Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTI2NKKV)

• DOT Name: tRNA-uridine aminocarboxypropyltransferase 2 (DTWD2)
• Synonyms: EC 2.5.1.25; DTW domain-containing protein 2
• Gene Name: DTWD2
• UniProt ID: DTWD2_HUMAN
• EC Number: 2.5.1.25
• Pfam ID: PF03942
• Sequence:
  MESQKEARTLQEPVARPSGASSSQTPNDKERREGGAVPAAAALGAEADDDSADGLWELPV
  EPAERRPECTRCSRPQKVCLCPFLPAHPLHISTHLYIIQHPAEENKVLRTVPLLAACLPQ
  DKCKVKIGRRFSEERDPELSTVCRKSGTLILYPGAEAANLEEFILDSPVYPSTIIIIDGT
  WSQAKDIFYKNSLFRHPKQVQLKTSISSQYVIRMQPTNRCLSTLECAAVALSILEKNNYI
  QETLLRPLQALCSFQLQHGAQIRLSKEHLLKNGLYPKPMPKNKRKLRKMELLMNSVKI
• Function: Catalyzes the formation of 3-(3-amino-3-carboxypropyl)uridine (acp3U) at position 20a in the D-loop of several cytoplasmic tRNAs (acp3U(20a)). Also has a weak activity to form acp3U at position 20 in the D-loop of tRNAs (acp3U(20)).

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of tRNA-uridine aminocarboxypropyltransferase 2 (DTWD2).	[1]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of tRNA-uridine aminocarboxypropyltransferase 2 (DTWD2).	[2]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of tRNA-uridine aminocarboxypropyltransferase 2 (DTWD2).	[3]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of tRNA-uridine aminocarboxypropyltransferase 2 (DTWD2).	[4]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of tRNA-uridine aminocarboxypropyltransferase 2 (DTWD2).	[5]
Folic acid	DMEMBJC	Approved	Folic acid decreases the expression of tRNA-uridine aminocarboxypropyltransferase 2 (DTWD2).	[6]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of tRNA-uridine aminocarboxypropyltransferase 2 (DTWD2).	[7]

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] 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] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [4] Minimal peroxide exposure of neuronal cells induces multifaceted adaptive responses. PLoS One. 2010 Dec 17;5(12):e14352. doi: 10.1371/journal.pone.0014352.
• [5] The proapoptotic effect of zoledronic acid is independent of either the bone microenvironment or the intrinsic resistance to bortezomib of myeloma cells and is enhanced by the combination with arsenic trioxide. Exp Hematol. 2011 Jan;39(1):55-65.
• [6] Folic acid supplementation dysregulates gene expression in lymphoblastoid cells--implications in nutrition. Biochem Biophys Res Commun. 2011 Sep 9;412(4):688-92. doi: 10.1016/j.bbrc.2011.08.027. Epub 2011 Aug 16.
• [7] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.