MTM1_HUMAN
ID MTM1_HUMAN Reviewed; 603 AA.
AC Q13496; A6NDB1; B7Z491; F2Z330; Q8NEL1;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 15-JUL-1998, sequence version 2.
DT 03-AUG-2022, entry version 196.
DE RecName: Full=Myotubularin {ECO:0000305};
DE AltName: Full=Phosphatidylinositol-3,5-bisphosphate 3-phosphatase;
DE EC=3.1.3.95 {ECO:0000269|PubMed:12646134, ECO:0000269|PubMed:14722070};
DE AltName: Full=Phosphatidylinositol-3-phosphate phosphatase;
DE EC=3.1.3.64 {ECO:0000269|PubMed:10900271, ECO:0000269|PubMed:11001925, ECO:0000269|PubMed:12646134, ECO:0000269|PubMed:12847286, ECO:0000269|PubMed:14722070};
GN Name=MTM1 {ECO:0000312|HGNC:HGNC:7448}; Synonyms=CG2;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=8640223; DOI=10.1038/ng0696-175;
RA Laporte J., Hu L.-J., Kretz C., Mandel J.-L., Kioschis P., Coy J.,
RA Klauck S.M., Poutska A., Dahl N.;
RT "A gene mutated in X-linked myotubular myopathy defines a new putative
RT tyrosine phosphatase family conserved in yeast.";
RL Nat. Genet. 13:175-182(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=9781038; DOI=10.1038/sj.ejhg.5200189;
RA Laporte J., Guiraud-Chaumeil C., Tanner S.M., Blondeau F., Hu L.J.,
RA Vicaire S., Liechti-Gallati S., Mandel J.-L.;
RT "Genomic organization of the MTM1 gene implicated in X-linked myotubular
RT myopathy.";
RL Eur. J. Hum. Genet. 6:325-330(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Umbilical cord blood;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15772651; DOI=10.1038/nature03440;
RA Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D.,
RA Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L.,
RA Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C.,
RA Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A.,
RA Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P.,
RA Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D.,
RA Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D.,
RA Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L.,
RA Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P.,
RA Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G.,
RA Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J.,
RA Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D.,
RA Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L.,
RA Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z.,
RA Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S.,
RA Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S.,
RA Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O.,
RA Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H.,
RA Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T.,
RA Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L.,
RA Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R.,
RA Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y.,
RA Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K.,
RA Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J.,
RA Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L.,
RA Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S.,
RA Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A.,
RA Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L.,
RA Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D.,
RA Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H.,
RA McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S.,
RA Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C.,
RA Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S.,
RA Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V.,
RA Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K.,
RA Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K.,
RA Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D.,
RA Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R.,
RA Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B.,
RA Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C.,
RA d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q.,
RA Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N.,
RA Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A.,
RA Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J.,
RA Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A.,
RA Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F.,
RA Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L.,
RA Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S.,
RA Rogers J., Bentley D.R.;
RT "The DNA sequence of the human X chromosome.";
RL Nature 434:325-337(2005).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=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).
RN [7]
RP FUNCTION, AND INTERACTION WITH KMT2A/MLL1.
RX PubMed=9537414; DOI=10.1038/ng0498-331;
RA Cui X., De Vivo I., Slany R., Miyamoto A., Firestein R., Cleary M.L.;
RT "Association of SET domain and myotubularin-related proteins modulates
RT growth control.";
RL Nat. Genet. 18:331-337(1998).
RN [8]
RP REVIEW ON VARIANTS CNMX.
RX PubMed=10790201;
RX DOI=10.1002/(sici)1098-1004(200005)15:5<393::aid-humu1>3.0.co;2-r;
RA Laporte J., Biancalana V., Tanner S.M., Kress W., Schneider V.,
RA Wallgren-Pettersson C., Herger F., Buj-Bello A., Blondeau F.,
RA Liechti-Gallati S., Mandel J.-L.;
RT "MTM1 mutations in X-linked myotubular myopathy.";
RL Hum. Mutat. 15:393-409(2000).
RN [9]
RP FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, AND MUTAGENESIS OF
RP ASP-278; CYS-375; ASP-377; ASP-380; ASP-394; GLU-410 AND ASP-443.
RX PubMed=11001925; DOI=10.1093/oxfordjournals.hmg.a018913;
RA Blondeau F., Laporte J., Bodin S., Superti-Furga G., Payrastre B.,
RA Mandel J.L.;
RT "Myotubularin, a phosphatase deficient in myotubular myopathy, acts on
RT phosphatidylinositol 3-kinase and phosphatidylinositol 3-phosphate
RT pathway.";
RL Hum. Mol. Genet. 9:2223-2229(2000).
RN [10]
RP FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, CHARACTERIZATION OF
RP VARIANTS LEU-205; LEU-241; ASN-376; ARG-378 AND CYS-397, AND MUTAGENESIS OF
RP CYS-375.
RX PubMed=10900271; DOI=10.1073/pnas.160255697;
RA Taylor G.S., Maehama T., Dixon J.E.;
RT "Myotubularin, a protein tyrosine phosphatase mutated in myotubular
RT myopathy, dephosphorylates the lipid second messenger, phosphatidylinositol
RT 3-phosphate.";
RL Proc. Natl. Acad. Sci. U.S.A. 97:8910-8915(2000).
RN [11]
RP SUBCELLULAR LOCATION, AND MUTAGENESIS OF ASP-257; ASP-278; CYS-375; ASP-377
RP AND ASP-380.
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 [12]
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, CHARACTERIZATION OF
RP VARIANTS CYS-69; GLY-184; LEU-241 AND GLN-421, AND MUTAGENESIS OF LYS-114;
RP ARG-220 AND CYS-375.
RX PubMed=12646134; DOI=10.1016/s0960-9822(03)00132-5;
RA Schaletzky J., Dove S.K., Short B., Lorenzo O., Clague M.J., Barr F.A.;
RT "Phosphatidylinositol-5-phosphate activation and conserved substrate
RT specificity of the myotubularin phosphatidylinositol 3-phosphatases.";
RL Curr. Biol. 13:504-509(2003).
