Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTQTR1G2)

• DOT Name: Leukocyte immunoglobulin-like receptor subfamily B member 4 (LILRB4)
• Synonyms: B4; CD85 antigen-like family member K; Immunoglobulin-like transcript 3; ILT-3; Leukocyte immunoglobulin-like receptor 5; LIR-5; Monocyte inhibitory receptor HM18; CD antigen CD85k
• Gene Name: LILRB4
• UniProt ID: LIRB4_HUMAN
• PDB ID: 3P2T; 6K7O
• Pfam ID: PF00047 ; PF13895
• Sequence:
  MIPTFTALLCLGLSLGPRTHMQAGPLPKPTLWAEPGSVISWGNSVTIWCQGTLEAREYRL
  DKEESPAPWDRQNPLEPKNKARFSIPSMTEDYAGRYRCYYRSPVGWSQPSDPLELVMTGA
  YSKPTLSALPSPLVTSGKSVTLLCQSRSPMDTFLLIKERAAHPLLHLRSEHGAQQHQAEF
  PMSPVTSVHGGTYRCFSSHGFSHYLLSHPSDPLELIVSGSLEDPRPSPTRSVSTAAGPED
  QPLMPTGSVPHSGLRRHWEVLIGVLVVSILLLSLLLFLLLQHWRQGKHRTLAQRQADFQR
  PPGAAEPEPKDGGLQRRSSPAADVQGENFCAAVKNTQPEDGVEMDTRQSPHDEDPQAVTY
  AKVKHSRPRREMASPPSPLSGEFLDTKDRQAEEDRQMDTEAAASEAPQDVTYAQLHSFTL
  RQKATEPPPSQEGASPAEPSVYATLAIH
• Function: Inhibitory receptor involved in the down-regulation of the immune response and the development of immune tolerance. Receptor for FN1. Receptor for apolipoprotein APOE. Receptor for ALCAM/CD166. Inhibits receptor-mediated phosphorylation of cellular proteins and mobilization of intracellular calcium ions. Inhibits FCGR1A/CD64-mediated monocyte activation by inducing phosphatase-mediated down-regulation of the phosphorylation of multiple proteins including LCK, SYK, LAT and ERK, leading to a reduction in TNF production. This inhibition of monocyte activation occurs at least in part via binding to FN1. Inhibits T cell proliferation, inducing anergy, suppressing the differentiation of IFNG-producing CD8+ cytoxic T cells and enhancing the generation of CD8+ T suppressor cells. Induces up-regulation of CD86 on dendritic cells. Interferes with TNFRSF5-signaling and NF-kappa-B up-regulation.
• Tissue Specificity: Detected on monocytes, macrophages, dendritic cells, natural killer cells and B-cells (at protein level). Expressed in the lung.
• 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 Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Leukocyte immunoglobulin-like receptor subfamily B member 4 (LILRB4).	[1]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Leukocyte immunoglobulin-like receptor subfamily B member 4 (LILRB4).	[2]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Leukocyte immunoglobulin-like receptor subfamily B member 4 (LILRB4).	[4]

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 affects the methylation of Leukocyte immunoglobulin-like receptor subfamily B member 4 (LILRB4).	[3]

References

• [1] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [2] Identification of vitamin D3 target genes in human breast cancer tissue. J Steroid Biochem Mol Biol. 2016 Nov;164:90-97.
• [3] 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.
• [4] 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.