Details of Drug Off-Target (DOT)

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

• DOT Name: Splicing factor 3B subunit 5 (SF3B5)
• Synonyms: SF3b5; Pre-mRNA-splicing factor SF3b 10 kDa subunit
• Gene Name: SF3B5
• UniProt ID: SF3B5_HUMAN
• PDB ID: 5IFE ; 5O9Z ; 5Z56 ; 5Z57 ; 5Z58 ; 5ZYA ; 6AH0 ; 6EN4 ; 6FF4 ; 6FF7 ; 6QX9 ; 6Y50 ; 6Y5Q ; 7ABG ; 7ABH ; 7ABI ; 7B0I ; 7B91 ; 7B92 ; 7B9C ; 7DVQ ; 7EVN ; 7EVO ; 7KTS ; 7OMF ; 7ONB ; 7OPI ; 7Q3L ; 7Q4O ; 7Q4P ; 7QTT ; 7VPX ; 8CH6 ; 8H7G ; 8HK1
• Pfam ID: PF07189
• Sequence:
  MTDRYTIHSQLEHLQSKYIGTGHADTTKWEWLVNQHRDSYCSYMGHFDLLNYFAIAENES
  KARVRFNLMEKMLQPCGPPADKPEEN
• Function: Component of the 17S U2 SnRNP complex of the spliceosome, a large ribonucleoprotein complex that removes introns from transcribed pre-mRNAs. The 17S U2 SnRNP complex (1) directly participates in early spliceosome assembly and (2) mediates recognition of the intron branch site during pre-mRNA splicing by promoting the selection of the pre-mRNA branch-site adenosine, the nucleophile for the first step of splicing. Within the 17S U2 SnRNP complex, SF3B4 is part of the SF3B subcomplex, which is required for 'A' complex assembly formed by the stable binding of U2 snRNP to the branchpoint sequence in pre-mRNA. Sequence independent binding of SF3A and SF3B subcomplexes upstream of the branch site is essential, it may anchor U2 snRNP to the pre-mRNA. Also acts as a component of the minor spliceosome, which is involved in the splicing of U12-type introns in pre-mRNAs.
• KEGG Pathway: Spliceosome (hsa03040)
• Reactome Pathway:
  mRNA Splicing - Minor Pathway (R-HSA-72165)
  mRNA Splicing - Major Pathway (R-HSA-72163)

Molecular Interaction Atlas (MIA) of This DOT

11 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 Splicing factor 3B subunit 5 (SF3B5).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Splicing factor 3B subunit 5 (SF3B5).	[2]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Splicing factor 3B subunit 5 (SF3B5).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Splicing factor 3B subunit 5 (SF3B5).	[4]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Splicing factor 3B subunit 5 (SF3B5).	[5]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Splicing factor 3B subunit 5 (SF3B5).	[6]
Resveratrol	DM3RWXL	Phase 3	Resveratrol increases the expression of Splicing factor 3B subunit 5 (SF3B5).	[7]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Splicing factor 3B subunit 5 (SF3B5).	[7]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Splicing factor 3B subunit 5 (SF3B5).	[8]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Splicing factor 3B subunit 5 (SF3B5).	[7]
chloropicrin	DMSGBQA	Investigative	chloropicrin increases the expression of Splicing factor 3B subunit 5 (SF3B5).	[10]

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 affects the methylation of Splicing factor 3B subunit 5 (SF3B5).	[9]

References

• [1] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [2] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [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] 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.
• [6] Minimal peroxide exposure of neuronal cells induces multifaceted adaptive responses. PLoS One. 2010 Dec 17;5(12):e14352. doi: 10.1371/journal.pone.0014352.
• [7] Gene expression profiling in Ishikawa cells: a fingerprint for estrogen active compounds. Toxicol Appl Pharmacol. 2009 Apr 1;236(1):85-96.
• [8] 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.
• [9] 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.
• [10] Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.