Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTJA81JU)

DOT Name NACHT, LRR and PYD domains-containing protein 2 (NLRP2)
Synonyms Nucleotide-binding site protein 1; PYRIN domain and NACHT domain-containing protein 1; PYRIN-containing APAF1-like protein 2
Gene Name NLRP2
Related Disease
Childhood acute lymphoblastic leukemia ( )
Chromosomal disorder ( )
Gastric cancer ( )
Stomach cancer ( )
Adenocarcinoma ( )
Ataxia-telangiectasia ( )
Bladder cancer ( )
Breast neoplasm ( )
Carcinoma ( )
Clear cell renal carcinoma ( )
Fanconi anemia complementation group A ( )
Fanconi's anemia ( )
Glioma ( )
Head and neck cancer ( )
Head and neck carcinoma ( )
Head-neck squamous cell carcinoma ( )
Hepatocellular carcinoma ( )
Isolated congenital microcephaly ( )
leukaemia ( )
Lymphoma, non-Hodgkin, familial ( )
Nasopharyngeal carcinoma ( )
Plasma cell myeloma ( )
Prostate cancer ( )
Prostate carcinoma ( )
Renal cell carcinoma ( )
Squamous cell carcinoma ( )
Systemic lupus erythematosus ( )
Urinary bladder cancer ( )
Urinary bladder neoplasm ( )
Venous thromboembolism ( )
Cutaneous melanoma ( )
Glioblastoma multiforme ( )
Liver cancer ( )
Lung cancer ( )
Lung carcinoma ( )
Adult glioblastoma ( )
Aplastic anemia ( )
Cervical cancer ( )
Cervical carcinoma ( )
Acute lymphocytic leukaemia ( )
Acute myelogenous leukaemia ( )
Colorectal carcinoma ( )
Leukemia ( )
Lymphoma ( )
Non-small-cell lung cancer ( )
Oocyte/zygote/embryo maturation arrest 18 ( )
Pancreatic cancer ( )
Rheumatoid arthritis ( )
UniProt ID
NALP2_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
Pfam ID
PF13516 ; PF05729 ; PF17776 ; PF17779 ; PF02758
Sequence
MVSSAQMGFNLQALLEQLSQDELSKFKYLITTFSLAHELQKIPHKEVDKADGKQLVEILT
THCDSYWVEMASLQVFEKMHRMDLSERAKDEVREAALKSFNKRKPLSLGITRKERPPLDV
DEMLERFKTEAQAFTETKGNVICLGKEVFKGKKPDKDNRCRYILKTKFREMWKSWPGDSK
EVQVMAERYKMLIPFSNPRVLPGPFSYTVVLYGPAGLGKTTLAQKLMLDWAEDNLIHKFK
YAFYLSCRELSRLGPCSFAELVFRDWPELQDDIPHILAQARKILFVIDGFDELGAAPGAL
IEDICGDWEKKKPVPVLLGSLLNRVMLPKAALLVTTRPRALRDLRILAEEPIYIRVEGFL
EEDRRAYFLRHFGDEDQAMRAFELMRSNAALFQLGSAPAVCWIVCTTLKLQMEKGEDPVP
TCLTRTGLFLRFLCSRFPQGAQLRGALRTLSLLAAQGLWAQTSVLHREDLERLGVQESDL
RLFLDGDILRQDRVSKGCYSFIHLSFQQFLTALFYTLEKEEEEDRDGHTWDIGDVQKLLS
GVERLRNPDLIQAGYYSFGLANEKRAKELEATFGCRMSPDIKQELLRCDISCKGGHSTVT
DLQELLGCLYESQEEELVKEVMAQFKEISLHLNAVDVVPSSFCVKHCRNLQKMSLQVIKE
NLPENVTASESDAEVERSQDDQHMLPFWTDLCSIFGSNKDLMGLAINDSFLSASLVRILC
EQIASDTCHLQRVVFKNISPADAHRNLCLALRGHKTVTYLTLQGNDQDDMFPALCEVLRH
PECNLRYLGLVSCSATTQQWADLSLALEVNQSLTCVNLSDNELLDEGAKLLYTTLRHPKC
FLQRLSLENCHLTEANCKDLAAVLVVSRELTHLCLAKNPIGNTGVKFLCEGLRYPECKLQ
TLVLWNCDITSDGCCDLTKLLQEKSSLLCLDLGLNHIGVKGMKFLCEALRKPLCNLRCLW
LWGCSIPPFSCEDLCSALSCNQSLVTLDLGQNPLGSSGVKMLFETLTCSSGTLRTLRLKI
DDFNDELNKLLEEIEEKNPQLIIDTEKHHPWAERPSSHDFMI
Function
Suppresses TNF- and CD40-induced NFKB1 activity at the level of the IKK complex, by inhibiting NFKBIA degradation induced by TNF. When associated with PYCARD, activates CASP1, leading to the secretion of mature pro-inflammatory cytokine IL1B. May be a component of the inflammasome, a protein complex which also includes PYCARD, CARD8 and CASP1 and whose function would be the activation of pro-inflammatory caspases.
