Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTHN0TD7)

DOT Name Poly(rC)-binding protein 1 (PCBP1)
Synonyms Alpha-CP1; Heterogeneous nuclear ribonucleoprotein E1; hnRNP E1; Nucleic acid-binding protein SUB2.3
Gene Name PCBP1
Related Disease
Rheumatoid arthritis ( )
Breast cancer ( )
Breast carcinoma ( )
Breast neoplasm ( )
Burkitt lymphoma ( )
Cardiomyopathy ( )
Cardiovascular disease ( )
Colorectal carcinoma ( )
Hepatocellular carcinoma ( )
Huntington disease ( )
Metastatic malignant neoplasm ( )
Multiple sclerosis ( )
Myopathy ( )
Neoplasm ( )
Nervous system inflammation ( )
Pancreatic cancer ( )
Prostate neoplasm ( )
Carcinoma ( )
Gastric cancer ( )
Prostate cancer ( )
Prostate carcinoma ( )
Stomach cancer ( )
Advanced cancer ( )
Amyotrophic lateral sclerosis ( )
Cutaneous squamous cell carcinoma ( )
Gallbladder cancer ( )
Gallbladder carcinoma ( )
Hereditary spastic paraplegia ( )
IRIDA syndrome ( )
Lung cancer ( )
Lung carcinoma ( )
Squamous cell carcinoma ( )
Thyroid cancer ( )
Thyroid gland carcinoma ( )
Thyroid tumor ( )
UniProt ID
PCBP1_HUMAN
3D Structure
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2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
PDB ID
1WVN; 1ZTG; 3VKE
Pfam ID
PF00013
Sequence
MDAGVTESGLNVTLTIRLLMHGKEVGSIIGKKGESVKRIREESGARINISEGNCPERIIT
LTGPTNAIFKAFAMIIDKLEEDINSSMTNSTAASRPPVTLRLVVPATQCGSLIGKGGCKI
KEIRESTGAQVQVAGDMLPNSTERAITIAGVPQSVTECVKQICLVMLETLSQSPQGRVMT
IPYQPMPASSPVICAGGQDRCSDAAGYPHATHDLEGPPLDAYSIQGQHTISPLDLAKLNQ
VARQQSHFAMMHGGTGFAGIDSSSPEVKGYWASLDASTQTTHELTIPNNLIGCIIGRQGA
NINEIRQMSGAQIKIANPVEGSSGRQVTITGSAASISLAQYLINARLSSEKGMGCS
Function
Single-stranded nucleic acid binding protein that binds preferentially to oligo dC. Together with PCBP2, required for erythropoiesis, possibly by regulating mRNA splicing; (Microbial infection) In case of infection by poliovirus, plays a role in initiation of viral RNA replication in concert with the viral protein 3CD.
Tissue Specificity
Abundantly expressed in skeletal muscle, thymus and peripheral blood leukocytes while a lower expression is observed in prostate, spleen, testis, ovary, small intestine, heart, liver, adrenal and thyroid glands.
