MTM1_MOUSE
ID MTM1_MOUSE Reviewed; 603 AA.
AC Q9Z2C5; Q5BKQ5;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT 28-JUN-2011, sequence version 2.
DT 03-AUG-2022, entry version 160.
DE RecName: Full=Myotubularin;
DE AltName: Full=Phosphatidylinositol-3,5-bisphosphate 3-phosphatase;
DE EC=3.1.3.95 {ECO:0000250|UniProtKB:Q13496};
DE AltName: Full=Phosphatidylinositol-3-phosphate phosphatase;
DE EC=3.1.3.64 {ECO:0000250|UniProtKB:Q13496};
GN Name=Mtm1;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=9736772; DOI=10.1093/hmg/7.11.1703;
RA Laporte J., Blondeau F., Buj-Bello A., Tentler D., Kretz C., Dahl N.,
RA Mandel J.-L.;
RT "Characterization of the myotubularin dual specificity phosphatase gene
RT family from yeast to human.";
RL Hum. Mol. Genet. 7:1703-1712(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=CD-1; TISSUE=Pituitary;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=12118066; DOI=10.1242/jcs.115.15.3105;
RA Laporte J., Blondeau F., Gansmuller A., Lutz Y., Vonesch J.L., Mandel J.L.;
RT "The PtdIns3P phosphatase myotubularin is a cytoplasmic protein that also
RT localizes to Rac1-inducible plasma membrane ruffles.";
RL J. Cell Sci. 115:3105-3117(2002).
RN [5]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=12391329; DOI=10.1073/pnas.212498399;
RA Buj-Bello A., Laugel V., Messaddeq N., Zahreddine H., Laporte J.,
RA Pellissier J.F., Mandel J.L.;
RT "The lipid phosphatase myotubularin is essential for skeletal muscle
RT maintenance but not for myogenesis in mice.";
RL Proc. Natl. Acad. Sci. U.S.A. 99:15060-15065(2002).
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas, and
RC Spleen;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [7]
RP FUNCTION, INTERACTION WITH DES, AND DISRUPTION PHENOTYPE.
RX PubMed=21135508; DOI=10.1172/jci44021;
RA Hnia K., Tronchere H., Tomczak K.K., Amoasii L., Schultz P., Beggs A.H.,
RA Payrastre B., Mandel J.L., Laporte J.;
RT "Myotubularin controls desmin intermediate filament architecture and
RT mitochondrial dynamics in human and mouse skeletal muscle.";
RL J. Clin. Invest. 121:70-85(2011).
RN [8]
RP FUNCTION, INTERACTION WITH MTMR12, SUBCELLULAR LOCATION, TISSUE
RP SPECIFICITY, AND DEVELOPMENTAL STAGE.
RX PubMed=23818870; DOI=10.1371/journal.pgen.1003583;
RA Gupta V.A., Hnia K., Smith L.L., Gundry S.R., McIntire J.E., Shimazu J.,
RA Bass J.R., Talbot E.A., Amoasii L., Goldman N.E., Laporte J., Beggs A.H.;
RT "Loss of catalytically inactive lipid phosphatase myotubularin-related
RT protein 12 impairs myotubularin stability and promotes centronuclear
RT myopathy in zebrafish.";
RL PLoS Genet. 9:E1003583-E1003583(2013).
CC -!- FUNCTION: Lipid phosphatase which dephosphorylates phosphatidylinositol
CC 3-monophosphate (PI3P) and phosphatidylinositol 3,5-bisphosphate
CC (PI(3,5)P2). Has also been shown to dephosphorylate
CC phosphotyrosine- and phosphoserine-containing peptides. Negatively
CC regulates EGFR degradation through regulation of EGFR trafficking from
CC the late endosome to the lysosome. Plays a role in vacuolar formation
CC and morphology (By similarity). Regulates desmin intermediate filament
CC assembly and architecture. Plays a role in mitochondrial morphology and
CC positioning (PubMed:21135508). Required for skeletal muscle maintenance
CC but not for myogenesis (PubMed:12391329). In skeletal muscles,
CC stabilizes MTMR12 protein levels (PubMed:23818870).
