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Q13496 (MTM1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 132. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Myotubularin

EC=3.1.3.64
Gene names
Name:MTM1
Synonyms:CG2
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length603 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Lipid 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. Ref.6 Ref.8 Ref.9 Ref.11 Ref.13 Ref.18

Catalytic activity

1-phosphatidyl-1D-myo-inositol 3-phosphate + H2O = 1-phosphatidyl-1D-myo-inositol + phosphate.

Enzyme regulation

Allosterically activated by phosphatidylinositol 5-phosphate (PI5P). Ref.11

Subunit structure

Interacts 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. Ref.6 Ref.12 Ref.18

Subcellular location

Cytoplasm. Cell membrane; Peripheral membrane protein. Cell projectionfilopodium. Cell projectionruffle. Late endosome. 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. Ref.8 Ref.9 Ref.10 Ref.12 Ref.13

Domain

The GRAM domain mediates binding to PI(3,5)P2 and, with lower affinity, to other phosphoinositides. Ref.13

Involvement in disease

Myopathy, 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.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.19 Ref.20 Ref.21 Ref.22 Ref.23 Ref.24 Ref.25 Ref.26 Ref.27 Ref.28 Ref.29 Ref.30

Sequence similarities

Belongs to the protein-tyrosine phosphatase family. Non-receptor class myotubularin subfamily.

Contains 1 GRAM domain.

Contains 1 myotubularin phosphatase domain.

Biophysicochemical properties

Kinetic parameters:

KM=39 µM for PI3P Ref.13

KM=17 µM for PI(3,5)P2

Ontologies

Keywords
   Biological processProtein transport
Transport
   Cellular componentCell membrane
Cell projection
Cytoplasm
Endosome
Membrane
   DiseaseDisease mutation
   Molecular functionHydrolase
Protein phosphatase
   PTMPhosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processendosome to lysosome transport

Inferred from direct assay Ref.13. Source: UniProtKB

intermediate filament organization

Inferred from mutant phenotype Ref.18. Source: UniProtKB

mitochondrion distribution

Inferred from mutant phenotype Ref.18. Source: UniProtKB

mitochondrion morphogenesis

Inferred from direct assay Ref.18. Source: UniProtKB

muscle cell cellular homeostasis

Inferred from electronic annotation. Source: Ensembl

phosphatidylinositol biosynthetic process

Traceable author statement. Source: Reactome

phosphatidylinositol dephosphorylation

Inferred from direct assay Ref.9Ref.11. Source: UniProtKB

phospholipid metabolic process

Traceable author statement. Source: Reactome

protein dephosphorylation

Inferred from direct assay Ref.6. Source: UniProtKB

protein transport

Inferred from electronic annotation. Source: UniProtKB-KW

regulation of vacuole organization

Inferred from direct assay Ref.13. Source: UniProtKB

small molecule metabolic process

Traceable author statement. Source: Reactome

   Cellular_componentI band

Inferred from electronic annotation. Source: Ensembl

cytoplasm

Inferred from direct assay Ref.9Ref.10PubMed 12217958. Source: UniProtKB

cytosol

Traceable author statement. Source: Reactome

filopodium

Inferred from direct assay Ref.10. Source: UniProtKB

late endosome

Inferred from direct assay Ref.13. Source: UniProtKB

plasma membrane

Inferred from direct assay Ref.10PubMed 12217958Ref.12. Source: UniProtKB

ruffle

Inferred from direct assay Ref.10. Source: UniProtKB

   Molecular_functionintermediate filament binding

Inferred from direct assay Ref.18. Source: UniProtKB

phosphatidylinositol binding

Inferred from direct assay Ref.13. Source: UniProtKB

phosphatidylinositol-3,5-bisphosphate 3-phosphatase activity

Inferred from direct assay Ref.11. Source: UniProtKB

phosphatidylinositol-3-phosphatase activity

Inferred from direct assay Ref.9. Source: UniProtKB

phosphoprotein phosphatase activity

Inferred from direct assay Ref.6. Source: UniProtKB

protein tyrosine phosphatase activity

Inferred from electronic annotation. Source: InterPro

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

DESP1766113EBI-2864109,EBI-1055572
DesP310014EBI-2864109,EBI-298565From a different organism.
MTMR12Q9C0I14EBI-2864109,EBI-2829520

