Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT00N6UJ)

DOT Name Killer cell immunoglobulin-like receptor 2DS4 (KIR2DS4)
Synonyms CD158 antigen-like family member I; Natural killer-associated transcript 8; NKAT-8; P58 natural killer cell receptor clones CL-39/CL-17; p58 NK receptor CL-39/CL-17; CD antigen CD158i
Gene Name KIR2DS4
Related Disease
Acute graft versus host disease ( )
Cervical Intraepithelial neoplasia ( )
Cytomegalovirus infection ( )
Hepatitis C virus infection ( )
Hepatocellular carcinoma ( )
Hirschsprung disease ( )
Juvenile idiopathic arthritis ( )
Kidney failure ( )
leukaemia ( )
Leukemia ( )
Liver cirrhosis ( )
Melanoma ( )
Syphilis ( )
Ulcerative colitis ( )
Head-neck squamous cell carcinoma ( )
Neoplasm ( )
Ankylosing spondylitis ( )
Rectal carcinoma ( )
Rheumatoid arthritis ( )
Type-1 diabetes ( )
UniProt ID
KI2S4_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
3H8N
Pfam ID
PF00047
Sequence
MSLMVIIMACVGFFLLQGAWPQEGVHRKPSFLALPGHLVKSEETVILQCWSDVMFEHFLL
HREGKFNNTLHLIGEHHDGVSKANFSIGPMMPVLAGTYRCYGSVPHSPYQLSAPSDPLDM
VIIGLYEKPSLSAQPGPTVQAGENVTLSCSSRSSYDMYHLSREGEAHERRLPAVRSINGT
FQADFPLGPATHGGTYRCFGSFRDAPYEWSNSSDPLLVSVTGNPSNSWPSPTEPSSKTGN
PRHLHVLIGTSVVKIPFTILLFFLLHRWCSDKKNAAVMDQEPAGNRTVNSEDSDEQDHQE
VSYA
Function Receptor on natural killer (NK) cells for HLA-C alleles. Does not inhibit the activity of NK cells.
KEGG Pathway
Antigen processing and presentation (hsa04612 )
.tural killer cell mediated cytotoxicity (hsa04650 )
Reactome Pathway
DAP12 interactions (R-HSA-2172127 )

Molecular Interaction Atlas (MIA) of This DOT

20 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Acute graft versus host disease DIS8KLVM Strong Biomarker [1]
Cervical Intraepithelial neoplasia DISXP757 Strong Genetic Variation [2]
Cytomegalovirus infection DISCEMGC Strong Biomarker [3]
Hepatitis C virus infection DISQ0M8R Strong Biomarker [4]
Hepatocellular carcinoma DIS0J828 Strong Genetic Variation [5]
Hirschsprung disease DISUUSM1 Strong Genetic Variation [6]
Juvenile idiopathic arthritis DISQZGBV Strong Biomarker [7]
Kidney failure DISOVQ9P Strong Biomarker [8]
leukaemia DISS7D1V Strong Biomarker [9]
Leukemia DISNAKFL Strong Biomarker [9]
Liver cirrhosis DIS4G1GX Strong Biomarker [10]
Melanoma DIS1RRCY Strong Altered Expression [11]
Syphilis DISJ73BS Strong Biomarker [12]
Ulcerative colitis DIS8K27O Strong Genetic Variation [13]
Head-neck squamous cell carcinoma DISF7P24 moderate Genetic Variation [14]
Neoplasm DISZKGEW Disputed Biomarker [15]
Ankylosing spondylitis DISRC6IR Limited Genetic Variation [16]
Rectal carcinoma DIS8FRR7 Limited Biomarker [17]
Rheumatoid arthritis DISTSB4J Limited Biomarker [18]
Type-1 diabetes DIS7HLUB Limited Biomarker [19]
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⏷ Show the Full List of 20 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
3 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 2DS4 (KIR2DS4). [20]
Ciclosporin DMAZJFX Approved Ciclosporin increases the methylation of Killer cell immunoglobulin-like receptor 2DS4 (KIR2DS4). [21]
Bisphenol A DM2ZLD7 Investigative Bisphenol A increases the methylation of Killer cell immunoglobulin-like receptor 2DS4 (KIR2DS4). [25]
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3 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Bortezomib DMNO38U Approved Bortezomib decreases the expression of Killer cell immunoglobulin-like receptor 2DS4 (KIR2DS4). [22]
Azacitidine DMTA5OE Approved Azacitidine increases the expression of Killer cell immunoglobulin-like receptor 2DS4 (KIR2DS4). [23]
(+)-JQ1 DM1CZSJ Phase 1 (+)-JQ1 decreases the expression of Killer cell immunoglobulin-like receptor 2DS4 (KIR2DS4). [24]
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References

