Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTADVEE2)

• DOT Name: ATP synthase subunit e, mitochondrial (ATP5ME)
• Synonyms: ATPase subunit e; ATP synthase membrane subunit e
• Gene Name: ATP5ME
• UniProt ID: ATP5I_HUMAN
• PDB ID: 8H9F; 8H9J; 8H9M; 8H9Q; 8H9S; 8H9T; 8H9U; 8H9V
• Pfam ID: PF05680
• Sequence:
  MVPPVQVSPLIKLGRYSALFLGVAYGATRYNYLKPRAEEERRIAAEEKKKQDELKRIARE
  LAEDDSILK
• Function: Mitochondrial membrane ATP synthase (F(1)F(0) ATP synthase or Complex V) produces ATP from ADP in the presence of a proton gradient across the membrane which is generated by electron transport complexes of the respiratory chain. F-type ATPases consist of two structural domains, F(1) - containing the extramembraneous catalytic core, and F(0) - containing the membrane proton channel, linked together by a central stalk and a peripheral stalk. During catalysis, ATP synthesis in the catalytic domain of F(1) is coupled via a rotary mechanism of the central stalk subunits to proton translocation. Part of the complex F(0) domain. Minor subunit located with subunit a in the membrane.
• KEGG Pathway:
  Oxidative phosphorylation (hsa00190)
  Metabolic pathways (hsa01100)
  Thermogenesis (hsa04714)
• Reactome Pathway:
  Cristae formation (R-HSA-8949613)
  Formation of ATP by chemiosmotic coupling (R-HSA-163210)
• BioCyc Pathway: MetaCyc:HS09866-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Drug Response of 2 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Vinblastine	DM5TVS3	Approved	ATP synthase subunit e, mitochondrial (ATP5ME) affects the response to substance of Vinblastine.	[15]
PEITC	DMOMN31	Phase 2	ATP synthase subunit e, mitochondrial (ATP5ME) affects the binding of PEITC.	[16]

1 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 ATP synthase subunit e, mitochondrial (ATP5ME).	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of ATP synthase subunit e, mitochondrial (ATP5ME).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of ATP synthase subunit e, mitochondrial (ATP5ME).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of ATP synthase subunit e, mitochondrial (ATP5ME).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of ATP synthase subunit e, mitochondrial (ATP5ME).	[5]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of ATP synthase subunit e, mitochondrial (ATP5ME).	[6]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of ATP synthase subunit e, mitochondrial (ATP5ME).	[7]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of ATP synthase subunit e, mitochondrial (ATP5ME).	[8]
Selenium	DM25CGV	Approved	Selenium decreases the expression of ATP synthase subunit e, mitochondrial (ATP5ME).	[9]
Indomethacin	DMSC4A7	Approved	Indomethacin increases the expression of ATP synthase subunit e, mitochondrial (ATP5ME).	[10]
Zidovudine	DM4KI7O	Approved	Zidovudine increases the expression of ATP synthase subunit e, mitochondrial (ATP5ME).	[11]
Bicalutamide	DMZMSPF	Approved	Bicalutamide increases the expression of ATP synthase subunit e, mitochondrial (ATP5ME).	[12]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of ATP synthase subunit e, mitochondrial (ATP5ME).	[9]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of ATP synthase subunit e, mitochondrial (ATP5ME).	[13]
Lithium chloride	DMHYLQ2	Investigative	Lithium chloride decreases the expression of ATP synthase subunit e, mitochondrial (ATP5ME).	[14]

References

• [1] Integrated 'omics analysis reveals new drug-induced mitochondrial perturbations in human hepatocytes. Toxicol Lett. 2018 Jun 1;289:1-13.
• [2] 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.
• [3] 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.
• [4] 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.
• [5] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [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] Essential role of cell cycle regulatory genes p21 and p27 expression in inhibition of breast cancer cells by arsenic trioxide. Med Oncol. 2011 Dec;28(4):1225-54.
• [8] Minimal peroxide exposure of neuronal cells induces multifaceted adaptive responses. PLoS One. 2010 Dec 17;5(12):e14352. doi: 10.1371/journal.pone.0014352.
• [9] 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.
• [10] Mechanisms of indomethacin-induced alterations in the choline phospholipid metabolism of breast cancer cells. Neoplasia. 2006 Sep;8(9):758-71.
• [11] Morphological and molecular course of mitochondrial pathology in cultured human cells exposed long-term to Zidovudine. Environ Mol Mutagen. 2007 Apr-May;48(3-4):179-89. doi: 10.1002/em.20245.
• [12] Differentially expressed genes in the prostate cancer cell line LNCaP after exposure to androgen and anti-androgen. Cancer Genet Cytogenet. 2006 Apr 15;166(2):130-8. doi: 10.1016/j.cancergencyto.2005.09.012.
• [13] 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.
• [14] Early gene response in lithium chloride induced apoptosis. Apoptosis. 2005 Jan;10(1):75-90. doi: 10.1007/s10495-005-6063-x.
• [15] Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.
• [16] Identification of potential protein targets of isothiocyanates by proteomics. Chem Res Toxicol. 2011 Oct 17;24(10):1735-43. doi: 10.1021/tx2002806. Epub 2011 Aug 26.