ID MTMR2_HUMAN Reviewed; 643 AA. AC Q13614; A6NN98; Q9UPS9; DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot. DT 04-NOV-2008, sequence version 4. DT 11-NOV-2015, entry version 163. DE RecName: Full=Myotubularin-related protein 2; DE AltName: Full=Phosphatidylinositol-3,5-bisphosphate 3-phosphatase; DE EC=3.1.3.95 {ECO:0000269|PubMed:12668758}; DE AltName: Full=Phosphatidylinositol-3-phosphate phosphatase; DE EC=3.1.3.64 {ECO:0000269|PubMed:11733541, ECO:0000269|PubMed:12668758}; GN Name=MTMR2; Synonyms=KIAA1073; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT THR-3. RC TISSUE=Brain; RX PubMed=10470851; DOI=10.1093/dnares/6.3.197; RA Kikuno R., Nagase T., Ishikawa K., Hirosawa M., Miyajima N., RA Tanaka A., Kotani H., Nomura N., Ohara O.; RT "Prediction of the coding sequences of unidentified human genes. XIV. RT The complete sequences of 100 new cDNA clones from brain which code RT for large proteins in vitro."; RL DNA Res. 6:197-205(1999). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=Testis; 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., RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., RA 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., RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., RA Nakai K., Yada T., Nakamura Y., Ohara O., 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 [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16554811; DOI=10.1038/nature04632; RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K., RA Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., RA Bloom T., Bruford E., Chang J.L., Cuomo C.A., Eichler E., RA FitzGerald M.G., Jaffe D.B., LaButti K., Nicol R., Park H.-S., RA Seaman C., Sougnez C., Yang X., Zimmer A.R., Zody M.C., Birren B.W., RA Nusbaum C., Fujiyama A., Hattori M., Rogers J., Lander E.S., RA Sakaki Y.; RT "Human chromosome 11 DNA sequence and analysis including novel gene RT identification."; RL Nature 440:497-500(2006). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R., RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., RA Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT THR-3. RC TISSUE=Uterus; 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 RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [6] RP NUCLEOTIDE SEQUENCE [MRNA] OF 384-643 (ISOFORM 1). 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 RT gene family from yeast to human."; RL Hum. Mol. Genet. 7:1703-1712(1998). RN [7] RP NUCLEOTIDE SEQUENCE [MRNA] OF 384-514 (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 [8] RP INVOLVEMENT IN CMT4B1. RX PubMed=10802647; DOI=10.1038/75542; RA Bolino A., Muglia M., Conforti F.L., LeGuern E., Salih M.A.M., RA Georgiou D.-M., Christodoulou K., Hausmanowa-Petrusewicz I., RA Mandich P., Schenone A., Gambardella A., Bono F., Quattrone A., RA Devoto M., Monaco A.P.; RT "Charcot-Marie-Tooth type 4B is caused by mutations in the gene RT encoding myotubularin-related protein-2."; RL Nat. Genet. 