1 KIR2DS4 and Its Variant KIR1D Are Associated with Acute Graft-versus-Host Disease, Cytomegalovirus, and Overall Survival after Sibling-Related HLA-Matched Transplantation in Patients with Donors with KIR Gene Haplotype A.Biol Blood Marrow Transplant. 2016 Feb;22(2):220-225. doi: 10.1016/j.bbmt.2015.10.004. Epub 2015 Oct 22.
2 A population-based cohort study of KIR genes and genotypes in relation to cervical intraepithelial neoplasia.Tissue Antigens. 2005 Mar;65(3):252-9. doi: 10.1111/j.1399-0039.2005.00359.x.
3 Expression of activating KIR2DS2 and KIR2DS4 genes after hematopoietic cell transplantation: relevance to cytomegalovirus infection.Biol Blood Marrow Transplant. 2011 Nov;17(11):1662-72. doi: 10.1016/j.bbmt.2011.04.008. Epub 2011 Apr 29.
4 Protective KIR-HLA interactions for HCV infection in intravenous drug users.Mol Immunol. 2009 Aug;46(13):2723-7. doi: 10.1016/j.molimm.2009.05.014. Epub 2009 Jun 24.
5 KIR and HLA loci are associated with hepatocellular carcinoma development in patients with hepatitis B virus infection: a case-control study.PLoS One. 2011;6(10):e25682. doi: 10.1371/journal.pone.0025682. Epub 2011 Oct 5.
6 Genome-wide association study identifies NRG1 as a susceptibility locus for Hirschsprung's disease.Proc Natl Acad Sci U S A. 2009 Feb 24;106(8):2694-9. doi: 10.1073/pnas.0809630105. Epub 2009 Feb 5.
7 Natural killer cell activity and frequency of killer cell immunoglobulin-like receptors in children with different forms of juvenile idiopathic arthritis.Pediatr Allergy Immunol. 2013 Nov;24(7):691-6. doi: 10.1111/pai.12130.
8 Are killer cell immunoglobulin-like receptor genes important for the prediction of kidney graft rejection?.Arch Immunol Ther Exp (Warsz). 2013 Aug;61(4):321-5. doi: 10.1007/s00005-013-0225-2. Epub 2013 Apr 4.
9 Killer cell immunoglobulin-like receptor gene polymorphisms in patients with leukemia: possible association with susceptibility to the disease.Leuk Res. 2010 Jan;34(1):55-8. doi: 10.1016/j.leukres.2009.04.022. Epub 2009 May 18.
10 The Clinical Features of Patients with Chronic Hepatitis C Virus Infections Are Associated with Killer Cell Immunoglobulin-Like Receptor Genes and Their Expression on the Surface of Natural Killer Cells.Front Immunol. 2018 Jan 5;8:1912. doi: 10.3389/fimmu.2017.01912. eCollection 2017.
11 MHC class I-independent recognition of NK-activating receptor KIR2DS4.J Immunol. 2004 Aug 1;173(3):1819-25. doi: 10.4049/jimmunol.173.3.1819.
12 Association of KIR2DS4 and its variant KIR1D with syphilis in a Chinese Han population.Int J Immunogenet. 2012 Apr;39(2):114-8. doi: 10.1111/j.1744-313X.2011.01063.x. Epub 2011 Dec 1.
13 Association between KIR-HLA combination and ulcerative colitis and Crohn's disease in a Japanese population.PLoS One. 2018 Apr 12;13(4):e0195778. doi: 10.1371/journal.pone.0195778. eCollection 2018.
14 KIR2DS4, KIR2DL2, and KIR2DS4del are linked with basaloid tumors, lymph node metastasis, advanced stage and metastatic risk in head and neck squamous cell carcinoma.Exp Mol Pathol. 2020 Feb;112:104345. doi: 10.1016/j.yexmp.2019.104345. Epub 2019 Nov 18.
15 Analysis of KIR gene frequencies in HLA class I characterised bladder, colorectal and laryngeal tumours.Tissue Antigens. 2007 Mar;69(3):220-6. doi: 10.1111/j.1399-0039.2006.00792.x.
16 Human Leukocyte Antigen C*12:02:02 and Killer Immunoglobulin-Like Receptor 2DL5 are Distinctly Associated with Ankylosing Spondylitis in the Taiwanese.Int J Mol Sci. 2017 Aug 16;18(8):1775. doi: 10.3390/ijms18081775.
17 HLA-Cw polypmorphism and killer cell immunoglobulin-like receptor (KIR) gene analysis in Korean colorectal cancer patients.Int J Surg. 2014;12(8):815-20. doi: 10.1016/j.ijsu.2014.06.012. Epub 2014 Jul 4.
18 Killer cell immunoglobulin-like receptor gene's repertoire in rheumatoid arthritis.Scand J Rheumatol. 2006 Mar-Apr;35(2):124-7. doi: 10.1080/03009740500381252.
19 Killer cell immunoglobulin-like receptor along with HLA-C ligand genes are associated with type 1 diabetes in Chinese Han population.Diabetes Metab Res Rev. 2011 Nov;27(8):872-7. doi: 10.1002/dmrr.1264.
20 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.
21 Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
22 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.
23 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.
24 BET bromodomain inhibition as a novel strategy for reactivation of HIV-1. J Leukoc Biol. 2012 Dec;92(6):1147-54. doi: 10.1189/jlb.0312165. Epub 2012 Jul 16.
25 DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.