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MGP001972

UniProt Annotations

Entry Information
Gene Namemyotubularin 1
Protein EntryMTM1_HUMAN
UniProt IDQ13496
SpeciesHuman
Comments
Comment typeDescription
Alternative ProductsEvent=Alternative splicing; Named isoforms=2; Name=1; IsoId=Q13496-1; Sequence=Displayed; Name=2; IsoId=Q13496-2; Sequence=VSP_056208; Note=No experimental confirmation available.;
Biophysicochemical PropertiesKinetic parameters: KM=39 uM for PI3P {ECO:0000269|PubMed:14722070}; KM=17 uM for PI(3,5)P2 {ECO:0000269|PubMed:14722070};
Catalytic Activity1-phosphatidyl-1D-myo-inositol 3,5- bisphosphate + H(2)O = 1-phosphatidyl-1D-myo-inositol 5-phosphate + phosphate. {ECO:0000269|PubMed:12646134}.
Catalytic Activity1-phosphatidyl-1D-myo-inositol 3-phosphate + H(2)O = 1-phosphatidyl-1D-myo-inositol + phosphate. {ECO:0000269|PubMed:10900271, ECO:0000269|PubMed:11001925, ECO:0000269|PubMed:12646134, ECO:0000269|PubMed:12847286}.
DiseaseMyopathy, centronuclear, 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. {ECO:0000269|PubMed:10063835, ECO:0000269|PubMed:10466421, ECO:0000269|PubMed:10502779, ECO:0000269|PubMed:11793470, ECO:0000269|PubMed:12031625, ECO:0000269|PubMed:12522554, ECO:0000269|PubMed:12859411, ECO:0000269|PubMed:17005396, ECO:0000269|PubMed:19129059, ECO:0000269|PubMed:9285787, ECO:0000269|PubMed:9305655, ECO:0000269|PubMed:9829274}. Note=The disease is caused by mutations affecting the gene represented in this entry.
DomainThe GRAM domain mediates binding to PI(3,5)P2 and, with lower affinity, to other phosphoinositides.
Enzyme RegulationAllosterically activated by phosphatidylinositol 5-phosphate (PI5P). {ECO:0000269|PubMed:12646134}.
FunctionLipid 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. {ECO:0000269|PubMed:10900271, ECO:0000269|PubMed:11001925, ECO:0000269|PubMed:12646134, ECO:0000269|PubMed:14722070, ECO:0000269|PubMed:21135508, ECO:0000269|PubMed:9537414}.
InteractionO00499:BIN1; NbExp=6; IntAct=EBI-2864109, EBI-719094; P17661:DES; NbExp=13; IntAct=EBI-2864109, EBI-1055572; P31001:Des (xeno); NbExp=4; IntAct=EBI-2864109, EBI-298565; Q9C0I1:MTMR12; NbExp=4; IntAct=EBI-2864109, EBI-2829520;
SimilarityBelongs to the protein-tyrosine phosphatase family. Non-receptor class myotubularin subfamily. {ECO:0000305}.
SimilarityContains 1 GRAM domain. {ECO:0000305}.
SimilarityContains 1 myotubularin phosphatase domain. {ECO:0000255|PROSITE-ProRule:PRU00669}.
Subcellular LocationCytoplasm {ECO:0000269|PubMed:10900271, ECO:0000269|PubMed:11001925}. Cell membrane; Peripheral membrane protein {ECO:0000269|PubMed:11001925}. Cell projection, filopodium {ECO:0000269|PubMed:12118066}. Cell projection, ruffle {ECO:0000269|PubMed:12118066}. Late endosome {ECO:0000269|PubMed:14722070}. 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. {ECO:0000269|PubMed:11001925, ECO:0000269|PubMed:12118066}.
SubunitInteracts with MTMR12; the interaction modulates MTM1 intracellular localization. Interacts with KMT2A/MLL1 (via SET domain). Interacts with DES in skeletal muscle but not in cardiac muscle. Interacts with SPEG. {ECO:0000269|PubMed:12847286, ECO:0000269|PubMed:21135508, ECO:0000269|PubMed:25087613, ECO:0000269|PubMed:9537414}.
Web ResourceName=Leiden Muscular Dystrophy pages, Myotubularin 1 (MTM1); Note=Leiden Open Variation Database (LOVD); URL="http://www.lovd.nl/MTM1";
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