Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTSTT8JG)

• DOT Name: V-type proton ATPase subunit F (ATP6V1F)
• Synonyms: V-ATPase subunit F; V-ATPase 14 kDa subunit; Vacuolar proton pump subunit F
• Gene Name: ATP6V1F
• Related Disease:
  Invasive candidiasis
  Prostate carcinoma
• UniProt ID: VATF_HUMAN
• PDB ID: 6WLZ; 6WM2; 6WM3; 6WM4; 7U4T; 7UNF
• Pfam ID: PF01990
• Sequence:
  MAGRGKLIAVIGDEDTVTGFLLGGIGELNKNRHPNFLVVEKDTTINEIEDTFRQFLNRDD
  IGIILINQYIAEMVRHALDAHQQSIPAVLEIPSKEHPYDAAKDSILRRARGMFTAEDLR
• Function: Subunit of the V1 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.
• KEGG Pathway:
  Oxidative phosphorylation (hsa00190)
  Metabolic pathways (hsa01100)
  Phagosome (hsa04145)
  mTOR sig.ling pathway (hsa04150)
  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:HS05192-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Invasive candidiasis	DIS5EI0L	Strong	Genetic Variation	[1]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[2]

6 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 V-type proton ATPase subunit F (ATP6V1F).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of V-type proton ATPase subunit F (ATP6V1F).	[4]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of V-type proton ATPase subunit F (ATP6V1F).	[5]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol decreases the expression of V-type proton ATPase subunit F (ATP6V1F).	[6]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of V-type proton ATPase subunit F (ATP6V1F).	[7]
chloropicrin	DMSGBQA	Investigative	chloropicrin increases the expression of V-type proton ATPase subunit F (ATP6V1F).	[8]

References

• [1] The putative vacuolar ATPase subunit Vma7p of Candida albicans is involved in vacuole acidification, hyphal development and virulence.Microbiology (Reading). 2005 May;151(Pt 5):1645-1655. doi: 10.1099/mic.0.27505-0.
• [2] Up-regulated expression of the MAT-8 gene in prostate cancer and its siRNA-mediated inhibition of expression induces a decrease in proliferation of human prostate carcinoma cells.Int J Oncol. 2004 Jan;24(1):97-105.
• [3] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [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] 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] 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.
• [7] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [8] Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.