Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT2YFPI2)

DOT Name Ribosomal oxygenase 2 (RIOX2)
Synonyms
60S ribosomal protein L27a histidine hydroxylase; Bifunctional lysine-specific demethylase and histidyl-hydroxylase MINA; EC 1.14.11.79; Histone lysine demethylase MINA; MYC-induced nuclear antigen; Mineral dust-induced gene protein; Nucleolar protein 52; Ribosomal oxygenase MINA; ROX
Gene Name RIOX2
Related Disease
Advanced cancer ( )
Carcinoma of esophagus ( )
Esophageal cancer ( )
Neoplasm of esophagus ( )
Adenocarcinoma ( )
Adenoma ( )
Adult glioblastoma ( )
Allergic asthma ( )
Breast cancer ( )
Breast carcinoma ( )
Breast neoplasm ( )
Carcinoma ( )
Carcinoma of liver and intrahepatic biliary tract ( )
Clear cell renal carcinoma ( )
Colon cancer ( )
Colon carcinoma ( )
Colonic neoplasm ( )
Colorectal carcinoma ( )
Gastric adenocarcinoma ( )
Gastric cancer ( )
Glioblastoma multiforme ( )
Hepatitis B virus infection ( )
Hepatocellular carcinoma ( )
Liver cancer ( )
Lung cancer ( )
Lung carcinoma ( )
Lung neoplasm ( )
Lung squamous cell carcinoma ( )
Medulloblastoma ( )
Neoplasm ( )
Pancreatic cancer ( )
Papillary renal cell carcinoma ( )
Plasma cell myeloma ( )
Renal cell carcinoma ( )
Squamous cell carcinoma ( )
Factor IX deficiency ( )
Neuroblastoma ( )
Stomach cancer ( )
Asthma ( )
Lymphoma ( )
Nematode infection ( )
Subarachnoid hemorrhage ( )
UniProt ID
RIOX2_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
2XDV; 4BU2; 4BXF
EC Number
1.14.11.79
Pfam ID
PF08007 ; PF20514
Sequence
MPKKAKPTGSGKEEGPAPCKQMKLEAAGGPSALNFDSPSSLFESLISPIKTETFFKEFWE
QKPLLIQRDDPALATYYGSLFKLTDLKSLCSRGMYYGRDVNVCRCVNGKKKVLNKDGKAH
FLQLRKDFDQKRATIQFHQPQRFKDELWRIQEKLECYFGSLVGSNVYITPAGSQGLPPHY
DDVEVFILQLEGEKHWRLYHPTVPLAREYSVEAEERIGRPVHEFMLKPGDLLYFPRGTIH
QADTPAGLAHSTHVTISTYQNNSWGDFLLDTISGLVFDTAKEDVELRTGIPRQLLLQVES
TTVATRRLSGFLRTLADRLEGTKELLSSDMKKDFIMHRLPPYSAGDGAELSTPGGKLPRL
DSVVRLQFKDHIVLTVLPDQDQSDEAQEKMVYIYHSLKNSRETHMMGNEEETEFHGLRFP
LSHLDALKQIWNSPAISVKDLKLTTDEEKESLVLSLWTECLIQVV
Function
Oxygenase that can act as both a histone lysine demethylase and a ribosomal histidine hydroxylase. Is involved in the demethylation of trimethylated 'Lys-9' on histone H3 (H3K9me3), leading to an increase in ribosomal RNA expression. Also catalyzes the hydroxylation of 60S ribosomal protein L27a on 'His-39'. May play an important role in cell growth and survival. May be involved in ribosome biogenesis, most likely during the assembly process of pre-ribosomal particles.
Tissue Specificity
Expressed in liver, skeletal muscle, heart, pancreas, and placenta. Not detected in brain, lung or kidney. Expressed in several lung cancer tissues, but is barely detected in the adjacent non-cancerous tissues. Also highly expressed in several esophageal squamous cell carcinoma (ESCC), and colon cancer tissues, and in various cancer cell lines.
