Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT1OS3H3)

DOT Name Serine/threonine-protein kinase RIO1 (RIOK1)
Synonyms EC 2.7.11.1; EC 3.6.3.-; RIO kinase 1
Gene Name RIOK1
Related Disease
Adult glioblastoma ( )
Advanced cancer ( )
Breast cancer ( )
Breast carcinoma ( )
Colon cancer ( )
Colon carcinoma ( )
Glioblastoma multiforme ( )
Lung cancer ( )
Lung carcinoma ( )
Multiple sclerosis ( )
Neoplasm ( )
UniProt ID
RIOK1_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
4OTP; 6G5I; 6V0N; 6ZV6; 6ZXD; 6ZXE; 6ZXF; 6ZXG; 6ZXH; 7BOC
EC Number
2.7.11.1; 3.6.3.-
Pfam ID
PF01163
Sequence
MDYRRLLMSRVVPGQFDDADSSDSENRDLKTVKEKDDILFEDLQDNVNENGEGEIEDEEE
EGYDDDDDDWDWDEGVGKLAKGYVWNGGSNPQANRQTSDSSSAKMSTPADKVLRKFENKI
NLDKLNVTDSVINKVTEKSRQKEADMYRIKDKADRATVEQVLDPRTRMILFKMLTRGIIT
EINGCISTGKEANVYHASTANGESRAIKIYKTSILVFKDRDKYVSGEFRFRHGYCKGNPR
KMVKTWAEKEMRNLIRLNTAEIPCPEPIMLRSHVLVMSFIGKDDMPAPLLKNVQLSESKA
RELYLQVIQYMRRMYQDARLVHADLSEFNMLYHGGGVYIIDVSQSVEHDHPHALEFLRKD
CANVNDFFMRHSVAVMTVRELFEFVTDPSITHENMDAYLSKAMEIASQRTKEERSSQDHV
DEEVFKRAYIPRTLNEVKNYERDMDIIMKLKEEDMAMNAQQDNILYQTVTGLKKDLSGVQ
KVPALLENQVEERTCSDSEDIGSSECSDTDSEEQGDHARPKKHTTDPDIDKKERKKMVKE
AQREKRKNKIPKHVKKRKEKTAKTKKGK
Function
Involved in the final steps of cytoplasmic maturation of the 40S ribosomal subunit. Involved in processing of 18S-E pre-rRNA to the mature 18S rRNA. Required for the recycling of NOB1 and PNO1 from the late 40S precursor. The association with the very late 40S subunit intermediate may involve a translation-like checkpoint point cycle preceeding the binding to the 60S ribosomal subunit. Despite the protein kinase domain is proposed to act predominantly as an ATPase. The catalytic activity regulates its dynamic association with the 40S subunit. In addition to its role in ribosomal biogenesis acts as an adapter protein by recruiting NCL/nucleolin the to PRMT5 complex for its symmetrical methylation.
KEGG Pathway
Ribosome biogenesis in eukaryotes (hsa03008 )
Reactome Pathway
Major pathway of rRNA processing in the nucleolus and cytosol (R-HSA-6791226 )

Molecular Interaction Atlas (MIA) of This DOT

11 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Adult glioblastoma DISVP4LU Strong Altered Expression [1]
Advanced cancer DISAT1Z9 Strong Altered Expression [2]
Breast cancer DIS7DPX1 Strong Altered Expression [3]
Breast carcinoma DIS2UE88 Strong Altered Expression [3]
Colon cancer DISVC52G Strong Altered Expression [4]
Colon carcinoma DISJYKUO Strong Altered Expression [4]
Glioblastoma multiforme DISK8246 Strong Altered Expression [1]
Lung cancer DISCM4YA Strong Biomarker [3]
Lung carcinoma DISTR26C Strong Biomarker [3]
Multiple sclerosis DISB2WZI Strong Biomarker [5]
Neoplasm DISZKGEW Strong Biomarker [6]
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⏷ Show the Full List of 11 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
8 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 Serine/threonine-protein kinase RIO1 (RIOK1). [7]
Ciclosporin DMAZJFX Approved Ciclosporin increases the expression of Serine/threonine-protein kinase RIO1 (RIOK1). [8]
Tretinoin DM49DUI Approved Tretinoin decreases the expression of Serine/threonine-protein kinase RIO1 (RIOK1). [9]
Estradiol DMUNTE3 Approved Estradiol increases the expression of Serine/threonine-protein kinase RIO1 (RIOK1). [10]
Temozolomide DMKECZD Approved Temozolomide increases the expression of Serine/threonine-protein kinase RIO1 (RIOK1). [11]
Marinol DM70IK5 Approved Marinol decreases the expression of Serine/threonine-protein kinase RIO1 (RIOK1). [12]
Formaldehyde DM7Q6M0 Investigative Formaldehyde decreases the expression of Serine/threonine-protein kinase RIO1 (RIOK1). [14]
QUERCITRIN DM1DH96 Investigative QUERCITRIN increases the expression of Serine/threonine-protein kinase RIO1 (RIOK1). [15]
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⏷ Show the Full List of 8 Drug(s)
1 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
PMID28870136-Compound-52 DMFDERP Patented PMID28870136-Compound-52 decreases the phosphorylation of Serine/threonine-protein kinase RIO1 (RIOK1). [13]
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References

1 A kinome-wide RNAi screen in Drosophila Glia reveals that the RIO kinases mediate cell proliferation and survival through TORC2-Akt signaling in glioblastoma.PLoS Genet. 2013;9(2):e1003253. doi: 10.1371/journal.pgen.1003253. Epub 2013 Feb 14.
2 Integrating Rio1 activities discloses its nutrient-activated network in Saccharomyces cerevisiae.Nucleic Acids Res. 2018 Sep 6;46(15):7586-7611. doi: 10.1093/nar/gky618.
3 The Atypical Kinase RIOK1 Promotes Tumor Growth and Invasive Behavior.EBioMedicine. 2017 Jun;20:79-97. doi: 10.1016/j.ebiom.2017.04.015. Epub 2017 Apr 12.
4 Characterisation of tumour-associated antigens in colon cancer.Cancer Immunol Immunother. 2002 Nov;51(10):574-82. doi: 10.1007/s00262-002-0322-2. Epub 2002 Sep 19.
5 Hypothalamic damage in multiple sclerosis correlates with disease activity, disability, depression, and fatigue.Neurol Res. 2017 Apr;39(4):323-330. doi: 10.1080/01616412.2016.1275460. Epub 2017 Feb 13.
6 The Rio1 protein kinases/ATPases: conserved regulators of growth, division, and genomic stability.Curr Genet. 2019 Apr;65(2):457-466. doi: 10.1007/s00294-018-0912-y. Epub 2018 Dec 4.
7 Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
8 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.
9 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.
10 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.
11 Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
12 THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders. Transl Psychiatry. 2018 Apr 25;8(1):89. doi: 10.1038/s41398-018-0137-3.
13 Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
14 Gene expression changes in primary human nasal epithelial cells exposed to formaldehyde in vitro. Toxicol Lett. 2010 Oct 5;198(2):289-95.
15 Molecular mechanisms of quercitrin-induced apoptosis in non-small cell lung cancer. Arch Med Res. 2014 Aug;45(6):445-54.