MTM1_PONAB
ID MTM1_PONAB Reviewed; 603 AA.
AC Q5R9S3;
DT 08-APR-2008, integrated into UniProtKB/Swiss-Prot.
DT 21-DEC-2004, sequence version 1.
DT 03-AUG-2022, entry version 92.
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 Pongo abelii (Sumatran orangutan) (Pongo pygmaeus abelii).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Pongo.
OX NCBI_TaxID=9601;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Kidney;
RG The German cDNA consortium;
RL Submitted (NOV-2004) 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}.
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DR EMBL; CR859309; CAH91487.1; -; mRNA.
DR RefSeq; NP_001127425.1; NM_001133953.1.
DR AlphaFoldDB; Q5R9S3; -.
DR SMR; Q5R9S3; -.
DR STRING; 9601.ENSPPYP00000023299; -.
DR GeneID; 100174495; -.
DR KEGG; pon:100174495; -.
DR CTD; 4534; -.
DR eggNOG; KOG4471; Eukaryota.
DR InParanoid; Q5R9S3; -.
DR OrthoDB; 824298at2759; -.
DR Proteomes; UP000001595; Unplaced.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0030175; C:filopodium; ISS:UniProtKB.
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:0030017; C:sarcomere; IEA:UniProtKB-SubCell.
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: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; IEA:InterPro.
DR GO; GO:0006661; P:phosphatidylinositol biosynthetic process; IEA:UniProt.
DR GO; GO:0046856; P:phosphatidylinositol dephosphorylation; ISS:UniProtKB.
DR GO; GO:0006470; P:protein dephosphorylation; ISS:UniProtKB.
DR GO; GO:0015031; P:protein transport; IEA:UniProtKB-KW.
DR GO; GO:0044088; P:regulation of vacuole organization; ISS:UniProtKB.
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_0000328656"
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..25
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 579..603
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 580..603
FT /note="Polar 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; 69900 MW; C4A50B462190D484 CRC64;
MASASTSKYN SHSLENESIK RTSRDGVNRD LTEAVPRLPG ETLITDKEVI YICPFNGPIK
GRVYITNYRL YLRSLETDSA LILDVPLGVI SRIEKMGGAT SRGENSYGLD ITCKDMRNLR
FALKQEGHSR RDMFEILTRY AFPLAHSLPL FAFLNEEKFN VDGWTVYNPV EEYRRQGLPN
HHWRITFINK CYELCDTYPA PLVVPYRASD DDLRRVATFR SRNRIPVLSW IHPENKTVIV
RCSQPLVGMS GKRNKDDEKY LDVIRETNKQ ISKLTIYDAR PSVNAVANKA TGGGYESDDA
YHNAELFFLD IHNIHVMRES LKKVKDIVYP NVEESHWLSS LESTHWLEHI KLVLTGAIQV
ADKVSSGKSS VLVHCSDGWD RTAQLTSLAM LMLDSFYRSI EGFEILVQKE WISFGHKFAS
RIGHGDKNHT DADRSPIFLQ FIDCVWQMSK QFPTAFEFNE QFLIIILDHL YSCRFGTFLF
NCESARERQK VTERTVSLWS LINSNKEKFK NPFYTKEINR VLYPVASMRH LELWVNYYIR
WNPRIKQQQP NPVEQRYMEL LALRDEYIKR LEELQLANSA KLSDPPTSPS SPSQMMPHVQ
THF
