Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTM5W0BK)

• DOT Name: Coatomer subunit zeta-2 (COPZ2)
• Synonyms: Zeta-2-coat protein; Zeta-2 COP
• Gene Name: COPZ2
• Related Disease:
  Neoplasm
  Endometrial cancer
  Endometrial carcinoma
• UniProt ID: COPZ2_HUMAN
• Pfam ID: PF01217
• Sequence:
  MQRPEAWPRPHPGEGAAAAQAGGPAPPARAGEPSGLRLQEPSLYTIKAVFILDNDGRRLL
  AKYYDDTFPSMKEQMVFEKNVFNKTSRTESEIAFFGGMTIVYKNSIDLFLYVVGSSYENE
  LMLMSVLTCLFESLNHMLRKNVEKRWLLENMDGAFLVLDEIVDGGVILESDPQQVIQKVN
  FRADDGGLTEQSVAQVLQSAKEQIKWSLLK
• 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

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Neoplasm	DISZKGEW	Definitive	Biomarker	[1]
Endometrial cancer	DISW0LMR	Strong	Posttranslational Modification	[2]
Endometrial carcinoma	DISXR5CY	Strong	Posttranslational Modification	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Coatomer subunit zeta-2 (COPZ2).	[3]
Estradiol	DMUNTE3	Approved	Estradiol affects the expression of Coatomer subunit zeta-2 (COPZ2).	[4]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Coatomer subunit zeta-2 (COPZ2).	[5]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Coatomer subunit zeta-2 (COPZ2).	[6]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Coatomer subunit zeta-2 (COPZ2).	[7]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Coatomer subunit zeta-2 (COPZ2).	[8]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Coatomer subunit zeta-2 (COPZ2).	[9]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Coatomer subunit zeta-2 (COPZ2).	[10]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A increases the expression of Coatomer subunit zeta-2 (COPZ2).	[11]

References

• [1] Tumor-specific silencing of COPZ2 gene encoding coatomer protein complex subunit 2 renders tumor cells dependent on its paralogous gene COPZ1.Proc Natl Acad Sci U S A. 2011 Jul 26;108(30):12449-54. doi: 10.1073/pnas.1103842108. Epub 2011 Jul 11.
• [2] miR-152 is a tumor suppressor microRNA that is silenced by DNA hypermethylation in endometrial cancer.Cancer Res. 2011 Oct 15;71(20):6450-62. doi: 10.1158/0008-5472.CAN-11-0364. Epub 2011 Aug 25.
• [3] 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.
• [4] Identification of novel low-dose bisphenol a targets in human foreskin fibroblast cells derived from hypospadias patients. PLoS One. 2012;7(5):e36711. doi: 10.1371/journal.pone.0036711. Epub 2012 May 4.
• [5] 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.
• [6] Identification of vitamin D3 target genes in human breast cancer tissue. J Steroid Biochem Mol Biol. 2016 Nov;164:90-97.
• [7] 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.
• [8] 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.
• [9] 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.
• [10] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [11] Linking site-specific loss of histone acetylation to repression of gene expression by the mycotoxin ochratoxin A. Arch Toxicol. 2018 Feb;92(2):995-1014.