Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTL1LBQJ)

• DOT Name: Killer cell immunoglobulin-like receptor 2DL1 (KIR2DL1)
• Synonyms: CD158 antigen-like family member A; Natural killer-associated transcript 1; NKAT-1; p58 natural killer cell receptor clones CL-42/47.11; p58 NK receptor CL-42/47.11; p58.1 MHC class-I-specific NK receptor; CD antigen CD158a
• Gene Name: KIR2DL1
• UniProt ID: KI2L1_HUMAN
• PDB ID: 1IM9; 1NKR
• Pfam ID: PF00047
• Sequence:
  MSLLVVSMACVGFFLLQGAWPHEGVHRKPSLLAHPGRLVKSEETVILQCWSDVMFEHFLL
  HREGMFNDTLRLIGEHHDGVSKANFSISRMTQDLAGTYRCYGSVTHSPYQVSAPSDPLDI
  VIIGLYEKPSLSAQLGPTVLAGENVTLSCSSRSSYDMYHLSREGEAHERRLPAGPKVNGT
  FQADFPLGPATHGGTYRCFGSFHDSPYEWSKSSDPLLVSVTGNPSNSWPSPTEPSSKTGN
  PRHLHILIGTSVVIILFILLFFLLHRWCSNKKNAAVMDQESAGNRTANSEDSDEQDPQEV
  TYTQLNHCVFTQRKITRPSQRPKTPPTDIIVYTELPNAESRSKVVSCP
• Function: Receptor on natural killer (NK) cells for some HLA-C alleles such as w4 and w6. Inhibits the activity of NK cells thus preventing cell lysis.
• Tissue Specificity: Expressed by NK cells.
• 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 2DL1 (KIR2DL1).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Killer cell immunoglobulin-like receptor 2DL1 (KIR2DL1).	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the expression of Killer cell immunoglobulin-like receptor 2DL1 (KIR2DL1).	[2]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Killer cell immunoglobulin-like receptor 2DL1 (KIR2DL1).	[3]
Azacitidine	DMTA5OE	Approved	Azacitidine increases the expression of Killer cell immunoglobulin-like receptor 2DL1 (KIR2DL1).	[4]

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] 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.
• [3] The proapoptotic effect of zoledronic acid is independent of either the bone microenvironment or the intrinsic resistance to bortezomib of myeloma cells and is enhanced by the combination with arsenic trioxide. Exp Hematol. 2011 Jan;39(1):55-65.
• [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.