Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTBKHBT7)

• DOT Name: Coatomer subunit epsilon (COPE)
• Synonyms: Epsilon-coat protein; Epsilon-COP
• Gene Name: COPE
• Related Disease:
  Mixed anxiety and depressive disorder
  Advanced cancer
  Arteriosclerosis
  Atherosclerosis
  Bipolar disorder
  Colorectal carcinoma
  Depression
  Irritable bowel syndrome
  Lung cancer
  Lung carcinoma
  Motion sickness
  Parkinson disease
  Prostate neoplasm
  Psoriasis
  Schizophrenia
  Anxiety
  Anxiety disorder
  Post-traumatic stress disorder
• UniProt ID: COPE_HUMAN
• PDB ID: 6TZT; 6U3V
• Pfam ID: PF04733
• Sequence:
  MAPPAPGPASGGSGEVDELFDVKNAFYIGSYQQCINEAQRVKLSSPERDVERDVFLYRAY
  LAQRKFGVVLDEIKPSSAPELQAVRMFADYLAHESRRDSIVAELDREMSRSVDVTNTTFL
  LMAASIYLHDQNPDAALRALHQGDSLECTAMTVQILLKLDRLDLARKELKRMQDLDEDAT
  LTQLATAWVSLATGGEKLQDAYYIFQEMADKCSPTLLLLNGQAACHMAQGRWEAAEGLLQ
  EALDKDSGYPETLVNLIVLSQHLGKPPEVTNRYLSQLKDAHRSHPFIKEYQAKENDFDRL
  VLQYAPSA
• Function: The coatomer is a cytosolic protein complex that binds to dilysine motifs and reversibly associates with Golgi non-clathrin-coated vesicles, which further mediate biosynthetic protein transport from the ER, via the Golgi up to the trans Golgi network. The coatomer complex is required for budding from Golgi membranes, and is essential for the retrograde Golgi-to-ER transport of dilysine-tagged proteins. In mammals, the coatomer can only be recruited by membranes associated with ADP-ribosylation factors (ARFs), which are small GTP-binding proteins; the complex also influences the Golgi structural integrity, as well as the processing, activity, and endocytic recycling of LDL receptors.
• Reactome Pathway:
  COPI-dependent Golgi-to-ER retrograde traffic (R-HSA-6811434)
  COPI-mediated anterograde transport (R-HSA-6807878)

Molecular Interaction Atlas (MIA) of This DOT

18 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Mixed anxiety and depressive disorder	DISV809X	Definitive	Biomarker	[1]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[2]
Arteriosclerosis	DISK5QGC	Strong	Biomarker	[3]
Atherosclerosis	DISMN9J3	Strong	Biomarker	[3]
Bipolar disorder	DISAM7J2	Strong	Biomarker	[4]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[5]
Depression	DIS3XJ69	Strong	Biomarker	[6]
Irritable bowel syndrome	DIS27206	Strong	Biomarker	[7]
Lung cancer	DISCM4YA	Strong	Genetic Variation	[8]
Lung carcinoma	DISTR26C	Strong	Genetic Variation	[8]
Motion sickness	DISZ2WZW	Strong	Genetic Variation	[9]
Parkinson disease	DISQVHKL	Strong	Genetic Variation	[10]
Prostate neoplasm	DISHDKGQ	Strong	Altered Expression	[11]
Psoriasis	DIS59VMN	Strong	Biomarker	[12]
Schizophrenia	DISSRV2N	Strong	Biomarker	[13]
Anxiety	DISIJDBA	Limited	Genetic Variation	[14]
Anxiety disorder	DISBI2BT	Limited	Genetic Variation	[14]
Post-traumatic stress disorder	DISHL1EY	Limited	Biomarker	[15]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Paclitaxel	DMLB81S	Approved	Coatomer subunit epsilon (COPE) affects the response to substance of Paclitaxel.	[25]

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 Coatomer subunit epsilon (COPE).	[16]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the phosphorylation of Coatomer subunit epsilon (COPE).	[23]
Coumarin	DM0N8ZM	Investigative	Coumarin increases the phosphorylation of Coatomer subunit epsilon (COPE).	[23]

7 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 Coatomer subunit epsilon (COPE).	[17]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Coatomer subunit epsilon (COPE).	[18]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Coatomer subunit epsilon (COPE).	[19]
Selenium	DM25CGV	Approved	Selenium increases the expression of Coatomer subunit epsilon (COPE).	[20]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Coatomer subunit epsilon (COPE).	[20]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Coatomer subunit epsilon (COPE).	[22]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Coatomer subunit epsilon (COPE).	[24]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
DNCB	DMDTVYC	Phase 2	DNCB affects the binding of Coatomer subunit epsilon (COPE).	[21]

