Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTRC7TRW)

• DOT Name: tRNA (THUMPD3)
• Synonyms: guanine(6)-N2)-methyltransferase THUMP3 (EC 2.1.1.256; THUMP domain-containing protein 3
• Gene Name: THUMPD3
• UniProt ID: THUM3_HUMAN
• EC Number: 2.1.1.256
• Pfam ID: PF02926 ; PF01170
• Sequence:
  MCDIEEATNQLLDVNLHENQKSVQVTESDLGSESELLVTIGATVPTGFEQTAADEVREKL
  GSSCKISRDRGKIYFVISVESLAQVHCLRSVDNLFVVVQEFQDYQFKQTKEEVLKDFEDL
  AGKLPWSNPLKVWKINASFKKKKAKRKKINQNSSKEKINNGQEVKIDQRNVKKEFTSHAL
  DSHILDYYENPAIKEDVSTLIGDDLASCKDETDESSKEETEPQVLKFRVTCNRAGEKHCF
  TSNEAARDFGGAVQDYFKWKADMTNFDVEVLLNIHDNEVIVGIALTEESLHRRNITHFGP
  TTLRSTLAYGMLRLCDPLPYDIIVDPMCGTGAIPIEGATEWSDCFHIAGDNNPLAVNRAA
  NNIASLLTKSQIKEGKPSWGLPIDAVQWDICNLPLRTGSVDIIVTDLPFGKRMGSKKRNW
  NLYPACLREMSRVCTPTTGRAVLLTQDTKCFTKALSGMRHVWRKVDTVWVNVGGLRAAVY
  VLIRTPQAFVHPSEQDGERGTLWQCKE
• Function: Methyltransferase which catalyzes the formation of N(2)-methylguanosine at position 6 in a broad range of tRNA substrates containing the characteristic 3'-CCA terminus of mature tRNAs. Also catalyzes the formation of N(2)-methylguanosine at position 7 of tRNA(Trp). Requires the methyltransferase adapter protein TRM112 for tRNA methyltransferase activity.

Molecular Interaction Atlas (MIA) of This DOT

8 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 tRNA (THUMPD3).	[1]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of tRNA (THUMPD3).	[2]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of tRNA (THUMPD3).	[3]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of tRNA (THUMPD3).	[4]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of tRNA (THUMPD3).	[6]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of tRNA (THUMPD3).	[7]
Torcetrapib	DMDHYM7	Discontinued in Phase 2	Torcetrapib increases the expression of tRNA (THUMPD3).	[9]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of tRNA (THUMPD3).	[10]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of tRNA (THUMPD3).	[5]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of tRNA (THUMPD3).	[8]
Coumarin	DM0N8ZM	Investigative	Coumarin increases the phosphorylation of tRNA (THUMPD3).	[8]
Octanal	DMTN0OK	Investigative	Octanal increases the methylation of tRNA (THUMPD3).	[11]

References

• [1] 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.
• [2] 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.
• [3] 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.
• [4] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [5] 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.
• [6] Synergistic effect of JQ1 and rapamycin for treatment of human osteosarcoma. Int J Cancer. 2015 May 1;136(9):2055-64.
• [7] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [8] 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.
• [9] Clarifying off-target effects for torcetrapib using network pharmacology and reverse docking approach. BMC Syst Biol. 2012 Dec 10;6:152.
• [10] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [11] DNA Methylome Analysis of Saturated Aliphatic Aldehydes in Pulmonary Toxicity. Sci Rep. 2018 Jul 12;8(1):10497. doi: 10.1038/s41598-018-28813-z.