Details of Drug Off-Target (DOT)

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

• DOT Name: TLR4 interactor with leucine rich repeats (TRIL)
• Synonyms: Leucine-rich repeat-containing protein KIAA0644
• Gene Name: TRIL
• UniProt ID: TRIL_HUMAN
• Pfam ID: PF13855
• Sequence:
  MEAARALRLLLVVCGCLALPPLAEPVCPERCDCQHPQHLLCTNRGLRVVPKTSSLPSPHD
  VLTYSLGGNFITNITAFDFHRLGQLRRLDLQYNQIRSLHPKTFEKLSRLEELYLGNNLLQ
  ALAPGTLAPLRKLRILYANGNEISRLSRGSFEGLESLVKLRLDGNALGALPDAVFAPLGN
  LLYLHLESNRIRFLGKNAFAQLGKLRFLNLSANELQPSLRHAATFAPLRSLSSLILSANN
  LQHLGPRIFQHLPRLGLLSLRGNQLTHLAPEAFWGLEALRELRLEGNRLSQLPTALLEPL
  HSLEALDLSGNELSALHPATFGHLGRLRELSLRNNALSALSGDIFAASPALYRLDLDGNG
  WTCDCRLRGLKRWMGDWHSQGRLLTVFVQCRHPPALRGKYLDYLDDQQLQNGSCADPSPS
  ASLTADRRRQPLPTAAGEEMTPPAGLAEELPPQPQLQQQGRFLAGVAWDGAARELVGNRS
  ALRLSRRGPGLQQPSPSVAAAAGPAPQSLDLHKKPQRGRPTRADPALAEPTPTASPGSAP
  SPAGDPWQRATKHRLGTEHQERAAQSDGGAGLPPLVSDPCDFNKFILCNLTVEAVGADSA
  SVRWAVREHRSPRPLGGARFRLLFDRFGQQPKFHRFVYLPESSDSATLRELRGDTPYLVC
  VEGVLGGRVCPVAPRDHCAGLVTLPEAGSRGGVDYQLLTLALLTVNALLVLLALAAWASR
  WLRRKLRARRKGGAPVHVRHMYSTRRPLRSMGTGVSADFSGFQSHRPRTTVCALSEADLI
  EFPCDRFMDSAGGGAGGSLRREDRLLQRFAD
• Function: Component of the TLR4 signaling complex. Mediates the innate immune response to bacterial lipopolysaccharide (LPS) leading to cytokine secretion.
• Tissue Specificity: Highly expressed in the brain, ovary, small intestine and spleen.

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 increases the methylation of TLR4 interactor with leucine rich repeats (TRIL).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of TLR4 interactor with leucine rich repeats (TRIL).	[8]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of TLR4 interactor with leucine rich repeats (TRIL).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of TLR4 interactor with leucine rich repeats (TRIL).	[3]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of TLR4 interactor with leucine rich repeats (TRIL).	[4]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of TLR4 interactor with leucine rich repeats (TRIL).	[5]
Testosterone enanthate	DMB6871	Approved	Testosterone enanthate affects the expression of TLR4 interactor with leucine rich repeats (TRIL).	[6]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of TLR4 interactor with leucine rich repeats (TRIL).	[7]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of TLR4 interactor with leucine rich repeats (TRIL).	[9]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of TLR4 interactor with leucine rich repeats (TRIL).	[5]

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] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [3] 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.
• [4] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [5] Identification of transcriptome signatures and biomarkers specific for potential developmental toxicants inhibiting human neural crest cell migration. Arch Toxicol. 2016 Jan;90(1):159-80.
• [6] Transcriptional profiling of testosterone-regulated genes in the skeletal muscle of human immunodeficiency virus-infected men experiencing weight loss. J Clin Endocrinol Metab. 2007 Jul;92(7):2793-802. doi: 10.1210/jc.2006-2722. Epub 2007 Apr 17.
• [7] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [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] Bisphenol A and bisphenol S induce distinct transcriptional profiles in differentiating human primary preadipocytes. PLoS One. 2016 Sep 29;11(9):e0163318.