Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTG6BNPG)

• DOT Name: Periodic tryptophan protein 2 homolog (PWP2)
• Gene Name: PWP2
• Related Disease:
  Progressive myoclonus epilepsy
  Unverricht-Lundborg syndrome
• UniProt ID: PWP2_HUMAN
• PDB ID: 7MQ8; 7MQ9; 7MQA
• Pfam ID: PF04003 ; PF00400
• Sequence:
  MKFAYRFSNLLGTVYRRGNLNFTCDGNSVISPVGNRVTVFDLKNNKSDTLPLATRYNVKC
  VGLSPDGRLAIIVDEGGDALLVSLVCRSVLHHFHFKGSVHSVSFSPDGRKFVVTKGNIAQ
  MYHAPGKKREFNAFVLDKTYFGPYDETTCIDWTDDSRCFVVGSKDMSTWVFGAERWDNLI
  YYALGGHKDAIVACFFESNSLDLYSLSQDGVLCMWQCDTPPEGLRLKPPAGWKADLLQRE
  EEEEEEEDQEGDRETTIRGKATPAEEEKTGKVKYSRLAKYFFNKEGDFNNLTAAAFHKKS
  HLLVTGFASGIFHLHELPEFNLIHSLSISDQSIASVAINSSGDWIAFGCSGLGQLLVWEW
  QSESYVLKQQGHFNSMVALAYSPDGQYIVTGGDDGKVKVWNTLSGFCFVTFTEHSSGVTG
  VTFTATGYVVVTSSMDGTVRAFDLHRYRNFRTFTSPRPTQFSCVAVDASGEIVSAGAQDS
  FEIFVWSMQTGRLLDVLSGHEGPISGLCFNPMKSVLASASWDKTVRLWDMFDSWRTKETL
  ALTSDALAVTFRPDGAELAVATLNSQITFWDPENAVQTGSIEGRHDLKTGRKELDKITAK
  HAAKGKAFTALCYSADGHSILAGGMSKFVCIYHVREQILMKRFEISCNLSLDAMEEFLNR
  RKMTEFGNLALIDQDAGQEDGVAIPLPGVRKGDMSSRHFKPEIRVTSLRFSPTGRCWAAT
  TTEGLLIYSLDTRVLFDPFELDTSVTPGRVREALRQQDFTRAILMALRLNESKLVQEALE
  AVPRGEIEVVTSSLPELYVEKVLEFLASSFEVSRHLEFYLLWTHKLLMLHGQKLKSRAGT
  LLPVIQFLQKSIQRHLDDLSKLCSWNHYNMQYALAVSKQRGTKRSLDPLGSEEEAEASED
  DSLHLLGGGGRDSEEEMLA
• Function: 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.
• 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

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Progressive myoclonus epilepsy	DISAMCNS	Strong	Biomarker	[1]
Unverricht-Lundborg syndrome	DISG4WLX	Strong	Biomarker	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Periodic tryptophan protein 2 homolog (PWP2).	[2]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Periodic tryptophan protein 2 homolog (PWP2).	[3]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Periodic tryptophan protein 2 homolog (PWP2).	[4]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Periodic tryptophan protein 2 homolog (PWP2).	[5]
Clozapine	DMFC71L	Approved	Clozapine increases the expression of Periodic tryptophan protein 2 homolog (PWP2).	[6]
Benzatropine	DMF7EXL	Approved	Benzatropine increases the expression of Periodic tryptophan protein 2 homolog (PWP2).	[6]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Periodic tryptophan protein 2 homolog (PWP2).	[4]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Periodic tryptophan protein 2 homolog (PWP2).	[7]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Periodic tryptophan protein 2 homolog (PWP2).	[8]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Periodic tryptophan protein 2 homolog (PWP2).	[10]

2 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 Periodic tryptophan protein 2 homolog (PWP2).	[9]
Coumarin	DM0N8ZM	Investigative	Coumarin affects the phosphorylation of Periodic tryptophan protein 2 homolog (PWP2).	[9]

References

• [1] A periodic tryptophan protein 2 gene homologue (PWP2H) in the candidate region of progressive myoclonus epilepsy on 21q22.3.Cytogenet Cell Genet. 1996;74(1-2):140-5. doi: 10.1159/000134402.
• [2] 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.
• [3] 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.
• [4] Changes in gene expressions elicited by physiological concentrations of genistein on human endometrial cancer cells. Mol Carcinog. 2006 Oct;45(10):752-63.
• [5] Integrated assessment by multiple gene expression analysis of quercetin bioactivity on anticancer-related mechanisms in colon cancer cells in vitro. Eur J Nutr. 2005 Mar;44(3):143-56. doi: 10.1007/s00394-004-0503-1. Epub 2004 Apr 30.
• [6] Cannabidiol Displays Proteomic Similarities to Antipsychotics in Cuprizone-Exposed Human Oligodendrocytic Cell Line MO3.13. Front Mol Neurosci. 2021 May 28;14:673144. doi: 10.3389/fnmol.2021.673144. eCollection 2021.
• [7] New insights into BaP-induced toxicity: role of major metabolites in transcriptomics and contribution to hepatocarcinogenesis. Arch Toxicol. 2016 Jun;90(6):1449-58.
• [8] 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.
• [9] 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.
• [10] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.