25:17-19(2000). RN [9] RP FUNCTION, CATALYTIC ACTIVITY, AND SUBCELLULAR LOCATION. RX PubMed=11733541; DOI=10.1074/jbc.M111087200; RA Kim S.A., Taylor G.S., Torgersen K.M., Dixon J.E.; RT "Myotubularin and MTMR2, phosphatidylinositol 3-phosphatases mutated RT in myotubular myopathy and type 4B Charcot-Marie-Tooth disease."; RL J. Biol. Chem. 277:4526-4531(2002). RN [10] RP FUNCTION, CATALYTIC ACTIVITY, ENZYME REGULATION, IDENTIFICATION BY RP MASS SPECTROMETRY, SUBUNIT, SUBCELLULAR LOCATION, MUTAGENESIS OF RP LEU-607, AND INTERACTION WITH SBF1. RX PubMed=12668758; DOI=10.1073/pnas.0431052100; RA Kim S.-A., Vacratsis P.O., Firestein R., Cleary M.L., Dixon J.E.; RT "Regulation of myotubularin-related (MTMR)2 phosphatidylinositol RT phosphatase by MTMR5, a catalytically inactive phosphatase."; RL Proc. Natl. Acad. Sci. U.S.A. 100:4492-4497(2003). RN [11] RP INTERACTION WITH SBF2, SUBUNIT, AND SUBCELLULAR LOCATION. RX PubMed=15998640; DOI=10.1074/jbc.M505159200; RA Robinson F.L., Dixon J.E.; RT "The phosphoinositide-3-phosphatase MTMR2 associates with MTMR13, a RT membrane-associated pseudophosphatase also mutated in type 4B Charcot- RT Marie-Tooth disease."; RL J. Biol. Chem. 280:31699-31707(2005). RN [12] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-58, AND IDENTIFICATION RP BY 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 [13] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19413330; DOI=10.1021/ac9004309; RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., RA Mohammed S.; RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in RT a refined SCX-based approach."; RL Anal. Chem. 81:4493-4501(2009). RN [14] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-58, AND IDENTIFICATION RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Leukemic T-cell; RX PubMed=19690332; DOI=10.1126/scisignal.2000007; RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., RA Rodionov V., Han D.K.; RT "Quantitative phosphoproteomic analysis of T cell receptor signaling RT reveals system-wide modulation of protein-protein interactions."; RL Sci. Signal. 2:RA46-RA46(2009). RN [15] RP IDENTIFICATION BY 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., RA Mann M.; RT "Quantitative phosphoproteomics reveals widespread full RT phosphorylation site occupancy during mitosis."; RL Sci. Signal. 3:RA3-RA3(2010). RN [16] RP FUNCTION, SUBCELLULAR LOCATION, AND PHOSPHORYLATION AT SER-58. RX PubMed=21372139; DOI=10.1074/jbc.M110.209122; RA Franklin N.E., Taylor G.S., Vacratsis P.O.; RT "Endosomal targeting of the phosphoinositide 3-phosphatase MTMR2 is RT regulated by an N-terminal phosphorylation site."; RL J. Biol. Chem. 286:15841-15853(2011). RN [17] RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF MUTANT SER-417 IN COMPLEX RP WITH PHOSPHOINOSITIDE, IDENTIFICATION BY MASS SPECTROMETRY, AND RP MUTAGENESIS OF CYS-417; ASP-419 AND ASP-422. RX PubMed=14690594; DOI=10.1016/S1097-2765(03)00486-6; RA Begley M.J., Taylor G.S., Kim S.