Details of Drug Off-Target (DOT)

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

• DOT Name: Trem-like transcript 2 protein (TREML2)
• Synonyms: TLT-2; Triggering receptor expressed on myeloid cells-like protein 2
• Gene Name: TREML2
• Related Disease:
  Alzheimer disease
  Hepatitis B virus infection
  High blood pressure
  Ankylosing spondylitis
• UniProt ID: TRML2_HUMAN
• Sequence:
  MAPAFLLLLLLWPQGCVSGPSADSVYTKVRLLEGETLSVQCSYKGYKNRVEGKVWCKIRK
  KKCEPGFARVWVKGPRYLLQDDAQAKVVNITMVALKLQDSGRYWCMRNTSGILYPLMGFQ
  LDVSPAPQTERNIPFTHLDNILKSGTVTTGQAPTSGPDAPFTTGVMVFTPGLITLPRLLA
  STRPASKTGYSFTATSTTSQGPRRTMGSQTVTASPSNARDSSAGPESISTKSGDLSTRSP
  TTGLCLTSRSLLNRLPSMPSIRHQDVYSTVLGVVLTLLVLMLIMVYGFWKKRHMASYSMC
  SDPSTRDPPGRPEPYVEVYLI
• Function: Cell surface receptor that may play a role in the innate and adaptive immune response. Acts as a counter-receptor for CD276 and interaction with CD276 on T-cells enhances T-cell activation.
• Tissue Specificity: Detected in cultured B-cells, T-cell leukemia and monocyte leukemia. Expressed constitutively on CD8 T-cells and induced on CD4 T-cells after activation.
• Reactome Pathway: Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell (R-HSA-198933)

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Alzheimer disease	DISF8S70	Strong	Genetic Variation	[1]
Hepatitis B virus infection	DISLQ2XY	Strong	Biomarker	[2]
High blood pressure	DISY2OHH	moderate	Genetic Variation	[3]
Ankylosing spondylitis	DISRC6IR	Limited	Biomarker	[4]

4 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 Trem-like transcript 2 protein (TREML2).	[5]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Trem-like transcript 2 protein (TREML2).	[6]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Trem-like transcript 2 protein (TREML2).	[8]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane increases the expression of Trem-like transcript 2 protein (TREML2).	[9]

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 2 protein (TREML2).	[7]

References

• [1] A Missense Variant in TREML2 Reduces Risk of Alzheimer's Disease in a Han Chinese Population.Mol Neurobiol. 2017 Mar;54(2):977-982. doi: 10.1007/s12035-016-9706-8. Epub 2016 Jan 21.
• [2] Myeloid cell-like transcript 2 is related to liver inflammation and the pathogenesis of hepatitis B via the involvement of CD8(+)T cell activation.Clin Exp Med. 2019 Feb;19(1):93-104. doi: 10.1007/s10238-018-0534-1. Epub 2018 Oct 25.
• [3] Male-specific genetic effect on hypertension and metabolic disorders.Hum Genet. 2014 Mar;133(3):311-9. doi: 10.1007/s00439-013-1382-4. Epub 2013 Oct 20.
• [4] Genetic variants of TREML2 are associated with HLA-B27-positive ankylosing spondylitis.Gene. 2018 Aug 20;668:121-128. doi: 10.1016/j.gene.2018.05.057. Epub 2018 May 17.
• [5] 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.
• [6] 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.
• [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] CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.
• [9] Sulforaphane-induced apoptosis in human leukemia HL-60 cells through extrinsic and intrinsic signal pathways and altering associated genes expression assayed by cDNA microarray. Environ Toxicol. 2017 Jan;32(1):311-328.