Details of Drug Off-Target (DOT)

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

• DOT Name: Ribosomal RNA-processing protein 7 homolog A (RRP7A)
• Synonyms: Gastric cancer antigen Zg14
• Gene Name: RRP7A
• Related Disease: Microcephaly 28, primary, autosomal recessive
• UniProt ID: RRP7A_HUMAN
• PDB ID: 7MQ8; 7MQ9; 7MQA
• Pfam ID: PF17799 ; PF12923
• Sequence:
  MVARRRKCAARDPEDRIPSPLGYAAIPIKFSEKQQASHYLYVRAHGVRQGTKSTWPQKRT
  LFVLNVPPYCTEESLSRLLSTCGLVQSVELQEKPDLAESPKESRSKFFHPKPVPGFQVAY
  VVFQKPSGVSAALALKGPLLVSTESHPVKSGIHKWISDYADSVPDPEALRVEVDTFMEAY
  DQKIAEEEAKAKEEEGVPDEEGWVKVTRRGRRPVLPRTEAASLRVLERERRKRSRKELLN
  FYAWQHRESKMEHLAQLRKKFEEDKQRIELLRAQRKFRPY
• Function: Nucleolar protein that is involved in ribosomal RNA (rRNA) processing. Also plays a role in primary cilia resorption, and cell cycle progression in neurogenesis and neocortex development. Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit. During the assembly of the SSU processome in the nucleolus, many ribosome biogenesis factors, an RNA chaperone and ribosomal proteins associate with the nascent pre-rRNA and work in concert to generate RNA folding, modifications, rearrangements and cleavage as well as targeted degradation of pre-ribosomal RNA by the RNA exosome.
• Tissue Specificity: Expressed in the apical radial glial cells in the developing brain.
• KEGG Pathway: Ribosome biogenesis in eukaryotes (hsa03008)
• Reactome Pathway:
  Major pathway of rRNA processing in the nucleolus and cytosol (R-HSA-6791226)
  rRNA modification in the nucleus and cytosol (R-HSA-6790901)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Microcephaly 28, primary, autosomal recessive	DISQT53F	Limited	Autosomal recessive	[1]

13 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Ribosomal RNA-processing protein 7 homolog A (RRP7A).	[2]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Ribosomal RNA-processing protein 7 homolog A (RRP7A).	[3]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Ribosomal RNA-processing protein 7 homolog A (RRP7A).	[4]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Ribosomal RNA-processing protein 7 homolog A (RRP7A).	[5]
Decitabine	DMQL8XJ	Approved	Decitabine increases the expression of Ribosomal RNA-processing protein 7 homolog A (RRP7A).	[6]
Selenium	DM25CGV	Approved	Selenium increases the expression of Ribosomal RNA-processing protein 7 homolog A (RRP7A).	[7]
Demecolcine	DMCZQGK	Approved	Demecolcine decreases the expression of Ribosomal RNA-processing protein 7 homolog A (RRP7A).	[8]
Testosterone enanthate	DMB6871	Approved	Testosterone enanthate affects the expression of Ribosomal RNA-processing protein 7 homolog A (RRP7A).	[9]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Ribosomal RNA-processing protein 7 homolog A (RRP7A).	[7]
GSK2110183	DMZHB37	Phase 2	GSK2110183 decreases the expression of Ribosomal RNA-processing protein 7 homolog A (RRP7A).	[10]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of Ribosomal RNA-processing protein 7 homolog A (RRP7A).	[13]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Ribosomal RNA-processing protein 7 homolog A (RRP7A).	[8]
[3H]methyltrienolone	DMTSGOW	Investigative	[3H]methyltrienolone increases the expression of Ribosomal RNA-processing protein 7 homolog A (RRP7A).	[15]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Ribosomal RNA-processing protein 7 homolog A (RRP7A).	[11]
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of Ribosomal RNA-processing protein 7 homolog A (RRP7A).	[12]
Coumarin	DM0N8ZM	Investigative	Coumarin increases the phosphorylation of Ribosomal RNA-processing protein 7 homolog A (RRP7A).	[14]

References

• [1] RRP7A links primary microcephaly to dysfunction of ribosome biogenesis, resorption of primary cilia, and neurogenesis. Nat Commun. 2020 Nov 16;11(1):5816. doi: 10.1038/s41467-020-19658-0.
• [2] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [3] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [4] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [5] 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.
• [6] Gene induction and apoptosis in human hepatocellular carci-noma cells SMMC-7721 exposed to 5-aza-2'-deoxycytidine. Chin Med J (Engl). 2007 Sep 20;120(18):1626-31.
• [7] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [8] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [9] Transcriptional profiling of testosterone-regulated genes in the skeletal muscle of human immunodeficiency virus-infected men experiencing weight loss. J Clin Endocrinol Metab. 2007 Jul;92(7):2793-802. doi: 10.1210/jc.2006-2722. Epub 2007 Apr 17.
• [10] Novel ATP-competitive Akt inhibitor afuresertib suppresses the proliferation of malignant pleural mesothelioma cells. Cancer Med. 2017 Nov;6(11):2646-2659. doi: 10.1002/cam4.1179. Epub 2017 Sep 27.
• [11] Effect of aflatoxin B(1), benzo[a]pyrene, and methapyrilene on transcriptomic and epigenetic alterations in human liver HepaRG cells. Food Chem Toxicol. 2018 Nov;121:214-223. doi: 10.1016/j.fct.2018.08.034. Epub 2018 Aug 26.
• [12] Inhibiting ubiquitination causes an accumulation of SUMOylated newly synthesized nuclear proteins at PML bodies. J Biol Chem. 2019 Oct 18;294(42):15218-15234. doi: 10.1074/jbc.RA119.009147. Epub 2019 Jul 8.
• [13] A trichostatin A expression signature identified by TempO-Seq targeted whole transcriptome profiling. PLoS One. 2017 May 25;12(5):e0178302. doi: 10.1371/journal.pone.0178302. eCollection 2017.
• [14] 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.
• [15] Analysis of the prostate cancer cell line LNCaP transcriptome using a sequencing-by-synthesis approach. BMC Genomics. 2006 Sep 29;7:246. doi: 10.1186/1471-2164-7-246.