Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTH5YKSL)

• DOT Name: Copine-1 (CPNE1)
• Synonyms: Chromobindin 17; Copine I
• Gene Name: CPNE1
• Related Disease:
  Castration-resistant prostate carcinoma
  Lung cancer
  Lung carcinoma
  Neoplasm
  Non-small-cell lung cancer
  Open-angle glaucoma
  Prostate cancer
  Prostate carcinoma
  Bone osteosarcoma
  Osteosarcoma
• UniProt ID: CPNE1_HUMAN
• Pfam ID: PF00168 ; PF07002
• Sequence:
  MAHCVTLVQLSISCDHLIDKDIGSKSDPLCVLLQDVGGGSWAELGRTERVRNCSSPEFSK
  TLQLEYRFETVQKLRFGIYDIDNKTPELRDDDFLGGAECSLGQIVSSQVLTLPLMLKPGK
  PAGRGTITVSAQELKDNRVVTMEVEARNLDKKDFLGKSDPFLEFFRQGDGKWHLVYRSEV
  IKNNLNPTWKRFSVPVQHFCGGNPSTPIQVQCSDYDSDGSHDLIGTFHTSLAQLQAVPAE
  FECIHPEKQQKKKSYKNSGTIRVKICRVETEYSFLDYVMGGCQINFTVGVDFTGSNGDPS
  SPDSLHYLSPTGVNEYLMALWSVGSVVQDYDSDKLFPAFGFGAQVPPDWQVSHEFALNFN
  PSNPYCAGIQGIVDAYRQALPQVRLYGPTNFAPIINHVARFAAQAAHQGTASQYFMLLLL
  TDGAVTDVEATREAVVRASNLPMSVIIVGVGGADFEAMEQLDADGGPLHTRSGQAAARDI
  VQFVPYRRFQNAPREALAQTVLAEVPTQLVSYFRAQGWAPLKPLPPSAKDPAQAPQA
• Function: Calcium-dependent phospholipid-binding protein that plays a role in calcium-mediated intracellular processes. Involved in the TNF-alpha receptor signaling pathway in a calcium-dependent manner. Exhibits calcium-dependent phospholipid binding properties. Plays a role in neuronal progenitor cell differentiation; induces neurite outgrowth via a AKT-dependent signaling cascade and calcium-independent manner. May recruit target proteins to the cell membrane in a calcium-dependent manner. May function in membrane trafficking. Involved in TNF-alpha-induced NF-kappa-B transcriptional repression by inducing endoprotease processing of the transcription factor NF-kappa-B p65/RELA subunit. Also induces endoprotease processing of NF-kappa-B p50/NFKB1, p52/NFKB2, RELB and REL.
• Tissue Specificity: Expressed in neutrophils (at protein level) . Widely expressed. Expressed in the brain. Expressed in neutrophil precursors from bone marrow and peripheral blood .
• Reactome Pathway:
  Neutrophil degranulation (R-HSA-6798695)
  Glycerophospholipid biosynthesis (R-HSA-1483206)

Molecular Interaction Atlas (MIA) of This DOT

10 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Castration-resistant prostate carcinoma	DISVGAE6	Strong	Altered Expression	[1]
Lung cancer	DISCM4YA	Strong	Biomarker	[2]
Lung carcinoma	DISTR26C	Strong	Biomarker	[2]
Neoplasm	DISZKGEW	Strong	Altered Expression	[1]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[2]
Open-angle glaucoma	DISSZEE8	Strong	Altered Expression	[3]
Prostate cancer	DISF190Y	Strong	Altered Expression	[1]
Prostate carcinoma	DISMJPLE	Strong	Altered Expression	[1]
Bone osteosarcoma	DIST1004	Limited	Biomarker	[4]
Osteosarcoma	DISLQ7E2	Limited	Biomarker	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Copine-1 (CPNE1).	[5]
Cisplatin	DMRHGI9	Approved	Cisplatin affects the expression of Copine-1 (CPNE1).	[6]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Copine-1 (CPNE1).	[7]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Copine-1 (CPNE1).	[8]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Copine-1 (CPNE1).	[6]
Aspirin	DM672AH	Approved	Aspirin increases the expression of Copine-1 (CPNE1).	[9]
Clozapine	DMFC71L	Approved	Clozapine decreases the expression of Copine-1 (CPNE1).	[10]
Sulindac	DM2QHZU	Approved	Sulindac decreases the expression of Copine-1 (CPNE1).	[9]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Copine-1 (CPNE1).	[11]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN decreases the expression of Copine-1 (CPNE1).	[14]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Copine-1 (CPNE1).	[15]
CH-223191	DMMJZYC	Investigative	CH-223191 decreases the expression of Copine-1 (CPNE1).	[16]

1 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 decreases the methylation of Copine-1 (CPNE1).	[12]

1 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
PMID28870136-Compound-48	DMPIM9L	Patented	PMID28870136-Compound-48 affects the binding of Copine-1 (CPNE1).	[13]

References

• [1] CPNE1 Is a Useful Prognostic Marker and Is Associated with TNF Receptor-Associated Factor 2 (TRAF2) Expression in Prostate Cancer.Med Sci Monit. 2017 Nov 19;23:5504-5514. doi: 10.12659/msm.904720.
• [2] High expression of Copine1 promotes cell growth and metastasis in human lung adenocarcinoma.Int J Oncol. 2018 Dec;53(6):2369-2378. doi: 10.3892/ijo.2018.4558. Epub 2018 Sep 12.
• [3] Upregulation of Copine1 in trabecular meshwork cells of POAG patients: a membrane proteomics approach.Mol Vis. 2008 May 30;14:1028-36.
• [4] CPNE1 silencing inhibits the proliferation, invasion and migration of human osteosarcoma cells.Oncol Rep. 2018 Feb;39(2):643-650. doi: 10.3892/or.2017.6128. Epub 2017 Dec 4.
• [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] Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
• [7] 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.
• [8] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [9] Expression profile analysis of colon cancer cells in response to sulindac or aspirin. Biochem Biophys Res Commun. 2002 Mar 29;292(2):498-512.
• [10] 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.
• [11] 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.
• [12] 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.
• [13] Oxidative stress modulates theophylline effects on steroid responsiveness. Biochem Biophys Res Commun. 2008 Dec 19;377(3):797-802.
• [14] Proteomic signatures in thapsigargin-treated hepatoma cells. Chem Res Toxicol. 2011 Aug 15;24(8):1215-22. doi: 10.1021/tx200109y. Epub 2011 Jul 1.
• [15] 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.
• [16] Adaptive changes in global gene expression profile of lung carcinoma A549 cells acutely exposed to distinct types of AhR ligands. Toxicol Lett. 2018 Aug;292:162-174.