MTMR2_HUMAN
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 03-AUG-2022, entry version 212.
DE RecName: Full=Myotubularin-related protein 2 {ECO:0000305};
DE AltName: Full=Phosphatidylinositol-3,5-bisphosphate 3-phosphatase;
DE EC=3.1.3.95 {ECO:0000269|PubMed:12668758, ECO:0000269|PubMed:14690594, ECO:0000269|PubMed:21372139};
DE AltName: Full=Phosphatidylinositol-3-phosphate phosphatase;
DE EC=3.1.3.64 {ECO:0000269|PubMed:11733541, ECO:0000269|PubMed:12668758, ECO:0000269|PubMed:14690594, ECO:0000269|PubMed:21372139};
GN Name=MTMR2 {ECO:0000312|HGNC:HGNC:7450}; Synonyms=KIAA1073;
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 [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., Tanaka A.,
RA Kotani H., Nomura N., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XIV. The
RT complete sequences of 100 new cDNA clones from brain which code for large
RT 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., 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 [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., Bloom T.,
RA Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G.,
RA Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C.,
RA Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A.,
RA Hattori M., Rogers J., Lander E.S., 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., 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 [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 project:
RT 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 gene
RT 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., Mandich P.,
RA Schenone A., Gambardella A., Bono F., Quattrone A., Devoto M., Monaco A.P.;
RT "Charcot-Marie-Tooth type 4B is caused by mutations in the gene encoding
RT 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 in
RT myotubular myopathy and type 4B Charcot-Marie-Tooth disease.";
RL J. Biol. Chem. 277:4526-4531(2002).
RN [10]
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, SUBUNIT, INTERACTION
RP WITH SBF1, SUBCELLULAR LOCATION, DOMAIN, AND MUTAGENESIS OF
RP 589-PRO--VAL-643 AND LEU-607.
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 MTMR12.
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 [12]
RP INTERACTION WITH SBF2, SUBUNIT, SUBCELLULAR LOCATION, AND DOMAIN.
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 [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-58, 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 [14]
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., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-58, AND IDENTIFICATION BY
RP 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 [16]
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., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [17]
RP FUNCTION, CATALYTIC ACTIVITY, INTERACTION WITH SBF1, SUBUNIT, SUBCELLULAR
RP 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 [18]
RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF MUTANT SER-417 IN COMPLEX WITH
RP PHOSPHOINOSITIDE, FUNCTION, CATALYTIC ACTIVITY, IDENTIFICATION BY MASS
RP SPECTROMETRY, ACTIVE SITE, AND 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., Stuckey J.A.;
RT "Crystal structure of a phosphoinositide phosphatase, MTMR2: insights into
RT myotubular myopathy and Charcot-Marie-Tooth syndrome.";
RL Mol. Cell 12:1391-1402(2003).
RN [19]
RP X-RAY CRYSTALLOGRAPHY (1.82 ANGSTROMS) OF 71-586 OF MUTANT SER-417 IN
RP COMPLEX WITH PHOSPHOINOSITIDES, COILED-COIL DOMAIN, ACTIVE SITE,
RP IDENTIFICATION BY 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., Dixon J.E.;
RT "Molecular basis for substrate recognition by MTMR2, a myotubularin family
RT phosphoinositide phosphatase.";
RL Proc. Natl. Acad. Sci. U.S.A. 103:927-932(2006).
RN [20]
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 protein 2
RT gene associated with recessive Charcot-Marie-Tooth disease with irregularly
RT 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 3-
CC phosphate and phosphatidylinositol 3,5-bisphosphate (PubMed:11733541,
CC PubMed:12668758, PubMed:21372139, PubMed:14690594). Binds
CC phosphatidylinositol 4-phosphate, phosphatidylinositol 5-phosphate,
CC phosphatidylinositol 3,5-bisphosphate and phosphatidylinositol 3,4,5-
CC trisphosphate (By similarity). Stabilizes SBF2/MTMR13 at the membranes
CC (By similarity). Specifically in peripheral nerves, stabilizes
CC SBF2/MTMR13 protein (By similarity). {ECO:0000250|UniProtKB:Q9Z2D1,
CC ECO:0000269|PubMed:11733541, ECO:0000269|PubMed:12668758,
CC ECO:0000269|PubMed:14690594, ECO:0000269|PubMed:21372139}.
