Details of Drug Off-Target (DOT)

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

• DOT Name: Polyadenylate-binding protein 4 (PABPC4)
• Synonyms: PABP-4; Poly(A)-binding protein 4; Activated-platelet protein 1; APP-1; Inducible poly(A)-binding protein; iPABP
• Gene Name: PABPC4
• Related Disease:
  Colorectal carcinoma
  Alzheimer disease
  Cryptococcosis
  Hepatocellular carcinoma
  Lung adenocarcinoma
  Neoplasm
  Non-insulin dependent diabetes
  Neuroblastoma
• UniProt ID: PABP4_HUMAN
• Pfam ID: PF00658 ; PF00076
• Sequence:
  MNAAASSYPMASLYVGDLHSDVTEAMLYEKFSPAGPVLSIRVCRDMITRRSLGYAYVNFQ
  QPADAERALDTMNFDVIKGKPIRIMWSQRDPSLRKSGVGNVFIKNLDKSIDNKALYDTFS
  AFGNILSCKVVCDENGSKGYAFVHFETQEAADKAIEKMNGMLLNDRKVFVGRFKSRKERE
  AELGAKAKEFTNVYIKNFGEEVDDESLKELFSQFGKTLSVKVMRDPNGKSKGFGFVSYEK
  HEDANKAVEEMNGKEISGKIIFVGRAQKKVERQAELKRKFEQLKQERISRYQGVNLYIKN
  LDDTIDDEKLRKEFSPFGSITSAKVMLEDGRSKGFGFVCFSSPEEATKAVTEMNGRIVGS
  KPLYVALAQRKEERKAHLTNQYMQRVAGMRALPANAILNQFQPAAGGYFVPAVPQAQGRP
  PYYTPNQLAQMRPNPRWQQGGRPQGFQGMPSAIRQSGPRPTLRHLAPTGSECPDRLAMDF
  GGAGAAQQGLTDSCQSGGVPTAVQNLAPRAAVAAAAPRAVAPYKYASSVRSPHPAIQPLQ
  APQPAVHVQGQEPLTASMLAAAPPQEQKQMLGERLFPLIQTMHSNLAGKITGMLLEIDNS
  ELLHMLESPESLRSKVDEAVAVLQAHHAKKEAAQKVGAVAAATS
• Function: Binds the poly(A) tail of mRNA. May be involved in cytoplasmic regulatory processes of mRNA metabolism. Can probably bind to cytoplasmic RNA sequences other than poly(A) in vivo.
• Tissue Specificity: Expressed at low levels in resting normal T cells; following T-cell activation, however, mRNA levels are rapidly up-regulated.
• KEGG Pathway:
  mR. surveillance pathway (hsa03015)
  R. degradation (hsa03018)

Molecular Interaction Atlas (MIA) of This DOT

8 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Colorectal carcinoma	DIS5PYL0	Definitive	Biomarker	[1]
Alzheimer disease	DISF8S70	Strong	Biomarker	[2]
Cryptococcosis	DISDYDTK	Strong	Biomarker	[3]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[4]
Lung adenocarcinoma	DISD51WR	Strong	Biomarker	[5]
Neoplasm	DISZKGEW	Strong	Genetic Variation	[6]
Non-insulin dependent diabetes	DISK1O5Z	Strong	Genetic Variation	[7]
Neuroblastoma	DISVZBI4	moderate	Biomarker	[8]

2 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 Polyadenylate-binding protein 4 (PABPC4).	[9]
TAK-243	DM4GKV2	Phase 1	TAK-243 decreases the sumoylation of Polyadenylate-binding protein 4 (PABPC4).	[17]

