Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTVE2XD1)

DOT Name Eosinophil cationic protein (RNASE3)
Synonyms ECP; EC 3.1.27.-; Ribonuclease 3; RNase 3
Gene Name RNASE3
Related Disease
Prostate cancer ( )
Prostate carcinoma ( )
Small-cell lung cancer ( )
Acute myelogenous leukaemia ( )
Asthma ( )
Atopic dermatitis ( )
Bone osteosarcoma ( )
Breast cancer ( )
Breast carcinoma ( )
Bullous pemphigoid ( )
Carcinoma ( )
Cataract ( )
Cervical carcinoma ( )
Clear cell renal carcinoma ( )
Colorectal carcinoma ( )
Endometriosis ( )
Epithelial ovarian cancer ( )
Gastric cancer ( )
Glioblastoma multiforme ( )
Hepatocellular carcinoma ( )
leukaemia ( )
Li-Fraumeni syndrome ( )
Lung cancer ( )
Lung carcinoma ( )
Lymphoma, non-Hodgkin, familial ( )
Melanoma ( )
Nasal polyp ( )
Non-hodgkin lymphoma ( )
Non-small-cell lung cancer ( )
Osteosarcoma ( )
Ovarian cancer ( )
Ovarian neoplasm ( )
Periodontitis ( )
Renal cell carcinoma ( )
Squamous cell carcinoma ( )
Stomach cancer ( )
Stroke ( )
Type-1/2 diabetes ( )
Chronic obstructive pulmonary disease ( )
Gram-negative bacterial infection ( )
Gram-positive bacterial infection ( )
Leukemia ( )
Inflammatory bowel disease ( )
Malaria ( )
Malignant soft tissue neoplasm ( )
Neoplasm ( )
Sarcoma ( )
Tuberous sclerosis 2 ( )
UniProt ID
ECP_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
PDB ID
1DYT; 1H1H; 1QMT; 2KB5; 2LVZ; 4A2O; 4A2Y; 4OWZ; 4OXB; 4OXF; 4X08
EC Number
3.1.27.-
Pfam ID
PF00074
Sequence
MVPKLFTSQICLLLLLGLMGVEGSLHARPPQFTRAQWFAIQHISLNPPRCTIAMRAINNY
RWRCKNQNTFLRTTFANVVNVCGNQSIRCPHNRTLNNCHRSRFRVPLLHCDLINPGAQNI
SNCTYADRPGRRFYVVACDNRDPRDSPRYPVVPVHLDTTI
Function
Cytotoxin and helminthotoxin with low-efficiency ribonuclease activity. Possesses a wide variety of biological activities. Exhibits antibacterial activity, including cytoplasmic membrane depolarization of preferentially Gram-negative, but also Gram-positive strains. Promotes E.coli outer membrane detachment, alteration of the overall cell shape and partial loss of cell content.
KEGG Pathway
Asthma (hsa05310 )
Reactome Pathway
Antimicrobial peptides (R-HSA-6803157 )
Neutrophil degranulation (R-HSA-6798695 )

Molecular Interaction Atlas (MIA) of This DOT

48 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Prostate cancer DISF190Y Definitive Altered Expression [1]
Prostate carcinoma DISMJPLE Definitive Altered Expression [1]
Small-cell lung cancer DISK3LZD Definitive Biomarker [2]
Acute myelogenous leukaemia DISCSPTN Strong Biomarker [3]
Asthma DISW9QNS Strong Altered Expression [4]
Atopic dermatitis DISTCP41 Strong Biomarker [5]
Bone osteosarcoma DIST1004 Strong Biomarker [6]
Breast cancer DIS7DPX1 Strong Biomarker [7]
Breast carcinoma DIS2UE88 Strong Biomarker [8]
Bullous pemphigoid DISOJLKV Strong Biomarker [9]
Carcinoma DISH9F1N Strong Altered Expression [10]
Cataract DISUD7SL Strong Biomarker [11]
Cervical carcinoma DIST4S00 Strong Altered Expression [12]
Clear cell renal carcinoma DISBXRFJ Strong Biomarker [13]
Colorectal carcinoma DIS5PYL0 Strong Altered Expression [14]
Endometriosis DISX1AG8 Strong Biomarker [15]
Epithelial ovarian cancer DIS56MH2 Strong Altered Expression [16]
Gastric cancer DISXGOUK Strong Biomarker [17]
Glioblastoma multiforme DISK8246 Strong Biomarker [18]
Hepatocellular carcinoma DIS0J828 Strong Altered Expression [19]
leukaemia DISS7D1V Strong Biomarker [20]
Li-Fraumeni syndrome DISR64XA Strong Genetic Variation [21]
Lung cancer DISCM4YA Strong Biomarker [22]
Lung carcinoma DISTR26C Strong Biomarker [22]
Lymphoma, non-Hodgkin, familial DISCXYIZ Strong Genetic Variation [23]
Melanoma DIS1RRCY Strong Biomarker [24]
