of GTP during the formation of the 70S ribosomal complex.
• Tissue Specificity: Expressed in all tissues examined. Highest level in skeletal muscle.
• Reactome Pathway: Mitochondrial translation initiation (R-HSA-5368286)

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Drug Response of 3 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Josamycin	DMKJ8LB	Approved	Translation initiation factor IF-2, mitochondrial (MTIF2) decreases the response to substance of Josamycin.	[10]
Chloramphenicol	DMFXEWT	Approved	Translation initiation factor IF-2, mitochondrial (MTIF2) decreases the response to substance of Chloramphenicol.	[10]
Clarithromycin	DM4M1SG	Approved	Translation initiation factor IF-2, mitochondrial (MTIF2) decreases the response to substance of Clarithromycin.	[10]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Translation initiation factor IF-2, mitochondrial (MTIF2).	[1]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Translation initiation factor IF-2, mitochondrial (MTIF2).	[2]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Translation initiation factor IF-2, mitochondrial (MTIF2).	[3]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Translation initiation factor IF-2, mitochondrial (MTIF2).	[5]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Translation initiation factor IF-2, mitochondrial (MTIF2).	[6]
Nicotine	DMWX5CO	Approved	Nicotine increases the expression of Translation initiation factor IF-2, mitochondrial (MTIF2).	[7]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Translation initiation factor IF-2, mitochondrial (MTIF2).	[8]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of Translation initiation factor IF-2, mitochondrial (MTIF2).	[9]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Translation initiation factor IF-2, mitochondrial (MTIF2).	[4]

References

• [1] 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.
• [2] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [3] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [4] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [5] 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.
• [6] 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.
• [7] Nicotinic modulation of gene expression in SH-SY5Y neuroblastoma cells. Brain Res. 2006 Oct 20;1116(1):39-49.
• [8] Epigenetic influences of low-dose bisphenol A in primary human breast epithelial cells. Toxicol Appl Pharmacol. 2010 Oct 15;248(2):111-21.
• [9] A trichostatin A expression signature identified by TempO-Seq targeted whole transcriptome profiling. PLoS One. 2017 May 25;12(5):e0178302. doi: 10.1371/journal.pone.0178302. eCollection 2017.
• [10] 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.