Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTL2F5T5)

• DOT Name: Polyadenylate-binding protein-interacting protein 1 (PAIP1)
• Synonyms: PABP-interacting protein 1; PAIP-1; Poly(A)-binding protein-interacting protein 1
• Gene Name: PAIP1
• Related Disease:
  Gastric cancer
  Stomach cancer
  Breast cancer
  Lung adenocarcinoma
• UniProt ID: PAIP1_HUMAN
• PDB ID: 1JH4; 3NTW; 3RK6; 6YXJ
• Pfam ID: PF02854 ; PF07145
• Sequence:
  MSDGFDRAPGAGRGRSRGLGRGGGGPEGGGFPNGAGPAERARHQPPQPKAPGFLQPPPLR
  QPRTTPPPGAQCEVPASPQRPSRPGALPEQTRPLRAPPSSQDKIPQQNSESAMAKPQVVV
  APVLMSKLSVNAPEFYPSGYSSSYTESYEDGCEDYPTLSEYVQDFLNHLTEQPGSFETEI
  EQFAETLNGCVTTDDALQELVELIYQQATSIPNFSYMGARLCNYLSHHLTISPQSGNFRQ
  LLLQRCRTEYEVKDQAAKGDEVTRKRFHAFVLFLGELYLNLEIKGTNGQVTRADILQVGL
  RELLNALFSNPMDDNLICAVKLLKLTGSVLEDAWKEKGKMDMEEIIQRIENVVLDANCSR
  DVKQMLLKLVELRSSNWGRVHATSTYREATPENDPNYFMNEPTFYTSDGVPFTAADPDYQ
  EKYQELLEREDFFPDYEENGTDLSGAGDPYLDDIDDEMDPEIEEAYEKFCLESERKRKQ
• Function: Acts as a coactivator in the regulation of translation initiation of poly(A)-containing mRNAs. Its stimulatory activity on translation is mediated via its action on PABPC1. Competes with PAIP2 for binding to PABPC1. Its association with EIF4A and PABPC1 may potentiate contacts between mRNA termini. May also be involved in translationally coupled mRNA turnover. Implicated with other RNA-binding proteins in the cytoplasmic deadenylation/translational and decay interplay of the FOS mRNA mediated by the major coding-region determinant of instability (mCRD) domain; (Microbial infection) Upon interaction with SARS coronavirus SARS-CoV NSP3 protein, plays an important role in viral protein synthesis.
• Reactome Pathway:
  M-decay (R-HSA-9820841)
  Z-decay (R-HSA-9820865)
  Deadenylation of mRNA (R-HSA-429947)

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Gastric cancer	DISXGOUK	Definitive	Biomarker	[1]
Stomach cancer	DISKIJSX	Definitive	Biomarker	[1]
Breast cancer	DIS7DPX1	Strong	Altered Expression	[2]
Lung adenocarcinoma	DISD51WR	Strong	Altered Expression	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Polyadenylate-binding protein-interacting protein 1 (PAIP1).	[4]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Polyadenylate-binding protein-interacting protein 1 (PAIP1).	[5]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Polyadenylate-binding protein-interacting protein 1 (PAIP1).	[6]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Polyadenylate-binding protein-interacting protein 1 (PAIP1).	[7]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Polyadenylate-binding protein-interacting protein 1 (PAIP1).	[8]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Polyadenylate-binding protein-interacting protein 1 (PAIP1).	[9]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Polyadenylate-binding protein-interacting protein 1 (PAIP1).	[10]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide decreases the expression of Polyadenylate-binding protein-interacting protein 1 (PAIP1).	[11]
Demecolcine	DMCZQGK	Approved	Demecolcine decreases the expression of Polyadenylate-binding protein-interacting protein 1 (PAIP1).	[12]
Amphotericin B	DMTAJQE	Approved	Amphotericin B decreases the expression of Polyadenylate-binding protein-interacting protein 1 (PAIP1).	[9]
Cyclophosphamide	DM4O2Z7	Approved	Cyclophosphamide decreases the expression of Polyadenylate-binding protein-interacting protein 1 (PAIP1).	[9]
Gentamicin	DMKINJO	Approved	Gentamicin decreases the expression of Polyadenylate-binding protein-interacting protein 1 (PAIP1).	[9]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Polyadenylate-binding protein-interacting protein 1 (PAIP1).	[15]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Polyadenylate-binding protein-interacting protein 1 (PAIP1).	[16]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of Polyadenylate-binding protein-interacting protein 1 (PAIP1).	[17]
Deguelin	DMXT7WG	Investigative	Deguelin decreases the expression of Polyadenylate-binding protein-interacting protein 1 (PAIP1).	[18]
4-hydroxy-2-nonenal	DM2LJFZ	Investigative	4-hydroxy-2-nonenal decreases the expression of Polyadenylate-binding protein-interacting protein 1 (PAIP1).	[11]

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 decreases the methylation of Polyadenylate-binding protein-interacting protein 1 (PAIP1).	[13]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Polyadenylate-binding protein-interacting protein 1 (PAIP1).	[14]

References

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• [2] Paip1 affects breast cancer cell growth and represents a novel prognostic biomarker.Hum Pathol. 2018 Mar;73:33-40. doi: 10.1016/j.humpath.2017.10.037. Epub 2017 Dec 16.
• [3] Paip1 predicts poor prognosis and promotes tumor progression through AKT/GSK-3 pathway in lung adenocarcinoma.Hum Pathol. 2019 Apr;86:233-242. doi: 10.1016/j.humpath.2018.11.017. Epub 2018 Nov 26.
• [4] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [5] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [6] 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.
• [7] 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.
• [8] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [9] Effect of nephrotoxicants and hepatotoxicants on gene expression profile in human peripheral blood mononuclear cells. Biochem Biophys Res Commun. 2010 Oct 15;401(2):245-50. doi: 10.1016/j.bbrc.2010.09.039. Epub 2010 Sep 16.
• [10] 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.
• [11] Microarray analysis of H2O2-, HNE-, or tBH-treated ARPE-19 cells. Free Radic Biol Med. 2002 Nov 15;33(10):1419-32.
• [12] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [13] 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.
• [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] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [16] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [17] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [18] Neurotoxicity and underlying cellular changes of 21 mitochondrial respiratory chain inhibitors. Arch Toxicol. 2021 Feb;95(2):591-615. doi: 10.1007/s00204-020-02970-5. Epub 2021 Jan 29.