Details of Drug Off-Target (DOT)

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

DOT Name Nucleoside diphosphate kinase B (NME2)
Synonyms NDK B; NDP kinase B; EC 2.7.4.6; C-myc purine-binding transcription factor PUF; Histidine protein kinase NDKB; EC 2.7.13.3; nm23-H2
Gene Name NME2
Related Disease
Adenocarcinoma ( )
Alzheimer disease ( )
Arteriosclerosis ( )
Atherosclerosis ( )
Bladder cancer ( )
Bone osteosarcoma ( )
Breast cancer ( )
Breast carcinoma ( )
Breast neoplasm ( )
Carcinoma ( )
Cholangiocarcinoma ( )
Clear cell renal carcinoma ( )
Colonic neoplasm ( )
Colorectal carcinoma ( )
Diabetic retinopathy ( )
Epithelial ovarian cancer ( )
Ewing sarcoma ( )
Gastric cancer ( )
Hepatocellular carcinoma ( )
Leukemia ( )
Lung cancer ( )
Lung carcinoma ( )
Metastatic malignant neoplasm ( )
Osteosarcoma ( )
Ovarian cancer ( )
Ovarian neoplasm ( )
Psoriasis ( )
Renal cell carcinoma ( )
Skin disease ( )
Squamous cell carcinoma ( )
Stomach cancer ( )
Urinary bladder cancer ( )
Urinary bladder neoplasm ( )
Mesothelioma ( )
Colorectal neoplasm ( )
Acute myelogenous leukaemia ( )
Adult glioblastoma ( )
Advanced cancer ( )
Glioblastoma multiforme ( )
Lung squamous cell carcinoma ( )
Melanoma ( )
Neoplasm ( )
Neuroblastoma ( )
Non-small-cell lung cancer ( )
Osteoarthritis ( )
UniProt ID
NDKB_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
PDB ID
1NSK; 1NUE; 3BBB; 3BBC; 3BBF; 7KPF
EC Number
2.7.13.3; 2.7.4.6
Pfam ID
PF00334
Sequence
MANLERTFIAIKPDGVQRGLVGEIIKRFEQKGFRLVAMKFLRASEEHLKQHYIDLKDRPF
FPGLVKYMNSGPVVAMVWEGLNVVKTGRVMLGETNPADSKPGTIRGDFCIQVGRNIIHGS
DSVKSAEKEISLWFKPEELVDYKSCAHDWVYE
Function
Major role in the synthesis of nucleoside triphosphates other than ATP. The ATP gamma phosphate is transferred to the NDP beta phosphate via a ping-pong mechanism, using a phosphorylated active-site intermediate. Negatively regulates Rho activity by interacting with AKAP13/LBC. Acts as a transcriptional activator of the MYC gene; binds DNA non-specifically. Binds to both single-stranded guanine- and cytosine-rich strands within the nuclease hypersensitive element (NHE) III(1) region of the MYC gene promoter. Does not bind to duplex NHE III(1). Has G-quadruplex (G4) DNA-binding activity, which is independent of its nucleotide-binding and kinase activity. Binds both folded and unfolded G4 with similar low nanomolar affinities. Stabilizes folded G4s regardless of whether they are prefolded or not. Exhibits histidine protein kinase activity.
Tissue Specificity .Ubiquitously expressed.; [Isoform 3]: Ubiquitously expressed.
