Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTX4VZ4R)

• DOT Name: Pre-mRNA-splicing factor 18 (PRPF18)
• Synonyms: PRP18 homolog; hPRP18
• Gene Name: PRPF18
• Related Disease: Influenza
• UniProt ID: PRP18_HUMAN
• PDB ID: 2DK4
• Pfam ID: PF02840 ; PF08799
• Sequence:
  MDILKSEILRKRQLVEDRNLLVENKKYFKRSELAKKEEEAYFERCGYKIQPKEEDQKPLT
  SSNPVLELELAEEKLPMTLSRQEVIRRLRERGEPIRLFGETDYDAFQRLRKIEILTPEVN
  KGLRNDLKAALDKIDQQYLNEIVGGQEPGEEDTQNDLKVHEENTTIEELEALGESLGKGD
  DHKDMDIITKFLKFLLGVWAKELNAREDYVKRSVQGKLNSATQKQTESYLRPLFRKLRKR
  NLPADIKESITDIIKFMLQREYVKANDAYLQMAIGNAPWPIGVTMVGIHARTGREKIFSK
  HVAHVLNDETQRKYIQGLKRLMTICQKHFPTDPSKCVEYNAL
• Function: Participates in the second step of pre-mRNA splicing.
• KEGG Pathway: Spliceosome (hsa03040)
• Reactome Pathway: mRNA Splicing - Major Pathway (R-HSA-72163)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Influenza	DIS3PNU3	Strong	Biomarker	[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 Pre-mRNA-splicing factor 18 (PRPF18).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Pre-mRNA-splicing factor 18 (PRPF18).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Pre-mRNA-splicing factor 18 (PRPF18).	[4]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Pre-mRNA-splicing factor 18 (PRPF18).	[5]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil decreases the expression of Pre-mRNA-splicing factor 18 (PRPF18).	[6]
Piroxicam	DMTK234	Approved	Piroxicam decreases the expression of Pre-mRNA-splicing factor 18 (PRPF18).	[7]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Pre-mRNA-splicing factor 18 (PRPF18).	[8]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of Pre-mRNA-splicing factor 18 (PRPF18).	[9]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Pre-mRNA-splicing factor 18 (PRPF18).	[11]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Pre-mRNA-splicing factor 18 (PRPF18).	[13]

2 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 increases the methylation of Pre-mRNA-splicing factor 18 (PRPF18).	[10]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Pre-mRNA-splicing factor 18 (PRPF18).	[12]

References

• [1] Pre-mRNA Processing Factor Prp18 Is a Stimulatory Factor of Influenza Virus RNA Synthesis and Possesses Nucleoprotein Chaperone Activity.J Virol. 2017 Jan 18;91(3):e01398-16. doi: 10.1128/JVI.01398-16. Print 2017 Feb 1.
• [2] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [3] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [4] Systems analysis of transcriptome and proteome in retinoic acid/arsenic trioxide-induced cell differentiation/apoptosis of promyelocytic leukemia. Proc Natl Acad Sci U S A. 2005 May 24;102(21):7653-8.
• [5] 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.
• [6] 5-Fluorouracil up-regulates interferon pathway gene expression in esophageal cancer cells. Anticancer Res. 2005 Sep-Oct;25(5):3271-8.
• [7] Apoptosis induced by piroxicam plus cisplatin combined treatment is triggered by p21 in mesothelioma. PLoS One. 2011;6(8):e23569.
• [8] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [9] 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.
• [10] 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.
• [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] 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.
• [13] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.