Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT0TJQYZ)

• DOT Name: Proteasome assembly chaperone 3 (PSMG3)
• Synonyms: PAC-3; hPAC3
• Gene Name: PSMG3
• Related Disease:
  Distal myopathy
  Distal myopathy, Welander type
• UniProt ID: PSMG3_HUMAN
• PDB ID: 2Z5E; 6JPT
• Pfam ID: PF10178
• Sequence:
  MEDTPLVISKQKTEVVCGVPTQVVCTAFSSHILVVVTQFGKMGTLVSLEPSSVASDVSKP
  VLTTKVLLGQDEPLIHVFAKNLVAFVSQEAGNRAVLLAVAVKDKSMEGLKALREVIRVCQ
  VW
• Function: Chaperone protein which promotes assembly of the 20S proteasome. May cooperate with PSMG1-PSMG2 heterodimers to orchestrate the correct assembly of proteasomes.

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Distal myopathy	DIS7F5R0	Strong	Genetic Variation	[1]
Distal myopathy, Welander type	DISM5DNL	Strong	Biomarker	[1]

2 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 Proteasome assembly chaperone 3 (PSMG3).	[2]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Proteasome assembly chaperone 3 (PSMG3).	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Proteasome assembly chaperone 3 (PSMG3).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Proteasome assembly chaperone 3 (PSMG3).	[4]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Proteasome assembly chaperone 3 (PSMG3).	[5]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Proteasome assembly chaperone 3 (PSMG3).	[6]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of Proteasome assembly chaperone 3 (PSMG3).	[8]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Proteasome assembly chaperone 3 (PSMG3).	[9]

References

• [1] Refined mapping of the Welander distal myopathy region on chromosome 2p13 positions the new candidate region telomeric of the DYSF locus.Neurogenetics. 2003 Aug;4(4):173-7. doi: 10.1007/s10048-003-0154-z. Epub 2003 Jun 27.
• [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] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [4] 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.
• [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] 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.
• [7] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [8] A trichostatin A expression signature identified by TempO-Seq targeted whole transcriptome profiling. PLoS One. 2017 May 25;12(5):e0178302. doi: 10.1371/journal.pone.0178302. eCollection 2017.
• [9] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.