Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTL9X02U)

• DOT Name: T-complex protein 11-like protein 1 (TCP11L1)
• Gene Name: TCP11L1
• Related Disease: Rheumatoid arthritis
• UniProt ID: T11L1_HUMAN
• Pfam ID: PF05794
• Sequence:
  MSENLDKSNVNEAGKSKSNDSEEGLEDAVEGADEALQKAIKSDSSSPQRVQRPHSSPPRF
  VTVEELLETARGVTNMALAHEIVVNGDFQIKPVELPENSLKKRVKEIVHKAFWDCLSVQL
  SEDPPAYDHAIKLVGEIKETLLSFLLPGHTRLRNQITEVLDLDLIKQEAENGALDISKLA
  EFIIGMMGTLCAPARDEEVKKLKDIKEIVPLFREIFSVLDLMKVDMANFAISSIRPHLMQ
  QSVEYERKKFQEILERQPNSLDFVTQWLEEASEDLMTQKYKHALPVGGMAAGSGDMPRLS
  PVAVQNYAYLKLLKWDHLQRPFPETVLMDQSRFHELQLQLEQLTILGAVLLVTFSMAAPG
  ISSQADFAEKLKMIVKILLTDMHLPSFHLKDVLTTIGEKVCLEVSSCLSLCGSSPFTTDK
  ETVLKGQIQAVASPDDPIRRIMESRILTFLETYLASGHQKPLPTVPGGLSPVQRELEEVA
  IKFARLVNYNKMVFCPYYDAILSKILVRS

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Rheumatoid arthritis	DISTSB4J	Strong	Genetic Variation	[1]

7 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 T-complex protein 11-like protein 1 (TCP11L1).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of T-complex protein 11-like protein 1 (TCP11L1).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of T-complex protein 11-like protein 1 (TCP11L1).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of T-complex protein 11-like protein 1 (TCP11L1).	[5]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of T-complex protein 11-like protein 1 (TCP11L1).	[6]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of T-complex protein 11-like protein 1 (TCP11L1).	[8]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of T-complex protein 11-like protein 1 (TCP11L1).	[10]

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 T-complex protein 11-like protein 1 (TCP11L1).	[7]
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of T-complex protein 11-like protein 1 (TCP11L1).	[9]

References

• [1] Genome-wide association analysis implicates the involvement of eight loci with response to tocilizumab for the treatment of rheumatoid arthritis.Pharmacogenomics J. 2013 Jun;13(3):235-41. doi: 10.1038/tpj.2012.8. Epub 2012 Apr 10.
• [2] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [3] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [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] 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.
• [6] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [7] 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.
• [8] Isobaric tags for relative and absolute quantitation-based proteomics analysis of the effect of ginger oil on bisphenol A-induced breast cancer cell proliferation. Oncol Lett. 2021 Feb;21(2):101. doi: 10.3892/ol.2020.12362. Epub 2020 Dec 8.
• [9] 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.
• [10] Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047. doi: 10.1016/j.fct.2019.111047. Epub 2019 Dec 12.