Details of Drug Off-Target (DOT)

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

DOT Name Probable rRNA-processing protein EBP2 (EBNA1BP2)
Synonyms EBNA1-binding protein 2; Nucleolar protein p40
Gene Name EBNA1BP2
Related Disease
Colorectal carcinoma ( )
Abdominal aortic aneurysm ( )
Adenoma ( )
Advanced cancer ( )
Alzheimer disease ( )
Autoimmune disease ( )
Breast cancer ( )
Carcinoma ( )
Dementia ( )
Ewing sarcoma ( )
Hepatitis C virus infection ( )
Hepatocellular carcinoma ( )
HIV infectious disease ( )
Immunodeficiency ( )
Inflammatory bowel disease ( )
Lung adenocarcinoma ( )
Lung carcinoma ( )
Multiple sclerosis ( )
Mycobacterium infection ( )
Nervous system inflammation ( )
Non-hodgkin lymphoma ( )
Non-small-cell lung cancer ( )
Osteoarthritis ( )
Prostate cancer ( )
Prostate carcinoma ( )
Psoriasis ( )
Pulmonary disease ( )
Rheumatoid arthritis ( )
Systemic lupus erythematosus ( )
Tuberculosis ( )
Ulcerative colitis ( )
Ankylosing spondylitis ( )
Arteriosclerosis ( )
Atherosclerosis ( )
Bipolar disorder ( )
Breast carcinoma ( )
Small-cell lung cancer ( )
Type-1/2 diabetes ( )
Malaria ( )
Arthritis ( )
Asthma ( )
Atopic dermatitis ( )
Colitis ( )
Lung cancer ( )
Neoplasm ( )
Type-1 diabetes ( )
UniProt ID
EBP2_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
PDB ID
8FKP; 8FKQ; 8FKR; 8FKS; 8FKT; 8FKU; 8FKV; 8FKW; 8FKX; 8FKY
Pfam ID
PF05890
Sequence
MDTPPLSDSESESDESLVTDRELQDAFSRGLLKPGLNVVLEGPKKAVNDVNGLKQCLAEF
KRDLEWVERLDVTLGPVPEIGGSEAPAPQNKDQKAVDPEDDFQREMSFYRQAQAAVLAVL
PRLHQLKVPTKRPTDYFAEMAKSDLQMQKIRQKLQTKQAAMERSEKAKQLRALRKYGKKV
QTEVLQKRQQEKAHMMNAIKKYQKGFSDKLDFLEGDQKPLAQRKKAGAKGQQMRKGPSAK
RRYKNQKFGFGGKKKGSKWNTRESYDDVSSFRAKTAHGRGLKRPGKKGSNKRPGKRTREK
MKNRTH
Function Required for the processing of the 27S pre-rRNA.
Tissue Specificity Ubiquitous.
