Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTN9M7QG)

• DOT Name: U7 snRNA-associated Sm-like protein LSm11 (LSM11)
• Gene Name: LSM11
• Related Disease:
  Aicardi-Goutieres syndrome 8
  Tourette syndrome
• UniProt ID: LSM11_HUMAN
• PDB ID: 6V4X; 8G1U
• Sequence:
  MEERERGARSAGAGSPARPPSPRLDVSSDSFDPLLALYAPRLPPIPYPNAPCFNNVAEYE
  SFLRTGVRGGGRGRGRARGAAAGSGVPAAPGPSGRTRRRPDAPAPDPERIQRLRRLMVAK
  EEGDGAAGAGRRGPGRSRKAPRNVLTRMPLHEGSPLGELHRCIREGVKVNVHIRTFKGLR
  GVCTGFLVAFDKFWNMALTDVDETYRKPVLGKAYERDSSLTLTRLFDRLKLQDSSKKEAD
  SKSAVEDSTLSRYSQTSTWKLASVWGRADTGRGSHKRSRSVPSSLQASAREESRSELSGR
  TTRTDGSSVGGTFSRATTLSRGQSRKKKRKPKVDYQQVFTRHINQIFIRGENVLLVHLAQ
• Function: Component of the U7 snRNP complex that is involved in the histone 3'-end pre-mRNA processing. Increases U7 snRNA levels but not histone 3'-end pre-mRNA processing activity, when overexpressed. Required for cell cycle progression from G1 to S phases. Binds specifically to the Sm-binding site of U7 snRNA.
• Reactome Pathway:
  RNA Polymerase II Transcription Termination (R-HSA-73856)
  SLBP Dependent Processing of Replication-Dependent Histone Pre-mRNAs (R-HSA-77588)
  SLBP independent Processing of Histone Pre-mRNAs (R-HSA-111367)

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Aicardi-Goutieres syndrome 8	DISRF42A	Limited	Unknown	[1]
Tourette syndrome	DISX9D54	No Known	Unknown	[2]

7 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 U7 snRNA-associated Sm-like protein LSm11 (LSM11).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of U7 snRNA-associated Sm-like protein LSm11 (LSM11).	[4]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of U7 snRNA-associated Sm-like protein LSm11 (LSM11).	[5]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of U7 snRNA-associated Sm-like protein LSm11 (LSM11).	[6]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of U7 snRNA-associated Sm-like protein LSm11 (LSM11).	[7]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of U7 snRNA-associated Sm-like protein LSm11 (LSM11).	[8]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of U7 snRNA-associated Sm-like protein LSm11 (LSM11).	[9]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of U7 snRNA-associated Sm-like protein LSm11 (LSM11).	[10]

References

• [1] cGAS-mediated induction of type I interferon due to inborn errors of histone pre-mRNA processing. Nat Genet. 2020 Dec;52(12):1364-1372. doi: 10.1038/s41588-020-00737-3. Epub 2020 Nov 23.
• [2] De Novo Coding Variants Are Strongly Associated with Tourette Disorder. Neuron. 2017 May 3;94(3):486-499.e9. doi: 10.1016/j.neuron.2017.04.024.
• [3] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [4] 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.
• [5] Essential role of cell cycle regulatory genes p21 and p27 expression in inhibition of breast cancer cells by arsenic trioxide. Med Oncol. 2011 Dec;28(4):1225-54.
• [6] 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.
• [7] Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
• [8] A trichostatin A expression signature identified by TempO-Seq targeted whole transcriptome profiling. PLoS One. 2017 May 25;12(5):e0178302. doi: 10.1371/journal.pone.0178302. eCollection 2017.
• [9] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [10] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.