Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTSASU6U)

• DOT Name: Trafficking protein particle complex subunit 1 (TRAPPC1)
• Synonyms: BET5 homolog; Multiple myeloma protein 2; MUM-2
• Gene Name: TRAPPC1
• Related Disease: Chronic hepatitis B virus infection
• UniProt ID: TPPC1_HUMAN
• Pfam ID: PF04099
• Sequence:
  MTVHNLYLFDRNGVCLHYSEWHRKKQAGIPKEEEYKLMYGMLFSIRSFVSKMSPLDMKDG
  FLAFQTSRYKLHYYETPTGIKVVMNTDLGVGPIRDVLHHIYSALYVELVVKNPLCPLGQT
  VQSELFRSRLDSYVRSLPFFSARAG
• Function: May play a role in vesicular transport from endoplasmic reticulum to Golgi.
• Reactome Pathway:
  Neutrophil degranulation (R-HSA-6798695)
  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
Chronic hepatitis B virus infection	DISHL4NT	moderate	Biomarker	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Trafficking protein particle complex subunit 1 (TRAPPC1).	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Trafficking protein particle complex subunit 1 (TRAPPC1).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Trafficking protein particle complex subunit 1 (TRAPPC1).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Trafficking protein particle complex subunit 1 (TRAPPC1).	[5]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Trafficking protein particle complex subunit 1 (TRAPPC1).	[6]

References

• [1] Comparison of hepatic oxidative DNA damage in patients with chronic hepatitis B and C.J Viral Hepat. 2008 Jul;15(7):498-507. doi: 10.1111/j.1365-2893.2008.00972.x. Epub 2008 Mar 6.
• [2] 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.
• [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] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [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.