Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTCDIRF4)

• DOT Name: tRNA-specific adenosine deaminase 1 (ADAT1)
• Synonyms: hADAT1; EC 3.5.4.34; tRNA-specific adenosine-37 deaminase
• Gene Name: ADAT1
• UniProt ID: ADAT1_HUMAN
• EC Number: 3.5.4.34
• Pfam ID: PF02137
• Sequence:
  MWTADEIAQLCYEHYGIRLPKKGKPEPNHEWTLLAAVVKIQSPADKACDTPDKPVQVTKE
  VVSMGTGTKCIGQSKMRKNGDILNDSHAEVIARRSFQRYLLHQLQLAATLKEDSIFVPGT
  QKGVWKLRRDLIFVFFSSHTPCGDASIIPMLEFEDQPCCPVFRNWAHNSSVEASSNLEAP
  GNERKCEDPDSPVTKKMRLEPGTAAREVTNGAAHHQSFGKQKSGPISPGIHSCDLTVEGL
  ATVTRIAPGSAKVIDVYRTGAKCVPGEAGDSGKPGAAFHQVGLLRVKPGRGDRTRSMSCS
  DKMARWNVLGCQGALLMHLLEEPIYLSAVVIGKCPYSQEAMQRALIGRCQNVSALPKGFG
  VQELKILQSDLLFEQSRSAVQAKRADSPGRLVPCGAAISWSAVPEQPLDVTANGFPQGTT
  KKTIGSLQARSQISKVELFRSFQKLLSRIARDKWPHSLRVQKLDTYQEYKEAASSYQEAW
  STLRKQVFGSWIRNPPDYHQFK
• Function: Specifically deaminates adenosine-37 to inosine in tRNA-Ala.
• Tissue Specificity: Ubiquitously expressed.
• Reactome Pathway: tRNA modification in the nucleus and cytosol (R-HSA-6782315)

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 tRNA-specific adenosine deaminase 1 (ADAT1).	[1]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of tRNA-specific adenosine deaminase 1 (ADAT1).	[2]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of tRNA-specific adenosine deaminase 1 (ADAT1).	[3]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of tRNA-specific adenosine deaminase 1 (ADAT1).	[4]
Ethanol	DMDRQZU	Approved	Ethanol decreases the expression of tRNA-specific adenosine deaminase 1 (ADAT1).	[5]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of tRNA-specific adenosine deaminase 1 (ADAT1).	[8]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the phosphorylation of tRNA-specific adenosine deaminase 1 (ADAT1).	[6]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of tRNA-specific adenosine deaminase 1 (ADAT1).	[7]

References

• [1] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [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] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [5] Comparison of replicative senescence and stress-induced premature senescence combining differential display and low-density DNA arrays. FEBS Lett. 2005 Jul 4;579(17):3651-9. doi: 10.1016/j.febslet.2005.05.056.
• [6] 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.
• [7] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [8] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.