Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTPX5PSQ)

• DOT Name: 3'(2'),5'-bisphosphate nucleotidase 1 (BPNT1)
• Synonyms: EC 3.1.3.7; 3'-phosphoadenosine 5'-phosphate phosphatase; PAP phosphatase; Bisphosphate 3'-nucleotidase 1; BPntase 1; HsPIP; Inositol-polyphosphate 1-phosphatase; EC 3.1.3.57
• Gene Name: BPNT1
• Related Disease:
  Head-neck squamous cell carcinoma
  Iron-deficiency anemia
• UniProt ID: BPNT1_HUMAN
• PDB ID: 2WEF
• EC Number: 3.1.3.57; 3.1.3.7
• Pfam ID: PF00459
• Sequence:
  MASSNTVLMRLVASAYSIAQKAGMIVRRVIAEGDLGIVEKTCATDLQTKADRLAQMSICS
  SLARKFPKLTIIGEEDLPSEEVDQELIEDSQWEEILKQPCPSQYSAIKEEDLVVWVDPLD
  GTKEYTEGLLDNVTVLIGIAYEGKAIAGVINQPYYNYEAGPDAVLGRTIWGVLGLGAFGF
  QLKEVPAGKHIITTTRSHSNKLVTDCVAAMNPDAVLRVGGAGNKIIQLIEGKASAYVFAS
  PGCKKWDTCAPEVILHAVGGKLTDIHGNVLQYHKDVKHMNSAGVLATLRNYDYYASRVPE
  SIKNALVP
• Function: Phosphatase that converts 3'(2')-phosphoadenosine 5'-phosphate (PAP) to AMP and inositol 1,4-bisphosphate (Ins(1,4)P2) to inositol 4-phosphate. Is also able to hydrolyze adenosine 3'-phosphate 5'-phosphosulfate (PAPS) to adenosine 5'-phosphosulfate (APS). Probably prevents the toxic accumulation of PAP, a compound which inhibits a variety of proteins, including PAPS-utilizing enzymes such as sulfotransferases, and RNA processing enzymes. Could also play a role in inositol recycling and phosphoinositide metabolism. Is not active on 3'-AMP, inositol-1-phosphate and inositol-1,4,5-triphosphate.
• Tissue Specificity: Highly expressed in kidney, liver, pancreas and heart. Detected at lower levels in brain, placenta, lung and skeletal muscle.
• KEGG Pathway:
  Sulfur metabolism (hsa00920)
  Metabolic pathways (hsa01100)
• Reactome Pathway: Cytosolic sulfonation of small molecules (R-HSA-156584)

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Head-neck squamous cell carcinoma	DISF7P24	Strong	Biomarker	[1]
Iron-deficiency anemia	DIS0VQYF	Limited	Biomarker	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of 3'(2'),5'-bisphosphate nucleotidase 1 (BPNT1).	[3]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of 3'(2'),5'-bisphosphate nucleotidase 1 (BPNT1).	[4]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of 3'(2'),5'-bisphosphate nucleotidase 1 (BPNT1).	[5]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of 3'(2'),5'-bisphosphate nucleotidase 1 (BPNT1).	[6]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of 3'(2'),5'-bisphosphate nucleotidase 1 (BPNT1).	[7]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of 3'(2'),5'-bisphosphate nucleotidase 1 (BPNT1).	[9]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of 3'(2'),5'-bisphosphate nucleotidase 1 (BPNT1).	[10]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of 3'(2'),5'-bisphosphate nucleotidase 1 (BPNT1).	[11]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of 3'(2'),5'-bisphosphate nucleotidase 1 (BPNT1).	[12]

1 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of 3'(2'),5'-bisphosphate nucleotidase 1 (BPNT1).	[8]

References

• [1] Subpath analysis of each subtype of head and neck cancer based on the regulatory relationship between miRNAs and biological pathways.Oncol Rep. 2015 Oct;34(4):1745-54. doi: 10.3892/or.2015.4150. Epub 2015 Jul 24.
• [2] Modulation of intestinal sulfur assimilation metabolism regulates iron homeostasis.Proc Natl Acad Sci U S A. 2018 Mar 20;115(12):3000-3005. doi: 10.1073/pnas.1715302115. Epub 2018 Mar 5.
• [3] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [4] 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.
• [5] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [6] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [7] 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.
• [8] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [9] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [10] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [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.
• [12] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.