Recombinant Human Myotubularin (MTM1)

Function

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

Subcellular Location

Cytoplasm; Cell membrane (Peripheral membrane protein); Cell projection, filopodium; Cell projection, ruffle; Late endosome; Cytoplasm, myofibril, sarcomere

Disease Association

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. [The disease is caused by variants affecting the gene represented in this entry]

Subunit

Heterodimer with MTMR12 (PubMed:12847286, PubMed:23818870). Interacts with KMT2A/MLL1 (via SET domain) (PubMed:9537414). Interacts with DES in skeletal muscle but not in cardiac muscle (PubMed:21135508). Interacts with SPEG (PubMed:25087613)

• Laporte J. et al. A gene mutated in X-linked myotubular myopathy defines a new putative tyrosine phosphatase family conserved in yeast. — Nat. Genet. (1996)
• Laporte J. et al. Genomic organization of the MTM1 gene implicated in X-linked myotubular myopathy. — Eur. J. Hum. Genet. (1998)
• Ota T. et al. Complete sequencing and characterization of 21,243 full-length human cDNAs. — Nat. Genet. (2004)
• Ross M.T. et al. The DNA sequence of the human X chromosome. — Nature (2005)
• Mural R.J. et al. PubMed: CI-56FT96O07V0QG (JUL-)
• The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). — Genome Res. (2004)
• Cui X. et al. Association of SET domain and myotubularin-related proteins modulates growth control. — Nat. Genet. (1998)
• Laporte J. et al. MTM1 mutations in X-linked myotubular myopathy. — Hum. Mutat. (2000)