11 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 Polyadenylate-binding protein 4 (PABPC4).	[10]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Polyadenylate-binding protein 4 (PABPC4).	[11]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Polyadenylate-binding protein 4 (PABPC4).	[12]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Polyadenylate-binding protein 4 (PABPC4).	[13]
Marinol	DM70IK5	Approved	Marinol decreases the expression of Polyadenylate-binding protein 4 (PABPC4).	[14]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Polyadenylate-binding protein 4 (PABPC4).	[15]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Polyadenylate-binding protein 4 (PABPC4).	[16]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Polyadenylate-binding protein 4 (PABPC4).	[18]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Polyadenylate-binding protein 4 (PABPC4).	[19]
chloropicrin	DMSGBQA	Investigative	chloropicrin decreases the expression of Polyadenylate-binding protein 4 (PABPC4).	[20]
methyl p-hydroxybenzoate	DMO58UW	Investigative	methyl p-hydroxybenzoate increases the expression of Polyadenylate-binding protein 4 (PABPC4).	[21]

References

• [1] Cytoplasmic poly(A) binding protein 4 is highly expressed in human colorectal cancer and correlates with better prognosis.J Genet Genomics. 2012 Aug 20;39(8):369-74. doi: 10.1016/j.jgg.2012.05.007. Epub 2012 Jun 8.
• [2] Frameshift proteins in autosomal dominant forms of Alzheimer disease and other tauopathies.Neurology. 2006 Jan 24;66(2 Suppl 1):S86-92. doi: 10.1212/01.wnl.0000193882.46003.6d.
• [3] Role of glucose in the expression of Cryptococcus neoformans antiphagocytic protein 1, App1.Eukaryot Cell. 2011 Mar;10(3):293-301. doi: 10.1128/EC.00252-10. Epub 2011 Jan 14.
• [4] miR-192-5p Silencing by Genetic Aberrations Is a Key Event in Hepatocellular Carcinomas with Cancer Stem Cell Features.Cancer Res. 2019 Mar 1;79(5):941-953. doi: 10.1158/0008-5472.CAN-18-1675. Epub 2018 Dec 7.
• [5] c-Myc targeted regulators of cell metabolism in a transgenic mouse model of papillary lung adenocarcinoma.Oncotarget. 2016 Oct 4;7(40):65514-65539. doi: 10.18632/oncotarget.11804.
• [6] (18)F-Labeled Pyrido[3,4-d]pyrimidine as an Effective Probe for Imaging of L858R Mutant Epidermal Growth Factor Receptor.ACS Med Chem Lett. 2017 Mar 20;8(4):418-422. doi: 10.1021/acsmedchemlett.6b00520. eCollection 2017 Apr 13.
• [7] Leveraging Polygenic Functional Enrichment to Improve GWAS Power.Am J Hum Genet. 2019 Jan 3;104(1):65-75. doi: 10.1016/j.ajhg.2018.11.008. Epub 2018 Dec 27.
• [8] A dinucleotide deletion in amyloid precursor protein (APP) mRNA associated with sporadic Alzheimer's disease results in efficient secretion of truncated APP isoforms from neuroblastoma cell cultures.J Neurochem. 2001 Mar;76(5):1308-14. doi: 10.1046/j.1471-4159.2001.00122.x.
• [9] 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.
• [10] 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.
• [11] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [12] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [13] 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.
• [14] JunD is involved in the antiproliferative effect of Delta9-tetrahydrocannabinol on human breast cancer cells. Oncogene. 2008 Aug 28;27(37):5033-44.
• [15] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [16] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [17] Inhibiting ubiquitination causes an accumulation of SUMOylated newly synthesized nuclear proteins at PML bodies. J Biol Chem. 2019 Oct 18;294(42):15218-15234. doi: 10.1074/jbc.RA119.009147. Epub 2019 Jul 8.
• [18] Alternatives for the worse: Molecular insights into adverse effects of bisphenol a and substitutes during human adipocyte differentiation. Environ Int. 2021 Nov;156:106730. doi: 10.1016/j.envint.2021.106730. Epub 2021 Jun 27.
• [19] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [20] Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.
• [21] Transcriptome dynamics of alternative splicing events revealed early phase of apoptosis induced by methylparaben in H1299 human lung carcinoma cells. Arch Toxicol. 2020 Jan;94(1):127-140. doi: 10.1007/s00204-019-02629-w. Epub 2019 Nov 20.