Details of Drug Off-Target (DOT)

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

• DOT Name: Trafficking protein particle complex subunit 3 (TRAPPC3)
• Synonyms: BET3 homolog
• Gene Name: TRAPPC3
• Related Disease: Schizophrenia
• UniProt ID: TPPC3_HUMAN
• PDB ID: 1SZ7; 2C0J; 2CFH; 3KXC
• Pfam ID: PF04051
• Sequence:
  MSRQANRGTESKKMSSELFTLTYGALVTQLCKDYENDEDVNKQLDKMGFNIGVRLIEDFL
  ARSNVGRCHDFRETADVIAKVAFKMYLGITPSITNWSPAGDEFSLILENNPLVDFVELPD
  NHSSLIYSNLLCGVLRGALEMVQMAVEAKFVQDTLKGDGVTEIRMRFIRRIEDNLPAGEE
• Function: May play a role in vesicular transport from endoplasmic reticulum to Golgi.
• Reactome Pathway:
  RAB GEFs exchange GTP for GDP on RABs (R-HSA-8876198)
  COPII-mediated vesicle transport (R-HSA-204005)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Schizophrenia	DISSRV2N	Limited	Genetic Variation	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Trafficking protein particle complex subunit 3 (TRAPPC3).	[2]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Trafficking protein particle complex subunit 3 (TRAPPC3).	[3]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Trafficking protein particle complex subunit 3 (TRAPPC3).	[4]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Trafficking protein particle complex subunit 3 (TRAPPC3).	[5]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Trafficking protein particle complex subunit 3 (TRAPPC3).	[6]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Trafficking protein particle complex subunit 3 (TRAPPC3).	[7]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Trafficking protein particle complex subunit 3 (TRAPPC3).	[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 affects the methylation of Trafficking protein particle complex subunit 3 (TRAPPC3).	[8]

References

• [1] Genome-wide association study of schizophrenia in Ashkenazi Jews.Am J Med Genet B Neuropsychiatr Genet. 2015 Dec;168(8):649-59. doi: 10.1002/ajmg.b.32349. Epub 2015 Jul 21.
• [2] Stem cell transcriptome responses and corresponding biomarkers that indicate the transition from adaptive responses to cytotoxicity. Chem Res Toxicol. 2017 Apr 17;30(4):905-922.
• [3] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [4] 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.
• [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] Proteomic analysis revealed association of aberrant ROS signaling with suberoylanilide hydroxamic acid-induced autophagy in Jurkat T-leukemia cells. Autophagy. 2010 Aug;6(6):711-24. doi: 10.4161/auto.6.6.12397. Epub 2010 Aug 17.
• [7] 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.
• [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] Isobaric tags for relative and absolute quantitation-based proteomics analysis of the effect of ginger oil on bisphenol A-induced breast cancer cell proliferation. Oncol Lett. 2021 Feb;21(2):101. doi: 10.3892/ol.2020.12362. Epub 2020 Dec 8.