Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT323X9J)

DOT Name Cytoplasmic tRNA 2-thiolation protein 2 (CTU2)
Synonyms Cytosolic thiouridylase subunit 2
Gene Name CTU2
Related Disease
Breast cancer ( )
Breast carcinoma ( )
Breast neoplasm ( )
Microcephaly, facial dysmorphism, renal agenesis, and ambiguous genitalia syndrome ( )
UniProt ID
CTU2_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Pfam ID
PF10288
Sequence
MCQVGEDYGEPAPEEPPPAPRPSREQKCVKCKEAQPVVVIRAGDAFCRDCFKAFYVHKFR
AMLGKNRLIFPGEKVLLAWSGGPSSSSMVWQVLEGLSQDSAKRLRFVAGVIFVDEGAACG
QSLEERSKTLAEVKPILQATGFPWHVVALEEVFSLPPSVLWCSAQELVGSEGAYKAAVDS
FLQQQHVLGAGGGPGPTQGEEQPPQPPLDPQNLARPPAPAQTEALSQLFCSVRTLTAKEE
LLQTLRTHLILHMARAHGYSKVMTGDSCTRLAIKLMTNLALGRGAFLAWDTGFSDERHGD
VVVVRPMRDHTLKEVAFYNRLFSVPSVFTPAVDTKAPEKASIHRLMEAFILRLQTQFPST
VSTVYRTSEKLVKGPRDGPAAGDSGPRCLLCMCALDVDAADSATAFGAQTSSRLSQMQSP
IPLTETRTPPGPCCSPGVGWAQRCGQGACRREDPQACIEEQLCYSCRVNMKDLPSLDPLP
PYILAEAQLRTQRAWGLQEIRDCLIEDSDDEAGQS
Function
Plays a central role in 2-thiolation of mcm(5)S(2)U at tRNA wobble positions of tRNA(Lys), tRNA(Glu) and tRNA(Gln). May act by forming a heterodimer with CTU1/ATPBD3 that ligates sulfur from thiocarboxylated URM1 onto the uridine of tRNAs at wobble position.
KEGG Pathway
Sulfur relay system (hsa04122 )
Reactome Pathway
tRNA modification in the nucleus and cytosol (R-HSA-6782315 )
BioCyc Pathway
MetaCyc:MONOMER-20243

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Breast cancer DIS7DPX1 Strong Biomarker [1]
Breast carcinoma DIS2UE88 Strong Biomarker [1]
Breast neoplasm DISNGJLM Strong Biomarker [1]
Microcephaly, facial dysmorphism, renal agenesis, and ambiguous genitalia syndrome DISNHYD0 Strong Autosomal recessive [2]
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Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
3 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate increases the methylation of Cytoplasmic tRNA 2-thiolation protein 2 (CTU2). [3]
PMID28870136-Compound-52 DMFDERP Patented PMID28870136-Compound-52 decreases the phosphorylation of Cytoplasmic tRNA 2-thiolation protein 2 (CTU2). [9]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the methylation of Cytoplasmic tRNA 2-thiolation protein 2 (CTU2). [10]
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6 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 Cytoplasmic tRNA 2-thiolation protein 2 (CTU2). [4]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of Cytoplasmic tRNA 2-thiolation protein 2 (CTU2). [5]
Calcitriol DM8ZVJ7 Approved Calcitriol decreases the expression of Cytoplasmic tRNA 2-thiolation protein 2 (CTU2). [6]
Testosterone DM7HUNW Approved Testosterone decreases the expression of Cytoplasmic tRNA 2-thiolation protein 2 (CTU2). [6]
Zoledronate DMIXC7G Approved Zoledronate decreases the expression of Cytoplasmic tRNA 2-thiolation protein 2 (CTU2). [7]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 increases the expression of Cytoplasmic tRNA 2-thiolation protein 2 (CTU2). [8]
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⏷ Show the Full List of 6 Drug(s)

References

1 Elp3 links tRNA modification to IRES-dependent translation of LEF1 to sustain metastasis in breast cancer.J Exp Med. 2016 Oct 17;213(11):2503-2523. doi: 10.1084/jem.20160397. Epub 2016 Oct 10.
2 Biallelic variants in CTU2 cause DREAM-PL syndrome and impair thiolation of tRNA wobble U34. Hum Mutat. 2019 Nov;40(11):2108-2120. doi: 10.1002/humu.23870. Epub 2019 Jul 29.
3 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.
4 Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
5 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.
6 Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
7 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.
8 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.
9 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.
10 DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.