MTM1_BOVIN
ID MTM1_BOVIN Reviewed; 603 AA.
AC A6QLT4;
DT 08-APR-2008, integrated into UniProtKB/Swiss-Prot.
DT 08-APR-2008, sequence version 2.
DT 03-AUG-2022, entry version 104.
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 Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Hereford; TISSUE=Hypothalamus;
RG NIH - Mammalian Gene Collection (MGC) project;
RL Submitted (JUN-2007) to the EMBL/GenBank/DDBJ databases.
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. Regulates desmin intermediate filament assembly and
CC architecture. Plays a role in mitochondrial morphology and positioning.
CC Required for skeletal muscle maintenance but not for myogenesis. In
CC skeletal muscles, stabilizes MTMR12 protein levels.
CC {ECO:0000250|UniProtKB:Q13496}.
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. Interacts with KMT2A/MLL1 (via SET
CC domain). Interacts with DES in skeletal muscle but not in cardiac
CC muscle. Interacts with SPEG. {ECO:0000250|UniProtKB:Q13496}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q13496}. Cell
CC membrane {ECO:0000250|UniProtKB:Q13496}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:Q13496}. Cell projection, filopodium
CC {ECO:0000250|UniProtKB:Q13496}. Cell projection, ruffle
CC {ECO:0000250|UniProtKB:Q13496}. Late endosome
CC {ECO:0000250|UniProtKB:Q13496}. Cytoplasm, myofibril, sarcomere
CC {ECO:0000250|UniProtKB:Q9Z2C5}. 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 (By
CC similarity). {ECO:0000250|UniProtKB:Q13496,
CC ECO:0000250|UniProtKB:Q9Z2C5}.
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 -!- SIMILARITY: Belongs to the protein-tyrosine phosphatase family. Non-
CC receptor class myotubularin subfamily. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAI48079.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; BC148078; AAI48079.1; ALT_INIT; mRNA.
DR RefSeq; NP_001193354.1; NM_001206425.2.
DR AlphaFoldDB; A6QLT4; -.
DR SMR; A6QLT4; -.
DR STRING; 9913.ENSBTAP00000018789; -.
DR PaxDb; A6QLT4; -.
DR PRIDE; A6QLT4; -.
DR Ensembl; ENSBTAT00000018789; ENSBTAP00000018789; ENSBTAG00000014138.
DR Ensembl; ENSBTAT00000068194; ENSBTAP00000066432; ENSBTAG00000014138.
DR GeneID; 533622; -.
DR KEGG; bta:533622; -.
DR CTD; 4534; -.
DR VEuPathDB; HostDB:ENSBTAG00000014138; -.
DR VGNC; VGNC:31735; MTM1.
DR eggNOG; KOG4471; Eukaryota.
DR GeneTree; ENSGT00940000157029; -.
DR HOGENOM; CLU_001839_4_1_1; -.
DR InParanoid; A6QLT4; -.
DR OMA; DDAYHNT; -.
DR OrthoDB; 824298at2759; -.
DR TreeFam; TF315197; -.
DR Proteomes; UP000009136; Chromosome X.
DR Bgee; ENSBTAG00000014138; Expressed in oocyte and 106 other tissues.
DR ExpressionAtlas; A6QLT4; baseline.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; IEA:Ensembl.
DR GO; GO:0030175; C:filopodium; ISS:UniProtKB.
DR GO; GO:0031674; C:I band; IEA:Ensembl.
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; IEA:Ensembl.
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; ISS:UniProtKB.
DR GO; GO:0070584; P:mitochondrion morphogenesis; ISS:UniProtKB.
DR GO; GO:0046716; P:muscle cell cellular homeostasis; IBA:GO_Central.
DR GO; GO:1902902; P:negative regulation of autophagosome assembly; IBA:GO_Central.
DR GO; GO:0032435; P:negative regulation of proteasomal ubiquitin-dependent protein catabolic process; IEA:Ensembl.
DR GO; GO:0051898; P:negative regulation of protein kinase B signaling; IEA:Ensembl.
DR GO; GO:0032007; P:negative regulation of TOR signaling; IEA:Ensembl.
DR GO; GO:0046856; P:phosphatidylinositol dephosphorylation; ISS:UniProtKB.
DR GO; GO:0048633; P:positive regulation of skeletal muscle tissue growth; IEA:Ensembl.
DR GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; IEA:Ensembl.
DR GO; GO:0006470; P:protein dephosphorylation; ISS:UniProtKB.
DR GO; GO:0043491; P:protein kinase B signaling; IEA:Ensembl.
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; IEA:Ensembl.
DR GO; GO:0031929; P:TOR signaling; IEA:Ensembl.
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 2: Evidence at transcript 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_0000328655"
FT DOMAIN 29..97
FT /note="GRAM"
FT DOMAIN 163..538
FT /note="Myotubularin phosphatase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00669"
FT REGION 1..32
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 580..603
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 14..31
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
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"
SQ SEQUENCE 603 AA; 70020 MW; 7A7E7929C26FF8F9 CRC64;
MASAPTSKYN SHSLENESIK RTSRDGVNRD VGETLPRLPG EIRITDKEVI YICPFNGPIK
GRVYITNYRL YLRSLETDSA LILDVPLGVI SRIEKMGGAT SRGENSYGLD ITCKDLRNLR
FALKQEGHSR RDMFEILTRY AFPLAHSLPI FAFLNEEKFN VDGWTVYNPV EEYRRQGLPN
HHWRITFINK CYKLCDTYPA LLVVPYRASD EDLRRVATFR SRNRIPVLSW IHPENKTVIV
RCSQPLVGMS GKRNKEDERY LDVIRETNRQ VNKLTIYDAR PNVNAVANKA TGGGYESDDV
YHNAELFFLD IHNIHVMRES LKKVKDIVYP NVEESHWLSS LESTHWLEHI KLVLTGAIQV
ADRVSSGKSS VVVHCSDGWD RTAQLTSLAM LMLDSFYRSI EGFEILVQKE WISFGHKFAS
RIGHGDKNHA DADRSPIFLQ FIDCVWQMSK QFPTAFEFNE RFLITILDHL YSCRFGTFLY
NCESAREKQK VTERTVSLWS LINSNKDKFK NPFYTKEINR VLYPVASMRH LELWVNYYIR
WNPRIKQQQP NPVEQRYMEL LALRDEYIKR LDELQLANSA KLSDPSASPS SPSQMMPHVQ
THF
