Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT50CV12)

• DOT Name: Coatomer subunit beta (COPB1)
• Synonyms: Beta-coat protein; Beta-COP
• Gene Name: COPB1
• Related Disease:
  Prostate cancer
  Prostate carcinoma
  Baralle-Macken syndrome
• UniProt ID: COPB_HUMAN
• Pfam ID: PF01602 ; PF07718 ; PF14806
• Sequence:
  MTAAENVCYTLINVPMDSEPPSEISLKNDLEKGDVKSKTEALKKVIIMILNGEKLPGLLM
  TIIRFVLPLQDHTIKKLLLVFWEIVPKTTPDGRLLHEMILVCDAYRKDLQHPNEFIRGST
  LRFLCKLKEAELLEPLMPAIRACLEHRHSYVRRNAVLAIYTIYRNFEHLIPDAPELIHDF
  LVNEKDASCKRNAFMMLIHADQDRALDYLSTCIDQVQTFGDILQLVIVELIYKVCHANPS
  ERARFIRCIYNLLQSSSPAVKYEAAGTLVTLSSAPTAIKAAAQCYIDLIIKESDNNVKLI
  VLDRLIELKEHPAHERVLQDLVMDILRVLSTPDLEVRKKTLQLALDLVSSRNVEELVIVL
  KKEVIKTNNVSEHEDTDKYRQLLVRTLHSCSVRFPDMAANVIPVLMEFLSDNNEAAAADV
  LEFVREAIQRFDNLRMLIVEKMLEVFHAIKSVKIYRGALWILGEYCSTKEDIQSVMTEIR
  RSLGEIPIVESEIKKEAGELKPEEEITVGPVQKLVTEMGTYATQSALSSSRPTKKEEDRP
  PLRGFLLDGDFFVAASLATTLTKIALRYVALVQEKKKQNSFVAEAMLLMATILHLGKSSL
  PKKPITDDDVDRISLCLKVLSECSPLMNDIFNKECRQSLSHMLSAKLEEEKLSQKKESEK
  RNVTVQPDDPISFMQLTAKNEMNCKEDQFQLSLLAAMGNTQRKEAADPLASKLNKVTQLT
  GFSDPVYAEAYVHVNQYDIVLDVLVVNQTSDTLQNCTLELATLGDLKLVEKPSPLTLAPH
  DFANIKANVKVASTENGIIFGNIVYDVSGAASDRNCVVLSDIHIDIMDYIQPATCTDAEF
  RQMWAEFEWENKVTVNTNMVDLNDYLQHILKSTNMKCLTPEKALSGYCGFMAANLYARSI
  FGEDALANVSIEKPIHQGPDAAVTGHIRIRAKSQGMALSLGDKINLSQKKTSI
• 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. In mammals, the coatomer can only be recruited by membranes associated to 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. Plays a functional role in facilitating the transport of kappa-type opioid receptor mRNAs into axons and enhances translation of these proteins. Required for limiting lipid storage in lipid droplets. Involved in lipid homeostasis by regulating the presence of perilipin family members PLIN2 and PLIN3 at the lipid droplet surface and promoting the association of adipocyte surface triglyceride lipase (PNPLA2) with the lipid droplet to mediate lipolysis. Involved in the Golgi disassembly and reassembly processes during cell cycle. Involved in autophagy by playing a role in early endosome function. Plays a role in organellar compartmentalization of secretory compartments including endoplasmic reticulum (ER)-Golgi intermediate compartment (ERGIC), Golgi, trans-Golgi network (TGN) and recycling endosomes, and in biosynthetic transport of CAV1. Promotes degradation of Nef cellular targets CD4 and MHC class I antigens by facilitating their trafficking to degradative compartments.
• Reactome Pathway:
  COPI-mediated anterograde transport (R-HSA-6807878)
  COPI-dependent Golgi-to-ER retrograde traffic (R-HSA-6811434)
  Neutrophil degranulation (R-HSA-6798695)

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Prostate cancer	DISF190Y	Strong	Biomarker	[1]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[1]
Baralle-Macken syndrome	DISRMDAX	Limited	Unknown	[2]

6 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 beta (COPB1).	[3]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Coatomer subunit beta (COPB1).	[4]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Coatomer subunit beta (COPB1).	[5]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Coatomer subunit beta (COPB1).	[6]
Marinol	DM70IK5	Approved	Marinol decreases the expression of Coatomer subunit beta (COPB1).	[7]
chloropicrin	DMSGBQA	Investigative	chloropicrin increases the expression of Coatomer subunit beta (COPB1).	[9]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Coatomer subunit beta (COPB1).	[8]

References

• [1] Coatomer subunit beta 2 (COPB2), identified by label-free quantitative proteomics, regulates cell proliferation and apoptosis in human prostate carcinoma cells.Biochem Biophys Res Commun. 2018 Jan 1;495(1):473-480. doi: 10.1016/j.bbrc.2017.11.040. Epub 2017 Nov 10.
• [2] Biallelic variants in COPB1 cause a novel, severe intellectual disability syndrome with cataracts and variable microcephaly. Genome Med. 2021 Feb 25;13(1):34. doi: 10.1186/s13073-021-00850-w.
• [3] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [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] 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.
• [6] Essential role of cell cycle regulatory genes p21 and p27 expression in inhibition of breast cancer cells by arsenic trioxide. Med Oncol. 2011 Dec;28(4):1225-54.
• [7] THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders. Transl Psychiatry. 2018 Apr 25;8(1):89. doi: 10.1038/s41398-018-0137-3.
• [8] 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.
• [9] Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.