RN [13]
RP CATALYTIC ACTIVITY, INTERACTION WITH MTMR12, SUBCELLULAR LOCATION, AND
RP IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=12847286; DOI=10.1073/pnas.1033097100;
RA Nandurkar H.H., Layton M., Laporte J., Selan C., Corcoran L.,
RA Caldwell K.K., Mochizuki Y., Majerus P.W., Mitchell C.A.;
RT "Identification of myotubularin as the lipid phosphatase catalytic subunit
RT associated with the 3-phosphatase adapter protein, 3-PAP.";
RL Proc. Natl. Acad. Sci. U.S.A. 100:8660-8665(2003).
RN [14]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, SUBCELLULAR
RP LOCATION, ROLE OF GRAM DOMAIN, AND CHARACTERIZATION OF VARIANTS PHE-49;
RP CYS-69; PHE-70 AND PRO-87.
RX PubMed=14722070; DOI=10.1074/jbc.m312294200;
RA Tsujita K., Itoh T., Ijuin T., Yamamoto A., Shisheva A., Laporte J.,
RA Takenawa T.;
RT "Myotubularin regulates the function of the late endosome through the gram
RT domain-phosphatidylinositol 3,5-bisphosphate interaction.";
RL J. Biol. Chem. 279:13817-13824(2004).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-495, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=16964243; DOI=10.1038/nbt1240;
RA Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.;
RT "A probability-based approach for high-throughput protein phosphorylation
RT analysis and site localization.";
RL Nat. Biotechnol. 24:1285-1292(2006).
RN [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-588, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-588, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [18]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [19]
RP FUNCTION, INTERACTION WITH DES, CHARACTERIZATION OF VARIANTS GLY-184;
RP LEU-205; CYS-241 AND GLN-421, AND MUTAGENESIS OF HIS-181; TYR-206; SER-209;
RP LYS-255; LYS-269; ASP-278; CYS-375; ASP-380 AND SER-420.
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 [20]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-13 AND SER-18, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [21]
RP FUNCTION, INTERACTION WITH MTMR12, MUTAGENESIS OF CYS-375 AND
RP 421-ARG--PHE-603, AND VARIANTS CNMX PHE-49; CYS-69; GLY-184; LEU-205;
RP CYS-241 AND GLN-421.
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).
RN [22]
RP INTERACTION WITH SPEG.
RX PubMed=25087613; DOI=10.1016/j.ajhg.2014.07.004;
RA Agrawal P.B., Pierson C.R., Joshi M., Liu X., Ravenscroft G.,
RA Moghadaszadeh B., Talabere T., Viola M., Swanson L.C., Haliloglu G.,
RA Talim B., Yau K.S., Allcock R.J., Laing N.G., Perrella M.A., Beggs A.H.;
RT "SPEG interacts with myotubularin, and its deficiency causes centronuclear
RT myopathy with dilated cardiomyopathy.";
RL Am. J. Hum. Genet. 95:218-226(2014).
RN [23]
RP VARIANTS CNMX CYS-69; GLY-184; ASN-198; LEU-241; ARG-317; CYS-397; LYS-404;
RP PRO-406; GLN-421 AND ARG-499.
RX PubMed=9285787; DOI=10.1093/hmg/6.9.1499;
RA de Gouyon B.M., Zhao W., Laporte J., Mandel J.-L., Metzenberg A.,
RA Herman G.E.;
RT "Characterization of mutations in the myotubularin gene in twenty six
RT patients with X-linked myotubular myopathy.";
RL Hum. Mol. Genet. 6:1499-1504(1997).
RN [24]
RP VARIANTS CNMX CYS-69; PHE-70; PRO-87; SER-189; LEU-205; PRO-229; CYS-241;
RP ASN-376; ARG-378; CYS-397; ALA-402; GLN-421; ASN-431; ASN-433 AND PRO-469.
RX PubMed=9305655; DOI=10.1093/hmg/6.9.1505;
RA Laporte J., Guiraud-Chaumeil C., Vincent M.-C., Mandel J.-L., Tanner S.M.,
RA Liechti-Gallati S., Wallgren-Pettersson C., Dahl N., Kress W.,
RA Bolhuis P.A., Fardeau M., Samson F., Bertini E.;
RT "Mutations in the MTM1 gene implicated in X-linked myotubular myopathy.";
RL Hum. Mol. Genet. 6:1505-1511(1997).
RN [25]
RP VARIANT CNMX VAL-402.
RX PubMed=9829274; DOI=10.1016/s0960-8966(98)00075-3;
RA Nishino I., Minami N., Kobayashi O., Ikezawa M., Goto Y., Arahata K.,
RA Nonaka I.;
RT "MTM1 gene mutations in Japanese patients with the severe infantile form of
RT myotubular myopathy.";
RL Neuromuscul. Disord. 8:453-458(1998).
RN [26]
RP VARIANT CNMX GLU-378.
RX PubMed=10466421; DOI=10.1034/j.1399-0004.1999.560111.x;
RA Haene B.G., Rogers R.C., Schwartz C.E.;
RT "Germline mosaicism in X-linked myotubular myopathy.";
RL Clin. Genet. 56:77-81(1999).
RN [27]
RP VARIANTS CNMX SER-179; THR-225; CYS-241; SER-264; GLY-294 DEL; ARG-378 AND
RP ASN-510.
RX PubMed=10502779;
RX DOI=10.1002/(sici)1098-1004(199910)14:4<320::aid-humu7>3.0.co;2-o;
RA Buj-Bello A., Biancalana V., Moutou C., Laporte J., Mandel J.-L.;
RT "Identification of novel mutations in the MTM1 gene causing severe and mild
RT forms of X-linked myotubular myopathy.";
RL Hum. Mutat. 14:320-325(1999).
RN [28]
RP VARIANTS CNMX LEU-205; THR-225; CYS-230; ARG-232; CYS-241; ARG-402 AND
RP TYR-444.
