Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT5WDPXB)

• DOT Name: Tyrosine-protein phosphatase non-receptor type 23 (PTPN23)
• Synonyms: EC 3.1.3.48; His domain-containing protein tyrosine phosphatase; HD-PTP; Protein tyrosine phosphatase TD14; PTP-TD14
• Gene Name: PTPN23
• Related Disease:
  Advanced cancer
  Breast neoplasm
  Germ cell tumor
  Intellectual disability
  Myopia
  Neurodevelopmental disorder and structural brain anomalies with or without seizures and spasticity
  Non-insulin dependent diabetes
  Sarcoidosis
  Neoplasm
  Breast cancer
  Breast carcinoma
• UniProt ID: PTN23_HUMAN
• PDB ID: 3RAU; 5CRU; 5CRV; 5LM1; 5LM2; 5MJY; 5MJZ; 5MK0; 5MK1; 5MK2; 5MK3
• EC Number: 3.1.3.48
• Pfam ID: PF13949 ; PF03097 ; PF00102
• Sequence:
  MEAVPRMPMIWLDLKEAGDFHFQPAVKKFVLKNYGENPEAYNEELKKLELLRQNAVRVPR
  DFEGCSVLRKYLGQLHYLQSRVPMGSGQEAAVPVTWTEIFSGKSVAHEDIKYEQACILYN
  LGALHSMLGAMDKRVSEEGMKVSCTHFQCAAGAFAYLREHFPQAYSVDMSRQILTLNVNL
  MLGQAQECLLEKSMLDNRKSFLVARISAQVVDYYKEACRALENPDTASLLGRIQKDWKKL
  VQMKIYYFAAVAHLHMGKQAEEQQKFGERVAYFQSALDKLNEAIKLAKGQPDTVQDALRF
  TMDVIGGKYNSAKKDNDFIYHEAVPALDTLQPVKGAPLVKPLPVNPTDPAVTGPDIFAKL
  VPMAAHEASSLYSEEKAKLLREMMAKIEDKNEVLDQFMDSMQLDPETVDNLDAYSHIPPQ
  LMEKCAALSVRPDTVRNLVQSMQVLSGVFTDVEASLKDIRDLLEEDELLEQKFQEAVGQA
  GAISITSKAELAEVRREWAKYMEVHEKASFTNSELHRAMNLHVGNLRLLSGPLDQVRAAL
  PTPALSPEDKAVLQNLKRILAKVQEMRDQRVSLEQQLRELIQKDDITASLVTTDHSEMKK
  LFEEQLKKYDQLKVYLEQNLAAQDRVLCALTEANVQYAAVRRVLSDLDQKWNSTLQTLVA
  SYEAYEDLMKKSQEGRDFYADLESKVAALLERTQSTCQAREAARQQLLDRELKKKPPPRP
  TAPKPLLPRREESEAVEAGDPPEELRSLPPDMVAGPRLPDTFLGSATPLHFPPSPFPSST
  GPGPHYLSGPLPPGTYSGPTQLIQPRAPGPHAMPVAPGPALYPAPAYTPELGLVPRSSPQ
  HGVVSSPYVGVGPAPPVAGLPSAPPPQFSGPELAMAVRPATTTVDSIQAPIPSHTAPRPN
  PTPAPPPPCFPVPPPQPLPTPYTYPAGAKQPIPAQHHFSSGIPAGFPAPRIGPQPQPHPQ
  PHPSQAFGPQPPQQPLPLQHPHLFPPQAPGLLPPQSPYPYAPQPGVLGQPPPPLHTQLYP
  GPAQDPLPAHSGALPFPSPGPPQPPHPPLAYGPAPSTRPMGPQAAPLTIRGPSSAGQSTP
  SPHLVPSPAPSPGPGPVPPRPPAAEPPPCLRRGAAAADLLSSSPESQHGGTQSPGGGQPL
  LQPTKVDAAEGRRPQALRLIERDPYEHPERLRQLQQELEAFRGQLGDVGALDTVWRELQD
  AQEHDARGRSIAIARCYSLKNRHQDVMPYDSNRVVLRSGKDDYINASCVEGLSPYCPPLV
  ATQAPLPGTAADFWLMVHEQKVSVIVMLVSEAEMEKQKVARYFPTERGQPMVHGALSLAL
  SSVRSTETHVERVLSLQFRDQSLKRSLVHLHFPTWPELGLPDSPSNLLRFIQEVHAHYLH
  QRPLHTPIIVHCSSGVGRTGAFALLYAAVQEVEAGNGIPELPQLVRRMRQQRKHMLQEKL
  HLRFCYEAVVRHVEQVLQRHGVPPPCKPLASASISQKNHLPQDSQDLVLGGDVPISSIQA
  TIAKLSIRPPGGLESPVASLPGPAEPPGLPPASLPESTPIPSSSPPPLSSPLPEAPQPKE
  EPPVPEAPSSGPPSSSLELLASLTPEAFSLDSSLRGKQRMSKHNFLQAHNGQGLRATRPS
  DDPLSLLDPLWTLNKT
• Function: Plays a role in sorting of endocytic ubiquitinated cargos into multivesicular bodies (MVBs) via its interaction with the ESCRT-I complex (endosomal sorting complex required for transport I), and possibly also other ESCRT complexes. May act as a negative regulator of Ras-mediated mitogenic activity. Plays a role in ciliogenesis.
• Reactome Pathway: Interleukin-37 signaling (R-HSA-9008059)