References

• [1] COPE for Adolescent Syrian Refugees in Lebanon: A Brief Cognitive-Behavioral Skill-Building Intervention to Improve Quality of Life and Promote Positive Mental Health.Clin Nurs Res. 2020 May;29(4):226-234. doi: 10.1177/1054773818808114. Epub 2018 Nov 26.
• [2] Role of Patient Coping Strategies in Understanding the Effects of Early Palliative Care on Quality of Life and Mood.J Clin Oncol. 2018 Jan 1;36(1):53-60. doi: 10.1200/JCO.2017.73.7221. Epub 2017 Nov 15.
• [3] Circulating Anti-Coatomer Protein Complex Subunit Epsilon (COPE) Autoantibodies as a Potential Biomarker for Cardiovascular and Cerebrovascular Events in Patients with Obstructive Sleep Apnea.J Clin Sleep Med. 2017 Mar 15;13(3):393-400. doi: 10.5664/jcsm.6488.
• [4] Predominant polarity in bipolar disorder patients: The COPE bipolar sample.J Affect Disord. 2019 May 1;250:43-50. doi: 10.1016/j.jad.2019.02.053. Epub 2019 Feb 20.
• [5] Coping With Prediagnosis Symptoms of Colorectal Cancer: A Study of 244 Individuals With Recent Diagnosis.Cancer Nurs. 2017 Mar/Apr;40(2):145-151. doi: 10.1097/NCC.0000000000000361.
• [6] Cognitive and behavioral coping in people with Chronic fatigue syndrome: An exploratory study searching for intervention targets for depressive symptoms.J Health Psychol. 2019 Nov;24(13):1878-1883. doi: 10.1177/1359105317707259. Epub 2017 May 17.
• [7] Relations between symptom severity, illness perceptions, visceral sensitivity, coping strategies and well-being in irritable bowel syndrome guided by the common sense model of illness.Psychol Health Med. 2017 Jun;22(5):524-534. doi: 10.1080/13548506.2016.1168932. Epub 2016 Apr 4.
• [8] The reciprocal relationship between coping mechanisms and lung cancer diagnosis: findings of a prospective study.Cancer Manag Res. 2018 Jan 4;10:33-40. doi: 10.2147/CMAR.S148341. eCollection 2018.
• [9] Sensation Seeking and Adaptation in Parabonauts.Front Psychol. 2018 Mar 9;9:296. doi: 10.3389/fpsyg.2018.00296. eCollection 2018.
• [10] Optimism, Pessimism, Coping, and Depression: A Study on Individuals With Parkinson's Disease.Int J Aging Hum Dev. 2019 Apr;88(3):231-249. doi: 10.1177/0091415018763401. Epub 2018 Mar 20.
• [11] Ubiquitylation of epsilon-COP by PIRH2 and regulation of the secretion of PSA.Mol Cell Biochem. 2008 Jan;307(1-2):73-82. doi: 10.1007/s11010-007-9586-3. Epub 2007 Aug 25.
• [12] Dermatology Life Quality Index and disease coping strategies in psoriasis patients.Postepy Dermatol Alergol. 2019 Aug;36(4):419-424. doi: 10.5114/ada.2018.75810. Epub 2019 Aug 30.
• [13] Coping and psychopathology in children with malignancy and bronchiectasis.Pediatr Pulmonol. 2020 Jan;55(1):214-220. doi: 10.1002/ppul.24534. Epub 2019 Dec 9.
• [14] Coping and Anxiety in Caregivers of Dependent Older Adult Relatives.Int J Environ Res Public Health. 2019 May 12;16(9):1651. doi: 10.3390/ijerph16091651.
• [15] Concurrent treatment of substance use disorders and PTSD using prolonged exposure: A randomized clinical trial in military veterans.Addict Behav. 2019 Mar;90:369-377. doi: 10.1016/j.addbeh.2018.11.032. Epub 2018 Nov 27.
• [16] 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.
• [17] 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.
• [18] 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.
• [19] 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.
• [20] 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.
• [21] Proteomic analysis of the cellular response to a potent sensitiser unveils the dynamics of haptenation in living cells. Toxicology. 2020 Dec 1;445:152603. doi: 10.1016/j.tox.2020.152603. Epub 2020 Sep 28.
• [22] 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.
• [23] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [24] Low-dose Bisphenol A exposure alters the functionality and cellular environment in a human cardiomyocyte model. Environ Pollut. 2023 Oct 15;335:122359. doi: 10.1016/j.envpol.2023.122359. Epub 2023 Aug 9.
• [25] Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.