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 603603Myotubularin
PRO_0000094930

Regions

Domain29 – 9769GRAM
Domain163 – 538376Myotubularin phosphatase

Sites

Active site3751Phosphocysteine intermediate By similarity

Amino acid modifications

Modified residue4951Phosphothreonine Ref.14
Modified residue5881Phosphoserine Ref.15 Ref.16

Natural variations

Natural variant471Missing in CNMX. Ref.28
VAR_006386
Natural variant491V → F in CNMX; greatly reduced binding to PI(3,5)P2; does not translocate to the late endosome following EGF stimulation; shows normal EGFR degradation. Ref.13 Ref.25
VAR_018227
Natural variant681Y → D in CNMX. Ref.28
VAR_018228
Natural variant691R → C in CNMX; mild; reduced response to PI5P and reduced binding to PI(3,5)P2. Ref.11 Ref.13 Ref.19 Ref.20 Ref.25
VAR_006387
Natural variant691R → P in CNMX. Ref.28
VAR_018229
Natural variant691R → S in CNMX; severe. Ref.28
VAR_018230
Natural variant701L → F in CNMX; mild; reduced binding to PI(3,5)P2. Ref.13 Ref.20 Ref.28
VAR_006388
Natural variant871L → P in CNMX; mild; reduced binding to PI(3,5)P2. Ref.13 Ref.20
VAR_006389
Natural variant1571E → K in CNMX. Ref.27
VAR_018231
Natural variant1791P → S in CNMX; mild. Ref.23 Ref.25
VAR_009217
Natural variant1801N → K in CNMX; very mild. Ref.28
VAR_018232
Natural variant1841R → G in CNMX; severe; loss of activity; abolishes interaction with DES. Ref.11 Ref.18 Ref.19
VAR_006390
Natural variant1841R → L in CNMX; reduced activity and response to PI5P. Ref.28
VAR_018233
Natural variant1861T → I in CNMX. Ref.25
VAR_018234
Natural variant1891N → S in CNMX. Ref.20
VAR_006391
Natural variant1971T → I in CNMX. Ref.26
VAR_018235
Natural variant1981Y → N in CNMX; severe. Ref.19
VAR_006392
Natural variant1991P → S in CNMX. Ref.26
VAR_018236
Natural variant2021L → S in CNMX; severe. Ref.28
VAR_018237
Natural variant2051P → L in CNMX; severe; dramatic decrease in phosphatase activity; abolishes interaction with DES. Ref.9 Ref.18 Ref.20 Ref.24 Ref.25 Ref.28
VAR_006393
Natural variant2251I → T in CNMX; mild. Ref.23 Ref.24
VAR_009218
Natural variant2261P → T in CNMX. Ref.28
VAR_018238
Natural variant2271V → M in CNMX. Ref.25
VAR_018239
Natural variant2281L → P in CNMX. Ref.25
VAR_018240
Natural variant2291S → P in CNMX; mild. Ref.20
VAR_006394
Natural variant2301W → C in CNMX. Ref.24 Ref.28
VAR_018241
Natural variant2321H → R in CNMX. Ref.24
VAR_018242
Natural variant2411R → C in CNMX; mild to moderate; abolishes interaction with DES. Ref.18 Ref.20 Ref.23 Ref.24 Ref.25 Ref.28
VAR_006395
Natural variant2411R → L in CNMX; severe; loss of activity. Ref.9 Ref.11 Ref.19
VAR_006396
Natural variant2641I → S in CNMX; severe. Ref.23
VAR_009219
Natural variant2791A → G in CNMX. Ref.25
VAR_018243
Natural variant2941Missing in CNMX; mild. Ref.23
VAR_009220
Natural variant3171M → R in CNMX; mild. Ref.19
VAR_006397
Natural variant3461W → C in CNMX; mild. Ref.28
VAR_018244
Natural variant3461W → S in CNMX.
VAR_018245
Natural variant3641V → G in CNMX. Ref.28
VAR_018246
Natural variant3741H → D in CNMX.
VAR_018247
Natural variant3761S → N in CNMX; dramatic decrease in phosphatase activity. Ref.9 Ref.20
VAR_006398
Natural variant3781G → E in CNMX. Ref.22
VAR_018248
Natural variant3781G → R in CNMX; severe; dramatic decrease in phosphatase activity; does not affect EGFR degradation. Ref.9 Ref.20 Ref.23 Ref.25 Ref.26
VAR_006399
Natural variant3871S → Y in CNMX. Ref.30
VAR_068846
Natural variant3891A → D in CNMX; severe. Ref.28
VAR_018249
Natural variant3911L → P in CNMX. Ref.25
VAR_018250
Natural variant3971Y → C in CNMX; severe; dramatic decrease in phosphatase activity. Ref.9 Ref.19 Ref.20 Ref.25 Ref.28
VAR_006400
Natural variant4021G → A in CNMX; mild. Ref.20
VAR_006401
Natural variant4021G → R in CNMX. Ref.24 Ref.25 Ref.26
VAR_018251
Natural variant4021G → V in CNMX. Ref.21
VAR_018252
Natural variant4041E → K in CNMX; mild. Ref.19 Ref.29
VAR_006402
Natural variant4061L → P in CNMX; severe. Ref.19
VAR_006403
Natural variant4111W → C in CNMX.
VAR_018253
Natural variant4201S → SFIQ in CNMX; severe.
VAR_009221
Natural variant4211R → Q in CNMX; severe; reduced activity and response to PI5P; does not affect interaction with DES. Ref.11 Ref.18 Ref.19 Ref.20 Ref.25 Ref.28
VAR_006404
Natural variant4211R → RFIQ in CNMX; severe.
VAR_006405
Natural variant4311D → N in CNMX. Ref.20
VAR_006406
Natural variant4331D → N in CNMX. Ref.20
VAR_006407
Natural variant4441C → Y in CNMX. Ref.24
VAR_018254
Natural variant4691H → P in CNMX; loss of activity. Ref.11 Ref.20 Ref.28
VAR_006408
Natural variant4701L → P in CNMX; severe. Ref.28
VAR_018255
Natural variant4811N → Y in CNMX; mild. Ref.28
VAR_018256
Natural variant4991W → R in CNMX; mild. Ref.19
VAR_006409
Natural variant5101K → N in CNMX; severe. Ref.23
VAR_009222

