Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTYINI36)

• DOT Name: U5 small nuclear ribonucleoprotein TSSC4 (TSSC4)
• Synonyms: Tumor-suppressing STF cDNA 4 protein; Tumor-suppressing subchromosomal transferable fragment candidate gene 4 protein
• Gene Name: TSSC4
• UniProt ID: TSSC4_HUMAN
• PDB ID: 7PX3
• Pfam ID: PF15264
• Sequence:
  MAEAGTGEPSPSVEGEHGTEYDTLPSDTVSLSDSDSDLSLPGGAEVEALSPMGLPGEEDS
  GPDEPPSPPSGLLPATVQPFHLRGMSSTFSQRSRDIFDCLEGAARRAPSSVAHTSMSDNG
  GFKRPLAPSGRSPVEGLGRAHRSPASPRVPPVPDYVAHPERWTKYSLEDVTEVSEQSNQA
  TALAFLGSQSLAAPTDCVSSFNQDPSSCGEGRVIFTKPVRGVEARHERKRVLGKVGEPGR
  GGLGNPATDRGEGPVELAHLAGPGSPEAEEWGSHHGGLQEVEALSGSVHSGSVPGLPPVE
  TVGFHGSRKRSRDHFRNKSSSPEDPGAEV
• Function: Protein associated with the U5 snRNP, during its maturation and its post-splicing recycling and which is required for spliceosomal tri-snRNP complex assembly in the nucleus. Has a molecular sequestering activity and transiently hinders SNRNP200 binding sites for constitutive splicing factors that intervene later during the assembly of the spliceosome and splicing. Together with its molecular sequestering activity, may also function as a molecular adapter and placeholder, coordinating the assembly of the U5 snRNP and its association with the U4/U6 di-snRNP.
• Tissue Specificity: Expressed in fetal brain, lung, liver and kidney. Widely expressed in adult tissues.

Molecular Interaction Atlas (MIA) 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 U5 small nuclear ribonucleoprotein TSSC4 (TSSC4).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of U5 small nuclear ribonucleoprotein TSSC4 (TSSC4).	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of U5 small nuclear ribonucleoprotein TSSC4 (TSSC4).	[2]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of U5 small nuclear ribonucleoprotein TSSC4 (TSSC4).	[3]
Selenium	DM25CGV	Approved	Selenium increases the expression of U5 small nuclear ribonucleoprotein TSSC4 (TSSC4).	[4]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of U5 small nuclear ribonucleoprotein TSSC4 (TSSC4).	[5]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of U5 small nuclear ribonucleoprotein TSSC4 (TSSC4).	[7]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of U5 small nuclear ribonucleoprotein TSSC4 (TSSC4).	[8]

References

• [1] 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.
• [2] 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.
• [3] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [4] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [5] Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 30.
• [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] Isobaric tags for relative and absolute quantitation-based proteomics analysis of the effect of ginger oil on bisphenol A-induced breast cancer cell proliferation. Oncol Lett. 2021 Feb;21(2):101. doi: 10.3892/ol.2020.12362. Epub 2020 Dec 8.
• [8] A trichostatin A expression signature identified by TempO-Seq targeted whole transcriptome profiling. PLoS One. 2017 May 25;12(5):e0178302. doi: 10.1371/journal.pone.0178302. eCollection 2017.