Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT6EX9N6)

• DOT Name: Poly(rC)-binding protein 3 (PCBP3)
• Synonyms: Alpha-CP3; PCBP3-overlapping transcript; PCBP3-overlapping transcript 1
• Gene Name: PCBP3
• Related Disease:
  Pancreatic cancer
  Acute myelogenous leukaemia
• UniProt ID: PCBP3_HUMAN
• Pfam ID: PF00013
• Sequence:
  MGEGDAFWAPSVLPHSTLSTLSHHPQPQFGRRMESKVSEGGLNVTLTIRLLMHGKEVGSI
  IGKKGETVKKMREESGARINISEGNCPERIVTITGPTDAIFKAFAMIAYKFEEDIINSMS
  NSPATSKPPVTLRLVVPASQCGSLIGKGGSKIKEIRESTGAQVQVAGDMLPNSTERAVTI
  SGTPDAIIQCVKQICVVMLESPPKGATIPYRPKPASTPVIFAGGQAYTIQGQYAIPHPDQ
  LTKLHQLAMQQTPFPPLGQTNPAFPGEKLPLHSSEEAQNLMGQSSGLDASPPASTHELTI
  PNDLIGCIIGRQGTKINEIRQMSGAQIKIANATEGSSERQITITGTPANISLAQYLINAR
  LTSEVTGMGTL
• Function: Single-stranded nucleic acid binding protein that binds preferentially to oligo dC.

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Pancreatic cancer	DISJC981	moderate	Biomarker	[1]
Acute myelogenous leukaemia	DISCSPTN	Limited	Genetic Variation	[2]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
N1-(naphthalen-1-yl)ethane-1,2-diamine	DMYGCSV	Investigative	Poly(rC)-binding protein 3 (PCBP3) affects the response to substance of N1-(naphthalen-1-yl)ethane-1,2-diamine.	[12]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Poly(rC)-binding protein 3 (PCBP3).	[3]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Poly(rC)-binding protein 3 (PCBP3).	[6]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Poly(rC)-binding protein 3 (PCBP3).	[8]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Poly(rC)-binding protein 3 (PCBP3).	[10]

5 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 Poly(rC)-binding protein 3 (PCBP3).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Poly(rC)-binding protein 3 (PCBP3).	[5]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of Poly(rC)-binding protein 3 (PCBP3).	[7]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Poly(rC)-binding protein 3 (PCBP3).	[9]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of Poly(rC)-binding protein 3 (PCBP3).	[11]

References

• [1] Proteomic Identification of FLT3 and PCBP3 as Potential Prognostic Biomarkers for Pancreatic Cancer.Anticancer Res. 2018 Oct;38(10):5759-5765. doi: 10.21873/anticanres.12914.
• [2] Genome-wide haplotype association study identify the FGFR2 gene as a risk gene for acute myeloid leukemia.Oncotarget. 2017 Jan 31;8(5):7891-7899. doi: 10.18632/oncotarget.13631.
• [3] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [4] 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.
• [5] 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.
• [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] Unique transcriptome, pathways, and networks in the human endometrial fibroblast response to progesterone in endometriosis. Biol Reprod. 2011 Apr;84(4):801-15.
• [8] 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.
• [9] Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
• [10] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [11] A trichostatin A expression signature identified by TempO-Seq targeted whole transcriptome profiling. PLoS One. 2017 May 25;12(5):e0178302. doi: 10.1371/journal.pone.0178302. eCollection 2017.
• [12] Population-based in vitro hazard and concentration-response assessment of chemicals: the 1000 genomes high-throughput screening study. Environ Health Perspect. 2015 May;123(5):458-66. doi: 10.1289/ehp.1408775. Epub 2015 Jan 13.