Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTN3D4ZM)

• DOT Name: Pyridoxal phosphate phosphatase PHOSPHO2 (PHOSPHO2)
• Synonyms: EC 3.1.3.74
• Gene Name: PHOSPHO2
• UniProt ID: PHOP2_HUMAN
• EC Number: 3.1.3.74
• Pfam ID: PF06888
• Sequence:
  MKILLVFDFDNTIIDDNSDTWIVQCAPNKKLPIELRDSYRKGFWTEFMGRVFKYLGDKGV
  REHEMKRAVTSLPFTPGMVELFNFIRKNKDKFDCIIISDSNSVFIDWVLEAASFHDIFDK
  VFTNPAAFNSNGHLTVENYHTHSCNRCPKNLCKKVVLIEFVDKQLQQGVNYTQIVYIGDG
  GNDVCPVTFLKNDDVAMPRKGYTLQKTLSRMSQNLEPMEYSVVVWSSGVDIISHLQFLIK
  D
• Function: Phosphatase that has high activity toward pyridoxal 5'-phosphate (PLP). Also active at much lower level toward pyrophosphate, phosphoethanolamine (PEA), phosphocholine (PCho), phospho-l-tyrosine, fructose-6-phosphate, p-nitrophenyl phosphate, and h-glycerophosphate.
• KEGG Pathway:
  Vitamin B6 metabolism (hsa00750)
  Metabolic pathways (hsa01100)
  Biosynthesis of cofactors (hsa01240)
• BioCyc Pathway: MetaCyc:HS07168-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Pyridoxal phosphate phosphatase PHOSPHO2 (PHOSPHO2).	[1]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Pyridoxal phosphate phosphatase PHOSPHO2 (PHOSPHO2).	[2]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Pyridoxal phosphate phosphatase PHOSPHO2 (PHOSPHO2).	[3]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Pyridoxal phosphate phosphatase PHOSPHO2 (PHOSPHO2).	[4]
Quercetin	DM3NC4M	Approved	Quercetin affects the expression of Pyridoxal phosphate phosphatase PHOSPHO2 (PHOSPHO2).	[5]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of Pyridoxal phosphate phosphatase PHOSPHO2 (PHOSPHO2).	[6]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Pyridoxal phosphate phosphatase PHOSPHO2 (PHOSPHO2).	[7]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Pyridoxal phosphate phosphatase PHOSPHO2 (PHOSPHO2).	[8]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Pyridoxal phosphate phosphatase PHOSPHO2 (PHOSPHO2).	[9]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Pyridoxal phosphate phosphatase PHOSPHO2 (PHOSPHO2).	[10]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of Pyridoxal phosphate phosphatase PHOSPHO2 (PHOSPHO2).	[11]

References

• [1] 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.
• [2] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [3] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [4] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [5] 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.
• [6] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
• [7] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [8] Differentially expressed genes in the prostate cancer cell line LNCaP after exposure to androgen and anti-androgen. Cancer Genet Cytogenet. 2006 Apr 15;166(2):130-8. doi: 10.1016/j.cancergencyto.2005.09.012.
• [9] Synergistic effect of JQ1 and rapamycin for treatment of human osteosarcoma. Int J Cancer. 2015 May 1;136(9):2055-64.
• [10] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [11] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.