-A., Veine D.M., Dixon J.E., RA Stuckey J.A.; RT "Crystal structure of a phosphoinositide phosphatase, MTMR2: insights RT into myotubular myopathy and Charcot-Marie-Tooth syndrome."; RL Mol. Cell 12:1391-1402(2003). RN [18] RP X-RAY CRYSTALLOGRAPHY (1.82 ANGSTROMS) OF 71-586 OF MUTANT SER-417 IN RP COMPLEX WITH PHOSPHOINOSITIDES, COILED-COIL DOMAIN, IDENTIFICATION BY RP MASS SPECTROMETRY, AND MUTAGENESIS OF CYS-417. RX PubMed=16410353; DOI=10.1073/pnas.0510006103; RA Begley M.J., Taylor G.S., Brock M.A., Ghosh P., Woods V.L., RA Dixon J.E.; RT "Molecular basis for substrate recognition by MTMR2, a myotubularin RT family phosphoinositide phosphatase."; RL Proc. Natl. Acad. Sci. U.S.A. 103:927-932(2006). RN [19] RP VARIANT CMT4B1 TRP-283. RX PubMed=12398840; DOI=10.1016/S0960-8966(02)00046-9; RA Nelis E., Erdem S., Tan E., Loefgren A., Ceuterick C., De Jonghe P., RA Van Broeckhoven C., Timmerman V., Topaloglu H.; RT "A novel homozygous missense mutation in the myotubularin-related RT protein 2 gene associated with recessive Charcot-Marie-Tooth disease RT with irregularly folded myelin sheaths."; RL Neuromuscul. Disord. 12:869-873(2002). CC -!- FUNCTION: Phosphatase that acts on lipids with a phosphoinositol CC headgroup. Has phosphatase activity towards phosphatidylinositol CC 3-phosphate and phosphatidylinositol 3,5-bisphosphate. CC {ECO:0000269|PubMed:11733541, ECO:0000269|PubMed:12668758, CC ECO:0000269|PubMed:21372139}. CC -!- CATALYTIC ACTIVITY: 1-phosphatidyl-1D-myo-inositol 3-phosphate + CC H(2)O = 1-phosphatidyl-1D-myo-inositol + phosphate. CC {ECO:0000269|PubMed:11733541, ECO:0000269|PubMed:12668758}. CC -!- CATALYTIC ACTIVITY: 1-phosphatidyl-1D-myo-inositol 3,5- CC bisphosphate + H(2)O = 1-phosphatidyl-1D-myo-inositol 5-phosphate CC + phosphate. {ECO:0000269|PubMed:12668758}. CC -!- ENZYME REGULATION: Interaction with SBF1 increases phosphatase CC activity. {ECO:0000269|PubMed:12668758}. CC -!- SUBUNIT: Homooligomer and heterooligomer. Interacts with SBF1 and CC SBF2. {ECO:0000269|PubMed:12668758, ECO:0000269|PubMed:14690594, CC ECO:0000269|PubMed:15998640, ECO:0000269|PubMed:16410353}. CC -!- INTERACTION: CC P07196:NEFL; NbExp=2; IntAct=EBI-475631, EBI-475646; CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:11733541, CC ECO:0000269|PubMed:12668758}. Early endosome membrane CC {ECO:0000269|PubMed:21372139}; Peripheral membrane protein CC {ECO:0000269|PubMed:21372139}. Note=Partly associated with CC membranes. {ECO:0000269|PubMed:12668758, CC ECO:0000269|PubMed:21372139, ECO:0000305}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q13614-1; Sequence=Displayed; CC Name=2; CC IsoId=Q13614-2; Sequence=VSP_044933; CC Note=No experimental confirmation available.; CC -!- DOMAIN: The coiled-coil domain mediates interaction with SBF2. CC -!- PTM: Phosphorylation at Ser-58 decreases MTMR2 localization to CC endocytic vesicular structures. {ECO:0000269|PubMed:21372139}. CC -!