MTMR6_HUMAN
ID MTMR6_HUMAN Reviewed; 621 AA.
AC Q9Y217; B2RBB5; B3KSB4; Q5JRG6; Q86TB7; Q86YH4; Q96P80;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT 11-JAN-2011, sequence version 3.
DT 03-AUG-2022, entry version 194.
DE RecName: Full=Myotubularin-related protein 6 {ECO:0000305};
DE AltName: Full=Phosphatidylinositol-3,5-bisphosphate 3-phosphatase {ECO:0000305};
DE EC=3.1.3.95 {ECO:0000269|PubMed:22647598};
DE AltName: Full=Phosphatidylinositol-3-phosphate phosphatase {ECO:0000305};
DE EC=3.1.3.64 {ECO:0000269|PubMed:19038970, ECO:0000269|PubMed:22647598, ECO:0000305|PubMed:24591580};
GN Name=MTMR6 {ECO:0000312|HGNC:HGNC:7453};
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), AND INTERACTION WITH MTMR9.
RX PubMed=12890864; DOI=10.1073/pnas.1333958100;
RA Mochizuki Y., Majerus P.W.;
RT "Characterization of myotubularin-related protein 7 and its binding
RT partner, myotubularin-related protein 9.";
RL Proc. Natl. Acad. Sci. U.S.A. 100:9768-9773(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT VAL-319.
RA Hong W.;
RL Submitted (AUG-2001) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), AND VARIANT
RP VAL-319.
RC TISSUE=Testis, and Trachea;
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 MRNA] (ISOFORM 1), AND VARIANT VAL-319.
RC TISSUE=Skeletal muscle;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15057823; DOI=10.1038/nature02379;
RA Dunham A., Matthews L.H., Burton J., Ashurst J.L., Howe K.L.,
RA Ashcroft K.J., Beare D.M., Burford D.C., Hunt S.E., Griffiths-Jones S.,
RA Jones M.C., Keenan S.J., Oliver K., Scott C.E., Ainscough R., Almeida J.P.,
RA Ambrose K.D., Andrews D.T., Ashwell R.I.S., Babbage A.K., Bagguley C.L.,
RA Bailey J., Bannerjee R., Barlow K.F., Bates K., Beasley H., Bird C.P.,
RA Bray-Allen S., Brown A.J., Brown J.Y., Burrill W., Carder C., Carter N.P.,
RA Chapman J.C., Clamp M.E., Clark S.Y., Clarke G., Clee C.M., Clegg S.C.,
RA Cobley V., Collins J.E., Corby N., Coville G.J., Deloukas P., Dhami P.,
RA Dunham I., Dunn M., Earthrowl M.E., Ellington A.G., Faulkner L.,
RA Frankish A.G., Frankland J., French L., Garner P., Garnett J.,
RA Gilbert J.G.R., Gilson C.J., Ghori J., Grafham D.V., Gribble S.M.,
RA Griffiths C., Hall R.E., Hammond S., Harley J.L., Hart E.A., Heath P.D.,
RA Howden P.J., Huckle E.J., Hunt P.J., Hunt A.R., Johnson C., Johnson D.,
RA Kay M., Kimberley A.M., King A., Laird G.K., Langford C.J., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Lloyd C., Loveland J.E., Lovell J.,
RA Martin S., Mashreghi-Mohammadi M., McLaren S.J., McMurray A., Milne S.,
RA Moore M.J.F., Nickerson T., Palmer S.A., Pearce A.V., Peck A.I., Pelan S.,
RA Phillimore B., Porter K.M., Rice C.M., Searle S., Sehra H.K., Shownkeen R.,
RA Skuce C.D., Smith M., Steward C.A., Sycamore N., Tester J., Thomas D.W.,
RA Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P.,
RA Whitehead S.L., Willey D.L., Wilming L., Wray P.W., Wright M.W., Young L.,
RA Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Beck S., Bentley D.R.,
RA Rogers J., Ross M.T.;
RT "The DNA sequence and analysis of human chromosome 13.";
RL Nature 428:522-528(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT VAL-319.
RC TISSUE=Eye;
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 NUCLEOTIDE SEQUENCE [MRNA] OF 157-621 (ISOFORM 1), AND VARIANT VAL-319.
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 [8]
RP CATALYTIC ACTIVITY.
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 [9]
RP FUNCTION, AND INTERACTION WITH KCNN4.