Nasal polyp DISLP3XE Strong Biomarker [25]
Non-hodgkin lymphoma DISS2Y8A Strong Biomarker [26]
Non-small-cell lung cancer DIS5Y6R9 Strong Altered Expression [27]
Osteosarcoma DISLQ7E2 Strong Biomarker [6]
Ovarian cancer DISZJHAP Strong Altered Expression [16]
Ovarian neoplasm DISEAFTY Strong Altered Expression [16]
Periodontitis DISI9JOI Strong Biomarker [28]
Renal cell carcinoma DISQZ2X8 Strong Biomarker [13]
Squamous cell carcinoma DISQVIFL Strong Genetic Variation [29]
Stomach cancer DISKIJSX Strong Biomarker [17]
Stroke DISX6UHX Strong Altered Expression [30]
Type-1/2 diabetes DISIUHAP Strong Biomarker [31]
Chronic obstructive pulmonary disease DISQCIRF moderate Biomarker [32]
Gram-negative bacterial infection DIS8MM3L moderate Therapeutic [33]
Gram-positive bacterial infection DISZ44JH moderate Therapeutic [33]
Leukemia DISNAKFL moderate Biomarker [34]
Inflammatory bowel disease DISGN23E Limited Biomarker [35]
Malaria DISQ9Y50 Limited Genetic Variation [36]
Malignant soft tissue neoplasm DISTC6NO Limited Genetic Variation [37]
Neoplasm DISZKGEW Limited Biomarker [38]
Sarcoma DISZDG3U Limited Genetic Variation [37]
Tuberous sclerosis 2 DISR6GKZ Limited Biomarker [39]
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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
1 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 Eosinophil cationic protein (RNASE3). [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 Eosinophil cationic protein (RNASE3). [41]
Diphenylpyraline DMW4X37 Approved Diphenylpyraline increases the expression of Eosinophil cationic protein (RNASE3). [42]
Budesonide DMJIBAW Approved Budesonide decreases the expression of Eosinophil cationic protein (RNASE3). [43]
Zafirlukast DMHNQOG Approved Zafirlukast decreases the expression of Eosinophil cationic protein (RNASE3). [43]
Salmeterol DMIEU69 Approved Salmeterol decreases the expression of Eosinophil cationic protein (RNASE3). [44]
Arformoterol DMYM974 Approved Arformoterol decreases the expression of Eosinophil cationic protein (RNASE3). [45]
Beclomethasone dipropionate DM5NW1E Phase 4 Beclomethasone dipropionate decreases the expression of Eosinophil cationic protein (RNASE3). [46]
Phencyclidine DMQBEYX Investigative Phencyclidine decreases the expression of Eosinophil cationic protein (RNASE3). [47]
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⏷ Show the Full List of 8 Drug(s)

References

1 Clinical significance of RKIP mRNA expression in non-small cell lung cancer.Tumour Biol. 2014 May;35(5):4377-80. doi: 10.1007/s13277-013-1575-4. Epub 2014 Jan 14.
2 Raf-1 causes growth suppression and alteration of neuroendocrine markers in DMS53 human small-cell lung cancer cells.Am J Respir Cell Mol Biol. 1999 Apr;20(4):543-9. doi: 10.1165/ajrcmb.20.4.3406.
3 PTPIP51 is phosphorylated by Lyn and c-Src kinases lacking dephosphorylation by PTP1B in acute myeloid leukemia.Leuk Res. 2011 Oct;35(10):1367-75. doi: 10.1016/j.leukres.2011.03.024. Epub 2011 Apr 22.
4 Association Between Epithelial Cytokines and Clinical Phenotypes of Elderly Asthma.Allergy Asthma Immunol Res. 2019 Jan;11(1):79-89. doi: 10.4168/aair.2019.11.1.79.
5 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.
6 Transcription factor CEBPB inhibits the proliferation of osteosarcoma by regulating downstream target gene CLEC5A.J Clin Lab Anal. 2019 Nov;33(9):e22985. doi: 10.1002/jcla.22985. Epub 2019 Jul 31.
7 Structure-activity relationships of 2, 4-disubstituted pyrimidines as dual ER/VEGFR-2 ligands with anti-breast cancer activity.Eur J Med Chem. 2018 Apr 25;150:783-795. doi: 10.1016/j.ejmech.2018.03.018. Epub 2018 Mar 7.
