Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT20M764)

DOT Name Natural cytotoxicity triggering receptor 3 (NCR3)
Synonyms Activating natural killer receptor p30; Natural killer cell p30-related protein; NK-p30; NKp30; CD antigen CD337
Gene Name NCR3
Related Disease
Cone-rod dystrophy 2 ( )
Rheumatoid arthritis ( )
Acquired immune deficiency syndrome ( )
Acute myelogenous leukaemia ( )
Adult glioblastoma ( )
Adult lymphoma ( )
Arthritis ( )
Autoimmune disease ( )
Cryptococcosis ( )
Endometriosis ( )
Gastrointestinal stromal tumour ( )
Glioblastoma multiforme ( )
Graves disease ( )
Griscelli syndrome ( )
Hepatocellular carcinoma ( )
HIV infectious disease ( )
leukaemia ( )
Leukemia ( )
Lymphoma ( )
Malaria ( )
Myocardial infarction ( )
Neoplasm ( )
Non-small-cell lung cancer ( )
Pediatric lymphoma ( )
Promyelocytic leukaemia ( )
Sjogren syndrome ( )
Clear cell renal carcinoma ( )
Renal cell carcinoma ( )
Advanced cancer ( )
Hepatitis C virus infection ( )
Nervous system inflammation ( )
Plasma cell myeloma ( )
Pregnancy disorder ( )
Small lymphocytic lymphoma ( )
UniProt ID
NCTR3_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
PDB ID
3NOI; 3PV6; 6YJP
Pfam ID
PF07686
Sequence
MAWMLLLILIMVHPGSCALWVSQPPEIRTLEGSSAFLPCSFNASQGRLAIGSVTWFRDEV
VPGKEVRNGTPEFRGRLAPLASSRFLHDHQAELHIRDVRGHDASIYVCRVEVLGLGVGTG
NGTRLVVEKEHPQLGAGTVLLLRAGFYAVSFLSVAVGSTVYYQGKCLTWKGPRRQLPAVV
PAPLPPPCGSSAHLLPPVPGG
Function
Cell membrane receptor of natural killer/NK cells that is activated by binding of extracellular ligands including BAG6 and NCR3LG1. Stimulates NK cells cytotoxicity toward neighboring cells producing these ligands. It controls, for instance, NK cells cytotoxicity against tumor cells. Engagement of NCR3 by BAG6 also promotes myeloid dendritic cells (DC) maturation, both through killing DCs that did not acquire a mature phenotype, and inducing the release by NK cells of TNFA and IFNG which promote DC maturation.
Tissue Specificity Selectively expressed by all resting and activated NK cells and weakly expressed in spleen.
KEGG Pathway
.tural killer cell mediated cytotoxicity (hsa04650 )
Reactome Pathway
Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell (R-HSA-198933 )

