Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTCCIJ8I)

• DOT Name: Polynucleotide 5'-hydroxyl-kinase NOL9 (NOL9)
• Synonyms: EC 2.7.1.78; Nucleolar protein 9
• Gene Name: NOL9
• Related Disease:
  Breast cancer
  Breast carcinoma
  Neoplasm
  Breast neoplasm
• UniProt ID: NOL9_HUMAN
• EC Number: 2.7.1.78
• Pfam ID: PF16575
• Sequence:
  MADSGLLLKRGSCRSTWLRVRKARPQLILSRRPRRRLGSLRWCGRRRLRWRLLQAQASGV
  DWREGARQVSRAAAARRPNTATPSPIPSPTPASEPESEPELESASSCHRPLLIPPVRPVG
  PGRALLLLPVEQGFTFSGICRVTCLYGQVQVFGFTISQGQPAQDIFSVYTHSCLSIHALH
  YSQPEKSKKELKREARNLLKSHLNLDDRRWSMQNFSPQCSIVLLEHLKTATVNFITSYPG
  SSYIFVQESPTPQIKPEYLALRSVGIRREKKRKGLQLTESTLSALEELVNVSCEEVDGCP
  VILVCGSQDVGKSTFNRYLINHLLNSLPCVDYLECDLGQTEFTPPGCISLLNITEPVLGP
  PFTHLRTPQKMVYYGKPSCKNNYENYIDIVKYVFSAYKRESPLIVNTMGWVSDQGLLLLI
  DLIRLLSPSHVVQFRSDHSKYMPDLTPQYVDDMDGLYTKSKTKMRNRRFRLAAFADALEF
  ADEEKESPVEFTGHKLIGVYTDFAFRITPRNRESHNKILRDLSILSYLSQLQPPMPKPLS
  PLHSLTPYQVPFNAVALRITHSDVAPTHILYAVNASWVGLCKIQDDVRGYTNGPILLAQT
  PICDCLGFGICRGIDMEKRLYHILTPVPPEELRTVNCLLVGAIAIPHCVLKCQRGIEGTV
  PYVTTDYNFKLPGASEKIGAREPEEAHKEKPYRRPKFCRKMK
• Function: Polynucleotide kinase that can phosphorylate the 5'-hydroxyl groups of single-stranded and double-stranded RNA and DNA substrates. Involved in rRNA processing and its kinase activity is required for the processing of the 32S precursor into 5.8S and 28S rRNAs, more specifically for the generation of the major 5.8S(S) form. Required for the efficient pre-rRNA processing of internal transcribed spacer 2 (ITS2). Associates with LAS1L to form an ITS2 pre-rRNA endonuclease-kinase complex and is responsible for the transport of this complex into the nucleolus.
• Reactome Pathway: Major pathway of rRNA processing in the nucleolus and cytosol (R-HSA-6791226)

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Breast cancer	DIS7DPX1	Strong	Biomarker	[1]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[1]
Neoplasm	DISZKGEW	Strong	Altered Expression	[1]
Breast neoplasm	DISNGJLM	Limited	Altered Expression	[1]

10 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 Polynucleotide 5'-hydroxyl-kinase NOL9 (NOL9).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Polynucleotide 5'-hydroxyl-kinase NOL9 (NOL9).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Polynucleotide 5'-hydroxyl-kinase NOL9 (NOL9).	[5]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Polynucleotide 5'-hydroxyl-kinase NOL9 (NOL9).	[6]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Polynucleotide 5'-hydroxyl-kinase NOL9 (NOL9).	[7]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Polynucleotide 5'-hydroxyl-kinase NOL9 (NOL9).	[8]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Polynucleotide 5'-hydroxyl-kinase NOL9 (NOL9).	[9]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol increases the expression of Polynucleotide 5'-hydroxyl-kinase NOL9 (NOL9).	[10]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Polynucleotide 5'-hydroxyl-kinase NOL9 (NOL9).	[11]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Polynucleotide 5'-hydroxyl-kinase NOL9 (NOL9).	[12]

1 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the methylation of Polynucleotide 5'-hydroxyl-kinase NOL9 (NOL9).	[3]

References

• [1] Expression of tetraspanins NET-6 and CD151 in breast cancer as a potential tumor biomarker.Clin Exp Med. 2019 Aug;19(3):377-384. doi: 10.1007/s10238-019-00554-x. Epub 2019 Apr 20.
• [2] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [3] 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.
• [4] 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.
• [5] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [6] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [7] Genistein and bisphenol A exposure cause estrogen receptor 1 to bind thousands of sites in a cell type-specific manner. Genome Res. 2012 Nov;22(11):2153-62.
• [8] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [9] 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.
• [10] Identification of biomarkers and outcomes of endocrine disruption in human ovarian cortex using In Vitro Models. Toxicology. 2023 Feb;485:153425. doi: 10.1016/j.tox.2023.153425. Epub 2023 Jan 5.
• [11] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [12] Gene expression profiling analysis of bisphenol A-induced perturbation in biological processes in ER-negative HEK293 cells. PLoS One. 2014 Jun 5;9(6):e98635.