Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT8Z4FNE)

DOT Name Non-secretory ribonuclease (RNASE2)
Synonyms EC 4.6.1.18; Eosinophil-derived neurotoxin; RNase UpI-2; Ribonuclease 2; RNase 2; Ribonuclease US
Gene Name RNASE2
Related Disease
Ovarian neoplasm ( )
Achalasia ( )
Advanced cancer ( )
Allergic asthma ( )
Allergic rhinitis ( )
Asthma ( )
Bullous pemphigoid ( )
Cerebellar ataxia ( )
Crohn disease ( )
Essential hypertension ( )
Gastroesophageal reflux disease ( )
Hypopigmentation of the skin ( )
Idiopathic hypereosinophilic syndrome ( )
Inflammatory bowel disease ( )
Multiple sclerosis ( )
Myocardial infarction ( )
Nasal polyp ( )
Neoplasm ( )
Obesity ( )
Obstructive sleep apnea ( )
Plasma cell myeloma ( )
Respiratory syncytial virus infection ( )
Rheumatoid arthritis ( )
Systemic lupus erythematosus ( )
Ulcerative colitis ( )
Visceral leishmaniasis ( )
Chronic renal failure ( )
End-stage renal disease ( )
Bronchiolitis ( )
Atopic dermatitis ( )
Eosinophilic esophagitis ( )
Kaposi sarcoma ( )
Migraine disorder ( )
Severe acute respiratory syndrome (SARS) ( )
Stroke ( )
Thyroid gland papillary carcinoma ( )
UniProt ID
RNAS2_HUMAN
3D Structure
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2D Sequence (FASTA)
Download
3D Structure (PDB)
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PDB ID
1GQV; 1HI2; 1HI3; 1HI4; 1HI5; 1K2A; 2BEX; 2BZZ; 2C01; 2C02; 2C05; 5E13; 6SSO; 8F5X
EC Number
4.6.1.18
Pfam ID
PF00074
Sequence
MVPKLFTSQICLLLLLGLLAVEGSLHVKPPQFTWAQWFETQHINMTSQQCTNAMQVINNY
QRRCKNQNTFLLTTFANVVNVCGNPNMTCPSNKTRKNCHHSGSQVPLIHCNLTTPSPQNI
SNCRYAQTPANMFYIVACDNRDQRRDPPQYPVVPVHLDRII
Function
This is a non-secretory ribonuclease. It is a pyrimidine specific nuclease with a slight preference for U. Cytotoxin and helminthotoxin. Selectively chemotactic for dendritic cells. Possesses a wide variety of biological activities.
Tissue Specificity Liver, lung, spleen, leukocytes and body fluids.
Reactome Pathway
Neutrophil degranulation (R-HSA-6798695 )

Molecular Interaction Atlas (MIA) of This DOT

36 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Ovarian neoplasm DISEAFTY Definitive Biomarker [1]
Achalasia DISK845N Strong Biomarker [2]
Advanced cancer DISAT1Z9 Strong Biomarker [3]
Allergic asthma DISHF0H3 Strong Biomarker [4]
Allergic rhinitis DIS3U9HN Strong Genetic Variation [5]
Asthma DISW9QNS Strong Altered Expression [6]
Bullous pemphigoid DISOJLKV Strong Biomarker [7]
Cerebellar ataxia DIS9IRAV Strong Biomarker [8]
Crohn disease DIS2C5Q8 Strong Biomarker [9]
Essential hypertension DIS7WI98 Strong Biomarker [10]
Gastroesophageal reflux disease DISQ8G5S Strong Biomarker [11]
Hypopigmentation of the skin DIS39YKC Strong Biomarker [12]
Idiopathic hypereosinophilic syndrome DISXAPO9 Strong Altered Expression [13]
Inflammatory bowel disease DISGN23E Strong Biomarker [14]
Multiple sclerosis DISB2WZI Strong Biomarker [15]
Myocardial infarction DIS655KI Strong Biomarker [16]
Nasal polyp DISLP3XE Strong Biomarker [17]
Neoplasm DISZKGEW Strong Biomarker [18]
Obesity DIS47Y1K Strong Genetic Variation [19]
Obstructive sleep apnea DIS0SVD1 Strong Biomarker [20]
Plasma cell myeloma DIS0DFZ0 Strong Altered Expression [21]
Respiratory syncytial virus infection DIS7FWHY Strong Biomarker [22]
Rheumatoid arthritis DISTSB4J Strong Biomarker [23]
Systemic lupus erythematosus DISI1SZ7 Strong Biomarker [23]
Ulcerative colitis DIS8K27O Strong Biomarker [9]
Visceral leishmaniasis DISTKEYK Strong Biomarker [24]
Chronic renal failure DISGG7K6 moderate Genetic Variation [25]
End-stage renal disease DISXA7GG moderate Genetic Variation [25]
Bronchiolitis DISEE9BG Disputed Biomarker [26]
Atopic dermatitis DISTCP41 Limited Biomarker [27]
Eosinophilic esophagitis DISR8WSB Limited Biomarker [11]
Kaposi sarcoma DISC1H1Z Limited Biomarker [28]
Migraine disorder DISFCQTG Limited Genetic Variation [29]
Severe acute respiratory syndrome (SARS) DISYW14W Limited Altered Expression [30]
Stroke DISX6UHX Limited Genetic Variation [29]
Thyroid gland papillary carcinoma DIS48YMM Limited Biomarker [31]
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⏷ Show the Full List of 36 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 decreases the methylation of Non-secretory ribonuclease (RNASE2). [32]
Ciclosporin DMAZJFX Approved Ciclosporin increases the methylation of Non-secretory ribonuclease (RNASE2). [33]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene decreases the methylation of Non-secretory ribonuclease (RNASE2). [40]
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8 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Tretinoin DM49DUI Approved Tretinoin increases the expression of Non-secretory ribonuclease (RNASE2). [34]
Acetaminophen DMUIE76 Approved Acetaminophen decreases the expression of Non-secretory ribonuclease (RNASE2). [35]
Cytarabine DMZD5QR Approved Cytarabine increases the expression of Non-secretory ribonuclease (RNASE2). [36]
Cyclophosphamide DM4O2Z7 Approved Cyclophosphamide decreases the expression of Non-secretory ribonuclease (RNASE2). [37]
Salmeterol DMIEU69 Approved Salmeterol decreases the expression of Non-secretory ribonuclease (RNASE2). [38]
Urethane DM7NSI0 Phase 4 Urethane decreases the expression of Non-secretory ribonuclease (RNASE2). [39]
Beclomethasone dipropionate DM5NW1E Phase 4 Beclomethasone dipropionate decreases the expression of Non-secretory ribonuclease (RNASE2). [38]
Milchsaure DM462BT Investigative Milchsaure increases the expression of Non-secretory ribonuclease (RNASE2). [41]
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⏷ Show the Full List of 8 Drug(s)