Tissue Specificity
Expressed at high levels in lung, placenta and thymus and at lower levels in ovary, intestine and brain . Highly abundant in oocytes and early embryos, however poorly expressed in somatic tissues such as brain, kidney, liver and spinal cord .

Molecular Interaction Atlas (MIA) of This DOT

48 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Childhood acute lymphoblastic leukemia DISJ5D6U Definitive Genetic Variation [1]
Chromosomal disorder DISM5BB5 Definitive Genetic Variation [1]
Gastric cancer DISXGOUK Definitive Genetic Variation [2]
Stomach cancer DISKIJSX Definitive Genetic Variation [2]
Adenocarcinoma DIS3IHTY Strong Altered Expression [3]
Ataxia-telangiectasia DISP3EVR Strong Biomarker [4]
Bladder cancer DISUHNM0 Strong Genetic Variation [5]
Breast neoplasm DISNGJLM Strong Genetic Variation [6]
Carcinoma DISH9F1N Strong Altered Expression [7]
Clear cell renal carcinoma DISBXRFJ Strong Biomarker [8]
Fanconi anemia complementation group A DIS8PZLI Strong Biomarker [9]
Fanconi's anemia DISGW6Q8 Strong Biomarker [9]
Glioma DIS5RPEH Strong Biomarker [10]
Head and neck cancer DISBPSQZ Strong Biomarker [11]
Head and neck carcinoma DISOU1DS Strong Biomarker [11]
Head-neck squamous cell carcinoma DISF7P24 Strong Biomarker [12]
Hepatocellular carcinoma DIS0J828 Strong Biomarker [13]
Isolated congenital microcephaly DISUXHZ6 Strong Biomarker [14]
leukaemia DISS7D1V Strong Genetic Variation [15]
Lymphoma, non-Hodgkin, familial DISCXYIZ Strong Genetic Variation [16]
Nasopharyngeal carcinoma DISAOTQ0 Strong Altered Expression [17]
Plasma cell myeloma DIS0DFZ0 Strong Genetic Variation [18]
Prostate cancer DISF190Y Strong Altered Expression [19]
Prostate carcinoma DISMJPLE Strong Genetic Variation [19]
Renal cell carcinoma DISQZ2X8 Strong Biomarker [8]
Squamous cell carcinoma DISQVIFL Strong Altered Expression [20]
Systemic lupus erythematosus DISI1SZ7 Strong Genetic Variation [21]
Urinary bladder cancer DISDV4T7 Strong Genetic Variation [5]
Urinary bladder neoplasm DIS7HACE Strong Genetic Variation [5]
Venous thromboembolism DISUR7CR Strong Genetic Variation [22]
Cutaneous melanoma DIS3MMH9 moderate Biomarker [23]
Glioblastoma multiforme DISK8246 moderate Biomarker [24]
Liver cancer DISDE4BI moderate Genetic Variation [25]
Lung cancer DISCM4YA moderate Genetic Variation [26]
Lung carcinoma DISTR26C moderate Genetic Variation [26]
Adult glioblastoma DISVP4LU Disputed Biomarker [24]
Aplastic anemia DISJRSC0 Disputed Genetic Variation [1]
Cervical cancer DISFSHPF Disputed Genetic Variation [27]
Cervical carcinoma DIST4S00 Disputed Genetic Variation [27]
Acute lymphocytic leukaemia DISPX75S Limited Genetic Variation [15]
Acute myelogenous leukaemia DISCSPTN Limited Genetic Variation [28]
Colorectal carcinoma DIS5PYL0 Limited Genetic Variation [29]
Leukemia DISNAKFL Limited Genetic Variation [15]
Lymphoma DISN6V4S Limited Posttranslational Modification [30]
Non-small-cell lung cancer DIS5Y6R9 Limited Genetic Variation [31]
Oocyte/zygote/embryo maturation arrest 18 DISJ2BPG Limited Unknown [32]
Pancreatic cancer DISJC981 Limited Genetic Variation [33]
Rheumatoid arthritis DISTSB4J Limited Genetic Variation [34]
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⏷ Show the Full List of 48 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas 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 NACHT, LRR and PYD domains-containing protein 2 (NLRP2). [35]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene affects the methylation of NACHT, LRR and PYD domains-containing protein 2 (NLRP2). [40]
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4 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Acetaminophen DMUIE76 Approved Acetaminophen decreases the expression of NACHT, LRR and PYD domains-containing protein 2 (NLRP2). [36]
Ivermectin DMDBX5F Approved Ivermectin increases the expression of NACHT, LRR and PYD domains-containing protein 2 (NLRP2). [37]
Temozolomide DMKECZD Approved Temozolomide increases the expression of NACHT, LRR and PYD domains-containing protein 2 (NLRP2). [38]
Testosterone DM7HUNW Approved Testosterone decreases the expression of NACHT, LRR and PYD domains-containing protein 2 (NLRP2). [39]
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References

1 A rare polymorphic variant of NBS1 reduces DNA repair activity and elevates chromosomal instability.Cancer Res. 2014 Jul 15;74(14):3707-15. doi: 10.1158/0008-5472.CAN-13-3037. Epub 2014 May 15.