RX PubMed=10063835; DOI=10.1016/s0960-8966(98)00090-x;
RA Tanner S.M., Schneider V., Thomas N.S.T., Clarke A., Lazarou L.,
RA Liechti-Gallati S.;
RT "Characterization of 34 novel and six known MTM1 gene mutations in 47
RT unrelated X-linked myotubular myopathy patients.";
RL Neuromuscul. Disord. 9:41-49(1999).
RN [29]
RP VARIANTS CNMX PHE-49; CYS-69; SER-179; ILE-186; LEU-205; MET-227; PRO-228;
RP CYS-241; GLY-279; ARG-378; PRO-391; CYS-397; ARG-402 AND GLN-421.
RX PubMed=11793470; DOI=10.1002/humu.10033;
RA Herman G.E., Kopacz K., Zhao W., Mills P.L., Metzenberg A., Das S.;
RT "Characterization of mutations in fifty North American patients with X-
RT linked myotubular myopathy.";
RL Hum. Mutat. 19:114-121(2002).
RN [30]
RP VARIANTS CNMX ILE-197; SER-199; ARG-378 AND ARG-402.
RX PubMed=12031625; DOI=10.1016/s0960-8966(01)00328-5;
RA Flex E., De Luca A., D'Apice M.R., Buccino A., Dallapiccola B., Novelli G.;
RT "Rapid scanning of myotubularin (MTM1) gene by denaturing high-performance
RT liquid chromatography (DHPLC).";
RL Neuromuscul. Disord. 12:501-505(2002).
RN [31]
RP VARIANT CNMX LYS-157.
RX PubMed=12859411; DOI=10.1034/j.1399-0004.2003.00118.x;
RA Yu S., Manson J., White S., Bourne A., Waddy H., Davis M., Haan E.;
RT "X-linked myotubular myopathy in a family with three adult survivors.";
RL Clin. Genet. 64:148-152(2003).
RN [32]
RP VARIANTS CNMX LYS-47 DEL; ASP-68; PRO-69; SER-69; PHE-70; LYS-180; LEU-184;
RP SER-202; LEU-205; THR-226; CYS-230; CYS-241; CYS-346; GLY-364; ASP-389;
RP CYS-397; GLN-421; PRO-469; PRO-470 AND TYR-481.
RX PubMed=12522554; DOI=10.1007/s00439-002-0869-1;
RA Biancalana V., Caron O., Gallati S., Baas F., Kress W., Novelli G.,
RA D'Apice M.R., Lagier-Tourenne C., Buj-Bello A., Romero N.B., Mandel J.-L.;
RT "Characterisation of mutations in 77 patients with X-linked myotubular
RT myopathy, including a family with a very mild phenotype.";
RL Hum. Genet. 112:135-142(2003).
RN [33]
RP VARIANT CNMX LYS-404.
RX PubMed=17005396; DOI=10.1016/j.nmd.2006.07.020;
RA Hoffjan S., Thiels C., Vorgerd M., Neuen-Jacob E., Epplen J.T., Kress W.;
RT "Extreme phenotypic variability in a German family with X-linked myotubular
RT myopathy associated with E404K mutation in MTM1.";
RL Neuromuscul. Disord. 16:749-753(2006).
RN [34]
RP VARIANT CNMX TYR-387.
RX PubMed=19129059; DOI=10.1016/s0929-6646(09)60022-x;
RA Chang C.Y., Lin S.P., Lin H.Y., Chuang C.K., Ho C.S., Su Y.N.;
RT "X-linked myotubular myopathy with a novel MTM1 mutation in a Taiwanese
RT child.";
RL J. Formos. Med. Assoc. 107:965-970(2008).
CC -!- FUNCTION: Lipid phosphatase which dephosphorylates phosphatidylinositol
CC 3-monophosphate (PI3P) and phosphatidylinositol 3,5-bisphosphate
CC (PI(3,5)P2) (PubMed:11001925, PubMed:10900271, PubMed:12646134,
CC PubMed:14722070). Has also been shown to dephosphorylate
CC phosphotyrosine- and phosphoserine-containing peptides
CC (PubMed:9537414). Negatively regulates EGFR degradation through
CC regulation of EGFR trafficking from the late endosome to the lysosome
CC (PubMed:14722070). Plays a role in vacuolar formation and morphology.
CC Regulates desmin intermediate filament assembly and architecture
CC (PubMed:21135508). Plays a role in mitochondrial morphology and
CC positioning (PubMed:21135508). Required for skeletal muscle maintenance
CC but not for myogenesis (PubMed:21135508). In skeletal muscles,
CC stabilizes MTMR12 protein levels (PubMed:23818870).
CC {ECO:0000269|PubMed:10900271, ECO:0000269|PubMed:11001925,
CC ECO:0000269|PubMed:12646134, ECO:0000269|PubMed:14722070,
CC ECO:0000269|PubMed:21135508, ECO:0000269|PubMed:23818870,
CC ECO:0000269|PubMed:9537414}.
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:0000269|PubMed:10900271, ECO:0000269|PubMed:11001925,
CC ECO:0000269|PubMed:12646134, ECO:0000269|PubMed:12847286,
CC ECO:0000269|PubMed:14722070};
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:0000269|PubMed:12646134, ECO:0000269|PubMed:14722070};
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:0000269|PubMed:12646134};
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:0000269|PubMed:12646134};
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:0000269|PubMed:12646134};
CC -!- ACTIVITY REGULATION: Allosterically activated by phosphatidylinositol
CC 5-phosphate (PI5P). {ECO:0000269|PubMed:12646134}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=39 uM for PI3P {ECO:0000269|PubMed:14722070};
CC KM=17 uM for PI(3,5)P2 {ECO:0000269|PubMed:14722070};
CC -!- SUBUNIT: Heterodimer with MTMR12 (PubMed:12847286, PubMed:23818870).
CC Interacts with KMT2A/MLL1 (via SET domain) (PubMed:9537414). Interacts
CC with DES in skeletal muscle but not in cardiac muscle
CC (PubMed:21135508). Interacts with SPEG (PubMed:25087613).
CC {ECO:0000269|PubMed:12847286, ECO:0000269|PubMed:21135508,
CC ECO:0000269|PubMed:23818870, ECO:0000269|PubMed:25087613,
CC ECO:0000269|PubMed:9537414}.
