Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT8YMDJJ)

• DOT Name: Elongation factor Tu, mitochondrial
• Synonyms: EF-Tu; P43
• Gene Name: TUFM
• Related Disease: Combined oxidative phosphorylation defect type 4
• UniProt ID: EFTU_HUMAN
• PDB ID: 7A5G; 7O9K
• Pfam ID: PF00009 ; PF03144 ; PF03143
• Sequence:
  MTTMAAATLLRATPHFSGLAAGRTFLLQGLLRLLKAPALPLLCRGLAVEAKKTYVRDKPH
  VNVGTIGHVDHGKTTLTAAITKILAEGGGAKFKKYEEIDNAPEERARGITINAAHVEYST
  AARHYAHTDCPGHADYVKNMITGTAPLDGCILVVAANDGPMPQTREHLLLARQIGVEHVV
  VYVNKADAVQDSEMVELVELEIRELLTEFGYKGEETPVIVGSALCALEGRDPELGLKSVQ
  KLLDAVDTYIPVPARDLEKPFLLPVEAVYSVPGRGTVVTGTLERGILKKGDECELLGHSK
  NIRTVVTGIEMFHKSLERAEAGDNLGALVRGLKREDLRRGLVMVKPGSIKPHQKVEAQVY
  ILSKEEGGRHKPFVSHFMPVMFSLTWDMACRIILPPEKELAMPGEDLKFNLILRQPMILE
  KGQRFTLRDGNRTIGTGLVTNTLAMTEEEKNIKWG
• Function: Promotes the GTP-dependent binding of aminoacyl-tRNA to the A-site of ribosomes during protein biosynthesis. Also plays a role in the regulation of autophagy and innate immunity. Recruits ATG5-ATG12 and NLRX1 at mitochondria and serves as a checkpoint of the RIGI-MAVS pathway. In turn, inhibits RLR-mediated type I interferon while promoting autophagy.
• Reactome Pathway:
  SARS-CoV-2 modulates autophagy (R-HSA-9754560)
  Mitochondrial translation elongation (R-HSA-5389840)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Combined oxidative phosphorylation defect type 4	DISOFV38	Strong	Autosomal recessive	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Temozolomide	DMKECZD	Approved	Elongation factor Tu, mitochondrial affects the response to substance of Temozolomide.	[13]
DTI-015	DMXZRW0	Approved	Elongation factor Tu, mitochondrial affects the response to substance of DTI-015.	[13]
Artesunate	DMR27C8	Approved	Elongation factor Tu, mitochondrial decreases the response to substance of Artesunate.	[14]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Elongation factor Tu, mitochondrial.	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Elongation factor Tu, mitochondrial.	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Elongation factor Tu, mitochondrial.	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Elongation factor Tu, mitochondrial.	[5]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Elongation factor Tu, mitochondrial.	[6]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Elongation factor Tu, mitochondrial.	[7]
Dopamine	DMPGUCF	Approved	Dopamine increases the expression of Elongation factor Tu, mitochondrial.	[8]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Elongation factor Tu, mitochondrial.	[9]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Elongation factor Tu, mitochondrial.	[10]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Elongation factor Tu, mitochondrial.	[11]
Paraoxon	DMN4ZKC	Investigative	Paraoxon increases the expression of Elongation factor Tu, mitochondrial.	[12]

References

• [1] Infantile encephalopathy and defective mitochondrial DNA translation in patients with mutations of mitochondrial elongation factors EFG1 and EFTu. Am J Hum Genet. 2007 Jan;80(1):44-58. doi: 10.1086/510559. Epub 2006 Nov 15.
• [2] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [3] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [4] Human 3D multicellular microtissues: an upgraded model for the in vitro mechanistic investigation of inflammation-associated drug toxicity. Toxicol Lett. 2019 Sep 15;312:34-44.
• [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] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [7] Quantitative proteomic analysis of HepG2 cells treated with quercetin suggests IQGAP1 involved in quercetin-induced regulation of cell proliferation and migration. OMICS. 2009 Apr;13(2):93-103. doi: 10.1089/omi.2008.0075.
• [8] Mitochondrial proteomics investigation of a cellular model of impaired dopamine homeostasis, an early step in Parkinson's disease pathogenesis. Mol Biosyst. 2014 Jun;10(6):1332-44.
• [9] Differential protein expression of peroxiredoxin I and II by benzo(a)pyrene and quercetin treatment in 22Rv1 and PrEC prostate cell lines. Toxicol Appl Pharmacol. 2007 Apr 15;220(2):197-210. doi: 10.1016/j.taap.2006.12.030. Epub 2007 Jan 9.
• [10] 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.
• [11] Alternatives for the worse: Molecular insights into adverse effects of bisphenol a and substitutes during human adipocyte differentiation. Environ Int. 2021 Nov;156:106730. doi: 10.1016/j.envint.2021.106730. Epub 2021 Jun 27.
• [12] Paraoxon-induced protein expression changes to SH-SY5Y cells. Chem Res Toxicol. 2010 Nov 15;23(11):1656-62. doi: 10.1021/tx100192f. Epub 2010 Oct 8.
• [13] Tumor necrosis factor-alpha-induced protein 3 as a putative regulator of nuclear factor-kappaB-mediated resistance to O6-alkylating agents in human glioblastomas. J Clin Oncol. 2006 Jan 10;24(2):274-87. doi: 10.1200/JCO.2005.02.9405. Epub 2005 Dec 19.
• [14] Factors determining sensitivity or resistance of tumor cell lines towards artesunate. Chem Biol Interact. 2010 Apr 15;185(1):42-52.