Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT8AG6ZN)

• DOT Name: tRNA-specific adenosine deaminase 2 (ADAT2)
• Synonyms: EC 3.5.4.33; Deaminase domain-containing protein 1; tRNA-specific adenosine-34 deaminase subunit ADAT2
• Gene Name: ADAT2
• Related Disease:
  Pancreatic cancer
  Neoplasm
  Thyroid gland papillary carcinoma
• UniProt ID: ADAT2_HUMAN
• PDB ID: 3DH1
• EC Number: 3.5.4.33
• Pfam ID: PF14437
• Sequence:
  MEAKAAPKPAASGACSVSAEETEKWMEEAMHMAKEALENTEVPVGCLMVYNNEVVGKGRN
  EVNQTKNATRHAEMVAIDQVLDWCRQSGKSPSEVFEHTVLYVTVEPCIMCAAALRLMKIP
  LVVYGCQNERFGGCGSVLNIASADLPNTGRPFQCIPGYRAEEAVEMLKTFYKQENPNAPK
  SKVRKKECQKS
• Function: Probably participates in deamination of adenosine-34 to inosine in many tRNAs.
• Reactome Pathway: tRNA modification in the nucleus and cytosol (R-HSA-6782315)

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Pancreatic cancer	DISJC981	Strong	Genetic Variation	[1]
Neoplasm	DISZKGEW	Limited	Biomarker	[2]
Thyroid gland papillary carcinoma	DIS48YMM	Limited	Altered Expression	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of tRNA-specific adenosine deaminase 2 (ADAT2).	[4]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of tRNA-specific adenosine deaminase 2 (ADAT2).	[5]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of tRNA-specific adenosine deaminase 2 (ADAT2).	[6]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of tRNA-specific adenosine deaminase 2 (ADAT2).	[7]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of tRNA-specific adenosine deaminase 2 (ADAT2).	[8]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of tRNA-specific adenosine deaminase 2 (ADAT2).	[9]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of tRNA-specific adenosine deaminase 2 (ADAT2).	[10]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of tRNA-specific adenosine deaminase 2 (ADAT2).	[11]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of tRNA-specific adenosine deaminase 2 (ADAT2).	[12]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of tRNA-specific adenosine deaminase 2 (ADAT2).	[13]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of tRNA-specific adenosine deaminase 2 (ADAT2).	[14]
methyl p-hydroxybenzoate	DMO58UW	Investigative	methyl p-hydroxybenzoate decreases the expression of tRNA-specific adenosine deaminase 2 (ADAT2).	[15]

References

• [1] A p53 Super-tumor Suppressor Reveals a Tumor Suppressive p53-Ptpn14-Yap Axis in Pancreatic Cancer.Cancer Cell. 2017 Oct 9;32(4):460-473.e6. doi: 10.1016/j.ccell.2017.09.007.
• [2] The Transactivation Domains of the p53 Protein.Cold Spring Harb Perspect Med. 2017 Jan 3;7(1):a026047. doi: 10.1101/cshperspect.a026047.
• [3] Dicer expression and microRNA dysregulation associate with aggressive features in thyroid cancer.Surgery. 2014 Dec;156(6):1342-50; discussion 1350. doi: 10.1016/j.surg.2014.08.007. Epub 2014 Nov 11.
• [4] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [5] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [6] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [7] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [8] 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.
• [9] Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 30.
• [10] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [11] BET bromodomain inhibition as a therapeutic strategy to target c-Myc. Cell. 2011 Sep 16;146(6):904-17.
• [12] 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.
• [13] Gene expression changes in primary human nasal epithelial cells exposed to formaldehyde in vitro. Toxicol Lett. 2010 Oct 5;198(2):289-95.
• [14] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [15] Transcriptome dynamics of alternative splicing events revealed early phase of apoptosis induced by methylparaben in H1299 human lung carcinoma cells. Arch Toxicol. 2020 Jan;94(1):127-140. doi: 10.1007/s00204-019-02629-w. Epub 2019 Nov 20.