Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTMMBFY8)

• DOT Name: Glutathione S-transferase Mu 5 (GSTM5)
• Synonyms: EC 2.5.1.18; GST class-mu 5; GSTM5-5
• Gene Name: GSTM5
• Related Disease:
  Age-related macular degeneration
  Breast cancer
  Breast carcinoma
  Colon cancer
  Colonic neoplasm
  High blood pressure
  Ovarian serous cystadenocarcinoma
  Prostate cancer
  Prostate carcinoma
  Psychotic disorder
• UniProt ID: GSTM5_HUMAN
• EC Number: 2.5.1.18
• Pfam ID: PF00043 ; PF02798
• Sequence:
  MPMTLGYWDIRGLAHAIRLLLEYTDSSYVEKKYTLGDAPDYDRSQWLNEKFKLGLDFPNL
  PYLIDGAHKITQSNAILRYIARKHNLCGETEEEKIRVDILENQVMDNHMELVRLCYDPDF
  EKLKPKYLEELPEKLKLYSEFLGKRPWFAGDKITFVDFLAYDVLDMKRIFEPKCLDAFLN
  LKDFISRFEGLKKISAYMKSSQFLRGLLFGKSATWNSK
• Function: Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles.
• 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

10 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Age-related macular degeneration	DIS0XS2C	Strong	Biomarker	[1]
Breast cancer	DIS7DPX1	Strong	Genetic Variation	[2]
Breast carcinoma	DIS2UE88	Strong	Genetic Variation	[2]
Colon cancer	DISVC52G	Strong	Biomarker	[3]
Colonic neoplasm	DISSZ04P	Strong	Biomarker	[3]
High blood pressure	DISY2OHH	Strong	Genetic Variation	[4]
Ovarian serous cystadenocarcinoma	DISMYAWR	Strong	Biomarker	[5]
Prostate cancer	DISF190Y	Strong	Biomarker	[6]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[6]
Psychotic disorder	DIS4UQOT	Disputed	Biomarker	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Paclitaxel	DMLB81S	Approved	Glutathione S-transferase Mu 5 (GSTM5) decreases the response to substance of Paclitaxel.	[14]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Glutathione S-transferase Mu 5 (GSTM5).	[8]
Dasatinib	DMJV2EK	Approved	Dasatinib increases the expression of Glutathione S-transferase Mu 5 (GSTM5).	[9]
Beta-carotene	DM0RXBT	Approved	Beta-carotene increases the expression of Glutathione S-transferase Mu 5 (GSTM5).	[10]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Glutathione S-transferase Mu 5 (GSTM5).	[11]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Glutathione S-transferase Mu 5 (GSTM5).	[13]

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 Mu 5 (GSTM5).	[12]

References

• [1] GSTM1 and GSTM5 Genetic Polymorphisms and Expression in Age-Related Macular Degeneration.Curr Eye Res. 2016;41(3):410-6. doi: 10.3109/02713683.2015.1016179. Epub 2015 Apr 21.
• [2] Genetic variants in GSTM3 gene within GSTM4-GSTM2-GSTM1-GSTM5-GSTM3 cluster influence breast cancer susceptibility depending on GSTM1.Breast Cancer Res Treat. 2010 Jun;121(2):485-96. doi: 10.1007/s10549-009-0585-9. Epub 2009 Oct 24.
• [3] Global gene expression analysis of rat colon cancers induced by a food-borne carcinogen, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine.Carcinogenesis. 2004 Aug;25(8):1495-505. doi: 10.1093/carcin/bgh155. Epub 2004 Apr 1.
• [4] Glutathione S-transferase variants and hypertension.J Hypertens. 2008 Jul;26(7):1343-52. doi: 10.1097/HJH.0b013e3282fe1d67.
• [5] A comprehensive understanding of ovarian carcinoma survival prognosis by novel biomarkers.Eur Rev Med Pharmacol Sci. 2019 Oct;23(19):8257-8264. doi: 10.26355/eurrev_201910_19136.
• [6] Bioinformatics Analysis of Stromal Molecular Signatures Associated with Breast and Prostate Cancer.J Comput Biol. 2019 Oct;26(10):1130-1139. doi: 10.1089/cmb.2019.0045. Epub 2019 Jun 11.
• [7] Longitudinal Analyses of Blood Transcriptome During Conversion to Psychosis.Schizophr Bull. 2019 Jan 1;45(1):247-255. doi: 10.1093/schbul/sby009.
• [8] Identification of biomarkers for the initiation of apoptosis in human preneoplastic colonocytes by proteome analysis. Int J Cancer. 2004 Mar 20;109(2):220-9. doi: 10.1002/ijc.11692.
• [9] Dasatinib reverses cancer-associated fibroblasts (CAFs) from primary lung carcinomas to a phenotype comparable to that of normal fibroblasts. Mol Cancer. 2010 Jun 27;9:168.
• [10] Beta-carotene and apocarotenals promote retinoid signaling in BEAS-2B human bronchioepithelial cells. Arch Biochem Biophys. 2006 Nov 1;455(1):48-60.
• [11] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [12] 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.
• [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] cDNA microarray analysis of isogenic paclitaxel- and doxorubicin-resistant breast tumor cell lines reveals distinct drug-specific genetic signatures of resistance. Breast Cancer Res Treat. 2006 Mar;96(1):17-39. doi: 10.1007/s10549-005-9026-6. Epub 2005 Dec 2.