- DISEASE: Charcot-Marie-Tooth disease 4B1 (CMT4B1) [MIM:601382]: A CC recessive demyelinating form of Charcot-Marie-Tooth disease, a CC disorder of the peripheral nervous system, characterized by CC progressive weakness and atrophy, initially of the peroneal CC muscles and later of the distal muscles of the arms. Charcot- CC Marie-Tooth disease is classified in two main groups on the basis CC of electrophysiologic properties and histopathology: primary CC peripheral demyelinating neuropathies (designated CMT1 when they CC are dominantly inherited) and primary peripheral axonal CC neuropathies (CMT2). Demyelinating neuropathies are characterized CC by severely reduced nerve conduction velocities (less than 38 CC m/sec), segmental demyelination and remyelination with onion bulb CC formations on nerve biopsy, slowly progressive distal muscle CC atrophy and weakness, absent deep tendon reflexes, and hollow CC feet. By convention autosomal recessive forms of demyelinating CC Charcot-Marie-Tooth disease are designated CMT4. CC {ECO:0000269|PubMed:10802647, ECO:0000269|PubMed:12398840}. CC Note=The disease is caused by mutations affecting the gene CC represented in this entry. CC -!- SIMILARITY: Belongs to the protein-tyrosine phosphatase family. CC Non-receptor class myotubularin subfamily. {ECO:0000305}. CC -!- SIMILARITY: Contains 1 GRAM domain. {ECO:0000305}. CC -!- SIMILARITY: Contains 1 myotubularin phosphatase domain. CC {ECO:0000255|PROSITE-ProRule:PRU00669}. CC -!- SEQUENCE CAUTION: CC Sequence=BAA83025.2; Type=Erroneous initiation; Evidence={ECO:0000305}; CC -!- WEB RESOURCE: Name=Inherited peripheral neuropathies mutation db; CC URL="http://www.molgen.ua.ac.be/CMTMutations/"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AB028996; BAA83025.2; ALT_INIT; mRNA. DR EMBL; AK302940; BAG64098.1; -; mRNA. DR EMBL; AP000870; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AP001877; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471065; EAW66971.1; -; Genomic_DNA. DR EMBL; BC052990; AAH52990.1; -; mRNA. DR EMBL; U58033; AAC79118.1; -; mRNA. DR CCDS; CCDS8305.1; -. [Q13614-1] DR CCDS; CCDS8306.1; -. [Q13614-2] DR PIR; T09497; T09497. DR RefSeq; NP_001230500.1; NM_001243571.1. [Q13614-2] DR RefSeq; NP_057240.3; NM_016156.5. [Q13614-1] DR RefSeq; NP_958435.1; NM_201278.2. [Q13614-2] DR RefSeq; NP_958438.1; NM_201281.2. [Q13614-2] DR RefSeq; XP_005274431.1; XM_005274374.1. [Q13614-2] DR RefSeq; XP_005274432.1; XM_005274375.1. [Q13614-2] DR RefSeq; XP_006718997.1; XM_006718934.1. [Q13614-2] DR RefSeq; XP_006718998.1; XM_006718935.1. [Q13614-2] DR RefSeq; XP_006718999.1; XM_006718936.2. [Q13614-2] DR UniGene; Hs.181326; -. DR PDB; 1LW3; X-ray; 2.30 A; A=1-643. DR PDB; 1M7R; X-ray; 2.60 A; A/B=1-643. DR PDB; 1ZSQ; X-ray; 1.82 A; A=73-586. DR PDB; 1ZVR; X-ray; 1.98 A; A=73-586. DR PDBsum; 1LW3; -. DR PDBsum; 1M7R; -. DR PDBsum; 1ZSQ; -. DR PDBsum; 1ZVR; -. DR ProteinModelPortal; Q13614; -. DR SMR; Q13614; 73-585. DR BioGrid; 114415; 13. DR