Details of Drug Off-Target (DOT)

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

• DOT Name: Coatomer subunit zeta-1 (COPZ1)
• Synonyms: Zeta-1-coat protein; Zeta-1 COP
• Gene Name: COPZ1
• Related Disease:
  Neoplasm
  Venous thromboembolism
  Thyroid cancer
  Thyroid gland carcinoma
  Thyroid tumor
• UniProt ID: COPZ1_HUMAN
• PDB ID: 2HF6; 5MC7
• Pfam ID: PF01217
• Sequence:
  MEALILEPSLYTVKAILILDNDGDRLFAKYYDDTYPSVKEQKAFEKNIFNKTHRTDSEIA
  LLEGLTVVYKSSIDLYFYVIGSSYENELMLMAVLNCLFDSLSQMLRKNVEKRALLENMEG
  LFLAVDEIVDGGVILESDPQQVVHRVALRGEDVPLTEQTVSQVLQSAKEQIKWSLLR
• 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. Coatomer complex is required for budding from Golgi membranes, and is essential for the retrograde Golgi-to-ER transport of dilysine-tagged proteins. The zeta subunit may be involved in regulating the coat assembly and, hence, the rate of biosynthetic protein transport due to its association-dissociation properties with the coatomer complex.
• 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

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Neoplasm	DISZKGEW	Strong	Biomarker	[1]
Venous thromboembolism	DISUR7CR	Strong	Genetic Variation	[2]
Thyroid cancer	DIS3VLDH	Limited	Biomarker	[1]
Thyroid gland carcinoma	DISMNGZ0	Limited	Biomarker	[1]
Thyroid tumor	DISLVKMD	Limited	Biomarker	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate affects the expression of Coatomer subunit zeta-1 (COPZ1).	[3]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Coatomer subunit zeta-1 (COPZ1).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Coatomer subunit zeta-1 (COPZ1).	[5]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Coatomer subunit zeta-1 (COPZ1).	[6]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Coatomer subunit zeta-1 (COPZ1).	[7]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Coatomer subunit zeta-1 (COPZ1).	[8]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Coatomer subunit zeta-1 (COPZ1).	[9]

References

• [1] Targeting COPZ1 non-oncogene addiction counteracts the viability of thyroid tumor cells.Cancer Lett. 2017 Dec 1;410:201-211. doi: 10.1016/j.canlet.2017.09.024. Epub 2017 Sep 23.
• [2] Genomic and transcriptomic association studies identify 16 novel susceptibility loci for venous thromboembolism.Blood. 2019 Nov 7;134(19):1645-1657. doi: 10.1182/blood.2019000435.
• [3] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [4] 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.
• [5] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [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] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [8] New insights into BaP-induced toxicity: role of major metabolites in transcriptomics and contribution to hepatocarcinogenesis. Arch Toxicol. 2016 Jun;90(6):1449-58.
• [9] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.