Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTUYWQ4Z)

• DOT Name: Prefoldin subunit 2 (PFDN2)
• Gene Name: PFDN2
• Related Disease: Non-insulin dependent diabetes
• UniProt ID: PFD2_HUMAN
• PDB ID: 6NR8; 6NR9; 6NRB; 6NRC; 6NRD; 7WU7
• Pfam ID: PF01920
• Sequence:
  MAENSGRAGKSSGSGAGKGAVSAEQVIAGFNRLRQEQRGLASKAAELEMELNEHSLVIDT
  LKEVDETRKCYRMVGGVLVERTVKEVLPALENNKEQIQKIIETLTQQLQAKGKELNEFRE
  KHNIRLMGEDEKPAAKENSEGAGAKASSAGVLVS
• Function: Binds specifically to cytosolic chaperonin (c-CPN) and transfers target proteins to it. Binds to nascent polypeptide chain and promotes folding in an environment in which there are many competing pathways for nonnative proteins.
• Reactome Pathway: Prefoldin mediated transfer of substrate to CCT/TriC (R-HSA-389957)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Non-insulin dependent diabetes	DISK1O5Z	Limited	Biomarker	[1]

13 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 Prefoldin subunit 2 (PFDN2).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Prefoldin subunit 2 (PFDN2).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Prefoldin subunit 2 (PFDN2).	[4]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Prefoldin subunit 2 (PFDN2).	[5]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide increases the expression of Prefoldin subunit 2 (PFDN2).	[7]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Prefoldin subunit 2 (PFDN2).	[8]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Prefoldin subunit 2 (PFDN2).	[9]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Prefoldin subunit 2 (PFDN2).	[11]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Prefoldin subunit 2 (PFDN2).	[12]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Prefoldin subunit 2 (PFDN2).	[13]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Prefoldin subunit 2 (PFDN2).	[14]
methyl p-hydroxybenzoate	DMO58UW	Investigative	methyl p-hydroxybenzoate increases the expression of Prefoldin subunit 2 (PFDN2).	[15]
Okadaic acid	DM47CO1	Investigative	Okadaic acid increases the expression of Prefoldin subunit 2 (PFDN2).	[16]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Prefoldin subunit 2 (PFDN2).	[6]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Prefoldin subunit 2 (PFDN2).	[10]

References

• [1] Autoantibodies against PFDN2 are associated with an increased risk of type 2 diabetes: A case-control study.Diabetes Metab Res Rev. 2017 Nov;33(8):10.1002/dmrr.2922. doi: 10.1002/dmrr.2922. Epub 2017 Aug 30.
• [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] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [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] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [7] MS4A3-HSP27 target pathway reveals potential for haematopoietic disorder treatment in alimentary toxic aleukia. Cell Biol Toxicol. 2023 Feb;39(1):201-216. doi: 10.1007/s10565-021-09639-4. Epub 2021 Sep 28.
• [8] Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 30.
• [9] 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.
• [10] 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.
• [11] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [12] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [13] Alternatives for the worse: Molecular insights into adverse effects of bisphenol a and substitutes during human adipocyte differentiation. Environ Int. 2021 Nov;156:106730. doi: 10.1016/j.envint.2021.106730. Epub 2021 Jun 27.
• [14] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [15] Transcriptome dynamics of alternative splicing events revealed early phase of apoptosis induced by methylparaben in H1299 human lung carcinoma cells. Arch Toxicol. 2020 Jan;94(1):127-140. doi: 10.1007/s00204-019-02629-w. Epub 2019 Nov 20.
• [16] Whole genome mRNA transcriptomics analysis reveals different modes of action of the diarrheic shellfish poisons okadaic acid and dinophysis toxin-1 versus azaspiracid-1 in Caco-2 cells. Toxicol In Vitro. 2018 Feb;46:102-112.