Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTHZ2XPX)

• DOT Name: U6 snRNA-associated Sm-like protein LSm7 (LSM7)
• Gene Name: LSM7
• Related Disease: Advanced cancer
• UniProt ID: LSM7_HUMAN
• PDB ID: 3JCR; 5O9Z; 6AH0; 6AHD; 6QW6; 6QX9; 7ABG
• Pfam ID: PF01423
• Sequence:
  MADKEKKKKESILDLSKYIDKTIRVKFQGGREASGILKGFDPLLNLVLDGTIEYMRDPDD
  QYKLTEDTRQLGLVVCRGTSVVLICPQDGMEAIPNPFIQQQDA
• 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
Advanced cancer	DISAT1Z9	Limited	Genetic Variation	[1]

This DOT Affected the Drug Response of 2 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Irinotecan	DMP6SC2	Approved	U6 snRNA-associated Sm-like protein LSm7 (LSM7) increases the response to substance of Irinotecan.	[10]
Vinblastine	DM5TVS3	Approved	U6 snRNA-associated Sm-like protein LSm7 (LSM7) affects the response to substance of Vinblastine.	[11]

1 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 U6 snRNA-associated Sm-like protein LSm7 (LSM7).	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of U6 snRNA-associated Sm-like protein LSm7 (LSM7).	[3]
Marinol	DM70IK5	Approved	Marinol decreases the expression of U6 snRNA-associated Sm-like protein LSm7 (LSM7).	[4]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of U6 snRNA-associated Sm-like protein LSm7 (LSM7).	[5]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of U6 snRNA-associated Sm-like protein LSm7 (LSM7).	[6]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of U6 snRNA-associated Sm-like protein LSm7 (LSM7).	[7]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of U6 snRNA-associated Sm-like protein LSm7 (LSM7).	[8]
PP-242	DM2348V	Investigative	PP-242 increases the expression of U6 snRNA-associated Sm-like protein LSm7 (LSM7).	[9]

References

• [1] A six-gene model for differentiating benign from malignant thyroid tumors on the basis of gene expression.Surgery. 2005 Dec;138(6):1050-6; discussion 1056-7. doi: 10.1016/j.surg.2005.09.010.
• [2] 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.
• [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] Cannabis-induced cytotoxicity in leukemic cell lines: the role of the cannabinoid receptors and the MAPK pathway. Blood. 2005 Feb 1;105(3):1214-21. doi: 10.1182/blood-2004-03-1182. Epub 2004 Sep 28.
• [5] 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.
• [6] Comprehensive analysis of transcriptomic changes induced by low and high doses of bisphenol A in HepG2 spheroids in vitro and rat liver in vivo. Environ Res. 2019 Jun;173:124-134. doi: 10.1016/j.envres.2019.03.035. Epub 2019 Mar 18.
• [7] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [8] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [9] Marine biogenics in sea spray aerosols interact with the mTOR signaling pathway. Sci Rep. 2019 Jan 24;9(1):675.
• [10] Gene expression analysis using human cancer xenografts to identify novel predictive marker genes for the efficacy of 5-fluorouracil-based drugs. Cancer Sci. 2006 Jun;97(6):510-22. doi: 10.1111/j.1349-7006.2006.00204.x.
• [11] Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.