Details of Drug Off-Target (DOT)

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

• DOT Name: V-type proton ATPase subunit e 1 (ATP6V0E1)
• Synonyms: V-ATPase subunit e 1; V-ATPase 9.2 kDa membrane accessory protein; V-ATPase M9.2 subunit; Vacuolar proton pump subunit e 1
• Gene Name: ATP6V0E1
• Related Disease: Alzheimer disease
• UniProt ID: VA0E1_HUMAN
• PDB ID: 6WLW; 6WM2; 6WM3; 6WM4; 7U4T; 7UNF
• Pfam ID: PF05493
• Sequence:
  MAYHGLTVPLIVMSVFWGFVGFLVPWFIPKGPNRGVIITMLVTCSVCCYLFWLIAILAQL
  NPLFGPQLKNETIWYLKYHWP
• Function: Subunit of the V0 complex of vacuolar(H+)-ATPase (V-ATPase), a multisubunit enzyme composed of a peripheral complex (V1) that hydrolyzes ATP and a membrane integral complex (V0) that translocates protons. V-ATPase is responsible for acidifying and maintaining the pH of intracellular compartments and in some cell types, is targeted to the plasma membrane, where it is responsible for acidifying the extracellular environment.
• Tissue Specificity: Ubiquitous.
• KEGG Pathway:
  Oxidative phosphorylation (hsa00190)
  Metabolic pathways (hsa01100)
  Phagosome (hsa04145)
  Sy.ptic vesicle cycle (hsa04721)
  Collecting duct acid secretion (hsa04966)
  Vibrio cholerae infection (hsa05110)
  Epithelial cell sig.ling in Helicobacter pylori infection (hsa05120)
  Human papillomavirus infection (hsa05165)
  Rheumatoid arthritis (hsa05323)
• Reactome Pathway:
  Insulin receptor recycling (R-HSA-77387)
  Transferrin endocytosis and recycling (R-HSA-917977)
  Amino acids regulate mTORC1 (R-HSA-9639288)
  Ion channel transport (R-HSA-983712)
  ROS and RNS production in phagocytes (R-HSA-1222556)
• BioCyc Pathway: MetaCyc:HS03712-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Alzheimer disease	DISF8S70	Strong	Altered Expression	[1]

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 V-type proton ATPase subunit e 1 (ATP6V0E1).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of V-type proton ATPase subunit e 1 (ATP6V0E1).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of V-type proton ATPase subunit e 1 (ATP6V0E1).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of V-type proton ATPase subunit e 1 (ATP6V0E1).	[5]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of V-type proton ATPase subunit e 1 (ATP6V0E1).	[6]
Marinol	DM70IK5	Approved	Marinol increases the expression of V-type proton ATPase subunit e 1 (ATP6V0E1).	[7]
Bortezomib	DMNO38U	Approved	Bortezomib increases the expression of V-type proton ATPase subunit e 1 (ATP6V0E1).	[8]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of V-type proton ATPase subunit e 1 (ATP6V0E1).	[10]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of V-type proton ATPase subunit e 1 (ATP6V0E1).	[11]
chloropicrin	DMSGBQA	Investigative	chloropicrin affects the expression of V-type proton ATPase subunit e 1 (ATP6V0E1).	[12]
Deguelin	DMXT7WG	Investigative	Deguelin decreases the expression of V-type proton ATPase subunit e 1 (ATP6V0E1).	[13]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of V-type proton ATPase subunit e 1 (ATP6V0E1).	[9]

References

• [1] Proteomic profiling of brain cortex tissues in a Tau transgenic mouse model of Alzheimer's disease.Biochem Biophys Res Commun. 2013 Jan 11;430(2):670-5. doi: 10.1016/j.bbrc.2012.11.093. Epub 2012 Dec 2.
• [2] The neuroprotective action of the mood stabilizing drugs lithium chloride and sodium valproate is mediated through the up-regulation of the homeodomain protein Six1. Toxicol Appl Pharmacol. 2009 Feb 15;235(1):124-34.
• [3] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [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] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [7] Single-cell Transcriptome Mapping Identifies Common and Cell-type Specific Genes Affected by Acute Delta9-tetrahydrocannabinol in Humans. Sci Rep. 2020 Feb 26;10(1):3450. doi: 10.1038/s41598-020-59827-1.
• [8] The proapoptotic effect of zoledronic acid is independent of either the bone microenvironment or the intrinsic resistance to bortezomib of myeloma cells and is enhanced by the combination with arsenic trioxide. Exp Hematol. 2011 Jan;39(1):55-65.
• [9] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [10] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [11] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [12] Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.
• [13] Neurotoxicity and underlying cellular changes of 21 mitochondrial respiratory chain inhibitors. Arch Toxicol. 2021 Feb;95(2):591-615. doi: 10.1007/s00204-020-02970-5. Epub 2021 Jan 29.