Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT8GTI1V)

• DOT Name: V-type proton ATPase 21 kDa proteolipid subunit c'' (ATP6V0B)
• Synonyms: V-ATPase 21 kDa proteolipid subunit c''; Vacuolar proton pump 21 kDa proteolipid subunit c''; hATPL
• Gene Name: ATP6V0B
• Related Disease: Diphtheria
• UniProt ID: VATO_HUMAN
• PDB ID: 6WLW; 6WM2; 6WM3; 6WM4; 7U4T; 7UNF
• Pfam ID: PF00137
• Sequence:
  MTGLALLYSGVFVAFWACALAVGVCYTIFDLGFRFDVAWFLTETSPFMWSNLGIGLAISL
  SVVGAAWGIYITGSSIIGGGVKAPRIKTKNLVSIIFCEAVAIYGIIMAIVISNMAEPFSA
  TDPKAIGHRNYHAGYSMFGAGLTVGLSNLFCGVCVGIVGSGAALADAQNPSLFVKILIVE
  IFGSAIGLFGVIVAILQTSRVKMGD
• Function: Proton-conducting pore forming subunit of the V0 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: Ubiquitous.
• KEGG Pathway:
  Oxidative phosphorylation (hsa00190)
  Metabolic pathways (hsa01100)
  Lysosome (hsa04142)
  Phagosome (hsa04145)
  Sy.ptic vesicle cycle (hsa04721)
  Vibrio cholerae infection (hsa05110)
  Epithelial cell sig.ling in Helicobacter pylori infection (hsa05120)
  Tuberculosis (hsa05152)
  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:ENSG00000117410-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Diphtheria	DISZWM55	Limited	Biomarker	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Irinotecan	DMP6SC2	Approved	V-type proton ATPase 21 kDa proteolipid subunit c'' (ATP6V0B) increases the response to substance of Irinotecan.	[13]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of V-type proton ATPase 21 kDa proteolipid subunit c'' (ATP6V0B).	[2]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of V-type proton ATPase 21 kDa proteolipid subunit c'' (ATP6V0B).	[12]

9 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 21 kDa proteolipid subunit c'' (ATP6V0B).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of V-type proton ATPase 21 kDa proteolipid subunit c'' (ATP6V0B).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of V-type proton ATPase 21 kDa proteolipid subunit c'' (ATP6V0B).	[5]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of V-type proton ATPase 21 kDa proteolipid subunit c'' (ATP6V0B).	[6]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of V-type proton ATPase 21 kDa proteolipid subunit c'' (ATP6V0B).	[7]
Marinol	DM70IK5	Approved	Marinol decreases the expression of V-type proton ATPase 21 kDa proteolipid subunit c'' (ATP6V0B).	[8]
Isotretinoin	DM4QTBN	Approved	Isotretinoin decreases the expression of V-type proton ATPase 21 kDa proteolipid subunit c'' (ATP6V0B).	[9]
Aspirin	DM672AH	Approved	Aspirin decreases the expression of V-type proton ATPase 21 kDa proteolipid subunit c'' (ATP6V0B).	[10]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of V-type proton ATPase 21 kDa proteolipid subunit c'' (ATP6V0B).	[11]

References

• [1] In Silico Design of Fusion Toxin DT(389)GCSF and a Comparative Study.Curr Comput Aided Drug Des. 2020;16(3):238-244. doi: 10.2174/1573409914666181012151242.
• [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] 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.
• [7] A comprehensive analysis of Wnt/beta-catenin signaling pathway-related genes and crosstalk pathways in the treatment of As2O3 in renal cancer. Ren Fail. 2018 Nov;40(1):331-339.
• [8] THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders. Transl Psychiatry. 2018 Apr 25;8(1):89. doi: 10.1038/s41398-018-0137-3.
• [9] Temporal changes in gene expression in the skin of patients treated with isotretinoin provide insight into its mechanism of action. Dermatoendocrinol. 2009 May;1(3):177-87.
• [10] Expression profile analysis of human peripheral blood mononuclear cells in response to aspirin. Arch Immunol Ther Exp (Warsz). 2005 Mar-Apr;53(2):151-8.
• [11] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [12] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [13] Gene expression analysis using human cancer xenografts to identify novel predictive marker genes for the efficacy of 5-fluorouracil-based drugs. Cancer Sci. 2006 Jun;97(6):510-22. doi: 10.1111/j.1349-7006.2006.00204.x.