Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTG7ID8U)

• DOT Name: Glutathione S-transferase A5 (GSTA5)
• Synonyms: EC 2.5.1.18; GST class-alpha member 5; Glutathione S-transferase A5-5
• Gene Name: GSTA5
• Related Disease: High blood pressure
• UniProt ID: GSTA5_HUMAN
• EC Number: 2.5.1.18
• Pfam ID: PF00043 ; PF02798
• Sequence:
  MAEKPKLHYSNARGSMESIRWLLAAAGVELEEKFLESAEDLDKLRNDGSLLFQQVPMVEI
  DGMKLVQTRAILNYIASKYNLYGKDMKERALIDMYTEGIVDLTEMILLLLICQPEERDAK
  TALVKEKIKNRYFPAFEKVLKSHRQDYLVGNKLSWADIHLVELFYYVEELDSSLISSFPL
  LKALKTRISNLPTVKKFLQPGSQRKPPMDEKSLEEARKIFRF
• Tissue Specificity: Expression not detected.
• KEGG Pathway:
  Glutathione metabolism (hsa00480)
  Metabolism of xenobiotics by cytochrome P450 (hsa00980)
  Drug metabolism - cytochrome P450 (hsa00982)
  Drug metabolism - other enzymes (hsa00983)
  Metabolic pathways (hsa01100)
  Platinum drug resistance (hsa01524)
  Pathways in cancer (hsa05200)
  Chemical carcinogenesis - D. adducts (hsa05204)
  Chemical carcinogenesis - receptor activation (hsa05207)
  Chemical carcinogenesis - reactive oxygen species (hsa05208)
  Hepatocellular carcinoma (hsa05225)
  Fluid shear stress and atherosclerosis (hsa05418)
• Reactome Pathway: Glutathione conjugation (R-HSA-156590)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
High blood pressure	DISY2OHH	Strong	Biomarker	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Glutathione S-transferase A5 (GSTA5).	[2]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Glutathione S-transferase A5 (GSTA5).	[3]
Phenobarbital	DMXZOCG	Approved	Phenobarbital decreases the expression of Glutathione S-transferase A5 (GSTA5).	[4]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Glutathione S-transferase A5 (GSTA5).	[3]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Glutathione S-transferase A5 (GSTA5).	[5]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Glutathione S-transferase A5 (GSTA5).	[7]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde decreases the expression of Glutathione S-transferase A5 (GSTA5).	[8]

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 increases the methylation of Glutathione S-transferase A5 (GSTA5).	[6]

References

• [1] A custom rat and baboon hypertension gene array to compare experimental models.Exp Biol Med (Maywood). 2012 Jan;237(1):99-110. doi: 10.1258/ebm.2011.011188. Epub 2012 Jan 6.
• [2] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [3] 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.
• [4] Dose- and time-dependent effects of phenobarbital on gene expression profiling in human hepatoma HepaRG cells. Toxicol Appl Pharmacol. 2009 Feb 1;234(3):345-60.
• [5] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [6] 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.
• [7] Bisphenol A-associated alterations in the expression and epigenetic regulation of genes encoding xenobiotic metabolizing enzymes in human fetal liver. Environ Mol Mutagen. 2014 Apr;55(3):184-95.
• [8] Transcriptome profile analysis of saturated aliphatic aldehydes reveals carbon number-specific molecules involved in pulmonary toxicity. Chem Res Toxicol. 2014 Aug 18;27(8):1362-70.