Reviewed,
UniProtKB/Swiss-Prot Q13496 (MTM1_HUMAN)
Last modified
November 25, 2008.
Version 77.
History...
Clusters with 100%,
90%,
50% identity |
Documents (5) |
Third-party data |
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Names and origin
| Protein names | Recommended name: Myotubularin EC=3.1.3.48 | ||||
| Gene names |
| ||||
| Organism | Homo sapiens (Human) | ||||
| Taxonomic identifier | 9606 [NCBI] | ||||
| Taxonomic lineage | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Protein attributes
| Sequence length | 603 AA. |
| Sequence status | Complete. |
| Sequence processing | The displayed sequence is not processed. |
| Protein existence | Evidence at protein level. |
General annotation (Comments)
| Function | Dual-specificity phosphatase that acts on both phosphotyrosine and phosphoserine. Could be involved in a signal transduction pathway necessary for late myogenesis, although its ubiquitous expression suggests a wider function. |
| Catalytic activity | Protein tyrosine phosphate + H(2)O = protein tyrosine + phosphate. |
| Involvement in disease | Defects in MTM1 are the cause of X-linked centronuclear myopathy X-linked (XCNM) [MIM:310400]; also known as X-linked myotubular myopathy (XLMTM) or myotubular myopathy type 1 (MTM1). Centronuclear myopathies are congenital muscle disorders 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. |
| Sequence similarities | Belongs to the protein-tyrosine phosphatase family. Non-receptor class myotubularin subfamily. Contains 1 GRAM domain. Contains 1 myotubularin phosphatase domain. |
Ontologies
Keywords | |
|---|---|
| Disease | Disease mutation |
| Molecular function | Hydrolase Protein phosphatase |
| PTM | Phosphoprotein |
Gene Ontology (GO) | |
| Biological process | muscle development Ref.1 Traceable author statement. Source: ProtInc protein amino acid dephosphorylation Ref.1Non-traceable author statement. Source: UniProtKB |
| Cellular component | cytoplasm Inferred from direct assay. Source: HPA extracellular matrixInferred from direct assay. Source: HPA plasma membraneInferred from direct assay. Source: HPA |
| Molecular function | protein serine/threonine phosphatase activity Non-traceable author statement. Source: UniProtKB protein tyrosine phosphatase activity Ref.1Non-traceable author statement. Source: UniProtKB |
| Complete GO annotation... | |
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | ||||
Molecule processing | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Chain | 1 – 603 | 603 | Myotubularin | PRO_0000094930 | |||||
Regions | |||||||||
| Domain | 29 – 97 | 69 | GRAM | ||||||
| Domain | 163 – 538 | 376 | Myotubularin phosphatase | ||||||
Sites | |||||||||
| Active site | 375 | 1 | Phosphocysteine intermediate By similarity | ||||||
Amino acid modifications | |||||||||
| Modified residue | 13 | 1 | Phosphoserine | ||||||
| Modified residue | 495 | 1 | Phosphothreonine | ||||||
| Modified residue | 588 | 1 | Phosphoserine | ||||||
| Modified residue | 591 | 1 | Phosphoserine | ||||||
Natural variations | |||||||||
| Natural variant | 47 | 1 | Missing in XCNM. | VAR_006386 | |||||
| Natural variant | 49 | 1 | V → F in XCNM. | VAR_018227 | |||||
| Natural variant | 68 | 1 | Y → D in XCNM. | VAR_018228 | |||||
| Natural variant | 69 | 1 | R → C in XCNM; mild. | VAR_006387 | |||||
| Natural variant | 69 | 1 | R → P in XCNM. | VAR_018229 | |||||
| Natural variant | 69 | 1 | R → S in XCNM; severe. | VAR_018230 | |||||
| Natural variant | 70 | 1 | L → F in XCNM; mild. | VAR_006388 | |||||
| Natural variant | 87 | 1 | L → P in XCNM; mild. | VAR_006389 | |||||
| Natural variant | 157 | 1 | E → K in XCNM. | VAR_018231 | |||||
| Natural variant | 179 | 1 | P → S in XCNM; mild. | VAR_009217 | |||||
| Natural variant | 180 | 1 | N → K in XCNM; very mild. | VAR_018232 | |||||
| Natural variant | 184 | 1 | R → G in XCNM; severe. | VAR_006390 | |||||
| Natural variant | 184 | 1 | R → L in XCNM. | VAR_018233 | |||||
| Natural variant | 186 | 1 | T → I in XCNM. | VAR_018234 | |||||
| Natural variant | 189 | 1 | N → S in XCNM. | VAR_006391 | |||||
| Natural variant | 197 | 1 | T → I in XCNM. | VAR_018235 | |||||