8 Galectin-1 knockdown improves drug sensitivity of breast cancer by reducing P-glycoprotein expression through inhibiting the Raf-1/AP-1 signaling pathway.Oncotarget. 2017 Apr 11;8(15):25097-25106. doi: 10.18632/oncotarget.15341.
9 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.
10 Raf-1 kinase, epidermal growth factor receptors, and mutant Ras proteins in colonic carcinomas.Dig Dis Sci. 1996 Jun;41(6):1069-75. doi: 10.1007/BF02088221.
11 Phacoemulsification plus endoscopic cyclophotocoagulation versus phacoemulsification alone in primary open-angle glaucoma.Eur J Ophthalmol. 2018 Mar;28(2):168-174. doi: 10.5301/ejo.5001034.
12 MicroRNA-497 accelerates apoptosis while inhibiting proliferation, migration, and invasion through negative regulation of the MAPK/ERK signaling pathway via RAF-1.J Cell Physiol. 2018 Oct;233(10):6578-6588. doi: 10.1002/jcp.26272. Epub 2018 May 9.
13 Differentiation between papillary and nonpapillary renal cell carcinomas by DNA analysis.J Natl Cancer Inst. 1989 Apr 5;81(7):527-30. doi: 10.1093/jnci/81.7.527.
14 miRNA biogenesis-associated RNase III nucleases Drosha and Dicer are upregulated in colorectal adenocarcinoma.Oncol Lett. 2017 Oct;14(4):4379-4383. doi: 10.3892/ol.2017.6674. Epub 2017 Jul 26.
15 USP10 promotes proliferation and migration and inhibits apoptosis of endometrial stromal cells in endometriosis through activating the Raf-1/MEK/ERK pathway.Am J Physiol Cell Physiol. 2018 Dec 1;315(6):C863-C872. doi: 10.1152/ajpcell.00272.2018. Epub 2018 Oct 3.
16 Comparison of strategies targeting Raf-1 mRNA in ovarian cancer.Int J Cancer. 2006 Mar 15;118(6):1565-71. doi: 10.1002/ijc.21520.
17 p42.3 gene expression in gastric cancer cell and its protein regulatory network analysis.Theor Biol Med Model. 2012 Dec 11;9(1):53. doi: 10.1186/1742-4682-9-53.
18 PTPIP51, a positive modulator of the MAPK/Erk pathway, is upregulated in glioblastoma and interacts with 14-3-3 and PTP1B in situ.Histol Histopathol. 2011 Dec;26(12):1531-43. doi: 10.14670/HH-26.1531.
19 Downregulation of Raf-1 kinase inhibitory protein as a sorafenib resistance mechanism in hepatocellular carcinoma cell lines.J Cancer Res Clin Oncol. 2018 Aug;144(8):1487-1501. doi: 10.1007/s00432-018-2672-y. Epub 2018 Jun 1.
20 Mechanisms of acquired resistance to ERK1/2 pathway inhibitors.Oncogene. 2013 Mar 7;32(10):1207-15. doi: 10.1038/onc.2012.160. Epub 2012 May 7.
21 Abnormal pattern of post-gamma-ray DNA replication in radioresistant fibroblast strains from affected members of a cancer-prone family with Li-Fraumeni syndrome.Br J Cancer. 1995 Jun;71(6):1221-30. doi: 10.1038/bjc.1995.237.
22 Lung-targeted expression of the c-Raf-1 kinase in transgenic mice exposes a novel oncogenic character of the wild-type protein.Cell Growth Differ. 2000 Apr;11(4):185-90.
23 Allelic variation of the c-raf-1 proto-oncogene in human lymphoma and leukemia.Oncogene. 1989 Apr;4(4):507-10.
24 Eosinophil-cationic protein - a novel liquid prognostic biomarker in melanoma.BMC Cancer. 2019 Mar 7;19(1):207. doi: 10.1186/s12885-019-5384-z.
25 Associations Between Inflammatory Endotypes and Clinical Presentations in Chronic Rhinosinusitis.J Allergy Clin Immunol Pract. 2019 Nov-Dec;7(8):2812-2820.e3. doi: 10.1016/j.jaip.2019.05.009. Epub 2019 May 22.
26 Rituximab (chimeric anti-CD20 monoclonal antibody) inhibits the constitutive nuclear factor-{kappa}B signaling pathway in non-Hodgkin's lymphoma B-cell lines: role in sensitization to chemotherapeutic drug-induced apoptosis.Cancer Res. 2005 Jan 1;65(1):264-76.
27 Non-canonical Raf-1/p70S6K signalling in non-small-cell lung cancer.J Cell Mol Med. 2019 Nov;23(11):7632-7640. doi: 10.1111/jcmm.14636. Epub 2019 Sep 21.
