Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTM1DSKL)

• DOT Name: V-type proton ATPase subunit G 2 (ATP6V1G2)
• Synonyms: V-ATPase subunit G 2; V-ATPase 13 kDa subunit 2; Vacuolar proton pump subunit G 2
• Gene Name: ATP6V1G2
• Related Disease:
  Dilated cardiomyopathy
  Hepatitis C virus infection
  Myasthenia gravis
  Myositis disease
  Rheumatoid arthritis
  Systemic lupus erythematosus
• UniProt ID: VATG2_HUMAN
• Pfam ID: PF03179
• Sequence:
  MASQSQGIQQLLQAEKRAAEKVADARKRKARRLKQAKEEAQMEVEQYRREREHEFQSKQQ
  AAMGSQGNLSAEVEQATRRQVQGMQSSQQRNRERVLAQLLGMVCDVRPQVHPNYRISA
• 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.
• Tissue Specificity: Brain.
• 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:HS10685-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Dilated cardiomyopathy	DISX608J	Strong	Genetic Variation	[1]
Hepatitis C virus infection	DISQ0M8R	Strong	Genetic Variation	[1]
Myasthenia gravis	DISELRCI	Strong	Genetic Variation	[2]
Myositis disease	DISCIXF0	Limited	Genetic Variation	[3]
Rheumatoid arthritis	DISTSB4J	Limited	Genetic Variation	[4]
Systemic lupus erythematosus	DISI1SZ7	Limited	Genetic Variation	[5]

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 G 2 (ATP6V1G2) affects the response to substance of Cisplatin.	[13]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate affects the expression of V-type proton ATPase subunit G 2 (ATP6V1G2).	[6]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of V-type proton ATPase subunit G 2 (ATP6V1G2).	[7]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of V-type proton ATPase subunit G 2 (ATP6V1G2).	[8]
GSK2110183	DMZHB37	Phase 2	GSK2110183 increases the expression of V-type proton ATPase subunit G 2 (ATP6V1G2).	[9]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of V-type proton ATPase subunit G 2 (ATP6V1G2).	[11]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of V-type proton ATPase subunit G 2 (ATP6V1G2).	[12]

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 G 2 (ATP6V1G2).	[10]

References

• [1] The haplotype block, NFKBIL1-ATP6V1G2-BAT1-MICB-MICA, within the class III-class I boundary region of the human major histocompatibility complex may control susceptibility to hepatitis C virus-associated dilated cardiomyopathy.Tissue Antigens. 2005 Sep;66(3):200-8. doi: 10.1111/j.1399-0039.2005.00457.x.
• [2] Genome-Wide Association Study of Late-Onset Myasthenia Gravis: Confirmation of TNFRSF11A and Identification of ZBTB10 and Three Distinct HLA Associations.Mol Med. 2016 Mar;21(1):769-781. doi: 10.2119/molmed.2015.00232. Epub 2015 Nov 10.
• [3] Genome-wide association study identifies HLA 8.1 ancestral haplotype alleles as major genetic risk factors for myositis phenotypes.Genes Immun. 2015 Oct;16(7):470-80. doi: 10.1038/gene.2015.28. Epub 2015 Aug 20.
• [4] A genome-wide association study suggests contrasting associations in ACPA-positive versus ACPA-negative rheumatoid arthritis.Ann Rheum Dis. 2011 Feb;70(2):259-65. doi: 10.1136/ard.2009.126821. Epub 2010 Dec 14.
• [5] GWAS identifies novel SLE susceptibility genes and explains the association of the HLA region.Genes Immun. 2014 Sep;15(6):347-54. doi: 10.1038/gene.2014.23. Epub 2014 May 29.
• [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] 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.
• [8] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [9] Novel ATP-competitive Akt inhibitor afuresertib suppresses the proliferation of malignant pleural mesothelioma cells. Cancer Med. 2017 Nov;6(11):2646-2659. doi: 10.1002/cam4.1179. Epub 2017 Sep 27.
• [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] Cystathionine metabolic enzymes play a role in the inflammation resolution of human keratinocytes in response to sub-cytotoxic formaldehyde exposure. Toxicol Appl Pharmacol. 2016 Nov 1;310:185-194.
• [13] 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.