Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTV5TXNN)

• DOT Name: Receptor-type tyrosine-protein phosphatase T (PTPRT)
• Synonyms: R-PTP-T; EC 3.1.3.48; Receptor-type tyrosine-protein phosphatase rho; RPTP-rho
• Gene Name: PTPRT
• Related Disease:
  Acute myelogenous leukaemia
  Adult glioblastoma
  Glioblastoma multiforme
  Stomach cancer
  Anxiety disorder
  Astrocytoma
  Autism spectrum disorder
  Brain neoplasm
  Carcinoma
  Clear cell renal carcinoma
  Colitis
  Colon cancer
  Colon carcinoma
  Colorectal carcinoma
  Esophageal squamous cell carcinoma
  Head and neck cancer
  Head and neck carcinoma
  Head-neck squamous cell carcinoma
  Hepatocellular carcinoma
  Lung adenocarcinoma
  Lung cancer
  Mental disorder
  Metastatic malignant neoplasm
  Neoplasm
  Non-small-cell lung cancer
  Noonan syndrome
  Pancreatic adenocarcinoma
  Prostate cancer
  Prostate carcinoma
  Renal cell carcinoma
  Advanced cancer
  Neuroblastoma
  Type-1/2 diabetes
  Glioma
  Non-insulin dependent diabetes
• UniProt ID: PTPRT_HUMAN
• PDB ID: 2OOQ
• EC Number: 3.1.3.48
• Pfam ID: PF00041 ; PF00629 ; PF00102
• Sequence:
  MASLAALALSLLLRLQLPPLPGARAQSAAGGCSFDEHYSNCGYSVALGTNGFTWEQINTW
  EKPMLDQAVPTGSFMMVNSSGRASGQKAHLLLPTLKENDTHCIDFHYYFSSRDRSSPGAL
  NVYVKVNGGPQGNPVWNVSGVVTEGWVKAELAISTFWPHFYQVIFESVSLKGHPGYIAVD
  EVRVLAHPCRKAPHFLRLQNVEVNVGQNATFQCIAGGKWSQHDKLWLQQWNGRDTALMVT
  RVVNHRRFSATVSVADTAQRSVSKYRCVIRSDGGSGVSNYAELIVKEPPTPIAPPELLAV
  GATYLWIKPNANSIIGDGPIILKEVEYRTTTGTWAETHIVDSPNYKLWHLDPDVEYEIRV
  LLTRPGEGGTGPPGPPLTTRTKCADPVHGPQNVEIVDIRARQLTLQWEPFGYAVTRCHSY
  NLTVQYQYVFNQQQYEAEEVIQTSSHYTLRGLRPFMTIRLRLLLSNPEGRMESEELVVQT
  EEDVPGAVPLESIQGGPFEEKIYIQWKPPNETNGVITLYEINYKAVGSLDPSADLSSQRG
  KVFKLRNETHHLFVGLYPGTTYSFTIKASTAKGFGPPVTTRIATKISAPSMPEYDTDTPL
  NETDTTITVMLKPAQSRGAPVSVYQLVVKEERLQKSRRAADIIECFSVPVSYRNASSLDS
  LHYFAAELKPANLPVTQPFTVGDNKTYNGYWNPPLSPLKSYSIYFQALSKANGETKINCV
  RLATKGASTQNSNTVEPEKQVDNTVKMAGVIAGLLMFIIILLGVMLTIKRRRNAYSYSYY
  LKLAKKQKETQSGAQREMGPVASADKPTTKLSASRNDEGFSSSSQDVNGFTDGSRGELSQ
  PTLTIQTHPYRTCDPVEMSYPRDQFQPAIRVADLLQHITQMKRGQGYGFKEEYEALPEGQ
  TASWDTAKEDENRNKNRYGNIISYDHSRVRLLVLDGDPHSDYINANYIDGYHRPRHYIAT
  QGPMQETVKDFWRMIWQENSASIVMVTNLVEVGRVKCVRYWPDDTEVYGDIKVTLIETEP
  LAEYVIRTFTVQKKGYHEIRELRLFHFTSWPDHGVPCYATGLLGFVRQVKFLNPPEAGPI
  VVHCSAGAGRTGCFIAIDTMLDMAENEGVVDIFNCVRELRAQRVNLVQTEEQYVFVHDAI
  LEACLCGNTAIPVCEFRSLYYNISRLDPQTNSSQIKDEFQTLNIVTPRVRPEDCSIGLLP
  RNHDKNRSMDVLPLDRCLPFLISVDGESSNYINAALMDSHKQPAAFVVTQHPLPNTVADF
  WRLVFDYNCSSVVMLNEMDTAQFCMQYWPEKTSGCYGPIQVEFVSADIDEDIIHRIFRIC
  NMARPQDGYRIVQHLQYIGWPAYRDTPPSKRSLLKVVRRLEKWQEQYDGREGRTVVHCLN
  GGGRSGTFCAICSVCEMIQQQNIIDVFHIVKTLRNNKSNMVETLEQYKFVYEVALEYLSS
  F
• Function: May be involved in both signal transduction and cellular adhesion in the CNS.
• Tissue Specificity: Expressed in colon, lung, heart and testis, as well as in fetal and adult brain. Not detected in muscle and peripheral blood leukocytes.

