Details of Drug Off-Target (DOT)

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

• DOT Name: Protein tyrosine phosphatase type IVA 3 (PTP4A3)
• Synonyms: EC 3.1.3.48; PRL-R; Protein-tyrosine phosphatase 4a3; Protein-tyrosine phosphatase of regenerating liver 3; PRL-3
• Gene Name: PTP4A3
• UniProt ID: TP4A3_HUMAN
• PDB ID: 1R6H; 1V3A; 2MBC; 5TSR
• EC Number: 3.1.3.48
• Pfam ID: PF00102
• Sequence:
  MARMNRPAPVEVSYKHMRFLITHNPTNATLSTFIEDLKKYGATTVVRVCEVTYDKTPLEK
  DGITVVDWPFDDGAPPPGKVVEDWLSLVKAKFCEAPGSCVAVHCVAGLGRAPVLVALALI
  ESGMKYEDAIQFIRQKRRGAINSKQLTYLEKYRPKQRLRFKDPHTHKTRCCVM
• Function: Protein tyrosine phosphatase which stimulates progression from G1 into S phase during mitosis. Enhances cell proliferation, cell motility and invasive activity, and promotes cancer metastasis. May be involved in the progression of cardiac hypertrophy by inhibiting intracellular calcium mobilization in response to angiotensin II.
• Tissue Specificity: Mainly expressed in cardiomyocytes and skeletal muscle; also found in pancreas. Consistently overexpressed in colon cancer metastasis.

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Protein tyrosine phosphatase type IVA 3 (PTP4A3).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Protein tyrosine phosphatase type IVA 3 (PTP4A3).	[8]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Protein tyrosine phosphatase type IVA 3 (PTP4A3).	[2]
Estradiol	DMUNTE3	Approved	Estradiol affects the expression of Protein tyrosine phosphatase type IVA 3 (PTP4A3).	[3]
Quercetin	DM3NC4M	Approved	Quercetin affects the expression of Protein tyrosine phosphatase type IVA 3 (PTP4A3).	[4]
Bortezomib	DMNO38U	Approved	Bortezomib decreases the expression of Protein tyrosine phosphatase type IVA 3 (PTP4A3).	[5]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Protein tyrosine phosphatase type IVA 3 (PTP4A3).	[6]
Belinostat	DM6OC53	Phase 2	Belinostat decreases the expression of Protein tyrosine phosphatase type IVA 3 (PTP4A3).	[7]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Protein tyrosine phosphatase type IVA 3 (PTP4A3).	[9]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Protein tyrosine phosphatase type IVA 3 (PTP4A3).	[10]

References

• [1] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [2] 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.
• [3] Identification of novel low-dose bisphenol a targets in human foreskin fibroblast cells derived from hypospadias patients. PLoS One. 2012;7(5):e36711. doi: 10.1371/journal.pone.0036711. Epub 2012 May 4.
• [4] 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.
• [5] The proapoptotic effect of zoledronic acid is independent of either the bone microenvironment or the intrinsic resistance to bortezomib of myeloma cells and is enhanced by the combination with arsenic trioxide. Exp Hematol. 2011 Jan;39(1):55-65.
• [6] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [7] 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.
• [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.