Reactome Pathway
Major pathway of rRNA processing in the nucleolus and cytosol (R-HSA-6791226 )

Molecular Interaction Atlas (MIA) of This DOT

46 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Colorectal carcinoma DIS5PYL0 Definitive Biomarker [1]
Abdominal aortic aneurysm DISD06OF Strong Biomarker [2]
Adenoma DIS78ZEV Strong Altered Expression [3]
Advanced cancer DISAT1Z9 Strong Biomarker [4]
Alzheimer disease DISF8S70 Strong Biomarker [5]
Autoimmune disease DISORMTM Strong Biomarker [6]
Breast cancer DIS7DPX1 Strong Altered Expression [7]
Carcinoma DISH9F1N Strong Genetic Variation [8]
Dementia DISXL1WY Strong Biomarker [5]
Ewing sarcoma DISQYLV3 Strong Altered Expression [9]
Hepatitis C virus infection DISQ0M8R Strong Biomarker [10]
Hepatocellular carcinoma DIS0J828 Strong Biomarker [11]
HIV infectious disease DISO97HC Strong Genetic Variation [12]
Immunodeficiency DIS093I0 Strong Altered Expression [13]
Inflammatory bowel disease DISGN23E Strong Biomarker [14]
Lung adenocarcinoma DISD51WR Strong Biomarker [15]
Lung carcinoma DISTR26C Strong Biomarker [16]
Multiple sclerosis DISB2WZI Strong Biomarker [17]
Mycobacterium infection DISNSMUD Strong Genetic Variation [18]
Nervous system inflammation DISB3X5A Strong Biomarker [19]
Non-hodgkin lymphoma DISS2Y8A Strong Altered Expression [20]
Non-small-cell lung cancer DIS5Y6R9 Strong Biomarker [21]
Osteoarthritis DIS05URM Strong Altered Expression [22]
Prostate cancer DISF190Y Strong Altered Expression [4]
Prostate carcinoma DISMJPLE Strong Altered Expression [4]
Psoriasis DIS59VMN Strong Biomarker [23]
Pulmonary disease DIS6060I Strong Altered Expression [24]
Rheumatoid arthritis DISTSB4J Strong Altered Expression [22]
Systemic lupus erythematosus DISI1SZ7 Strong Biomarker [6]
Tuberculosis DIS2YIMD Strong Altered Expression [25]
Ulcerative colitis DIS8K27O Strong Biomarker [26]
Ankylosing spondylitis DISRC6IR moderate Biomarker [22]
Arteriosclerosis DISK5QGC moderate Genetic Variation [27]
Atherosclerosis DISMN9J3 moderate Genetic Variation [27]
Bipolar disorder DISAM7J2 moderate Genetic Variation [28]
Breast carcinoma DIS2UE88 moderate Altered Expression [29]
Small-cell lung cancer DISK3LZD moderate Altered Expression [30]
Type-1/2 diabetes DISIUHAP moderate Genetic Variation [27]
Malaria DISQ9Y50 Disputed Biomarker [31]
Arthritis DIST1YEL Limited Biomarker [32]
Asthma DISW9QNS Limited Altered Expression [33]
Atopic dermatitis DISTCP41 Limited Biomarker [34]
Colitis DISAF7DD Limited Altered Expression [35]
Lung cancer DISCM4YA Limited Biomarker [36]
Neoplasm DISZKGEW Limited Biomarker [37]
Type-1 diabetes DIS7HLUB Limited Altered Expression [38]
------------------------------------------------------------------------------------
⏷ Show the Full List of 46 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
14 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate increases the expression of Probable rRNA-processing protein EBP2 (EBNA1BP2). [39]
Ciclosporin DMAZJFX Approved Ciclosporin decreases the expression of Probable rRNA-processing protein EBP2 (EBNA1BP2). [40]
Tretinoin DM49DUI Approved Tretinoin decreases the expression of Probable rRNA-processing protein EBP2 (EBNA1BP2). [41]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of Probable rRNA-processing protein EBP2 (EBNA1BP2). [42]
Cisplatin DMRHGI9 Approved Cisplatin decreases the expression of Probable rRNA-processing protein EBP2 (EBNA1BP2). [43]
Ivermectin DMDBX5F Approved Ivermectin decreases the expression of Probable rRNA-processing protein EBP2 (EBNA1BP2). [44]
Hydrogen peroxide DM1NG5W Approved Hydrogen peroxide affects the expression of Probable rRNA-processing protein EBP2 (EBNA1BP2). [45]
Menadione DMSJDTY Approved Menadione affects the expression of Probable rRNA-processing protein EBP2 (EBNA1BP2). [45]
Piroxicam DMTK234 Approved Piroxicam decreases the expression of Probable rRNA-processing protein EBP2 (EBNA1BP2). [46]
(+)-JQ1 DM1CZSJ Phase 1 (+)-JQ1 decreases the expression of Probable rRNA-processing protein EBP2 (EBNA1BP2). [47]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the expression of Probable rRNA-processing protein EBP2 (EBNA1BP2). [49]
Milchsaure DM462BT Investigative Milchsaure decreases the expression of Probable rRNA-processing protein EBP2 (EBNA1BP2). [50]
chloropicrin DMSGBQA Investigative chloropicrin decreases the expression of Probable rRNA-processing protein EBP2 (EBNA1BP2). [51]
Deguelin DMXT7WG Investigative Deguelin decreases the expression of Probable rRNA-processing protein EBP2 (EBNA1BP2). [52]
------------------------------------------------------------------------------------
⏷ Show the Full List of 14 Drug(s)
1 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
TAK-243 DM4GKV2 Phase 1 TAK-243 increases the sumoylation of Probable rRNA-processing protein EBP2 (EBNA1BP2). [48]
------------------------------------------------------------------------------------

References

1 Role of anthocyanin-enriched purple-fleshed sweet potato p40 in colorectal cancer prevention.Mol Nutr Food Res. 2013 Nov;57(11):1908-17. doi: 10.1002/mnfr.201300040. Epub 2013 Jun 19.