IntAct; Q13614; 5. DR MINT; MINT-6774021; -. DR STRING; 9606.ENSP00000345752; -. DR DEPOD; Q13614; -. DR PhosphoSite; Q13614; -. DR BioMuta; MTMR2; -. DR DMDM; 212276520; -. DR MaxQB; Q13614; -. DR PaxDb; Q13614; -. DR PRIDE; Q13614; -. DR Ensembl; ENST00000346299; ENSP00000345752; ENSG00000087053. [Q13614-1] DR Ensembl; ENST00000352297; ENSP00000343737; ENSG00000087053. [Q13614-2] DR Ensembl; ENST00000393223; ENSP00000376915; ENSG00000087053. [Q13614-2] DR Ensembl; ENST00000409459; ENSP00000386882; ENSG00000087053. [Q13614-2] DR GeneID; 8898; -. DR KEGG; hsa:8898; -. DR UCSC; uc001pfs.3; human. [Q13614-1] DR CTD; 8898; -. DR GeneCards; MTMR2; -. DR GeneReviews; MTMR2; -. DR HGNC; HGNC:7450; MTMR2. DR HPA; HPA049831; -. DR MIM; 601382; phenotype. DR MIM; 603557; gene. DR neXtProt; NX_Q13614; -. DR Orphanet; 99955; Charcot-Marie-Tooth disease type 4B1. DR PharmGKB; PA31253; -. DR eggNOG; KOG1089; Eukaryota. DR eggNOG; ENOG410XPTU; LUCA. DR GeneTree; ENSGT00760000118832; -. DR HOGENOM; HOG000210598; -. DR HOVERGEN; HBG000220; -. DR InParanoid; Q13614; -. DR KO; K18081; -. DR OMA; GVPNDMW; -. DR OrthoDB; EOG7XDBF9; -. DR PhylomeDB; Q13614; -. DR TreeFam; TF315197; -. DR BRENDA; 3.1.3.64; 2681. DR BRENDA; 3.1.3.95; 2681. 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 ChiTaRS; MTMR2; human. DR EvolutionaryTrace; Q13614; -. DR GeneWiki; MTMR2; -. DR GenomeRNAi; 8898; -. DR NextBio; 33423; -. DR PRO; PR:Q13614; -. DR Proteomes; UP000005640; Chromosome 11. DR Bgee; Q13614; -. DR CleanEx; HS_MTMR2; -. DR ExpressionAtlas; Q13614; baseline and differential. DR Genevisible; Q13614; HS. DR GO; GO:0030424; C:axon; ISS:BHF-UCL. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0005829; C:cytosol; IDA:UniProtKB. DR GO; GO:0030425; C:dendrite; ISS:BHF-UCL. DR GO; GO:0043197; C:dendritic spine; ISS:BHF-UCL. DR GO; GO:0031901; C:early endosome membrane; IEA:UniProtKB-SubCell. DR GO; GO:0070062; C:extracellular exosome; IDA:UniProtKB. DR GO; GO:0097481; C:neuronal postsynaptic density; ISS:BHF-UCL. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0097060; C:synaptic membrane; ISS:BHF-UCL. DR GO; GO:0008021; C:synaptic vesicle; ISS:BHF-UCL. DR GO; GO:0005774; C:vacuolar membrane; IEA:Ensembl. 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:0004725; F:protein tyrosine phosphatase activity; IEA:InterPro. DR GO; GO:0008138; F:protein tyrosine/serine/threonine phosphatase activity; NAS:UniProtKB. DR GO; GO:0097062; P:dendritic spine maintenance; ISS:BHF-UCL. DR GO; GO:0046855; P:inositol phosphate dephosphorylation; IEA:Ensembl. DR GO; GO:0032288; P:myelin assembly; IEA:Ensembl. DR GO; GO:0045806; P:negative regulation of endocytosis; ISS:BHF-UCL. DR GO; GO:0090394; P:negative regulation of excitatory postsynaptic potential; ISS:BHF-UCL. DR GO; GO:0031642; P:negative regulation of myelination; IEA:Ensembl. DR GO; GO:2000645; P:negative regulation of receptor catabolic process; ISS:BHF-UCL. DR GO; GO:0002091; P:negative regulation of