Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTCQHXK5)

• DOT Name: U6 snRNA-associated Sm-like protein LSm5 (LSM5)
• Gene Name: LSM5
• Related Disease: Polycystic ovarian syndrome
• UniProt ID: LSM5_HUMAN
• PDB ID: 3JCR; 5O9Z; 6AH0; 6AHD; 6QW6; 6QX9; 7ABG
• Pfam ID: PF01423
• Sequence:
  MAANATTNPSQLLPLELVDKCIGSRIHIVMKSDKEIVGTLLGFDDFVNMVLEDVTEFEIT
  PEGRRITKLDQILLNGNNITMLVPGGEGPEV
• 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

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Polycystic ovarian syndrome	DISZ2BNG	Strong	Biomarker	[1]

14 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 U6 snRNA-associated Sm-like protein LSm5 (LSM5).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of U6 snRNA-associated Sm-like protein LSm5 (LSM5).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of U6 snRNA-associated Sm-like protein LSm5 (LSM5).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of U6 snRNA-associated Sm-like protein LSm5 (LSM5).	[5]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of U6 snRNA-associated Sm-like protein LSm5 (LSM5).	[6]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of U6 snRNA-associated Sm-like protein LSm5 (LSM5).	[7]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of U6 snRNA-associated Sm-like protein LSm5 (LSM5).	[8]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of U6 snRNA-associated Sm-like protein LSm5 (LSM5).	[9]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol increases the expression of U6 snRNA-associated Sm-like protein LSm5 (LSM5).	[10]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of U6 snRNA-associated Sm-like protein LSm5 (LSM5).	[12]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of U6 snRNA-associated Sm-like protein LSm5 (LSM5).	[13]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of U6 snRNA-associated Sm-like protein LSm5 (LSM5).	[14]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of U6 snRNA-associated Sm-like protein LSm5 (LSM5).	[15]
methyl p-hydroxybenzoate	DMO58UW	Investigative	methyl p-hydroxybenzoate decreases the expression of U6 snRNA-associated Sm-like protein LSm5 (LSM5).	[16]

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 LSm5 (LSM5).	[11]

References

• [1] Progesterone resistance in PCOS endometrium: a microarray analysis in clomiphene citrate-treated and artificial menstrual cycles.J Clin Endocrinol Metab. 2011 Jun;96(6):1737-46. doi: 10.1210/jc.2010-2600. Epub 2011 Mar 16.
• [2] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [3] 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.
• [4] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [5] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [6] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [7] 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.
• [8] Minimal peroxide exposure of neuronal cells induces multifaceted adaptive responses. PLoS One. 2010 Dec 17;5(12):e14352. doi: 10.1371/journal.pone.0014352.
• [9] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [10] Identification of biomarkers and outcomes of endocrine disruption in human ovarian cortex using In Vitro Models. Toxicology. 2023 Feb;485:153425. doi: 10.1016/j.tox.2023.153425. Epub 2023 Jan 5.
• [11] 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.
• [12] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [13] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
• [14] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [15] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [16] 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.