Experimental info

Mutagenesis1141K → A: Reduced response to PI5P. Ref.11
Mutagenesis1811H → A: Disrupts interaction with DES. Does not affect lipid phosphatase activity. Ref.18
Mutagenesis2061Y → A: Disrupts interaction with DES. Does not affect lipid phosphatase activity. Ref.18
Mutagenesis2091S → A: Disrupts interaction with DES. Does not affect lipid phosphatase activity. Ref.18
Mutagenesis2201R → A: Loss of activity. Ref.11
Mutagenesis2551K → A: Disrupts interaction with DES. Ref.18
Mutagenesis2571D → A: No effect on subcellular location. Ref.10
Mutagenesis2691K → A: Disrupts interaction with DES. Does not affect lipid phosphatase activity. Ref.18
Mutagenesis2781D → A: Localizes to plasma membrane extensions. Does not affect interaction with DES. Ref.8 Ref.10 Ref.18
Mutagenesis3751C → A: No effect on subcellular location. Ref.8 Ref.9 Ref.10 Ref.11 Ref.18
Mutagenesis3751C → S: Lacks activity toward PI3P. Does not affect interaction with DES. Ref.8 Ref.9 Ref.10 Ref.11 Ref.18
Mutagenesis3771D → A: No effect on subcellular location. Ref.8 Ref.10
Mutagenesis3801D → A: Does not affect interaction with DES. Ref.8 Ref.10 Ref.18
Mutagenesis3941D → A: Produces an unstable protein. Ref.8
Mutagenesis4101E → A: Produces an unstable protein. Ref.8
Mutagenesis4201S → D: Does not affect interaction with DES. Ref.18
Mutagenesis4431D → A: Produces an unstable protein. Ref.8
Sequence conflict4101E → K in AAH30779. Ref.5

Sequences

Sequence LengthMass (Da)Tools
Q13496 [UniParc].

