Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTXIGC6I)

• DOT Name: Leukocyte-associated immunoglobulin-like receptor 1 (LAIR1)
• Synonyms: LAIR-1; hLAIR1; CD antigen CD305
• Gene Name: LAIR1
• UniProt ID: LAIR1_HUMAN
• PDB ID: 3KGR; 3RP1; 7F9L; 7F9M; 7F9N
• Pfam ID: PF13895
• Sequence:
  MSPHPTALLGLVLCLAQTIHTQEEDLPRPSISAEPGTVIPLGSHVTFVCRGPVGVQTFRL
  ERDSRSTYNDTEDVSQASPSESEARFRIDSVREGNAGLYRCIYYKPPKWSEQSDYLELLV
  KESSGGPDSPDTEPGSSAGPTQRPSDNSHNEHAPASQGLKAEHLYILIGVSVVFLFCLLL
  LVLFCLHRQNQIKQGPPRSKDEEQKPQQRPDLAVDVLERTADKATVNGLPEKDRETDTSA
  LAAGSSQEVTYAQLDHWALTQRTARAVSPQSTKPMAESITYAAVARH
• Function: Functions as an inhibitory receptor that plays a constitutive negative regulatory role on cytolytic function of natural killer (NK) cells, B-cells and T-cells. Activation by Tyr phosphorylation results in recruitment and activation of the phosphatases PTPN6 and PTPN11. It also reduces the increase of intracellular calcium evoked by B-cell receptor ligation. May also play its inhibitory role independently of SH2-containing phosphatases. Modulates cytokine production in CD4+ T-cells, down-regulating IL2 and IFNG production while inducing secretion of transforming growth factor beta. Down-regulates also IgG and IgE production in B-cells as well as IL8, IL10 and TNF secretion. Inhibits proliferation and induces apoptosis in myeloid leukemia cell lines as well as prevents nuclear translocation of NF-kappa-B p65 subunit/RELA and phosphorylation of I-kappa-B alpha/CHUK in these cells. Inhibits the differentiation of peripheral blood precursors towards dendritic cells.
• Tissue Specificity: Expressed on the majority of peripheral mononuclear cells, including natural killer (NK) cells, T-cells, B-cells, monocytes, and dendritic cells. Highly expressed in naive T-cells and B-cells but no expression on germinal center B-cells. Abnormally low expression in naive B-cells from HIV-1 infected patients. Very low expression in NK cells from a patient with chronic active Epstein-Barr virus infection.
• Reactome Pathway:
  Neutrophil degranulation (R-HSA-6798695)
  Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell (R-HSA-198933)

Molecular Interaction Atlas (MIA) of This DOT

9 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 Leukocyte-associated immunoglobulin-like receptor 1 (LAIR1).	[1]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Leukocyte-associated immunoglobulin-like receptor 1 (LAIR1).	[2]
Cannabidiol	DM0659E	Approved	Cannabidiol increases the expression of Leukocyte-associated immunoglobulin-like receptor 1 (LAIR1).	[3]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone increases the expression of Leukocyte-associated immunoglobulin-like receptor 1 (LAIR1).	[4]
DTI-015	DMXZRW0	Approved	DTI-015 increases the expression of Leukocyte-associated immunoglobulin-like receptor 1 (LAIR1).	[5]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Leukocyte-associated immunoglobulin-like receptor 1 (LAIR1).	[7]
PMID27336223-Compound-5	DM6E50A	Patented	PMID27336223-Compound-5 increases the expression of Leukocyte-associated immunoglobulin-like receptor 1 (LAIR1).	[4]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Leukocyte-associated immunoglobulin-like receptor 1 (LAIR1).	[8]
chloropicrin	DMSGBQA	Investigative	chloropicrin affects the expression of Leukocyte-associated immunoglobulin-like receptor 1 (LAIR1).	[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 decreases the methylation of Leukocyte-associated immunoglobulin-like receptor 1 (LAIR1).	[6]

References

• [1] 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.
• [2] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [3] A novel mechanism of cannabidiol in suppressing ovarian cancer through LAIR-1 mediated mitochondrial dysfunction and apoptosis. Environ Toxicol. 2023 May;38(5):1118-1132. doi: 10.1002/tox.23752. Epub 2023 Feb 22.
• [4] PPARgamma controls CD1d expression by turning on retinoic acid synthesis in developing human dendritic cells. J Exp Med. 2006 Oct 2;203(10):2351-62.
• [5] Gene expression profile induced by BCNU in human glioma cell lines with differential MGMT expression. J Neurooncol. 2005 Jul;73(3):189-98.
• [6] 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.
• [7] Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem. 2012 Dec 14;287(51):43137-55.
• [8] Alternatives for the worse: Molecular insights into adverse effects of bisphenol a and substitutes during human adipocyte differentiation. Environ Int. 2021 Nov;156:106730. doi: 10.1016/j.envint.2021.106730. Epub 2021 Jun 27.
• [9] Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.