2 Novel somatic frameshift mutations of genes related to cell cycle and DNA damage response in gastric and colorectal cancers with microsatellite instability.Tumori. 2010 Nov-Dec;96(6):1004-9.
3 The biological and therapeutic importance of gastrin gene expression in pancreatic adenocarcinomas.Cancer Res. 2004 Aug 15;64(16):5624-31. doi: 10.1158/0008-5472.CAN-04-0106.
4 Role and clinical significance of lymphocyte mitochondrial dysfunction in type 2 diabetes mellitus.Transl Res. 2011 Dec;158(6):344-59. doi: 10.1016/j.trsl.2011.08.007. Epub 2011 Sep 13.
5 NBS1 Glu185Gln polymorphism and susceptibility to urinary system cancer: a meta-analysis.Tumour Biol. 2014 Nov;35(11):10723-9. doi: 10.1007/s13277-014-2346-6. Epub 2014 Jul 30.
6 NBS1 657del5 mutation may contribute only to a limited fraction of breast cancer cases in Russia.Int J Cancer. 2005 Apr 20;114(4):585-9. doi: 10.1002/ijc.20765.
7 Expression of MRE11 complex (MRE11, RAD50, NBS1) and hRap1 and its relation with telomere regulation, telomerase activity in human gastric carcinomas.Pathobiology. 2001;69(4):219-24. doi: 10.1159/000055946.
8 DNA repair system and renal cell carcinoma prognosis: under the influence of NBS1.Med Oncol. 2015 Nov;32(11):255. doi: 10.1007/s12032-015-0701-0. Epub 2015 Oct 22.
9 MRE11-RAD50-NBS1 promotes Fanconi Anemia R-loop suppression at transcription-replication conflicts.Nat Commun. 2019 Sep 19;10(1):4265. doi: 10.1038/s41467-019-12271-w.
10 SMAD3 silencing enhances DNA damage in radiation therapy by interacting with MRE11-RAD50-NBS1 complex in glioma.J Biochem. 2019 Apr 1;165(4):317-322. doi: 10.1093/jb/mvy110.
11 Molecular disruption of NBS1 with targeted gene delivery enhances chemosensitisation in head and neck cancer.Br J Cancer. 2010 Dec 7;103(12):1822-30. doi: 10.1038/sj.bjc.6605980. Epub 2010 Nov 9.
12 Dual disruption of DNA repair and telomere maintenance for the treatment of head and neck cancer.Clin Cancer Res. 2014 Dec 15;20(24):6465-78. doi: 10.1158/1078-0432.CCR-14-0176. Epub 2014 Oct 16.
13 Mutation inactivation of Nijmegen breakage syndrome gene (NBS1) in hepatocellular carcinoma and intrahepatic cholangiocarcinoma.PLoS One. 2013 Dec 13;8(12):e82426. doi: 10.1371/journal.pone.0082426. eCollection 2013.
14 MRI evidence of white matter damage in a mouse model of Nijmegen breakage syndrome.Exp Neurol. 2008 Jan;209(1):181-91. doi: 10.1016/j.expneurol.2007.09.021. Epub 2007 Oct 2.
15 Functional polymorphisms in the NBS1 gene and acute lymphoblastic leukemia susceptibility in a Chinese population.Eur J Haematol. 2011 Mar;86(3):199-205. doi: 10.1111/j.1600-0609.2010.01562.x. Epub 2011 Jan 25.
16 Haplotypic variation in MRE11, RAD50 and NBS1 and risk of non-Hodgkin's lymphoma.Leuk Lymphoma. 2006 Dec;47(12):2567-83. doi: 10.1080/10428190600909743.