Molecular Interaction Atlas (MIA) of This DOT

34 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Cone-rod dystrophy 2 DISX2RWY Definitive Altered Expression [1]
Rheumatoid arthritis DISTSB4J Definitive Altered Expression [2]
Acquired immune deficiency syndrome DISL5UOX Strong Altered Expression [3]
Acute myelogenous leukaemia DISCSPTN Strong Biomarker [4]
Adult glioblastoma DISVP4LU Strong Biomarker [5]
Adult lymphoma DISK8IZR Strong Biomarker [6]
Arthritis DIST1YEL Strong Biomarker [7]
Autoimmune disease DISORMTM Strong Biomarker [7]
Cryptococcosis DISDYDTK Strong Biomarker [8]
Endometriosis DISX1AG8 Strong Biomarker [9]
Gastrointestinal stromal tumour DIS6TJYS Strong Altered Expression [10]
Glioblastoma multiforme DISK8246 Strong Biomarker [5]
Graves disease DISU4KOQ Strong Biomarker [11]
Griscelli syndrome DISTHCOQ Strong Biomarker [12]
Hepatocellular carcinoma DIS0J828 Strong Biomarker [13]
HIV infectious disease DISO97HC Strong Altered Expression [14]
leukaemia DISS7D1V Strong Biomarker [15]
Leukemia DISNAKFL Strong Biomarker [15]
Lymphoma DISN6V4S Strong Biomarker [6]
Malaria DISQ9Y50 Strong Genetic Variation [16]
Myocardial infarction DIS655KI Strong Biomarker [17]
Neoplasm DISZKGEW Strong Altered Expression [13]
Non-small-cell lung cancer DIS5Y6R9 Strong Altered Expression [18]
Pediatric lymphoma DIS51BK2 Strong Biomarker [6]
Promyelocytic leukaemia DISYGG13 Strong Altered Expression [19]
Sjogren syndrome DISUBX7H Strong Biomarker [20]
Clear cell renal carcinoma DISBXRFJ moderate Altered Expression [21]
Renal cell carcinoma DISQZ2X8 moderate Altered Expression [21]
Advanced cancer DISAT1Z9 Limited Biomarker [22]
Hepatitis C virus infection DISQ0M8R Limited Biomarker [23]
Nervous system inflammation DISB3X5A Limited Biomarker [7]
Plasma cell myeloma DIS0DFZ0 Limited Altered Expression [24]
Pregnancy disorder DIS5V7J6 Limited Genetic Variation [25]
Small lymphocytic lymphoma DIS30POX Limited Altered Expression [26]
------------------------------------------------------------------------------------
⏷ Show the Full List of 34 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
5 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Ciclosporin DMAZJFX Approved Ciclosporin increases the expression of Natural cytotoxicity triggering receptor 3 (NCR3). [27]
Tretinoin DM49DUI Approved Tretinoin decreases the expression of Natural cytotoxicity triggering receptor 3 (NCR3). [28]
Acetaminophen DMUIE76 Approved Acetaminophen increases the expression of Natural cytotoxicity triggering receptor 3 (NCR3). [29]
Tacrolimus DMZ7XNQ Approved Tacrolimus increases the expression of Natural cytotoxicity triggering receptor 3 (NCR3). [27]
(+)-JQ1 DM1CZSJ Phase 1 (+)-JQ1 decreases the expression of Natural cytotoxicity triggering receptor 3 (NCR3). [31]
------------------------------------------------------------------------------------
2 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 affects the methylation of Natural cytotoxicity triggering receptor 3 (NCR3). [30]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the methylation of Natural cytotoxicity triggering receptor 3 (NCR3). [32]
------------------------------------------------------------------------------------