KEGG Pathway
Purine metabolism (hsa00230 )
Pyrimidine metabolism (hsa00240 )
Drug metabolism - other enzymes (hsa00983 )
Metabolic pathways (hsa01100 )
Nucleotide metabolism (hsa01232 )
Biosynthesis of cofactors (hsa01240 )
Reactome Pathway
Neutrophil degranulation (R-HSA-6798695 )
Azathioprine ADME (R-HSA-9748787 )
Ribavirin ADME (R-HSA-9755088 )
Interconversion of nucleotide di- and triphosphates (R-HSA-499943 )
BioCyc Pathway
MetaCyc:HS04463-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

45 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Adenocarcinoma DIS3IHTY Strong Biomarker [1]
Alzheimer disease DISF8S70 Strong Altered Expression [2]
Arteriosclerosis DISK5QGC Strong Biomarker [3]
Atherosclerosis DISMN9J3 Strong Biomarker [3]
Bladder cancer DISUHNM0 Strong Biomarker [4]
Bone osteosarcoma DIST1004 Strong Altered Expression [5]
Breast cancer DIS7DPX1 Strong Biomarker [6]
Breast carcinoma DIS2UE88 Strong Biomarker [6]
Breast neoplasm DISNGJLM Strong Biomarker [7]
Carcinoma DISH9F1N Strong Genetic Variation [8]
Cholangiocarcinoma DIS71F6X Strong Altered Expression [9]
Clear cell renal carcinoma DISBXRFJ Strong Altered Expression [10]
Colonic neoplasm DISSZ04P Strong Altered Expression [8]
Colorectal carcinoma DIS5PYL0 Strong Biomarker [6]
Diabetic retinopathy DISHGUJM Strong Biomarker [11]
Epithelial ovarian cancer DIS56MH2 Strong Biomarker [12]
Ewing sarcoma DISQYLV3 Strong Altered Expression [13]
Gastric cancer DISXGOUK Strong Biomarker [6]
Hepatocellular carcinoma DIS0J828 Strong Biomarker [14]
Leukemia DISNAKFL Strong Altered Expression [15]
Lung cancer DISCM4YA Strong Altered Expression [16]
Lung carcinoma DISTR26C Strong Altered Expression [16]
Metastatic malignant neoplasm DIS86UK6 Strong Biomarker [17]
Osteosarcoma DISLQ7E2 Strong Altered Expression [5]
Ovarian cancer DISZJHAP Strong Therapeutic [18]
Ovarian neoplasm DISEAFTY Strong Therapeutic [18]
Psoriasis DIS59VMN Strong Altered Expression [19]
Renal cell carcinoma DISQZ2X8 Strong Altered Expression [10]
Skin disease DISDW8R6 Strong Altered Expression [19]
Squamous cell carcinoma DISQVIFL Strong Biomarker [20]
Stomach cancer DISKIJSX Strong Biomarker [6]
Urinary bladder cancer DISDV4T7 Strong Biomarker [4]
Urinary bladder neoplasm DIS7HACE Strong Biomarker [4]
Mesothelioma DISKWK9M moderate Biomarker [21]
Colorectal neoplasm DISR1UCN Disputed Biomarker [22]
Acute myelogenous leukaemia DISCSPTN Limited Altered Expression [23]
Adult glioblastoma DISVP4LU Limited Biomarker [24]
Advanced cancer DISAT1Z9 Limited Biomarker [25]
Glioblastoma multiforme DISK8246 Limited Biomarker [24]
Lung squamous cell carcinoma DISXPIBD Limited Altered Expression [26]
Melanoma DIS1RRCY Limited Altered Expression [27]
Neoplasm DISZKGEW Limited Altered Expression [28]
Neuroblastoma DISVZBI4 Limited Altered Expression [29]
Non-small-cell lung cancer DIS5Y6R9 Limited Altered Expression [26]
Osteoarthritis DIS05URM Limited Biomarker [30]
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⏷ Show the Full List of 45 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
18 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Tretinoin DM49DUI Approved Tretinoin decreases the expression of Nucleoside diphosphate kinase B (NME2). [31]
Doxorubicin DMVP5YE Approved Doxorubicin increases the expression of Nucleoside diphosphate kinase B (NME2). [32]
Ivermectin DMDBX5F Approved Ivermectin decreases the expression of Nucleoside diphosphate kinase B (NME2). [33]
Arsenic DMTL2Y1 Approved Arsenic decreases the expression of Nucleoside diphosphate kinase B (NME2). [34]
Calcitriol DM8ZVJ7 Approved Calcitriol decreases the expression of Nucleoside diphosphate kinase B (NME2). [35]
