Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT0HFPCD)

• DOT Name: Leukocyte immunoglobulin-like receptor subfamily B member 2 (LILRB2)
• Synonyms: LIR-2; Leukocyte immunoglobulin-like receptor 2; CD85 antigen-like family member D; Immunoglobulin-like transcript 4; ILT-4; Monocyte/macrophage immunoglobulin-like receptor 10; MIR-10; CD antigen CD85d
• Gene Name: LILRB2
• UniProt ID: LIRB2_HUMAN
• PDB ID: 2DYP; 2GW5; 4LLA; 6AED; 6BCS
• Pfam ID: PF00047 ; PF13895
• Sequence:
  MTPIVTVLICLGLSLGPRTRVQTGTIPKPTLWAEPDSVITQGSPVTLSCQGSLEAQEYRL
  YREKKSASWITRIRPELVKNGQFHIPSITWEHTGRYGCQYYSRARWSELSDPLVLVMTGA
  YPKPTLSAQPSPVVTSGGRVTLQCESQVAFGGFILCKEGEDEHPQCLNSQPHARGSSRAI
  FSVGPVSPNRRWSHRCYGYDLNSPYVWSSPSDLLELLVPGVSKKPSLSVQPGPVMAPGES
  LTLQCVSDVGYDRFVLYKEGERDLRQLPGRQPQAGLSQANFTLGPVSRSYGGQYRCYGAH
  NLSSECSAPSDPLDILITGQIRGTPFISVQPGPTVASGENVTLLCQSWRQFHTFLLTKAG
  AADAPLRLRSIHEYPKYQAEFPMSPVTSAHAGTYRCYGSLNSDPYLLSHPSEPLELVVSG
  PSMGSSPPPTGPISTPGPEDQPLTPTGSDPQSGLGRHLGVVIGILVAVVLLLLLLLLLFL
  ILRHRRQGKHWTSTQRKADFQHPAGAVGPEPTDRGLQWRSSPAADAQEENLYAAVKDTQP
  EDGVEMDTRAAASEAPQDVTYAQLHSLTLRRKATEPPPSQEREPPAEPSIYATLAIH
• Function: Receptor for class I MHC antigens. Recognizes a broad spectrum of HLA-A, HLA-B, HLA-C, HLA-G and HLA-F alleles. Involved in the down-regulation of the immune response and the development of tolerance. Recognizes HLA-G in complex with B2M/beta-2 microglobulin and a nonamer self-peptide (peptide-bound HLA-G-B2M) triggering differentiation of type 1 regulatory T cells and myeloid-derived suppressor cells, both of which actively maintain maternal-fetal tolerance. Competes with CD8A for binding to class I MHC antigens. Inhibits FCGR1A-mediated phosphorylation of cellular proteins and mobilization of intracellular calcium ions.
• Tissue Specificity: Expressed in monocytes and at lower levels in myeloid and plasmacytoid dendritic cells. Expressed in tolerogenic IL10-producing dendritic cells . Expressed in myeloid-derived suppressor cells during pregnancy . Detected at low levels in natural killer (NK) cells. Expressed in B cells.
• KEGG Pathway:
  Osteoclast differentiation (hsa04380)
  B cell receptor sig.ling pathway (hsa04662)
• 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

3 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 immunoglobulin-like receptor subfamily B member 2 (LILRB2).	[1]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Leukocyte immunoglobulin-like receptor subfamily B member 2 (LILRB2).	[2]
Fenretinide	DMRD5SP	Phase 3	Fenretinide decreases the expression of Leukocyte immunoglobulin-like receptor subfamily B member 2 (LILRB2).	[3]

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 immunoglobulin-like receptor subfamily B member 2 (LILRB2).	[4]

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] The contribution of methotrexate exposure and host factors on transcriptional variance in human liver. Toxicol Sci. 2007 Jun;97(2):582-94.
• [3] 4-HPR modulates gene expression in ovarian cells. Int J Cancer. 2006 Sep 1;119(5):1005-13. doi: 10.1002/ijc.21797.
• [4] 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.