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Protein

Myotubularin

Gene

Mtm1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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.By similarity2 Publications

Catalytic activityi

1-phosphatidyl-1D-myo-inositol 3-phosphate + H2O = 1-phosphatidyl-1D-myo-inositol + phosphate.By similarity
1-phosphatidyl-1D-myo-inositol 3,5-bisphosphate + H2O = 1-phosphatidyl-1D-myo-inositol 5-phosphate + phosphate.By similarity

Enzyme regulationi

Allosterically activated by phosphatidylinositol 5-phosphate (PI5P).By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei375Phosphocysteine intermediatePROSITE-ProRule annotation1

GO - Molecular functioni

GO - Biological processi

  • endosome to lysosome transport Source: UniProtKB
  • intermediate filament organization Source: UniProtKB
  • mitochondrion distribution Source: UniProtKB
  • mitochondrion morphogenesis Source: UniProtKB
  • muscle cell cellular homeostasis Source: CACAO
  • negative regulation of autophagosome assembly Source: MGI
  • negative regulation of proteasomal ubiquitin-dependent protein catabolic process Source: MGI
  • negative regulation of protein kinase B signaling Source: MGI
  • negative regulation of TOR signaling Source: MGI
  • phosphatidylinositol dephosphorylation Source: UniProtKB
  • positive regulation of skeletal muscle tissue growth Source: MGI
  • protein dephosphorylation Source: UniProtKB
  • protein transport Source: UniProtKB-KW
  • regulation of vacuole organization Source: UniProtKB

Keywordsi

Molecular functionHydrolase, Protein phosphatase
Biological processLipid metabolism, Protein transport, Transport

Enzyme and pathway databases

ReactomeiR-MMU-1660499 Synthesis of PIPs at the plasma membrane
R-MMU-1660516 Synthesis of PIPs at the early endosome membrane
R-MMU-1660517 Synthesis of PIPs at the late endosome membrane

Names & Taxonomyi

Protein namesi
Recommended name:
Myotubularin
Alternative name(s):
Phosphatidylinositol-3,5-bisphosphate 3-phosphatase (EC:3.1.3.95By similarity)
Phosphatidylinositol-3-phosphate phosphatase (EC:3.1.3.64By similarity)
Gene namesi
Name:Mtm1
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome X

Organism-specific databases

MGIiMGI:1099452 Mtm1

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cell membrane, Cell projection, Cytoplasm, Endosome, Membrane

Pathology & Biotechi

Disruption phenotypei

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.2 Publications

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000949311 – 603MyotubularinAdd BLAST603

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei13PhosphoserineBy similarity1
Modified residuei18PhosphoserineBy similarity1
Modified residuei495PhosphothreonineBy similarity1
Modified residuei588PhosphoserineBy similarity1

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiQ9Z2C5
PaxDbiQ9Z2C5
PRIDEiQ9Z2C5

PTM databases

iPTMnetiQ9Z2C5
PhosphoSitePlusiQ9Z2C5

Expressioni

Tissue specificityi

Widely expressed with highest levels detected in heart and muscle and low levels in brain (at protein level).1 Publication

Gene expression databases

BgeeiENSMUSG00000031337
CleanExiMM_MTM1
ExpressionAtlasiQ9Z2C5 baseline and differential
GenevisibleiQ9Z2C5 MM

Interactioni

Subunit structurei

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. Interacts with SPEG (By similarity).By similarity1 Publication

Binary interactionsi

Show more details

Protein-protein interaction databases

BioGridi201597, 1 interactor
IntActiQ9Z2C5, 5 interactors
MINTiQ9Z2C5
STRINGi10090.ENSMUSP00000057182

Structurei

3D structure databases

ProteinModelPortaliQ9Z2C5
SMRiQ9Z2C5
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini29 – 97GRAMAdd BLAST69
Domaini163 – 538Myotubularin phosphatasePROSITE-ProRule annotationAdd BLAST376

Domaini

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

Sequence similaritiesi

Phylogenomic databases

eggNOGiKOG1089 Eukaryota
ENOG410XPTU LUCA
GeneTreeiENSGT00760000118832
HOGENOMiHOG000210598
HOVERGENiHBG000220
InParanoidiQ9Z2C5
KOiK01108
OMAiPNHHWRI
OrthoDBiEOG091G04DS