CC {ECO:0000250|UniProtKB:Q13496, ECO:0000269|PubMed:12391329,
CC ECO:0000269|PubMed:21135508, ECO:0000269|PubMed:23818870}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-3-
CC phosphate) + H2O = a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-
CC inositol) + phosphate; Xref=Rhea:RHEA:12316, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:57880, ChEBI:CHEBI:58088; EC=3.1.3.64;
CC Evidence={ECO:0000250|UniProtKB:Q13496};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-3,5-
CC bisphosphate) + H2O = a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-
CC inositol-5-phosphate) + phosphate; Xref=Rhea:RHEA:39019,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:43474, ChEBI:CHEBI:57795,
CC ChEBI:CHEBI:57923; EC=3.1.3.95;
CC Evidence={ECO:0000250|UniProtKB:Q13496};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1,2-dioctanoyl-sn-glycero-3-phospho-(1-D-myo-inositol-3-
CC phosphate) + H2O = 1,2-dioctanoyl-sn-glycero-3-phospho-(1D-myo-
CC inositol) + phosphate; Xref=Rhea:RHEA:42328, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:65221, ChEBI:CHEBI:78934;
CC Evidence={ECO:0000250|UniProtKB:Q13496};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1,2-dioctanoyl-sn-glycero-3-phospho-(1D-myo-inositol-3,5-
CC bisphosphate) + H2O = 1,2-dioctanoyl-sn-glycero-3-phospho-(1D-myo-
CC inositol-5-phosphate) + phosphate; Xref=Rhea:RHEA:45632,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:43474, ChEBI:CHEBI:78911,
CC ChEBI:CHEBI:85342; Evidence={ECO:0000250|UniProtKB:Q13496};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1,2-dihexadecanoyl-sn-glycero-3-phospho-(1D-myo-inositol-3,5-
CC phosphate) + H2O = 1,2-dihexadecanoyl-sn-glycero-3-phospho-(1D-myo-
CC inositol-5-phosphate) + phosphate; Xref=Rhea:RHEA:45636,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:43474, ChEBI:CHEBI:78994,
CC ChEBI:CHEBI:84968; Evidence={ECO:0000250|UniProtKB:Q13496};
CC -!- ACTIVITY REGULATION: Allosterically activated by phosphatidylinositol
CC 5-phosphate (PI5P). {ECO:0000250|UniProtKB:Q13496}.
CC -!- SUBUNIT: Heterodimer with MTMR12 (PubMed:23818870). Interacts with
CC KMT2A/MLL1 (via SET domain) (By similarity). Interacts with DES in
CC skeletal muscle but not in cardiac muscle (PubMed:21135508). Interacts
CC with SPEG (By similarity). {ECO:0000250|UniProtKB:Q13496,
CC ECO:0000269|PubMed:21135508, ECO:0000269|PubMed:23818870}.
CC -!- INTERACTION:
CC Q9Z2C5; O08539: Bin1; NbExp=3; IntAct=EBI-6861578, EBI-775152;
CC Q9Z2C5; P31001: Des; NbExp=4; IntAct=EBI-6861578, EBI-298565;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:12118066}. Cell
CC membrane {ECO:0000250|UniProtKB:Q13496}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:Q13496}. Cell projection, filopodium
CC {ECO:0000269|PubMed:12118066}. Cell projection, ruffle
CC {ECO:0000269|PubMed:12118066}. Late endosome
CC {ECO:0000250|UniProtKB:Q13496}. Cytoplasm, myofibril, sarcomere
CC {ECO:0000269|PubMed:23818870}. Note=Localizes as a dense cytoplasmic
CC network. Also localizes to the plasma membrane, including plasma
CC membrane extensions such as filopodia and ruffles. Predominantly
CC located in the cytoplasm following interaction with MTMR12. Recruited
CC to the late endosome following EGF stimulation (By similarity). In
CC skeletal muscles, co-localizes with MTMR12 in the sarcomere
CC (PubMed:23818870). {ECO:0000250|UniProtKB:Q13496,
CC ECO:0000269|PubMed:23818870}.
CC -!- TISSUE SPECIFICITY: Widely expressed with highest levels detected in
CC heart and muscle and low levels in brain (at protein level)
CC (PubMed:12118066). Expressed in skeletal muscles (at protein level)
CC (PubMed:23818870). {ECO:0000269|PubMed:12118066,
CC ECO:0000269|PubMed:23818870}.
CC -!- DEVELOPMENTAL STAGE: Expression increases during skeletal muscle cell
CC differentiation. {ECO:0000269|PubMed:23818870}.
CC -!- DOMAIN: The GRAM domain mediates binding to PI(3,5)P2 and, with lower
CC affinity, to other phosphoinositides. {ECO:0000250|UniProtKB:Q13496}.
CC -!- DISRUPTION PHENOTYPE: Mice are viable although lifespan is severely
CC reduced. An under-representation of mutant males suggests some prenatal
CC lethality. Generalized and progressive myopathy starts at around 4
CC weeks of age with amyotrophy and accumulation of central nuclei in
CC skeletal muscle fibers, leading to death at 6-14 weeks. Mutants also
CC show mitochondrial disorganization and increased levels of desmin with
CC abnormal desmin intermediate filament formation and architecture.
CC {ECO:0000269|PubMed:12391329, ECO:0000269|PubMed:21135508}.