CC -!- INTERACTION:
CC Q13496; O00499: BIN1; NbExp=6; IntAct=EBI-2864109, EBI-719094;
CC Q13496; P17661: DES; NbExp=13; IntAct=EBI-2864109, EBI-1055572;
CC Q13496; Q96A65: EXOC4; NbExp=2; IntAct=EBI-2864109, EBI-355383;
CC Q13496; Q9C0I1: MTMR12; NbExp=4; IntAct=EBI-2864109, EBI-2829520;
CC Q13496; P31001: Des; Xeno; NbExp=4; IntAct=EBI-2864109, EBI-298565;
CC Q13496; O70172: Pip4k2a; Xeno; NbExp=2; IntAct=EBI-2864109, EBI-644828;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:10900271,
CC ECO:0000269|PubMed:11001925, ECO:0000269|PubMed:12847286}. Cell
CC membrane; Peripheral membrane protein {ECO:0000269|PubMed:11001925,
CC ECO:0000269|PubMed:12847286}. Cell projection, filopodium
CC {ECO:0000269|PubMed:12118066}. Cell projection, ruffle
CC {ECO:0000269|PubMed:12118066}. Late endosome
CC {ECO:0000269|PubMed:14722070}. Cytoplasm, myofibril, sarcomere
CC {ECO:0000250|UniProtKB:Q9Z2C5}. Note=Localizes as a dense cytoplasmic
CC network (PubMed:11001925). Also localizes to the plasma membrane,
CC including plasma membrane extensions such as filopodia and ruffles
CC (PubMed:12118066). Predominantly located in the cytoplasm following
CC interaction with MTMR12 (PubMed:12847286). Recruited to the late
CC endosome following EGF stimulation (PubMed:14722070). In skeletal
CC muscles, co-localizes with MTMR12 in the sarcomere (By similarity).
CC {ECO:0000250|UniProtKB:Q9Z2C5, ECO:0000269|PubMed:11001925,
CC ECO:0000269|PubMed:12118066, ECO:0000269|PubMed:12847286,
CC ECO:0000269|PubMed:14722070}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q13496-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q13496-2; Sequence=VSP_056208;
CC -!- DOMAIN: The GRAM domain mediates binding to PI(3,5)P2 and, with lower
CC affinity, to other phosphoinositides.
CC -!- DISEASE: Myopathy, centronuclear, X-linked (CNMX) [MIM:310400]: A
CC congenital muscle disorder characterized by progressive muscular
CC weakness and wasting involving mainly limb girdle, trunk, and neck
CC muscles. It may also affect distal muscles. Weakness may be present
CC during childhood or adolescence or may not become evident until the
CC third decade of life. Ptosis is a frequent clinical feature. The most
CC prominent histopathologic features include high frequency of centrally
CC located nuclei in muscle fibers not secondary to regeneration, radial
CC arrangement of sarcoplasmic strands around the central nuclei, and
CC predominance and hypotrophy of type 1 fibers.
CC {ECO:0000269|PubMed:10063835, ECO:0000269|PubMed:10466421,
CC ECO:0000269|PubMed:10502779, ECO:0000269|PubMed:10790201,
CC ECO:0000269|PubMed:11793470, ECO:0000269|PubMed:12031625,
CC ECO:0000269|PubMed:12522554, ECO:0000269|PubMed:12859411,
CC ECO:0000269|PubMed:17005396, ECO:0000269|PubMed:19129059,
CC ECO:0000269|PubMed:23818870, ECO:0000269|PubMed:9285787,
CC ECO:0000269|PubMed:9305655, ECO:0000269|PubMed:9829274}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- SIMILARITY: Belongs to the protein-tyrosine phosphatase family. Non-
CC receptor class myotubularin subfamily. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Leiden Muscular Dystrophy pages, Myotubularin 1
CC (MTM1); Note=Leiden Open Variation Database (LOVD);
CC URL="https://databases.lovd.nl/shared/genes/MTM1";
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DR EMBL; U46024; AAC51682.1; -; mRNA.
DR EMBL; AF020676; AAC12865.1; -; Genomic_DNA.
DR EMBL; AF020664; AAC12865.1; JOINED; Genomic_DNA.
DR EMBL; AF020665; AAC12865.1; JOINED; Genomic_DNA.
DR EMBL; AF020666; AAC12865.1; JOINED; Genomic_DNA.
DR EMBL; AF020667; AAC12865.1; JOINED; Genomic_DNA.
DR EMBL; AF020668; AAC12865.1; JOINED; Genomic_DNA.
DR EMBL; AF020669; AAC12865.1; JOINED; Genomic_DNA.
DR EMBL; AF020670; AAC12865.1; JOINED; Genomic_DNA.
DR EMBL; AF020671; AAC12865.1; JOINED; Genomic_DNA.
DR EMBL; AF020672; AAC12865.1; JOINED; Genomic_DNA.
DR EMBL; AF020673; AAC12865.1; JOINED; Genomic_DNA.
DR EMBL; AF020674; AAC12865.1; JOINED; Genomic_DNA.
DR EMBL; AF020675; AAC12865.1; JOINED; Genomic_DNA.
DR EMBL; AK297021; BAH12477.1; -; mRNA.
DR EMBL; AC109994; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AF002223; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471169; EAW99377.1; -; Genomic_DNA.
DR EMBL; BC030779; AAH30779.1; -; mRNA.
DR CCDS; CCDS14694.1; -. [Q13496-1]
DR RefSeq; NP_000243.1; NM_000252.2. [Q13496-1]
DR RefSeq; XP_005274744.1; XM_005274687.2. [Q13496-1]
DR RefSeq; XP_011529475.1; XM_011531173.2.
DR RefSeq; XP_016885039.1; XM_017029550.1.
DR AlphaFoldDB; Q13496; -.
DR SMR; Q13496; -.
DR BioGRID; 110630; 64.
DR DIP; DIP-61934N; -.
DR IntAct; Q13496; 18.
