Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTTAGM5L)

• DOT Name: Copine-4 (CPNE4)
• Synonyms: Copine IV; Copine-8
• Gene Name: CPNE4
• Related Disease:
  Amyotrophic lateral sclerosis
  Motion sickness
  Osteoarthritis
  Acute myelogenous leukaemia
• UniProt ID: CPNE4_HUMAN
• Pfam ID: PF00168 ; PF07002
• Sequence:
  MKKMSNIYESAANTLGIFNSPCLTKVELRVACKGISDRDALSKPDPCVILKMQSHGQWFE
  VDRTEVIRTCINPVYSKLFTVDFYFEEVQRLRFEVHDISSNHNGLKEADFLGGMECTLGQ
  IVSQRKLSKSLLKHGNTAGKSSITVIAEELSGNDDYVELAFNARKLDDKDFFSKSDPFLE
  IFRMNDDATQQLVHRTEVVMNNLSPAWKSFKVSVNSLCSGDPDRRLKCIVWDWDSNGKHD
  FIGEFTSTFKEMRGAMEGKQVQWECINPKYKAKKKNYKNSGTVILNLCKIHKMHSFLDYI
  MGGCQIQFTVAIDFTASNGDPRNSCSLHYIHPYQPNEYLKALVAVGEICQDYDSDKMFPA
  FGFGARIPPEYTVSHDFAINFNEDNPECAGIQGVVEAYQSCLPKLQLYGPTNIAPIIQKV
  AKSASEETNTKEASQYFILLILTDGVITDMADTREAIVHASHLPMSVIIVGVGNADFSDM
  QMLDGDDGILRSPKGEPVLRDIVQFVPFRNFKHASPAALAKSVLAEVPNQVVDYYNGKGI
  KPKCSSEMYESSRTLAP
• Function: Probable calcium-dependent phospholipid-binding protein that may play a role in calcium-mediated intracellular processes.
• Tissue Specificity: Widely expressed . Expressed strongly in the brain, heart and prostate . Expressed strongly in peripheral blood leukocytes .

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Amyotrophic lateral sclerosis	DISF7HVM	Strong	Genetic Variation	[1]
Motion sickness	DISZ2WZW	Strong	Genetic Variation	[2]
Osteoarthritis	DIS05URM	Strong	Genetic Variation	[3]
Acute myelogenous leukaemia	DISCSPTN	moderate	Genetic Variation	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Copine-4 (CPNE4).	[5]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Copine-4 (CPNE4).	[6]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Copine-4 (CPNE4).	[7]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Copine-4 (CPNE4).	[8]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Copine-4 (CPNE4).	[9]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Copine-4 (CPNE4).	[11]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Copine-4 (CPNE4).	[12]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Copine-4 (CPNE4).	[12]
Belinostat	DM6OC53	Phase 2	Belinostat increases the expression of Copine-4 (CPNE4).	[12]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Copine-4 (CPNE4).	[13]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Copine-4 (CPNE4).	[14]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Copine-4 (CPNE4).	[16]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Copine-4 (CPNE4).	[17]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Copine-4 (CPNE4).	[10]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Copine-4 (CPNE4).	[15]

References

• [1] Age of onset of amyotrophic lateral sclerosis is modulated by a locus on 1p34.1.Neurobiol Aging. 2013 Jan;34(1):357.e7-19. doi: 10.1016/j.neurobiolaging.2012.07.017. Epub 2012 Sep 5.
• [2] Genetic variants associated with motion sickness point to roles for inner ear development, neurological processes and glucose homeostasis.Hum Mol Genet. 2015 May 1;24(9):2700-8. doi: 10.1093/hmg/ddv028. Epub 2015 Jan 26.
• [3] Identification of new susceptibility loci for osteoarthritis (arcOGEN): a genome-wide association study.Lancet. 2012 Sep 1;380(9844):815-23. doi: 10.1016/S0140-6736(12)60681-3. Epub 2012 Jul 3.
• [4] Genome-wide haplotype association study identify the FGFR2 gene as a risk gene for acute myeloid leukemia.Oncotarget. 2017 Jan 31;8(5):7891-7899. doi: 10.18632/oncotarget.13631.
• [5] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [6] 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.
• [7] 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.
• [8] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [9] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [10] 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.
• [11] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [12] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [13] Benzo[a]pyrene-induced changes in microRNA-mRNA networks. Chem Res Toxicol. 2012 Apr 16;25(4):838-49.
• [14] 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.
• [15] 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.
• [16] 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.
• [17] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.