Details of Drug Off-Target (DOT)

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

• DOT Name: Glutathione hydrolase 6 (GGT6)
• Synonyms: EC 3.4.19.13; Gamma-glutamyltransferase 6; GGT 6; EC 2.3.2.2; Gamma-glutamyltranspeptidase 6
• Gene Name: GGT6
• Related Disease: Rheumatoid arthritis
• UniProt ID: GGT6_HUMAN
• EC Number: 2.3.2.2; 3.4.19.13
• Pfam ID: PF01019
• Sequence:
  MERAEEPVVYQKLLPWEPSLESEEEVEEEETSEALVLNPRRHQDSSRNKAGGLPGTWARV
  VAALLLLAVGCSLAVRQLQNQGRSTGSLGSVAPPPGGHSHGPGVYHHGAIISPAGRELLV
  AGGNVVDAGVGAALCLAVVHPHATGLGAMFWGLFHDSSSGNSTALTSGPAQTLAPGLGLP
  AALPTLHLLHARFGRLPWPRLLVGPTTLAQEGFLVDTPLARALVARGTEGLCPLLCHADG
  TPLGAGARATNPQLAAVLRSAALAPTSDLAGDALLSLLAGDLGVEVPSAVPRPTLEPAEQ
  LPVPQGILFTTPSPSAGPELLALLEAALRSGAPIPDPCPPFLQTAVSPESSALAAVDSSG
  SVLLLTSSLNCSFGSAHLSPSTGVLLSNLVAKSTTSAWACPLILRGSLDDTEADVLGLVA
  SGTPDVARAMTHTLLRHLAARPPTQAQHQHQGQQEPTEHPSTCGQGTLLQVAAHTEHAHV
  SSVPHACCPFQGF
• Function: Hydrolyzes and transfers gamma-glutamyl moieties from glutathione and other gamma-glutamyl compounds to acceptors.
• KEGG Pathway:
  Taurine and hypotaurine metabolism (hsa00430)
  Glutathione metabolism (hsa00480)
  Metabolic pathways (hsa01100)
• Reactome Pathway:
  Aflatoxin activation and detoxification (R-HSA-5423646)
  Paracetamol ADME (R-HSA-9753281)
  Glutathione synthesis and recycling (R-HSA-174403)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Rheumatoid arthritis	DISTSB4J	Disputed	Biomarker	[1]

2 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 hydrolase 6 (GGT6).	[2]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Glutathione hydrolase 6 (GGT6).	[8]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Glutathione hydrolase 6 (GGT6).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Glutathione hydrolase 6 (GGT6).	[4]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Glutathione hydrolase 6 (GGT6).	[5]
Cannabidiol	DM0659E	Approved	Cannabidiol decreases the expression of Glutathione hydrolase 6 (GGT6).	[6]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Glutathione hydrolase 6 (GGT6).	[7]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Glutathione hydrolase 6 (GGT6).	[9]

References

• [1] A Multinational Arab Genome-Wide Association Study Identifies New Genetic Associations for Rheumatoid Arthritis.Arthritis Rheumatol. 2017 May;69(5):976-985. doi: 10.1002/art.40051. Epub 2017 Mar 31.
• [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] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [4] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [5] Persistent and non-persistent changes in gene expression result from long-term estrogen exposure of MCF-7 breast cancer cells. J Steroid Biochem Mol Biol. 2011 Feb;123(3-5):140-50.
• [6] Cannabidiol enhances cytotoxicity of anti-cancer drugs in human head and neck squamous cell carcinoma. Sci Rep. 2020 Nov 26;10(1):20622. doi: 10.1038/s41598-020-77674-y.
• [7] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [8] 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.
• [9] CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.