2 Interleukin-12 and -23 blockade mitigates elastase-induced abdominal aortic aneurysm.Sci Rep. 2019 Jul 18;9(1):10447. doi: 10.1038/s41598-019-46909-y.
3 Investigation of IL-23 (p19, p40) and IL-23R identifies nuclear expression of IL-23 p19 as a favorable prognostic factor in colorectal cancer: a retrospective multicenter study of 675 patients.Oncotarget. 2014 Jul 15;5(13):4671-82. doi: 10.18632/oncotarget.2069.
4 Selective neutralization of IL-12 p40 monomer induces death in prostate cancer cells via IL-12-IFN-.Proc Natl Acad Sci U S A. 2017 Oct 24;114(43):11482-11487. doi: 10.1073/pnas.1705536114. Epub 2017 Oct 9.
5 Reduced cerebrospinal fluid concentration of interleukin-12/23 subunit p40 in patients with cognitive impairment.PLoS One. 2017 May 2;12(5):e0176760. doi: 10.1371/journal.pone.0176760. eCollection 2017.
6 High Prevalence and Disease Correlation of Autoantibodies Against p40 Encoded by Long Interspersed Nuclear Elements in Systemic Lupus Erythematosus.Arthritis Rheumatol. 2020 Jan;72(1):89-99. doi: 10.1002/art.41054.
7 Comparative expression of the LINE-1 p40 protein in human breast carcinomas and normal breast tissues.Oncol Res. 1996;8(6):239-47.
8 RETRACTED ARTICLE: Cervical adenosquamous carcinoma: detailed analysis of morphology, immunohistochemical profile, and clinical outcomes in 59 cases.Mod Pathol. 2019 Feb;32(2):269-279. doi: 10.1038/s41379-018-0123-6. Epub 2018 Sep 26.
9 Adamantinoma-like Ewing Sarcoma of the Salivary Glands: A Newly Recognized Mimicker of Basaloid Salivary Carcinomas.Am J Surg Pathol. 2019 Feb;43(2):187-194. doi: 10.1097/PAS.0000000000001171.
10 Impaired allostimulatory capacity of peripheral blood dendritic cells recovered from hepatitis C virus-infected individuals.J Immunol. 1999 May 1;162(9):5584-91.
11 PTK2 and EIF3S3 genes may be amplification targets at 8q23-q24 and are associated with large hepatocellular carcinomas.Hepatology. 2003 Nov;38(5):1242-9. doi: 10.1053/jhep.2003.50457.
12 Disruption of MAP kinase activation and nuclear factor binding to the IL-12 p40 promoter in HIV-infected myeloid cells.Clin Exp Immunol. 2004 Aug;137(2):329-40. doi: 10.1111/j.1365-2249.2004.02513.x.
