Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTCVZFL9)

• DOT Name: Pre-rRNA-processing protein TSR1 homolog (TSR1)
• Gene Name: TSR1
• UniProt ID: TSR1_HUMAN
• PDB ID: 6G18; 6G4S; 6G4W; 6G51; 6G53; 6ZMT; 6ZN5; 7WTS; 7WTT; 7WTU; 7WTV; 7WTW; 7WTX; 7WTZ; 7WU0
• Pfam ID: PF08142 ; PF04950
• Sequence:
  MAAHRPGPLKQQNKAHKGGRHRGRGSAQRDGKGRLALKTLSKKVRKELSRVDQRHRASQL
  RKQKKEAVLAEKRQLGGKDGPPHQVLVVPLHSRISLPEAMQLLQDRDTGTVHLNELGNTQ
  NFMLLCPRLKHRWFFTSARPGDLHVVLDMAKVADTILFLLDPLEGWDSTGDYCLSCLFAQ
  GLPTYTLAVQGISGLPLKKQIDTRKKLSKAVEKRFPHDKLLLLDTQQEAGMLLRQLANQK
  QQHLAFRDRRAYLFAHAVDFVPSEENNLVGTLKISGYVRGQTLNVNRLLHIVGYGDFQMK
  QIDAPGDPFPLNPRGIKPQKDPDMAMEICATDAVDDMEEGLKVLMKADPGRQESLQAEVI
  PDPMEGEQTWPTEEELSEAKDFLKESSKVVKKVPKGTSSYQAEWILDGGSQSGGEGDEYE
  YDDMEHEDFMEEESQDESSEEEEEYETMTIGESVHDDLYDKKVDEEAEAKMLEKYKQERL
  EEMFPDEVDTPRDVAARIRFQKYRGLKSFRTSPWDPKENLPQDYARIFQFQNFTNTRKSI
  FKEVEEKEVEGAEVGWYVTLHVSEVPVSVVECFRQGTPLIAFSLLPHEQKMSVLNMVVRR
  DPGNTEPVKAKEELIFHCGFRRFRASPLFSQHTAADKHKLQRFLTADMALVATVYAPITF
  PPASVLLFKQKSNGMHSLIATGHLMSVDPDRMVIKRVVLSGHPFKIFTKMAVVRYMFFNR
  EDVLWFKPVELRTKWGRRGHIKEPLGTHGHMKCSFDGKLKSQDTVLMNLYKRVFPKWTYD
  PYVPEPVPWLKSEISSTVPQGGME
• Function: Required during maturation of the 40S ribosomal subunit in the nucleolus.
• Reactome Pathway: Major pathway of rRNA processing in the nucleolus and cytosol (R-HSA-6791226)

Molecular Interaction Atlas (MIA) of This DOT

13 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 Pre-rRNA-processing protein TSR1 homolog (TSR1).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Pre-rRNA-processing protein TSR1 homolog (TSR1).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Pre-rRNA-processing protein TSR1 homolog (TSR1).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Pre-rRNA-processing protein TSR1 homolog (TSR1).	[4]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Pre-rRNA-processing protein TSR1 homolog (TSR1).	[5]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Pre-rRNA-processing protein TSR1 homolog (TSR1).	[6]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil decreases the expression of Pre-rRNA-processing protein TSR1 homolog (TSR1).	[8]
Dexamethasone	DMMWZET	Approved	Dexamethasone decreases the expression of Pre-rRNA-processing protein TSR1 homolog (TSR1).	[9]
Sodium phenylbutyrate	DMXLBCQ	Approved	Sodium phenylbutyrate decreases the expression of Pre-rRNA-processing protein TSR1 homolog (TSR1).	[10]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Pre-rRNA-processing protein TSR1 homolog (TSR1).	[11]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Pre-rRNA-processing protein TSR1 homolog (TSR1).	[14]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Pre-rRNA-processing protein TSR1 homolog (TSR1).	[15]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Pre-rRNA-processing protein TSR1 homolog (TSR1).	[16]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Pre-rRNA-processing protein TSR1 homolog (TSR1).	[7]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Pre-rRNA-processing protein TSR1 homolog (TSR1).	[12]
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of Pre-rRNA-processing protein TSR1 homolog (TSR1).	[13]

References

• [1] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [2] 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.
• [3] Retinoic acid-induced downmodulation of telomerase activity in human cancer cells. Exp Mol Pathol. 2005 Oct;79(2):108-17.
• [4] 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.
• [5] 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.
• [6] 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.
• [7] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [8] Pharmacogenomic identification of novel determinants of response to chemotherapy in colon cancer. Cancer Res. 2006 Mar 1;66(5):2765-77.
• [9] Gene expression profile of human lymphoid CEM cells sensitive and resistant to glucocorticoid-evoked apoptosis. Genomics. 2003 Jun;81(6):543-55.
• [10] Gene expression profile analysis of 4-phenylbutyrate treatment of IB3-1 bronchial epithelial cell line demonstrates a major influence on heat-shock proteins. Physiol Genomics. 2004 Jan 15;16(2):204-11.
• [11] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [12] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [13] 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.
• [14] 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.
• [15] Epigenetic influences of low-dose bisphenol A in primary human breast epithelial cells. Toxicol Appl Pharmacol. 2010 Oct 15;248(2):111-21.
• [16] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.