Molecular Interaction Atlas (MIA) of This DOT

35 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute myelogenous leukaemia	DISCSPTN	Definitive	Genetic Variation	[1]
Adult glioblastoma	DISVP4LU	Definitive	Altered Expression	[2]
Glioblastoma multiforme	DISK8246	Definitive	Altered Expression	[2]
Stomach cancer	DISKIJSX	Definitive	Biomarker	[3]
Anxiety disorder	DISBI2BT	Strong	Genetic Variation	[4]
Astrocytoma	DISL3V18	Strong	Altered Expression	[5]
Autism spectrum disorder	DISXK8NV	Strong	Biomarker	[6]
Brain neoplasm	DISY3EKS	Strong	Biomarker	[7]
Carcinoma	DISH9F1N	Strong	Genetic Variation	[8]
Clear cell renal carcinoma	DISBXRFJ	Strong	Biomarker	[9]
Colitis	DISAF7DD	Strong	Biomarker	[10]
Colon cancer	DISVC52G	Strong	Biomarker	[11]
Colon carcinoma	DISJYKUO	Strong	Biomarker	[11]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[12]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Genetic Variation	[13]
Head and neck cancer	DISBPSQZ	Strong	Posttranslational Modification	[14]
Head and neck carcinoma	DISOU1DS	Strong	Posttranslational Modification	[14]
Head-neck squamous cell carcinoma	DISF7P24	Strong	Biomarker	[14]
Hepatocellular carcinoma	DIS0J828	Strong	Genetic Variation	[8]
Lung adenocarcinoma	DISD51WR	Strong	Genetic Variation	[15]
Lung cancer	DISCM4YA	Strong	Genetic Variation	[8]
Mental disorder	DIS3J5R8	Strong	Biomarker	[6]
Metastatic malignant neoplasm	DIS86UK6	Strong	Biomarker	[16]
Neoplasm	DISZKGEW	Strong	Altered Expression	[17]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Posttranslational Modification	[18]
Noonan syndrome	DIS7Q7DN	Strong	Biomarker	[19]
Pancreatic adenocarcinoma	DISKHX7S	Strong	Genetic Variation	[20]
Prostate cancer	DISF190Y	Strong	Biomarker	[16]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[16]
Renal cell carcinoma	DISQZ2X8	Strong	Biomarker	[9]
Advanced cancer	DISAT1Z9	moderate	Altered Expression	[21]
Neuroblastoma	DISVZBI4	moderate	Altered Expression	[22]
Type-1/2 diabetes	DISIUHAP	moderate	Altered Expression	[23]
Glioma	DIS5RPEH	Limited	Altered Expression	[24]
Non-insulin dependent diabetes	DISK1O5Z	Limited	Genetic Variation	[25]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Receptor-type tyrosine-protein phosphatase T (PTPRT).	[26]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Receptor-type tyrosine-protein phosphatase T (PTPRT).	[27]
Niclosamide	DMJAGXQ	Approved	Niclosamide decreases the expression of Receptor-type tyrosine-protein phosphatase T (PTPRT).	[28]
Amphotericin B	DMTAJQE	Approved	Amphotericin B increases the expression of Receptor-type tyrosine-protein phosphatase T (PTPRT).	[29]

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 Receptor-type tyrosine-protein phosphatase T (PTPRT).	[30]

