Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTBHPD8H)

• DOT Name: U6 snRNA-associated Sm-like protein LSm3 (LSM3)
• Gene Name: LSM3
• UniProt ID: LSM3_HUMAN
• PDB ID: 3JCR; 5O9Z; 6AH0; 6AHD; 6QW6; 6QX9; 7ABG
• Pfam ID: PF01423
• Sequence:
  MADDVDQQQTTNTVEEPLDLIRLSLDERIYVKMRNDRELRGRLHAYDQHLNMILGDVEET
  VTTIEIDEETYEEIYKSTKRNIPMLFVRGDGVVLVAPPLRVG
• 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)
  mRNA decay by 5' to 3' exoribonuclease (R-HSA-430039)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin affects the expression of U6 snRNA-associated Sm-like protein LSm3 (LSM3).	[1]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of U6 snRNA-associated Sm-like protein LSm3 (LSM3).	[2]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of U6 snRNA-associated Sm-like protein LSm3 (LSM3).	[3]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of U6 snRNA-associated Sm-like protein LSm3 (LSM3).	[4]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of U6 snRNA-associated Sm-like protein LSm3 (LSM3).	[6]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of U6 snRNA-associated Sm-like protein LSm3 (LSM3).	[7]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of U6 snRNA-associated Sm-like protein LSm3 (LSM3).	[8]
AHPN	DM8G6O4	Investigative	AHPN decreases the expression of U6 snRNA-associated Sm-like protein LSm3 (LSM3).	[9]
PP-242	DM2348V	Investigative	PP-242 increases the expression of U6 snRNA-associated Sm-like protein LSm3 (LSM3).	[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 increases the methylation of U6 snRNA-associated Sm-like protein LSm3 (LSM3).	[5]

References

• [1] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [2] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [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] 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.
• [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] Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem. 2012 Dec 14;287(51):43137-55.
• [7] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [8] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [9] ST1926, a novel and orally active retinoid-related molecule inducing apoptosis in myeloid leukemia cells: modulation of intracellular calcium homeostasis. Blood. 2004 Jan 1;103(1):194-207.
• [10] Marine biogenics in sea spray aerosols interact with the mTOR signaling pathway. Sci Rep. 2019 Jan 24;9(1):675.