Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT7B6C6M)

• DOT Name: ATP synthase subunit ATP5MJ, mitochondrial (ATP5MJ)
• Synonyms: 6.8 kDa mitochondrial proteolipid protein; MLQ; ATP synthase membrane subunit 6.8PL
• Gene Name: ATP5MJ
• UniProt ID: ATP68_HUMAN
• PDB ID: 8H9F; 8H9J; 8H9M; 8H9Q; 8H9S; 8H9T; 8H9U; 8H9V
• Pfam ID: PF08039
• Sequence: MLQSIIKNIWIPMKPYYTKVYQEIWIGMGLMGFIVYKIRAADKRSKALKASAPAPGHH
• 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 (Probable). Minor subunit required to maintain the ATP synthase population in the mitochondria.

Molecular Interaction Atlas (MIA) of This DOT

9 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 ATP5MJ, mitochondrial (ATP5MJ).	[1]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of ATP synthase subunit ATP5MJ, mitochondrial (ATP5MJ).	[2]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of ATP synthase subunit ATP5MJ, mitochondrial (ATP5MJ).	[3]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide decreases the expression of ATP synthase subunit ATP5MJ, mitochondrial (ATP5MJ).	[4]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of ATP synthase subunit ATP5MJ, mitochondrial (ATP5MJ).	[5]
Marinol	DM70IK5	Approved	Marinol decreases the expression of ATP synthase subunit ATP5MJ, mitochondrial (ATP5MJ).	[6]
Isotretinoin	DM4QTBN	Approved	Isotretinoin decreases the expression of ATP synthase subunit ATP5MJ, mitochondrial (ATP5MJ).	[7]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of ATP synthase subunit ATP5MJ, mitochondrial (ATP5MJ).	[8]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of ATP synthase subunit ATP5MJ, mitochondrial (ATP5MJ).	[9]

References

• [1] 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.
• [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] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [4] Oxidative stress modulates theophylline effects on steroid responsiveness. Biochem Biophys Res Commun. 2008 Dec 19;377(3):797-802.
• [5] The contribution of methotrexate exposure and host factors on transcriptional variance in human liver. Toxicol Sci. 2007 Jun;97(2):582-94.
• [6] JunD is involved in the antiproliferative effect of Delta9-tetrahydrocannabinol on human breast cancer cells. Oncogene. 2008 Aug 28;27(37):5033-44.
• [7] Temporal changes in gene expression in the skin of patients treated with isotretinoin provide insight into its mechanism of action. Dermatoendocrinol. 2009 May;1(3):177-87.
• [8] Comparison of quantitation methods in proteomics to define relevant toxicological information on AhR activation of HepG2 cells by BaP. Toxicology. 2021 Jan 30;448:152652. doi: 10.1016/j.tox.2020.152652. Epub 2020 Dec 2.
• [9] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.