Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT6SXU5Y)

DOT Name	Tyrosine-protein phosphatase non-receptor type 4 (PTPN4)
Synonyms	EC 3.1.3.48; Protein-tyrosine phosphatase MEG1; MEG; PTPase-MEG1
Gene Name	PTPN4
Related Disease	Acromegaly ( ) Acute megakaryoblastic leukemia ( ) Advanced cancer ( ) Alzheimer disease ( ) Autism spectrum disorder ( ) B-cell neoplasm ( ) Colorectal carcinoma ( ) Depression ( ) Gastric adenocarcinoma ( ) Gastric cancer ( ) Hepatocellular carcinoma ( ) HIV infectious disease ( ) Multiple sclerosis ( ) Non-insulin dependent diabetes ( ) Non-small-cell lung cancer ( ) Oculocerebrofacial syndrome, Kaufman type ( ) Primary progressive aphasia ( ) Rectal carcinoma ( ) Schizophrenia ( ) Small lymphocytic lymphoma ( ) Stomach cancer ( ) Tuberous sclerosis ( ) Ulcerative colitis ( ) Psychotic disorder ( ) Hyperglycemia ( ) Immune system disorder ( ) Neoplasm ( ) Neurodevelopmental disorder ( ) Post-traumatic stress disorder ( ) Rett syndrome ( )
UniProt ID	PTN4_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
PDB ID	2CS5; 2I75; 2VPH; 3NFK; 3NFL; 5EYZ; 5EZ0; 7VZE
EC Number	3.1.3.48
Pfam ID	PF08736 ; PF09380 ; PF00373 ; PF09379 ; PF00595 ; PF00102
Sequence	MTSRFRLPAGRTYNVRASELARDRQHTEVVCNILLLDNTVQAFKVNKHDQGQVLLDVVFK HLDLTEQDYFGLQLADDSTDNPRWLDPNKPIRKQLKRGSPYSLNFRVKFFVSDPNKLQEE YTRYQYFLQIKQDILTGRLPCPSNTAALLASFAVQSELGDYDQSENLSGYLSDYSFIPNQ PQDFEKEIAKLHQQHIGLSPAEAEFNYLNTARTLELYGVEFHYARDQSNNEIMIGVMSGG ILIYKNRVRMNTFPWLKIVKISFKCKQFFIQLRKELHESRETLLGFNMVNYRACKNLWKA CVEHHTFFRLDRPLPPQKNFFAHYFTLGSKFRYCGRTEVQSVQYGKEKANKDRVFARSPS KPLARKLMDWEVVSRNSISDDRLETQSLPSRSPPGTPNHRNSTFTQEGTRLRPSSVGHLV DHMVHTSPSEVFVNQRSPSSTQANSIVLESSPSQETPGDGKPPALPPKQSKKNSWNQIHY SHSQQDLESHINETFDIPSSPEKPTPNGGIPHDNLVLIRMKPDENGRFGFNVKGGYDQKM PVIVSRVAPGTPADLCVPRLNEGDQVVLINGRDIAEHTHDQVVLFIKASCERHSGELMLL VRPNAVYDVVEEKLENEPDFQYIPEKAPLDSVHQDDHSLRESMIQLAEGLITGTVLTQFD QLYRKKPGMTMSCAKLPQNISKNRYRDISPYDATRVILKGNEDYINANYINMEIPSSSII NQYIACQGPLPHTCTDFWQMTWEQGSSMVVMLTTQVERGRVKCHQYWPEPTGSSSYGCYQ VTCHSEEGNTAYIFRKMTLFNQEKNESRPLTQIQYIAWPDHGVPDDSSDFLDFVCHVRNK RAGKEEPVVVHCSAGIGRTGVLITMETAMCLIECNQPVYPLDIVRTMRDQRAMMIQTPSQ YRFVCEAILKVYEEGFVKPLTTSTNK
Function	Phosphatase that plays a role in immunity, learning, synaptic plasticity or cell homeostasis. Regulates neuronal cell homeostasis by protecting neurons against apoptosis. Negatively regulates TLR4-induced interferon beta production by dephosphorylating adapter TICAM2 and inhibiting subsequent TRAM-TRIF interaction. Dephosphorylates also the immunoreceptor tyrosine-based activation motifs/ITAMs of the TCR zeta subunit and thereby negatively regulates TCR-mediated signaling pathway. May act at junctions between the membrane and the cytoskeleton.
Reactome Pathway	Interleukin-37 signaling (R-HSA-9008059 ) MECP2 regulates neuronal receptors and channels (R-HSA-9022699 ) Toll Like Receptor 4 (TLR4) Cascade (R-HSA-166016 )

