Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT76J5R9)

• DOT Name: V-type proton ATPase subunit E 1 (ATP6V1E1)
• Synonyms: V-ATPase subunit E 1; V-ATPase 31 kDa subunit; p31; Vacuolar proton pump subunit E 1
• Gene Name: ATP6V1E1
• Related Disease:
  Acquired immune deficiency syndrome
  Advanced cancer
  Alzheimer disease
  Autosomal recessive cutis laxa type 2A
  Autosomal recessive cutis laxa type 2C
  Autosomal recessive cutis laxa type 2D
  Carcinoma
  Hepatitis B virus infection
  Lung cancer
  Lung carcinoma
  Mesothelioma
  Non-small-cell lung cancer
  Autosomal recessive cutis laxa type 2, classic type
  Nasopharyngeal carcinoma
  Type-1 diabetes
• UniProt ID: VATE1_HUMAN
• PDB ID: 6WLZ; 6WM2; 6WM3; 6WM4; 7U4T; 7UNF
• Pfam ID: PF01991
• Sequence:
  MALSDADVQKQIKHMMAFIEQEANEKAEEIDAKAEEEFNIEKGRLVQTQRLKIMEYYEKK
  EKQIEQQKKIQMSNLMNQARLKVLRARDDLITDLLNEAKQRLSKVVKDTTRYQVLLDGLV
  LQGLYQLLEPRMIVRCRKQDFPLVKAAVQKAIPMYKIATKNDVDVQIDQESYLPEDIAGG
  VEIYNGDRKIKVSNTLESRLDLIAQQMMPEVRGALFGANANRKFLD
• 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: Kidney; localizes to early distal nephron, encompassing thick ascending limbs and distal convoluted tubules (at protein level) . Ubiquitous . High expression in the skin .
• 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:HS05489-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

15 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acquired immune deficiency syndrome	DISL5UOX	Strong	Biomarker	[1]
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[2]
Alzheimer disease	DISF8S70	Strong	Altered Expression	[3]
Autosomal recessive cutis laxa type 2A	DIS9CZA4	Strong	GermlineCausalMutation	[4]
Autosomal recessive cutis laxa type 2C	DISWWS8T	Strong	Autosomal recessive	[4]
Autosomal recessive cutis laxa type 2D	DISJUYUW	Strong	GermlineCausalMutation	[4]
Carcinoma	DISH9F1N	Strong	Altered Expression	[2]
Hepatitis B virus infection	DISLQ2XY	Strong	Biomarker	[5]
Lung cancer	DISCM4YA	Strong	Biomarker	[6]
Lung carcinoma	DISTR26C	Strong	Biomarker	[6]
Mesothelioma	DISKWK9M	Strong	Biomarker	[7]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[7]
Autosomal recessive cutis laxa type 2, classic type	DISMZ113	Supportive	Autosomal recessive	[4]
Nasopharyngeal carcinoma	DISAOTQ0	Limited	Altered Expression	[8]
Type-1 diabetes	DIS7HLUB	Limited	Biomarker	[9]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of V-type proton ATPase subunit E 1 (ATP6V1E1).	[10]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of V-type proton ATPase subunit E 1 (ATP6V1E1).	[11]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of V-type proton ATPase subunit E 1 (ATP6V1E1).	[12]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of V-type proton ATPase subunit E 1 (ATP6V1E1).	[13]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of V-type proton ATPase subunit E 1 (ATP6V1E1).	[14]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of V-type proton ATPase subunit E 1 (ATP6V1E1).	[16]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of V-type proton ATPase subunit E 1 (ATP6V1E1).	[17]
chloropicrin	DMSGBQA	Investigative	chloropicrin increases the expression of V-type proton ATPase subunit E 1 (ATP6V1E1).	[18]

1 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 1 (ATP6V1E1).	[15]

References

• [1] An HTLV-III peptide produced by recombinant DNA is immunoreactive with sera from patients with AIDS.Nature. 1985 May 9-15;315(6015):151-4. doi: 10.1038/315151a0.
• [2] Epstein-Barr virus gene expression in human breast cancer: protagonist or passenger?.Br J Cancer. 2003 Jul 7;89(1):113-9. doi: 10.1038/sj.bjc.6601027.
• [3] 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.
• [4] Mutations in ATP6V1E1 or ATP6V1A Cause Autosomal-Recessive Cutis Laxa. Am J Hum Genet. 2017 Feb 2;100(2):216-227. doi: 10.1016/j.ajhg.2016.12.010. Epub 2017 Jan 5.
• [5] Polypeptides coded for by the region pre-S and gene S of hepatitis B virus DNA with the receptor for polymerized human serum albumin: expression on hepatitis B particles produced in the HBeAg or anti-HBe phase of hepatitis B virus infection.J Immunol. 1986 May 1;136(9):3467-72.
• [6] Synergistic anticancer activity of arsenic trioxide with erlotinib is based on inhibition of EGFR-mediated DNA double-strand break repair.Mol Cancer Ther. 2013 Jun;12(6):1073-84. doi: 10.1158/1535-7163.MCT-13-0065. Epub 2013 Apr 2.
• [7] Bioenergetics of acquired cisplatin resistant H1299 non-small cell lung cancer and P31 mesothelioma cells.Oncotarget. 2017 Oct 16;8(55):94711-94725. doi: 10.18632/oncotarget.21885. eCollection 2017 Nov 7.
• [8] Expression of BARF1 gene encoded by Epstein-Barr virus in nasopharyngeal carcinoma biopsies.Cancer Res. 2000 Oct 1;60(19):5584-8.
• [9] Prevention of Type 1 Diabetes with Acetalated Dextran Microparticles Containing Rapamycin and Pancreatic Peptide P31.Adv Healthc Mater. 2018 Sep;7(18):e1800341. doi: 10.1002/adhm.201800341. Epub 2018 Jul 26.
• [10] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [11] 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.
• [12] Increased mitochondrial ROS formation by acetaminophen in human hepatic cells is associated with gene expression changes suggesting disruption of the mitochondrial electron transport chain. Toxicol Lett. 2015 Apr 16;234(2):139-50.
• [13] 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.
• [14] 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.
• [15] 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.
• [16] New insights into BaP-induced toxicity: role of major metabolites in transcriptomics and contribution to hepatocarcinogenesis. Arch Toxicol. 2016 Jun;90(6):1449-58.
• [17] Environmental pollutant induced cellular injury is reflected in exosomes from placental explants. Placenta. 2020 Jan 1;89:42-49. doi: 10.1016/j.placenta.2019.10.008. Epub 2019 Oct 17.
• [18] Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.