13 Molecular analysis of decreased interleukin-12 production in persons infected with human immunodeficiency virus.J Infect Dis. 1996 Jul;174(1):46-53. doi: 10.1093/infdis/174.1.46.
14 Allergic and Immunologic Perspectives of Inflammatory Bowel Disease.Clin Rev Allergy Immunol. 2019 Oct;57(2):179-193. doi: 10.1007/s12016-018-8690-3.
15 CDX-2 Expression in Primary Lung Adenocarcinoma.Appl Immunohistochem Mol Morphol. 2016 Jan;24(1):16-9. doi: 10.1097/PAI.0000000000000250.
16 Biomarkers in the diagnosis of pleural diseases: a 2018 update.Ther Adv Respir Dis. 2018 Jan-Dec;12:1753466618808660. doi: 10.1177/1753466618808660.
17 Meta-analysis of the IL23R and IL12B polymorphisms in multiple sclerosis.Int J Neurosci. 2016;126(3):205-12. doi: 10.3109/00207454.2015.1007508. Epub 2015 Jun 16.
18 Chronic Disseminated Salmonellosis in a Patient With Interleukin-12p40 Deficiency.Pediatr Infect Dis J. 2018 Jan;37(1):90-93. doi: 10.1097/INF.0000000000001701.
19 Silencing c-Rel in macrophages dampens Th1 and Th17 immune responses and alleviates experimental autoimmune encephalomyelitis in mice.Immunol Cell Biol. 2017 Aug;95(7):593-600. doi: 10.1038/icb.2017.11. Epub 2017 Feb 16.
20 Th1/Th2 cytokine expression and its relationship with tumor growth in B cell non-Hodgkin's lymphoma (NHL).Leuk Lymphoma. 2002 Jun;43(6):1313-21. doi: 10.1080/10428190290026385.
21 Non-small cell lung carcinoma with diffuse coexpression of thyroid transcription factor-1 and Np63/p40.Hum Pathol. 2018 Aug;78:177-181. doi: 10.1016/j.humpath.2018.01.023. Epub 2018 Feb 2.
22 IL-17A induces osteoblast differentiation by activating JAK2/STAT3 in ankylosing spondylitis.Arthritis Res Ther. 2018 Jun 7;20(1):115. doi: 10.1186/s13075-018-1582-3.
23 Anti-IL-12/IL-23p40 antibody ameliorates dermatitis and skin barrier dysfunction in mice with imiquimod-induced psoriasis-like dermatitis.Eur J Pharmacol. 2018 Jun 5;828:26-30. doi: 10.1016/j.ejphar.2018.03.018. Epub 2018 Mar 12.
24 Interleukin 23/interleukin 17 axis activated by Mycobacterium avium complex (MAC) is attenuated in patients with MAC-lung disease.Tuberculosis (Edinb). 2018 May;110:7-14. doi: 10.1016/j.tube.2018.03.001. Epub 2018 Mar 3.
25 Mycobacterium tuberculosis PPE44 (Rv2770c) is involved in response to multiple stresses and promotes the macrophage expression of IL-12 p40 and IL-6 via the p38, ERK, and NF-B signaling axis.Int Immunopharmacol. 2017 Sep;50:319-329. doi: 10.1016/j.intimp.2017.06.028. Epub 2017 Jul 22.
26 Expert opinion on interleukin-12/23 and interleukin-23 antagonists as potential therapeutic options for the treatment of inflammatory bowel disease.Expert Opin Investig Drugs. 2019 May;28(5):473-479. doi: 10.1080/13543784.2019.1597053. Epub 2019 Mar 26.
27 Polymorphism of the 3'-untranslated region of interleukin-12 p40 gene is not associated with the presence or severity of coronary artery disease.Circ J. 2005 Jul;69(7):793-7. doi: 10.1253/circj.69.793.