Molecular Interaction Atlas (MIA) of This DOT

11 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Breast neoplasm	DISNGJLM	Strong	Biomarker	[2]
Germ cell tumor	DIS62070	Strong	Biomarker	[3]
Intellectual disability	DISMBNXP	Strong	Biomarker	[4]
Myopia	DISK5S60	Strong	Altered Expression	[5]
Neurodevelopmental disorder and structural brain anomalies with or without seizures and spasticity	DISYBBKP	Strong	Autosomal recessive	[6]
Non-insulin dependent diabetes	DISK1O5Z	Strong	Genetic Variation	[7]
Sarcoidosis	DISE5B8Z	Strong	Biomarker	[8]
Neoplasm	DISZKGEW	moderate	Biomarker	[2]
Breast cancer	DIS7DPX1	Limited	Altered Expression	[2]
Breast carcinoma	DIS2UE88	Limited	Biomarker	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Tyrosine-protein phosphatase non-receptor type 23 (PTPN23).	[9]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Tyrosine-protein phosphatase non-receptor type 23 (PTPN23).	[10]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Tyrosine-protein phosphatase non-receptor type 23 (PTPN23).	[11]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Tyrosine-protein phosphatase non-receptor type 23 (PTPN23).	[12]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Tyrosine-protein phosphatase non-receptor type 23 (PTPN23).	[13]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Tyrosine-protein phosphatase non-receptor type 23 (PTPN23).	[15]
UNC0379	DMD1E4J	Preclinical	UNC0379 decreases the expression of Tyrosine-protein phosphatase non-receptor type 23 (PTPN23).	[17]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Tyrosine-protein phosphatase non-receptor type 23 (PTPN23).	[18]

2 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 affects the methylation of Tyrosine-protein phosphatase non-receptor type 23 (PTPN23).	[14]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Tyrosine-protein phosphatase non-receptor type 23 (PTPN23).	[16]

References

• [1] Role of ESCRT component HD-PTP/PTPN23 in cancer.Biochem Soc Trans. 2017 Jun 15;45(3):845-854. doi: 10.1042/BST20160332.
• [2] Suppression of protein tyrosine phosphatase N23 predisposes to breast tumorigenesis via activation of FYN kinase.Genes Dev. 2017 Oct 1;31(19):1939-1957. doi: 10.1101/gad.304261.117. Epub 2017 Oct 24.
• [3] Tumor-suppressive function of protein-tyrosine phosphatase non-receptor type 23 in testicular germ cell tumors is lost upon overexpression of miR142-3p microRNA.J Biol Chem. 2013 Aug 16;288(33):23990-9. doi: 10.1074/jbc.M113.478891. Epub 2013 Jul 10.
• [4] Accelerating novel candidate gene discovery in neurogenetic disorders via whole-exome sequencing of prescreened multiplex consanguineous families. Cell Rep. 2015 Jan 13;10(2):148-61. doi: 10.1016/j.celrep.2014.12.015. Epub 2014 Dec 31.
• [5] Myopic (HD-PTP, PTPN23) selectively regulates synaptic neuropeptide release.Proc Natl Acad Sci U S A. 2018 Feb 13;115(7):1617-1622. doi: 10.1073/pnas.1716801115. Epub 2018 Jan 29.
• [6] [An increase in health needs and the role of nursing. Re-evaluation of primary nursing - substantial expansion of the role of nurses]. Kango Tenbo. 1978 Feb;3(2):122-6.
• [7] Refining the accuracy of validated target identification through coding variant fine-mapping in type 2 diabetes.Nat Genet. 2018 Apr;50(4):559-571. doi: 10.1038/s41588-018-0084-1. Epub 2018 Apr 9.
• [8] Search for sarcoidosis candidate genes by integration of data from genomic, transcriptomic and proteomic studies.Med Sci Monit. 2009 Dec;15(12):SR22-8.
• [9] 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.
• [10] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [11] 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.
• [12] 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.
• [13] 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.
• [14] Effect of aflatoxin B(1), benzo[a]pyrene, and methapyrilene on transcriptomic and epigenetic alterations in human liver HepaRG cells. Food Chem Toxicol. 2018 Nov;121:214-223. doi: 10.1016/j.fct.2018.08.034. Epub 2018 Aug 26.
• [15] 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.
• [16] 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.
• [17] Epigenetic siRNA and chemical screens identify SETD8 inhibition as a therapeutic strategy for p53 activation in high-risk neuroblastoma. Cancer Cell. 2017 Jan 9;31(1):50-63.
• [18] Environmental pollutant induced cellular injury is reflected in exosomes from placental explants. Placenta. 2020 Jan 1;89:42-49. doi: 10.1016/j.placenta.2019.10.008. Epub 2019 Oct 17.