DR MINT; Q13496; -.
DR STRING; 9606.ENSP00000359423; -.
DR SwissLipids; SLP:000000846; -.
DR SwissLipids; SLP:000000847; -.
DR DEPOD; MTM1; -.
DR iPTMnet; Q13496; -.
DR PhosphoSitePlus; Q13496; -.
DR BioMuta; MTM1; -.
DR DMDM; 2851537; -.
DR EPD; Q13496; -.
DR jPOST; Q13496; -.
DR MassIVE; Q13496; -.
DR MaxQB; Q13496; -.
DR PaxDb; Q13496; -.
DR PeptideAtlas; Q13496; -.
DR PRIDE; Q13496; -.
DR ProteomicsDB; 59495; -. [Q13496-1]
DR ProteomicsDB; 6581; -.
DR Antibodypedia; 544; 319 antibodies from 36 providers.
DR DNASU; 4534; -.
DR Ensembl; ENST00000370396.7; ENSP00000359423.3; ENSG00000171100.16. [Q13496-1]
DR Ensembl; ENST00000685944.1; ENSP00000509266.1; ENSG00000171100.16. [Q13496-1]
DR Ensembl; ENST00000689694.1; ENSP00000508718.1; ENSG00000171100.16. [Q13496-1]
DR GeneID; 4534; -.
DR KEGG; hsa:4534; -.
DR MANE-Select; ENST00000370396.7; ENSP00000359423.3; NM_000252.3; NP_000243.1.
DR UCSC; uc004fef.5; human. [Q13496-1]
DR CTD; 4534; -.
DR DisGeNET; 4534; -.
DR GeneCards; MTM1; -.
DR GeneReviews; MTM1; -.
DR HGNC; HGNC:7448; MTM1.
DR HPA; ENSG00000171100; Low tissue specificity.
DR MalaCards; MTM1; -.
DR MIM; 300415; gene.
DR MIM; 310400; phenotype.
DR neXtProt; NX_Q13496; -.
DR OpenTargets; ENSG00000171100; -.
DR Orphanet; 596; X-linked centronuclear myopathy.
DR Orphanet; 456328; X-linked myotubular myopathy-abnormal genitalia syndrome.
DR PharmGKB; PA31251; -.
DR VEuPathDB; HostDB:ENSG00000171100; -.
DR eggNOG; KOG4471; Eukaryota.
DR GeneTree; ENSGT00940000157029; -.
DR HOGENOM; CLU_001839_4_1_1; -.
DR InParanoid; Q13496; -.
DR OMA; DDAYHNT; -.
DR OrthoDB; 824298at2759; -.
DR PhylomeDB; Q13496; -.
DR TreeFam; TF315197; -.
DR BRENDA; 3.1.3.64; 2681.
DR BRENDA; 3.1.3.95; 2681.
DR PathwayCommons; Q13496; -.
DR Reactome; R-HSA-1660499; Synthesis of PIPs at the plasma membrane.
DR Reactome; R-HSA-1660516; Synthesis of PIPs at the early endosome membrane.
DR Reactome; R-HSA-1660517; Synthesis of PIPs at the late endosome membrane.
DR SABIO-RK; Q13496; -.
DR SignaLink; Q13496; -.
DR BioGRID-ORCS; 4534; 13 hits in 707 CRISPR screens.
DR ChiTaRS; MTM1; human.
DR GeneWiki; Myotubularin_1; -.
DR GenomeRNAi; 4534; -.
DR Pharos; Q13496; Tbio.
DR PRO; PR:Q13496; -.
DR Proteomes; UP000005640; Chromosome X.
DR RNAct; Q13496; protein.
DR Bgee; ENSG00000171100; Expressed in secondary oocyte and 188 other tissues.
DR ExpressionAtlas; Q13496; baseline and differential.
DR Genevisible; Q13496; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0030175; C:filopodium; IDA:UniProtKB.
DR GO; GO:0031674; C:I band; IEA:Ensembl.
DR GO; GO:0005770; C:late endosome; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0001726; C:ruffle; IDA:UniProtKB.
DR GO; GO:0019215; F:intermediate filament binding; IDA:UniProtKB.
DR GO; GO:0035091; F:phosphatidylinositol binding; IDA:UniProtKB.
DR GO; GO:0052629; F:phosphatidylinositol-3,5-bisphosphate 3-phosphatase activity; IDA:UniProtKB.
DR GO; GO:0004438; F:phosphatidylinositol-3-phosphatase activity; IDA:UniProtKB.
DR GO; GO:0004721; F:phosphoprotein phosphatase activity; IDA:UniProtKB.
DR GO; GO:0000045; P:autophagosome assembly; IEA:Ensembl.
DR GO; GO:0008333; P:endosome to lysosome transport; IDA:UniProtKB.
DR GO; GO:0045109; P:intermediate filament organization; IMP:UniProtKB.
DR GO; GO:0048311; P:mitochondrion distribution; IMP:UniProtKB.
DR GO; GO:0070584; P:mitochondrion morphogenesis; IDA: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:0006661; P:phosphatidylinositol biosynthetic process; TAS:Reactome.
DR GO; GO:0046856; P:phosphatidylinositol dephosphorylation; IDA: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; IDA: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; IDA: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 1: Evidence at protein level;
KW Alternative splicing; Cell membrane; Cell projection; Cytoplasm;
KW Disease variant; Endosome; Hydrolase; Lipid metabolism; Membrane;
KW Phosphoprotein; Protein phosphatase; Protein transport; Reference proteome;
KW Transport.
