Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTV4QGY7)

• DOT Name: U6 snRNA-associated Sm-like protein LSm8 (LSM8)
• Gene Name: LSM8
• UniProt ID: LSM8_HUMAN
• PDB ID: 3JCR; 5O9Z; 6AH0; 6AHD; 6QW6; 6QX9; 7ABG
• Pfam ID: PF01423
• Sequence:
  MTSALENYINRTVAVITSDGRMIVGTLKGFDQTINLILDESHERVFSSSQGVEQVVLGLY
  IVRGDNVAVIGEIDEETDSALDLGNIRAEPLNSVAH
• Function: Plays a role in pre-mRNA splicing as component of the U4/U6-U5 tri-snRNP complex that is involved in spliceosome assembly, and as component of the precatalytic spliceosome (spliceosome B complex). The heptameric LSM2-8 complex binds specifically to the 3'-terminal U-tract of U6 snRNA.
• KEGG Pathway:
  R. degradation (hsa03018)
  Spliceosome (hsa03040)
• Reactome Pathway: mRNA Splicing - Major Pathway (R-HSA-72163)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of U6 snRNA-associated Sm-like protein LSm8 (LSM8).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of U6 snRNA-associated Sm-like protein LSm8 (LSM8).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of U6 snRNA-associated Sm-like protein LSm8 (LSM8).	[3]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of U6 snRNA-associated Sm-like protein LSm8 (LSM8).	[4]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of U6 snRNA-associated Sm-like protein LSm8 (LSM8).	[5]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of U6 snRNA-associated Sm-like protein LSm8 (LSM8).	[5]

1 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of U6 snRNA-associated Sm-like protein LSm8 (LSM8).	[6]

References

• [1] A comparative transcriptomic study on the effects of valproic acid on two different hESCs lines in a neural teratogenicity test system. Toxicol Lett. 2014 Nov 18;231(1):38-44.
• [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] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [4] 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.
• [5] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [6] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.