Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTKC3PA6)

DOT Name	Leukocyte immunoglobulin-like receptor subfamily A member 4 (LILRA4)
Synonyms	CD85 antigen-like family member G; Immunoglobulin-like transcript 7; ILT-7; CD antigen CD85g
Gene Name	LILRA4
UniProt ID	LIRA4_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
Pfam ID	PF00047 ; PF13895 ; PF13927
Sequence	MTLILTSLLFFGLSLGPRTRVQAENLLKPILWAEPGPVITWHNPVTIWCQGTLEAQGYRL DKEGNSMSRHILKTLESENKVKLSIPSMMWEHAGRYHCYYQSPAGWSEPSDPLELVVTAY SRPTLSALPSPVVTSGVNVTLRCASRLGLGRFTLIEEGDHRLSWTLNSHQHNHGKFQALF PMGPLTFSNRGTFRCYGYENNTPYVWSEPSDPLQLLVSGVSRKPSLLTLQGPVVTPGENL TLQCGSDVGYIRYTLYKEGADGLPQRPGRQPQAGLSQANFTLSPVSRSYGGQYRCYGAHN VSSEWSAPSDPLDILIAGQISDRPSLSVQPGPTVTSGEKVTLLCQSWDPMFTFLLTKEGA AHPPLRLRSMYGAHKYQAEFPMSPVTSAHAGTYRCYGSRSSNPYLLSHPSEPLELVVSGA TETLNPAQKKSDSKTAPHLQDYTVENLIRMGVAGLVLLFLGILLFEAQHSQRSPPRCSQE ANSRKDNAPFRVVEPWEQI
Function	Functions coreceptor to limit the innate immune responses to viral infections; signaling occurs via FCER1G. Down-regulates the production of IFNA1, IFNA2, IFNA4, IFNB1 and TNF by plasmacytoid dendritic cells that have been exposed to influenza virus or cytidine-phosphate-guanosine (CpG) dinucleotides, indicating it functions as a negative regulator of TLR7 and TLR9 signaling cascades. Down-regulates interferon production in response to interaction with BST2 on HIV-1 infected cells. Activates a signaling cascade in complex with FCER1G that results in phosphorylation of Src family and Syk kinases and thereby triggers mobilization of intracellular Ca(2+). Does not interfere with the differentiation of plasmacytoid dendritic cells into antigen-presenting cells.
Tissue Specificity	Detected on plasmacytoid dendritic cells (at protein level). Detected on plasmacytoid dendritic cells, but not on monocytes or B cells.
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

Molecular Interaction Atlas (MIA)

MIA Detail

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2 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 A member 4 (LILRA4).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Leukocyte immunoglobulin-like receptor subfamily A member 4 (LILRA4).	[3]
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1 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Rigosertib	DMOSTXF	Phase 3	Rigosertib decreases the expression of Leukocyte immunoglobulin-like receptor subfamily A member 4 (LILRA4).	[2]
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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	ON 01910.Na is selectively cytotoxic for chronic lymphocytic leukemia cells through a dual mechanism of action involving PI3K/AKT inhibition and induction of oxidative stress. Clin Cancer Res. 2012 Apr 1;18(7):1979-91. doi: 10.1158/1078-0432.CCR-11-2113. Epub 2012 Feb 20.
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.