References

• [1] Genome-wide haplotype association study identify the FGFR2 gene as a risk gene for acute myeloid leukemia.Oncotarget. 2017 Jan 31;8(5):7891-7899. doi: 10.18632/oncotarget.13631.
• [2] Comprehensive protein tyrosine phosphatase mRNA profiling identifies new regulators in the progression of glioma.Acta Neuropathol Commun. 2016 Sep 1;4(1):96. doi: 10.1186/s40478-016-0372-x.
• [3] Molecular Profiles and Metastasis Markers in Chinese Patients with Gastric Carcinoma.Sci Rep. 2019 Sep 30;9(1):13995. doi: 10.1038/s41598-019-50171-7.
• [4] Genetic Variants Associated With Anxiety and Stress-Related Disorders: A Genome-Wide Association Study and Mouse-Model Study.JAMA Psychiatry. 2019 Sep 1;76(9):924-932. doi: 10.1001/jamapsychiatry.2019.1119.
• [5] Expression and function of the receptor protein tyrosine phosphatase zeta and its ligand pleiotrophin in human astrocytomas.J Neuropathol Exp Neurol. 2003 Dec;62(12):1265-75. doi: 10.1093/jnen/62.12.1265.
• [6] Loss-of-function of PTPR and , observed in sporadic schizophrenia, causes brain region-specific deregulation of monoamine levels and altered behavior in mice.Psychopharmacology (Berl). 2017 Feb;234(4):575-587. doi: 10.1007/s00213-016-4490-8. Epub 2016 Dec 26.
• [7] The tyrosine phosphatase PTPRD is a tumor suppressor that is frequently inactivated and mutated in glioblastoma and other human cancers.Proc Natl Acad Sci U S A. 2009 Jun 9;106(23):9435-40. doi: 10.1073/pnas.0900571106. Epub 2009 May 28.
• [8] Mutational analysis of PTPRT phosphatase domains in common human cancers.APMIS. 2007 Jan;115(1):47-51. doi: 10.1111/j.1600-0463.2007.apm_554.x.
• [9] A homozygous deletion within the carbonic anhydrase-like domain of the Ptprg gene in murine L-cells.Cancer Res. 1993 Apr 1;53(7):1498-502.
• [10] Protein-tyrosine phosphatase sigma is associated with ulcerative colitis.Curr Biol. 2007 Jul 17;17(14):1212-8. doi: 10.1016/j.cub.2007.06.013. Epub 2007 Jul 5.
• [11] Tumour suppressor function of protein tyrosine phosphatase receptor-T.Biosci Rep. 2011 Oct;31(5):303-7. doi: 10.1042/BSR20100134.
• [12] Exome scale map of genetic alterations promoting metastasis in colorectal cancer.BMC Genet. 2018 Sep 19;19(1):85. doi: 10.1186/s12863-018-0673-0.
• [13] The Functional Variant in the 3'UTR of PTPRT with the Risk of Esophageal Squamous Cell Carcinoma in a Chinese Population.Cell Physiol Biochem. 2015;36(1):306-14. doi: 10.1159/000374073. Epub 2015 May 5.
• [14] Frequent promoter hypermethylation of PTPRT increases STAT3 activation and sensitivity to STAT3 inhibition in head and neck cancer.Oncogene. 2016 Mar 3;35(9):1163-9. doi: 10.1038/onc.2015.171. Epub 2015 May 18.
• [15] Recurrent PTPRT/JAK2 mutations in lung adenocarcinoma among African Americans.Nat Commun. 2019 Dec 16;10(1):5735. doi: 10.1038/s41467-019-13732-y.
• [16] Loss of receptor protein tyrosine phosphatase / (RPTP/) promotes prostate cancer metastasis.J Biol Chem. 2012 Nov 23;287(48):40339-49. doi: 10.1074/jbc.M112.405852. Epub 2012 Oct 11.
• [17] A novel splice variant of the protein tyrosine phosphatase PTPRJ that encodes for a soluble protein involved in angiogenesis.Oncotarget. 2017 Feb 7;8(6):10091-10102. doi: 10.18632/oncotarget.14350.
• [18] PTPRT epigenetic silencing defines lung cancer with STAT3 activation and can direct STAT3 targeted therapies.Epigenetics. 2020 Jun-Jul;15(6-7):604-617. doi: 10.1080/15592294.2019.1676597. Epub 2019 Oct 13.
• [19] Identification of demethylincisterol A(3) as a selective inhibitor of protein tyrosine phosphatase Shp2.Eur J Pharmacol. 2017 Jan 15;795:124-133. doi: 10.1016/j.ejphar.2016.12.012. Epub 2016 Dec 8.
• [20] Characterization of PCP-2, a novel receptor protein tyrosine phosphatase of the MAM domain family.Oncogene. 1996 Jun 20;12(12):2555-62.
• [21] The receptor protein tyrosine phosphatase PTPRJ negatively modulates the CD98hc oncoprotein in lung cancer cells.Oncotarget. 2018 May 4;9(34):23334-23348. doi: 10.18632/oncotarget.25101. eCollection 2018 May 4.
• [22] Distinct FAK-Src activation events promote alpha5beta1 and alpha4beta1 integrin-stimulated neuroblastoma cell motility.Oncogene. 2008 Feb 28;27(10):1439-48. doi: 10.1038/sj.onc.1210770. Epub 2007 Sep 10.
• [23] Molecular alterations underlie nodal and paranodal degeneration in type 1 diabetic neuropathy and are prevented by C-peptide.Diabetes. 2004 Jun;53(6):1556-63. doi: 10.2337/diabetes.53.6.1556.
• [24] Expression of a receptor protein tyrosine phosphatase in human glial tumors.J Neurooncol. 1998 Feb;36(3):209-17. doi: 10.1023/a:1005840420136.
• [25] Genetic variation in receptor protein tyrosine phosphatase sigma is associated with type 2 diabetes in Swedish Caucasians.Eur J Endocrinol. 2007 Oct;157(4):459-64. doi: 10.1530/EJE-07-0114.
• [26] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [27] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [28] Mitochondrial Uncoupling Induces Epigenome Remodeling and Promotes Differentiation in Neuroblastoma. Cancer Res. 2023 Jan 18;83(2):181-194. doi: 10.1158/0008-5472.CAN-22-1029.
• [29] Differential expression of microRNAs and their predicted targets in renal cells exposed to amphotericin B and its complex with copper (II) ions. Toxicol Mech Methods. 2017 Sep;27(7):537-543. doi: 10.1080/15376516.2017.1333554. Epub 2017 Jun 8.
• [30] 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.