Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTZLYE6J)

DOT Name Myotubularin-related protein 4 (MTMR4)
Synonyms EC 3.1.3.48; FYVE domain-containing dual specificity protein phosphatase 2; FYVE-DSP2; Zinc finger FYVE domain-containing protein 11
Gene Name MTMR4
Related Disease
Herpes simplex infection ( )
Malignant mesothelioma ( )
UniProt ID
MTMR4_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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EC Number
3.1.3.48
Pfam ID
PF01363 ; PF06602
Sequence
MGEEGPPSLEYIQAKDLFPPKELVKEEENLQVPFTVLQGEGVEFLGRAADALIAISNYRL
HIKFKDSVINVPLRMIDSVESRDMFQLHISCKDSKVVRCHFSTFKQCQEWLSRLSRATAR
PAKPEDLFAFAYHAWCLGLTEEDQHTHLCQPGEHIRCRQEAELARMGFDLQNVWRVSHIN
SNYKLCPSYPQKLLVPVWITDKELENVASFRSWKRIPVVVYRHLRNGAAIARCSQPEISW
WGWRNADDEYLVTSIAKACALDPGTRATGGSLSTGNNDTSEACDADFDSSLTACSGVEST
AAPQKLLILDARSYTAAVANRAKGGGCECEEYYPNCEVVFMGMANIHAIRNSFQYLRAVC
SQMPDPSNWLSALESTKWLQHLSVMLKAAVLVANTVDREGRPVLVHCSDGWDRTPQIVAL
AKILLDPYYRTLEGFQVLVESDWLDFGHKFGDRCGHQENVEDQNEQCPVFLQWLDSVHQL
LKQFPCLFEFNEAFLVKLVQHTYSCLYGTFLANNPCEREKRNIYKRTCSVWALLRAGNKN
FHNFLYTPSSDMVLHPVCHVRALHLWTAVYLPASSPCTLGEENMDLYLSPVAQSQEFSGR
SLDRLPKTRSMDDLLSACDTSSPLTRTSSDPNLNNHCQEVRVGLEPWHSNPEGSETSFVD
SGVGGPQQTVGEVGLPPPLPSSQKDYLSNKPFKSHKSCSPSYKLLNTAVPREMKSNTSDP
EIKVLEETKGPAPDPSAQDELGRTLDGIGEPPEHCPETEAVSALSKVISNKCDGVCNFPE
SSQNSPTGTPQQAQPDSMLGVPSKCVLDHSLSTVCNPPSAACQTPLDPSTDFLNQDPSGS
VASISHQEQLSSVPDLTHGEEDIGKRGNNRNGQLLENPRFGKMPLELVRKPISQSQISEF
SFLGSNWDSFQGMVTSFPSGEATPRRLLSYGCCSKRPNSKQMRATGPCFGGQWAQREGVK
SPVCSSHSNGHCTGPGGKNQMWLSSHPKQVSSTKPVPLNCPSPVPPLYLDDDGLPFPTDV
IQHRLRQIEAGYKQEVEQLRRQVRELQMRLDIRHCCAPPAEPPMDYEDDFTCLKESDGSD
TEDFGSDHSEDCLSEASWEPVDKKETEVTRWVPDHMASHCYNCDCEFWLAKRRHHCRNCG
NVFCAGCCHLKLPIPDQQLYDPVLVCNSCYEHIQVSRARELMSQQLKKPIATASS
Function
Dephosphorylates proteins phosphorylated on Ser, Thr, and Tyr residues and low molecular weight phosphatase substrate para-nitrophenylphosphate. Phosphorylates phosphatidylinositol 3,4,5-trisphosphate (PIP3).
Tissue Specificity Expressed in brain, heart, kidney, spleen, liver, colon, testis, muscle, placenta, thyroid gland, pancreas, ovary, prostate, skin, peripheral blood, and bone marrow.
KEGG Pathway
Inositol phosphate metabolism (hsa00562 )
Metabolic pathways (hsa01100 )
Phosphatidylinositol sig.ling system (hsa04070 )
Autophagy - animal (hsa04140 )
Reactome Pathway
Synthesis of PIPs at the late endosome membrane (R-HSA-1660517 )
Downregulation of TGF-beta receptor signaling (R-HSA-2173788 )
Synthesis of PIPs at the early endosome membrane (R-HSA-1660516 )

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Herpes simplex infection DISL1SAV Strong Biomarker [1]
Malignant mesothelioma DISTHJGH Strong Biomarker [2]
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Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
1 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate decreases the methylation of Myotubularin-related protein 4 (MTMR4). [3]
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10 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Ciclosporin DMAZJFX Approved Ciclosporin decreases the expression of Myotubularin-related protein 4 (MTMR4). [4]
Tretinoin DM49DUI Approved Tretinoin decreases the expression of Myotubularin-related protein 4 (MTMR4). [5]
Acetaminophen DMUIE76 Approved Acetaminophen decreases the expression of Myotubularin-related protein 4 (MTMR4). [6]
Cisplatin DMRHGI9 Approved Cisplatin decreases the expression of Myotubularin-related protein 4 (MTMR4). [7]
Quercetin DM3NC4M Approved Quercetin decreases the expression of Myotubularin-related protein 4 (MTMR4). [8]
Hydrogen peroxide DM1NG5W Approved Hydrogen peroxide affects the expression of Myotubularin-related protein 4 (MTMR4). [9]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene decreases the expression of Myotubularin-related protein 4 (MTMR4). [10]
Leflunomide DMR8ONJ Phase 1 Trial Leflunomide decreases the expression of Myotubularin-related protein 4 (MTMR4). [11]
Bisphenol A DM2ZLD7 Investigative Bisphenol A increases the expression of Myotubularin-related protein 4 (MTMR4). [12]
Formaldehyde DM7Q6M0 Investigative Formaldehyde decreases the expression of Myotubularin-related protein 4 (MTMR4). [13]
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⏷ Show the Full List of 10 Drug(s)

References

1 PtdIns3P phosphatases MTMR3 and MTMR4 negatively regulate innate immune responses to DNA through modulating STING trafficking.J Biol Chem. 2019 May 24;294(21):8412-8423. doi: 10.1074/jbc.RA118.005731. Epub 2019 Apr 3.
2 MicroRNA and mRNA features of malignant pleural mesothelioma and benign asbestos-related pleural effusion.Biomed Res Int. 2015;2015:635748. doi: 10.1155/2015/635748. Epub 2015 Feb 1.
3 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.
4 Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
5 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.
6 Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
7 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.
8 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.
9 Minimal peroxide exposure of neuronal cells induces multifaceted adaptive responses. PLoS One. 2010 Dec 17;5(12):e14352. doi: 10.1371/journal.pone.0014352.
10 Benzo[a]pyrene-induced changes in microRNA-mRNA networks. Chem Res Toxicol. 2012 Apr 16;25(4):838-49.
11 Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
12 Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
13 Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.