Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTFCN53B)

• DOT Name: Killer cell immunoglobulin-like receptor 2DL3 (KIR2DL3)
• Synonyms: CD158 antigen-like family member B2; KIR-023GB; Killer inhibitory receptor cl 2-3; NKAT2a; NKAT2b; Natural killer-associated transcript 2; NKAT-2; p58 natural killer cell receptor clone CL-6; p58 NK receptor CL-6; p58.2 MHC class-I-specific NK receptor; CD antigen CD158b2
• Gene Name: KIR2DL3
• UniProt ID: KI2L3_HUMAN
• PDB ID: 1B6U; 6PAG; 8TUI
• Pfam ID: PF00047
• Sequence:
  MSLMVVSMVCVGFFLLQGAWPHEGVHRKPSLLAHPGPLVKSEETVILQCWSDVRFQHFLL
  HREGKFKDTLHLIGEHHDGVSKANFSIGPMMQDLAGTYRCYGSVTHSPYQLSAPSDPLDI
  VITGLYEKPSLSAQPGPTVLAGESVTLSCSSRSSYDMYHLSREGEAHERRFSAGPKVNGT
  FQADFPLGPATHGGTYRCFGSFRDSPYEWSNSSDPLLVSVTGNPSNSWPSPTEPSSETGN
  PRHLHVLIGTSVVIILFILLLFFLLHRWCCNKKNAVVMDQEPAGNRTVNREDSDEQDPQE
  VTYAQLNHCVFTQRKITRPSQRPKTPPTDIIVYTELPNAEP
• Function: Receptor on natural killer (NK) cells for HLA-C alleles (HLA-Cw1, HLA-Cw3 and HLA-Cw7). Inhibits the activity of NK cells thus preventing cell lysis.
• KEGG Pathway:
  Antigen processing and presentation (hsa04612)
  .tural killer cell mediated cytotoxicity (hsa04650)
  Graft-versus-host disease (hsa05332)
• Reactome Pathway: Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell (R-HSA-198933)

Molecular Interaction Atlas (MIA) of This DOT

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 Killer cell immunoglobulin-like receptor 2DL3 (KIR2DL3).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Killer cell immunoglobulin-like receptor 2DL3 (KIR2DL3).	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Killer cell immunoglobulin-like receptor 2DL3 (KIR2DL3).	[2]
Arsenic	DMTL2Y1	Approved	Arsenic affects the expression of Killer cell immunoglobulin-like receptor 2DL3 (KIR2DL3).	[3]
Azacitidine	DMTA5OE	Approved	Azacitidine increases the expression of Killer cell immunoglobulin-like receptor 2DL3 (KIR2DL3).	[4]
PMID28870136-Compound-48	DMPIM9L	Patented	PMID28870136-Compound-48 decreases the expression of Killer cell immunoglobulin-like receptor 2DL3 (KIR2DL3).	[6]
QUERCITRIN	DM1DH96	Investigative	QUERCITRIN affects the expression of Killer cell immunoglobulin-like receptor 2DL3 (KIR2DL3).	[7]

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] 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.
• [3] Drinking-water arsenic exposure modulates gene expression in human lymphocytes from a U.S. population. Environ Health Perspect. 2008 Apr;116(4):524-31. doi: 10.1289/ehp.10861.
• [4] DNA methylation inhibition increases T cell KIR expression through effects on both promoter methylation and transcription factors. Clin Immunol. 2009 Feb;130(2):213-24. doi: 10.1016/j.clim.2008.08.009. Epub 2008 Oct 22.
• [5] 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.
• [6] Oxidative stress modulates theophylline effects on steroid responsiveness. Biochem Biophys Res Commun. 2008 Dec 19;377(3):797-802.
• [7] Molecular mechanisms of quercitrin-induced apoptosis in non-small cell lung cancer. Arch Med Res. 2014 Aug;45(6):445-54.