Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTKJMB1Q)

• DOT Name: Conserved oligomeric Golgi complex subunit 3 (COG3)
• Synonyms: COG complex subunit 3; Component of oligomeric Golgi complex 3; Vesicle-docking protein SEC34 homolog; p94
• Gene Name: COG3
• Related Disease:
  Autosomal recessive limb-girdle muscular dystrophy type 2A
  Neoplasm
• UniProt ID: COG3_HUMAN
• Pfam ID: PF20671 ; PF04136
• Sequence:
  MAEAALLLLPEAAAERDAREKLALWDRRPDTTAPLTDRQTDSVLELKAAAENLPVPAELP
  IEDLCSLTSQSLPIELTSVVPESTEDILLKGFTSLGMEEERIETAQQFFSWFAKLQTQMD
  QDEGTKYRQMRDYLSGFQEQCDAILNDVNSALQHLESLQKQYLFVSNKTGTLHEACEQLL
  KEQSELVDLAENIQQKLSYFNELETINTKLNSPTLSVNSDGFIPMLAKLDDCITYISSHP
  NFKDYPIYLLKFKQCLSKALHLMKTYTVNTLQTLTSQLLKRDPSSVPNADNAFTLFYVKF
  RAAAPKVRTLIEQIELRSEKIPEYQQLLNDIHQCYLDQRELLLGPSIACTVAELTSQNNR
  DHCALVRSGCAFMVHVCQDEHQLYNEFFTKPTSKLDELLEKLCVSLYDVFRPLIIHVIHL
  ETLSELCGILKNEVLEDHVQNNAEQLGAFAAGVKQMLEDVQERLVYRTHIYIQTDITGYK
  PAPGDLAYPDKLVMMEQIAQSLKDEQKKVPSEASFSDVHLEEGESNSLTKSGSTESLNPR
  PQTTISPADLHGMWYPTVRRTLVCLSKLYRCIDRAVFQGLSQEALSACIQSLLGASESIS
  KNKTQIDGQLFLIKHLLILREQIAPFHTEFTIKEISLDLKKTRDAAFKILNPMTVPRFFR
  LNSNNALIEFLLEGTPEIREHYLDSKKDVDRHLKSACEQFIQQQTKLFVEQLEEFMTKVS
  ALKTMASQGGPKYTLSQQPWAQPAKVNDLAATAYKTIKTKLPVTLRSMSLYLSNKDTEFI
  LFKPVRNNIQQVFQKFHALLKEEFSPEDIQIIACPSMEQLSLLLLVSK
• Function: Involved in ER-Golgi transport.
• Tissue Specificity: Widely expressed with highest levels in pancreas and testis and lowest levels in lung.
• Reactome Pathway:
  Intra-Golgi traffic (R-HSA-6811438)
  Retrograde transport at the Trans-Golgi-Network (R-HSA-6811440)
  COPI-mediated anterograde transport (R-HSA-6807878)

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Autosomal recessive limb-girdle muscular dystrophy type 2A	DISIHX4S	Strong	Biomarker	[1]
Neoplasm	DISZKGEW	Strong	Biomarker	[2]

10 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 Conserved oligomeric Golgi complex subunit 3 (COG3).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Conserved oligomeric Golgi complex subunit 3 (COG3).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Conserved oligomeric Golgi complex subunit 3 (COG3).	[5]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Conserved oligomeric Golgi complex subunit 3 (COG3).	[6]
Marinol	DM70IK5	Approved	Marinol decreases the expression of Conserved oligomeric Golgi complex subunit 3 (COG3).	[7]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Conserved oligomeric Golgi complex subunit 3 (COG3).	[8]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of Conserved oligomeric Golgi complex subunit 3 (COG3).	[9]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Conserved oligomeric Golgi complex subunit 3 (COG3).	[10]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Conserved oligomeric Golgi complex subunit 3 (COG3).	[11]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Conserved oligomeric Golgi complex subunit 3 (COG3).	[12]

References

• [1] Skeletal muscle-specific calpain is an intracellular Na+-dependent protease.J Biol Chem. 2010 Jul 23;285(30):22986-98. doi: 10.1074/jbc.M110.126946. Epub 2010 May 11.
• [2] Intravenous and intratumoral injection of Pluronic P94: The effect of administration route on biodistribution and tumor retention.Nanomedicine. 2017 Oct;13(7):2179-2188. doi: 10.1016/j.nano.2017.04.015. Epub 2017 May 20.
• [3] 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.
• [4] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [5] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [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] 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] 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.
• [9] Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.
• [10] Environmental pollutant induced cellular injury is reflected in exosomes from placental explants. Placenta. 2020 Jan 1;89:42-49. doi: 10.1016/j.placenta.2019.10.008. Epub 2019 Oct 17.
• [11] Gene expression changes in primary human nasal epithelial cells exposed to formaldehyde in vitro. Toxicol Lett. 2010 Oct 5;198(2):289-95.
• [12] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.