Molecular Interaction Atlas (MIA) of This DOT

30 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance
Acromegaly	DISCC73U	Strong	Biomarker	[1]
Acute megakaryoblastic leukemia	DIS0JX3M	Strong	Biomarker	[2]
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[3]
Alzheimer disease	DISF8S70	Strong	Biomarker	[4]
Autism spectrum disorder	DISXK8NV	Strong	Biomarker	[5]
B-cell neoplasm	DISVY326	Strong	Biomarker	[6]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[7]
Depression	DIS3XJ69	Strong	Altered Expression	[8]
Gastric adenocarcinoma	DISWWLTC	Strong	Altered Expression	[3]
Gastric cancer	DISXGOUK	Strong	Biomarker	[3]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[9]
HIV infectious disease	DISO97HC	Strong	Biomarker	[10]
Multiple sclerosis	DISB2WZI	Strong	Genetic Variation	[11]
Non-insulin dependent diabetes	DISK1O5Z	Strong	Biomarker	[12]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[13]
Oculocerebrofacial syndrome, Kaufman type	DISE8Q7Q	Strong	Altered Expression	[14]
Primary progressive aphasia	DISLRYFE	Strong	Altered Expression	[15]
Rectal carcinoma	DIS8FRR7	Strong	Altered Expression	[7]
Schizophrenia	DISSRV2N	Strong	Biomarker	[16]
Small lymphocytic lymphoma	DIS30POX	Strong	Biomarker	[17]
Stomach cancer	DISKIJSX	Strong	Biomarker	[3]
Tuberous sclerosis	DISEMUGZ	Strong	Biomarker	[18]
Ulcerative colitis	DIS8K27O	Strong	Biomarker	[19]
Psychotic disorder	DIS4UQOT	Disputed	Genetic Variation	[20]
Hyperglycemia	DIS0BZB5	Limited	Biomarker	[21]
Immune system disorder	DISAEGPH	Limited	Genetic Variation	[22]
Neoplasm	DISZKGEW	Limited	Biomarker	[7]
Neurodevelopmental disorder	DIS372XH	Limited	Biomarker	[22]
Post-traumatic stress disorder	DISHL1EY	Limited	Biomarker	[23]
Rett syndrome	DISGG5UV	Limited	Biomarker	[24]
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Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This DOT

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 4 (PTPN4).	[25]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Tyrosine-protein phosphatase non-receptor type 4 (PTPN4).	[26]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Tyrosine-protein phosphatase non-receptor type 4 (PTPN4).	[27]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Tyrosine-protein phosphatase non-receptor type 4 (PTPN4).	[28]
Testosterone enanthate	DMB6871	Approved	Testosterone enanthate affects the expression of Tyrosine-protein phosphatase non-receptor type 4 (PTPN4).	[29]
Crocin	DM5F24X	Phase 3	Crocin increases the expression of Tyrosine-protein phosphatase non-receptor type 4 (PTPN4).	[30]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Tyrosine-protein phosphatase non-receptor type 4 (PTPN4).	[31]
OXYBENZONE	DMMZYX6	Investigative	OXYBENZONE increases the expression of Tyrosine-protein phosphatase non-receptor type 4 (PTPN4).	[32]
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⏷ Show the Full List of 8 Drug(s)

