Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTS656HO)

• DOT Name: ATP synthase membrane subunit K, mitochondrial (ATP5MK)
• Synonyms: ATP synthase membrane subunit DAPIT, mitochondrial; Diabetes-associated protein in insulin-sensitive tissues; HCV F-transactivated protein 2; Up-regulated during skeletal muscle growth protein 5
• Gene Name: ATP5MK
• Related Disease: Leigh syndrome
• UniProt ID: ATPMK_HUMAN
• Pfam ID: PF14960
• Sequence: MAGPESDAQYQFTGIKKYFNSYTLTGRMNCVLATYGSIALIVLYFKLRSKKTPAVKAT
• 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. ATP5MK is a minor subunit of the mitochondrial membrane ATP synthase required for dimerization of the ATP synthase complex and as such regulates ATP synthesis in the mitochondria.

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Leigh syndrome	DISWQU45	Moderate	Autosomal recessive	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of ATP synthase membrane subunit K, mitochondrial (ATP5MK).	[2]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of ATP synthase membrane subunit K, mitochondrial (ATP5MK).	[3]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of ATP synthase membrane subunit K, mitochondrial (ATP5MK).	[4]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of ATP synthase membrane subunit K, mitochondrial (ATP5MK).	[5]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of ATP synthase membrane subunit K, mitochondrial (ATP5MK).	[6]
Marinol	DM70IK5	Approved	Marinol decreases the expression of ATP synthase membrane subunit K, mitochondrial (ATP5MK).	[7]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of ATP synthase membrane subunit K, mitochondrial (ATP5MK).	[8]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of ATP synthase membrane subunit K, mitochondrial (ATP5MK).	[9]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of ATP synthase membrane subunit K, mitochondrial (ATP5MK).	[10]

References

• [1] Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
• [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] 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.
• [5] 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.
• [6] Minimal peroxide exposure of neuronal cells induces multifaceted adaptive responses. PLoS One. 2010 Dec 17;5(12):e14352. doi: 10.1371/journal.pone.0014352.
• [7] JunD is involved in the antiproliferative effect of Delta9-tetrahydrocannabinol on human breast cancer cells. Oncogene. 2008 Aug 28;27(37):5033-44.
• [8] Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 30.
• [9] Low-dose Bisphenol A exposure alters the functionality and cellular environment in a human cardiomyocyte model. Environ Pollut. 2023 Oct 15;335:122359. doi: 10.1016/j.envpol.2023.122359. Epub 2023 Aug 9.
• [10] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.