Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT6WG6M2)

DOT Name tRNA pseudouridine(38/39) synthase (PUS3)
Synonyms EC 5.4.99.45; tRNA pseudouridine synthase 3; tRNA pseudouridylate synthase 3; tRNA-uridine isomerase 3
Gene Name PUS3
Related Disease
Herpes simplex infection ( )
Intellectual disability ( )
Isolated congenital microcephaly ( )
Severe growth deficiency-strabismus-extensive dermal melanocytosis-intellectual disability syndrome ( )
Hydrolethalus syndrome ( )
UniProt ID
PUS3_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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EC Number
5.4.99.45
Pfam ID
PF01416
Sequence
MAYNDTDRNQTEKLLKRVRELEQEVQRLKKEQAKNKEDSNIRENSAGAGKTKRAFDFSAH
GRRHVALRIAYMGWGYQGFASQENTNNTIEEKLFEALTKTRLVESRQTSNYHRCGRTDKG
VSAFGQVISLDLRSQFPRGRDSEDFNVKEEANAAAEEIRYTHILNRVLPPDIRILAWAPV
EPSFSARFSCLERTYRYFFPRADLDIVTMDYAAQKYVGTHDFRNLCKMDVANGVINFQRT
ILSAQVQLVGQSPGEGRWQEPFQLCQFEVTGQAFLYHQVRCMMAILFLIGQGMEKPEIID
ELLNIEKNPQKPQYSMAVEFPLVLYDCKFENVKWIYDQEAQEFNITHLQQLWANHAVKTH
MLYSMLQGLDTVPVPCGIGPKMDGMTEWGNVKPSVIKQTSAFVEGVKMRTYKPLMDRPKC
QGLESRIQHFVRRGRIEHPHLFHEEETKAKRDCNDTLEEENTNLETPTKRVCVDTEIKSI
I
Function Formation of pseudouridine at position 39 in the anticodon stem and loop of transfer RNAs.
Reactome Pathway
tRNA modification in the nucleus and cytosol (R-HSA-6782315 )

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Herpes simplex infection DISL1SAV Strong Biomarker [1]
Intellectual disability DISMBNXP Strong Altered Expression [2]
Isolated congenital microcephaly DISUXHZ6 Strong Biomarker [3]
Severe growth deficiency-strabismus-extensive dermal melanocytosis-intellectual disability syndrome DIS468TF Strong Autosomal recessive [3]
Hydrolethalus syndrome DISX56R3 moderate CausalMutation [4]
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Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
13 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate increases the expression of tRNA pseudouridine(38/39) synthase (PUS3). [5]
Ciclosporin DMAZJFX Approved Ciclosporin increases the expression of tRNA pseudouridine(38/39) synthase (PUS3). [6]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate decreases the expression of tRNA pseudouridine(38/39) synthase (PUS3). [7]
Cisplatin DMRHGI9 Approved Cisplatin decreases the expression of tRNA pseudouridine(38/39) synthase (PUS3). [8]
Temozolomide DMKECZD Approved Temozolomide increases the expression of tRNA pseudouridine(38/39) synthase (PUS3). [9]
Hydrogen peroxide DM1NG5W Approved Hydrogen peroxide affects the expression of tRNA pseudouridine(38/39) synthase (PUS3). [10]
Marinol DM70IK5 Approved Marinol decreases the expression of tRNA pseudouridine(38/39) synthase (PUS3). [11]
Etoposide DMNH3PG Approved Etoposide decreases the expression of tRNA pseudouridine(38/39) synthase (PUS3). [8]
Mitomycin DMH0ZJE Approved Mitomycin decreases the expression of tRNA pseudouridine(38/39) synthase (PUS3). [8]
Colchicine DM2POTE Approved Colchicine decreases the expression of tRNA pseudouridine(38/39) synthase (PUS3). [8]
Hydroxyurea DMOQVU9 Approved Hydroxyurea decreases the expression of tRNA pseudouridine(38/39) synthase (PUS3). [8]
Adenine DMZLHKJ Approved Adenine decreases the expression of tRNA pseudouridine(38/39) synthase (PUS3). [8]
GALLICACID DM6Y3A0 Investigative GALLICACID decreases the expression of tRNA pseudouridine(38/39) synthase (PUS3). [12]
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⏷ Show the Full List of 13 Drug(s)

References

1 Host Vesicle Fusion Protein VAPB Contributes to the Nuclear Egress Stage of Herpes Simplex Virus Type-1 (HSV-1) Replication.Cells. 2019 Feb 3;8(2):120. doi: 10.3390/cells8020120.
2 Role of Pseudouridine Formation by Deg1 for Functionality of Two Glutamine Isoacceptor tRNAs.Biomolecules. 2017 Jan 26;7(1):8. doi: 10.3390/biom7010008.
3 A homozygous truncating mutation in PUS3 expands the role of tRNA modification in normal cognition. Hum Genet. 2016 Jul;135(7):707-13. doi: 10.1007/s00439-016-1665-7. Epub 2016 Apr 7.
4 Unraveling the disease pathogenesis behind lethal hydrolethalus syndrome revealed multiple changes in molecular and cellular level.Pathogenetics. 2009 Apr 28;2(1):2. doi: 10.1186/1755-8417-2-2.
5 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.
6 Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
7 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
8 Utilization of CDKN1A/p21 gene for class discrimination of DNA damage-induced clastogenicity. Toxicology. 2014 Jan 6;315:8-16. doi: 10.1016/j.tox.2013.10.009. Epub 2013 Nov 6.
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 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.
11 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.
12 Gene expression profile analysis of gallic acid-induced cell death process. Sci Rep. 2021 Aug 18;11(1):16743. doi: 10.1038/s41598-021-96174-1.