Last modified July 15, 1998. Version 2.
Checksum: BE9770F2471957C0

FASTA60369,932
        10         20         30         40         50         60 
MASASTSKYN SHSLENESIK RTSRDGVNRD LTEAVPRLPG ETLITDKEVI YICPFNGPIK 

        70         80         90        100        110        120 
GRVYITNYRL YLRSLETDSS LILDVPLGVI SRIEKMGGAT SRGENSYGLD ITCKDMRNLR 

       130        140        150        160        170        180 
FALKQEGHSR RDMFEILTRY AFPLAHSLPL FAFLNEEKFN VDGWTVYNPV EEYRRQGLPN 

       190        200        210        220        230        240 
HHWRITFINK CYELCDTYPA LLVVPYRASD DDLRRVATFR SRNRIPVLSW IHPENKTVIV 

       250        260        270        280        290        300 
RCSQPLVGMS GKRNKDDEKY LDVIRETNKQ ISKLTIYDAR PSVNAVANKA TGGGYESDDA 

       310        320        330        340        350        360 
YHNAELFFLD IHNIHVMRES LKKVKDIVYP NVEESHWLSS LESTHWLEHI KLVLTGAIQV 

       370        380        390        400        410        420 
ADKVSSGKSS VLVHCSDGWD RTAQLTSLAM LMLDSFYRSI EGFEILVQKE WISFGHKFAS 

       430        440        450        460        470        480 
RIGHGDKNHT DADRSPIFLQ FIDCVWQMSK QFPTAFEFNE QFLIIILDHL YSCRFGTFLF 

       490        500        510        520        530        540 
NCESARERQK VTERTVSLWS LINSNKEKFK NPFYTKEINR VLYPVASMRH LELWVNYYIR 

       550        560        570        580        590        600 
WNPRIKQQQP NPVEQRYMEL LALRDEYIKR LEELQLANSA KLSDPPTSPS SPSQMMPHVQ 


