Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTUED31V)

• DOT Name: RNA-splicing ligase RtcB homolog (RTCB)
• Synonyms: EC 6.5.1.8; 3'-phosphate/5'-hydroxy nucleic acid ligase
• Gene Name: RTCB
• Related Disease:
  Breast cancer
  Breast carcinoma
  Neoplasm
• UniProt ID: RTCB_HUMAN
• PDB ID: 7P3B
• EC Number: 6.5.1.8
• Pfam ID: PF01139
• Sequence:
  MSRSYNDELQFLEKINKNCWRIKKGFVPNMQVEGVFYVNDALEKLMFEELRNACRGGGVG
  GFLPAMKQIGNVAALPGIVHRSIGLPDVHSGYGFAIGNMAAFDMNDPEAVVSPGGVGFDI
  NCGVRLLRTNLDESDVQPVKEQLAQAMFDHIPVGVGSKGVIPMNAKDLEEALEMGVDWSL
  REGYAWAEDKEHCEEYGRMLQADPNKVSARAKKRGLPQLGTLGAGNHYAEIQVVDEIFNE
  YAAKKMGIDHKGQVCVMIHSGSRGLGHQVATDALVAMEKAMKRDKIIVNDRQLACARIAS
  PEGQDYLKGMAAAGNYAWVNRSSMTFLTRQAFAKVFNTTPDDLDLHVIYDVSHNIAKVEQ
  HVVDGKERTLLVHRKGSTRAFPPHHPLIAVDYQLTGQPVLIGGTMGTCSYVLTGTEQGMT
  ETFGTTCHGAGRALSRAKSRRNLDFQDVLDKLADMGIAIRVASPKLVMEEAPESYKNVTD
  VVNTCHDAGISKKAIKLRPIAVIKG
• Function: Catalytic subunit of the tRNA-splicing ligase complex that acts by directly joining spliced tRNA halves to mature-sized tRNAs by incorporating the precursor-derived splice junction phosphate into the mature tRNA as a canonical 3',5'-phosphodiester. May act as an RNA ligase with broad substrate specificity, and may function toward other RNAs.
• Reactome Pathway: tRNA processing in the nucleus (R-HSA-6784531)
• BioCyc Pathway: MetaCyc:ENSG00000100220-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Breast cancer	DIS7DPX1	Strong	Altered Expression	[1]
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[1]
Neoplasm	DISZKGEW	Strong	Altered Expression	[1]

5 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate affects the expression of RNA-splicing ligase RtcB homolog (RTCB).	[2]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of RNA-splicing ligase RtcB homolog (RTCB).	[3]
Clozapine	DMFC71L	Approved	Clozapine increases the expression of RNA-splicing ligase RtcB homolog (RTCB).	[4]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of RNA-splicing ligase RtcB homolog (RTCB).	[6]
methyl p-hydroxybenzoate	DMO58UW	Investigative	methyl p-hydroxybenzoate increases the expression of RNA-splicing ligase RtcB homolog (RTCB).	[7]

1 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 decreases the methylation of RNA-splicing ligase RtcB homolog (RTCB).	[5]

References

• [1] Nanoparticle Delivery of miR-34a Eradicates Long-term-cultured Breast Cancer Stem Cells via Targeting C22ORF28 Directly.Theranostics. 2017 Oct 17;7(19):4805-4824. doi: 10.7150/thno.20771. eCollection 2017.
• [2] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [3] 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.
• [4] Cannabidiol Displays Proteomic Similarities to Antipsychotics in Cuprizone-Exposed Human Oligodendrocytic Cell Line MO3.13. Front Mol Neurosci. 2021 May 28;14:673144. doi: 10.3389/fnmol.2021.673144. eCollection 2021.
• [5] 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.
• [6] Alternatives for the worse: Molecular insights into adverse effects of bisphenol a and substitutes during human adipocyte differentiation. Environ Int. 2021 Nov;156:106730. doi: 10.1016/j.envint.2021.106730. Epub 2021 Jun 27.
• [7] Transcriptome dynamics of alternative splicing events revealed early phase of apoptosis induced by methylparaben in H1299 human lung carcinoma cells. Arch Toxicol. 2020 Jan;94(1):127-140. doi: 10.1007/s00204-019-02629-w. Epub 2019 Nov 20.