FT CHAIN 1..603
FT /note="Myotubularin"
FT /id="PRO_0000094930"
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:0007744|PubMed:23186163"
FT MOD_RES 18
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 495
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:16964243"
FT MOD_RES 588
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:20068231"
FT VAR_SEQ 78..114
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_056208"
FT VARIANT 47
FT /note="Missing (in CNMX; dbSNP:rs587783788)"
FT /evidence="ECO:0000269|PubMed:12522554"
FT /id="VAR_006386"
FT VARIANT 49
FT /note="V -> F (in CNMX; greatly reduced binding to
FT PI(3,5)P2; abolishes interaction with MTMR12; does not
FT translocate to the late endosome following EGF stimulation;
FT shows normal EGFR degradation; dbSNP:rs587783796)"
FT /evidence="ECO:0000269|PubMed:11793470,
FT ECO:0000269|PubMed:14722070, ECO:0000269|PubMed:23818870"
FT /id="VAR_018227"
FT VARIANT 68
FT /note="Y -> D (in CNMX)"
FT /evidence="ECO:0000269|PubMed:12522554"
FT /id="VAR_018228"
FT VARIANT 69
FT /note="R -> C (in CNMX; mild; reduced response to PI5P and
FT reduced binding to PI(3,5)P2; abolishes interaction with
FT MTMR12; dbSNP:rs132630304)"
FT /evidence="ECO:0000269|PubMed:11793470,
FT ECO:0000269|PubMed:12646134, ECO:0000269|PubMed:14722070,
FT ECO:0000269|PubMed:23818870, ECO:0000269|PubMed:9285787,
FT ECO:0000269|PubMed:9305655"
FT /id="VAR_006387"
FT VARIANT 69
FT /note="R -> P (in CNMX)"
FT /evidence="ECO:0000269|PubMed:12522554"
FT /id="VAR_018229"
FT VARIANT 69
FT /note="R -> S (in CNMX; severe)"
FT /evidence="ECO:0000269|PubMed:12522554"
FT /id="VAR_018230"
FT VARIANT 70
FT /note="L -> F (in CNMX; mild; reduced binding to PI(3,5)P2;
FT dbSNP:rs587783809)"
FT /evidence="ECO:0000269|PubMed:12522554,
FT ECO:0000269|PubMed:14722070, ECO:0000269|PubMed:9305655"
FT /id="VAR_006388"
FT VARIANT 87
FT /note="L -> P (in CNMX; mild; reduced binding to PI(3,5)P2;
FT dbSNP:rs587783816)"
FT /evidence="ECO:0000269|PubMed:14722070,
FT ECO:0000269|PubMed:9305655"
FT /id="VAR_006389"
FT VARIANT 157
FT /note="E -> K (in CNMX; dbSNP:rs132630307)"
FT /evidence="ECO:0000269|PubMed:12859411"
FT /id="VAR_018231"
FT VARIANT 179
FT /note="P -> S (in CNMX; mild; dbSNP:rs587783832)"
FT /evidence="ECO:0000269|PubMed:10502779,
FT ECO:0000269|PubMed:11793470"
FT /id="VAR_009217"
FT VARIANT 180
FT /note="N -> K (in CNMX; very mild)"
FT /evidence="ECO:0000269|PubMed:12522554"
FT /id="VAR_018232"
FT VARIANT 184
FT /note="R -> G (in CNMX; severe; loss of activity; abolishes
FT interaction with DES and MTMR12; dbSNP:rs587783835)"
FT /evidence="ECO:0000269|PubMed:12646134,
FT ECO:0000269|PubMed:21135508, ECO:0000269|PubMed:23818870,
FT ECO:0000269|PubMed:9285787"
FT /id="VAR_006390"
FT VARIANT 184
FT /note="R -> L (in CNMX)"
FT /evidence="ECO:0000269|PubMed:12522554"
FT /id="VAR_018233"
FT VARIANT 186
FT /note="T -> I (in CNMX; dbSNP:rs587783836)"
FT /evidence="ECO:0000269|PubMed:11793470"
FT /id="VAR_018234"
FT VARIANT 189
FT /note="N -> S (in CNMX; dbSNP:rs132630302)"
FT /evidence="ECO:0000269|PubMed:9305655"
FT /id="VAR_006391"
FT VARIANT 197
FT /note="T -> I (in CNMX)"
FT /evidence="ECO:0000269|PubMed:12031625"
FT /id="VAR_018235"
FT VARIANT 198
FT /note="Y -> N (in CNMX; severe)"
FT /evidence="ECO:0000269|PubMed:9285787"
FT /id="VAR_006392"
FT VARIANT 199
FT /note="P -> S (in CNMX)"
FT /evidence="ECO:0000269|PubMed:12031625"
FT /id="VAR_018236"
FT VARIANT 202
FT /note="L -> S (in CNMX; severe)"
FT /evidence="ECO:0000269|PubMed:12522554"
FT /id="VAR_018237"
FT VARIANT 205
FT /note="P -> L (in CNMX; severe; dramatic decrease in
FT phosphatase activity; abolishes interaction with DES and
FT MTMR12; dbSNP:rs587783841)"
FT /evidence="ECO:0000269|PubMed:10063835,
FT ECO:0000269|PubMed:10900271, ECO:0000269|PubMed:11793470,
FT ECO:0000269|PubMed:12522554, ECO:0000269|PubMed:21135508,
FT ECO:0000269|PubMed:23818870, ECO:0000269|PubMed:9305655"
FT /id="VAR_006393"
FT VARIANT 225
FT /note="I -> T (in CNMX; mild)"
FT /evidence="ECO:0000269|PubMed:10063835,
FT ECO:0000269|PubMed:10502779"
FT /id="VAR_009218"
FT VARIANT 226
FT /note="P -> T (in CNMX; dbSNP:rs587783848)"
FT /evidence="ECO:0000269|PubMed:12522554"
FT /id="VAR_018238"
FT VARIANT 227
FT /note="V -> M (in CNMX; dbSNP:rs587783850)"
FT /evidence="ECO:0000269|PubMed:11793470"
