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Q9Z2C5 (MTM1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 104. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Myotubularin

EC=3.1.3.64
Gene names
Name:Mtm1
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

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 By similarity. 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.5 Ref.6

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) By similarity.

Subunit structure

Interacts with MTMR12; the interaction modulates MTM1 intracellular localization. Interacts with KMT2A/MLL1 (via SET domain) By similarity. Interacts with DES in skeletal muscle but not in cardiac muscle. Ref.6

Subcellular location

Cytoplasm. Cell membrane; Peripheral membrane protein By similarity. Cell projectionfilopodium. Cell projectionruffle. Late endosome By similarity. 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.4

Tissue specificity

Widely expressed with highest levels detected in heart and muscle and low levels in brain (at protein level). Ref.4

Domain

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

Disruption phenotype

Mice are viable although lifespan is severely reduced. An under-representation of mutant males suggests some prenatal lethality. Generalized and progressive myopathy starts at around 4 weeks of age with amyotrophy and accumulation of central nuclei in skeletal muscle fibers, leading to death at 6-14 weeks. Mutants also show mitochondrial disorganization and increased levels of desmin with abnormal desmin intermediate filament formation and architecture. Ref.5 Ref.6

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

Inferred from sequence or structural similarity. Source: UniProtKB

intermediate filament organization

Inferred from sequence or structural similarity. Source: UniProtKB

mitochondrion distribution

Inferred from mutant phenotype Ref.6. Source: UniProtKB

mitochondrion morphogenesis

Inferred from mutant phenotype Ref.6. Source: UniProtKB

muscle cell cellular homeostasis

Inferred from mutant phenotype Ref.5. Source: MGI

phosphatidylinositol dephosphorylation

Inferred from sequence or structural similarity. Source: UniProtKB

protein dephosphorylation

Inferred from sequence or structural similarity. Source: UniProtKB

protein transport

Inferred from electronic annotation. Source: UniProtKB-KW

regulation of vacuole organization

Inferred from sequence or structural similarity. Source: UniProtKB

   Cellular_componentI band

Inferred from direct assay PubMed 18434328. Source: MGI

cytoplasm

Inferred from direct assay Ref.4. Source: UniProtKB

filopodium

Inferred from sequence or structural similarity. Source: UniProtKB

late endosome

Inferred from sequence or structural similarity. Source: UniProtKB

plasma membrane

Inferred from sequence or structural similarity. Source: UniProtKB

ruffle

Inferred from sequence or structural similarity. Source: UniProtKB

   Molecular_functionintermediate filament binding

Inferred from sequence or structural similarity. Source: UniProtKB

phosphatidylinositol binding

Inferred from sequence or structural similarity. Source: UniProtKB

phosphatidylinositol-3,5-bisphosphate 3-phosphatase activity

Inferred from sequence or structural similarity. Source: UniProtKB

phosphatidylinositol-3-phosphatase activity

Inferred from sequence or structural similarity. Source: UniProtKB

phosphoprotein phosphatase activity

Inferred from sequence or structural similarity. Source: UniProtKB

protein tyrosine phosphatase activity

Inferred from electronic annotation. Source: InterPro

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

DesP310014EBI-6861578,EBI-298565

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 603603Myotubularin
PRO_0000094931

Regions

Domain29 – 9769GRAM
Domain163 – 538376Myotubularin phosphatase

Sites

Active site3751Phosphocysteine intermediate By similarity

Amino acid modifications

Modified residue4951Phosphothreonine By similarity
Modified residue5881Phosphoserine By similarity

Experimental info

Sequence conflict951K → Y in AAC77821. Ref.1

Sequences

Sequence LengthMass (Da)Tools
Q9Z2C5 [UniParc].

Last modified June 28, 2011. Version 2.
Checksum: 65929312F07FFCC7

FASTA60369,559
        10         20         30         40         50         60 
MASASASKYN SHSLENESIK KVSQDGVSQD VSETVPRLPG ELLITEKEVI YICPFNGPIK 

        70         80         90        100        110        120 
GRVYITNYRL YLRSLETDSA LILDVPLGVI SRIEKMGGAT SRGENSYGLD ITCKDLRNLR 

       130        140        150        160        170        180 
FALKQEGHSR RDMFEILVKH AFPLAHNLPL FAFVNEEKFN VDGWTVYNPV EEYRRQGLPN 