28 Genome-wide association study of bipolar disorder accounting for effect of body mass index identifies a new risk allele in TCF7L2.Mol Psychiatry. 2014 Sep;19(9):1010-6. doi: 10.1038/mp.2013.159. Epub 2013 Dec 10.
29 Evaluation of p40 as a Myoepithelial Marker in Different Breast Lesions.Pathobiology. 2015 Sep;82(3-4):166-71. doi: 10.1159/000375127. Epub 2015 Aug 31.
30 P40 expression in small cell lung cancer: The presence of p40-positive cells does not always indicate squamous differentiation.Thorac Cancer. 2019 May;10(5):1188-1192. doi: 10.1111/1759-7714.13062. Epub 2019 Apr 7.
31 A replication study of the association between the IL12B promoter allele CTCTAA and susceptibility to cerebral malaria in Thai population.Malar J. 2009 Dec 11;8:290. doi: 10.1186/1475-2875-8-290.
32 Divergent effects of IL-12 and IL-23 on the production of IL-17 by human T cells.Eur J Immunol. 2006 Mar;36(3):661-70. doi: 10.1002/eji.200535239.
33 Associations of the IL12B promoter polymorphism in longitudinal data from asthmatic patients 7 to 42 years of age.J Allergy Clin Immunol. 2004 Mar;113(3):475-81. doi: 10.1016/j.jaci.2003.10.043.
34 Ustekinumab treatment in severe atopic dermatitis: Down-regulation of T-helper 2/22 expression.J Am Acad Dermatol. 2017 Jan;76(1):91-97.e3. doi: 10.1016/j.jaad.2016.07.047. Epub 2016 Oct 13.
35 Production of a Functional Factor, p40, by Lactobacillus rhamnosus GG Is Promoted by Intestinal Epithelial Cell-Secreted Extracellular Vesicles.Infect Immun. 2019 Jun 20;87(7):e00113-19. doi: 10.1128/IAI.00113-19. Print 2019 Jul.
36 Mucin staining is of limited value in addition to basic immunohistochemical analyses in the diagnostics of non-small cell lung cancer.Sci Rep. 2019 Feb 4;9(1):1319. doi: 10.1038/s41598-018-37722-0.
37 American Registry of Pathology Expert Opinions: Evaluation of poorly differentiated malignant neoplasms on limited samples - Gastrointestinal mucosal biopsies.Ann Diagn Pathol. 2020 Feb;44:151419. doi: 10.1016/j.anndiagpath.2019.151419. Epub 2019 Nov 15.
38 Alleles of the IL12B 3'UTR associate with late onset of type 1 diabetes.Hum Immunol. 2004 Dec;65(12):1432-6. doi: 10.1016/j.humimm.2004.09.001.
39 Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
40 Cyclosporine A--induced oxidative stress in human renal mesangial cells: a role for ERK 1/2 MAPK signaling. Toxicol Sci. 2012 Mar;126(1):101-13.
41 Retinoic acid-induced downmodulation of telomerase activity in human cancer cells. Exp Mol Pathol. 2005 Oct;79(2):108-17.
42 Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
43 Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
44 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.
45 Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
46 Apoptosis induced by piroxicam plus cisplatin combined treatment is triggered by p21 in mesothelioma. PLoS One. 2011;6(8):e23569.
47 BET bromodomain inhibition targets both c-Myc and IL7R in high-risk acute lymphoblastic leukemia. Blood. 2012 Oct 4;120(14):2843-52.
48 Inhibiting ubiquitination causes an accumulation of SUMOylated newly synthesized nuclear proteins at PML bodies. J Biol Chem. 2019 Oct 18;294(42):15218-15234. doi: 10.1074/jbc.RA119.009147. Epub 2019 Jul 8.
49 Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
50 Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
51 Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.
52 Neurotoxicity and underlying cellular changes of 21 mitochondrial respiratory chain inhibitors. Arch Toxicol. 2021 Feb;95(2):591-615. doi: 10.1007/s00204-020-02970-5. Epub 2021 Jan 29.