CC -!- SIMILARITY: Belongs to the protein-tyrosine phosphatase family. Non-
CC receptor class myotubularin subfamily. {ECO:0000305}.
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DR EMBL; AF073996; AAC77821.1; -; mRNA.
DR EMBL; AL731843; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL772294; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC090984; AAH90984.1; -; mRNA.
DR CCDS; CCDS30177.1; -.
DR RefSeq; NP_001157662.1; NM_001164190.1.
DR RefSeq; NP_001157663.1; NM_001164191.1.
DR RefSeq; NP_001157664.1; NM_001164192.1.
DR RefSeq; NP_064310.2; NM_019926.3.
DR AlphaFoldDB; Q9Z2C5; -.
DR SMR; Q9Z2C5; -.
DR BioGRID; 201597; 8.
DR IntAct; Q9Z2C5; 4.
DR MINT; Q9Z2C5; -.
DR STRING; 10090.ENSMUSP00000099040; -.
DR iPTMnet; Q9Z2C5; -.
DR PhosphoSitePlus; Q9Z2C5; -.
DR MaxQB; Q9Z2C5; -.
DR PaxDb; Q9Z2C5; -.
DR PRIDE; Q9Z2C5; -.
DR ProteomicsDB; 290111; -.
DR Antibodypedia; 544; 319 antibodies from 36 providers.
DR DNASU; 17772; -.
DR Ensembl; ENSMUST00000033700; ENSMUSP00000033700; ENSMUSG00000031337.
DR Ensembl; ENSMUST00000061970; ENSMUSP00000057182; ENSMUSG00000031337.
DR Ensembl; ENSMUST00000114617; ENSMUSP00000110264; ENSMUSG00000031337.
DR Ensembl; ENSMUST00000171933; ENSMUSP00000125798; ENSMUSG00000031337.
DR GeneID; 17772; -.
DR KEGG; mmu:17772; -.
DR UCSC; uc009tjq.2; mouse.
DR CTD; 4534; -.
DR MGI; MGI:1099452; Mtm1.
DR VEuPathDB; HostDB:ENSMUSG00000031337; -.
DR eggNOG; KOG4471; Eukaryota.
DR GeneTree; ENSGT00940000157029; -.
DR HOGENOM; CLU_001839_4_1_1; -.
DR InParanoid; Q9Z2C5; -.
DR OMA; DDAYHNT; -.
DR OrthoDB; 824298at2759; -.
DR PhylomeDB; Q9Z2C5; -.
DR Reactome; R-MMU-1660499; Synthesis of PIPs at the plasma membrane.
DR Reactome; R-MMU-1660516; Synthesis of PIPs at the early endosome membrane.
DR Reactome; R-MMU-1660517; Synthesis of PIPs at the late endosome membrane.
DR BioGRID-ORCS; 17772; 1 hit in 76 CRISPR screens.
DR ChiTaRS; Mtm1; mouse.
DR PRO; PR:Q9Z2C5; -.
DR Proteomes; UP000000589; Chromosome X.
DR RNAct; Q9Z2C5; protein.
DR Bgee; ENSMUSG00000031337; Expressed in left colon and 232 other tissues.
DR ExpressionAtlas; Q9Z2C5; baseline and differential.
DR Genevisible; Q9Z2C5; MM.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0030175; C:filopodium; ISS:UniProtKB.
DR GO; GO:0031674; C:I band; IDA:MGI.
DR GO; GO:0005770; C:late endosome; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0001726; C:ruffle; ISS:UniProtKB.
DR GO; GO:0019215; F:intermediate filament binding; ISS:UniProtKB.
DR GO; GO:0035091; F:phosphatidylinositol binding; ISS:UniProtKB.
DR GO; GO:0052629; F:phosphatidylinositol-3,5-bisphosphate 3-phosphatase activity; ISS:UniProtKB.
DR GO; GO:0004438; F:phosphatidylinositol-3-phosphatase activity; ISS:UniProtKB.
DR GO; GO:0004721; F:phosphoprotein phosphatase activity; ISS:UniProtKB.
DR GO; GO:0000045; P:autophagosome assembly; IMP:MGI.
DR GO; GO:0008333; P:endosome to lysosome transport; ISS:UniProtKB.
DR GO; GO:0045109; P:intermediate filament organization; ISS:UniProtKB.
DR GO; GO:0048311; P:mitochondrion distribution; IMP:UniProtKB.
DR GO; GO:0070584; P:mitochondrion morphogenesis; IMP:UniProtKB.
DR GO; GO:0046716; P:muscle cell cellular homeostasis; IMP:MGI.
DR GO; GO:1902902; P:negative regulation of autophagosome assembly; IMP:MGI.