References

1 Elevated plasma BDNF levels are correlated with NK cell activation in patients with traumatic spinal cord injury.Int Immunopharmacol. 2019 Sep;74:105722. doi: 10.1016/j.intimp.2019.105722. Epub 2019 Jun 28.
2 Conserved 33-kb haplotype in the MHC class III region regulates chronic arthritis.Proc Natl Acad Sci U S A. 2016 Jun 28;113(26):E3716-24. doi: 10.1073/pnas.1600567113. Epub 2016 Jun 14.
3 Successfully treated HIV-infected patients have differential expression of NK cell receptors (NKp46 and NKp30) according to AIDS status at presentation.Immunol Lett. 2013 Apr;152(1):16-24. doi: 10.1016/j.imlet.2013.03.003. Epub 2013 Mar 26.
4 Correction: NKp30 expression is a prognostic immune biomarker for stratification of patients with intermediate-risk acute myeloid leukemia.Oncotarget. 2019 Sep 10;10(52):5493. doi: 10.18632/oncotarget.27198. eCollection 2019 Sep 10.
5 NK cells impede glioblastoma virotherapy through NKp30 and NKp46 natural cytotoxicity receptors.Nat Med. 2012 Dec;18(12):1827-34. doi: 10.1038/nm.3013. Epub 2012 Nov 25.
6 An NKp30-based chimeric antigen receptor promotes T cell effector functions and antitumor efficacy in vivo.J Immunol. 2012 Sep 1;189(5):2290-9. doi: 10.4049/jimmunol.1103495. Epub 2012 Jul 30.
7 The Major Histocompatibility Complex Class III Haplotype Ltab-Ncr3 Regulates Adjuvant-Induced but Not Antigen-Induced Autoimmunity.Am J Pathol. 2017 May;187(5):987-998. doi: 10.1016/j.ajpath.2016.12.022. Epub 2017 Mar 18.
8 Identification of the fungal ligand triggering cytotoxic PRR-mediated NK cell killing of Cryptococcus and Candida.Nat Commun. 2018 Feb 21;9(1):751. doi: 10.1038/s41467-018-03014-4.
9 The dynamic changes in the number of uterine natural killer cells are specific to the eutopic but not to the ectopic endometrium in women and in a baboon model of endometriosis.Reprod Biol Endocrinol. 2018 Jul 18;16(1):67. doi: 10.1186/s12958-018-0385-3.
10 NKp30 isoforms and NKp30 ligands are predictive biomarkers of response to imatinib mesylate in metastatic GIST patients.Oncoimmunology. 2016 Apr 25;6(1):e1137418. doi: 10.1080/2162402X.2015.1137418. eCollection 2017.
11 NKG2A expression and impaired function of NK cells in patients with new onset of Graves' disease.Int Immunopharmacol. 2015 Jan;24(1):133-9. doi: 10.1016/j.intimp.2014.09.020. Epub 2014 Oct 1.
12 NK cytotoxicity mediated by CD16 but not by NKp30 is functional in Griscelli syndrome.Blood. 2007 May 15;109(10):4306-12. doi: 10.1182/blood-2006-09-047159. Epub 2007 Jan 25.
13 Deficient Natural Killer Cell NKp30-Mediated Function and Altered NCR3 Splice Variants in Hepatocellular Carcinoma.Hepatology. 2019 Mar;69(3):1165-1179. doi: 10.1002/hep.30235. Epub 2019 Feb 14.
14 Impaired plasmacytoid dendritic cell (PDC)-NK cell activity in viremic human immunodeficiency virus infection attributable to impairments in both PDC and NK cell function.J Virol. 2009 Nov;83(21):11175-87. doi: 10.1128/JVI.00753-09. Epub 2009 Aug 19.
15 Deficient expression of NCR in NK cells from acute myeloid leukemia: Evolution during leukemia treatment and impact of leukemia cells in NCRdull phenotype induction.Blood. 2007 Jan 1;109(1):323-30. doi: 10.1182/blood-2005-08-027979. Epub 2006 Aug 29.
16 Beyond genome-wide scan: Association of a cis-regulatory NCR3 variant with mild malaria in a population living in the Republic of Congo.PLoS One. 2017 Nov 9;12(11):e0187818. doi: 10.1371/journal.pone.0187818. eCollection 2017.
17 Identification of 13 novel susceptibility loci for early-onset myocardial infarction, hypertension, or chronic kidney disease.Int J Mol Med. 2018 Nov;42(5):2415-2436. doi: 10.3892/ijmm.2018.3852. Epub 2018 Sep 4.
18 Circulating innate immune markers and outcomes in treatment-nave advanced non-small cell lung cancer patients.Eur J Cancer. 2019 Feb;108:88-96. doi: 10.1016/j.ejca.2018.12.017. Epub 2019 Jan 14.
19 Tumour-derived PGD2 and NKp30-B7H6 engagement drives an immunosuppressive ILC2-MDSC axis.Nat Commun. 2017 Sep 19;8(1):593. doi: 10.1038/s41467-017-00678-2.
20 When killers become helpers.Sci Transl Med. 2013 Jul 24;5(195):195fs29. doi: 10.1126/scitranslmed.3006850.
21 Mutated Von Hippel-Lindau-renal cell carcinoma (RCC) promotes patients specific natural killer (NK) cytotoxicity.J Exp Clin Cancer Res. 2018 Dec 4;37(1):297. doi: 10.1186/s13046-018-0952-7.
22 B7H6 is a functional ligand for NKp30 in rat and cattle and determines NKp30 reactivity toward human cancer cell lines.Eur J Immunol. 2019 Jan;49(1):54-65. doi: 10.1002/eji.201847746. Epub 2018 Dec 13.
23 NKp30 isoforms in patients with chronic hepatitis C virus infection.Immunology. 2015 Oct;146(2):234-42. doi: 10.1111/imm.12495. Epub 2015 Jul 8.
24 Differential expression of natural killer cell activating receptors in blood versus bone marrow in patients with monoclonal gammopathy.Immunology. 2013 Jul;139(3):338-41. doi: 10.1111/imm.12082.
25 NKp44 and NKp30 splice variant profiles in decidua and tumor tissues: a comparative viewpoint.Oncotarget. 2016 Oct 25;7(43):70912-70923. doi: 10.18632/oncotarget.12292.
26 Dysregulated Expression of Tim-3 and NKp30 Receptors on NK Cells of Patients with Chronic Lymphocytic Leukemia.Oncol Res Treat. 2019;42(4):202-208. doi: 10.1159/000497208. Epub 2019 Mar 14.
27 Mycophenolic acid inhibits natural killer cell proliferation and cytotoxic function: a possible disadvantage of including mycophenolate mofetil in the graft-versus-host disease prophylaxis regimen. Biol Blood Marrow Transplant. 2011 Feb;17(2):205-13. doi: 10.1016/j.bbmt.2010.08.014. Epub 2010 Aug 22.
28 All-trans retinoic acid negatively regulates cytotoxic activities of nature killer cell line 92. Biochem Biophys Res Commun. 2007 Jan 5;352(1):42-7. doi: 10.1016/j.bbrc.2006.10.132. Epub 2006 Nov 2.
29 Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
30 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.
31 Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem. 2012 Dec 14;287(51):43137-55.
32 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.