Details of Drug Off-Target (DOT)

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

• DOT Name: ATP synthase F(0) complex subunit B1, mitochondrial (ATP5PB)
• Synonyms: ATP synthase peripheral stalk-membrane subunit b; ATP synthase proton-transporting mitochondrial F(0) complex subunit B1; ATP synthase subunit b; ATPase subunit b
• Gene Name: ATP5PB
• UniProt ID: AT5F1_HUMAN
• PDB ID: 8H9F; 8H9G; 8H9J; 8H9K; 8H9M; 8H9N; 8H9Q; 8H9R; 8H9S; 8H9T; 8H9U; 8H9V
• Pfam ID: PF05405
• Sequence:
  MLSRVVLSAAATAAPSLKNAAFLGPGVLQATRTFHTGQPHLVPVPPLPEYGGKVRYGLIP
  EEFFQFLYPKTGVTGPYVLGTGLILYALSKEIYVISAETFTALSVLGVMVYGIKKYGPFV
  ADFADKLNEQKLAQLEEAKQASIQHIQNAIDTEKSQQALVQKRHYLFDVQRNNIAMALEV
  TYRERLYRVYKEVKNRLDYHISVQNMMRRKEQEHMINWVEKHVVQSISTQQEKETIAKCI
  ADLKLLAKKAQAQPVM
• Function: Mitochondrial membrane ATP synthase (F(1)F(0) ATP synthase or Complex V) produces ATP from ADP in the presence of a proton gradient across the membrane which is generated by electron transport complexes of the respiratory chain. F-type ATPases consist of two structural domains, F(1) - containing the extramembraneous catalytic core, and F(0) - containing the membrane proton channel, linked together by a central stalk and a peripheral stalk. During catalysis, ATP synthesis in the catalytic domain of F(1) is coupled via a rotary mechanism of the central stalk subunits to proton translocation. Part of the complex F(0) domain and the peripheric stalk, which acts as a stator to hold the catalytic alpha(3)beta(3) subcomplex and subunit a/ATP6 static relative to the rotary elements.
• KEGG Pathway:
  Oxidative phosphorylation (hsa00190)
  Metabolic pathways (hsa01100)
  Thermogenesis (hsa04714)
  Alzheimer disease (hsa05010)
  Parkinson disease (hsa05012)
  Amyotrophic lateral sclerosis (hsa05014)
  Huntington disease (hsa05016)
  Prion disease (hsa05020)
  Pathways of neurodegeneration - multiple diseases (hsa05022)
  Chemical carcinogenesis - reactive oxygen species (hsa05208)
  Diabetic cardiomyopathy (hsa05415)
• Reactome Pathway:
  Cristae formation (R-HSA-8949613)
  Formation of ATP by chemiosmotic coupling (R-HSA-163210)
• BioCyc Pathway: MetaCyc:HS04013-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

14 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 ATP synthase F(0) complex subunit B1, mitochondrial (ATP5PB).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of ATP synthase F(0) complex subunit B1, mitochondrial (ATP5PB).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of ATP synthase F(0) complex subunit B1, mitochondrial (ATP5PB).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of ATP synthase F(0) complex subunit B1, mitochondrial (ATP5PB).	[4]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of ATP synthase F(0) complex subunit B1, mitochondrial (ATP5PB).	[5]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of ATP synthase F(0) complex subunit B1, mitochondrial (ATP5PB).	[6]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of ATP synthase F(0) complex subunit B1, mitochondrial (ATP5PB).	[7]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil affects the expression of ATP synthase F(0) complex subunit B1, mitochondrial (ATP5PB).	[8]
Niclosamide	DMJAGXQ	Approved	Niclosamide decreases the expression of ATP synthase F(0) complex subunit B1, mitochondrial (ATP5PB).	[9]
Zidovudine	DM4KI7O	Approved	Zidovudine increases the expression of ATP synthase F(0) complex subunit B1, mitochondrial (ATP5PB).	[10]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of ATP synthase F(0) complex subunit B1, mitochondrial (ATP5PB).	[11]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of ATP synthase F(0) complex subunit B1, mitochondrial (ATP5PB).	[12]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of ATP synthase F(0) complex subunit B1, mitochondrial (ATP5PB).	[13]
chloropicrin	DMSGBQA	Investigative	chloropicrin decreases the expression of ATP synthase F(0) complex subunit B1, mitochondrial (ATP5PB).	[14]

References

• [1] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [2] 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.
• [3] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [4] 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.
• [5] 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.
• [6] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [7] 1,25-Dihydroxyvitamin D3 suppresses gene expression of eukaryotic translation initiation factor 2 in human promyelocytic leukemia HL-60 cells. Cell Struct Funct. 2005;30(1):1-6. doi: 10.1247/csf.30.1.
• [8] New insights into the mechanisms underlying 5-fluorouracil-induced intestinal toxicity based on transcriptomic and metabolomic responses in human intestinal organoids. Arch Toxicol. 2021 Aug;95(8):2691-2718. doi: 10.1007/s00204-021-03092-2. Epub 2021 Jun 20.
• [9] Growth inhibition of ovarian tumor-initiating cells by niclosamide. Mol Cancer Ther. 2012 Aug;11(8):1703-12.
• [10] Morphological and molecular course of mitochondrial pathology in cultured human cells exposed long-term to Zidovudine. Environ Mol Mutagen. 2007 Apr-May;48(3-4):179-89. doi: 10.1002/em.20245.
• [11] Comparison of quantitation methods in proteomics to define relevant toxicological information on AhR activation of HepG2 cells by BaP. Toxicology. 2021 Jan 30;448:152652. doi: 10.1016/j.tox.2020.152652. Epub 2020 Dec 2.
• [12] 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.
• [13] 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.
• [14] Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.