ID:MTM1_HUMAN DESCRIPTION: RecName: Full=Myotubularin; EC=3.1.3.64; FUNCTION: Lipid phosphatase which dephosphorylates phosphatidylinositol 3-monophosphate (PI3P) and phosphatidylinositol 3,5-bisphosphate (PI(3,5)P2). Has also been shown to dephosphorylate phosphotyrosine- and phosphoserine- containing peptides. Negatively regulates EGFR degradation through regulation of EGFR trafficking from the late endosome to the lysosome. Plays a role in vacuolar formation and morphology. Regulates desmin intermediate filament assembly and architecture. Plays a role in mitochondrial morphology and positioning. Required for skeletal muscle maintenance but not for myogenesis. CATALYTIC ACTIVITY: 1-phosphatidyl-1D-myo-inositol 3-phosphate + H(2)O = 1-phosphatidyl-1D-myo-inositol + phosphate. ENZYME REGULATION: Allosterically activated by phosphatidylinositol 5-phosphate (PI5P). BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=39 uM for PI3P; KM=17 uM for PI(3,5)P2; SUBUNIT: Interacts with MTMR12; the interaction modulates MTM1 intracellular localization. Interacts with MLL (via SET domain). Interacts with DES in skeletal muscle but not in cardiac muscle. SUBCELLULAR LOCATION: Cytoplasm. Cell membrane; Peripheral membrane protein. Cell projection, filopodium. Cell projection, ruffle. Late endosome. Note=Localizes as a dense cytoplasmic network. Also localizes to the plasma membrane, including plasma membrane extensions such as filopodia and ruffles. Predominantly located in the cytoplasm following interaction with MTMR12. Recruited to the late endosome following EGF stimulation. DOMAIN: The GRAM domain mediates binding to PI(3,5)P2 and, with lower affinity, to other phosphoinositides. DISEASE: Defects in MTM1 are the cause of centronuclear myopathy X-linked (CNMX) [MIM:310400]. A congenital muscle disorder characterized by progressive muscular. weakness and wasting involving mainly limb girdle, trunk, and neck muscles. It may also affect distal muscles. Weakness may be present during childhood or adolescence or may not become evident until the third decade of life. Ptosis is a frequent clinical feature. The most prominent histopathologic features include high frequency of centrally located nuclei in muscle fibers not secondary to regeneration, radial arrangement of sarcoplasmic strands around the central nuclei, and predominance and hypotrophy of type 1 fibers. SIMILARITY: Belongs to the protein-tyrosine phosphatase family. Non-receptor class myotubularin subfamily. SIMILARITY: Contains 1 GRAM domain. SIMILARITY: Contains 1 myotubularin phosphatase domain. WEB RESOURCE: Name=GeneReviews; URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/MTM1"; WEB RESOURCE: Name=Leiden Muscular Dystrophy pages, Myotubularin 1 (MTM1); Note=Leiden Open Variation Database (LOVD); URL="http://www.lovd.nl/MTM1";
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on Q13496
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Biological Process: GO:0006470 protein dephosphorylation GO:0006629 lipid metabolic process GO:0006661 phosphatidylinositol biosynthetic process GO:0008333 endosome to lysosome transport GO:0015031 protein transport GO:0016311 dephosphorylation GO:0032007 negative regulation of TOR signaling GO:0032435 negative regulation of proteasomal ubiquitin-dependent protein catabolic process GO:0035335 peptidyl-tyrosine dephosphorylation GO:0044088 regulation of vacuole organization GO:0045109 intermediate filament organization GO:0046716 muscle cell cellular homeostasis GO:0046856 phosphatidylinositol dephosphorylation GO:0048311 mitochondrion distribution GO:0048633 positive regulation of skeletal muscle tissue growth GO:0051898 negative regulation of protein kinase B signaling GO:0070584 mitochondrion morphogenesis GO:1902902 negative regulation of autophagosome assembly