THF 

« Hide

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] [Europe PMC] [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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]"The DNA sequence of the human X chromosome."
Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D., Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L., Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C. expand/collapse author list , Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A., Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P., Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D., Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D., Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L., Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P., Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G., Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J., Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D., Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L., Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z., Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S., Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S., Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O., Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H., Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T., Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L., Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R., Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y., Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K., Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J., Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L., Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S., Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A., Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L., Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D., Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H., McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S., Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C., Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S., Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V., Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K., Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K., Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D., Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R., Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B., Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C., d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q., Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N., Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A., Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J., Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A., Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F., Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L., Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S., Rogers J., Bentley D.R.
Nature 434:325-337(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]"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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Testis.
[6]"Association of SET domain and myotubularin-related proteins modulates growth control."
Cui X., De Vivo I., Slany R., Miyamoto A., Firestein R., Cleary M.L.
Nat. Genet. 18:331-337(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH KMT2A/MLL1.
[7]"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] [Europe PMC] [Abstract]
Cited for: REVIEW ON VARIANTS CNMX.
[8]"Myotubularin, a phosphatase deficient in myotubular myopathy, acts on phosphatidylinositol 3-kinase and phosphatidylinositol 3-phosphate pathway."
Blondeau F., Laporte J., Bodin S., Superti-Furga G., Payrastre B., Mandel J.L.
Hum. Mol. Genet. 9:2223-2229(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, MUTAGENESIS OF ASP-278; CYS-375; ASP-377; ASP-380; ASP-394; GLU-410 AND ASP-443.
[9]"Myotubularin, a protein tyrosine phosphatase mutated in myotubular myopathy, dephosphorylates the lipid second messenger, phosphatidylinositol 3-phosphate."
Taylor G.S., Maehama T., Dixon J.E.
Proc. Natl. Acad. Sci. U.S.A. 97:8910-8915(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, CHARACTERIZATION OF VARIANTS LEU-205; LEU-241; ASN-376; ARG-378 AND CYS-397, MUTAGENESIS OF CYS-375.
[10]"The PtdIns3P phosphatase myotubularin is a cytoplasmic protein that also localizes to Rac1-inducible plasma membrane ruffles."
Laporte J., Blondeau F., Gansmuller A., Lutz Y., Vonesch J.L., Mandel J.L.
J. Cell Sci. 115:3105-3117(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION, MUTAGENESIS OF ASP-257; ASP-278; CYS-375; ASP-377 AND ASP-380.
[11]"Phosphatidylinositol-5-phosphate activation and conserved substrate specificity of the myotubularin phosphatidylinositol 3-phosphatases."
Schaletzky J., Dove S.K., Short B., Lorenzo O., Clague M.J., Barr F.A.
Curr. Biol. 13:504-509(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, ENZYME REGULATION, CHARACTERIZATION OF VARIANTS CYS-69; GLY-184; LEU-241; GLN-421 AND PRO-469, MUTAGENESIS OF LYS-114; ARG-220 AND CYS-375.
[12]"Identification of myotubularin as the lipid phosphatase catalytic subunit associated with the 3-phosphatase adapter protein, 3-PAP."
Nandurkar H.H., Layton M., Laporte J., Selan C., Corcoran L., Caldwell K.K., Mochizuki Y., Majerus P.W., Mitchell C.A.
Proc. Natl. Acad. Sci. U.S.A. 100:8660-8665(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH MTMR12, SUBCELLULAR LOCATION, IDENTIFICATION BY MASS SPECTROMETRY.
[13]"Myotubularin regulates the function of the late endosome through the gram domain-phosphatidylinositol 3,5-bisphosphate interaction."
Tsujita K., Itoh T., Ijuin T., Yamamoto A., Shisheva A., Laporte J., Takenawa T.
J. Biol. Chem. 279:13817-13824(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, SUBCELLULAR LOCATION, ROLE OF GRAM DOMAIN, CHARACTERIZATION OF VARIANTS PHE-49; CYS-69; PHE-70 AND PRO-87.
[14]"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] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-495, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[15]"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] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-588, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[16]"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.
Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-588, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[17]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[18]"Myotubularin controls desmin intermediate filament architecture and mitochondrial dynamics in human and mouse skeletal muscle."
Hnia K., Tronchere H., Tomczak K.K., Amoasii L., Schultz P., Beggs A.H., Payrastre B., Mandel J.L., Laporte J.
J. Clin. Invest. 121:70-85(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH DES, CHARACTERIZATION OF VARIANTS GLY-184; LEU-205; CYS-241 AND GLN-421, MUTAGENESIS OF HIS-181; TYR-206; SER-209; LYS-255; LYS-269; ASP-278; CYS-375; ASP-380 AND SER-420.
[19]"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] [Europe PMC] [Abstract]
Cited for: VARIANTS CNMX CYS-69; GLY-184; ASN-198; LEU-241; ARG-317; CYS-397; LYS-404; PRO-406; GLN-421 AND ARG-499.
[20]"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] [Europe PMC] [Abstract]
Cited for: VARIANTS CNMX 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.
[21]"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] [Europe PMC] [Abstract]
Cited for: VARIANT CNMX VAL-402.
[22]"Germline mosaicism in X-linked myotubular myopathy."
Haene B.G., Rogers R.C., Schwartz C.E.
Clin. Genet. 56:77-81(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT CNMX GLU-378.
[23]"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] [Europe PMC] [Abstract]
Cited for: VARIANTS CNMX SER-179; THR-225; CYS-241; SER-264; GLY-294 DEL; ARG-378 AND ASN-510.
[24]"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] [Europe PMC] [Abstract]
Cited for: VARIANTS CNMX LEU-205; THR-225; CYS-230; ARG-232; CYS-241; ARG-402 AND TYR-444.
[25]"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] [Europe PMC] [Abstract]
Cited for: VARIANTS CNMX 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.
[26]"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] [Europe PMC] [Abstract]
Cited for: VARIANTS CNMX ILE-197; SER-199; ARG-378 AND ARG-402.
[27]"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] [Europe PMC] [Abstract]
Cited for: VARIANT CNMX LYS-157.
[28]"Characterisation of mutations in 77 patients with X-linked myotubular myopathy, including a family with a very mild phenotype."
Biancalana V., Caron O., Gallati S., Baas F., Kress W., Novelli G., D'Apice M.R., Lagier-Tourenne C., Buj-Bello A., Romero N.B., Mandel J.-L.
Hum. Genet. 112:135-142(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS CNMX LYS-47 DEL; ASP-68; PRO-69; SER-69; PHE-70; LYS-180; LEU-184; SER-202; LEU-205; THR-226; CYS-230; CYS-241; CYS-346; GLY-364; ASP-389; CYS-397; GLN-421; PRO-469; PRO-470 AND TYR-481.
[29]"Extreme phenotypic variability in a German family with X-linked myotubular myopathy associated with E404K mutation in MTM1."
Hoffjan S., Thiels C., Vorgerd M., Neuen-Jacob E., Epplen J.T., Kress W.
Neuromuscul. Disord. 16:749-753(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT CNMX LYS-404.
[30]"X-linked myotubular myopathy with a novel MTM1 mutation in a Taiwanese child."
Chang C.Y., Lin S.P., Lin H.Y., Chuang C.K., Ho C.S., Su Y.N.
J. Formos. Med. Assoc. 107:965-970(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT CNMX TYR-387.
+Additional computationally mapped references.

