Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTVBE313)

DOT Name tRNA-dihydrouridine(20) synthase -like (DUS2)
Synonyms EC 1.3.1.91; Dihydrouridine synthase 2; Up-regulated in lung cancer protein 8; URLC8; tRNA-dihydrouridine synthase 2-like; hDUS2
Gene Name DUS2
Related Disease
Lung cancer ( )
Lung carcinoma ( )
Neoplasm ( )
Non-small-cell lung cancer ( )
UniProt ID
DUS2L_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
4WFS; 4WFT; 4XP7; 5OC4; 5OC5; 5OC6; 6EI8; 6EZA; 6EZB; 6EZC; 6F00
EC Number
1.3.1.91
Pfam ID
PF00035 ; PF01207
Sequence
MILNSLSLCYHNKLILAPMVRVGTLPMRLLALDYGADIVYCEELIDLKMIQCKRVVNEVL
STVDFVAPDDRVVFRTCEREQNRVVFQMGTSDAERALAVARLVENDVAGIDVNMGCPKQY
STKGGMGAALLSDPDKIEKILSTLVKGTRRPVTCKIRILPSLEDTLSLVKRIERTGIAAI
AVHGRKREERPQHPVSCEVIKAIADTLSIPVIANGGSHDHIQQYSDIEDFRQATAASSVM
VARAAMWNPSIFLKEGLRPLEEVMQKYIRYAVQYDNHYTNTKYCLCQMLREQLESPQGRL
LHAAQSSREICEAFGLGAFYEETTQELDAQQARLSAKTSEQTGEPAEDTSGVIKMAVKFD
RRAYPAQITPKMCLLEWCRREKLAQPVYETVQRPLDRLFSSIVTVAEQKYQSTLWDKSKK
LAEQAAAIVCLRSQGLPEGRLGEESPSLHKRKREAPDQDPGGPRAQELAQPGDLCKKPFV
ALGSGEESPLEGW
Function Dihydrouridine synthase. Catalyzes the NADPH-dependent synthesis of dihydrouridine, a modified base found in the D-loop of most tRNAs. Negatively regulates the activation of EIF2AK2/PKR.
Tissue Specificity Weak expression in heart, placenta and skeletal muscle. Up-regulated in most lung cancer cells (at protein level).
Reactome Pathway
PKR-mediated signaling (R-HSA-9833482 )
tRNA modification in the nucleus and cytosol (R-HSA-6782315 )

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Lung cancer DISCM4YA Disputed Biomarker [1]
Lung carcinoma DISTR26C Disputed Altered Expression [1]
Neoplasm DISZKGEW Disputed Altered Expression [1]
Non-small-cell lung cancer DIS5Y6R9 Disputed Altered Expression [1]
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Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
6 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Tretinoin DM49DUI Approved Tretinoin decreases the expression of tRNA-dihydrouridine(20) synthase -like (DUS2). [2]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of tRNA-dihydrouridine(20) synthase -like (DUS2). [3]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate decreases the expression of tRNA-dihydrouridine(20) synthase -like (DUS2). [4]
Arsenic trioxide DM61TA4 Approved Arsenic trioxide decreases the expression of tRNA-dihydrouridine(20) synthase -like (DUS2). [2]
Urethane DM7NSI0 Phase 4 Urethane decreases the expression of tRNA-dihydrouridine(20) synthase -like (DUS2). [5]
Milchsaure DM462BT Investigative Milchsaure decreases the expression of tRNA-dihydrouridine(20) synthase -like (DUS2). [8]
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⏷ Show the Full List of 6 Drug(s)
2 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 increases the methylation of tRNA-dihydrouridine(20) synthase -like (DUS2). [6]
TAK-243 DM4GKV2 Phase 1 TAK-243 increases the sumoylation of tRNA-dihydrouridine(20) synthase -like (DUS2). [7]
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References

1 A novel human tRNA-dihydrouridine synthase involved in pulmonary carcinogenesis.Cancer Res. 2005 Jul 1;65(13):5638-46. doi: 10.1158/0008-5472.CAN-05-0600.
2 Arsenic targets Pin1 and cooperates with retinoic acid to inhibit cancer-driving pathways and tumor-initiating cells. Nat Commun. 2018 Aug 9;9(1):3069. doi: 10.1038/s41467-018-05402-2.
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 Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
6 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.
7 Inhibiting ubiquitination causes an accumulation of SUMOylated newly synthesized nuclear proteins at PML bodies. J Biol Chem. 2019 Oct 18;294(42):15218-15234. doi: 10.1074/jbc.RA119.009147. Epub 2019 Jul 8.
8 Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.