Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT2LI8ZG)

• DOT Name: V-type proton ATPase subunit C 1 (ATP6V1C1)
• Synonyms: V-ATPase subunit C 1; Vacuolar proton pump subunit C 1
• Gene Name: ATP6V1C1
• Related Disease:
  Advanced cancer
  Neoplasm
  Oral cancer
  Breast cancer
  Breast carcinoma
• UniProt ID: VATC1_HUMAN
• PDB ID: 6WM2; 6WM3; 6WM4; 7U4T; 7UNF
• Pfam ID: PF03223
• Sequence:
  MTEFWLISAPGEKTCQQTWEKLHAATSKNNNLAVTSKFNIPDLKVGTLDVLVGLSDELAK
  LDAFVEGVVKKVAQYMADVLEDSKDKVQENLLANGVDLVTYITRFQWDMAKYPIKQSLKN
  ISEIIAKGVTQIDNDLKSRASAYNNLKGNLQNLERKNAGSLLTRSLAEIVKKDDFVLDSE
  YLVTLLVVVPKLNHNDWIKQYETLAEMVVPRSSNVLSEDQDSYLCNVTLFRKAVDDFRHK
  ARENKFIVRDFQYNEEEMKADKEEMNRLSTDKKKQFGPLVRWLKVNFSEAFIAWIHVKAL
  RVFVESVLRYGLPVNFQAMLLQPNKKTLKKLREVLHELYKHLDSSAAAIIDAPMDIPGLN
  LSQQEYYPYVYYKIDCNLLEFK
• 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. Subunit C is necessary for the assembly of the catalytic sector of the enzyme and is likely to have a specific function in its catalytic activity.
• Tissue Specificity: Ubiquitous.
• 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:HS08030-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Neoplasm	DISZKGEW	Strong	Biomarker	[1]
Oral cancer	DISLD42D	Strong	Biomarker	[2]
Breast cancer	DIS7DPX1	Limited	Altered Expression	[1]
Breast carcinoma	DIS2UE88	Limited	Altered Expression	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cisplatin	DMRHGI9	Approved	V-type proton ATPase subunit C 1 (ATP6V1C1) affects the response to substance of Cisplatin.	[15]

12 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 C 1 (ATP6V1C1).	[3]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of V-type proton ATPase subunit C 1 (ATP6V1C1).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of V-type proton ATPase subunit C 1 (ATP6V1C1).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of V-type proton ATPase subunit C 1 (ATP6V1C1).	[6]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of V-type proton ATPase subunit C 1 (ATP6V1C1).	[7]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of V-type proton ATPase subunit C 1 (ATP6V1C1).	[8]
Selenium	DM25CGV	Approved	Selenium decreases the expression of V-type proton ATPase subunit C 1 (ATP6V1C1).	[9]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of V-type proton ATPase subunit C 1 (ATP6V1C1).	[9]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of V-type proton ATPase subunit C 1 (ATP6V1C1).	[11]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of V-type proton ATPase subunit C 1 (ATP6V1C1).	[12]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of V-type proton ATPase subunit C 1 (ATP6V1C1).	[13]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of V-type proton ATPase subunit C 1 (ATP6V1C1).	[14]

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 C 1 (ATP6V1C1).	[10]

References

• [1] Osteoclast proton pump regulator Atp6v1c1 enhances breast cancer growth by activating the mTORC1 pathway and bone metastasis by increasing V-ATPase activity.Oncotarget. 2017 Jul 18;8(29):47675-47690. doi: 10.18632/oncotarget.17544.
• [2] Expression of ATP6V1C1 during oral carcinogenesis.Biotech Histochem. 2016;91(4):263-8. doi: 10.3109/10520295.2016.1144078. Epub 2016 Mar 16.
• [3] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [4] 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.
• [5] 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.
• [6] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [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] Integrated assessment by multiple gene expression analysis of quercetin bioactivity on anticancer-related mechanisms in colon cancer cells in vitro. Eur J Nutr. 2005 Mar;44(3):143-56. doi: 10.1007/s00394-004-0503-1. Epub 2004 Apr 30.
• [9] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [10] 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.
• [11] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [12] 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.
• [13] A trichostatin A expression signature identified by TempO-Seq targeted whole transcriptome profiling. PLoS One. 2017 May 25;12(5):e0178302. doi: 10.1371/journal.pone.0178302. eCollection 2017.
• [14] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [15] Role of transporter genes in cisplatin resistance. In Vivo. 2008 May-Jun;22(3):279-83.