Web resources

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U46024 mRNA. Translation: AAC51682.1.
AF020676 expand/collapse EMBL AC list , AF020664, AF020665, AF020666, AF020667, AF020668, AF020669, AF020670, AF020671, AF020672, AF020673, AF020674, AF020675 Genomic DNA. Translation: AAC12865.1.
AC109994 Genomic DNA. No translation available.
AF002223 Genomic DNA. No translation available.
CH471169 Genomic DNA. Translation: EAW99377.1.
BC030779 mRNA. Translation: AAH30779.1.
RefSeqNP_000243.1. NM_000252.2.
XP_005274744.1. XM_005274687.1.
UniGeneHs.655056.

3D structure databases

ProteinModelPortalQ13496.
SMRQ13496. Positions 33-543.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid110630. 3 interactions.
IntActQ13496. 6 interactions.
STRING9606.ENSP00000359423.

PTM databases

PhosphoSiteQ13496.

Polymorphism databases

DMDM2851537.

Proteomic databases

PaxDbQ13496.
PRIDEQ13496.

Protocols and materials databases

DNASU4534.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000370396; ENSP00000359423; ENSG00000171100.
ENST00000598147; ENSP00000472211; ENSG00000269031.
GeneID4534.
KEGGhsa:4534.
UCSCuc004fef.4. human.

Organism-specific databases

CTD4534.
GeneCardsGC0XP149738.
HGNCHGNC:7448. MTM1.
HPAHPA010008.
HPA010665.
MIM300415. gene.
310400. phenotype.
neXtProtNX_Q13496.
Orphanet596. X-linked centronuclear myopathy.
PharmGKBPA31251.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG322789.
HOGENOMHOG000210598.
HOVERGENHBG000220.
InParanoidQ13496.
KOK01108.
OMATDKEVIY.
PhylomeDBQ13496.
TreeFamTF315197.

Enzyme and pathway databases

BRENDA3.1.3.64. 2681.
ReactomeREACT_111217. Metabolism.

Gene expression databases

ArrayExpressQ13496.
BgeeQ13496.
CleanExHS_MTM1.
GenevestigatorQ13496.

Family and domain databases

Gene3D2.30.29.30. 1 hit.
InterProIPR004182. GRAM.
IPR010569. Myotubularin-like_Pase_dom.
IPR011993. PH_like_dom.
IPR000387. Tyr/Dual-sp_Pase.
IPR016130. Tyr_Pase_AS.
[Graphical view]
PfamPF02893. GRAM. 1 hit.
PF06602. Myotub-related. 1 hit.
[Graphical view]
SMARTSM00568. GRAM. 1 hit.
[Graphical view]
PROSITEPS51339. PPASE_MYOTUBULARIN. 1 hit.
PS00383. TYR_PHOSPHATASE_1. 1 hit.
PS50056. TYR_PHOSPHATASE_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSMTM1. human.
GeneWikiMyotubularin_1.
GenomeRNAi4534.
NextBio17492.
PROQ13496.
SOURCESearch...

Entry information

Entry nameMTM1_HUMAN
AccessionPrimary (citable) accession number: Q13496
Secondary accession number(s): A6NDB1, Q8NEL1
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: July 15, 1998
Last modified: April 16, 2014
This is version 132 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome X

Human chromosome X: entries, gene names and cross-references to MIM