MTMR2

Summary

Gene Symbol: MTMR2
Description: myotubularin related protein 2
Alias: CMT4B, CMT4B1, myotubularin-related protein 2, phosphatidylinositol-3,5-bisphosphate 3-phosphatase, phosphatidylinositol-3-phosphatase, phosphatidylinositol-3-phosphate phosphatase, phosphoinositide-3-phosphatase
Species: human
Products:     MTMR2

Top Publications

  1. Laporte J, Hu L, Kretz C, Mandel J, Kioschis P, Coy J, et al. A gene mutated in X-linked myotubular myopathy defines a new putative tyrosine phosphatase family conserved in yeast. Nat Genet. 1996;13:175-82 pubmed
    ..At least three other genes, one located within 100 kb distal from the MTM1 gene, encode proteins with very high sequence similarities and define, together with the MTM1 gene, a new family of putative tyrosine phosphatases in man...
  2. Bolino A, Muglia M, Conforti F, LeGuern E, Salih M, Georgiou D, et al. Charcot-Marie-Tooth type 4B is caused by mutations in the gene encoding myotubularin-related protein-2. Nat Genet. 2000;25:17-9 pubmed
    A gene mutated in Charcot-Marie-Tooth disease type 4B (CMT4B), an autosomal recessive demyelinating neuropathy with myelin outfoldings, has been mapped on chromosome 11q22...
  3. Laporte J, Liaubet L, Blondeau F, Tronchère H, Mandel J, Payrastre B. Functional redundancy in the myotubularin family. Biochem Biophys Res Commun. 2002;291:305-12 pubmed
    ..This might be explained by subtle differences in expression and/or in recruitment and regulation at their specific site of action. ..
  4. Robinson F, Dixon J. The phosphoinositide-3-phosphatase MTMR2 associates with MTMR13, a membrane-associated pseudophosphatase also mutated in type 4B Charcot-Marie-Tooth disease. J Biol Chem. 2005;280:31699-707 pubmed
    ..CMT4B is caused by recessively inherited mutations in either myotubularin-related 2 (MTMR2) or MTMR13 (also called SET-binding factor 2)...
  5. Kim S, Vacratsis P, Firestein R, Cleary M, Dixon J. Regulation of myotubularin-related (MTMR)2 phosphatidylinositol phosphatase by MTMR5, a catalytically inactive phosphatase. Proc Natl Acad Sci U S A. 2003;100:4492-7 pubmed
    ..In this study, we identified a protein that specifically interacts with MTMR2 but not MTM1...
  6. Begley M, Taylor G, Kim S, Veine D, Dixon J, Stuckey J. Crystal structure of a phosphoinositide phosphatase, MTMR2: insights into myotubular myopathy and Charcot-Marie-Tooth syndrome. Mol Cell. 2003;12:1391-402 pubmed
    ..The crystal structure of a representative member of this family, MTMR2, reveals a phosphatase domain that is structurally unique among PTPs...
  7. Chojnowski A, Ravisé N, Bachelin C, Depienne C, Ruberg M, Brugg B, et al. Silencing of the Charcot-Marie-Tooth associated MTMR2 gene decreases proliferation and enhances cell death in primary cultures of Schwann cells. Neurobiol Dis. 2007;26:323-31 pubmed
    Loss of function of the myotubularin (MTM)-related protein 2 (MTMR2) in Schwann cells causes Charcot-Marie-Tooth disease type 4B1, a severe demyelinating neuropathy, but the consequences of MTMR2 disruption in Schwann cells are unknown...
  8. Previtali S, Zerega B, Sherman D, Brophy P, Dina G, King R, et al. Myotubularin-related 2 protein phosphatase and neurofilament light chain protein, both mutated in CMT neuropathies, interact in peripheral nerve. Hum Mol Genet. 2003;12:1713-23 pubmed
    Charcot-Marie-Tooth disease type 4B1, CMT4B1, is a severe, autosomal-recessive, demyelinating peripheral neuropathy, due to mutations in the Myotubularin-related 2 gene, MTMR2...
  9. Birouk N. [Review of the recent literature on hereditary neuropathies]. Rev Neurol (Paris). 2014;170:846-9 pubmed publisher
    ..KIF1B controls vesicle motility on microtubules. MTMR2, MTMR13 and FIG4 regulate the metabolism of phosphoinositide at the level of endosomes...

