Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTR0BMH1)

DOT Name Tyrosine-protein phosphatase non-receptor type 14 (PTPN14)
Synonyms EC 3.1.3.48; Protein-tyrosine phosphatase pez
Gene Name PTPN14
Related Disease
Lymphedema-posterior choanal atresia syndrome ( )
UniProt ID
PTN14_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
2BZL; 6IWD; 6JJW
EC Number
3.1.3.48
Pfam ID
PF09380 ; PF00373 ; PF09379 ; PF00102
Sequence
MPFGLKLRRTRRYNVLSKNCFVTRIRLLDSNVIECTLSVESTGQECLEAVAQRLELRETH
YFGLWFLSKSQQARWVELEKPLKKHLDKFANEPLLFFGVMFYVPNVSWLQQEATRYQYYL
QVKKDVLEGRLRCTLDQVIRLAGLAVQADFGDYNQFDSQDFLREYVLFPMDLALEEAVLE
ELTQKVAQEHKAHSGILPAEAELMYINEVERLDGFGQEIFPVKDNHGNCVHLGIFFMGIF
VRNRIGRQAVIYRWNDMGNITHNKSTILVELINKEETALFHTDDIENAKYISRLFATRHK
FYKQNKICTEQSNSPPPIRRQPTWSRSSLPRQQPYILPPVHVQCGEHYSETHTSQDSIFH
GNEEALYCNSHNSLDLNYLNGTVTNGSVCSVHSVNSLNCSQSFIQASPVSSNLSIPGSDI
MRADYIPSHRHSAIIVPSYRPTPDYETVMRQMKRGILHTDSQSQSLRNLNIINTHAYNQP
EDLVYSQPEMRERHPYTVPYGPQGVYSNKLVSPSDQRNPKNNVVPSKPGASAISHTVSTP
ELANMQLQGSHNYSTAHMLKNYLFRPPPPYPRPRPATSTPDLASHRHKYVSGSSPDLVTR
KVQLSVKTFQEDSSPVVHQSLQEVSEPLTATKHHGTVNKRHSLEVMNSMVRGMEAMTLKS
LHLPMARRNTLREQGPPEEGSGSHEVPQLPQYHHKKTFSDATMLIHSSESEEEEEEAPES
VPQIPMLREKMEYSAQLQAALARIPNKPPPEYPGPRKSVSNGALRQDQASLPPAMARARV
LRHGPAKAISMSRTDPPAVNGASLGPSISEPDLTSVKERVKKEPVKERPVSEMFSLEDSI
IEREMMIRNLEKQKMAGLEAQKRPLMLAALNGLSVARVSGREENRVDATRVPMDERFRTL
KKKLEEGMVFTEYEQIPKKKANGIFSTAALPENAERSRIREVVPYEENRVELIPTKENNT
GYINASHIKVVVGGAEWHYIATQGPLPHTCHDFWQMVWEQGVNVIAMVTAEEEGGRTKSH
RYWPKLGSKHSSATYGKFKVTTKFRTDSVCYATTGLKVKHLLSGQERTVWHLQYTDWPDH
GCPEDVQGFLSYLEEIQSVRRHTNSMLEGTKNRHPPIVVHCSAGVGRTGVLILSELMIYC
LEHNEKVEVPMMLRLLREQRMFMIQTIAQYKFVYQVLIQFLQNSRLI
Function
Protein tyrosine phosphatase which may play a role in the regulation of lymphangiogenesis, cell-cell adhesion, cell-matrix adhesion, cell migration, cell growth and also regulates TGF-beta gene expression, thereby modulating epithelial-mesenchymal transition. Mediates beta-catenin dephosphorylation at adhesion junctions. Acts as a negative regulator of the oncogenic property of YAP, a downstream target of the hippo pathway, in a cell density-dependent manner. May function as a tumor suppressor.
Tissue Specificity Ubiquitous.
Reactome Pathway
Interleukin-37 signaling (R-HSA-9008059 )

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Lymphedema-posterior choanal atresia syndrome DIS7NHZL Strong Autosomal recessive [1]
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Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
12 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 Tyrosine-protein phosphatase non-receptor type 14 (PTPN14). [2]
Ciclosporin DMAZJFX Approved Ciclosporin increases the expression of Tyrosine-protein phosphatase non-receptor type 14 (PTPN14). [3]
Tretinoin DM49DUI Approved Tretinoin decreases the expression of Tyrosine-protein phosphatase non-receptor type 14 (PTPN14). [4]
Acetaminophen DMUIE76 Approved Acetaminophen increases the expression of Tyrosine-protein phosphatase non-receptor type 14 (PTPN14). [5]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of Tyrosine-protein phosphatase non-receptor type 14 (PTPN14). [6]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate increases the expression of Tyrosine-protein phosphatase non-receptor type 14 (PTPN14). [7]
Cisplatin DMRHGI9 Approved Cisplatin decreases the expression of Tyrosine-protein phosphatase non-receptor type 14 (PTPN14). [8]
Carbamazepine DMZOLBI Approved Carbamazepine affects the expression of Tyrosine-protein phosphatase non-receptor type 14 (PTPN14). [9]
Folic acid DMEMBJC Approved Folic acid decreases the expression of Tyrosine-protein phosphatase non-receptor type 14 (PTPN14). [10]
Seocalcitol DMKL9QO Phase 3 Seocalcitol increases the expression of Tyrosine-protein phosphatase non-receptor type 14 (PTPN14). [11]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene decreases the expression of Tyrosine-protein phosphatase non-receptor type 14 (PTPN14). [12]
Torcetrapib DMDHYM7 Discontinued in Phase 2 Torcetrapib increases the expression of Tyrosine-protein phosphatase non-receptor type 14 (PTPN14). [14]
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⏷ Show the Full List of 12 Drug(s)
2 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
PMID28870136-Compound-52 DMFDERP Patented PMID28870136-Compound-52 increases the phosphorylation of Tyrosine-protein phosphatase non-receptor type 14 (PTPN14). [13]
Bisphenol A DM2ZLD7 Investigative Bisphenol A affects the methylation of Tyrosine-protein phosphatase non-receptor type 14 (PTPN14). [15]
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References

1 Protein tyrosine phosphatase PTPN14 is a regulator of lymphatic function and choanal development in humans. Am J Hum Genet. 2010 Sep 10;87(3):436-44. doi: 10.1016/j.ajhg.2010.08.008.
2 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.
3 Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
4 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.
5 Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
6 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.
7 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
8 Real-time monitoring of cisplatin-induced cell death. PLoS One. 2011;6(5):e19714. doi: 10.1371/journal.pone.0019714. Epub 2011 May 16.
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 Folic acid supplementation dysregulates gene expression in lymphoblastoid cells--implications in nutrition. Biochem Biophys Res Commun. 2011 Sep 9;412(4):688-92. doi: 10.1016/j.bbrc.2011.08.027. Epub 2011 Aug 16.
11 Expression profiling in squamous carcinoma cells reveals pleiotropic effects of vitamin D3 analog EB1089 signaling on cell proliferation, differentiation, and immune system regulation. Mol Endocrinol. 2002 Jun;16(6):1243-56.
12 Comparative mechanisms of PAH toxicity by benzo[a]pyrene and dibenzo[def,p]chrysene in primary human bronchial epithelial cells cultured at air-liquid interface. Toxicol Appl Pharmacol. 2019 Sep 15;379:114644.
13 Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
14 Clarifying off-target effects for torcetrapib using network pharmacology and reverse docking approach. BMC Syst Biol. 2012 Dec 10;6:152.
15 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.