Details of Drug Off-Target (DOT)

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

• DOT Name: Toll-like receptor 1 (TLR1)
• Synonyms: Toll/interleukin-1 receptor-like protein; TIL; CD antigen CD281
• Gene Name: TLR1
• UniProt ID: TLR1_HUMAN
• PDB ID: 1FYV; 2Z7X; 6NIH; 7NT7; 7NUW; 7NUX
• Pfam ID: PF13855 ; PF01463 ; PF01582
• Sequence:
  MTSIFHFAIIFMLILQIRIQLSEESEFLVDRSKNGLIHVPKDLSQKTTILNISQNYISEL
  WTSDILSLSKLRILIISHNRIQYLDISVFKFNQELEYLDLSHNKLVKISCHPTVNLKHLD
  LSFNAFDALPICKEFGNMSQLKFLGLSTTHLEKSSVLPIAHLNISKVLLVLGETYGEKED
  PEGLQDFNTESLHIVFPTNKEFHFILDVSVKTVANLELSNIKCVLEDNKCSYFLSILAKL
  QTNPKLSNLTLNNIETTWNSFIRILQLVWHTTVWYFSISNVKLQGQLDFRDFDYSGTSLK
  ALSIHQVVSDVFGFPQSYIYEIFSNMNIKNFTVSGTRMVHMLCPSKISPFLHLDFSNNLL
  TDTVFENCGHLTELETLILQMNQLKELSKIAEMTTQMKSLQQLDISQNSVSYDEKKGDCS
  WTKSLLSLNMSSNILTDTIFRCLPPRIKVLDLHSNKIKSIPKQVVKLEALQELNVAFNSL
  TDLPGCGSFSSLSVLIIDHNSVSHPSADFFQSCQKMRSIKAGDNPFQCTCELGEFVKNID
  QVSSEVLEGWPDSYKCDYPESYRGTLLKDFHMSELSCNITLLIVTIVATMLVLAVTVTSL
  CSYLDLPWYLRMVCQWTQTRRRARNIPLEELQRNLQFHAFISYSGHDSFWVKNELLPNLE
  KEGMQICLHERNFVPGKSIVENIITCIEKSYKSIFVLSPNFVQSEWCHYELYFAHHNLFH
  EGSNSLILILLEPIPQYSIPSSYHKLKSLMARRTYLEWPKEKSKRGLFWANLRAAINIKL
  TEQAKK
• Function: Participates in the innate immune response to microbial agents. Specifically recognizes diacylated and triacylated lipopeptides. Cooperates with TLR2 to mediate the innate immune response to bacterial lipoproteins or lipopeptides. Forms the activation cluster TLR2:TLR1:CD14 in response to triacylated lipopeptides, this cluster triggers signaling from the cell surface and subsequently is targeted to the Golgi in a lipid-raft dependent pathway. Acts via MYD88 and TRAF6, leading to NF-kappa-B activation, cytokine secretion and the inflammatory response.
• Tissue Specificity: Ubiquitous. Highly expressed in spleen, ovary, peripheral blood leukocytes, thymus and small intestine.
• KEGG Pathway:
  Toll-like receptor sig.ling pathway (hsa04620)
  Tuberculosis (hsa05152)
• Reactome Pathway:
  Beta defensins (R-HSA-1461957)
  MyD88 (R-HSA-166058)
  Toll Like Receptor TLR1 (R-HSA-168179)
  MyD88 deficiency (TLR2/4) (R-HSA-5602498)
  IRAK4 deficiency (TLR2/4) (R-HSA-5603041)
  Regulation of TLR by endogenous ligand (R-HSA-5686938)
  SARS-CoV-2 activates/modulates innate and adaptive immune responses (R-HSA-9705671)
  ER-Phagosome pathway (R-HSA-1236974)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Toll-like receptor 1 (TLR1).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Toll-like receptor 1 (TLR1).	[10]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Toll-like receptor 1 (TLR1).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Toll-like receptor 1 (TLR1).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Toll-like receptor 1 (TLR1).	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Toll-like receptor 1 (TLR1).	[5]
Arsenic	DMTL2Y1	Approved	Arsenic increases the expression of Toll-like receptor 1 (TLR1).	[6]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Toll-like receptor 1 (TLR1).	[7]
Rifampicin	DM5DSFZ	Approved	Rifampicin increases the expression of Toll-like receptor 1 (TLR1).	[8]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Toll-like receptor 1 (TLR1).	[9]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Toll-like receptor 1 (TLR1).	[11]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Toll-like receptor 1 (TLR1).	[12]
Butanoic acid	DMTAJP7	Investigative	Butanoic acid increases the expression of Toll-like receptor 1 (TLR1).	[13]

References

• [1] 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.
• [2] 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.
• [3] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [4] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [5] 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.
• [6] Transcriptomics and methylomics of CD4-positive T cells in arsenic-exposed women. Arch Toxicol. 2017 May;91(5):2067-2078. doi: 10.1007/s00204-016-1879-4. Epub 2016 Nov 12.
• [7] Functional gene expression profile underlying methotrexate-induced senescence in human colon cancer cells. Tumour Biol. 2011 Oct;32(5):965-76.
• [8] Integrated analysis of rifampicin-induced microRNA and gene expression changes in human hepatocytes. Drug Metab Pharmacokinet. 2014;29(4):333-40.
• [9] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [10] 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.
• [11] Comparison of transcriptome expression alterations by chronic exposure to low-dose bisphenol A in different subtypes of breast cancer cells. Toxicol Appl Pharmacol. 2019 Dec 15;385:114814. doi: 10.1016/j.taap.2019.114814. Epub 2019 Nov 9.
• [12] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [13] Candida albicans and Saccharomyces cerevisiae induce interleukin-8 production from intestinal epithelial-like Caco-2 cells in the presence of butyric acid. FEMS Immunol Med Microbiol. 2004 Jul 1;41(3):227-35. doi: 10.1016/j.femsim.2004.03.006.