KEGG Pathway
Spliceosome (hsa03040 )
Ferroptosis (hsa04216 )
Cytosolic D.-sensing pathway (hsa04623 )
Reactome Pathway
Processing of Capped Intron-Containing Pre-mRNA (R-HSA-72203 )
mRNA Splicing - Major Pathway (R-HSA-72163 )

Molecular Interaction Atlas (MIA) of This DOT

35 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Rheumatoid arthritis DISTSB4J Definitive Biomarker [1]
Breast cancer DIS7DPX1 Strong Altered Expression [2]
Breast carcinoma DIS2UE88 Strong Altered Expression [2]
Breast neoplasm DISNGJLM Strong Altered Expression [3]
Burkitt lymphoma DIS9D5XU Strong Genetic Variation [4]
Cardiomyopathy DISUPZRG Strong Altered Expression [5]
Cardiovascular disease DIS2IQDX Strong Altered Expression [5]
Colorectal carcinoma DIS5PYL0 Strong Biomarker [6]
Hepatocellular carcinoma DIS0J828 Strong Biomarker [7]
Huntington disease DISQPLA4 Strong Biomarker [8]
Metastatic malignant neoplasm DIS86UK6 Strong Biomarker [9]
Multiple sclerosis DISB2WZI Strong Biomarker [10]
Myopathy DISOWG27 Strong Biomarker [11]
Neoplasm DISZKGEW Strong Biomarker [12]
Nervous system inflammation DISB3X5A Strong Biomarker [10]
Pancreatic cancer DISJC981 Strong Biomarker [13]
Prostate neoplasm DISHDKGQ Strong Biomarker [14]
Carcinoma DISH9F1N moderate Biomarker [15]
Gastric cancer DISXGOUK moderate Biomarker [16]
Prostate cancer DISF190Y moderate Biomarker [14]
Prostate carcinoma DISMJPLE moderate Biomarker [14]
Stomach cancer DISKIJSX moderate Biomarker [16]
Advanced cancer DISAT1Z9 Limited Altered Expression [17]
Amyotrophic lateral sclerosis DISF7HVM Limited Biomarker [18]
Cutaneous squamous cell carcinoma DIS3LXUG Limited Biomarker [19]
Gallbladder cancer DISXJUAF Limited Biomarker [20]
Gallbladder carcinoma DISD6ACL Limited Biomarker [20]
Hereditary spastic paraplegia DISGZQV1 Limited Genetic Variation [21]
IRIDA syndrome DISPN8YW Limited Biomarker [22]
Lung cancer DISCM4YA Limited Biomarker [23]
Lung carcinoma DISTR26C Limited Biomarker [23]
Squamous cell carcinoma DISQVIFL Limited Biomarker [24]
Thyroid cancer DIS3VLDH Limited Altered Expression [25]
Thyroid gland carcinoma DISMNGZ0 Limited Altered Expression [25]
Thyroid tumor DISLVKMD Limited Altered Expression [25]
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⏷ Show the Full List of 35 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
15 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 Poly(rC)-binding protein 1 (PCBP1). [26]
Ciclosporin DMAZJFX Approved Ciclosporin increases the expression of Poly(rC)-binding protein 1 (PCBP1). [27]
Ivermectin DMDBX5F Approved Ivermectin decreases the expression of Poly(rC)-binding protein 1 (PCBP1). [28]
Vorinostat DMWMPD4 Approved Vorinostat decreases the expression of Poly(rC)-binding protein 1 (PCBP1). [26]
Methotrexate DM2TEOL Approved Methotrexate decreases the expression of Poly(rC)-binding protein 1 (PCBP1). [29]
Selenium DM25CGV Approved Selenium increases the expression of Poly(rC)-binding protein 1 (PCBP1). [30]
Menadione DMSJDTY Approved Menadione affects the expression of Poly(rC)-binding protein 1 (PCBP1). [31]
Cannabidiol DM0659E Approved Cannabidiol increases the expression of Poly(rC)-binding protein 1 (PCBP1). [32]
Aspirin DM672AH Approved Aspirin decreases the expression of Poly(rC)-binding protein 1 (PCBP1). [33]
Clozapine DMFC71L Approved Clozapine increases the expression of Poly(rC)-binding protein 1 (PCBP1). [32]
Bisphenol A DM2ZLD7 Investigative Bisphenol A affects the expression of Poly(rC)-binding protein 1 (PCBP1). [36]
Trichostatin A DM9C8NX Investigative Trichostatin A affects the expression of Poly(rC)-binding protein 1 (PCBP1). [37]
chloropicrin DMSGBQA Investigative chloropicrin affects the expression of Poly(rC)-binding protein 1 (PCBP1). [38]
AHPN DM8G6O4 Investigative AHPN decreases the expression of Poly(rC)-binding protein 1 (PCBP1). [39]
Okadaic acid DM47CO1 Investigative Okadaic acid decreases the expression of Poly(rC)-binding protein 1 (PCBP1). [40]
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⏷ Show the Full List of 15 Drug(s)
3 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 Poly(rC)-binding protein 1 (PCBP1). [34]
PMID28870136-Compound-52 DMFDERP Patented PMID28870136-Compound-52 decreases the phosphorylation of Poly(rC)-binding protein 1 (PCBP1). [35]
Coumarin DM0N8ZM Investigative Coumarin affects the phosphorylation of Poly(rC)-binding protein 1 (PCBP1). [35]
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References

1 Integrative analysis for identification of shared markers from various functional cells/tissues for rheumatoid arthritis.Immunogenetics. 2017 Feb;69(2):77-86. doi: 10.1007/s00251-016-0956-4. Epub 2016 Nov 3.