FT /id="VAR_018239"
FT VARIANT 228
FT /note="L -> P (in CNMX; dbSNP:rs587783851)"
FT /evidence="ECO:0000269|PubMed:11793470"
FT /id="VAR_018240"
FT VARIANT 229
FT /note="S -> P (in CNMX; mild)"
FT /evidence="ECO:0000269|PubMed:9305655"
FT /id="VAR_006394"
FT VARIANT 230
FT /note="W -> C (in CNMX)"
FT /evidence="ECO:0000269|PubMed:10063835,
FT ECO:0000269|PubMed:12522554"
FT /id="VAR_018241"
FT VARIANT 232
FT /note="H -> R (in CNMX)"
FT /evidence="ECO:0000269|PubMed:10063835"
FT /id="VAR_018242"
FT VARIANT 241
FT /note="R -> C (in CNMX; mild to moderate; abolishes
FT interaction with DES, but not with MTMR12; reduces MTMR12
FT protein levels in myotubes; dbSNP:rs132630305)"
FT /evidence="ECO:0000269|PubMed:10063835,
FT ECO:0000269|PubMed:10502779, ECO:0000269|PubMed:11793470,
FT ECO:0000269|PubMed:12522554, ECO:0000269|PubMed:21135508,
FT ECO:0000269|PubMed:23818870, ECO:0000269|PubMed:9305655"
FT /id="VAR_006395"
FT VARIANT 241
FT /note="R -> L (in CNMX; severe; loss of activity)"
FT /evidence="ECO:0000269|PubMed:10900271,
FT ECO:0000269|PubMed:12646134, ECO:0000269|PubMed:9285787"
FT /id="VAR_006396"
FT VARIANT 264
FT /note="I -> S (in CNMX; severe; dbSNP:rs587783856)"
FT /evidence="ECO:0000269|PubMed:10502779"
FT /id="VAR_009219"
FT VARIANT 279
FT /note="A -> G (in CNMX)"
FT /evidence="ECO:0000269|PubMed:11793470"
FT /id="VAR_018243"
FT VARIANT 294
FT /note="Missing (in CNMX; mild)"
FT /evidence="ECO:0000269|PubMed:10502779"
FT /id="VAR_009220"
FT VARIANT 317
FT /note="M -> R (in CNMX; mild)"
FT /evidence="ECO:0000269|PubMed:9285787"
FT /id="VAR_006397"
FT VARIANT 346
FT /note="W -> C (in CNMX; mild)"
FT /evidence="ECO:0000269|PubMed:12522554"
FT /id="VAR_018244"
FT VARIANT 346
FT /note="W -> S (in CNMX)"
FT /id="VAR_018245"
FT VARIANT 364
FT /note="V -> G (in CNMX)"
FT /evidence="ECO:0000269|PubMed:12522554"
FT /id="VAR_018246"
FT VARIANT 374
FT /note="H -> D (in CNMX; dbSNP:rs587783754)"
FT /id="VAR_018247"
FT VARIANT 376
FT /note="S -> N (in CNMX; dramatic decrease in phosphatase
FT activity)"
FT /evidence="ECO:0000269|PubMed:10900271,
FT ECO:0000269|PubMed:9305655"
FT /id="VAR_006398"
FT VARIANT 378
FT /note="G -> E (in CNMX)"
FT /evidence="ECO:0000269|PubMed:10466421"
FT /id="VAR_018248"
FT VARIANT 378
FT /note="G -> R (in CNMX; severe; dramatic decrease in
FT phosphatase activity; does not affect EGFR degradation;
FT dbSNP:rs587783755)"
FT /evidence="ECO:0000269|PubMed:10502779,
FT ECO:0000269|PubMed:10900271, ECO:0000269|PubMed:11793470,
FT ECO:0000269|PubMed:12031625, ECO:0000269|PubMed:9305655"
FT /id="VAR_006399"
FT VARIANT 387
FT /note="S -> Y (in CNMX; dbSNP:rs587783759)"
FT /evidence="ECO:0000269|PubMed:19129059"
FT /id="VAR_068846"
FT VARIANT 389
FT /note="A -> D (in CNMX; severe)"
FT /evidence="ECO:0000269|PubMed:12522554"
FT /id="VAR_018249"
FT VARIANT 391
FT /note="L -> P (in CNMX)"
FT /evidence="ECO:0000269|PubMed:11793470"
FT /id="VAR_018250"
FT VARIANT 397
FT /note="Y -> C (in CNMX; severe; dramatic decrease in
FT phosphatase activity; dbSNP:rs132630303)"
FT /evidence="ECO:0000269|PubMed:10900271,
FT ECO:0000269|PubMed:11793470, ECO:0000269|PubMed:12522554,
FT ECO:0000269|PubMed:9285787, ECO:0000269|PubMed:9305655"
FT /id="VAR_006400"
FT VARIANT 402
FT /note="G -> A (in CNMX; mild; dbSNP:rs587783762)"
FT /evidence="ECO:0000269|PubMed:9305655"
FT /id="VAR_006401"
FT VARIANT 402
FT /note="G -> R (in CNMX; dbSNP:rs1569565525)"
FT /evidence="ECO:0000269|PubMed:10063835,
FT ECO:0000269|PubMed:11793470, ECO:0000269|PubMed:12031625"
FT /id="VAR_018251"
FT VARIANT 402
FT /note="G -> V (in CNMX)"
FT /evidence="ECO:0000269|PubMed:9829274"
FT /id="VAR_018252"
FT VARIANT 404
FT /note="E -> K (in CNMX; mild; dbSNP:rs781933660)"
FT /evidence="ECO:0000269|PubMed:17005396,
FT ECO:0000269|PubMed:9285787"
FT /id="VAR_006402"
FT VARIANT 406
FT /note="L -> P (in CNMX; severe)"
FT /evidence="ECO:0000269|PubMed:9285787"
FT /id="VAR_006403"
FT VARIANT 411
FT /note="W -> C (in CNMX; dbSNP:rs587783764)"
FT /id="VAR_018253"
FT VARIANT 420
FT /note="S -> SFIQ (in CNMX; severe)"
FT /id="VAR_009221"
FT VARIANT 421
FT /note="R -> Q (in CNMX; severe; reduced activity and
FT response to PI5P; does not affect interaction with DES or
FT MTMR12; dbSNP:rs587783772)"
FT /evidence="ECO:0000269|PubMed:11793470,