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:11733541, ECO:0000269|PubMed:12668758,
CC ECO:0000269|PubMed:14690594, ECO:0000269|PubMed:21372139};
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:12668758, ECO:0000269|PubMed:14690594,
CC ECO:0000269|PubMed:21372139};
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:11733541, ECO:0000269|PubMed:21372139};
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:21372139};
CC -!- ACTIVITY REGULATION: Interaction with SBF1/MTMR5 increases phosphatase
CC activity. {ECO:0000269|PubMed:12668758}.
CC -!- SUBUNIT: Homodimer (via coiled-coil domain) (PubMed:12668758,
CC PubMed:15998640). Heterotetramer consisting of one MTMR2 dimer and one
CC SBF2/MTMR13 dimer (PubMed:15998640). Heterodimer with SBF1/MTMR5
CC (PubMed:12668758, PubMed:21372139). Heterodimer with MTMR12
CC (PubMed:12847286). {ECO:0000269|PubMed:12668758,
CC ECO:0000269|PubMed:12847286, ECO:0000269|PubMed:15998640,
CC ECO:0000269|PubMed:21372139}.
CC -!- INTERACTION:
CC Q13614; Q9C0I1: MTMR12; NbExp=2; IntAct=EBI-475631, EBI-2829520;
CC Q13614; P07196: NEFL; NbExp=2; IntAct=EBI-475631, EBI-475646;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:11733541,
CC ECO:0000269|PubMed:12668758, ECO:0000269|PubMed:15998640}. Early
CC endosome membrane {ECO:0000269|PubMed:15998640,
CC ECO:0000269|PubMed:21372139}; Peripheral membrane protein
CC {ECO:0000269|PubMed:15998640, ECO:0000269|PubMed:21372139}. Cytoplasm,
CC perinuclear region {ECO:0000269|PubMed:12668758}. Cell projection, axon
CC {ECO:0000250|UniProtKB:Q9Z2D1}. Endosome membrane
CC {ECO:0000250|UniProtKB:Q9Z2D1}; Peripheral membrane protein
CC {ECO:0000305}. Note=Partly associated with membranes (PubMed:12668758,
CC PubMed:15998640, PubMed:21372139). Localizes to vacuoles in hypo-
CC osmotic conditions (By similarity). {ECO:0000250|UniProtKB:Q9Z2D1,
CC ECO:0000269|PubMed:12668758, ECO:0000269|PubMed:15998640,
CC ECO:0000269|PubMed:21372139}.
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 -!- DOMAIN: The coiled-coil domain mediates homodimerization
CC (PubMed:12668758, PubMed:15998640). Also mediates interaction with
CC SBF1/MTMR5 (PubMed:12668758). By mediating MTMR2 homodimerization,
CC indirectly involved in SBF2/MTMR13 and MTMR2 heterotetramerization (By
CC similarity). {ECO:0000250|UniProtKB:Q9Z2D1,
CC ECO:0000269|PubMed:12668758, ECO:0000269|PubMed:15998640}.
CC -!- DOMAIN: The GRAM domain mediates binding to phosphatidylinositol 4-
CC phosphate, phosphatidylinositol 5-phosphate, phosphatidylinositol 3,5-
CC bisphosphate and phosphatidylinositol 3,4,5-trisphosphate.
CC {ECO:0000250|UniProtKB:Q9Z2D1}.
