Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTSAP87C)

• DOT Name: Glutamyl-tRNA(Gln) amidotransferase subunit B, mitochondrial (GATB)
• Synonyms: Glu-AdT subunit B; EC 6.3.5.-; Cytochrome c oxidase assembly factor PET112 homolog
• Gene Name: GATB
• UniProt ID: GATB_HUMAN
• EC Number: 6.3.5.-
• Pfam ID: PF02934 ; PF02637
• Sequence:
  MAAPMLRWGCRGRRWAFARVDGGSCHRRGAPTGSTSNQIRGESSVAQQPLHTAQKTRKGE
  HKWAAVVGLEIHAQISSNSKLFSGSQVRFSAPPNSLVSFFDASLPGTLPVLNRRCVEAAV
  MTGLALNCHINKKSLFDRKHYFYADLPAGYQITQQRLPIAVNGSLIYGVCAGKKQSQVIP
  KTVRIKQIQLEQDSGKSLHDNLRSQTLIDLNRAGVGLLEVVLEPDMSCGEEAATAVRELQ
  LILQALGTSQANMAEGQLRVDANISVHHPGEPLGVRTEVKNLNSIRFLAKAIDYEIQRQI
  NELENGGEILNETRSFHHKLGCTMSMRDKEGKQDYRFMPEPNLPPLVLYDATSLPAGADP
  QQVINIDQIRETLPELPSVTREKLVQQYGMLLEHSFTLLNEVGLLEFFQNVIKETRAEPK
  KVTSWVLNTFLGYLKQQNLAVSESPVTPSALAELLDLLDSRTISSSAAKQVFEELWKREG
  KTPGQIVSEKQLELMQDQGALEQLCHSVMEAHPQVVMDVKNRNPRAINKLIGLVRKATQS
  RADPVMIKEILEKKLSL
• Function: Allows the formation of correctly charged Gln-tRNA(Gln) through the transamidation of misacylated Glu-tRNA(Gln) in the mitochondria. The reaction takes place in the presence of glutamine and ATP through an activated gamma-phospho-Glu-tRNA(Gln).
• Tissue Specificity: Predominantly expressed in tissues characterized by high rates of oxidative phosphorylation (OxPhos), including muscle and heart.
• KEGG Pathway:
  Aminoacyl-tR. biosynthesis (hsa00970)
  Metabolic pathways (hsa01100)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Glutamyl-tRNA(Gln) amidotransferase subunit B, mitochondrial (GATB).	[1]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Glutamyl-tRNA(Gln) amidotransferase subunit B, mitochondrial (GATB).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Glutamyl-tRNA(Gln) amidotransferase subunit B, mitochondrial (GATB).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Glutamyl-tRNA(Gln) amidotransferase subunit B, mitochondrial (GATB).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Glutamyl-tRNA(Gln) amidotransferase subunit B, mitochondrial (GATB).	[5]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Glutamyl-tRNA(Gln) amidotransferase subunit B, mitochondrial (GATB).	[6]

References

• [1] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [2] Retinoic acid receptor alpha amplifications and retinoic acid sensitivity in breast cancers. Clin Breast Cancer. 2013 Oct;13(5):401-8.
• [3] Increased mitochondrial ROS formation by acetaminophen in human hepatic cells is associated with gene expression changes suggesting disruption of the mitochondrial electron transport chain. Toxicol Lett. 2015 Apr 16;234(2):139-50.
• [4] 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.
• [5] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [6] 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.