Testosterone DM7HUNW Approved Testosterone decreases the expression of Nucleoside diphosphate kinase B (NME2). [36]
Progesterone DMUY35B Approved Progesterone increases the expression of Nucleoside diphosphate kinase B (NME2). [18]
Diethylstilbestrol DMN3UXQ Approved Diethylstilbestrol increases the expression of Nucleoside diphosphate kinase B (NME2). [39]
Sodium lauryl sulfate DMLJ634 Approved Sodium lauryl sulfate decreases the expression of Nucleoside diphosphate kinase B (NME2). [40]
Cocaine DMSOX7I Approved Cocaine affects the expression of Nucleoside diphosphate kinase B (NME2). [41]
Capsaicin DMGMF6V Approved Capsaicin increases the expression of Nucleoside diphosphate kinase B (NME2). [42]
Alitretinoin DMME8LH Approved Alitretinoin decreases the expression of Nucleoside diphosphate kinase B (NME2). [31]
(+)-JQ1 DM1CZSJ Phase 1 (+)-JQ1 decreases the expression of Nucleoside diphosphate kinase B (NME2). [44]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the expression of Nucleoside diphosphate kinase B (NME2). [46]
chloropicrin DMSGBQA Investigative chloropicrin decreases the expression of Nucleoside diphosphate kinase B (NME2). [47]
3R14S-OCHRATOXIN A DM2KEW6 Investigative 3R14S-OCHRATOXIN A decreases the expression of Nucleoside diphosphate kinase B (NME2). [48]
4-hydroxy-2-nonenal DM2LJFZ Investigative 4-hydroxy-2-nonenal decreases the expression of Nucleoside diphosphate kinase B (NME2). [49]
Tributylstannanyl DMHN7CB Investigative Tributylstannanyl decreases the expression of Nucleoside diphosphate kinase B (NME2). [50]
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⏷ Show the Full List of 18 Drug(s)
3 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Decitabine DMQL8XJ Approved Decitabine affects the methylation of Nucleoside diphosphate kinase B (NME2). [37]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the methylation of Nucleoside diphosphate kinase B (NME2). [43]
PMID28870136-Compound-52 DMFDERP Patented PMID28870136-Compound-52 increases the phosphorylation of Nucleoside diphosphate kinase B (NME2). [45]
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References

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2 Human brain nucleoside diphosphate kinase activity is decreased in Alzheimer's disease and Down syndrome.Biochem Biophys Res Commun. 2002 Aug 30;296(4):970-5. doi: 10.1016/s0006-291x(02)02035-1.
3 NM23-H2, an estrogen receptor beta-associated protein, shows diminished expression with progression of atherosclerosis.Am J Physiol Regul Integr Comp Physiol. 2007 Feb;292(2):R743-50. doi: 10.1152/ajpregu.00373.2006. Epub 2006 Aug 3.
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5 Nucleoside diphosphate kinase B promotes osteosarcoma proliferation through c-Myc.Cancer Biol Ther. 2018 Jul 3;19(7):565-572. doi: 10.1080/15384047.2017.1416273. Epub 2018 Apr 13.
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9 Recruited metastasis suppressor NM23-H2 attenuates expression and activity of peroxisome proliferator-activated receptor (PPAR) in human cholangiocarcinoma.Dig Liver Dis. 2015 Jan;47(1):62-7. doi: 10.1016/j.dld.2014.09.002. Epub 2014 Sep 29.
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11 O-GlcNAcylation of FoxO1 mediates nucleoside diphosphate kinase B deficiency induced endothelial damage.Sci Rep. 2018 Jul 12;8(1):10581. doi: 10.1038/s41598-018-28892-y.
12 THRA1 and D17S183 flank an interval of < 4 cM for the breast-ovarian cancer gene (BRCA1) on chromosome 17q21.Am J Hum Genet. 1993 Apr;52(4):718-22.
13 High nm23-H1/NDPK-A expression in Ewing tumors: paradoxical immunohistochemical reactivity and lack of prognostic significance.Int J Cancer. 1995 Apr 21;64(2):104-11. doi: 10.1002/ijc.2910640206.