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 disorder
CC of the peripheral nervous system, characterized by progressive weakness
CC and atrophy, initially of the peroneal muscles and later of the distal
CC muscles of the arms. Charcot-Marie-Tooth disease is classified in two
CC main groups on the basis of electrophysiologic properties and
CC histopathology: primary peripheral demyelinating neuropathies
CC (designated CMT1 when they are dominantly inherited) and primary
CC peripheral axonal neuropathies (CMT2). Demyelinating neuropathies are
CC characterized by severely reduced nerve conduction velocities (less
CC than 38 m/sec), segmental demyelination and remyelination with onion
CC bulb formations on nerve biopsy, slowly progressive distal muscle
CC atrophy and weakness, absent deep tendon reflexes, and hollow feet. By
CC convention autosomal recessive forms of demyelinating Charcot-Marie-
CC Tooth disease are designated CMT4. {ECO:0000269|PubMed:10802647,
CC ECO:0000269|PubMed:12398840}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the protein-tyrosine phosphatase family. Non-
CC receptor class myotubularin subfamily. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA83025.2; Type=Erroneous initiation; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=Inherited peripheral neuropathies mutation db;
CC URL="https://uantwerpen.vib.be/CMTMutations";
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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_005274374.2. [Q13614-2]
DR RefSeq; XP_005274432.1; XM_005274375.2. [Q13614-2]
DR RefSeq; XP_006718997.1; XM_006718934.2.
DR RefSeq; XP_006718998.1; XM_006718935.2.
DR RefSeq; XP_006718999.1; XM_006718936.3.
DR RefSeq; XP_016874006.1; XM_017018517.1.
DR RefSeq; XP_016874007.1; XM_017018518.1.
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 PDB; 5GNH; X-ray; 2.60 A; A/B=73-643.
DR PDBsum; 1LW3; -.
DR PDBsum; 1M7R; -.
DR PDBsum; 1ZSQ; -.
DR PDBsum; 1ZVR; -.
DR PDBsum; 5GNH; -.
DR AlphaFoldDB; Q13614; -.
DR SMR; Q13614; -.
DR BioGRID; 114415; 55.
DR IntAct; Q13614; 20.
DR MINT; Q13614; -.
DR STRING; 9606.ENSP00000345752; -.
DR SwissLipids; SLP:000001135; -.
DR DEPOD; MTMR2; -.
DR GlyGen; Q13614; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q13614; -.
DR MetOSite; Q13614; -.
DR PhosphoSitePlus; Q13614; -.
DR SwissPalm; Q13614; -.
DR BioMuta; MTMR2; -.
DR DMDM; 212276520; -.
DR EPD; Q13614; -.
DR jPOST; Q13614; -.
DR MassIVE; Q13614; -.
DR MaxQB; Q13614; -.
DR PaxDb; Q13614; -.
DR PeptideAtlas; Q13614; -.
DR PRIDE; Q13614; -.
DR ProteomicsDB; 1592; -.
DR ProteomicsDB; 59600; -. [Q13614-1]
DR Antibodypedia; 31676; 267 antibodies from 29 providers.
DR DNASU; 8898; -.
DR Ensembl; ENST00000346299.10; ENSP00000345752.6; ENSG00000087053.20. [Q13614-1]
DR Ensembl; ENST00000352297.11; ENSP00000343737.7; ENSG00000087053.20. [Q13614-2]
DR Ensembl; ENST00000393223.8; ENSP00000376915.3; ENSG00000087053.20. [Q13614-2]
DR Ensembl; ENST00000409459.5; ENSP00000386882.1; ENSG00000087053.20. [Q13614-2]
DR Ensembl; ENST00000444541.7; ENSP00000396020.2; ENSG00000087053.20. [Q13614-2]
DR Ensembl; ENST00000470293.6; ENSP00000502515.1; ENSG00000087053.20. [Q13614-2]
DR Ensembl; ENST00000481642.6; ENSP00000502505.1; ENSG00000087053.20. [Q13614-2]
DR Ensembl; ENST00000484818.6; ENSP00000501963.1; ENSG00000087053.20. [Q13614-2]