Reactome Pathway
Protein hydroxylation (R-HSA-9629569 )
HDMs demethylate histones (R-HSA-3214842 )
BioCyc Pathway
MetaCyc:ENSG00000170854-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

42 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Advanced cancer DISAT1Z9 Definitive Biomarker [1]
Carcinoma of esophagus DISS6G4D Definitive Altered Expression [2]
Esophageal cancer DISGB2VN Definitive Altered Expression [2]
Neoplasm of esophagus DISOLKAQ Definitive Altered Expression [2]
Adenocarcinoma DIS3IHTY Strong Altered Expression [3]
Adenoma DIS78ZEV Strong Altered Expression [3]
Adult glioblastoma DISVP4LU Strong Biomarker [1]
Allergic asthma DISHF0H3 Strong Genetic Variation [4]
Breast cancer DIS7DPX1 Strong Genetic Variation [5]
Breast carcinoma DIS2UE88 Strong Genetic Variation [5]
Breast neoplasm DISNGJLM Strong Genetic Variation [5]
Carcinoma DISH9F1N Strong Altered Expression [6]
Carcinoma of liver and intrahepatic biliary tract DIS8WA0W Strong Biomarker [7]
Clear cell renal carcinoma DISBXRFJ Strong Altered Expression [8]
Colon cancer DISVC52G Strong Altered Expression [3]
Colon carcinoma DISJYKUO Strong Altered Expression [3]
Colonic neoplasm DISSZ04P Strong Altered Expression [3]
Colorectal carcinoma DIS5PYL0 Strong Biomarker [9]
Gastric adenocarcinoma DISWWLTC Strong Biomarker [6]
Gastric cancer DISXGOUK Strong Altered Expression [6]
Glioblastoma multiforme DISK8246 Strong Biomarker [1]
Hepatitis B virus infection DISLQ2XY Strong Altered Expression [7]
Hepatocellular carcinoma DIS0J828 Strong Biomarker [7]
Liver cancer DISDE4BI Strong Biomarker [7]
Lung cancer DISCM4YA Strong Biomarker [10]
Lung carcinoma DISTR26C Strong Biomarker [10]
Lung neoplasm DISVARNB Strong Biomarker [11]
Lung squamous cell carcinoma DISXPIBD Strong Genetic Variation [10]
Medulloblastoma DISZD2ZL Strong Biomarker [12]
Neoplasm DISZKGEW Strong Altered Expression [9]
Pancreatic cancer DISJC981 Strong Biomarker [13]
Papillary renal cell carcinoma DIS25HBV Strong Altered Expression [8]
Plasma cell myeloma DIS0DFZ0 Strong Altered Expression [14]
Renal cell carcinoma DISQZ2X8 Strong Altered Expression [8]
Squamous cell carcinoma DISQVIFL Strong Biomarker [10]
Factor IX deficiency DISHN9SC moderate Biomarker [15]
Neuroblastoma DISVZBI4 moderate Biomarker [16]
Stomach cancer DISKIJSX moderate Altered Expression [6]
Asthma DISW9QNS Limited Genetic Variation [17]
Lymphoma DISN6V4S Limited Altered Expression [18]
Nematode infection DISVFLRK Limited Biomarker [19]
Subarachnoid hemorrhage DISI7I8Y Limited Biomarker [20]
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⏷ Show the Full List of 42 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
11 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate decreases the expression of Ribosomal oxygenase 2 (RIOX2). [21]
Ciclosporin DMAZJFX Approved Ciclosporin increases the expression of Ribosomal oxygenase 2 (RIOX2). [22]
Acetaminophen DMUIE76 Approved Acetaminophen decreases the expression of Ribosomal oxygenase 2 (RIOX2). [23]
Estradiol DMUNTE3 Approved Estradiol increases the expression of Ribosomal oxygenase 2 (RIOX2). [24]
Hydrogen peroxide DM1NG5W Approved Hydrogen peroxide affects the expression of Ribosomal oxygenase 2 (RIOX2). [25]
Phenobarbital DMXZOCG Approved Phenobarbital affects the expression of Ribosomal oxygenase 2 (RIOX2). [26]
Isotretinoin DM4QTBN Approved Isotretinoin decreases the expression of Ribosomal oxygenase 2 (RIOX2). [27]
Trichostatin A DM9C8NX Investigative Trichostatin A increases the expression of Ribosomal oxygenase 2 (RIOX2). [28]
Formaldehyde DM7Q6M0 Investigative Formaldehyde decreases the expression of Ribosomal oxygenase 2 (RIOX2). [29]
Milchsaure DM462BT Investigative Milchsaure decreases the expression of Ribosomal oxygenase 2 (RIOX2). [30]
Coumestrol DM40TBU Investigative Coumestrol decreases the expression of Ribosomal oxygenase 2 (RIOX2). [31]
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⏷ Show the Full List of 11 Drug(s)

References

1 MINA53 deficiency leads to glioblastoma cell apoptosis via inducing DNA replication stress and diminishing DNA damage response.Cell Death Dis. 2018 Oct 17;9(11):1062. doi: 10.1038/s41419-018-1084-x.