References

1 Proteomic-based discovery and characterization of glycosylated eosinophil-derived neurotoxin and COOH-terminal osteopontin fragments for ovarian cancer in urine.Clin Cancer Res. 2006 Jan 15;12(2):432-41. doi: 10.1158/1078-0432.CCR-05-0461.
2 Activated Eosinophils are Present in Esophageal Muscle in Patients with Achalasia of the Esophagus.Med Sci Monit. 2018 Apr 19;24:2377-2383. doi: 10.12659/msm.909727.
3 Unique recombinant human ribonuclease and inhibition of Kaposi's sarcoma cell growth.J Natl Cancer Inst. 1998 Dec 2;90(23):1787-91. doi: 10.1093/jnci/90.23.1787.
4 Peripheral blood eosinophils from patients with allergic asthma contain increased intracellular eosinophil-derived neurotoxin.J Allergy Clin Immunol. 2004 Sep;114(3):568-74. doi: 10.1016/j.jaci.2004.05.023.
5 Association of FLG single nucleotide variations with clinical phenotypes of atopic dermatitis.PLoS One. 2017 Dec 27;12(12):e0190077. doi: 10.1371/journal.pone.0190077. eCollection 2017.
6 Serum Levels of Eosinophil-Derived Neurotoxin: A Biomarker for Asthma Severity in Adult Asthmatics.Allergy Asthma Immunol Res. 2019 May;11(3):394-405. doi: 10.4168/aair.2019.11.3.394.
7 Mechanisms of pathogenic effects of eosinophil cationic protein and eosinophil-derived neurotoxin on human keratinocytes.Exp Dermatol. 2018 Dec;27(12):1322-1327. doi: 10.1111/exd.13782. Epub 2018 Oct 22.
8 Molecular cloning of the human eosinophil-derived neurotoxin: a member of the ribonuclease gene family.Proc Natl Acad Sci U S A. 1989 Jun;86(12):4460-4. doi: 10.1073/pnas.86.12.4460.
9 Prognostic significance of faecal eosinophil granule proteins in inflammatory bowel disease.Scand J Gastroenterol. 2019 Oct;54(10):1237-1244. doi: 10.1080/00365521.2019.1670251. Epub 2019 Oct 2.
10 Association of genetic polymorphisms of endothelin-converting enzyme-1 gene with hypertension in a Japanese population and rare missense mutation in preproendothelin-1 in Japanese hypertensives.Hypertens Res. 2007 Jun;30(6):513-20. doi: 10.1291/hypres.30.513.
11 Blind esophageal brushing offers a safe and accurate method to monitor inflammation in children and young adults with eosinophilic esophagitis.Dis Esophagus. 2018 Dec 1;31(12). doi: 10.1093/dote/doy056.
12 Epilation induces hair and skin pigmentation through an EDN3/EDNRB-dependent regenerative response of melanocyte stem cells.Sci Rep. 2017 Aug 4;7(1):7272. doi: 10.1038/s41598-017-07683-x.
13 Familial eosinophilia: a benign disorder?.Blood. 2004 Jun 1;103(11):4050-5. doi: 10.1182/blood-2003-11-3850. Epub 2004 Feb 26.
14 Inflammatory bowel disease detection and monitoring by measuring biomarkers in non-invasively collected colorectal mucus.J Gastroenterol Hepatol. 2017 May;32(5):992-1002. doi: 10.1111/jgh.13627.
15 The Toll-like Receptor 2 (TLR2)-related Immunopathological Responses in the Multiple Sclerosis and Experimental Autoimmune Encephalomyelitis.Iran J Allergy Asthma Immunol. 2019 Jun 8;18(3):230-250. doi: 10.18502/ijaai.v18i3.1117.
16 Identification of key genes involved in myocardial infarction.Eur J Med Res. 2019 Jul 3;24(1):22. doi: 10.1186/s40001-019-0381-x.
17 Eosinophil-derived neurotoxin enhances airway remodeling in eosinophilic chronic rhinosinusitis and correlates with disease severity.Int Immunol. 2019 Feb 6;31(1):33-40. doi: 10.1093/intimm/dxy061.
18 CCR4-expressing T cell tumors can be specifically controlled via delivery of toxins to chemokine receptors.J Immunol. 2007 Aug 1;179(3):1996-2004. doi: 10.4049/jimmunol.179.3.1996.