| Natural variant | 198 | 1 | Y → N in XCNM; severe. | VAR_006392 | |||||
| Natural variant | 199 | 1 | P → S in XCNM. | VAR_018236 | |||||
| Natural variant | 202 | 1 | L → S in XCNM; severe. | VAR_018237 | |||||
| Natural variant | 205 | 1 | P → L in XCNM; severe. | VAR_006393 | |||||
| Natural variant | 225 | 1 | I → T in XCNM; mild. | VAR_009218 | |||||
| Natural variant | 226 | 1 | P → T in XCNM. | VAR_018238 | |||||
| Natural variant | 227 | 1 | V → M in XCNM. | VAR_018239 | |||||
| Natural variant | 228 | 1 | L → P in XCNM. | VAR_018240 | |||||
| Natural variant | 229 | 1 | S → P in XCNM; mild. | VAR_006394 | |||||
| Natural variant | 230 | 1 | W → C in XCNM. | VAR_018241 | |||||
| Natural variant | 232 | 1 | H → R in XCNM. | VAR_018242 | |||||
| Natural variant | 241 | 1 | R → C in XCNM; mild to moderate. | VAR_006395 | |||||
| Natural variant | 241 | 1 | R → L in XCNM; severe. | VAR_006396 | |||||
| Natural variant | 264 | 1 | I → S in XCNM; severe. | VAR_009219 | |||||
| Natural variant | 279 | 1 | A → G in XCNM. | VAR_018243 | |||||
| Natural variant | 294 | 1 | Missing in XCNM; mild. | VAR_009220 | |||||
| Natural variant | 317 | 1 | M → R in XCNM; mild. | VAR_006397 | |||||
| Natural variant | 346 | 1 | W → C in XCNM; mild. | VAR_018244 | |||||
| Natural variant | 346 | 1 | W → S in XCNM. | VAR_018245 | |||||
| Natural variant | 364 | 1 | V → G in XCNM. | VAR_018246 | |||||
| Natural variant | 374 | 1 | H → D in XCNM. | VAR_018247 | |||||
| Natural variant | 376 | 1 | S → N in XCNM. | VAR_006398 | |||||
| Natural variant | 378 | 1 | G → E in XCNM. | VAR_018248 | |||||
| Natural variant | 378 | 1 | G → R in XCNM; severe. | VAR_006399 | |||||
| Natural variant | 389 | 1 | A → D in XCNM; severe. | VAR_018249 | |||||
| Natural variant | 391 | 1 | L → P in XCNM. | VAR_018250 | |||||
| Natural variant | 397 | 1 | Y → C in XCNM; severe. | VAR_006400 | |||||
| Natural variant | 402 | 1 | G → A in XCNM; mild. | VAR_006401 | |||||
| Natural variant | 402 | 1 | G → R in XCNM. | VAR_018251 | |||||
| Natural variant | 402 | 1 | G → V in XCNM. | VAR_018252 | |||||
| Natural variant | 404 | 1 | E → K in XCNM; mild. | VAR_006402 | |||||
| Natural variant | 406 | 1 | L → P in XCNM; severe. | VAR_006403 | |||||
| Natural variant | 411 | 1 | W → C in XCNM. | VAR_018253 | |||||
| Natural variant | 420 | 1 | S → SFIQ in XCNM; severe. | VAR_009221 | |||||
| Natural variant | 421 | 1 | R → Q in XCNM; severe. | VAR_006404 | |||||
| Natural variant | 421 | 1 | R → RFIQ in XCNM; severe. | VAR_006405 | |||||
| Natural variant | 431 | 1 | D → N in XCNM. | VAR_006406 | |||||
| Natural variant | 433 | 1 | D → N in XCNM. | VAR_006407 | |||||
| Natural variant | 444 | 1 | C → Y in XCNM. | VAR_018254 | |||||
| Natural variant | 469 | 1 | H → P in XCNM. | VAR_006408 | |||||
| Natural variant | 470 | 1 | L → P in XCNM; severe. | VAR_018255 | |||||
| Natural variant | 481 | 1 | N → Y in XCNM; mild. | VAR_018256 | |||||
| Natural variant | 499 | 1 | W → R in XCNM; mild. | VAR_006409 | |||||
| Natural variant | 510 | 1 | K → N in XCNM; severe. | VAR_009222 | |||||
Experimental info | |||||||||
| Sequence conflict | 410 | 1 | E → K in AAH30779. Ref.3 | ||||||
Sequences
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References
| « Hide 'large scale' references | |
| [1] | "A gene mutated in X-linked myotubular myopathy defines a new putative tyrosine phosphatase family conserved in yeast." Laporte J., Hu L.-J., Kretz C., Mandel J.-L., Kioschis P., Coy J., Klauck S.M., Poutska A., Dahl N. Nat. Genet. 13:175-182(1996) [PubMed: 8640223] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. |
| [2] | "Genomic organization of the MTM1 gene implicated in X-linked myotubular myopathy." Laporte J., Guiraud-Chaumeil C., Tanner S.M., Blondeau F., Hu L.J., Vicaire S., Liechti-Gallati S., Mandel J.-L. Eur. J. Hum. Genet. 6:325-330(1998) [PubMed: 9781038] [Abstract] Cited for: NUCLEOTIDE SEQUENCE. |
| [3] | "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Testis. |