FT ECO:0000269|PubMed:12522554, ECO:0000269|PubMed:12646134,
FT ECO:0000269|PubMed:21135508, ECO:0000269|PubMed:23818870,
FT ECO:0000269|PubMed:9285787, ECO:0000269|PubMed:9305655"
FT /id="VAR_006404"
FT VARIANT 421
FT /note="R -> RFIQ (in CNMX; severe)"
FT /id="VAR_006405"
FT VARIANT 431
FT /note="D -> N (in CNMX; dbSNP:rs886044782)"
FT /evidence="ECO:0000269|PubMed:9305655"
FT /id="VAR_006406"
FT VARIANT 433
FT /note="D -> N (in CNMX; dbSNP:rs886044783)"
FT /evidence="ECO:0000269|PubMed:9305655"
FT /id="VAR_006407"
FT VARIANT 444
FT /note="C -> Y (in CNMX)"
FT /evidence="ECO:0000269|PubMed:10063835"
FT /id="VAR_018254"
FT VARIANT 469
FT /note="H -> P (in CNMX; dbSNP:rs587783789)"
FT /evidence="ECO:0000269|PubMed:12522554,
FT ECO:0000269|PubMed:9305655"
FT /id="VAR_006408"
FT VARIANT 470
FT /note="L -> P (in CNMX; severe)"
FT /evidence="ECO:0000269|PubMed:12522554"
FT /id="VAR_018255"
FT VARIANT 481
FT /note="N -> Y (in CNMX; mild)"
FT /evidence="ECO:0000269|PubMed:12522554"
FT /id="VAR_018256"
FT VARIANT 499
FT /note="W -> R (in CNMX; mild; dbSNP:rs587783801)"
FT /evidence="ECO:0000269|PubMed:9285787"
FT /id="VAR_006409"
FT VARIANT 510
FT /note="K -> N (in CNMX; severe)"
FT /evidence="ECO:0000269|PubMed:10502779"
FT /id="VAR_009222"
FT MUTAGEN 114
FT /note="K->A: Reduced response to PI5P."
FT /evidence="ECO:0000269|PubMed:12646134"
FT MUTAGEN 181
FT /note="H->A: Disrupts interaction with DES. Does not affect
FT lipid phosphatase activity."
FT /evidence="ECO:0000269|PubMed:21135508"
FT MUTAGEN 206
FT /note="Y->A: Disrupts interaction with DES. Does not affect
FT lipid phosphatase activity."
FT /evidence="ECO:0000269|PubMed:21135508"
FT MUTAGEN 209
FT /note="S->A: Disrupts interaction with DES. Does not affect
FT lipid phosphatase activity."
FT /evidence="ECO:0000269|PubMed:21135508"
FT MUTAGEN 220
FT /note="R->A: Loss of activity."
FT /evidence="ECO:0000269|PubMed:12646134"
FT MUTAGEN 255
FT /note="K->A: Disrupts interaction with DES."
FT /evidence="ECO:0000269|PubMed:21135508"
FT MUTAGEN 257
FT /note="D->A: No effect on subcellular location."
FT /evidence="ECO:0000269|PubMed:12118066"
FT MUTAGEN 269
FT /note="K->A: Disrupts interaction with DES. Does not affect
FT lipid phosphatase activity."
FT /evidence="ECO:0000269|PubMed:21135508"
FT MUTAGEN 278
FT /note="D->A: Localizes to plasma membrane extensions. Does
FT not affect interaction with DES."
FT /evidence="ECO:0000269|PubMed:11001925,
FT ECO:0000269|PubMed:12118066, ECO:0000269|PubMed:21135508"
FT MUTAGEN 375
FT /note="C->A: No effect on subcellular location."
FT /evidence="ECO:0000269|PubMed:10900271,
FT ECO:0000269|PubMed:11001925, ECO:0000269|PubMed:12118066,
FT ECO:0000269|PubMed:12646134, ECO:0000269|PubMed:21135508"
FT MUTAGEN 375
FT /note="C->S: Lacks activity toward PI3P. Does not affect
FT interaction with DES or MTMR12."
FT /evidence="ECO:0000269|PubMed:10900271,
FT ECO:0000269|PubMed:11001925, ECO:0000269|PubMed:12118066,
FT ECO:0000269|PubMed:12646134, ECO:0000269|PubMed:21135508,
FT ECO:0000269|PubMed:23818870"
FT MUTAGEN 377
FT /note="D->A: No effect on subcellular location."
FT /evidence="ECO:0000269|PubMed:11001925,
FT ECO:0000269|PubMed:12118066"
FT MUTAGEN 380
FT /note="D->A: Does not affect interaction with DES."
FT /evidence="ECO:0000269|PubMed:11001925,
FT ECO:0000269|PubMed:12118066, ECO:0000269|PubMed:21135508"
FT MUTAGEN 394
FT /note="D->A: Produces an unstable protein."
FT /evidence="ECO:0000269|PubMed:11001925"
FT MUTAGEN 410
FT /note="E->A: Produces an unstable protein."
FT /evidence="ECO:0000269|PubMed:11001925"
FT MUTAGEN 420
FT /note="S->D: Does not affect interaction with DES."
FT /evidence="ECO:0000269|PubMed:21135508"
FT MUTAGEN 443
FT /note="D->A: Produces an unstable protein."
FT /evidence="ECO:0000269|PubMed:11001925"
FT MUTAGEN 474..603
FT /note="Missing: Reduces MTMR12 protein levels in myotubes."
FT /evidence="ECO:0000269|PubMed:23818870"
FT CONFLICT 410
FT /note="E -> K (in Ref. 6; AAH30779)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 603 AA; 69932 MW; BE9770F2471957C0 CRC64;
MASASTSKYN SHSLENESIK RTSRDGVNRD LTEAVPRLPG ETLITDKEVI YICPFNGPIK
GRVYITNYRL YLRSLETDSS LILDVPLGVI SRIEKMGGAT SRGENSYGLD ITCKDMRNLR
FALKQEGHSR RDMFEILTRY AFPLAHSLPL FAFLNEEKFN VDGWTVYNPV EEYRRQGLPN
HHWRITFINK CYELCDTYPA LLVVPYRASD 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
