Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTA1STFZ)

• DOT Name: Leukocyte immunoglobulin-like receptor subfamily B member 1 (LILRB1)
• Synonyms: LIR-1; Leukocyte immunoglobulin-like receptor 1; CD85 antigen-like family member J; Immunoglobulin-like transcript 2; ILT-2; Monocyte/macrophage immunoglobulin-like receptor 7; MIR-7; CD antigen CD85j
• Gene Name: LILRB1
• UniProt ID: LIRB1_HUMAN
• PDB ID: 1G0X; 1P7Q; 1UFU; 1UGN; 1VDG; 3D2U; 4LL9; 4NO0; 5KNM; 6AEE; 6EWA; 6EWC; 6EWO; 6K60; 6ZDX; 7KFK
• Pfam ID: PF00047 ; PF13895
• Sequence:
  MTPILTVLICLGLSLGPRTHVQAGHLPKPTLWAEPGSVITQGSPVTLRCQGGQETQEYRL
  YREKKTALWITRIPQELVKKGQFPIPSITWEHAGRYRCYYGSDTAGRSESSDPLELVVTG
  AYIKPTLSAQPSPVVNSGGNVILQCDSQVAFDGFSLCKEGEDEHPQCLNSQPHARGSSRA
  IFSVGPVSPSRRWWYRCYAYDSNSPYEWSLPSDLLELLVLGVSKKPSLSVQPGPIVAPEE
  TLTLQCGSDAGYNRFVLYKDGERDFLQLAGAQPQAGLSQANFTLGPVSRSYGGQYRCYGA
  HNLSSEWSAPSDPLDILIAGQFYDRVSLSVQPGPTVASGENVTLLCQSQGWMQTFLLTKE
  GAADDPWRLRSTYQSQKYQAEFPMGPVTSAHAGTYRCYGSQSSKPYLLTHPSDPLELVVS
  GPSGGPSSPTTGPTSTSGPEDQPLTPTGSDPQSGLGRHLGVVIGILVAVILLLLLLLLLF
  LILRHRRQGKHWTSTQRKADFQHPAGAVGPEPTDRGLQWRSSPAADAQEENLYAAVKHTQ
  PEDGVEMDTRSPHDEDPQAVTYAEVKHSRPRREMASPPSPLSGEFLDTKDRQAEEDRQMD
  TEAAASEAPQDVTYAQLHSLTLRREATEPPPSQEGPSPAVPSIYATLAIH
• Function: Receptor for class I MHC antigens. Recognizes a broad spectrum of HLA-A, HLA-B, HLA-C, HLA-G and HLA-F alleles. Receptor for H301/UL18, a human cytomegalovirus class I MHC homolog. Ligand binding results in inhibitory signals and down-regulation of the immune response. Engagement of LILRB1 present on natural killer cells or T-cells by class I MHC molecules protects the target cells from lysis. Interaction with HLA-B or HLA-E leads to inhibition of FCER1A signaling and serotonin release. Inhibits FCGR1A-mediated phosphorylation of cellular proteins and mobilization of intracellular calcium ions. Recognizes HLA-G in complex with B2M/beta-2 microglobulin and a nonamer self-peptide. Upon interaction with peptide-bound HLA-G-B2M complex, triggers secretion of growth-promoting factors by decidual NK cells. Reprograms B cells toward an immune suppressive phenotype.
• Tissue Specificity: Expressed in B cells, monocytes and various dendritic cell (DC) subsets including myeloid, plasmacytoid and tolerogenic DCs (at protein level) . Expressed in decidual macrophages (at protein level) . Expressed in decidual NK cells (at protein level) .
• KEGG Pathway:
  Osteoclast differentiation (hsa04380)
  B cell receptor sig.ling pathway (hsa04662)
• Reactome Pathway: Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell (R-HSA-198933)

Molecular Interaction Atlas (MIA) of This DOT

3 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 Leukocyte immunoglobulin-like receptor subfamily B member 1 (LILRB1).	[1]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Leukocyte immunoglobulin-like receptor subfamily B member 1 (LILRB1).	[2]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Leukocyte immunoglobulin-like receptor subfamily B member 1 (LILRB1).	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Leukocyte immunoglobulin-like receptor subfamily B member 1 (LILRB1).	[3]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Leukocyte immunoglobulin-like receptor subfamily B member 1 (LILRB1).	[4]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Leukocyte immunoglobulin-like receptor subfamily B member 1 (LILRB1).	[5]
Testosterone Undecanoate	DMZO10Y	Approved	Testosterone Undecanoate increases the expression of Leukocyte immunoglobulin-like receptor subfamily B member 1 (LILRB1).	[6]

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] 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.
• [3] Gene expression profile induced by arsenic trioxide in chronic lymphocytic leukemia cells reveals a central role for heme oxygenase-1 in apoptosis and regulation of matrix metalloproteinase-9. Oncotarget. 2016 Dec 13;7(50):83359-83377.
• [4] Minimal peroxide exposure of neuronal cells induces multifaceted adaptive responses. PLoS One. 2010 Dec 17;5(12):e14352. doi: 10.1371/journal.pone.0014352.
• [5] The contribution of methotrexate exposure and host factors on transcriptional variance in human liver. Toxicol Sci. 2007 Jun;97(2):582-94.
• [6] Levonorgestrel enhances spermatogenesis suppression by testosterone with greater alteration in testicular gene expression in men. Biol Reprod. 2009 Mar;80(3):484-92.
• [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.