Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTPESEM5)

• DOT Name: Copine-2 (CPNE2)
• Synonyms: Copine II
• Gene Name: CPNE2
• UniProt ID: CPNE2_HUMAN
• Pfam ID: PF00168 ; PF07002
• Sequence:
  MAHIPSGGAPAAGAAPMGPQYCVCKVELSVSGQNLLDRDVTSKSDPFCVLFTENNGRWIE
  YDRTETAINNLNPAFSKKFVLDYHFEEVQKLKFALFDQDKSSMRLDEHDFLGQFSCSLGT
  IVSSKKITRPLLLLNDKPAGKGLITIAAQELSDNRVITLSLAGRRLDKKDLFGKSDPFLE
  FYKPGDDGKWMLVHRTEVIKYTLDPVWKPFTVPLVSLCDGDMEKPIQVMCYDYDNDGGHD
  FIGEFQTSVSQMCEARDSVPLEFECINPKKQRKKKNYKNSGIIILRSCKINRDYSFLDYI
  LGGCQLMFTVGIDFTASNGNPLDPSSLHYINPMGTNEYLSAIWAVGQIIQDYDSDKMFPA
  LGFGAQLPPDWKVSHEFAINFNPTNPFCSGVDGIAQAYSACLPHIRFYGPTNFSPIVNHV
  ARFAAQATQQRTATQYFILLIITDGVISDMEETRHAVVQASKLPMSIIIVGVGNADFAAM
  EFLDGDSRMLRSHTGEEAARDIVQFVPFREFRNAAKETLAKAVLAELPQQVVQYFKHKNL
  PPTNSEPA
• Function: Calcium-dependent phospholipid-binding protein that plays a role in calcium-mediated intracellular processes. Exhibits calcium-dependent cell membrane binding properties.
• Tissue Specificity: Expressed in the brain. Expressed in neutrophil precursors from the bone marrow and peripheral blood .

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Copine-2 (CPNE2).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Copine-2 (CPNE2).	[9]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Copine-2 (CPNE2).	[11]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Copine-2 (CPNE2).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Copine-2 (CPNE2).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Copine-2 (CPNE2).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Copine-2 (CPNE2).	[5]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Copine-2 (CPNE2).	[6]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Copine-2 (CPNE2).	[7]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Copine-2 (CPNE2).	[8]
Belinostat	DM6OC53	Phase 2	Belinostat decreases the expression of Copine-2 (CPNE2).	[8]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Copine-2 (CPNE2).	[10]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Copine-2 (CPNE2).	[12]

References

• [1] 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.
• [2] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [3] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [4] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [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] 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.
• [7] 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.
• [8] 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.
• [9] 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.
• [10] 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.
• [11] 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.
• [12] 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.