DR Ensembl; ENST00000495134.6; ENSP00000501894.1; ENSG00000087053.20. [Q13614-2]
DR Ensembl; ENST00000497683.6; ENSP00000501753.1; ENSG00000087053.20. [Q13614-2]
DR Ensembl; ENST00000674528.1; ENSP00000501567.1; ENSG00000087053.20. [Q13614-2]
DR Ensembl; ENST00000674610.1; ENSP00000501688.1; ENSG00000087053.20. [Q13614-2]
DR Ensembl; ENST00000674924.1; ENSP00000502433.1; ENSG00000087053.20. [Q13614-2]
DR Ensembl; ENST00000674968.1; ENSP00000502567.1; ENSG00000087053.20. [Q13614-2]
DR Ensembl; ENST00000674989.1; ENSP00000502829.1; ENSG00000087053.20. [Q13614-2]
DR Ensembl; ENST00000675174.1; ENSP00000502032.1; ENSG00000087053.20. [Q13614-2]
DR Ensembl; ENST00000675196.1; ENSP00000501867.1; ENSG00000087053.20. [Q13614-2]
DR Ensembl; ENST00000675362.1; ENSP00000501989.1; ENSG00000087053.20. [Q13614-2]
DR Ensembl; ENST00000675454.1; ENSP00000501781.1; ENSG00000087053.20. [Q13614-2]
DR Ensembl; ENST00000675477.1; ENSP00000501751.1; ENSG00000087053.20. [Q13614-2]
DR Ensembl; ENST00000675489.1; ENSP00000501702.1; ENSG00000087053.20. [Q13614-2]
DR Ensembl; ENST00000675636.1; ENSP00000501850.1; ENSG00000087053.20. [Q13614-2]
DR Ensembl; ENST00000675652.1; ENSP00000502694.1; ENSG00000087053.20. [Q13614-2]
DR Ensembl; ENST00000675933.1; ENSP00000502575.1; ENSG00000087053.20. [Q13614-2]
DR Ensembl; ENST00000675981.1; ENSP00000502204.1; ENSG00000087053.20. [Q13614-2]
DR Ensembl; ENST00000676166.1; ENSP00000501632.1; ENSG00000087053.20. [Q13614-2]
DR Ensembl; ENST00000676261.1; ENSP00000501675.1; ENSG00000087053.20. [Q13614-2]
DR Ensembl; ENST00000676272.1; ENSP00000501601.1; ENSG00000087053.20. [Q13614-2]
DR Ensembl; ENST00000676378.1; ENSP00000502736.1; ENSG00000087053.20. [Q13614-2]
DR Ensembl; ENST00000676440.1; ENSP00000501926.1; ENSG00000087053.20. [Q13614-2]
DR GeneID; 8898; -.
DR KEGG; hsa:8898; -.
DR MANE-Select; ENST00000346299.10; ENSP00000345752.6; NM_016156.6; NP_057240.3.
DR UCSC; uc001pft.4; human. [Q13614-1]
DR CTD; 8898; -.
DR DisGeNET; 8898; -.
DR GeneCards; MTMR2; -.
DR GeneReviews; MTMR2; -.
DR HGNC; HGNC:7450; MTMR2.
DR HPA; ENSG00000087053; Low tissue specificity.
DR MalaCards; MTMR2; -.
DR MIM; 601382; phenotype.
DR MIM; 603557; gene.
DR neXtProt; NX_Q13614; -.
DR OpenTargets; ENSG00000087053; -.
DR Orphanet; 99955; Charcot-Marie-Tooth disease type 4B1.
DR PharmGKB; PA31253; -.
DR VEuPathDB; HostDB:ENSG00000087053; -.
DR eggNOG; KOG4471; Eukaryota.
DR GeneTree; ENSGT00940000153669; -.
DR InParanoid; Q13614; -.
DR OMA; ESYAICD; -.
DR OrthoDB; 824298at2759; -.
DR PhylomeDB; Q13614; -.
DR TreeFam; TF315197; -.
DR BRENDA; 3.1.3.64; 2681.
DR BRENDA; 3.1.3.95; 2681.
DR PathwayCommons; Q13614; -.
DR Reactome; R-HSA-1483248; Synthesis of PIPs at the ER membrane.
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 SignaLink; Q13614; -.
DR BioGRID-ORCS; 8898; 14 hits in 1086 CRISPR screens.
DR ChiTaRS; MTMR2; human.
DR EvolutionaryTrace; Q13614; -.
DR GeneWiki; MTMR2; -.
DR GenomeRNAi; 8898; -.
DR Pharos; Q13614; Tbio.
DR PRO; PR:Q13614; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; Q13614; protein.
DR Bgee; ENSG00000087053; Expressed in sperm and 211 other tissues.
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; HDA:UniProtKB.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0014069; C:postsynaptic density; ISS:BHF-UCL.