2 PCBP1/HNRNP E1 Protects Chromosomal Integrity by Translational Regulation of CDC27.Mol Cancer Res. 2016 Jul;14(7):634-46. doi: 10.1158/1541-7786.MCR-16-0018. Epub 2016 Apr 21.
3 The 3'-untranslated region of p21WAF1 mRNA is a composite cis-acting sequence bound by RNA-binding proteins from breast cancer cells, including HuR and poly(C)-binding protein.J Biol Chem. 2003 Jan 31;278(5):2937-46. doi: 10.1074/jbc.M208439200. Epub 2002 Nov 12.
4 The PCBP1 gene encoding poly(rC) binding protein I is recurrently mutated in Burkitt lymphoma.Genes Chromosomes Cancer. 2015 Sep;54(9):555-64. doi: 10.1002/gcc.22268. Epub 2015 Jul 14.
5 RNA-binding proteins heterogeneous nuclear ribonucleoprotein A1, E1, and K are involved in post-transcriptional control of collagen I and III synthesis.Circ Res. 2004 Nov 26;95(11):1058-66. doi: 10.1161/01.RES.0000149166.33833.08. Epub 2004 Oct 28.
6 Poly(C)-binding protein 1 mediates drug resistance in colorectal cancer.Oncotarget. 2017 Feb 21;8(8):13312-13319. doi: 10.18632/oncotarget.14516.
7 Proteomic and functional analyses reveal the potential involvement of endoplasmic reticulum stress and -CP1 in the anticancer activities of oridonin in HepG2 cells.Integr Cancer Ther. 2011 Jun;10(2):160-7. doi: 10.1177/1534735410383171. Epub 2010 Oct 6.
8 Expanded polyglutamine impairs normal nuclear distribution of fused in sarcoma and poly (rC)-binding protein 1 in Huntington's disease.Neuropathology. 2019 Oct;39(5):358-367. doi: 10.1111/neup.12600. Epub 2019 Oct 9.
9 3'-UTR-mediated post-transcriptional regulation of cancer metastasis: beginning at the end.RNA Biol. 2011 Jul-Aug;8(4):595-9. doi: 10.4161/rna.8.4.16018. Epub 2011 Jul 1.
10 Iron Drives T Helper Cell Pathogenicity by Promoting RNA-Binding Protein PCBP1-Mediated Proinflammatory Cytokine Production.Immunity. 2018 Jul 17;49(1):80-92.e7. doi: 10.1016/j.immuni.2018.05.008. Epub 2018 Jun 26.
11 Poly(C)-binding protein 1 (Pcbp1) regulates skeletal muscle differentiation by modulating microRNA processing in myoblasts.J Biol Chem. 2017 Jun 9;292(23):9540-9550. doi: 10.1074/jbc.M116.773671. Epub 2017 Apr 5.
12 TGF promotes breast cancer stem cell self-renewal through an ILEI/LIFR signaling axis.Oncogene. 2019 May;38(20):3794-3811. doi: 10.1038/s41388-019-0703-z. Epub 2019 Jan 28.
13 Fyn/heterogeneous nuclear ribonucleoprotein E1 signaling regulates pancreatic cancer metastasis by affecting the alternative splicing of integrin 1.Int J Oncol. 2017 Jul;51(1):169-183. doi: 10.3892/ijo.2017.4018. Epub 2017 May 24.
14 The RNA-Binding Protein PCBP1 Functions as a Tumor Suppressor in Prostate Cancer by Inhibiting Mitogen Activated Protein Kinase 1.Cell Physiol Biochem. 2018;48(4):1747-1754. doi: 10.1159/000492315. Epub 2018 Aug 3.