       190        200        210        220        230        240 
HHWRISFINK CYELCETYPA LLVVPYRTSD DDLRRIATFR SRNRLPVLSW IHPENKMVIM 

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

       310        320        330        340        350        360 
YQNSELSFLD IHNIHVMRES LKKVKDIVYP NIEESHWLSS LESTHWLEHI KLVLTGAIQV 

       370        380        390        400        410        420 
ADQVSSGKSS VLVHCSDGWD RTAQLTSLAM LMLDSFYRTI EGFEILVQKE WISFGHKFAS 

       430        440        450        460        470        480 
RIGHGDKNHA DADRSPIFLQ FIDCVWQMSK QFPTAFEFNE GFLITVLDHL YSCRFGTFLF 

       490        500        510        520        530        540 
NCDSARERQK LTERTVSLWS LINSNKDKFK NPFYTKEINR VLYPVASMRH LELWVNYYIR 

       550        560        570        580        590        600 
WNPRVKQQQP NPVEQRYMEL LALRDDYIKR LEELQLANSA KLADAPASTS SSSQMVPHVQ 


THF 

« Hide

References

« Hide 'large scale' references
[1]"Characterization of the myotubularin dual specificity phosphatase gene family from yeast to human."
Laporte J., Blondeau F., Buj-Bello A., Tentler D., Kretz C., Dahl N., Mandel J.-L.
Hum. Mol. Genet. 7:1703-1712(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]"Lineage-specific biology revealed by a finished genome assembly of the mouse."
Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S. expand/collapse author list , Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., Eichler E.E., Ponting C.P.
PLoS Biol. 7:E1000112-E1000112(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Strain: C57BL/6J.
[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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Strain: CD-1.
Tissue: Pituitary.
[4]"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, TISSUE SPECIFICITY.
[5]"The lipid phosphatase myotubularin is essential for skeletal muscle maintenance but not for myogenesis in mice."
Buj-Bello A., Laugel V., Messaddeq N., Zahreddine H., Laporte J., Pellissier J.F., Mandel J.L.
Proc. Natl. Acad. Sci. U.S.A. 99:15060-15065(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, DISRUPTION PHENOTYPE.
[6]"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, DISRUPTION PHENOTYPE.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF073996 mRNA. Translation: AAC77821.1.
AL731843, AL772294 Genomic DNA. Translation: CAM20185.1.
BC090984 mRNA. Translation: AAH90984.1.
RefSeqNP_001157662.1. NM_001164190.1.
NP_001157663.1. NM_001164191.1.
NP_001157664.1. NM_001164192.1.
NP_064310.2. NM_019926.3.
UniGeneMm.274981.
Mm.423278.

3D structure databases

ProteinModelPortalQ9Z2C5.
SMRQ9Z2C5. Positions 33-543.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

IntActQ9Z2C5. 5 interactions.
MINTMINT-4102552.
STRING10090.ENSMUSP00000099041.

PTM databases

PhosphoSiteQ9Z2C5.

Proteomic databases

PaxDbQ9Z2C5.
PRIDEQ9Z2C5.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000033700; ENSMUSP00000033700; ENSMUSG00000031337.
ENSMUST00000061970; ENSMUSP00000057182; ENSMUSG00000031337.
ENSMUST00000114617; ENSMUSP00000110264; ENSMUSG00000031337.
ENSMUST00000171933; ENSMUSP00000125798; ENSMUSG00000031337.
GeneID17772.
KEGGmmu:17772.
UCSCuc009tjq.2. mouse.

Organism-specific databases

CTD4534.
MGIMGI:1099452. Mtm1.

Phylogenomic databases

eggNOGNOG322789.
GeneTreeENSGT00670000097670.
HOGENOMHOG000210598.
HOVERGENHBG000220.
InParanoidQ5BKQ5.
KOK01108.
OMATDKEVIY.
OrthoDBEOG7XDBF9.

Gene expression databases

ArrayExpressQ9Z2C5.
BgeeQ9Z2C5.
CleanExMM_MTM1.
GenevestigatorQ9Z2C5.

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

NextBio292491.
PROQ9Z2C5.
SOURCESearch...

Entry information

Entry nameMTM1_MOUSE
AccessionPrimary (citable) accession number: Q9Z2C5
Secondary accession number(s): Q5BKQ5
Entry history
Integrated into UniProtKB/Swiss-Prot: December 1, 2000
Last sequence update: June 28, 2011
Last modified: April 16, 2014
This is version 104 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot