Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTUUEY6Q)

DOT Name Myotubularin-related protein 14 (MTMR14)
Synonyms EC 3.1.3.-; HCV NS5A-transactivated protein 4 splice variant A-binding protein 1; NS5ATP4ABP1; hJumpy
Gene Name MTMR14
Related Disease
Carcinoma of liver and intrahepatic biliary tract ( )
Cardiomyopathy ( )
Liver cancer ( )
Neoplasm ( )
Congenital structural myopathy ( )
Epithelial ovarian cancer ( )
Myopathy ( )
Obesity ( )
Centronuclear myopathy ( )
Autosomal dominant centronuclear myopathy ( )
UniProt ID
MTMRE_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.-
Sequence
MAGARAAAAAASAGSSASSGNQPPQELGLGELLEEFSRTQYRAKDGSGTGGSKVERIEKR
CLELFGRDYCFSVIPNTNGDICGHYPRHIVFLEYESSEKEKDTFESTVQVSKLQDLIHRS
KMARCRGRFVCPVILFKGKHICRSATLAGWGELYGRSGYNYFFSGGADDAWADVEDVTEE
DCALRSGDTHLFDKVRGYDIKLLRYLSVKYICDLMVENKKVKFGMNVTSSEKVDKAQRYA
DFTLLSIPYPGCEFFKEYKDRDYMAEGLIFNWKQDYVDAPLSIPDFLTHSLNIDWSQYQC
WDLVQQTQNYLKLLLSLVNSDDDSGLLVHCISGWDRTPLFISLLRLSLWADGLIHTSLKP
TEILYLTVAYDWFLFGHMLVDRLSKGEEIFFFCFNFLKHITSEEFSALKTQRRKSLPARD
GGFTLEDICMLRRKDRGSTTSLGSDFSLVMESSPGATGSFTYEAVELVPAGAPTQAAWRK
SHSSSPQSVLWNRPQPSEDRLPSQQGLAEARSSSSSSSNHSDNFFRMGSSPLEVPKPRSV
DHPLPGSSLSTDYGSWQMVTGCGSIQERAVLHTDSSLPFSFPDELPNSCLLAALSDRETR
LQEVRSAFLAAYSSTVGLRAVAPSPSGAIGGLLEQFARGVGLRSISSNAL
Function Lipid phosphatase which efficiently dephosphorylates phosphatidylinositol 3-phosphate (PtdIns3P) and PtdIns(3,5)P2; inactive toward PtdIns4P, PtdIns(3,4)P2, PtdIns(4,5)P2 and PtdIns(3,4,5)P3.
Tissue Specificity Expressed in various tissues, including heart, skeletal muscle, placenta, liver, lung, kidney and pancreas.
KEGG Pathway
Inositol phosphate metabolism (hsa00562 )
Metabolic pathways (hsa01100 )
Phosphatidylinositol sig.ling system (hsa04070 )
Autophagy - animal (hsa04140 )
Reactome Pathway
Synthesis of PIPs at the plasma membrane (R-HSA-1660499 )
Macroautophagy (R-HSA-1632852 )
BioCyc Pathway
MetaCyc:HS08920-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

10 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Carcinoma of liver and intrahepatic biliary tract DIS8WA0W Definitive Biomarker [1]
Cardiomyopathy DISUPZRG Definitive Biomarker [1]
Liver cancer DISDE4BI Definitive Biomarker [1]
Neoplasm DISZKGEW Definitive Biomarker [1]
Congenital structural myopathy DISZ9JP4 Strong Genetic Variation [2]
Epithelial ovarian cancer DIS56MH2 Strong Biomarker [3]
Myopathy DISOWG27 Strong Biomarker [4]
Obesity DIS47Y1K Strong Biomarker [5]
Centronuclear myopathy DISXBEJO moderate Biomarker [6]
Autosomal dominant centronuclear myopathy DISF2XWP Limited Digenic inheritance HP:0010984 [7]
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⏷ Show the Full List of 10 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
2 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate increases the methylation of Myotubularin-related protein 14 (MTMR14). [8]
PMID28870136-Compound-52 DMFDERP Patented PMID28870136-Compound-52 affects the phosphorylation of Myotubularin-related protein 14 (MTMR14). [13]
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5 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Tretinoin DM49DUI Approved Tretinoin increases the expression of Myotubularin-related protein 14 (MTMR14). [9]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate increases the expression of Myotubularin-related protein 14 (MTMR14). [10]
Folic acid DMEMBJC Approved Folic acid decreases the expression of Myotubularin-related protein 14 (MTMR14). [11]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the expression of Myotubularin-related protein 14 (MTMR14). [12]
Bisphenol A DM2ZLD7 Investigative Bisphenol A increases the expression of Myotubularin-related protein 14 (MTMR14). [14]
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References

1 Knockdown MTMR14 promotes cell apoptosis and inhibits migration in liver cancer cells.Gene. 2019 Apr 5;691:106-113. doi: 10.1016/j.gene.2018.11.099. Epub 2018 Dec 23.
2 A novel PtdIns3P and PtdIns(3,5)P2 phosphatase with an inactivating variant in centronuclear myopathy.Hum Mol Genet. 2006 Nov 1;15(21):3098-106. doi: 10.1093/hmg/ddl250. Epub 2006 Sep 28.
3 Downregulation of miR-145-5p in cancer cellsand theirderived exosomes may contribute tothedevelopment of ovarian cancer by targeting CT.Int J Mol Med. 2019 Jan;43(1):256-266. doi: 10.3892/ijmm.2018.3958. Epub 2018 Oct 25.
4 Deficiency of MTMR14 impairs male fertility in Mus musculus.PLoS One. 2018 Nov 9;13(11):e0206224. doi: 10.1371/journal.pone.0206224. eCollection 2018.
5 Mice lacking myotubularin-related protein 14 show accelerated high-fat diet-induced lipid accumulation and inflammation.J Physiol Biochem. 2017 Feb;73(1):17-28. doi: 10.1007/s13105-016-0520-6. Epub 2016 Nov 2.
6 EDTP/MTMR14: A novel target for improved survivorship to prolonged anoxia and cellular protein aggregates.Neurosci Lett. 2019 Jul 13;705:151-158. doi: 10.1016/j.neulet.2019.04.053. Epub 2019 Apr 25.
7 Flexible and scalable diagnostic filtering of genomic variants using G2P with Ensembl VEP. Nat Commun. 2019 May 30;10(1):2373. doi: 10.1038/s41467-019-10016-3.
8 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.
9 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.
10 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
11 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.
12 Label-free quantitative proteomic analysis identifies the oncogenic role of FOXA1 in BaP-transformed 16HBE cells. Toxicol Appl Pharmacol. 2020 Sep 15;403:115160. doi: 10.1016/j.taap.2020.115160. Epub 2020 Jul 25.
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 Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.