Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT4RUVCM)

DOT Name tRNA wybutosine-synthesizing protein 4 (LCMT2)
Synonyms
tRNA yW-synthesizing protein 4; EC 2.1.1.290; EC 2.3.1.231; Leucine carboxyl methyltransferase 2; tRNA(Phe; 7-(3-amino-3-(methoxycarbonyl)propyl)wyosine(37)-N)-methoxycarbonyltransferase; tRNA(Phe; 7-(3-amino-3-carboxypropyl)wyosine(37)-O)-methyltransferase
Gene Name LCMT2
UniProt ID
TYW4_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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EC Number
2.1.1.290; 2.3.1.231
Pfam ID
PF04072
Sequence
MGPRSRERRAGAVQNTNDSSALSKRSLAARGYVQDPFAALLVPGAARRAPLIHRGYYVRA
RAVRHCVRAFLEQIGAPQAALRAQILSLGAGFDSLYFRLKTAGRLARAAVWEVDFPDVAR
RKAERIGETPELCALTGPFERGEPASALCFESADYCILGLDLRQLQRVEEALGAAGLDAA
SPTLLLAEAVLTYLEPESAAALIAWAAQRFPNALFVVYEQMRPQDAFGQFMLQHFRQLNS
PLHGLERFPDVEAQRRRFLQAGWTACGAVDMNEFYHCFLPAEERRRVENIEPFDEFEEWH
LKCAHYFILAASRGDTLSHTLVFPSSEAFPRVNPASPSGVFPASVVSSEGQVPNLKRYGH
ASVFLSPDVILSAGGFGEQEGRHCRVSQFHLLSRDCDSEWKGSQIGSCGTGVQWDGRLYH
TMTRLSESRVLVLGGRLSPVSPALGVLQLHFFKSEDNNTEDLKVTITKAGRKDDSTLCCW
RHSTTEVSCQNQEYLFVYGGRSVVEPVLSDWHFLHVGTMAWVRIPVEGEVPEARHSHSAC
TWQGGALIAGGLGASEEPLNSVLFLRPISCGFLWESVDIQPPITPRYSHTAHVLNGKLLL
VGGIWIHSSSFPGVTVINLTTGLSSEYQIDTTYVPWPLMLHNHTSILLPEEQQLLLLGGG
GNCFSFGTYFNPHTVTLDLSSLSAGQ
Function
Probable S-adenosyl-L-methionine-dependent methyltransferase that acts as a component of the wybutosine biosynthesis pathway. Wybutosine is a hyper modified guanosine with a tricyclic base found at the 3'-position adjacent to the anticodon of eukaryotic phenylalanine tRNA. May methylate the carboxyl group of leucine residues to form alpha-leucine ester residues.
Reactome Pathway
Synthesis of wybutosine at G37 of tRNA(Phe) (R-HSA-6782861 )

Molecular Interaction Atlas (MIA) of This DOT

Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
17 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 wybutosine-synthesizing protein 4 (LCMT2). [1]
Ciclosporin DMAZJFX Approved Ciclosporin decreases the expression of tRNA wybutosine-synthesizing protein 4 (LCMT2). [2]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of tRNA wybutosine-synthesizing protein 4 (LCMT2). [3]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate decreases the expression of tRNA wybutosine-synthesizing protein 4 (LCMT2). [4]
Cisplatin DMRHGI9 Approved Cisplatin affects the expression of tRNA wybutosine-synthesizing protein 4 (LCMT2). [5]
Temozolomide DMKECZD Approved Temozolomide increases the expression of tRNA wybutosine-synthesizing protein 4 (LCMT2). [6]
Hydrogen peroxide DM1NG5W Approved Hydrogen peroxide affects the expression of tRNA wybutosine-synthesizing protein 4 (LCMT2). [7]
Decitabine DMQL8XJ Approved Decitabine affects the expression of tRNA wybutosine-synthesizing protein 4 (LCMT2). [5]
Marinol DM70IK5 Approved Marinol decreases the expression of tRNA wybutosine-synthesizing protein 4 (LCMT2). [8]
Niclosamide DMJAGXQ Approved Niclosamide decreases the expression of tRNA wybutosine-synthesizing protein 4 (LCMT2). [9]
Urethane DM7NSI0 Phase 4 Urethane decreases the expression of tRNA wybutosine-synthesizing protein 4 (LCMT2). [10]
Tocopherol DMBIJZ6 Phase 2 Tocopherol increases the expression of tRNA wybutosine-synthesizing protein 4 (LCMT2). [11]
(+)-JQ1 DM1CZSJ Phase 1 (+)-JQ1 increases the expression of tRNA wybutosine-synthesizing protein 4 (LCMT2). [12]
THAPSIGARGIN DMDMQIE Preclinical THAPSIGARGIN decreases the expression of tRNA wybutosine-synthesizing protein 4 (LCMT2). [13]
Formaldehyde DM7Q6M0 Investigative Formaldehyde decreases the expression of tRNA wybutosine-synthesizing protein 4 (LCMT2). [14]
Coumestrol DM40TBU Investigative Coumestrol increases the expression of tRNA wybutosine-synthesizing protein 4 (LCMT2). [15]
Pyrrolidine dithiocarbamate DM5ZAS6 Investigative Pyrrolidine dithiocarbamate increases the expression of tRNA wybutosine-synthesizing protein 4 (LCMT2). [11]
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⏷ Show the Full List of 17 Drug(s)

References

1 Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
2 Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
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 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
5 Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
6 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.
7 Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
8 THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders. Transl Psychiatry. 2018 Apr 25;8(1):89. doi: 10.1038/s41398-018-0137-3.
9 Mitochondrial Uncoupling Induces Epigenome Remodeling and Promotes Differentiation in Neuroblastoma. Cancer Res. 2023 Jan 18;83(2):181-194. doi: 10.1158/0008-5472.CAN-22-1029.
10 Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
11 Antioxidants enhance the cytotoxicity of chemotherapeutic agents in colorectal cancer: a p53-independent induction of p21WAF1/CIP1 via C/EBPbeta. Nat Med. 1997 Nov;3(11):1233-41. doi: 10.1038/nm1197-1233.
12 Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
13 Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.
14 Gene expression changes in primary human nasal epithelial cells exposed to formaldehyde in vitro. Toxicol Lett. 2010 Oct 5;198(2):289-95.
15 Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.