receptor internalization; ISS:BHF-UCL. DR GO; GO:0048666; P:neuron development; IEA:Ensembl. DR GO; GO:0006661; P:phosphatidylinositol biosynthetic process; TAS:Reactome. DR GO; GO:0046856; P:phosphatidylinositol dephosphorylation; IDA:UniProtKB. DR GO; GO:0006644; P:phospholipid metabolic process; TAS:Reactome. DR GO; GO:2000643; P:positive regulation of early endosome to late endosome transport; ISS:BHF-UCL. DR GO; GO:0006470; P:protein dephosphorylation; NAS:UniProtKB. DR GO; GO:0051262; P:protein tetramerization; IEA:Ensembl. DR GO; GO:0044281; P:small molecule metabolic process; TAS:Reactome. DR Gene3D; 2.30.29.30; -; 1. DR InterPro; IPR004182; GRAM. DR InterPro; IPR010569; Myotubularin-like_Pase_dom. DR InterPro; IPR030564; Myotubularin_fam. DR InterPro; IPR011993; PH/PTB_dom. DR InterPro; IPR029021; Prot-tyrosine_phosphatase-like. DR InterPro; IPR016130; Tyr_Pase_AS. DR InterPro; IPR000387; TYR_PHOSPHATASE_dom. DR PANTHER; PTHR10807; PTHR10807; 1. DR Pfam; PF02893; GRAM; 1. DR Pfam; PF06602; Myotub-related; 1. DR SMART; SM00568; GRAM; 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 3D-structure; Alternative splicing; Charcot-Marie-Tooth disease; KW Coiled coil; Complete proteome; Cytoplasm; Disease mutation; Endosome; KW Hydrolase; Lipid metabolism; Membrane; Neurodegeneration; Neuropathy; KW Phosphoprotein; Polymorphism; Reference proteome. FT CHAIN 1 643 Myotubularin-related protein 2. FT /FTId=PRO_0000094934. FT DOMAIN 68 139 GRAM. FT DOMAIN 205 580 Myotubularin phosphatase. FT {ECO:0000255|PROSITE-ProRule:PRU00669}. FT REGION 330 333 Substrate binding. FT REGION 355 356 Substrate binding. FT REGION 417 423 Substrate binding. FT COILED 593 627 {ECO:0000269|PubMed:16410353}. FT COMPBIAS 4 53 Ser-rich. FT ACT_SITE 417 417 Phosphocysteine intermediate. FT BINDING 463 463 Substrate. FT MOD_RES 6 6 Phosphoserine. FT {ECO:0000250|UniProtKB:Q9Z2D1}. FT MOD_RES 9 9 Phosphoserine. FT {ECO:0000250|UniProtKB:Q9Z2D1}. FT MOD_RES 58 58 Phosphoserine. FT {ECO:0000244|PubMed:18669648, FT ECO:0000244|PubMed:19690332, FT ECO:0000269|PubMed:21372139}. FT VAR_SEQ 1 72 Missing (in isoform 2). FT {ECO:0000303|PubMed:14702039}. FT /FTId=VSP_044933. FT VARIANT 3 3 K -> T (in dbSNP:rs3824874). FT {ECO:0000269|PubMed:10470851, FT ECO:0000269|PubMed:15489334}. FT /FTId=VAR_047255. FT VARIANT 283 283 R -> W (in CMT4B1). FT {ECO:0000269|PubMed:12398840}. FT /FTId=VAR_047947. FT VARIANT 545 545 N -> S (in dbSNP:rs558018). FT /FTId=VAR_047256. FT MUTAGEN 417 417 C->S: Loss of activity. FT {ECO:0000269|PubMed:14690594, FT ECO:0000269|PubMed:16410353}. FT MUTAGEN 419 419 D->A: No effect. FT {ECO:0000269|PubMed:14690594}. FT MUTAGEN 422 422 D->A: Loss of activity. FT {ECO:0000269|PubMed:14690594}. FT MUTAGEN 607 607 L->Y: Reduces homodimerization and FT interaction with SBF1. FT {ECO:0000269|PubMed:12668758}. FT STRAND 84 95 {ECO:0000244|PDB:1ZSQ}. FT TURN 96 98 {ECO:0000244|PDB:1ZSQ}. FT STRAND 99 121 {ECO:0000244|PDB:1ZSQ}. FT STRAND 