| [4] | "MTM1 mutations in X-linked myotubular myopathy." Laporte J., Biancalana V., Tanner S.M., Kress W., Schneider V., Wallgren-Pettersson C., Herger F., Buj-Bello A., Blondeau F., Liechti-Gallati S., Mandel J.-L. Hum. Mutat. 15:393-409(2000) [PubMed: 10790201] [Abstract] Cited for: REVIEW ON XCNM VARIANTS. |
| [5] | "A probability-based approach for high-throughput protein phosphorylation analysis and site localization." Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P. Nat. Biotechnol. 24:1285-1292(2006) [PubMed: 16964243] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-495, MASS SPECTROMETRY. Tissue: Epithelium. |
| [6] | "Phosphoproteome of resting human platelets." Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J., Schuetz C., Walter U., Gambaryan S., Sickmann A. J. Proteome Res. 7:526-534(2008) [PubMed: 18088087] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-13, MASS SPECTROMETRY. Tissue: Platelet. |
| [7] | "A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-588 AND SER-591, MASS SPECTROMETRY. |
| [8] | "Characterization of mutations in the myotubularin gene in twenty six patients with X-linked myotubular myopathy." de Gouyon B.M., Zhao W., Laporte J., Mandel J.-L., Metzenberg A., Herman G.E. Hum. Mol. Genet. 6:1499-1504(1997) [PubMed: 9285787] [Abstract] Cited for: VARIANTS XCNM CYS-69; GLY-184; ASN-198; LEU-241; ARG-317; CYS-397; LYS-404; PRO-406; GLN-421 AND ARG-499. |
| [9] | "Mutations in the MTM1 gene implicated in X-linked myotubular myopathy." Laporte J., Guiraud-Chaumeil C., Vincent M.-C., Mandel J.-L., Tanner S.M., Liechti-Gallati S., Wallgren-Pettersson C., Dahl N., Kress W., Bolhuis P.A., Fardeau M., Samson F., Bertini E. Hum. Mol. Genet. 6:1505-1511(1997) [PubMed: 9305655] [Abstract] Cited for: VARIANTS XCNM CYS-69; PHE-70; PRO-87; SER-189; LEU-205; PRO-229; CYS-241; ASN-376; ARG-378; CYS-397; ALA-402; GLN-421; ASN-431; ASN-433 AND PRO-469. |
| [10] | "MTM1 gene mutations in Japanese patients with the severe infantile form of myotubular myopathy." Nishino I., Minami N., Kobayashi O., Ikezawa M., Goto Y., Arahata K., Nonaka I. Neuromuscul. Disord. 8:453-458(1998) [PubMed: 9829274] [Abstract] Cited for: VARIANT XCNM VAL-402. |
| [11] | "Germline mosaicism in X-linked myotubular myopathy." Haene B.G., Rogers R.C., Schwartz C.E. Clin. Genet. 56:77-81(1999) [PubMed: 10466421] [Abstract] Cited for: VARIANT XCNM GLU-378. |
| [12] | "Identification of novel mutations in the MTM1 gene causing severe and mild forms of X-linked myotubular myopathy." Buj-Bello A., Biancalana V., Moutou C., Laporte J., Mandel J.-L. Hum. Mutat. 14:320-325(1999) [PubMed: 10502779] [Abstract] Cited for: VARIANTS XCNM SER-179; THR-225; CYS-241; SER-264; GLY-294 DEL; ARG-378 AND ASN-510. |
| [13] | "Characterization of 34 novel and six known MTM1 gene mutations in 47 unrelated X-linked myotubular myopathy patients." Tanner S.M., Schneider V., Thomas N.S.T., Clarke A., Lazarou L., Liechti-Gallati S. Neuromuscul. Disord. 9:41-49(1999) [PubMed: 10063835] [Abstract] Cited for: VARIANTS XCNM LEU-205; THR-225; CYS-230; ARG-232; CYS-241; ARG-402 AND TYR-444. |
| [14] | "Characterization of mutations in fifty North American patients with X-linked myotubular myopathy." Herman G.E., Kopacz K., Zhao W., Mills P.L., Metzenberg A., Das S. Hum. Mutat. 19:114-121(2002) [PubMed: 11793470] [Abstract] Cited for: VARIANTS XCNM PHE-49; CYS-69; SER-179; ILE-186; LEU-205; MET-227; PRO-228; CYS-241; GLY-279; ARG-378; PRO-391; CYS-397; ARG-402 AND GLN-421. |
| [15] | "Rapid scanning of myotubularin (MTM1) gene by denaturing high-performance liquid chromatography (DHPLC)." Flex E., De Luca A., D'Apice M.R., Buccino A., Dallapiccola B., Novelli G. Neuromuscul. Disord. 12:501-505(2002) [PubMed: 12031625] [Abstract] Cited for: VARIANTS XCNM ILE-197; SER-199; ARG-378 AND ARG-402. |
| [16] | "X-linked myotubular myopathy in a family with three adult survivors." Yu S., Manson J., White S., Bourne A., Waddy H., Davis M., Haan E. Clin. Genet. 64:148-152(2003) [PubMed: 12859411] [Abstract] Cited for: VARIANT XCNM LYS-157. |
| [17] | "Characterisation of mutations in 77 patients with X-linked myotubular myopathy, including a family with a very mild phenotype." Biancalana V., Caron O., Gall |

Clusters with