References

1	Gene Expression Signature in Adipose Tissue of Acromegaly Patients.PLoS One. 2015 Jun 18;10(6):e0129359. doi: 10.1371/journal.pone.0129359. eCollection 2015.
2	Arsenic trioxide mediates intrinsic and extrinsic pathways of apoptosis and cell cycle arrest in acute megakaryocytic leukemia. Int J Oncol. 2005 Aug;27(2):537-45.
3	PTPN3 and PTPN4 tyrosine phosphatase expression in human gastric adenocarcinoma.Anticancer Res. 2006 Mar-Apr;26(2B):1643-9.
4	What electrophysiology tells us about Alzheimer's disease: a window into the synchronization and connectivity of brain neurons.Neurobiol Aging. 2020 Jan;85:58-73. doi: 10.1016/j.neurobiolaging.2019.09.008. Epub 2019 Sep 19.
5	MeCP2+/- mouse model of RTT reproduces auditory phenotypes associated with Rett syndrome and replicate select EEG endophenotypes of autism spectrum disorder.Neurobiol Dis. 2012 Apr;46(1):88-92. doi: 10.1016/j.nbd.2011.12.048. Epub 2012 Jan 9.
6	Immune thrombocytopenia induces autophagy and suppresses apoptosis in megakaryocytes.Mol Med Rep. 2018 Oct;18(4):4016-4022. doi: 10.3892/mmr.2018.9373. Epub 2018 Aug 9.
7	Loss of PTPN4 activates STAT3 to promote the tumor growth in rectal cancer.Cancer Sci. 2019 Jul;110(7):2258-2272. doi: 10.1111/cas.14031. Epub 2019 May 23.
8	Cognitive reserve-mediated neural modulation of emotional control and regulation in people with late-life depression.Soc Cogn Affect Neurosci. 2019 Aug 31;14(8):849-860. doi: 10.1093/scan/nsz054.
9	Identification of human thrombin-activatable fibrinolysis inhibitor in vascular and inflammatory cells.Thromb Haemost. 2011 Jun;105(6):999-1009. doi: 10.1160/TH10-06-0413. Epub 2011 Apr 20.
10	The electrophysiology of neuroHIV: A systematic review of EEG and MEG studies in people with HIV infection since the advent of highly-active antiretroviral therapy.Clin Neurophysiol. 2017 Jun;128(6):965-976. doi: 10.1016/j.clinph.2017.03.035. Epub 2017 Mar 31.
11	Abnormal task driven neural oscillations in multiple sclerosis: A visuomotor MEG study.Hum Brain Mapp. 2017 May;38(5):2441-2453. doi: 10.1002/hbm.23531. Epub 2017 Feb 27.
12	Design, synthesis, biological evaluation and molecular dynamics simulation studies of (R)-5-methylthiazolidin-4-One derivatives as megakaryocyte protein tyrosine phosphatase 2 (PTP-MEG2) inhibitors for the treatment of type 2 diabetes.J Biomol Struct Dyn. 2020 Jul;38(11):3156-3165. doi: 10.1080/07391102.2019.1654410. Epub 2019 Aug 22.
13	MicroRNA-183 promotes migration and invasion of CD133(+)/CD326(+) lung adenocarcinoma initiating cells via PTPN4 inhibition.Tumour Biol. 2016 Aug;37(8):11289-97. doi: 10.1007/s13277-016-4955-8. Epub 2016 Mar 7.
14	Kagami-Ogata syndrome: a clinically recognizable upd(14)pat and related disorder affecting the chromosome 14q32.2 imprinted region.J Hum Genet. 2016 Feb;61(2):87-94. doi: 10.1038/jhg.2015.113. Epub 2015 Sep 17.
15	Slowing is slowing: Delayed neural responses to words are linked to abnormally slow resting state activity in primary progressive aphasia.Neuropsychologia. 2019 Jun;129:331-347. doi: 10.1016/j.neuropsychologia.2019.04.007. Epub 2019 Apr 25.
16	Deficit Versus Nondeficit Schizophrenia: An MEG-EEG Investigation of Resting State and Source Coherence-Preliminary Data.Clin EEG Neurosci. 2020 Jan;51(1):34-44. doi: 10.1177/1550059419867561. Epub 2019 Aug 4.
17	MiR-15a and miR-16-1 cluster functions in human leukemia. Proc Natl Acad Sci U S A. 2008 Apr 1;105(13):5166-71.
18	Resective surgery in tuberous Sclerosis complex, from Penfield to 2018: A critical review.Rev Neurol (Paris). 2019 Mar;175(3):163-182. doi: 10.1016/j.neurol.2018.11.002. Epub 2019 Jan 25.
19	In vitro and in vivo study of pH-sensitive and colon-targeting P(LE-IA-MEG) hydrogel microspheres used for ulcerative colitis therapy.Eur J Pharm Biopharm. 2018 Jan;122:70-77. doi: 10.1016/j.ejpb.2017.10.003. Epub 2017 Oct 7.
20	Towards a neurodynamical understanding of the prodrome in schizophrenia.Neuroimage. 2019 Apr 15;190:144-153. doi: 10.1016/j.neuroimage.2017.11.026. Epub 2017 Nov 22.
21	Hyperglycaemia suppresses microRNA expression in platelets to increase P2RY12 and SELP levels in type 2 diabetes mellitus.Thromb Haemost. 2017 Feb 28;117(3):529-542. doi: 10.1160/TH16-04-0322. Epub 2016 Dec 15.
22	Neurodevelopmental phenotype caused by a de novo PTPN4 single nucleotide variant disrupting protein localization in neuronal dendritic spines.Clin Genet. 2018 Dec;94(6):581-585. doi: 10.1111/cge.13450. Epub 2018 Oct 11.
23	Post-traumatic stress disorder and chronic hyperconnectivity in emotional processing.Neuroimage Clin. 2018 Jul 10;20:197-204. doi: 10.1016/j.nicl.2018.07.007. eCollection 2018.
24	Deletion of protein tyrosine phosphatase, non-receptor type 4 (PTPN4) in twins with a Rett syndrome-like phenotype.Eur J Hum Genet. 2015 Sep;23(9):1171-5. doi: 10.1038/ejhg.2014.249. Epub 2014 Nov 26.
25	Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
26	Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
27	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.
28	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.
29	Transcriptional profiling of testosterone-regulated genes in the skeletal muscle of human immunodeficiency virus-infected men experiencing weight loss. J Clin Endocrinol Metab. 2007 Jul;92(7):2793-802. doi: 10.1210/jc.2006-2722. Epub 2007 Apr 17.
30	Crocin induces ROS-mediated papillary thyroid cancer cell apoptosis by modulating the miR-34a-5p/PTPN4 axis in vitro. Toxicol Appl Pharmacol. 2022 Feb 15;437:115892. doi: 10.1016/j.taap.2022.115892. Epub 2022 Jan 25.
31	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.
32	Chromatin modifiers: A new class of pollutants with potential epigenetic effects revealed by in vitro assays and transcriptomic analyses. Toxicology. 2023 Jan 15;484:153413. doi: 10.1016/j.tox.2022.153413. Epub 2022 Dec 26.