Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT9DZ8P6)

• DOT Name: Pyridoxal phosphate homeostasis protein (PLPBP)
• Synonyms: PLP homeostasis protein; Proline synthase co-transcribed bacterial homolog protein; Pyridoxal phosphate-binding protein
• Gene Name: PLPBP
• Related Disease:
  Aromatic L-amino acid decarboxylase deficiency
  Epilepsy
  Epilepsy, early-onset, vitamin B6-dependent
  Hyperprolinemia type 2
  Hypophosphatasia
  Movement disorder
  Pyridoxine-dependent epilepsy
• UniProt ID: PLPHP_HUMAN
• Pfam ID: PF01168
• Sequence:
  MWRAGSMSAELGVGCALRAVNERVQQAVARRPRDLPAIQPRLVAVSKTKPADMVIEAYGH
  GQRTFGENYVQELLEKASNPKILSLCPEIKWHFIGHLQKQNVNKLMAVPNLFMLETVDSV
  KLADKVNSSWQRKGSPERLKVMVQINTSGEESKHGLPPSETIAIVEHINAKCPNLEFVGL
  MTIGSFGHDLSQGPNPDFQLLLSLREELCKKLNIPADQVELSMGMSADFQHAVEVGSTNV
  RIGSTIFGERDYSKKPTPDKCAADVKAPLEVAQEH
• Function: Pyridoxal 5'-phosphate (PLP)-binding protein, which may be involved in intracellular homeostatic regulation of pyridoxal 5'-phosphate (PLP), the active form of vitamin B6.
• Tissue Specificity: Ubiquitous.

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Aromatic L-amino acid decarboxylase deficiency	DIS3C407	Strong	Genetic Variation	[1]
Epilepsy	DISBB28L	Strong	Genetic Variation	[1]
Epilepsy, early-onset, vitamin B6-dependent	DISZ3FZU	Strong	Autosomal recessive	[2]
Hyperprolinemia type 2	DISSEJ2T	Strong	Biomarker	[3]
Hypophosphatasia	DISCQ0O2	Strong	Biomarker	[3]
Movement disorder	DISOJJ2D	Strong	Genetic Variation	[1]
Pyridoxine-dependent epilepsy	DISVYADQ	Supportive	Autosomal recessive	[2]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Mitoxantrone	DMM39BF	Approved	Pyridoxal phosphate homeostasis protein (PLPBP) affects the response to substance of Mitoxantrone.	[11]

7 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 Pyridoxal phosphate homeostasis protein (PLPBP).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Pyridoxal phosphate homeostasis protein (PLPBP).	[5]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Pyridoxal phosphate homeostasis protein (PLPBP).	[6]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Pyridoxal phosphate homeostasis protein (PLPBP).	[7]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Pyridoxal phosphate homeostasis protein (PLPBP).	[8]
Haloperidol	DM96SE0	Approved	Haloperidol increases the expression of Pyridoxal phosphate homeostasis protein (PLPBP).	[9]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Pyridoxal phosphate homeostasis protein (PLPBP).	[10]

References

• [1] PLPHP deficiency: clinical, genetic, biochemical, and mechanistic insights.Brain. 2019 Mar 1;142(3):542-559. doi: 10.1093/brain/awy346.
• [2] Mutations in PROSC Disrupt Cellular Pyridoxal Phosphate Homeostasis and Cause Vitamin-B(6)-Dependent Epilepsy. Am J Hum Genet. 2016 Dec 1;99(6):1325-1337. doi: 10.1016/j.ajhg.2016.10.011.
• [3] Disorders affecting vitamin B(6) metabolism.J Inherit Metab Dis. 2019 Jul;42(4):629-646. doi: 10.1002/jimd.12060. Epub 2019 Mar 20.
• [4] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [5] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [6] 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.
• [7] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [8] Minimal peroxide exposure of neuronal cells induces multifaceted adaptive responses. PLoS One. 2010 Dec 17;5(12):e14352. doi: 10.1371/journal.pone.0014352.
• [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] 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.
• [11] Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.