More Information

Publications37

  1. Brenner D, Amos C, Brhane Y, Timofeeva M, Caporaso N, Wang Y, et al. Identification of lung cancer histology-specific variants applying Bayesian framework variant prioritization approaches within the TRICL and ILCCO consortia. Carcinogenesis. 2015;36:1314-26 pubmed publisher
    ..2 (rs6448050, P = 4.6×10(-7)) and MTMR2 at 11q21 (rs10501831, P = 3.1×10(-6)) with SCC, as well as GAREM at 18q12.1 (rs11662168, P = 3...
  2. Bolino A, Piguet F, Alberizzi V, Pellegatta M, Rivellini C, Guerrero Valero M, et al. Niacin-mediated Tace activation ameliorates CMT neuropathies with focal hypermyelination. EMBO Mol Med. 2016;8:1438-1454 pubmed publisher
    ..drug known to enhance TACE activity, efficiently rescues myelination in the Mtmr2-/- mouse, a model of CMT4B1 with myelin outfoldings, and in the Pmp22+/- mouse, which reproduces HNPP (hereditary neuropathy with ..
  3. Yoo K, Son J, Lee J, Shin W, Im D, Kim S, et al. Structure of the catalytic phosphatase domain of MTMR8: implications for dimerization, membrane association and reversible oxidation. Acta Crystallogr D Biol Crystallogr. 2015;71:1528-39 pubmed publisher
    ..studies suggest that Lys255 of MTMR8 interacts with the substrate diacylglycerol moiety, similar to Lys333 of MTMR2, although the positions of these residues are different...
  4. Abdalla Moady T, Peleg A, Sadeh O, Badarneh K, Fares F. Whole-Exome Sequencing Identifies a Novel Homozygous Frameshift Mutation in the MTMR2 Gene as a Causative Mutation in a Patient with Charcot-Marie-Tooth Disease Type 4B1. Mol Neurobiol. 2018;55:3546-3550 pubmed publisher
    ..1877_1878insAGAG, p.Arg630fs) in the myotubularin-related protein-2 gene (MTMR2), which resulted in an erroneous C-terminal sequence and extension by 15 amino acids...
  5. Bong S, Son K, Yang S, Park J, Cho J, Kim K, et al. Crystal Structure of Human Myotubularin-Related Protein 1 Provides Insight into the Structural Basis of Substrate Specificity. PLoS ONE. 2016;11:e0152611 pubmed publisher
    ..The overall structure was highly similar to the previously reported MTMR2 structure...
  6. Xhabija B, Taylor G, Fujibayashi A, Sekiguchi K, Vacratsis P. Receptor mediated endocytosis 8 is a novel PI(3)P binding protein regulated by myotubularin-related 2. FEBS Lett. 2011;585:1722-8 pubmed publisher
    b>Myotubularin related protein 2 (MTMR2) is a member of the myotubularin family of phosphoinositide lipid phosphatases...
  7. Liska F, Chylíková B, Janků M, Seda O, Vernerova Z, Pravenec M, et al. Splicing mutation in Sbf1 causes nonsyndromic male infertility in the rat. Reproduction. 2016;152:215-23 pubmed publisher
    ..It probably modulates the activity of a phosphoinositol phosphatase MTMR2. Human homozygotes or compound heterozygotes for missense SBF1 mutations exhibit Charcot-Marie-Tooth disease (..
  8. Luigetti M, Bolino A, Scarlino S, Sabatelli M. A novel homozygous mutation in the MTMR2 gene in two siblings with 'hypermyelinating neuropathy'. J Peripher Nerv Syst. 2013;18:192-4 pubmed publisher
  9. Franklin N, Taylor G, Vacratsis P. Endosomal targeting of the phosphoinositide 3-phosphatase MTMR2 is regulated by an N-terminal phosphorylation site. J Biol Chem. 2011;286:15841-53 pubmed publisher
    b>MTMR2 is a member of the myotubularin family of inositol lipid phosphatases, a large protein-tyrosine phosphatase subgroup that is conserved from yeast to humans...
  10. Franklin N, Bonham C, Xhabija B, Vacratsis P. Differential phosphorylation of the phosphoinositide 3-phosphatase MTMR2 regulates its association with early endosomal subtypes. J Cell Sci. 2013;126:1333-44 pubmed publisher
