Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT5NRHER)

• DOT Name: Prefoldin subunit 4 (PFDN4)
• Synonyms: Protein C-1
• Gene Name: PFDN4
• Related Disease:
  Atopic dermatitis
  Breast cancer
  Breast carcinoma
  Breast neoplasm
  Colorectal carcinoma
  Hepatocellular carcinoma
  Retinoblastoma
  Neoplasm
• UniProt ID: PFD4_HUMAN
• PDB ID: 6NR8; 6NR9; 6NRB; 6NRC; 6NRD; 7WU7
• Pfam ID: PF01920
• Sequence:
  MAATMKKAAAEDVNVTFEDQQKINKFARNTSRITELKEEIEVKKKQLQNLEDACDDIMLA
  DDDCLMIPYQIGDVFISHSQEETQEMLEEAKKNLQEEIDALESRVESIQRVLADLKVQLY
  AKFGSNINLEADES
• 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

8 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Atopic dermatitis	DISTCP41	Strong	Genetic Variation	[1]
Breast cancer	DIS7DPX1	Strong	Altered Expression	[2]
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[2]
Breast neoplasm	DISNGJLM	Strong	Altered Expression	[2]
Colorectal carcinoma	DIS5PYL0	Strong	Altered Expression	[2]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[3]
Retinoblastoma	DISVPNPB	Strong	Altered Expression	[4]
Neoplasm	DISZKGEW	Limited	Genetic Variation	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Prefoldin subunit 4 (PFDN4).	[6]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Prefoldin subunit 4 (PFDN4).	[7]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Prefoldin subunit 4 (PFDN4).	[8]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Prefoldin subunit 4 (PFDN4).	[9]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Prefoldin subunit 4 (PFDN4).	[10]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Prefoldin subunit 4 (PFDN4).	[11]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide decreases the expression of Prefoldin subunit 4 (PFDN4).	[12]
Bortezomib	DMNO38U	Approved	Bortezomib increases the expression of Prefoldin subunit 4 (PFDN4).	[13]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Prefoldin subunit 4 (PFDN4).	[14]

References

• [1] Genome-wide association study identifies eight new susceptibility loci for atopic dermatitis in the Japanese population.Nat Genet. 2012 Nov;44(11):1222-6. doi: 10.1038/ng.2438. Epub 2012 Oct 7.
• [2] Abnormal expression of PFDN4 in colorectal cancer: a novel marker for prognosis.Ann Surg Oncol. 2010 Nov;17(11):3030-6. doi: 10.1245/s10434-010-1138-5. Epub 2010 Jun 15.
• [3] Multiple genes identified as targets for 20q13.12-13.33 gain contributing to unfavorable clinical outcomes in patients with hepatocellular carcinoma.Hepatol Int. 2015 Jul;9(3):438-46. doi: 10.1007/s12072-015-9642-0. Epub 2015 Jun 12.
• [4] Characterization of t(3;6)(q27;p21) breakpoints in B-cell non-Hodgkin's lymphoma and construction of the histone H4/BCL6 fusion gene, leading to altered expression of Bcl-6.Cancer Res. 2002 Nov 1;62(21):6224-30.
• [5] Comprehensive genome sequence analysis of a breast cancer amplicon.Genome Res. 2001 Jun;11(6):1034-42. doi: 10.1101/gr.gr1743r.
• [6] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [7] 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.
• [8] 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.
• [9] 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.
• [10] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [11] 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.
• [12] Microarray analysis of H2O2-, HNE-, or tBH-treated ARPE-19 cells. Free Radic Biol Med. 2002 Nov 15;33(10):1419-32.
• [13] The proapoptotic effect of zoledronic acid is independent of either the bone microenvironment or the intrinsic resistance to bortezomib of myeloma cells and is enhanced by the combination with arsenic trioxide. Exp Hematol. 2011 Jan;39(1):55-65.
• [14] 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.