MTM1

This gene encodes a dual-specificity phosphatase that acts on both phosphotyrosine and phosphoserine. It is required for muscle cell differentiation and mutations in this gene have been identified as being responsible for X-linked myotubular myopathy. [provided by RefSeq]

Full Name

myotubularin 1

Function

Lipid phosphatase which dephosphorylates phosphatidylinositol 3-monophosphate (PI3P) and phosphatidylinositol 3,5-bisphosphate (PI(3,5)P2) (PubMed:11001925, PubMed:10900271, PubMed:12646134, PubMed:14722070).

Has also been shown to dephosphorylate phosphotyrosine- and phosphoserine-containing peptides (PubMed:9537414).

Negatively regulates EGFR degradation through regulation of EGFR trafficking from the late endosome to the lysosome (PubMed:14722070).

Plays a role in vacuolar formation and morphology. Regulates desmin intermediate filament assembly and architecture (PubMed:21135508).

Plays a role in mitochondrial morphology and positioning (PubMed:21135508).

Required for skeletal muscle maintenance but not for myogenesis (PubMed:21135508).

In skeletal muscles, stabilizes MTMR12 protein levels (PubMed:23818870).

Biological Process

Endosome to lysosome transport Source: UniProtKB
Intermediate filament organization Source: UniProtKB
Mitochondrion distribution Source: UniProtKB
Mitochondrion morphogenesis Source: UniProtKB
Muscle cell cellular homeostasis Source: GO_Central
Negative regulation of autophagosome assembly Source: GO_Central
Negative regulation of proteasomal ubiquitin-dependent protein catabolic process Source: Ensembl
Negative regulation of protein kinase B signaling Source: Ensembl
Negative regulation of TOR signaling Source: Ensembl
Phosphatidylinositol biosynthetic process Source: Reactome
Phosphatidylinositol dephosphorylation Source: UniProtKB
Positive regulation of skeletal muscle tissue growth Source: Ensembl
Protein dephosphorylation Source: UniProtKB
Protein transport Source: UniProtKB-KW
Regulation of vacuole organization Source: UniProtKB

Cellular Location

Plasma membrane
Cell membrane
Cytoplasm
Endosome
Late endosome
Other locations
filopodium
ruffle
sarcomere
Note: Localizes as a dense cytoplasmic network (PubMed:11001925). Also localizes to the plasma membrane, including plasma membrane extensions such as filopodia and ruffles (PubMed:12118066). Predominantly located in the cytoplasm following interaction with MTMR12 (PubMed:12847286). Recruited to the late endosome following EGF stimulation (PubMed:14722070). In skeletal muscles, co-localizes with MTMR12 in the sarcomere (By similarity).

Involvement in disease

Myopathy, centronuclear, X-linked (CNMX):
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.