Myotubularin (MTM1)
The protein contains 603 amino acids for an estimated molecular weight of 69932 Da.
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). (updated: Dec. 5, 2018)
Protein identification was indicated in the following studies:
- Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
- Lange and co-workers. (2014) Annotating N termini for the human proteome project: N termini and Nα-acetylation status differentiate stable cleaved protein species from degradation remnants in the human erythrocyte proteome. J Proteome Res. 13(4), 2028-2044.
- Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
This protein is annotated as membranous in Gene Ontology, is annotated as membranous in UniProt.
(right-click above to access to more options from the contextual menu)
Biological Process
Endosome to lysosome transport
Intermediate filament organization
Mitochondrion distribution
Mitochondrion morphogenesis
Muscle cell cellular homeostasis
Negative regulation of autophagosome assembly
Negative regulation of proteasomal ubiquitin-dependent protein catabolic process
Negative regulation of protein kinase B signaling
Negative regulation of TOR signaling
Phosphatidylinositol biosynthetic process
Phosphatidylinositol dephosphorylation
Phospholipid metabolic process
Positive regulation of skeletal muscle tissue growth
Protein dephosphorylation
Protein transport
Regulation of vacuole organization
Small molecule metabolic process
Cellular Component
Cytoplasm
Cytosol
Extracellular exosome
Filopodium
I band
Late endosome
Obsolete cell
Plasma membrane
Ruffle
The reference OMIM entry for this protein is 300415
Myotubularin; mtm1
DESCRIPTION
The MTM1 gene encodes a protein that belongs to a family of putative tyrosine phosphatases. Myotubularin is required for muscle cell differentiation. Myotubularin is also a potent phosphatidylinositol 3-phosphate (PI3P) phosphatase (Blondeau et al., 2000; Taylor et al., 2000). According to Laporte et al. (1998), 8 different genes encoding human myotubularin-related proteins had been reported: MTMR1 (300171) on Xq28; MTMR2 (603557) on 11q22; MTMR3 (603558) on 22q12; MTMR4 (603559) on chromosome 17; SBF1, also known as MTMR5 (603560), on 22qter; MTMR6 (603561) on 13q12; MTMR7 (603562) on 8p22; and MTMR8 (606260) on 8p23-p22.CLONING
A consortium of 3 groups (Laporte et al., 1996) reported the isolation and characterization of the MTM1 gene (Laporte et al., 1996). They restricted the candidate region for the gene mutated in X-linked myotubular myopathy-1 (XLMTM; 310400) to 280 kb and then used positional cloning to characterize a 3.4-kb cDNA that encodes at least 621 amino acids and a polyadenylation site. Additional clones from liver and skeletal muscle showed an alternative upstream polyadenylation site. The protein encoded by the MTM1 gene, designated myotubularin, was found to be highly conserved in yeast. The protein contains the consensus sequence for the active site of tyrosine phosphatases, a wide class of proteins involved in signal transduction. Preliminary Northern analysis showed ubiquitous expression of a 3.9-kb MTM1 transcript, while a 2.4-kb message was detected in skeletal muscle and testis. Both the high conservation in yeast and the ubiquitous expression of the MTM1 transcript contrasted strikingly with the apparent muscle specificity of the disease myotubular myopathy. Laporte et al. (1996) stated that at least 3 other genes, 1 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 (PTPs) in man. Kioschis et al. (1996) constructed a 900-kb cosmid contig including the entire MTM1 candidate region and identified 10 new transcripts within the region.MAPPING
By positional cloning, Laporte et al. (1996) mapped the MTM1 gene to Xq28. Kioschis et al. (1998) determined that the MTM1 and MTMR1 genes are transcribed in the same direction and are separated by 20 kb. Analysis of the genomic region containing MTM1 and MTMR1 suggested that the 2 genes are related and arose from an intrachromosomal gene duplication. The authors stated that other examples of intrachromosomal gene duplication in Xq28 include the IDS (300823) gene duplication and a cluster of MAGE genes (see 300016). As part of an effort to clone the MTM1 gene, de Gouyon et al. (1996) developed a YAC contig of the mouse X chromosome which included loci homologous to those within the human MTM1 critical region, a 300-kb interval between IDS (300823) and GABRA3 (305660) on Xq28. They aligned the human and murine physical maps by isolating conserved mouse genomic fragments, including CpG islands and trapped exons.GENE FUNCTION
The SET (Suvar3-9, Enhancer of zeste, trithorax) domain was originally identified as a characteristic motif in several Drosophila proteins that contribute to epigenetic mechanisms of gene regulation. The human protooncoprotein HRX (159555) also contains a SET domain. Cui et al. (1998) determined that MTM1 and SBF1 (603560) interacted with HRX in vitro and in vivo ... More on the omim web site
Dec. 9, 2018: Protein entry updated
Automatic update: Entry updated from uniprot information.
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 300415 was added.