Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTNNHL6G)

• DOT Name: V-type proton ATPase subunit E 2 (ATP6V1E2)
• Synonyms: V-ATPase subunit E 2; Vacuolar proton pump subunit E 2
• Gene Name: ATP6V1E2
• Related Disease:
  Bipolar disorder
  Schizoaffective disorder
  Schizophrenia
• UniProt ID: VATE2_HUMAN
• Pfam ID: PF01991
• Sequence:
  MALSDVDVKKQIKHMMAFIEQEANEKAEEIDAKAEEEFNIEKGRLVQTQRLKIMEYYEKK
  EKQIEQQKKILMSTMRNQARLKVLRARNDLISDLLSEAKLRLSRIVEDPEVYQGLLDKLV
  LQGLLRLLEPVMIVRCRPQDLLLVEAAVQKAIPEYMTISQKHVEVQIDKEAYLAVNAAGG
  VEVYSGNQRIKVSNTLESRLDLSAKQKMPEIRMALFGANTNRKFFI
• 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: Testis specific.
• 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:HS10256-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Bipolar disorder	DISAM7J2	moderate	Genetic Variation	[1]
Schizoaffective disorder	DISLBW6B	moderate	Genetic Variation	[1]
Schizophrenia	DISSRV2N	moderate	Genetic Variation	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of V-type proton ATPase subunit E 2 (ATP6V1E2).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of V-type proton ATPase subunit E 2 (ATP6V1E2).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of V-type proton ATPase subunit E 2 (ATP6V1E2).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of V-type proton ATPase subunit E 2 (ATP6V1E2).	[5]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of V-type proton ATPase subunit E 2 (ATP6V1E2).	[6]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of V-type proton ATPase subunit E 2 (ATP6V1E2).	[8]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of V-type proton ATPase subunit E 2 (ATP6V1E2).	[9]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of V-type proton ATPase subunit E 2 (ATP6V1E2).	[10]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of V-type proton ATPase subunit E 2 (ATP6V1E2).	[7]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of V-type proton ATPase subunit E 2 (ATP6V1E2).	[11]

References

• [1] Genome-wide association studies of smooth pursuit and antisaccade eye movements in psychotic disorders: findings from the B-SNIP study.Transl Psychiatry. 2017 Oct 24;7(10):e1249. doi: 10.1038/tp.2017.210.
• [2] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [3] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [4] 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.
• [5] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [6] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [7] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [8] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [9] Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
• [10] 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.
• [11] 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.