Details of Drug Off-Target (DOT)

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

DOT Name	Glutathione S-transferase theta-2B (GSTT2B)
Synonyms	EC 2.5.1.18; Glutathione S-transferase theta-2; GST class-theta-2
Gene Name	GSTT2B
Related Disease	Advanced cancer ( ) Allergic rhinitis ( ) Alzheimer disease ( ) Asthma ( ) Charcot marie tooth disease ( ) Essential hypertension ( ) Hypothyroidism ( ) Schizophrenia ( )
UniProt ID	GSTT2_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
PDB ID	1LJR; 2LJR; 3LJR; 4MPG
EC Number	2.5.1.18
Pfam ID	PF00043 ; PF02798
Sequence	MGLELFLDLVSQPSRAVYIFAKKNGIPLELRTVDLVKGQHKSKEFLQINSLGKLPTLKDG DFILTESSAILIYLSCKYQTPDHWYPSDLQARARVHEYLGWHADCIRGTFGIPLWVQVLG PLIGVQVPEEKVERNRTAMDQALQWLEDKFLGDRPFLAGQQVTLADLMALEELMQPVALG YELFEGRPRLAAWRGRVEAFLGAELCQEAHSIILSILEQAAKKTLPTPSPEAYQAMLLRI ARIP
Function	Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles. Has a sulfatase activity.
Tissue Specificity	Expressed at low levels in liver. In lung, expressed at low levels in ciliated bronchiolar cells, alveolar macrophages and alveolar type II cells.
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

8 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance
Advanced cancer	DISAT1Z9	Strong	Genetic Variation	[1]
Allergic rhinitis	DIS3U9HN	Strong	Genetic Variation	[2]
Alzheimer disease	DISF8S70	Strong	Genetic Variation	[2]
Asthma	DISW9QNS	Strong	Genetic Variation	[2]
Charcot marie tooth disease	DIS3BT2L	Strong	Altered Expression	[3]
Essential hypertension	DIS7WI98	Strong	Genetic Variation	[2]
Hypothyroidism	DISR0H6D	Strong	Genetic Variation	[2]
Schizophrenia	DISSRV2N	Strong	Genetic Variation	[4]
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Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Glutathione S-transferase theta-2B (GSTT2B).	[5]
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2 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Glutathione S-transferase theta-2B (GSTT2B).	[6]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Glutathione S-transferase theta-2B (GSTT2B).	[7]
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References

1	Association of a deletion of GSTT2B with an altered risk of oesophageal squamous cell carcinoma in a South African population: a case-control study.PLoS One. 2011;6(12):e29366. doi: 10.1371/journal.pone.0029366. Epub 2011 Dec 27.
2	Explorative genetic association study of GSTT2B copy number variant in complex disease risks.Ann Hum Biol. 2016 May;43(3):279-84. doi: 10.3109/03014460.2015.1049206. Epub 2015 Jul 24.
3	Analysis of neural crest cells from Charcot-Marie-Tooth disease patients demonstrates disease-relevant molecular signature.Neuroreport. 2017 Sep 6;28(13):814-821. doi: 10.1097/WNR.0000000000000831.
4	Association of common copy number variants at the glutathione S-transferase genes and rare novel genomic changes with schizophrenia.Mol Psychiatry. 2010 Oct;15(10):1023-33. doi: 10.1038/mp.2009.53. Epub 2009 Jun 16.
5	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.
6	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.
7	Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.