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:0042802; F:identical protein binding; 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: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: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:0060304; P:regulation of phosphatidylinositol dephosphorylation; IDA:UniProtKB.
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-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 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 3D-structure; Alternative splicing; Cell projection;
KW Charcot-Marie-Tooth disease; Coiled coil; Cytoplasm; Disease variant;
KW Endosome; Hydrolase; Lipid metabolism; Membrane; Neurodegeneration;
KW Neuropathy; Phosphoprotein; Reference proteome.
FT CHAIN 1..643
FT /note="Myotubularin-related protein 2"
FT /id="PRO_0000094934"
FT DOMAIN 68..139
FT /note="GRAM"
FT /evidence="ECO:0000255"
FT DOMAIN 205..580
FT /note="Myotubularin phosphatase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00669"
FT REGION 1..56
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 615..643
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 593..627
FT /evidence="ECO:0000269|PubMed:16410353"
FT COMPBIAS 19..56
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 618..643
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 417
FT /note="Phosphocysteine intermediate"
FT /evidence="ECO:0000269|PubMed:14690594,
FT ECO:0000269|PubMed:16410353"
FT BINDING 330..333
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:14690594"
FT BINDING 355..356
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:14690594"
FT BINDING 417..423
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:14690594"
FT BINDING 463
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:16410353"
FT MOD_RES 6
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9Z2D1"
FT MOD_RES 9
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9Z2D1"
FT MOD_RES 58
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:21372139,
FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:19690332"
FT VAR_SEQ 1..72
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_044933"
FT VARIANT 3
FT /note="K -> T (in dbSNP:rs3824874)"
FT /evidence="ECO:0000269|PubMed:10470851,
FT ECO:0000269|PubMed:15489334"
FT /id="VAR_047255"
FT VARIANT 283
FT /note="R -> W (in CMT4B1; dbSNP:rs1590983932)"
FT /evidence="ECO:0000269|PubMed:12398840"
FT /id="VAR_047947"
FT VARIANT 545
FT /note="N -> S (in dbSNP:rs558018)"
FT /id="VAR_047256"
FT MUTAGEN 417
FT /note="C->S: Loss of activity."
FT /evidence="ECO:0000269|PubMed:14690594,
FT ECO:0000269|PubMed:16410353"
FT MUTAGEN 419
FT /note="D->A: No effect."
FT /evidence="ECO:0000269|PubMed:14690594"
FT MUTAGEN 422
FT /note="D->A: Loss of activity."
FT /evidence="ECO:0000269|PubMed:14690594"
FT MUTAGEN 589..643
FT /note="Missing: Loss of homodimerization and interaction
FT with SBF1."
FT /evidence="ECO:0000269|PubMed:12668758"
FT MUTAGEN 607
FT /note="L->Y: Reduces homodimerization and interaction with
FT SBF1."
FT /evidence="ECO:0000269|PubMed:12668758"
FT STRAND 84..95