28 Eosinophil cationic protein and histamine production by neutrophils from patients with periodontitis.J Periodontol. 2018 Feb;89(2):228-234. doi: 10.1902/jop.2017.160679. Epub 2018 Feb 20.
29 The 434(G>C) polymorphism in the eosinophil cationic protein gene and its association with tissue eosinophilia in oral squamous cell carcinomas.J Oral Pathol Med. 2010 Jan;39(1):56-62. doi: 10.1111/j.1600-0714.2009.00795.x. Epub 2009 Jun 28.
30 Eosinophil Cationic Protein, Carotid Plaque, and Incidence of Stroke.Stroke. 2017 Oct;48(10):2686-2692. doi: 10.1161/STROKEAHA.117.018450. Epub 2017 Sep 13.
31 Stimulation of -adrenergic receptors plays a protective role via increased expression of RAF-1 and PDX-1 in hyperglycemic rat pancreatic islet (RIN-m5F) cells.Arch Med Sci. 2017 Mar 1;13(2):470-480. doi: 10.5114/aoms.2016.64131. Epub 2016 Dec 5.
32 Application of Inflammatory Markers in Induced Sputum in Stable Chronic Obstructive Pulmonary Disease Patients with Positive Bronchodilation Tests.Curr Med Sci. 2019 Aug;39(4):560-567. doi: 10.1007/s11596-019-2074-7. Epub 2019 Jul 25.
33 Refining the eosinophil cationic protein antibacterial pharmacophore by rational structure minimization.J Med Chem. 2011 Jul 28;54(14):5237-44. doi: 10.1021/jm200701g. Epub 2011 Jul 1.
34 A maternal high-fat, high-sucrose diet alters insulin sensitivity and expression of insulin signalling and lipid metabolism genes and proteins in male rat offspring: effect of folic acid supplementation.Br J Nutr. 2017 Oct;118(8):580-588. doi: 10.1017/S0007114517002501.
35 Fecal Eosinophil Cationic Protein Is a Diagnostic and Predictive Biomarker in Young Adults with Inflammatory Bowel Disease.J Clin Med. 2019 Nov 20;8(12):2025. doi: 10.3390/jcm8122025.
36 Genetic variants of RNASE3 (ECP) and susceptibility to severe malaria in Senegalese population.Malar J. 2018 Feb 5;17(1):61. doi: 10.1186/s12936-018-2205-9.
37 Sequencing of DICER1 in sarcomas identifies biallelic somatic DICER1 mutations in an adult-onset embryonal rhabdomyosarcoma.Br J Cancer. 2017 Jun 6;116(12):1621-1626. doi: 10.1038/bjc.2017.147. Epub 2017 May 18.
38 HDAC inhibitors suppress c-Jun/Fra-1-mediated proliferation through transcriptionally downregulating MKK7 and Raf1 in neuroblastoma cells.Oncotarget. 2016 Feb 9;7(6):6727-47. doi: 10.18632/oncotarget.6797.
39 ERK crosstalks with 4EBP1 to activate cyclin D1 translation during quinol-thioether-induced tuberous sclerosis renal cell carcinoma.Toxicol Sci. 2011 Nov;124(1):75-87. doi: 10.1093/toxsci/kfr203. Epub 2011 Aug 2.
40 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.
41 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.
42 Asthma therapy modulates priming-associated blood eosinophil responsiveness in allergic asthmatics. Eur Respir J. 1999 Oct;14(4):915-22. doi: 10.1034/j.1399-3003.1999.14d31.x.
43 Effects of different anti-asthmatic agents on induced sputum and eosinophil cationic protein in mild asthmatics. Respirology. 2004 Nov;9(4):514-20. doi: 10.1111/j.1440-1843.2004.00631.x.
44 Salmeterol decreases eosinophilic cationic protein and rescue medication in patients inhaling beclomethasone dipropionate: preliminary study in mild and moderate asthma in Trinidad, West Indies. Int J Clin Pharmacol Res. 2003;23(2-3):69-74.
45 Formoterol compared with beclomethasone and placebo on allergen-induced asthmatic responses. Am Rev Respir Dis. 1992 Nov;146(5 Pt 1):1156-60. doi: 10.1164/ajrccm/146.5_Pt_1.1156.
46 Effect of inhaled beclomethasone dipropionate and budesonide dry powder on pulmonary function and serum eosinophil cationic protein in adult asthmatics. J Investig Allergol Clin Immunol. 1999 Jul-Aug;9(4):241-7.
47 Differential response of Mono Mac 6, BEAS-2B, and Jurkat cells to indoor dust. Environ Health Perspect. 2007 Sep;115(9):1325-32.