Family and domain databases

Gene3Di2.30.29.30, 1 hit
InterProiView protein in InterPro
IPR004182 GRAM
IPR030561 Myotubularin
IPR010569 Myotubularin-like_Pase_dom
IPR030564 Myotubularin_fam
IPR011993 PH-like_dom_sf
IPR029021 Prot-tyrosine_phosphatase-like
IPR016130 Tyr_Pase_AS
IPR003595 Tyr_Pase_cat
IPR000387 TYR_PHOSPHATASE_dom
PANTHERiPTHR10807 PTHR10807, 1 hit
PTHR10807:SF69 PTHR10807:SF69, 1 hit
PfamiView protein in Pfam
PF02893 GRAM, 1 hit
PF06602 Myotub-related, 1 hit
SMARTiView protein in SMART
SM00568 GRAM, 1 hit
SM00404 PTPc_motif, 1 hit
SUPFAMiSSF52799 SSF52799, 1 hit
PROSITEiView protein in PROSITE
PS51339 PPASE_MYOTUBULARIN, 1 hit
PS00383 TYR_PHOSPHATASE_1, 1 hit
PS50056 TYR_PHOSPHATASE_2, 1 hit

Sequencei

Sequence statusi: Complete.

Q9Z2C5-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MASASASKYN SHSLENESIK KVSQDGVSQD VSETVPRLPG ELLITEKEVI
60 70 80 90 100
YICPFNGPIK GRVYITNYRL YLRSLETDSA LILDVPLGVI SRIEKMGGAT
110 120 130 140 150
SRGENSYGLD ITCKDLRNLR FALKQEGHSR RDMFEILVKH AFPLAHNLPL
160 170 180 190 200
FAFVNEEKFN VDGWTVYNPV EEYRRQGLPN HHWRISFINK CYELCETYPA
210 220 230 240 250
LLVVPYRTSD DDLRRIATFR SRNRLPVLSW IHPENKMVIM RCSQPLVGMS
260 270 280 290 300
GKRNKDDEKY LDVIRETNKQ TSKLMIYDAR PSVNAVANKA TGGGYESDDA
310 320 330 340 350
YQNSELSFLD IHNIHVMRES LKKVKDIVYP NIEESHWLSS LESTHWLEHI
360 370 380 390 400
KLVLTGAIQV ADQVSSGKSS VLVHCSDGWD RTAQLTSLAM LMLDSFYRTI
410 420 430 440 450
EGFEILVQKE WISFGHKFAS RIGHGDKNHA DADRSPIFLQ FIDCVWQMSK
460 470 480 490 500
QFPTAFEFNE GFLITVLDHL YSCRFGTFLF NCDSARERQK LTERTVSLWS
510 520 530 540 550
LINSNKDKFK NPFYTKEINR VLYPVASMRH LELWVNYYIR WNPRVKQQQP
560 570 580 590 600
NPVEQRYMEL LALRDDYIKR LEELQLANSA KLADAPASTS SSSQMVPHVQ

THF
Length:603
Mass (Da):69,559
Last modified:June 28, 2011 - v2
Checksum:i65929312F07FFCC7
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti95K → Y in AAC77821 (PubMed:9736772).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF073996 mRNA Translation: AAC77821.1
AL731843, AL772294 Genomic DNA Translation: CAM20185.1
BC090984 mRNA Translation: AAH90984.1
CCDSiCCDS30177.1
RefSeqiNP_001157662.1, NM_001164190.1
NP_001157663.1, NM_001164191.1
NP_001157664.1, NM_001164192.1
NP_064310.2, NM_019926.3
UniGeneiMm.274981
Mm.423278

Genome annotation databases

EnsembliENSMUST00000033700; ENSMUSP00000033700; ENSMUSG00000031337
ENSMUST00000061970; ENSMUSP00000057182; ENSMUSG00000031337
ENSMUST00000114617; ENSMUSP00000110264; ENSMUSG00000031337
ENSMUST00000171933; ENSMUSP00000125798; ENSMUSG00000031337
GeneIDi17772
KEGGimmu:17772
UCSCiuc009tjq.2 mouse

Similar proteinsi

Entry informationi

Entry nameiMTM1_MOUSE
AccessioniPrimary (citable) accession number: Q9Z2C5
Secondary accession number(s): Q5BKQ5
Entry historyiIntegrated into UniProtKB/Swiss-Prot: December 1, 2000
Last sequence update: June 28, 2011
Last modified: March 28, 2018
This is version 138 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

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