    Myotubularin-related 2 (MTMR2) is a 3-phosphoinositide lipid phosphatase with specificity towards the D-3 position of phosphoinositol 3-phosphate [PI(3)P] and phosphoinositol 3,5-bisphosphate lipids enriched on endosomal structures...
  11. Lecompte O, Poch O, Laporte J. PtdIns5P regulation through evolution: roles in membrane trafficking?. Trends Biochem Sci. 2008;33:453-60 pubmed publisher
    ..By examining PtdIns5P metabolism in this new perspective, we propose a role for PtdIns5P in membrane trafficking from late endosomal compartments to the plasma membrane. ..
  12. Mansour R, Severin S, Xuereb J, Gratacap M, Laporte J, Buj Bello A, et al. Expression of myotubularins in blood platelets: Characterization and potential diagnostic of X-linked myotubular myopathy. Biochem Biophys Res Commun. 2016;476:167-73 pubmed publisher
    ..of this family are mutated in genetic diseases including myotubularin 1 (MTM1) and myotubularin-related protein 2 (MTMR2) which mutations are responsible of X-linked centronuclear myopathy and Charcot-Marie-Tooth neuropathy, ..
  13. Nelis E, Erdem S, Tan E, Lofgren A, Ceuterick C, De Jonghe P, et al. A novel homozygous missense mutation in the myotubularin-related protein 2 gene associated with recessive Charcot-Marie-Tooth disease with irregularly folded myelin sheaths. Neuromuscul Disord. 2002;12:869-73 pubmed
    ..847, resulting in an amino acid substitution of arginine to tryptophan at codon 283, was detected in exon 9 of the MTMR2 gene...
  14. Raess M, Cowling B, Bertazzi D, Kretz C, Rinaldi B, Xuereb J, et al. Expression of the neuropathy-associated MTMR2 gene rescues MTM1-associated myopathy. Hum Mol Genet. 2017;26:3736-3748 pubmed publisher
    ..called myotubular myopathy (or X-linked centronuclear myopathy) while mutations in the MTM1-related protein MTMR2 cause a recessive Charcot-Marie-Tooth peripheral neuropathy...
  15. Zambon A, Natali Sora M, Cantarella G, Cerri F, Quattrini A, Comi G, et al. Vocal cord paralysis in Charcot-Marie-Tooth type 4b1 disease associated with a novel mutation in the myotubularin-related protein 2 gene: A case report and review of the literature. Neuromuscul Disord. 2017;27:487-491 pubmed publisher
    Charcot-Marie-Tooth type 4B1 (CMT4B1) is an autosomal recessive motor and sensory demyelinating neuropathy characterized by the association of early-onset neurological symptoms and typical histological findings...
  16. Previtali S, Quattrini A, Bolino A. Charcot-Marie-Tooth type 4B demyelinating neuropathy: deciphering the role of MTMR phosphatases. Expert Rev Mol Med. 2007;9:1-16 pubmed
    ..but thus far, mutations in myotubularin-related 2 (MTMR2) and MTMR13 genes have been shown to underlie CMT4B1 and CMT4B2, respectively...
  17. Begley M, Taylor G, Brock M, Ghosh P, Woods V, Dixon J. Molecular basis for substrate recognition by MTMR2, a myotubularin family phosphoinositide phosphatase. Proc Natl Acad Sci U S A. 2006;103:927-32 pubmed
    ..crystallographic and deuterium-exchange mass spectrometry studies of human myotubularin-related protein-2 (MTMR2) in complex with phosphoinositides, we define the molecular basis for this unique substrate specificity...
  18. Laporte J, Bedez F, Bolino A, Mandel J. Myotubularins, a large disease-associated family of cooperating catalytically active and inactive phosphoinositides phosphatases. Hum Mol Genet. 2003;12 Spec No 2:R285-92 pubmed
    ..Myotubularins are thus proposed to be implicated in these cellular mechanisms, and recent observations on myotubularins homologues in the nematode Caenorhabditis elegans indicate a role in endocytosis. ..
