Details of Drug Off-Target (DOT)

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

• DOT Name: Protein tyrosine phosphatase type IVA 2 (PTP4A2)
• Synonyms: EC 3.1.3.48; HU-PP-1; OV-1; PTP(CAAXII); Protein-tyrosine phosphatase 4a2; Protein-tyrosine phosphatase of regenerating liver 2; PRL-2
• Gene Name: PTP4A2
• UniProt ID: TP4A2_HUMAN
• PDB ID: 5K22; 5K23; 5K25; 6WUR
• EC Number: 3.1.3.48
• Pfam ID: PF00102
• Sequence:
  MNRPAPVEISYENMRFLITHNPTNATLNKFTEELKKYGVTTLVRVCDATYDKAPVEKEGI
  HVLDWPFDDGAPPPNQIVDDWLNLLKTKFREEPGCCVAVHCVAGLGRAPVLVALALIECG
  MKYEDAVQFIRQKRRGAFNSKQLLYLEKYRPKMRLRFRDTNGHCCVQ
• Function: Protein tyrosine phosphatase which stimulates progression from G1 into S phase during mitosis. Promotes tumors. Inhibits geranylgeranyl transferase type II activity by blocking the association between RABGGTA and RABGGTB.
• Tissue Specificity: Ubiquitously expressed, with highest levels in skeletal muscle, heart and thymus. Overexpressed in prostate tumor tissue.
• Reactome Pathway: RAB geranylgeranylation (R-HSA-8873719)

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 Protein tyrosine phosphatase type IVA 2 (PTP4A2).	[1]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Protein tyrosine phosphatase type IVA 2 (PTP4A2).	[2]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Protein tyrosine phosphatase type IVA 2 (PTP4A2).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Protein tyrosine phosphatase type IVA 2 (PTP4A2).	[4]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Protein tyrosine phosphatase type IVA 2 (PTP4A2).	[5]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Protein tyrosine phosphatase type IVA 2 (PTP4A2).	[6]
Piroxicam	DMTK234	Approved	Piroxicam decreases the expression of Protein tyrosine phosphatase type IVA 2 (PTP4A2).	[7]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Protein tyrosine phosphatase type IVA 2 (PTP4A2).	[9]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Protein tyrosine phosphatase type IVA 2 (PTP4A2).	[10]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Protein tyrosine phosphatase type IVA 2 (PTP4A2).	[11]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Protein tyrosine phosphatase type IVA 2 (PTP4A2).	[12]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Protein tyrosine phosphatase type IVA 2 (PTP4A2).	[8]

References

• [1] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [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] 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.
• [4] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [5] 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.
• [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] Apoptosis induced by piroxicam plus cisplatin combined treatment is triggered by p21 in mesothelioma. PLoS One. 2011;6(8):e23569.
• [8] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [9] Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem. 2012 Dec 14;287(51):43137-55.
• [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] Characterization of the Molecular Alterations Induced by the Prolonged Exposure of Normal Colon Mucosa and Colon Cancer Cells to Low-Dose Bisphenol A. Int J Mol Sci. 2022 Oct 1;23(19):11620. doi: 10.3390/ijms231911620.
• [12] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.