15 PCBP1 depletion promotes tumorigenesis through attenuation of p27(Kip1) mRNA stability and translation.J Exp Clin Cancer Res. 2018 Aug 7;37(1):187. doi: 10.1186/s13046-018-0840-1.
16 Expression of both poly r(C) binding protein 1 (PCBP1) and miRNA-3978 is suppressed in peritoneal gastric cancer metastasis.Sci Rep. 2017 Nov 14;7(1):15488. doi: 10.1038/s41598-017-15448-9.
17 TGF-beta signaling in cancer: post-transcriptional regulation of EMT via hnRNP E1.Cytokine. 2019 Jun;118:19-26. doi: 10.1016/j.cyto.2017.12.032. Epub 2018 Feb 1.
18 Species-dependent neuropathology in transgenic SOD1 pigs.Cell Res. 2014 Apr;24(4):464-81. doi: 10.1038/cr.2014.25. Epub 2014 Feb 28.
19 Poly r(C) binding protein is post-transcriptionally repressed by MiR-490-3p to potentiate squamous cell carcinoma.Tumour Biol. 2016 Nov;37(11):14773-14778. doi: 10.1007/s13277-016-5234-4. Epub 2016 Sep 15.
20 PCBP1 is an important mediator of TGF--induced epithelial to mesenchymal transition in gall bladder cancer cell line GBC-SD.Mol Biol Rep. 2014 Aug;41(8):5519-24. doi: 10.1007/s11033-014-3428-7. Epub 2014 Jun 3.
21 Mutant HSPB1 causes loss of translational repression by binding to PCBP1, an RNA binding protein with a possible role in neurodegenerative disease.Acta Neuropathol Commun. 2017 Jan 11;5(1):5. doi: 10.1186/s40478-016-0407-3.
22 PCBP1 and NCOA4 regulate erythroid iron storage and heme biosynthesis.J Clin Invest. 2017 May 1;127(5):1786-1797. doi: 10.1172/JCI90519. Epub 2017 Apr 4.
23 MicroRNA-490 regulates lung cancer metastasis by targeting poly r(C)-binding protein 1.Tumour Biol. 2016 Nov;37(11):15221-15228. doi: 10.1007/s13277-016-5347-9. Epub 2016 Sep 28.
24 PCBP1 inhibits the expression of oncogenic STAT3 isoform by targeting alternative splicing of STAT3 exon 23.Int J Biol Sci. 2019 May 7;15(6):1177-1186. doi: 10.7150/ijbs.33103. eCollection 2019.
25 Poly r(C) binding protein (PCBP) 1 expression is regulated at the post-translation level in thyroid carcinoma.Am J Transl Res. 2017 Feb 15;9(2):708-714. eCollection 2017.
26 A genomic approach to predict synergistic combinations for breast cancer treatment. Pharmacogenomics J. 2013 Feb;13(1):94-104. doi: 10.1038/tpj.2011.48. Epub 2011 Nov 15.
27 Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
28 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.
29 Proteomic identification of differentially expressed proteins associated with the multiple drug resistance in methotrexate-resistant human breast cancer cells. Int J Oncol. 2014 Jul;45(1):448-58.
30 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.
31 Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
32 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.
33 Expression profile analysis of human peripheral blood mononuclear cells in response to aspirin. Arch Immunol Ther Exp (Warsz). 2005 Mar-Apr;53(2):151-8.
34 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.
35 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.
36 Comprehensive analysis of transcriptomic changes induced by low and high doses of bisphenol A in HepG2 spheroids in vitro and rat liver in vivo. Environ Res. 2019 Jun;173:124-134. doi: 10.1016/j.envres.2019.03.035. Epub 2019 Mar 18.
37 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.
38 Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.
39 ST1926, a novel and orally active retinoid-related molecule inducing apoptosis in myeloid leukemia cells: modulation of intracellular calcium homeostasis. Blood. 2004 Jan 1;103(1):194-207.
40 Proteomic analysis reveals multiple patterns of response in cells exposed to a toxin mixture. Chem Res Toxicol. 2009 Jun;22(6):1077-85.