Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTWBC4YL)

• DOT Name: Proteasome assembly chaperone 4 (PSMG4)
• Synonyms: PAC-4; hPAC4
• Gene Name: PSMG4
• Related Disease:
  Multiple sclerosis
  Primary biliary cholangitis
  Inflammatory bowel disease
• UniProt ID: PSMG4_HUMAN
• PDB ID: 5WTQ
• Pfam ID: PF16093
• Sequence:
  MEGLVVAAGGDVSLHNFSARLWEQLVHFHVMRLTDSLFLWVGATPHLRNLAVAMCSRYDS
  IPVSTSLLGDTSDTTSTGLAQRLARKTNKQVFVSYNLQNTDSNFALLVENRIKEEMEAFP
  EKF
• Function: Chaperone protein which promotes assembly of the 20S proteasome.

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Multiple sclerosis	DISB2WZI	Strong	Genetic Variation	[1]
Primary biliary cholangitis	DIS43E0O	Strong	Genetic Variation	[2]
Inflammatory bowel disease	DISGN23E	Disputed	Genetic Variation	[3]

11 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 Proteasome assembly chaperone 4 (PSMG4).	[4]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Proteasome assembly chaperone 4 (PSMG4).	[5]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Proteasome assembly chaperone 4 (PSMG4).	[6]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Proteasome assembly chaperone 4 (PSMG4).	[7]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Proteasome assembly chaperone 4 (PSMG4).	[8]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Proteasome assembly chaperone 4 (PSMG4).	[9]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Proteasome assembly chaperone 4 (PSMG4).	[10]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Proteasome assembly chaperone 4 (PSMG4).	[11]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Proteasome assembly chaperone 4 (PSMG4).	[12]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Proteasome assembly chaperone 4 (PSMG4).	[13]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Proteasome assembly chaperone 4 (PSMG4).	[14]

References

• [1] Genetic modifiers of multiple sclerosis progression, severity and onset.Clin Immunol. 2017 Jul;180:100-105. doi: 10.1016/j.clim.2017.05.009. Epub 2017 May 10.
• [2] A genome-wide association study identifies six novel risk loci for primary biliary cholangitis.Nat Commun. 2017 Apr 20;8:14828. doi: 10.1038/ncomms14828.
• [3] Clinical and genetic risk factors for decreased bone mineral density in Japanese patients with inflammatory bowel disease.J Gastroenterol Hepatol. 2018 Nov;33(11):1873-1881. doi: 10.1111/jgh.14149. Epub 2018 May 8.
• [4] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [5] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [6] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [7] 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.
• [8] 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.
• [9] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [10] 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.
• [11] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [12] Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem. 2012 Dec 14;287(51):43137-55.
• [13] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
• [14] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.