  19. Boerkoel C, Takashima H, Garcia C, Olney R, Johnson J, Berry K, et al. Charcot-Marie-Tooth disease and related neuropathies: mutation distribution and genotype-phenotype correlation. Ann Neurol. 2002;51:190-201 pubmed
    ..myelin protein 22, myelin protein zero, connexin 32, early growth response factor 2, periaxin, myotubularin related protein 2, N-myc downstream regulated gene 1 product, neurofilament light chain, and kinesin 1B...
  20. Nouioua S, Hamadouche T, Funalot B, Bernard R, Bellatache N, Bouderba R, et al. Novel mutations in the PRX and the MTMR2 genes are responsible for unusual Charcot-Marie-Tooth disease phenotypes. Neuromuscul Disord. 2011;21:543-50 pubmed publisher
    ..1090C>T (p.Arg364X) respectively, and peculiar clinical phenotypes. The three patients with MTMR2 mutations (CMT4B1 family) had a typical phenotype of severe early onset motor and sensory neuropathy with typical focally folded ..
  21. Kim Y, Wu Q, Chen J, Xuan Z, Jung Y, Zhang M, et al. The transcriptome of human CD34+ hematopoietic stem-progenitor cells. Proc Natl Acad Sci U S A. 2009;106:8278-83 pubmed publisher
    ..The data generated from our study provide a comprehensive and uniform resource for studying hematopoiesis and stem cell biology. ..
  22. Nicot A, Laporte J. Endosomal phosphoinositides and human diseases. Traffic. 2008;9:1240-9 pubmed publisher
    ..3-phosphatase myotubularin gene is mutated in X-linked centronuclear myopathy, whereas its homologs MTMR2 and MTMR13 and the PtdIns(3,5)P(2) 5-phosphatase SAC3/FIG4 are implicated in Charcot-Marie-Tooth peripheral ..
  23. Fogarty E, Brewer M, Rodriguez Molina J, Law W, Ma K, Steinberg N, et al. SOX10 regulates an alternative promoter at the Charcot-Marie-Tooth disease locus MTMR2. Hum Mol Genet. 2016;25:3925-3936 pubmed publisher
    ..mutations in the gene encoding myotubularin-related protein 2 (MTMR2) cause Charcot-Marie-Tooth disease type 4B1 (CMT4B1), a severe demyelinating peripheral neuropathy characterized by myelin outfoldings along peripheral nerves...
  24. Laporte J, Blondeau F, Buj Bello A, Tentler D, Kretz C, Dahl N, et al. Characterization of the myotubularin dual specificity phosphatase gene family from yeast to human. Hum Mol Genet. 1998;7:1703-12 pubmed
    ..Comparison of the various genes allowed construction of a phylogenetic tree and reveals conserved residues which may be essential for function. These genes may be good candidates for other genetic diseases. ..
  25. Zhang R, Guo P, Ren Z, Zhao G, Liu S, Liu T, et al. [Mutation analysis of LITAF, RAB7, LMNA and MTMR2 genes in Chinese Charcot-Marie-Tooth disease.]. Yi Chuan. 2010;32:817-23 pubmed
    ..factor (LITAF), ras-associated protein RAB7 (RAB7), lamin A/C (LMNA) and myotubularin-related protein 2 (MTMR2) genes in Chinese Charcot-Marie-Tooth disease (CMT) patients...
  26. Lee H, Kim Y, Han K, Kim H, Kim E. The phosphoinositide 3-phosphatase MTMR2 interacts with PSD-95 and maintains excitatory synapses by modulating endosomal traffic. J Neurosci. 2010;30:5508-18 pubmed publisher
    b>MTMR2 is a 3-phosphatase specific for the phosphoinositides PI(3)P and PI(3,5)P(2), which are mainly present on endosomes...
  27. Lorenzo O, Urbé S, Clague M. Systematic analysis of myotubularins: heteromeric interactions, subcellular localisation and endosome related functions. J Cell Sci. 2006;119:2953-9 pubmed
    ..All active MTMs we have tested (MTM1, MTMR2-MTMR4) reduce endosomal PtdIns3P levels upon overexpression...