Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTH5FQHP)

DOT Name tRNA-splicing endonuclease subunit Sen34 (TSEN34)
Synonyms EC 4.6.1.16; Leukocyte receptor cluster member 5; tRNA-intron endonuclease Sen34; HsSen34
Gene Name TSEN34
Related Disease
Intellectual disability ( )
Microlissencephaly ( )
Movement disorder ( )
Vision disorder ( )
Isolated congenital microcephaly ( )
Pontocerebellar hypoplasia ( )
Pontocerebellar hypoplasia type 2C ( )
Pontocerebellar hypoplasia type 2 ( )
UniProt ID
SEN34_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
6Z9U; 7UXA; 7ZRZ; 8HMY; 8HMZ; 8ISS
EC Number
4.6.1.16
Pfam ID
PF01974
Sequence
MLVVEVANGRSLVWGAEAVQALRERLGVGGRTVGALPRGPRQNSRLGLPLLLMPEEARLL
AEIGAVTLVSAPRPDSRHHSLALTSFKRQQEESFQEQSALAAEARETRRQELLEKITEGQ
AAKKQKLEQASGASSSQEAGSSQAAKEDETSDGQASGEQEEAGPSSSQAGPSNGVAPLPR
SALLVQLATARPRPVKARPLDWRVQSKDWPHAGRPAHELRYSIYRDLWERGFFLSAAGKF
GGDFLVYPGDPLRFHAHYIAQCWAPEDTIPLQDLVAAGRLGTSVRKTLLLCSPQPDGKVV
YTSLQWASLQ
Function
Constitutes one of the two catalytic subunit of the tRNA-splicing endonuclease complex, a complex responsible for identification and cleavage of the splice sites in pre-tRNA. It cleaves pre-tRNA at the 5'- and 3'-splice sites to release the intron. The products are an intron and two tRNA half-molecules bearing 2',3'-cyclic phosphate and 5'-OH termini. There are no conserved sequences at the splice sites, but the intron is invariably located at the same site in the gene, placing the splice sites an invariant distance from the constant structural features of the tRNA body. It probably carries the active site for 3'-splice site cleavage. The tRNA splicing endonuclease is also involved in mRNA processing via its association with pre-mRNA 3'-end processing factors, establishing a link between pre-tRNA splicing and pre-mRNA 3'-end formation, suggesting that the endonuclease subunits function in multiple RNA-processing events.
Reactome Pathway
tRNA processing in the nucleus (R-HSA-6784531 )
BioCyc Pathway
MetaCyc:HS10201-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

8 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Intellectual disability DISMBNXP Definitive Biomarker [1]
Microlissencephaly DISUCKNT Definitive Biomarker [1]
Movement disorder DISOJJ2D Definitive Biomarker [1]
Vision disorder DIS8R6NJ Definitive Biomarker [1]
Isolated congenital microcephaly DISUXHZ6 Strong Biomarker [1]
Pontocerebellar hypoplasia DISRICMU Strong Genetic Variation [2]
Pontocerebellar hypoplasia type 2C DISHC8YI Strong Autosomal recessive [3]
Pontocerebellar hypoplasia type 2 DISXV76G Supportive Autosomal recessive [1]
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⏷ Show the Full List of 8 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
2 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 tRNA-splicing endonuclease subunit Sen34 (TSEN34). [4]
TAK-243 DM4GKV2 Phase 1 TAK-243 increases the sumoylation of tRNA-splicing endonuclease subunit Sen34 (TSEN34). [8]
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4 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate decreases the expression of tRNA-splicing endonuclease subunit Sen34 (TSEN34). [5]
Cisplatin DMRHGI9 Approved Cisplatin increases the expression of tRNA-splicing endonuclease subunit Sen34 (TSEN34). [6]
Ivermectin DMDBX5F Approved Ivermectin decreases the expression of tRNA-splicing endonuclease subunit Sen34 (TSEN34). [7]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 increases the expression of tRNA-splicing endonuclease subunit Sen34 (TSEN34). [9]
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References

1 tRNA splicing endonuclease mutations cause pontocerebellar hypoplasia. Nat Genet. 2008 Sep;40(9):1113-8. doi: 10.1038/ng.204.
2 Clinical, neuroradiological and genetic findings in pontocerebellar hypoplasia.Brain. 2011 Jan;134(Pt 1):143-56. doi: 10.1093/brain/awq287. Epub 2010 Oct 15.
3 Flexible and scalable diagnostic filtering of genomic variants using G2P with Ensembl VEP. Nat Commun. 2019 May 30;10(1):2373. doi: 10.1038/s41467-019-10016-3.
4 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.
5 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
6 Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
7 Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
8 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.
9 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.