Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTKZ7CO9)

DOT Name Ribonuclease pancreatic (RNASE1)
Synonyms EC 4.6.1.18; HP-RNase; RIB-1; RNase UpI-1; Ribonuclease 1; RNase 1; Ribonuclease A; RNase A
Gene Name RNASE1
Related Disease
Familial hypocalciuric hypercalcemia ( )
Familial hypocalciuric hypercalcemia 1 ( )
Gastric neoplasm ( )
Advanced cancer ( )
Alzheimer disease ( )
Arteriosclerosis ( )
Atherosclerosis ( )
Atrial fibrillation ( )
Cardiovascular disease ( )
Colonic neoplasm ( )
Colorectal carcinoma ( )
Endometrial cancer ( )
Endometrial carcinoma ( )
Esophageal squamous cell carcinoma ( )
Gastric cancer ( )
Gaucher disease ( )
Hepatitis B virus infection ( )
Hepatitis C virus infection ( )
Herpes simplex infection ( )
Influenza ( )
Lesch-Nyhan syndrome ( )
Lung cancer ( )
Lung carcinoma ( )
Myocardial infarction ( )
Neoplasm ( )
Osteogenesis imperfecta ( )
Pancreatic cancer ( )
Rhinitis ( )
Squamous cell carcinoma ( )
Stomach cancer ( )
Urinary tract infection ( )
Noonan syndrome 1 ( )
Ornithine aminotransferase deficiency ( )
Parkinson disease ( )
Dengue ( )
Kaposi sarcoma ( )
Motor neurone disease ( )
Rheumatoid arthritis ( )
Thyroid cancer ( )
Thyroid gland carcinoma ( )
UniProt ID
RNAS1_HUMAN
3D Structure
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2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
PDB ID
1DZA; 1E21; 1H8X; 1Z7X; 2E0J; 2E0L; 2E0M; 2E0O; 2K11; 2Q4G; 3F8G; 4KXH
EC Number
4.6.1.18
Pfam ID
PF00074
Sequence
MALEKSLVRLLLLVLILLVLGWVQPSLGKESRAKKFQRQHMDSDSSPSSSSTYCNQMMRR
RNMTQGRCKPVNTFVHEPLVDVQNVCFQEKVTCKNGQGNCYKSNSSMHITDCRLTNGSRY
PNCAYRTSPKERHIIVACEGSPYVPVHFDASVEDST
Function Endonuclease that catalyzes the cleavage of RNA on the 3' side of pyrimidine nucleotides. Acts on single-stranded and double-stranded RNA.
Tissue Specificity Pancreas and other tissues and body fluids (indicating it may have other physiological functions besides its role in digestion).
Reactome Pathway
Late endosomal microautophagy (R-HSA-9615710 )
Chaperone Mediated Autophagy (R-HSA-9613829 )

Molecular Interaction Atlas (MIA) of This DOT

40 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Familial hypocalciuric hypercalcemia DIS0K7FK Definitive Genetic Variation [1]
Familial hypocalciuric hypercalcemia 1 DISPW6O5 Definitive Genetic Variation [1]
Gastric neoplasm DISOKN4Y Definitive Altered Expression [2]
Advanced cancer DISAT1Z9 Strong Biomarker [3]
Alzheimer disease DISF8S70 Strong Biomarker [4]
Arteriosclerosis DISK5QGC Strong Altered Expression [5]
Atherosclerosis DISMN9J3 Strong Altered Expression [5]
Atrial fibrillation DIS15W6U Strong Biomarker [6]
Cardiovascular disease DIS2IQDX Strong Biomarker [7]
Colonic neoplasm DISSZ04P Strong Biomarker [8]
Colorectal carcinoma DIS5PYL0 Strong Biomarker [9]
Endometrial cancer DISW0LMR Strong Genetic Variation [10]
Endometrial carcinoma DISXR5CY Strong Genetic Variation [10]
Esophageal squamous cell carcinoma DIS5N2GV Strong Biomarker [11]
Gastric cancer DISXGOUK Strong Biomarker [12]
Gaucher disease DISTW5JG Strong Genetic Variation [13]
Hepatitis B virus infection DISLQ2XY Strong Altered Expression [14]
Hepatitis C virus infection DISQ0M8R Strong Biomarker [15]
Herpes simplex infection DISL1SAV Strong Biomarker [16]
Influenza DIS3PNU3 Strong Biomarker [17]
Lesch-Nyhan syndrome DISGXKU7 Strong Biomarker [18]
Lung cancer DISCM4YA Strong Biomarker [19]
Lung carcinoma DISTR26C Strong Biomarker [19]
Myocardial infarction DIS655KI Strong Biomarker [20]
Neoplasm DISZKGEW Strong Biomarker [21]
Osteogenesis imperfecta DIS7XQSD Strong Biomarker [22]
Pancreatic cancer DISJC981 Strong Biomarker [23]
Rhinitis DISKLMN7 Strong Biomarker [24]
Squamous cell carcinoma DISQVIFL Strong Altered Expression [25]
Stomach cancer DISKIJSX Strong Biomarker [12]
Urinary tract infection DISMT6UV Strong Genetic Variation [26]
Noonan syndrome 1 DIS7M92N moderate Biomarker [27]
Ornithine aminotransferase deficiency DISHMWCY moderate Biomarker [28]
Parkinson disease DISQVHKL moderate Genetic Variation [29]
Dengue DISKH221 Limited Biomarker [30]
Kaposi sarcoma DISC1H1Z Limited Biomarker [31]
Motor neurone disease DISUHWUI Limited Genetic Variation [29]
Rheumatoid arthritis DISTSB4J Limited Biomarker [32]
Thyroid cancer DIS3VLDH Limited Altered Expression [33]
Thyroid gland carcinoma DISMNGZ0 Limited Altered Expression [33]
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⏷ Show the Full List of 40 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 Ribonuclease pancreatic (RNASE1). [34]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene decreases the methylation of Ribonuclease pancreatic (RNASE1). [41]
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9 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 Ribonuclease pancreatic (RNASE1). [35]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of Ribonuclease pancreatic (RNASE1). [36]
Calcitriol DM8ZVJ7 Approved Calcitriol decreases the expression of Ribonuclease pancreatic (RNASE1). [37]
Triclosan DMZUR4N Approved Triclosan decreases the expression of Ribonuclease pancreatic (RNASE1). [38]
Carbamazepine DMZOLBI Approved Carbamazepine affects the expression of Ribonuclease pancreatic (RNASE1). [39]
Aspirin DM672AH Approved Aspirin increases the expression of Ribonuclease pancreatic (RNASE1). [40]
Sulindac DM2QHZU Approved Sulindac decreases the expression of Ribonuclease pancreatic (RNASE1). [40]
(+)-JQ1 DM1CZSJ Phase 1 (+)-JQ1 decreases the expression of Ribonuclease pancreatic (RNASE1). [42]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the expression of Ribonuclease pancreatic (RNASE1). [43]
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⏷ Show the Full List of 9 Drug(s)

