Details of Drug Off-Target (DOT)

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

• DOT Name: Leukocyte-associated immunoglobulin-like receptor 2 (LAIR2)
• Synonyms: LAIR-2; CD antigen CD306
• Gene Name: LAIR2
• Related Disease:
  Osteoarthritis
  Pemphigus
  Primary cutaneous T-cell lymphoma
  Rheumatic heart disease
  Rheumatoid arthritis
  Skin disease
  Systemic lupus erythematosus
  Ankylosing spondylitis
• UniProt ID: LAIR2_HUMAN
• Pfam ID: PF13895
• Sequence:
  MSPHLTALLGLVLCLAQTIHTQEGALPRPSISAEPGTVISPGSHVTFMCRGPVGVQTFRL
  EREDRAKYKDSYNVFRLGPSESEARFHIDSVSEGNAGLYRCLYYKPPGWSEHSDFLELLV
  KESSGGPDSPDTEPGSSAGTVPGTEASGFDAP
• Reactome Pathway: Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell (R-HSA-198933)

Molecular Interaction Atlas (MIA) of This DOT

8 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Osteoarthritis	DIS05URM	Strong	Altered Expression	[1]
Pemphigus	DISZAZ6M	Strong	Genetic Variation	[2]
Primary cutaneous T-cell lymphoma	DIS35WVW	Strong	Biomarker	[3]
Rheumatic heart disease	DISCI8JQ	Strong	Altered Expression	[4]
Rheumatoid arthritis	DISTSB4J	Strong	Altered Expression	[1]
Skin disease	DISDW8R6	Strong	Altered Expression	[2]
Systemic lupus erythematosus	DISI1SZ7	Strong	Biomarker	[5]
Ankylosing spondylitis	DISRC6IR	Limited	Biomarker	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Leukocyte-associated immunoglobulin-like receptor 2 (LAIR2).	[7]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Leukocyte-associated immunoglobulin-like receptor 2 (LAIR2).	[8]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Leukocyte-associated immunoglobulin-like receptor 2 (LAIR2).	[9]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Leukocyte-associated immunoglobulin-like receptor 2 (LAIR2).	[10]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Leukocyte-associated immunoglobulin-like receptor 2 (LAIR2).	[7]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Leukocyte-associated immunoglobulin-like receptor 2 (LAIR2).	[12]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Leukocyte-associated immunoglobulin-like receptor 2 (LAIR2).	[13]
Demecolcine	DMCZQGK	Approved	Demecolcine increases the expression of Leukocyte-associated immunoglobulin-like receptor 2 (LAIR2).	[14]
Ampicillin	DMHWE7P	Approved	Ampicillin decreases the expression of Leukocyte-associated immunoglobulin-like receptor 2 (LAIR2).	[12]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Leukocyte-associated immunoglobulin-like receptor 2 (LAIR2).	[16]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Leukocyte-associated immunoglobulin-like receptor 2 (LAIR2).	[14]

2 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Leukocyte-associated immunoglobulin-like receptor 2 (LAIR2).	[11]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Leukocyte-associated immunoglobulin-like receptor 2 (LAIR2).	[15]

References

• [1] The soluble leukocyte-associated Ig-like receptor (LAIR)-2 antagonizes the collagen/LAIR-1 inhibitory immune interaction.J Immunol. 2008 Feb 1;180(3):1662-9. doi: 10.4049/jimmunol.180.3.1662.
• [2] Differential gene expression levels might explain association of LAIR2 polymorphisms with pemphigus.Hum Genet. 2016 Feb;135(2):233-44. doi: 10.1007/s00439-015-1626-6. Epub 2015 Dec 31.
• [3] Novel cell adhesion/migration pathways are predictive markers of HDAC inhibitor resistance in cutaneous T cell lymphoma. EBioMedicine. 2019 Aug;46:170-183.
• [4] Development and evaluation of a sandwich ELISA method for the detection of human CD306.J Immunol Methods. 2013 Oct 31;396(1-2):65-73. doi: 10.1016/j.jim.2013.07.013. Epub 2013 Aug 13.
• [5] C1q limits dendritic cell differentiation and activation by engaging LAIR-1.Proc Natl Acad Sci U S A. 2012 Nov 13;109(46):E3160-7. doi: 10.1073/pnas.1212753109. Epub 2012 Oct 23.
• [6] A high density SNP genotyping approach within the 19q13 chromosome region identifies an association of a CNOT3 polymorphism with ankylosing spondylitis.Ann Rheum Dis. 2012 May;71(5):714-7. doi: 10.1136/annrheumdis-2011-200661. Epub 2012 Jan 31.
• [7] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [8] 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.
• [9] 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.
• [10] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [11] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [12] 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.
• [13] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [14] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [15] 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.
• [16] 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.