Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTI8IPNC)

• DOT Name: Prefoldin subunit 6 (PFDN6)
• Synonyms: Protein Ke2
• Gene Name: PFDN6
• Related Disease:
  Advanced cancer
  Childhood acute lymphoblastic leukemia
• UniProt ID: PFD6_HUMAN
• PDB ID: 6NR8; 6NR9; 6NRB; 6NRC; 6NRD; 7WU7
• Pfam ID: PF01920
• Sequence:
  MAELIQKKLQGEVEKYQQLQKDLSKSMSGRQKLEAQLTENNIVKEELALLDGSNVVFKLL
  GPVLVKQELGEARATVGKRLDYITAEIKRYESQLRDLERQSEQQRETLAQLQQEFQRAQA
  AKAGAPGKA
• 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

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Childhood acute lymphoblastic leukemia	DISJ5D6U	Strong	Altered Expression	[2]

3 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 Prefoldin subunit 6 (PFDN6).	[3]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Prefoldin subunit 6 (PFDN6).	[8]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Prefoldin subunit 6 (PFDN6).	[9]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Prefoldin subunit 6 (PFDN6).	[4]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Prefoldin subunit 6 (PFDN6).	[5]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol decreases the expression of Prefoldin subunit 6 (PFDN6).	[6]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Prefoldin subunit 6 (PFDN6).	[7]

References

• [1] Characterization of HKE2: an ancient antigen encoded in the major histocompatibility complex.Tissue Antigens. 2007 Feb;69(2):181-8. doi: 10.1111/j.1399-0039.2006.00730.x.
• [2] Identification of potential predictive markers of dexamethasone resistance in childhood acute lymphoblastic leukemia.J Cell Commun Signal. 2017 Jun;11(2):137-145. doi: 10.1007/s12079-016-0357-3. Epub 2016 Oct 24.
• [3] 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.
• [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] Identification of biomarkers and outcomes of endocrine disruption in human ovarian cortex using In Vitro Models. Toxicology. 2023 Feb;485:153425. doi: 10.1016/j.tox.2023.153425. Epub 2023 Jan 5.
• [7] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [8] 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.
• [9] 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.