Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTCR3WG2)

• DOT Name: Copine-3 (CPNE3)
• Synonyms: Copine III
• Gene Name: CPNE3
• Related Disease:
  Acute myelogenous leukaemia
  Acute myocardial infarction
  Breast cancer
  Breast carcinoma
  Colorectal carcinoma
  Coronary heart disease
  Fanconi anemia complementation group A
  Fanconi's anemia
  Friedreich ataxia 1
  Lung cancer
  Lung carcinoma
  Ovarian neoplasm
  Prostate neoplasm
  Hepatocellular carcinoma
  Non-small-cell lung cancer
  Prostate cancer
• UniProt ID: CPNE3_HUMAN
• Pfam ID: PF00168 ; PF07002
• Sequence:
  MAAQCVTKVALNVSCANLLDKDIGSKSDPLCVLFLNTSGQQWYEVERTERIKNCLNPQFS
  KTFIIDYYFEVVQKLKFGVYDIDNKTIELSDDDFLGECECTLGQIVSSKKLTRPLVMKTG
  RPAGKGSITISAEEIKDNRVVLFEMEARKLDNKDLFGKSDPYLEFHKQTSDGNWLMVHRT
  EVVKNNLNPVWRPFKISLNSLCYGDMDKTIKVECYDYDNDGSHDLIGTFQTTMTKLKEAS
  RSSPVEFECINEKKRQKKKSYKNSGVISVKQCEITVECTFLDYIMGGCQLNFTVGVDFTG
  SNGDPRSPDSLHYISPNGVNEYLTALWSVGLVIQDYDADKMFPAFGFGAQIPPQWQVSHE
  FPMNFNPSNPYCNGIQGIVEAYRSCLPQIKLYGPTNFSPIINHVARFAAAATQQQTASQY
  FVLLIITDGVITDLDETRQAIVNASRLPMSIIIVGVGGADFSAMEFLDGDGGSLRSPLGE
  VAIRDIVQFVPFRQFQNAPKEALAQCVLAEIPQQVVGYFNTYKLLPPKNPATKQQKQ
• Function: Calcium-dependent phospholipid-binding protein that plays a role in ERBB2-mediated tumor cell migration in response to growth factor heregulin stimulation.
• Tissue Specificity: Expressed in breast and weakly in prostate and ovarian tissues . Expressed in neutrophils (at protein level) . Widely expressed . Expressed in the brain. Expressed in neutrophil precursors from the bone marrow and peripheral blood . Expressed in primary breast tumors and ovarian endometrioid adenocarcinoma .
• Reactome Pathway:
  Neutrophil degranulation (R-HSA-6798695)
  Glycerophospholipid biosynthesis (R-HSA-1483206)

Molecular Interaction Atlas (MIA) of This DOT

16 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute myelogenous leukaemia	DISCSPTN	Strong	Altered Expression	[1]
Acute myocardial infarction	DISE3HTG	Strong	Altered Expression	[2]
Breast cancer	DIS7DPX1	Strong	Biomarker	[3]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[3]
Colorectal carcinoma	DIS5PYL0	Strong	Altered Expression	[4]
Coronary heart disease	DIS5OIP1	Strong	Altered Expression	[2]
Fanconi anemia complementation group A	DIS8PZLI	Strong	Altered Expression	[5]
Fanconi's anemia	DISGW6Q8	Strong	Altered Expression	[5]
Friedreich ataxia 1	DIS285GE	Strong	Altered Expression	[5]
Lung cancer	DISCM4YA	Strong	Biomarker	[6]
Lung carcinoma	DISTR26C	Strong	Biomarker	[6]
Ovarian neoplasm	DISEAFTY	Strong	Biomarker	[3]
Prostate neoplasm	DISHDKGQ	Strong	Biomarker	[7]
Hepatocellular carcinoma	DIS0J828	Limited	Altered Expression	[8]
Non-small-cell lung cancer	DIS5Y6R9	Limited	Biomarker	[5]
Prostate cancer	DISF190Y	Limited	Biomarker	[7]