123 128 {ECO:0000244|PDB:1ZSQ}. FT HELIX 129 131 {ECO:0000244|PDB:1ZSQ}. FT STRAND 132 138 {ECO:0000244|PDB:1ZSQ}. FT STRAND 145 147 {ECO:0000244|PDB:1ZVR}. FT STRAND 149 155 {ECO:0000244|PDB:1ZSQ}. FT TURN 156 158 {ECO:0000244|PDB:1ZSQ}. FT STRAND 159 164 {ECO:0000244|PDB:1ZSQ}. FT HELIX 167 169 {ECO:0000244|PDB:1ZSQ}. FT HELIX 172 182 {ECO:0000244|PDB:1ZSQ}. FT TURN 185 189 {ECO:0000244|PDB:1ZSQ}. FT HELIX 193 195 {ECO:0000244|PDB:1ZSQ}. FT HELIX 205 207 {ECO:0000244|PDB:1ZSQ}. FT HELIX 211 217 {ECO:0000244|PDB:1ZSQ}. FT STRAND 223 228 {ECO:0000244|PDB:1ZSQ}. FT TURN 230 233 {ECO:0000244|PDB:1ZSQ}. FT STRAND 234 236 {ECO:0000244|PDB:1ZSQ}. FT STRAND 242 247 {ECO:0000244|PDB:1ZSQ}. FT HELIX 252 261 {ECO:0000244|PDB:1ZSQ}. FT HELIX 263 265 {ECO:0000244|PDB:1ZSQ}. FT STRAND 269 273 {ECO:0000244|PDB:1ZSQ}. FT TURN 275 277 {ECO:0000244|PDB:1ZSQ}. FT STRAND 280 284 {ECO:0000244|PDB:1ZSQ}. FT TURN 290 293 {ECO:0000244|PDB:1ZSQ}. FT HELIX 297 309 {ECO:0000244|PDB:1ZSQ}. FT STRAND 310 312 {ECO:0000244|PDB:1ZSQ}. FT STRAND 314 320 {ECO:0000244|PDB:1ZSQ}. FT HELIX 324 333 {ECO:0000244|PDB:1ZSQ}. FT TURN 340 342 {ECO:0000244|PDB:1ZSQ}. FT STRAND 346 350 {ECO:0000244|PDB:1ZSQ}. FT HELIX 356 370 {ECO:0000244|PDB:1ZSQ}. FT HELIX 376 378 {ECO:0000244|PDB:1ZSQ}. FT HELIX 379 386 {ECO:0000244|PDB:1ZSQ}. FT HELIX 388 407 {ECO:0000244|PDB:1ZSQ}. FT STRAND 413 416 {ECO:0000244|PDB:1ZSQ}. FT STRAND 418 422 {ECO:0000244|PDB:1ZSQ}. FT HELIX 423 435 {ECO:0000244|PDB:1ZSQ}. FT HELIX 437 440 {ECO:0000244|PDB:1ZSQ}. FT HELIX 442 452 {ECO:0000244|PDB:1ZSQ}. FT TURN 453 457 {ECO:0000244|PDB:1ZSQ}. FT HELIX 460 464 {ECO:0000244|PDB:1ZSQ}. FT TURN 465 467 {ECO:0000244|PDB:1ZSQ}. FT HELIX 479 493 {ECO:0000244|PDB:1ZSQ}. FT TURN 495 497 {ECO:0000244|PDB:1ZSQ}. FT HELIX 502 514 {ECO:0000244|PDB:1ZSQ}. FT STRAND 516 518 {ECO:0000244|PDB:1ZSQ}. FT STRAND 522 524 {ECO:0000244|PDB:1ZSQ}. FT HELIX 525 530 {ECO:0000244|PDB:1ZSQ}. FT HELIX 533 536 {ECO:0000244|PDB:1ZSQ}. FT HELIX 540 545 {ECO:0000244|PDB:1ZSQ}. FT HELIX 548 551 {ECO:0000244|PDB:1ZSQ}. FT TURN 554 557 {ECO:0000244|PDB:1ZSQ}. FT STRAND 560 562 {ECO:0000244|PDB:1ZSQ}. FT TURN 570 572 {ECO:0000244|PDB:1ZSQ}. FT HELIX 577 580 {ECO:0000244|PDB:1ZSQ}. SQ SEQUENCE 643 AA; 73381 MW; 10FD6508D0CDA719 CRC64; MEKSSSCESL GSQPAAARPP SVDSLSSAST SHSENSVHTK SASVVSSDSI STSADNFSPD LRVLRESNKL AEMEEPPLLP GENIKDMAKD VTYICPFTGA VRGTLTVTNY RLYFKSMERD PPFVLDASLG VINRVEKIGG ASSRGENSYG LETVCKDIRN LRFAHKPEGR TRRSIFENLM KYAFPVSNNL PLFAFEYKEV FPENGWKLYD PLLEYRRQGI PNESWRITKI NERYELCDTY PALLVVPANI PDEELKRVAS FRSRGRIPVL SWIHPESQAT ITRCSQPMVG VSGKRSKEDE KYLQAIMDSN AQSHKIFIFD ARPSVNAVAN KAKGGGYESE DAYQNAELVF LDIHNIHVMR ESLRKLKEIV YPNIEETHWL SNLESTHWLE HIKLILAGAL RIADKVESGK TSVVVHCSDG WDRTAQLTSL AMLMLDGYYR TIRGFEVLVE KEWLSFGHRF QLRVGHGDKN HADADRSPVF LQFIDCVWQM TRQFPTAFEF NEYFLITILD HLYSCLFGTF LCNSEQQRGK ENLPKRTVSL WSYINSQLED FTNPLYGSYS NHVLYPVASM RHLELWVGYY IRWNPRMKPQ EPIHNRYKEL LAKRAELQKK VEELQREISN RSTSSSERAS SPAQCVTPVQ TVV //