LF211510 - JP 2014500723-A/19013: Polycomb-Associated Non-Coding RNAs. AK291710 - Homo sapiens cDNA FLJ76887 complete cds, highly similar to Homo sapiens myotubularin 1 (MTM1), mRNA. U46024 - Homo sapiens myotubularin (MTM1) mRNA, complete cds. LP895642 - Sequence 506 from Patent EP3253886. AK304036 - Homo sapiens cDNA FLJ52391 complete cds, highly similar to Myotubularin (EC 3.1.3.48). AK297057 - Homo sapiens cDNA FLJ50571 complete cds, highly similar to Myotubularin (EC 3.1.3.48). AL832715 - Homo sapiens mRNA; cDNA DKFZp313N1835 (from clone DKFZp313N1835). AK297021 - Homo sapiens cDNA FLJ50569 complete cds, highly similar to Myotubularin (EC 3.1.3.48). BC030779 - Homo sapiens myotubularin 1, mRNA (cDNA clone MGC:26338 IMAGE:4824189), complete cds. AB384901 - Synthetic construct DNA, clone: pF1KB4121, Homo sapiens MTM1 gene for myotubularin, complete cds, without stop codon, in Flexi system. JF432327 - Synthetic construct Homo sapiens clone IMAGE:100073513 myotubularin 1 (MTM1) gene, encodes complete protein. KJ897208 - Synthetic construct Homo sapiens clone ccsbBroadEn_06602 MTM1 gene, encodes complete protein. KR709490 - Synthetic construct Homo sapiens clone CCSBHm_00002694 MTM1 (MTM1) mRNA, encodes complete protein. KR709491 - Synthetic construct Homo sapiens clone CCSBHm_00002711 MTM1 (MTM1) mRNA, encodes complete protein. KR709492 - Synthetic construct Homo sapiens clone CCSBHm_00002768 MTM1 (MTM1) mRNA, encodes complete protein. MA447087 - JP 2018138019-A/19013: Polycomb-Associated Non-Coding RNAs. JD104849 - Sequence 85873 from Patent EP1572962. JD069186 - Sequence 50210 from Patent EP1572962. CU689004 - Synthetic construct Homo sapiens gateway clone IMAGE:100020389 5' read MTM1 mRNA. LF380594 - JP 2014500723-A/188097: Polycomb-Associated Non-Coding RNAs. LF380599 - JP 2014500723-A/188102: Polycomb-Associated Non-Coding RNAs. LF380607 - JP 2014500723-A/188110: Polycomb-Associated Non-Coding RNAs. MA616171 - JP 2018138019-A/188097: Polycomb-Associated Non-Coding RNAs. MA616176 - JP 2018138019-A/188102: Polycomb-Associated Non-Coding RNAs. MA616184 - JP 2018138019-A/188110: Polycomb-Associated Non-Coding RNAs. LF380612 - JP 2014500723-A/188115: Polycomb-Associated Non-Coding RNAs. JD110764 - Sequence 91788 from Patent EP1572962. LF380613 - JP 2014500723-A/188116: Polycomb-Associated Non-Coding RNAs. JD288593 - Sequence 269617 from Patent EP1572962. JD303064 - Sequence 284088 from Patent EP1572962. JD130205 - Sequence 111229 from Patent EP1572962. JD298135 - Sequence 279159 from Patent EP1572962. JD305902 - Sequence 286926 from Patent EP1572962. JD298102 - Sequence 279126 from Patent EP1572962. JD041504 - Sequence 22528 from Patent EP1572962. JD408111 - Sequence 389135 from Patent EP1572962. JD276486 - Sequence 257510 from Patent EP1572962. JD232344 - Sequence 213368 from Patent EP1572962. JD400212 - Sequence 381236 from Patent EP1572962. MA616189 - JP 2018138019-A/188115: Polycomb-Associated Non-Coding RNAs. MA616190 - JP 2018138019-A/188116: Polycomb-Associated Non-Coding RNAs.
Biochemical and Signaling Pathways
Reactome (by CSHL, EBI, and GO)
Protein Q13496 (Reactome details) participates in the following event(s):
R-HSA-6809680 MTMR12 binds MTM1 R-HSA-6809720 PI3P is dephosphorylated to PI by MTM1:MTMR12 R-HSA-1676203 PI(3,5)P2 is dephosphorylated to PI5P by SYNJ/MTMs at the plasma membrane R-HSA-1675994 PI3P is dephosphorylated to PI by SYNJ/MTMs at the plasma membrane R-HSA-1675795 PI3P is dephosphorylated to PI by MTM proteins at the late endosome membrane R-HSA-1676065 PI(3,5)P2 is dephosphorylated to PI5P by MTM proteins at the late endosome membrane R-HSA-1676141 PI3P is dephosphorylated to PI by MTM proteins at the early endosome membrane R-HSA-1676105 PI(3,5)P2 is dephosphorylated to PI5P by MTM proteins at the early endosome membrane R-HSA-1660516 Synthesis of PIPs at the early endosome membrane R-HSA-1483255 PI Metabolism R-HSA-1660499 Synthesis of PIPs at the plasma membrane R-HSA-1660517 Synthesis of PIPs at the late endosome membrane R-HSA-1483257 Phospholipid metabolism R-HSA-556833 Metabolism of lipids R-HSA-1430728 Metabolism
US Server
Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