FT /evidence="ECO:0007829|PDB:1ZSQ"
FT TURN 96..98
FT /evidence="ECO:0007829|PDB:1ZSQ"
FT STRAND 99..121
FT /evidence="ECO:0007829|PDB:1ZSQ"
FT STRAND 123..128
FT /evidence="ECO:0007829|PDB:1ZSQ"
FT HELIX 129..131
FT /evidence="ECO:0007829|PDB:1ZSQ"
FT STRAND 132..138
FT /evidence="ECO:0007829|PDB:1ZSQ"
FT STRAND 145..147
FT /evidence="ECO:0007829|PDB:1ZVR"
FT STRAND 149..155
FT /evidence="ECO:0007829|PDB:1ZSQ"
FT TURN 156..158
FT /evidence="ECO:0007829|PDB:1ZSQ"
FT STRAND 159..164
FT /evidence="ECO:0007829|PDB:1ZSQ"
FT HELIX 167..169
FT /evidence="ECO:0007829|PDB:1ZSQ"
FT HELIX 172..182
FT /evidence="ECO:0007829|PDB:1ZSQ"
FT TURN 185..189
FT /evidence="ECO:0007829|PDB:1ZSQ"
FT HELIX 193..195
FT /evidence="ECO:0007829|PDB:1ZSQ"
FT HELIX 205..207
FT /evidence="ECO:0007829|PDB:1ZSQ"
FT HELIX 211..217
FT /evidence="ECO:0007829|PDB:1ZSQ"
FT STRAND 223..228
FT /evidence="ECO:0007829|PDB:1ZSQ"
FT TURN 230..233
FT /evidence="ECO:0007829|PDB:1ZSQ"
FT STRAND 234..236
FT /evidence="ECO:0007829|PDB:1ZSQ"
FT STRAND 242..247
FT /evidence="ECO:0007829|PDB:1ZSQ"
FT HELIX 252..261
FT /evidence="ECO:0007829|PDB:1ZSQ"
FT HELIX 263..265
FT /evidence="ECO:0007829|PDB:1ZSQ"
FT STRAND 269..273
FT /evidence="ECO:0007829|PDB:1ZSQ"
FT TURN 275..277
FT /evidence="ECO:0007829|PDB:1ZSQ"
FT STRAND 280..284
FT /evidence="ECO:0007829|PDB:1ZSQ"
FT TURN 290..293
FT /evidence="ECO:0007829|PDB:1ZSQ"
FT HELIX 297..309
FT /evidence="ECO:0007829|PDB:1ZSQ"
FT STRAND 310..312
FT /evidence="ECO:0007829|PDB:1ZSQ"
FT STRAND 314..320
FT /evidence="ECO:0007829|PDB:1ZSQ"
FT HELIX 324..333
FT /evidence="ECO:0007829|PDB:1ZSQ"
FT TURN 340..342
FT /evidence="ECO:0007829|PDB:1ZSQ"
FT STRAND 346..350
FT /evidence="ECO:0007829|PDB:1ZSQ"
FT HELIX 356..370
FT /evidence="ECO:0007829|PDB:1ZSQ"
FT HELIX 376..378
FT /evidence="ECO:0007829|PDB:1ZSQ"
FT HELIX 379..386
FT /evidence="ECO:0007829|PDB:1ZSQ"
FT HELIX 388..407
FT /evidence="ECO:0007829|PDB:1ZSQ"
FT STRAND 413..416
FT /evidence="ECO:0007829|PDB:1ZSQ"
FT STRAND 418..422
FT /evidence="ECO:0007829|PDB:1ZSQ"
FT HELIX 423..435
FT /evidence="ECO:0007829|PDB:1ZSQ"
FT HELIX 437..440
FT /evidence="ECO:0007829|PDB:1ZSQ"
FT HELIX 442..452
FT /evidence="ECO:0007829|PDB:1ZSQ"
FT TURN 453..457
FT /evidence="ECO:0007829|PDB:1ZSQ"
FT HELIX 460..464
FT /evidence="ECO:0007829|PDB:1ZSQ"
FT TURN 465..467
FT /evidence="ECO:0007829|PDB:1ZSQ"
FT HELIX 479..493
FT /evidence="ECO:0007829|PDB:1ZSQ"
FT TURN 495..497
FT /evidence="ECO:0007829|PDB:1ZSQ"
FT HELIX 502..514
FT /evidence="ECO:0007829|PDB:1ZSQ"
FT STRAND 516..518
FT /evidence="ECO:0007829|PDB:1ZSQ"
FT STRAND 522..524
FT /evidence="ECO:0007829|PDB:1ZSQ"
FT HELIX 525..530
FT /evidence="ECO:0007829|PDB:1ZSQ"
FT HELIX 533..536
FT /evidence="ECO:0007829|PDB:1ZSQ"
FT HELIX 540..545
FT /evidence="ECO:0007829|PDB:1ZSQ"
FT HELIX 548..551
FT /evidence="ECO:0007829|PDB:1ZSQ"
FT TURN 554..557
FT /evidence="ECO:0007829|PDB:1ZSQ"
FT STRAND 560..562
FT /evidence="ECO:0007829|PDB:1ZSQ"
FT TURN 570..572
FT /evidence="ECO:0007829|PDB:1ZSQ"
FT HELIX 577..580
FT /evidence="ECO:0007829|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