References

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16 Genetic analysis of herpes simplex virus type 1 isolates from recurrent lesions and clinical reinfections.J Infect Dis. 1995 Dec;172(6):1602-5. doi: 10.1093/infdis/172.6.1602.
17 Screening of influenza mutations using base-specific cleavage and MALDI mass spectrometry.Clin Chim Acta. 2013 May;420:89-93. doi: 10.1016/j.cca.2012.10.013. Epub 2012 Oct 15.
18 Identification and localization of mutations at the Lesch-Nyhan locus by ribonuclease A cleavage.Science. 1987 Apr 17;236(4799):303-5. doi: 10.1126/science.3563511.
19 Evidence that phosphatidylinositol 3-kinase- and mitogen-activated protein kinase kinase-4/c-Jun NH2-terminal kinase-dependent Pathways cooperate to maintain lung cancer cell survival.J Biol Chem. 2003 Jun 27;278(26):23630-8. doi: 10.1074/jbc.M300997200. Epub 2003 Apr 24.
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21 Nanoscale ATP-Responsive Zeolitic Imidazole Framework-90 as a General Platform for Cytosolic Protein Delivery and Genome Editing.J Am Chem Soc. 2019 Mar 6;141(9):3782-3786. doi: 10.1021/jacs.8b11996. Epub 2019 Feb 8.
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23 Increased N-glycosylation of Asn in serum pancreatic ribonuclease 1 is a novel diagnostic marker for pancreatic cancer.Sci Rep. 2014 Oct 22;4:6715. doi: 10.1038/srep06715.
24 Picornavirus RNA is protected from cleavage by ribonuclease during virion uncoating and transfer across cellular and model membranes.PLoS Pathog. 2017 Feb 6;13(2):e1006197. doi: 10.1371/journal.ppat.1006197. eCollection 2017 Feb.
25 Overexpression of Rac-1 small GTPase binding protein in oral squamous cell carcinoma.J Oral Maxillofac Surg. 2004 Jun;62(6):702-7. doi: 10.1016/j.joms.2004.02.002.
26 The Responses of the Ribonuclease A Superfamily to Urinary Tract Infection.Front Immunol. 2019 Nov 29;10:2786. doi: 10.3389/fimmu.2019.02786. eCollection 2019.
27 Proteomic analysis of chicken embryo fibroblast cells infected with recombinant H5N1 avian influenza viruses with and without NS1 eIF4GI binding domain.Oncotarget. 2017 Dec 22;9(9):8350-8367. doi: 10.18632/oncotarget.23615. eCollection 2018 Feb 2.
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32 Influence of Extracellular RNAs, Released by Rheumatoid Arthritis Synovial Fibroblasts, on Their Adhesive and Invasive Properties.J Immunol. 2016 Oct 1;197(7):2589-97. doi: 10.4049/jimmunol.1501580. Epub 2016 Aug 22.
33 Analysis of ribonuclease activity in sub-nanoliter droplets by label-free fluorescence measurements.Analyst. 2017 Jul 10;142(14):2610-2616. doi: 10.1039/c6an02724e.
34 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.
35 Retinoic acid receptor alpha amplifications and retinoic acid sensitivity in breast cancers. Clin Breast Cancer. 2013 Oct;13(5):401-8.
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37 Identification of vitamin D3 target genes in human breast cancer tissue. J Steroid Biochem Mol Biol. 2016 Nov;164:90-97.
38 Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
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40 Expression profile analysis of colon cancer cells in response to sulindac or aspirin. Biochem Biophys Res Commun. 2002 Mar 29;292(2):498-512.
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42 CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.
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