3 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 Copine-3 (CPNE3).	[9]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Copine-3 (CPNE3).	[12]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Copine-3 (CPNE3).	[18]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Copine-3 (CPNE3).	[10]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Copine-3 (CPNE3).	[11]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Copine-3 (CPNE3).	[13]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Copine-3 (CPNE3).	[14]
Testosterone enanthate	DMB6871	Approved	Testosterone enanthate affects the expression of Copine-3 (CPNE3).	[15]
Benzatropine	DMF7EXL	Approved	Benzatropine decreases the expression of Copine-3 (CPNE3).	[16]
Haloperidol	DM96SE0	Approved	Haloperidol decreases the expression of Copine-3 (CPNE3).	[16]
DNCB	DMDTVYC	Phase 2	DNCB decreases the expression of Copine-3 (CPNE3).	[17]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Copine-3 (CPNE3).	[19]
Geldanamycin	DMS7TC5	Discontinued in Phase 2	Geldanamycin increases the expression of Copine-3 (CPNE3).	[20]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Copine-3 (CPNE3).	[21]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Copine-3 (CPNE3).	[22]
Deguelin	DMXT7WG	Investigative	Deguelin decreases the expression of Copine-3 (CPNE3).	[23]

References

• [1] High expression of CPNE3 predicts adverse prognosis in acute myeloid leukemia.Cancer Sci. 2017 Sep;108(9):1850-1857. doi: 10.1111/cas.13311. Epub 2017 Aug 20.
• [2] Low CPNE3 expression is associated with risk of acute myocardial infarction: A feasible genetic marker of acute myocardial infarction in patients with stable coronary artery disease.Cardiol J. 2019;26(2):186-193. doi: 10.5603/CJ.a2017.0155. Epub 2018 Jan 3.
• [3] Copine-III interacts with ErbB2 and promotes tumor cell migration.Oncogene. 2010 Mar 18;29(11):1598-610. doi: 10.1038/onc.2009.456. Epub 2009 Dec 14.
• [4] Circulating exosomal CPNE3 as a diagnostic and prognostic biomarker for colorectal cancer.J Cell Physiol. 2019 Feb;234(2):1416-1425. doi: 10.1002/jcp.26936. Epub 2018 Aug 5.
• [5] CPNE3 promotes migration and invasion in non-small cell lung cancer by interacting with RACK1 via FAK signaling activation.J Cancer. 2018 Oct 20;9(22):4215-4222. doi: 10.7150/jca.25872. eCollection 2018.
• [6] Quantitative proteomic analysis identifies CPNE3 as a novel metastasis-promoting gene in NSCLC.J Proteome Res. 2013 Jul 5;12(7):3423-33. doi: 10.1021/pr400273z. Epub 2013 Jun 6.
• [7] Multiple loci identified in a genome-wide association study of prostate cancer.Nat Genet. 2008 Mar;40(3):310-5. doi: 10.1038/ng.91. Epub 2008 Feb 10.
• [8] Silencing the expression of copine-III enhances the sensitivity of hepatocellular carcinoma cells to the molecular targeted agent sorafenib.Cancer Manag Res. 2018 Aug 29;10:3057-3067. doi: 10.2147/CMAR.S167781. eCollection 2018.
• [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] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [11] 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.
• [12] 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.
• [13] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [14] The proapoptotic effect of zoledronic acid is independent of either the bone microenvironment or the intrinsic resistance to bortezomib of myeloma cells and is enhanced by the combination with arsenic trioxide. Exp Hematol. 2011 Jan;39(1):55-65.
• [15] Transcriptional profiling of testosterone-regulated genes in the skeletal muscle of human immunodeficiency virus-infected men experiencing weight loss. J Clin Endocrinol Metab. 2007 Jul;92(7):2793-802. doi: 10.1210/jc.2006-2722. Epub 2007 Apr 17.
• [16] 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.
• [17] Microarray analyses in dendritic cells reveal potential biomarkers for chemical-induced skin sensitization. Mol Immunol. 2007 May;44(12):3222-33.
• [18] 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.
• [19] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [20] Identification of transcriptome signatures and biomarkers specific for potential developmental toxicants inhibiting human neural crest cell migration. Arch Toxicol. 2016 Jan;90(1):159-80.
• [21] 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.
• [22] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [23] 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.