Details of Drug Off-Target (DOT)

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

• DOT Name: Polyadenylate-binding protein-interacting protein 2 (PAIP2)
• Synonyms: PABP-interacting protein 2; PAIP-2; Poly(A)-binding protein-interacting protein 2
• Gene Name: PAIP2
• Related Disease:
  Colorectal carcinoma
  Colorectal neoplasm
  Carcinoma
  Head and neck cancer
  Head and neck carcinoma
  Neoplasm
• UniProt ID: PAIP2_HUMAN
• PDB ID: 1JGN; 3KUS; 3KUT
• Pfam ID: PF07145
• Sequence:
  MKDPSRSSTSPSIINEDVIINGHSHEDDNPFAEYMWMENEEEFNRQIEEELWEEEFIERC
  FQEMLEEEEEHEWFIPARDLPQTMDQIQDQFNDLVISDGSSLEDLVVKSNLNPNAKEFVP
  GVKYGNI
• Function: Acts as a repressor in the regulation of translation initiation of poly(A)-containing mRNAs. Its inhibitory activity on translation is mediated via its action on PABPC1. Displaces the interaction of PABPC1 with poly(A) RNA and competes with PAIP1 for binding to PABPC1. Its association with PABPC1 results in disruption of the cytoplasmic poly(A) RNP structure organization.
• Tissue Specificity: Expressed at highest level in testis, but also abundant in brain, cervix, lung, ovary, placenta, adipose tissue, thymus and thyroid.

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Colorectal carcinoma	DIS5PYL0	Definitive	Biomarker	[1]
Colorectal neoplasm	DISR1UCN	Definitive	Biomarker	[1]
Carcinoma	DISH9F1N	Strong	Altered Expression	[2]
Head and neck cancer	DISBPSQZ	Strong	Altered Expression	[2]
Head and neck carcinoma	DISOU1DS	Strong	Altered Expression	[2]
Neoplasm	DISZKGEW	Strong	Altered Expression	[2]

4 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 2 (PAIP2).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Polyadenylate-binding protein-interacting protein 2 (PAIP2).	[4]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Polyadenylate-binding protein-interacting protein 2 (PAIP2).	[5]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Polyadenylate-binding protein-interacting protein 2 (PAIP2).	[8]

2 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 Polyadenylate-binding protein-interacting protein 2 (PAIP2).	[6]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Polyadenylate-binding protein-interacting protein 2 (PAIP2).	[7]

References

• [1] Highly Expressed Genes in Rapidly Proliferating Tumor Cells as New Targets for Colorectal Cancer Treatment.Clin Cancer Res. 2015 Aug 15;21(16):3695-704. doi: 10.1158/1078-0432.CCR-14-2457. Epub 2015 May 5.
• [2] Vascular endothelial growth factor-A and Poly(A) binding protein-interacting protein 2 expression in human head and neck carcinomas: correlation and prognostic significance.Br J Cancer. 2006 May 22;94(10):1516-23. doi: 10.1038/sj.bjc.6603108.
• [3] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [4] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [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] 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.
• [7] 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.
• [8] Low-dose Bisphenol A exposure alters the functionality and cellular environment in a human cardiomyocyte model. Environ Pollut. 2023 Oct 15;335:122359. doi: 10.1016/j.envpol.2023.122359. Epub 2023 Aug 9.