Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTMJD2HI)

• DOT Name: Trem-like transcript 1 protein (TREML1)
• Synonyms: TLT-1; Triggering receptor expressed on myeloid cells-like protein 1
• Gene Name: TREML1
• Related Disease:
  Malaria
  Acute myelogenous leukaemia
  Adult respiratory distress syndrome
  Alzheimer disease
  Juvenile idiopathic arthritis
• UniProt ID: TRML1_HUMAN
• PDB ID: 2FRG
• Sequence:
  MGLTLLLLLLLGLEGQGIVGSLPEVLQAPVGSSILVQCHYRLQDVKAQKVWCRFLPEGCQ
  PLVSSAVDRRAPAGRRTFLTDLGGGLLQVEMVTLQEEDAGEYGCMVDGARGPQILHRVSL
  NILPPEEEEETHKIGSLAENAFSDPAGSANPLEPSQDEKSIPLIWGAVLLVGLLVAAVVL
  FAVMAKRKQGNRLGVCGRFLSSRVSGMNPSSVVHHVSDSGPAAELPLDVPHIRLDSPPSF
  DNTTYTSLPLDSPSGKPSLPAPSSLPPLPPKVLVCSKPVTYATVIFPGGNKGGGTSCGPA
  QNPPNNQTPSS
• Function: Cell surface receptor that may play a role in the innate and adaptive immune response.
• Tissue Specificity: Detected in platelets, monocytic leukemia and in T-cell leukemia.
• Reactome Pathway: Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell (R-HSA-198933)

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Malaria	DISQ9Y50	Definitive	Genetic Variation	[1]
Acute myelogenous leukaemia	DISCSPTN	Strong	Genetic Variation	[2]
Adult respiratory distress syndrome	DISIJV47	Strong	Altered Expression	[3]
Alzheimer disease	DISF8S70	Strong	Genetic Variation	[4]
Juvenile idiopathic arthritis	DISQZGBV	Strong	Biomarker	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Folic acid	DMEMBJC	Approved	Folic acid decreases the expression of Trem-like transcript 1 protein (TREML1).	[6]

1 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 increases the methylation of Trem-like transcript 1 protein (TREML1).	[7]

References

• [1] Triggering receptor expressed on myeloid cells 1 (TREM-1) and cytokine gene variants in complicated and uncomplicated malaria.Trop Med Int Health. 2016 Dec;21(12):1592-1601. doi: 10.1111/tmi.12787. Epub 2016 Oct 24.
• [2] Downregulation of TREM-like transcript-1 and collagen receptor 2 subunit, two novel RUNX1-targets, contributes to platelet dysfunction in familial platelet disorder with predisposition to acute myelogenous leukemia.Haematologica. 2019 Jun;104(6):1244-1255. doi: 10.3324/haematol.2018.188904. Epub 2018 Dec 13.
• [3] High Levels of Soluble Triggering Receptor Expressed on Myeloid Cells-Like Transcript (TLT)-1 Are Associated With Acute Respiratory Distress Syndrome.Clin Appl Thromb Hemost. 2018 Oct;24(7):1122-1127. doi: 10.1177/1076029618774149. Epub 2018 May 14.
• [4] A Candidate Regulatory Variant at the TREM Gene Cluster Confer Alzheimer's Disease Risk by Modulating Both Amyloid- Pathology and Neuronal Degeneration.Front Neurosci. 2019 Jul 17;13:742. doi: 10.3389/fnins.2019.00742. eCollection 2019.
• [5] Gene expression signatures in polyarticular juvenile idiopathic arthritis demonstrate disease heterogeneity and offer a molecular classification of disease subsets.Arthritis Rheum. 2009 Jul;60(7):2113-23. doi: 10.1002/art.24534.
• [6] Folic acid supplementation dysregulates gene expression in lymphoblastoid cells--implications in nutrition. Biochem Biophys Res Commun. 2011 Sep 9;412(4):688-92. doi: 10.1016/j.bbrc.2011.08.027. Epub 2011 Aug 16.
• [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.