Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT65C86U)

• DOT Name: Golgi-resident adenosine 3',5'-bisphosphate 3'-phosphatase (BPNT2)
• Synonyms: Golgi-resident PAP phosphatase; gPAPP; EC 3.1.3.7; 3'(2'), 5'-bisphosphate nucleotidase 2; Inositol monophosphatase domain-containing protein 1; Myo-inositol monophosphatase A3; Phosphoadenosine phosphate 3'-nucleotidase
• Gene Name: BPNT2
• Related Disease: Chondrodysplasia with joint dislocations, gPAPP type
• UniProt ID: IMPA3_HUMAN
• EC Number: 3.1.3.7
• Pfam ID: PF00459
• Sequence:
  MAPMGIRLSPLGVAVFCLLGLGVLYHLYSGFLAGRFSLFGLGGEPGGGAAGPAAAADGGT
  VDLREMLAVSVLAAVRGGDEVRRVRESNVLHEKSKGKTREGAEDKMTSGDVLSNRKMFYL
  LKTAFPSVQINTEEHVDAADQEVILWDHKIPEDILKEVTTPKEVPAESVTVWIDPLDATQ
  EYTEDLRKYVTTMVCVAVNGKPMLGVIHKPFSEYTAWAMVDGGSNVKARSSYNEKTPRIV
  VSRSHSGMVKQVALQTFGNQTTIIPAGGAGYKVLALLDVPDKSQEKADLYIHVTYIKKWD
  ICAGNAILKALGGHMTTLSGEEISYTGSDGIEGGLLASIRMNHQALVRKLPDLEKTGHK
• Function: Exhibits 3'-nucleotidase activity toward adenosine 3',5'-bisphosphate (PAP), namely hydrolyzes adenosine 3',5'-bisphosphate into adenosine 5'-monophosphate (AMP) and a phosphate. May play a role in the formation of skeletal elements derived through endochondral ossification, possibly by clearing adenosine 3',5'-bisphosphate produced by Golgi sulfotransferases during glycosaminoglycan sulfation. Has no activity toward 3'-phosphoadenosine 5'-phosphosulfate (PAPS) or inositol phosphate (IP) substrates including I(1)P, I(1,4)P2, I(1,3,4)P3, I(1,4,5)P3 and I(1,3,4,5)P4.
• KEGG Pathway:
  Sulfur metabolism (hsa00920)
  Metabolic pathways (hsa01100)
  Phosphatidylinositol sig.ling system (hsa04070)
• Reactome Pathway: Cytosolic sulfonation of small molecules (R-HSA-156584)
• BioCyc Pathway: MetaCyc:HS02567-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Chondrodysplasia with joint dislocations, gPAPP type	DISCOG8O	Definitive	Autosomal recessive	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
NAPQI	DM8F5LR	Investigative	Golgi-resident adenosine 3',5'-bisphosphate 3'-phosphatase (BPNT2) affects the response to substance of NAPQI.	[14]

11 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 Golgi-resident adenosine 3',5'-bisphosphate 3'-phosphatase (BPNT2).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Golgi-resident adenosine 3',5'-bisphosphate 3'-phosphatase (BPNT2).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Golgi-resident adenosine 3',5'-bisphosphate 3'-phosphatase (BPNT2).	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Golgi-resident adenosine 3',5'-bisphosphate 3'-phosphatase (BPNT2).	[5]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Golgi-resident adenosine 3',5'-bisphosphate 3'-phosphatase (BPNT2).	[6]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Golgi-resident adenosine 3',5'-bisphosphate 3'-phosphatase (BPNT2).	[7]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Golgi-resident adenosine 3',5'-bisphosphate 3'-phosphatase (BPNT2).	[8]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Golgi-resident adenosine 3',5'-bisphosphate 3'-phosphatase (BPNT2).	[9]
Cytarabine	DMZD5QR	Approved	Cytarabine decreases the expression of Golgi-resident adenosine 3',5'-bisphosphate 3'-phosphatase (BPNT2).	[10]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Golgi-resident adenosine 3',5'-bisphosphate 3'-phosphatase (BPNT2).	[11]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Golgi-resident adenosine 3',5'-bisphosphate 3'-phosphatase (BPNT2).	[13]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Golgi-resident adenosine 3',5'-bisphosphate 3'-phosphatase (BPNT2).	[12]

References

• [1] Chondrodysplasia and abnormal joint development associated with mutations in IMPAD1, encoding the Golgi-resident nucleotide phosphatase, gPAPP. Am J Hum Genet. 2011 May 13;88(5):608-15. doi: 10.1016/j.ajhg.2011.04.002. Epub 2011 May 5.
• [2] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [3] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [4] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [5] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [6] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [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] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [9] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [10] Cytosine arabinoside induces ectoderm and inhibits mesoderm expression in human embryonic stem cells during multilineage differentiation. Br J Pharmacol. 2011 Apr;162(8):1743-56.
• [11] New insights into BaP-induced toxicity: role of major metabolites in transcriptomics and contribution to hepatocarcinogenesis. Arch Toxicol. 2016 Jun;90(6):1449-58.
• [12] 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.
• [13] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [14] Acetaminophen-NAPQI hepatotoxicity: a cell line model system genome-wide association study. Toxicol Sci. 2011 Mar;120(1):33-41. doi: 10.1093/toxsci/kfq375. Epub 2010 Dec 22.