Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTEMF20S)

• DOT Name: Proteasome assembly chaperone 2 (PSMG2)
• Synonyms: PAC-2; Hepatocellular carcinoma-susceptibility protein 3; Tumor necrosis factor superfamily member 5-induced protein 1
• Gene Name: PSMG2
• Related Disease:
  Carcinoma of liver and intrahepatic biliary tract
  Hepatocellular carcinoma
  Herpes simplex infection
  Liver cancer
  Neoplasm
  Myelodysplastic syndrome
  Proteasome-associated autoinflammatory syndrome 4
• UniProt ID: PSMG2_HUMAN
• Pfam ID: PF09754
• Sequence:
  MFVPCGESAPDLAGFTLLMPAVSVGNVGQLAMDLIISTLNMSKIGYFYTDCLVPMVGNNP
  YATTEGNSTELSINAEVYSLPSRKLVALQLRSIFIKYKSKPFCEKLLSWVKSSGCARVIV
  LSSSHSYQRNDLQLRSTPFRYLLTPSMQKSVQNKIKSLNWEEMEKSRCIPEIDDSEFCIR
  IPGGGITKTLYDESCSKEIQMAVLLKFVSEGDNIPDALGLVEYLNEWLQILKPLSDDPTV
  SASRWKIPSSWRLLFGSGLPPALF
• Function: Chaperone protein which promotes assembly of the 20S proteasome as part of a heterodimer with PSMG1. The PSMG1-PSMG2 heterodimer binds to the PSMA5 and PSMA7 proteasome subunits, promotes assembly of the proteasome alpha subunits into the heteroheptameric alpha ring and prevents alpha ring dimerization.
• Tissue Specificity: Widely expressed with highest levels in lung, brain and colon. Moderately expressed in muscle, stomach, spleen and heart. Weakly expressed in small intestine, pancreas and liver. Highly expressed in hepatocellular carcinomas with low levels in surrounding liver tissue.

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Carcinoma of liver and intrahepatic biliary tract	DIS8WA0W	Strong	Genetic Variation	[1]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[1]
Herpes simplex infection	DISL1SAV	Strong	Biomarker	[2]
Liver cancer	DISDE4BI	Strong	Genetic Variation	[1]
Neoplasm	DISZKGEW	Strong	Biomarker	[1]
Myelodysplastic syndrome	DISYHNUI	moderate	Biomarker	[3]
Proteasome-associated autoinflammatory syndrome 4	DIS9ALLL	Limited	Unknown	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Proteasome assembly chaperone 2 (PSMG2).	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Proteasome assembly chaperone 2 (PSMG2).	[6]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Proteasome assembly chaperone 2 (PSMG2).	[7]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Proteasome assembly chaperone 2 (PSMG2).	[8]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Proteasome assembly chaperone 2 (PSMG2).	[9]

References

• [1] Expression of liver cancer associated gene HCCA3.World J Gastroenterol. 2001 Dec;7(6):821-5. doi: 10.3748/wjg.v7.i6.821.
• [2] A host cell protein binds to a highly conserved sequence element (pac-2) within the cytomegalovirus a sequence.J Virol. 1989 Nov;63(11):4715-28. doi: 10.1128/JVI.63.11.4715-4728.1989.
• [3] Short- and long-term benefits of lenalidomide treatment in patients with lower-risk del(5q) myelodysplastic syndromes.Ann Oncol. 2016 Jan;27(1):62-8. doi: 10.1093/annonc/mdv488. Epub 2015 Oct 26.
• [4] Novel proteasome assembly chaperone mutations in PSMG2/PAC2 cause the autoinflammatory interferonopathy CANDLE/PRAAS4. J Allergy Clin Immunol. 2019 May;143(5):1939-1943.e8. doi: 10.1016/j.jaci.2018.12.1012. Epub 2019 Jan 18.
• [5] 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.
• [6] 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.
• [7] 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.
• [8] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [9] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.