Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT95QT6P)

• DOT Name: tRNA-uridine aminocarboxypropyltransferase 1 (DTWD1)
• Synonyms: EC 2.5.1.25; DTW domain-containing protein 1
• Gene Name: DTWD1
• Related Disease: Bipolar disorder
• UniProt ID: DTWD1_HUMAN
• EC Number: 2.5.1.25
• Pfam ID: PF03942
• Sequence:
  MSLNPPIFLKRSEENSSKFVETKQSQTTSIASEDPLQNLCLASQEVLQKAQQSGRSKCLK
  CGGSRMFYCYTCYVPVENVPIEQIPLVKLPLKIDIIKHPNETDGKSTAIHAKLLAPEFVN
  IYTYPCIPEYEEKDHEVALIFPGPQSISIKDISFHLQKRIQNNVRGKNDDPDKPSFKRKR
  TEEQEFCDLNDSKCKGTTLKKIIFIDSTWNQTNKIFTDERLQGLLQVELKTRKTCFWRHQ
  KGKPDTFLSTIEAIYYFLVDYHTDILKEKYRGQYDNLLFFYSFMYQLIKNAKCSGDKETG
  KLTH
• Function: Catalyzes the formation of 3-(3-amino-3-carboxypropyl)uridine (acp3U) at position 20 in the D-loop of several cytoplasmic tRNAs (acp3U(20)).

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Bipolar disorder	DISAM7J2	Strong	Biomarker	[1]

18 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-uridine aminocarboxypropyltransferase 1 (DTWD1).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of tRNA-uridine aminocarboxypropyltransferase 1 (DTWD1).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of tRNA-uridine aminocarboxypropyltransferase 1 (DTWD1).	[4]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of tRNA-uridine aminocarboxypropyltransferase 1 (DTWD1).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of tRNA-uridine aminocarboxypropyltransferase 1 (DTWD1).	[6]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of tRNA-uridine aminocarboxypropyltransferase 1 (DTWD1).	[7]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of tRNA-uridine aminocarboxypropyltransferase 1 (DTWD1).	[8]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of tRNA-uridine aminocarboxypropyltransferase 1 (DTWD1).	[9]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of tRNA-uridine aminocarboxypropyltransferase 1 (DTWD1).	[10]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of tRNA-uridine aminocarboxypropyltransferase 1 (DTWD1).	[11]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil increases the expression of tRNA-uridine aminocarboxypropyltransferase 1 (DTWD1).	[12]
Panobinostat	DM58WKG	Approved	Panobinostat decreases the expression of tRNA-uridine aminocarboxypropyltransferase 1 (DTWD1).	[12]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of tRNA-uridine aminocarboxypropyltransferase 1 (DTWD1).	[13]
Camptothecin	DM6CHNJ	Phase 3	Camptothecin increases the expression of tRNA-uridine aminocarboxypropyltransferase 1 (DTWD1).	[12]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of tRNA-uridine aminocarboxypropyltransferase 1 (DTWD1).	[14]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of tRNA-uridine aminocarboxypropyltransferase 1 (DTWD1).	[15]
QUERCITRIN	DM1DH96	Investigative	QUERCITRIN decreases the expression of tRNA-uridine aminocarboxypropyltransferase 1 (DTWD1).	[16]
Butanoic acid	DMTAJP7	Investigative	Butanoic acid decreases the expression of tRNA-uridine aminocarboxypropyltransferase 1 (DTWD1).	[12]

References

• [1] Efficient region-based test strategy uncovers genetic risk factors for functional outcome in bipolar disorder.Eur Neuropsychopharmacol. 2019 Jan;29(1):156-170. doi: 10.1016/j.euroneuro.2018.10.005. Epub 2018 Nov 29.
• [2] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [3] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [4] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [5] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [6] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [7] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [8] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [9] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [10] Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol. 2005 Nov;19(11):2685-95.
• [11] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [12] Development and validation of the TGx-HDACi transcriptomic biomarker to detect histone deacetylase inhibitors in human TK6 cells. Arch Toxicol. 2021 May;95(5):1631-1645. doi: 10.1007/s00204-021-03014-2. Epub 2021 Mar 26.
• [13] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [14] 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.
• [15] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [16] Molecular mechanisms of quercitrin-induced apoptosis in non-small cell lung cancer. Arch Med Res. 2014 Aug;45(6):445-54.