2 Overexpression of the myc target gene Mina53 in advanced renal cell carcinoma.Pathol Int. 2007 Oct;57(10):672-80. doi: 10.1111/j.1440-1827.2007.02156.x.
3 Increased expression of a Myc target gene Mina53 in human colon cancer.Am J Pathol. 2004 Jan;164(1):205-16. doi: 10.1016/S0002-9440(10)63111-2.
4 Mina: a Th2 response regulator meets TGF.Curr Opin Immunol. 2014 Dec;31:38-43. doi: 10.1016/j.coi.2014.09.005. Epub 2014 Oct 1.
5 The human ROX gene: genomic structure and mutation analysis in human breast tumors.Genomics. 1998 Apr 15;49(2):275-82. doi: 10.1006/geno.1998.5241.
6 Mina53, a novel molecular marker for the diagnosis and prognosis of gastric adenocarcinoma.Oncol Rep. 2014 Feb;31(2):634-40. doi: 10.3892/or.2013.2918. Epub 2013 Dec 12.
7 Dysfunction of IKZF1/MYC/MDIG axis contributes to liver cancer progression through regulating H3K9me3/p21 activity.Cell Death Dis. 2017 May 4;8(5):e2766. doi: 10.1038/cddis.2017.165.
8 SETDB2 and RIOX2 are differentially expressed among renal cell tumor subtypes, associating with prognosis and metastization.Epigenetics. 2017;12(12):1057-1064. doi: 10.1080/15592294.2017.1385685. Epub 2018 Jan 22.
9 Mina53 nuclear localization is an important indicator of prognosis in patients with colorectal cancer after adjuvant chemotherapy.Oncol Rep. 2018 Jul;40(1):101-110. doi: 10.3892/or.2018.6407. Epub 2018 Apr 30.
10 Expression of Mina53, a novel c-Myc target gene, is a favorable prognostic marker in early stage lung cancer.Lung Cancer. 2010 Aug;69(2):232-8. doi: 10.1016/j.lungcan.2009.10.010. Epub 2009 Nov 14.
11 The Human mineral dust-induced gene, mdig, is a cell growth regulating gene associated with lung cancer.Oncogene. 2005 Jul 21;24(31):4873-82. doi: 10.1038/sj.onc.1208668.
12 Analysis of transcripts from 17p13.3 in medulloblastoma suggests ROX/MNT as a potential tumour suppressor gene.Eur J Cancer. 2004 Nov;40(16):2525-32. doi: 10.1016/j.ejca.2004.08.005.
13 Potential effects of Mina53 on tumor growth in human pancreatic cancer.Cell Biochem Biophys. 2014 Jul;69(3):619-25. doi: 10.1007/s12013-014-9841-7.
14 Proteomic Characterization of the World Trade Center dust-activated mdig and c-myc signaling circuit linked to multiple myeloma.Sci Rep. 2016 Nov 11;6:36305. doi: 10.1038/srep36305.
15 Qualification of a select one-stage activated partial thromboplastin time-based clotting assay and two chromogenic assays for the post-administration monitoring of nonacog beta pegol.J Thromb Haemost. 2017 Oct;15(10):1901-1912. doi: 10.1111/jth.13787. Epub 2017 Sep 11.
16 Immunohistochemical expressions of Cap43 and Mina53 proteins in neuroblastoma.J Pediatr Surg. 2007 Nov;42(11):1831-40. doi: 10.1016/j.jpedsurg.2007.07.008.
17 Associations of the single-nucleotide polymorphisms of the Mina gene with the development of asthma in Chinese Han children: a case-control study.Genet Test Mol Biomarkers. 2011 Jul-Aug;15(7-8):531-6. doi: 10.1089/gtmb.2010.0240. Epub 2011 Jun 1.
18 Expression of Myc target gene mina53 in subtypes of human lymphoma.Oncol Rep. 2007 Oct;18(4):841-8.
19 Myc-induced nuclear antigen constrains a latent intestinal epithelial cell-intrinsic anthelmintic pathway.PLoS One. 2019 Feb 26;14(2):e0211244. doi: 10.1371/journal.pone.0211244. eCollection 2019.
20 A novel fluorescent imaging technique for assessment of cerebral vasospasm after experimental subarachnoid hemorrhage.Sci Rep. 2017 Aug 22;7(1):9126. doi: 10.1038/s41598-017-09070-y.
21 Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
22 Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
23 Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
24 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
25 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.
26 Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 30.
27 Temporal changes in gene expression in the skin of patients treated with isotretinoin provide insight into its mechanism of action. Dermatoendocrinol. 2009 May;1(3):177-87.
28 From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
29 Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
30 Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
31 Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.