Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTBX8CPZ)

• DOT Name: Schlafen family member 13 (SLFN13)
• Synonyms: EC 3.1.-.-; Schlafen-13; hSLFN13
• Gene Name: SLFN13
• UniProt ID: SLN13_HUMAN
• EC Number: 3.1.-.-
• Pfam ID: PF17057 ; PF09848 ; PF04326 ; PF21026
• Sequence:
  MEANHCSLGVYPSYPDLVIDVGEVTLGEENRKKLQKTQRDQERARVIRAACALLNSGGGV
  IQMEMANRDERPTEMGLDLEESLRKLIQYPYLQAFFETKQHGRCFYIFVKSWSGDPFLKD
  GSFNSRICSLSSSLYCRSGTSVLHMNSRQAFDFLKTKERQSKYNLINEGSPPSKIMKAVY
  QNISESNPAYEVFQTDTIEYGEILSFPESPSIEFKQFSTKHIQQYVENIIPEYISAFANT
  EGGYLFIGVDDKSRKVLGCAKEQVDPDSLKNVIARAISKLPIVHFCSSKPRVEYSTKIVE
  VFCGKELYGYLCVIKVKAFCCVVFSEAPKSWMVREKYIRPLTTEEWVEKMMDADPEFPPD
  FAEAFESQLSLSDSPSLCRPVYSKKGLEHKADLQQHLFPVPPGHLECTPESLWKELSLQH
  EGLKELIHKQMRPFSQGIVILSRSWAVDLNLQEKPGVICDALLIAQNSTPILYTILREQD
  AEGQDYCTRTAFTLKQKLVNMGGYTGKVCVRAKVLCLSPESSAEALEAAVSPMDYPASYS
  LAGTQHMEALLQSLVIVLLGFRSLLSDQLGCEVLNLLTAQQYEIFSRSLRKNRELFVHGL
  PGSGKTIMAMKIMEKIRNVFHCEAHRILYVCENQPLRNFISDRNICRAETRETFLREKFE
  HIQHIVIDEAQNFRTEDGDWYRKAKTITQREKDCPGVLWIFLDYFQTSHLGHSGLPPLSA
  QYPREELTRVVRNADEIAEYIQQEMQLIIENPPINIPHGYLAILSEAKWVPGVPGNTKII
  KNFTLEQIVTYVADTCRCFFERGYSPKDVAVLVSTVTEVEQYQSKLLKAMRKKMVVQLSD
  ACDMLGVHIVLDSVRRFSGLERSIVFGIHPRTADPAILPNILICLASRAKQHLYIFL
• Function: Endoribonuclease that cleaves tRNAs and rRNAs. Cleaves tRNAs 11 nucleotides from the 3'-terminus at the acceptor stem. Does not act on tRNA(Sec). Able to restrict HIV-1 virus replication; ability to inhibit HIV-1 replication is dependent on endoribonuclease activity.

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
Valproate	DMCFE9I	Approved	Valproate increases the expression of Schlafen family member 13 (SLFN13).	[1]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Schlafen family member 13 (SLFN13).	[2]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Schlafen family member 13 (SLFN13).	[3]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Schlafen family member 13 (SLFN13).	[4]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Schlafen family member 13 (SLFN13).	[5]
Demecolcine	DMCZQGK	Approved	Demecolcine decreases the expression of Schlafen family member 13 (SLFN13).	[6]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Schlafen family member 13 (SLFN13).	[7]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Schlafen family member 13 (SLFN13).	[9]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Schlafen family member 13 (SLFN13).	[11]

2 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 decreases the methylation of Schlafen family member 13 (SLFN13).	[8]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the methylation of Schlafen family member 13 (SLFN13).	[10]

References

• [1] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [2] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [3] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [4] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [5] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [6] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [7] 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.
• [8] 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.
• [9] 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.
• [10] 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.
• [11] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.