19 Polymorphisms in endothelin system genes, arsenic levels and obesity risk.PLoS One. 2015 Mar 23;10(3):e0118471. doi: 10.1371/journal.pone.0118471. eCollection 2015.
20 Polymorphisms in nitric oxide synthase and endothelin genes among children with obstructive sleep apnea.BMC Med Genomics. 2013 Sep 6;6:29. doi: 10.1186/1755-8794-6-29.
21 Endothelin-1 receptor blockade as new possible therapeutic approach in multiple myeloma.Br J Haematol. 2017 Sep;178(5):781-793. doi: 10.1111/bjh.14771. Epub 2017 Jun 9.
22 Analysis of the predicting factors of recurrent wheezing in infants.Ital J Pediatr. 2019 Jan 29;45(1):19. doi: 10.1186/s13052-019-0609-y.
23 Caught in a Trap? Proteomic Analysis of Neutrophil Extracellular Traps in Rheumatoid Arthritis and Systemic Lupus Erythematosus.Front Immunol. 2019 Mar 11;10:423. doi: 10.3389/fimmu.2019.00423. eCollection 2019.
24 The genetically determined production of the alarmin eosinophil-derived neurotoxin is reduced in visceral leishmaniasis.APMIS. 2018 Jan;126(1):85-91. doi: 10.1111/apm.12780. Epub 2017 Nov 29.
25 Associations of genetic variants of endothelin with cardiovascular complications in patients with renal failure.BMC Nephrol. 2017 Sep 7;18(1):291. doi: 10.1186/s12882-017-0707-2.
26 Comparison of serum eosinophil-derived neurotoxin levels between wheezing and non-wheezing groups in children with respiratory tract infection.J Asthma. 2020 Nov;57(11):1211-1215. doi: 10.1080/02770903.2019.1642349. Epub 2019 Aug 20.
27 Eosinophil-derived neurotoxin as a biomarker for disease severity and relapse in recalcitrant atopic dermatitis.Ann Allergy Asthma Immunol. 2017 Nov;119(5):441-445. doi: 10.1016/j.anai.2017.06.022. Epub 2017 Aug 31.
28 Crystallographic and functional studies of a modified form of eosinophil-derived neurotoxin (EDN) with novel biological activities.J Mol Biol. 2002 Mar 15;317(1):119-30. doi: 10.1006/jmbi.2002.5406.
29 Relation of candidate genes that encode for endothelial function to migraine and stroke: the Stroke Prevention in Young Women study.Stroke. 2009 Oct;40(10):e550-7. doi: 10.1161/STROKEAHA.109.557462. Epub 2009 Aug 6.
30 Molecular signature of clinical severity in recovering patients with severe acute respiratory syndrome coronavirus (SARS-CoV).BMC Genomics. 2005 Sep 21;6:132. doi: 10.1186/1471-2164-6-132.
31 Gene profiling identifies genes specific for well-differentiated epithelial thyroid tumors.Cell Mol Biol (Noisy-le-grand). 2005 Sep 5;51(2):177-86.
32 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.
33 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.
34 Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
35 Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
36 The DNA methyltransferase inhibitors azacitidine, decitabine and zebularine exert differential effects on cancer gene expression in acute myeloid leukemia cells. Leukemia. 2009 Jun;23(6):1019-28.
37 Comparative gene expression analysis of a chronic myelogenous leukemia cell line resistant to cyclophosphamide using oligonucleotide arrays and response to tyrosine kinase inhibitors. Leuk Res. 2007 Nov;31(11):1511-20.
38 Comparison of anti-inflammatory and clinical effects of beclomethasone dipropionate and salmeterol in moderate asthma. Eur Respir J. 2002 Jul;20(1):66-72. doi: 10.1183/09031936.02.00094202.
39 Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
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.
41 Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.