Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTE4TBG9)

• DOT Name: ATP synthase subunit f, mitochondrial (ATP5MF)
• Synonyms: ATP synthase membrane subunit f
• Gene Name: ATP5MF
• UniProt ID: ATPK_HUMAN
• PDB ID: 8H9F; 8H9J; 8H9M; 8H9Q; 8H9S; 8H9T; 8H9U; 8H9V
• Pfam ID: PF10206
• Sequence:
  MASVGECPAPVPVKDKKLLEVKLGELPSWILMRDFSPSGIFGAFQRGYYRYYNKYINVKK
  GSISGITMVLACYVLFSYSFSYKHLKHERLRKYH
• 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:HS08550-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Vinblastine	DM5TVS3	Approved	ATP synthase subunit f, mitochondrial (ATP5MF) affects the response to substance of Vinblastine.	[16]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of ATP synthase subunit f, mitochondrial (ATP5MF).	[1]

15 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 f, mitochondrial (ATP5MF).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of ATP synthase subunit f, mitochondrial (ATP5MF).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of ATP synthase subunit f, mitochondrial (ATP5MF).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of ATP synthase subunit f, mitochondrial (ATP5MF).	[5]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of ATP synthase subunit f, mitochondrial (ATP5MF).	[6]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of ATP synthase subunit f, mitochondrial (ATP5MF).	[7]
Marinol	DM70IK5	Approved	Marinol decreases the expression of ATP synthase subunit f, mitochondrial (ATP5MF).	[8]
Niclosamide	DMJAGXQ	Approved	Niclosamide decreases the expression of ATP synthase subunit f, mitochondrial (ATP5MF).	[9]
Isotretinoin	DM4QTBN	Approved	Isotretinoin decreases the expression of ATP synthase subunit f, mitochondrial (ATP5MF).	[10]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol decreases the expression of ATP synthase subunit f, mitochondrial (ATP5MF).	[11]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of ATP synthase subunit f, mitochondrial (ATP5MF).	[12]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the expression of ATP synthase subunit f, mitochondrial (ATP5MF).	[3]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN decreases the expression of ATP synthase subunit f, mitochondrial (ATP5MF).	[13]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of ATP synthase subunit f, mitochondrial (ATP5MF).	[14]
chloropicrin	DMSGBQA	Investigative	chloropicrin increases the expression of ATP synthase subunit f, mitochondrial (ATP5MF).	[15]

References

• [1] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [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] Gene expression changes associated with cytotoxicity identified using cDNA arrays. Funct Integr Genomics. 2000 Sep;1(2):114-26.
• [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] 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.
• [7] 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.
• [8] JunD is involved in the antiproliferative effect of Delta9-tetrahydrocannabinol on human breast cancer cells. Oncogene. 2008 Aug 28;27(37):5033-44.
• [9] Growth inhibition of ovarian tumor-initiating cells by niclosamide. Mol Cancer Ther. 2012 Aug;11(8):1703-12.
• [10] 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.
• [11] Identification of biomarkers and outcomes of endocrine disruption in human ovarian cortex using In Vitro Models. Toxicology. 2023 Feb;485:153425. doi: 10.1016/j.tox.2023.153425. Epub 2023 Jan 5.
• [12] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [13] Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.
• [14] 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.
• [15] Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.
• [16] 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.