DR GO; GO:0032435; P:negative regulation of proteasomal ubiquitin-dependent protein catabolic process; IMP:MGI.
DR GO; GO:0051898; P:negative regulation of protein kinase B signaling; IMP:MGI.
DR GO; GO:0032007; P:negative regulation of TOR signaling; IMP:MGI.
DR GO; GO:0046856; P:phosphatidylinositol dephosphorylation; ISS:UniProtKB.
DR GO; GO:0048633; P:positive regulation of skeletal muscle tissue growth; IMP:MGI.
DR GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; IMP:MGI.
DR GO; GO:0006470; P:protein dephosphorylation; ISS:UniProtKB.
DR GO; GO:0043491; P:protein kinase B signaling; IMP:MGI.
DR GO; GO:0015031; P:protein transport; IEA:UniProtKB-KW.
DR GO; GO:0044088; P:regulation of vacuole organization; ISS:UniProtKB.
DR GO; GO:0048630; P:skeletal muscle tissue growth; IMP:MGI.
DR GO; GO:0031929; P:TOR signaling; IMP:MGI.
DR Gene3D; 2.30.29.30; -; 1.
DR InterPro; IPR004182; GRAM.
DR InterPro; IPR030561; Myotubularin.
DR InterPro; IPR010569; Myotubularin-like_Pase_dom.
DR InterPro; IPR030564; Myotubularin_fam.
DR InterPro; IPR011993; PH-like_dom_sf.
DR InterPro; IPR029021; Prot-tyrosine_phosphatase-like.
DR InterPro; IPR016130; Tyr_Pase_AS.
DR InterPro; IPR003595; Tyr_Pase_cat.
DR InterPro; IPR000387; Tyr_Pase_dom.
DR PANTHER; PTHR10807; PTHR10807; 1.
DR PANTHER; PTHR10807:SF69; PTHR10807:SF69; 1.
DR Pfam; PF02893; GRAM; 1.
DR Pfam; PF06602; Myotub-related; 1.
DR SMART; SM00568; GRAM; 1.
DR SMART; SM00404; PTPc_motif; 1.
DR SUPFAM; SSF52799; SSF52799; 1.
DR PROSITE; PS51339; PPASE_MYOTUBULARIN; 1.
DR PROSITE; PS00383; TYR_PHOSPHATASE_1; 1.
DR PROSITE; PS50056; TYR_PHOSPHATASE_2; 1.
PE 1: Evidence at protein level;
KW Cell membrane; Cell projection; Cytoplasm; Endosome; Hydrolase;
KW Lipid metabolism; Membrane; Phosphoprotein; Protein phosphatase;
KW Protein transport; Reference proteome; Transport.
FT CHAIN 1..603
FT /note="Myotubularin"
FT /id="PRO_0000094931"
FT DOMAIN 29..97
FT /note="GRAM"
FT DOMAIN 163..538
FT /note="Myotubularin phosphatase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00669"
FT ACT_SITE 375
FT /note="Phosphocysteine intermediate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10044"
FT MOD_RES 13
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q13496"
FT MOD_RES 18
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q13496"
FT MOD_RES 495
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q13496"
FT MOD_RES 588
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q13496"
FT CONFLICT 95
FT /note="K -> Y (in Ref. 1; AAC77821)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 603 AA; 69559 MW; 65929312F07FFCC7 CRC64;
MASASASKYN SHSLENESIK KVSQDGVSQD VSETVPRLPG ELLITEKEVI YICPFNGPIK
GRVYITNYRL YLRSLETDSA LILDVPLGVI SRIEKMGGAT SRGENSYGLD ITCKDLRNLR
FALKQEGHSR RDMFEILVKH AFPLAHNLPL FAFVNEEKFN VDGWTVYNPV EEYRRQGLPN
HHWRISFINK CYELCETYPA LLVVPYRTSD DDLRRIATFR SRNRLPVLSW IHPENKMVIM
RCSQPLVGMS GKRNKDDEKY LDVIRETNKQ TSKLMIYDAR PSVNAVANKA TGGGYESDDA
YQNSELSFLD IHNIHVMRES LKKVKDIVYP NIEESHWLSS LESTHWLEHI KLVLTGAIQV
ADQVSSGKSS VLVHCSDGWD RTAQLTSLAM LMLDSFYRTI EGFEILVQKE WISFGHKFAS
RIGHGDKNHA DADRSPIFLQ FIDCVWQMSK QFPTAFEFNE GFLITVLDHL YSCRFGTFLF
NCDSARERQK LTERTVSLWS LINSNKDKFK NPFYTKEINR VLYPVASMRH LELWVNYYIR
WNPRVKQQQP NPVEQRYMEL LALRDDYIKR LEELQLANSA KLADAPASTS SSSQMVPHVQ
THF
