MTM1_RAT
ID MTM1_RAT Reviewed; 602 AA.
AC Q6AXQ4; Q5BK31;
DT 08-APR-2008, integrated into UniProtKB/Swiss-Prot.
DT 08-APR-2008, sequence version 2.
DT 03-AUG-2022, entry version 118.
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 Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Kidney, and Testis;
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).
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 -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q6AXQ4-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q6AXQ4-2; Sequence=VSP_032751;
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=AAH79400.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=AAH91225.1; Type=Erroneous termination; Note=Truncated C-terminus.; Evidence={ECO:0000305};
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DR EMBL; BC079400; AAH79400.1; ALT_INIT; mRNA.
DR EMBL; BC091225; AAH91225.1; ALT_SEQ; mRNA.
DR RefSeq; NP_001013065.1; NM_001013047.1.
DR AlphaFoldDB; Q6AXQ4; -.
DR SMR; Q6AXQ4; -.
DR STRING; 10116.ENSRNOP00000058761; -.
DR iPTMnet; Q6AXQ4; -.
DR PhosphoSitePlus; Q6AXQ4; -.
DR PaxDb; Q6AXQ4; -.
DR PRIDE; Q6AXQ4; -.
DR Ensembl; ENSRNOT00000062057; ENSRNOP00000058761; ENSRNOG00000002516. [Q6AXQ4-2]
DR GeneID; 288762; -.
DR KEGG; rno:288762; -.
DR UCSC; RGD:1304582; rat. [Q6AXQ4-1]
DR CTD; 4534; -.
DR RGD; 1304582; Mtm1.
DR eggNOG; KOG4471; Eukaryota.
DR GeneTree; ENSGT00940000157029; -.
DR HOGENOM; CLU_001839_4_1_1; -.
DR InParanoid; Q6AXQ4; -.
DR OrthoDB; 824298at2759; -.
DR PhylomeDB; Q6AXQ4; -.
DR Reactome; R-RNO-1660499; Synthesis of PIPs at the plasma membrane.
DR Reactome; R-RNO-1660516; Synthesis of PIPs at the early endosome membrane.
DR Reactome; R-RNO-1660517; Synthesis of PIPs at the late endosome membrane.
DR PRO; PR:Q6AXQ4; -.
DR Proteomes; UP000002494; Chromosome 6.
DR Genevisible; Q6AXQ4; RN.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0030175; C:filopodium; ISS:UniProtKB.
DR GO; GO:0031674; C:I band; ISO:RGD.
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: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; ISO:RGD.
DR GO; GO:1902902; P:negative regulation of autophagosome assembly; ISO:RGD.
DR GO; GO:0032435; P:negative regulation of proteasomal ubiquitin-dependent protein catabolic process; ISO:RGD.
DR GO; GO:0051898; P:negative regulation of protein kinase B signaling; ISO:RGD.
DR GO; GO:0032007; P:negative regulation of TOR signaling; ISO:RGD.
DR GO; GO:0046856; P:phosphatidylinositol dephosphorylation; ISS:UniProtKB.
DR GO; GO:0048633; P:positive regulation of skeletal muscle tissue growth; ISO:RGD.
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 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.
PE 2: Evidence at transcript level;
KW Alternative splicing; Cell membrane; Cell projection; Cytoplasm; Endosome;
KW Hydrolase; Lipid metabolism; Membrane; Phosphoprotein; Protein phosphatase;
KW Protein transport; Reference proteome; Transport.
FT CHAIN 1..602
FT /note="Myotubularin"
FT /id="PRO_0000328657"
FT DOMAIN 28..97
FT /note="GRAM"
FT DOMAIN 163..538
FT /note="Myotubularin phosphatase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00669"
FT REGION 1..40
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 578..602
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 10..27
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 18
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q13496"
FT MOD_RES 495
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q13496"
FT VAR_SEQ 546
FT /note="R -> RQ (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_032751"
SQ SEQUENCE 602 AA; 69352 MW; 15F32DE9EE95288B CRC64;
MASSSASDCD AHPVERESMR KVSQDGVRQD MSKSGPRLPG ESAITDKEVI YICPFSGPVK
GRLYITNYRL YLRSLETDLA PILDVPLGVI SRIEKMGGVT SRGENSYGLD ITCKDLRNLR
FALKQEGHSR RDIFDVLTRH AFPLAYNLPL FAFVNEEKFK VDGWAIYNPV EEYRRQGLPD
RHWRISFVNQ RYELCDTYPA LLVVPYRASD DDLRRVATFR SRNRIPVLSW IHPENRAAIM
RCSQPLVGVG GKRSRDDERY LDIIRETNKQ TSKLTIYDAR PGVNAVANKA TGGGYEGEDA
YPHAELSFLD IHNIHVMRES LRRVRDIVYP HVEEAHWLSS LESTHWLEHI KLLLTGAIRV
ADKVASGLSS VLVHCSDGWD RTAQLTTLAM LMLDGFYRSI EGFEILVQKE WISFGHKFSS
RIGHGDKNHA DADRSPIFLQ FIDCVWQMTK QFPTAFEFNE CFLVAILDHL YSCRFGTFLL
NCEAARERQR LAERTVSVWS LINSNKDEFT NPFYARESNR VIYPVTSVRH LELWVNYYIR
WNPRIRQQPH PMEQRYNELL ALRDDYIKKL EELQLATPTK LTDSSTPPSG SAQIAPRMQT
HF
