Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTW4IO3I)

• DOT Name: Glutathione hydrolase 7 (GGT7)
• Synonyms: EC 3.4.19.13; Gamma-glutamyltransferase 7; GGT 7; EC 2.3.2.2; Gamma-glutamyltransferase-like 3; Gamma-glutamyltransferase-like 5; Gamma-glutamyltranspeptidase 7
• Gene Name: GGT7
• UniProt ID: GGT7_HUMAN
• EC Number: 2.3.2.2; 3.4.19.13
• Pfam ID: PF01019
• Sequence:
  MAAENEASQESALGAYSPVDYMSITSFPRLPEDEPAPAAPLRGRKDEDAFLGDPDTDPDS
  FLKSARLQRLPSSSSEMGSQDGSPLRETRKDPFSAAAAECSCRQDGLTVIVTACLTFATG
  VTVALVMQIYFGDPQIFQQGAVVTDAARCTSLGIEVLSKQGSSVDAAVAAALCLGIVAPH
  SSGLGGGGVMLVHDIRRNESHLIDFRESAPGALREETLQRSWETKPGLLVGVPGMVKGLH
  EAHQLYGRLPWSQVLAFAAAVAQDGFNVTHDLARALAEQLPPNMSERFRETFLPSGRPPL
  PGSLLHRPDLAEVLDVLGTSGPAAFYAGGNLTLEMVAEAQHAGGVITEEDFSNYSALVEK
  PVCGVYRGHLVLSPPPPHTGPALISALNILEGFNLTSLVSREQALHWVAETLKIALALAS
  RLGDPVYDSTITESMDDMLSKVEAAYLRGHINDSQAAPAPLLPVYELDGAPTAAQVLIMG
  PDDFIVAMVSSLNQPFGSGLITPSGILLNSQMLDFSWPNRTANHSAPSLENSVQPGKRPL
  SFLLPTVVRPAEGLCGTYLALGANGAARGLSGLTQVLLNVLTLNRNLSDSLARGRLHPDL
  QSNLLQVDSEFTEEEIEFLEARGHHVEKVDVLSWVHGSRRTNNFIIAVKDPRSPDAAGAT
  IL
• Function: Hydrolyzes and transfers gamma-glutamyl moieties from glutathione and other gamma-glutamyl compounds to acceptors.
• Tissue Specificity: Widely expressed, but at low level, except in the airway epithelial cells. Detected in brain, heart, kidney, liver, lung, spleen, testis and trachea.
• 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

This DOT Affected the Drug Response of 2 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Phenytoin	DMNOKBV	Approved	Glutathione hydrolase 7 (GGT7) increases the Jaundice ADR of Phenytoin.	[10]
Primidone	DM0WX6I	Approved	Glutathione hydrolase 7 (GGT7) increases the Jaundice ADR of Primidone.	[10]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Glutathione hydrolase 7 (GGT7).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Glutathione hydrolase 7 (GGT7).	[5]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the phosphorylation of Glutathione hydrolase 7 (GGT7).	[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 7 (GGT7).	[2]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Glutathione hydrolase 7 (GGT7).	[3]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Glutathione hydrolase 7 (GGT7).	[4]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Glutathione hydrolase 7 (GGT7).	[6]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Glutathione hydrolase 7 (GGT7).	[7]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of Glutathione hydrolase 7 (GGT7).	[9]

References

• [1] 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.
• [2] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [3] 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.
• [4] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [5] 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.
• [6] Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem. 2012 Dec 14;287(51):43137-55.
• [7] 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.
• [8] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [9] A trichostatin A expression signature identified by TempO-Seq targeted whole transcriptome profiling. PLoS One. 2017 May 25;12(5):e0178302. doi: 10.1371/journal.pone.0178302. eCollection 2017.
• [10] ADReCS-Target: target profiles for aiding drug safety research and application. Nucleic Acids Res. 2018 Jan 4;46(D1):D911-D917. doi: 10.1093/nar/gkx899.