17 Downregulation of FoxM1 sensitizes nasopharyngeal carcinoma cells to cisplatin via inhibition of MRN-ATM-mediated DNA repair.BMB Rep. 2019 Mar;52(3):208-213. doi: 10.5483/BMBRep.2019.52.3.249.
18 Differential Expression of Non-Shelterin Genes Associated with High Telomerase Levels and Telomere Shortening in Plasma Cell Disorders.PLoS One. 2015 Sep 14;10(9):e0137972. doi: 10.1371/journal.pone.0137972. eCollection 2015.
19 The prognostic impact of high Nijmegen breakage syndrome (NBS1) gene expression in ERG-negative prostate cancers lacking PTEN deletion is driven by KPNA2 expression.Int J Cancer. 2014 Sep 15;135(6):1399-407. doi: 10.1002/ijc.28778. Epub 2014 Feb 26.
20 Radiosensitization of head/neck squamous cell carcinoma by adenovirus-mediated expression of the Nbs1 protein.Int J Radiat Oncol Biol Phys. 2007 Jan 1;67(1):273-8. doi: 10.1016/j.ijrobp.2006.09.019.
21 The NBS1 genetic polymorphisms and the risk of the systemic lupus erythematosus in Taiwanese patients.J Clin Immunol. 2010 Sep;30(5):643-8. doi: 10.1007/s10875-010-9427-0. Epub 2010 Jun 23.
22 Genomic and transcriptomic association studies identify 16 novel susceptibility loci for venous thromboembolism.Blood. 2019 Nov 7;134(19):1645-1657. doi: 10.1182/blood.2019000435.
23 Molecular genetic analysis of NBS1 in German melanoma patients.Melanoma Res. 2007 Apr;17(2):109-16. doi: 10.1097/CMR.0b013e3280dec638.
24 L1CAM regulates DNA damage checkpoint response of glioblastoma stem cells through NBS1.EMBO J. 2011 Mar 2;30(5):800-13. doi: 10.1038/emboj.2011.10. Epub 2011 Feb 4.
25 Genetic variation in the NBS1 gene is associated with hepatic cancer risk in a Chinese population.DNA Cell Biol. 2012 May;31(5):678-82. doi: 10.1089/dna.2011.1421. Epub 2011 Nov 9.
26 Polymorphisms in DNA repair genes in lung cancer patients living in a coal-mining region.Eur J Cancer Prev. 2019 Nov;28(6):522-528. doi: 10.1097/CEJ.0000000000000504.
27 Effect of NBS1 gene polymorphism on the risk of cervix carcinoma in a northern Indian population.Int J Biol Markers. 2008 Jul-Sep;23(3):133-9. doi: 10.1177/172460080802300301.
28 NBS1 rs1805794G>C polymorphism is associated with decreased risk of acute myeloid leukemia in a Chinese population.Mol Biol Rep. 2013 May;40(5):3749-56. doi: 10.1007/s11033-012-2451-9. Epub 2013 Jan 3.
29 rs2735383, located at a microRNA binding site in the 3'UTR of NBS1, is not associated with breast cancer risk.Sci Rep. 2016 Nov 15;6:36874. doi: 10.1038/srep36874.
30 No evidence for deletions of the NBS1 gene in lymphomas.Cancer Genet Cytogenet. 2001 Apr 1;126(1):60-2. doi: 10.1016/s0165-4608(00)00390-3.
31 Tobacco smoking, NBS1 polymorphisms, and survival in lung and upper aerodigestive tract cancers with semi-Bayes adjustment for hazard ratio variation.Cancer Causes Control. 2014 Jan;25(1):11-23. doi: 10.1007/s10552-013-0303-0. Epub 2013 Oct 29.
32 Germline mutation in NLRP2 (NALP2) in a familial imprinting disorder (Beckwith-Wiedemann Syndrome). PLoS Genet. 2009 Mar;5(3):e1000423. doi: 10.1371/journal.pgen.1000423. Epub 2009 Mar 20.
33 Do founder mutations characteristic of some cancer sites also predispose to pancreatic cancer?.Int J Cancer. 2016 Aug 1;139(3):601-6. doi: 10.1002/ijc.30116. Epub 2016 Apr 18.
34 Association of polymorphisms in SPARC and NLRP2 genes with rheumatoid arthritis in a Chinese Han population.Mod Rheumatol. 2015 Jan;25(1):67-71. doi: 10.3109/14397595.2014.903595. Epub 2014 Apr 23.
35 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.
36 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.
37 Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
38 Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
39 The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
40 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.