Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT003Y7X)

• DOT Name: Glutathione hydrolase light chain 2 (GGTLC2)
• Synonyms: Gamma-glutamyltransferase light chain 2; Gamma-glutamyltransferase-like protein 4
• Gene Name: GGTLC2
• UniProt ID: GGTL2_HUMAN
• Pfam ID: PF01019
• Sequence:
  MTSEFFAAQLRAQISDDTTHPISYYKPEFYTPVDGGTAHLSVVAEDGSAVSATSTINLYF
  GSKVRSPVSEILFNDEMDDFSSPNITNEFGVPPSPANFIQPGKQPLSSMCPTIMVGQDGQ
  PPSHADHTPMPQAIIYNLWFGYDVKRAVEEPRLHNQLLPNVTTVERNIDQAVTAALETRH
  HHTQIASTFIAVVQAIVRTAGGWAAASDSRKGGEPAGY
• Tissue Specificity: Placenta and sigmoid tissues.

Molecular Interaction Atlas (MIA) of This DOT

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 light chain 2 (GGTLC2).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Glutathione hydrolase light chain 2 (GGTLC2).	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Glutathione hydrolase light chain 2 (GGTLC2).	[2]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Glutathione hydrolase light chain 2 (GGTLC2).	[3]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Glutathione hydrolase light chain 2 (GGTLC2).	[4]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Glutathione hydrolase light chain 2 (GGTLC2).	[5]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Glutathione hydrolase light chain 2 (GGTLC2).	[5]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of Glutathione hydrolase light chain 2 (GGTLC2).	[6]

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] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [3] Essential role of cell cycle regulatory genes p21 and p27 expression in inhibition of breast cancer cells by arsenic trioxide. Med Oncol. 2011 Dec;28(4):1225-54.
• [4] 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.
• [5] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [6] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [7] 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.