Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTD3WGV1)

• DOT Name: Phosducin-like protein 3 (PDCL3)
• Synonyms: HTPHLP; PhPL3; Viral IAP-associated factor 1; VIAF-1
• Gene Name: PDCL3
• Related Disease: Alzheimer disease
• UniProt ID: PDCL3_HUMAN
• PDB ID: 7NVM
• Pfam ID: PF02114
• Sequence:
  MQDPNADTEWNDILRKKGILPPKESLKELEEEAEEEQRILQQSVVKTYEDMTLEELEDHE
  DEFNEEDERAIEMYRRRRLAEWKATKLKNKFGEVLEISGKDYVQEVTKAGEGLWVILHLY
  KQGIPLCALINQHLSGLARKFPDVKFIKAISTTCIPNYPDRNLPTIFVYLEGDIKAQFIG
  PLVFGGMNLTRDELEWKLSESGAIMTDLEENPKKPIEDVLLSSVRRSVLMKRDSDSEGD
• Function: Acts as a chaperone for the angiogenic VEGF receptor KDR/VEGFR2, increasing its abundance by inhibiting its ubiquitination and degradation. Inhibits the folding activity of the chaperonin-containing T-complex (CCT) which leads to inhibition of cytoskeletal actin folding. Acts as a chaperone during heat shock alongside HSP90 and HSP40/70 chaperone complexes. Modulates the activation of caspases during apoptosis.
• Tissue Specificity: Expressed in endothelial cells (at protein level) . Expressed in all tissues examined including spleen, thymus, prostate, testis, ovary, small intestine and colon .

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Alzheimer disease	DISF8S70	Strong	Biomarker	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Phosducin-like protein 3 (PDCL3).	[2]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Phosducin-like protein 3 (PDCL3).	[3]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Phosducin-like protein 3 (PDCL3).	[4]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Phosducin-like protein 3 (PDCL3).	[5]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Phosducin-like protein 3 (PDCL3).	[6]
Progesterone	DMUY35B	Approved	Progesterone decreases the expression of Phosducin-like protein 3 (PDCL3).	[7]
Cannabidiol	DM0659E	Approved	Cannabidiol decreases the expression of Phosducin-like protein 3 (PDCL3).	[8]
Benzatropine	DMF7EXL	Approved	Benzatropine decreases the expression of Phosducin-like protein 3 (PDCL3).	[9]
PEITC	DMOMN31	Phase 2	PEITC decreases the expression of Phosducin-like protein 3 (PDCL3).	[10]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Phosducin-like protein 3 (PDCL3).	[11]

References

• [1] Family-based association analyses of imputed genotypes reveal genome-wide significant association of Alzheimer's disease with OSBPL6, PTPRG, and PDCL3.Mol Psychiatry. 2016 Nov;21(11):1608-1612. doi: 10.1038/mp.2015.218. Epub 2016 Feb 2.
• [2] 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.
• [3] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [4] 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.
• [5] Arsenic targets Pin1 and cooperates with retinoic acid to inhibit cancer-driving pathways and tumor-initiating cells. Nat Commun. 2018 Aug 9;9(1):3069. doi: 10.1038/s41467-018-05402-2.
• [6] Minimal peroxide exposure of neuronal cells induces multifaceted adaptive responses. PLoS One. 2010 Dec 17;5(12):e14352. doi: 10.1371/journal.pone.0014352.
• [7] Gene expression in endometrial cancer cells (Ishikawa) after short time high dose exposure to progesterone. Steroids. 2008 Jan;73(1):116-28.
• [8] Cannabidiol Modulates the Immunophenotype and Inhibits the Activation of the Inflammasome in Human Gingival Mesenchymal Stem Cells. Front Physiol. 2016 Nov 24;7:559. doi: 10.3389/fphys.2016.00559. eCollection 2016.
• [9] Cannabidiol Displays Proteomic Similarities to Antipsychotics in Cuprizone-Exposed Human Oligodendrocytic Cell Line MO3.13. Front Mol Neurosci. 2021 May 28;14:673144. doi: 10.3389/fnmol.2021.673144. eCollection 2021.
• [10] Phenethyl isothiocyanate alters the gene expression and the levels of protein associated with cell cycle regulation in human glioblastoma GBM 8401 cells. Environ Toxicol. 2017 Jan;32(1):176-187.
• [11] Low-dose Bisphenol A exposure alters the functionality and cellular environment in a human cardiomyocyte model. Environ Pollut. 2023 Oct 15;335:122359. doi: 10.1016/j.envpol.2023.122359. Epub 2023 Aug 9.