Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTBLY3PP)

• DOT Name: Glutamyl-tRNA(Gln) amidotransferase subunit C, mitochondrial (GATC)
• Synonyms: Glu-AdT subunit C; EC 6.3.5.-; Protein 15E1.2
• Gene Name: GATC
• Related Disease:
  Cervical cancer
  Cervical carcinoma
  Combined oxidative phosphorylation deficiency 42
• UniProt ID: GATC_HUMAN
• EC Number: 6.3.5.-
• Pfam ID: PF02686
• Sequence:
  MWSRLVWLGLRAPLGGRQGFTSKADPQGSGRITAAVIEHLERLALVDFGSREAVARLEKA
  IAFADRLRAVDTDGVEPMESVLEDRCLYLRSDNVVEGNCADELLQNSHRVVEEYFVAPPG
  NISLPKLDEQEPFPHS
• 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).
• KEGG Pathway:
  Aminoacyl-tR. biosynthesis (hsa00970)
  Metabolic pathways (hsa01100)

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Cervical cancer	DISFSHPF	Strong	Genetic Variation	[1]
Cervical carcinoma	DIST4S00	Strong	Genetic Variation	[1]
Combined oxidative phosphorylation deficiency 42	DISG9H1T	Limited	Unknown	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate affects the expression of Glutamyl-tRNA(Gln) amidotransferase subunit C, mitochondrial (GATC).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Glutamyl-tRNA(Gln) amidotransferase subunit C, mitochondrial (GATC).	[4]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Glutamyl-tRNA(Gln) amidotransferase subunit C, mitochondrial (GATC).	[5]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Glutamyl-tRNA(Gln) amidotransferase subunit C, mitochondrial (GATC).	[6]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Glutamyl-tRNA(Gln) amidotransferase subunit C, mitochondrial (GATC).	[7]
Tamibarotene	DM3G74J	Phase 3	Tamibarotene affects the expression of Glutamyl-tRNA(Gln) amidotransferase subunit C, mitochondrial (GATC).	[4]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Glutamyl-tRNA(Gln) amidotransferase subunit C, mitochondrial (GATC).	[8]

References

• [1] Association of TLR4 and TLR9 polymorphisms and haplotypes with cervical cancer susceptibility.Sci Rep. 2019 Jul 5;9(1):9729. doi: 10.1038/s41598-019-46077-z.
• [2] Pathogenic variants in glutamyl-tRNA(Gln) amidotransferase subunits cause a lethal mitochondrial cardiomyopathy disorder. Nat Commun. 2018 Oct 3;9(1):4065. doi: 10.1038/s41467-018-06250-w.
• [3] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [4] Differential modulation of PI3-kinase/Akt pathway during all-trans retinoic acid- and Am80-induced HL-60 cell differentiation revealed by DNA microarray analysis. Biochem Pharmacol. 2004 Dec 1;68(11):2177-86.
• [5] 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.
• [6] 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.
• [7] 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.
• [8] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.