14 The protein histidine phosphatase LHPP is a tumour suppressor.Nature. 2018 Mar 29;555(7698):678-682. doi: 10.1038/nature26140. Epub 2018 Mar 21.
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16 CARMA3 Represses Metastasis Suppressor NME2 to Promote Lung Cancer Stemness and Metastasis.Am J Respir Crit Care Med. 2015 Jul 1;192(1):64-75. doi: 10.1164/rccm.201411-1957OC.
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18 Identification of ATF-3, caveolin-1, DLC-1, and NM23-H2 as putative antitumorigenic, progesterone-regulated genes for ovarian cancer cells by gene profiling. Oncogene. 2005 Mar 3;24(10):1774-87. doi: 10.1038/sj.onc.1207991.
19 Novel roles of NM23 proteins in skin homeostasis, repair and disease.Oncogene. 2007 Jan 25;26(4):532-42. doi: 10.1038/sj.onc.1209822. Epub 2006 Jul 24.
20 Gene expression profiling of Nm23-H2 overexpressing CAL 27 cells using DNA microarray.Neoplasma. 2008;55(5):447-54.
21 Identification of novel candidate oncogenes and tumor suppressors in malignant pleural mesothelioma using large-scale transcriptional profiling.Am J Pathol. 2005 Jun;166(6):1827-40. doi: 10.1016/S0002-9440(10)62492-3.
22 Variance in the expression of 5-Fluorouracil pathway genes in colorectal cancer.Clin Cancer Res. 2005 Apr 1;11(7):2612-9. doi: 10.1158/1078-0432.CCR-04-1258.
23 Differentiation inhibitory factor nm23 as a new prognostic factor in acute monocytic leukemia.Blood. 1996 Nov 1;88(9):3555-61.
24 Naphthalene diimide-derivatives G-quadruplex ligands induce cell proliferation inhibition, mild telomeric dysfunction and cell cycle perturbation in U251MG glioma cells.FEBS J. 2018 Oct;285(20):3769-3785. doi: 10.1111/febs.14628. Epub 2018 Sep 24.
25 Development of a Risk Score to Predict Anastomotic Leak After Left-Sided Colectomy: Which Patients Warrant Diversion?.J Gastrointest Surg. 2020 Jan;24(1):132-143. doi: 10.1007/s11605-019-04293-y. Epub 2019 Jun 26.
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27 Cationic folate-mediated liposomal delivery of bis-arylidene oxindole induces efficient melanoma tumor regression.Biomater Sci. 2017 Aug 22;5(9):1898-1909. doi: 10.1039/c7bm00405b.
28 Inhibition of miR31 and miR92a as Oncological Biomarkers in RKO Colon Cancer Cells Treated with Kaempferol-3-O-Glycoside Isolated from Black Bean.J Med Food. 2020 Jan;23(1):50-55. doi: 10.1089/jmf.2019.0059. Epub 2019 Aug 23.
29 Read-through transcript from NM23-H1 into the neighboring NM23-H2 gene encodes a novel protein, NM23-LV.Genomics. 2006 Apr;87(4):483-9. doi: 10.1016/j.ygeno.2005.11.004. Epub 2006 Jan 25.
30 Mitochondrial dysregulation of osteoarthritic human articular chondrocytes analyzed by proteomics: a decrease in mitochondrial superoxide dismutase points to a redox imbalance.Mol Cell Proteomics. 2009 Jan;8(1):172-89. doi: 10.1074/mcp.M800292-MCP200. Epub 2008 Sep 9.
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33 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.
34 Nucleophosmin in the pathogenesis of arsenic-related bladder carcinogenesis revealed by quantitative proteomics. Toxicol Appl Pharmacol. 2010 Jan 15;242(2):126-35. doi: 10.1016/j.taap.2009.09.016. Epub 2009 Oct 7.
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36 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.
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39 Analysis of gene expression induced by diethylstilbestrol (DES) in human primitive Mullerian duct cells using microarray. Cancer Lett. 2005 Apr 8;220(2):197-210.
40 Identification of potential biomarkers for predicting acute dermal irritation by proteomic analysis. J Appl Toxicol. 2011 Nov;31(8):762-72.
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