RX PubMed=15831468; DOI=10.1128/mcb.25.9.3630-3638.2005;
RA Srivastava S., Li Z., Lin L., Liu G., Ko K., Coetzee W.A., Skolnik E.Y.;
RT "The phosphatidylinositol 3-phosphate phosphatase myotubularin-related
RT protein 6 (MTMR6) is a negative regulator of the Ca2+-activated K+ channel
RT KCa3.1.";
RL Mol. Cell. Biol. 25:3630-3638(2005).
RN [10]
RP SUBCELLULAR LOCATION, AND INTERACTION WITH MTMR9.
RX PubMed=16787938; DOI=10.1242/jcs.03040;
RA Lorenzo O., Urbe S., Clague M.J.;
RT "Systematic analysis of myotubularins: heteromeric interactions,
RT subcellular localisation and endosome related functions.";
RL J. Cell Sci. 119:2953-2959(2006).
RN [11]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=16847315; DOI=10.1128/mcb.00352-06;
RA Srivastava S., Ko K., Choudhury P., Li Z., Johnson A.K., Nadkarni V.,
RA Unutmaz D., Coetzee W.A., Skolnik E.Y.;
RT "Phosphatidylinositol-3 phosphatase myotubularin-related protein 6
RT negatively regulates CD4 T cells.";
RL Mol. Cell. Biol. 26:5595-5602(2006).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-561 AND SER-589, AND
RP IDENTIFICATION 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 FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, BIOPHYSICOCHEMICAL
RP PROPERTIES, INTERACTION WITH MTMR9, SUBUNIT, AND SUBCELLULAR LOCATION.
RX PubMed=19038970; DOI=10.1074/jbc.m804292200;
RA Zou J., Chang S.C., Marjanovic J., Majerus P.W.;
RT "MTMR9 increases MTMR6 enzyme activity, stability, and role in apoptosis.";
RL J. Biol. Chem. 284:2064-2071(2009).
RN [14]
RP INTERACTION WITH ALKBH4.
RX PubMed=23145062; DOI=10.1371/journal.pone.0049045;
RA Bjornstad L.G., Meza T.J., Otterlei M., Olafsrud S.M., Meza-Zepeda L.A.,
RA Falnes P.O.;
RT "Human ALKBH4 interacts with proteins associated with transcription.";
RL PLoS ONE 7:E49045-E49045(2012).
RN [15]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=22647598; DOI=10.1073/pnas.1207021109;
RA Zou J., Zhang C., Marjanovic J., Kisseleva M.V., Majerus P.W., Wilson M.P.;
RT "Myotubularin-related protein (MTMR) 9 determines the enzymatic activity,
RT substrate specificity, and role in autophagy of MTMR8.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:9539-9544(2012).
RN [16]
RP INTERACTION WITH MTMR9 AND RAB1B, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=23188820; DOI=10.1074/jbc.m112.395087;
RA Mochizuki Y., Ohashi R., Kawamura T., Iwanari H., Kodama T., Naito M.,
RA Hamakubo T.;
RT "Phosphatidylinositol 3-phosphatase myotubularin-related protein 6 (MTMR6)
RT is regulated by small GTPase Rab1B in the early secretory and autophagic
RT pathways.";
RL J. Biol. Chem. 288:1009-1021(2013).
RN [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-561 AND SER-611, 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 [18]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-556 AND SER-561, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [19]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=24591580; DOI=10.1073/pnas.1311029111;
RA Maekawa M., Terasaka S., Mochizuki Y., Kawai K., Ikeda Y., Araki N.,
RA Skolnik E.Y., Taguchi T., Arai H.;
RT "Sequential breakdown of 3-phosphorylated phosphoinositides is essential
RT for the completion of macropinocytosis.";
RL Proc. Natl. Acad. Sci. U.S.A. 111:E978-E987(2014).
CC -!- FUNCTION: Phosphatase that acts on lipids with a phosphoinositol
CC headgroup (PubMed:19038970, PubMed:22647598). Dephosphorylates
CC phosphatidylinositol 3-phosphate (PtdIns(3)P) and phosphatidylinositol
CC 3,5-bisphosphate (PubMed:19038970, PubMed:22647598) (Probable). Binds
CC with high affinity to phosphatidylinositol 3,5-bisphosphate
CC (PtdIns(3,5)P2) but also to phosphatidylinositol 3-phosphate
CC (PtdIns(3)P), phosphatidylinositol 4-phosphate (PtdIns(4)P), and
CC phosphatidylinositol 5-phosphate (PtdIns(5)P), phosphatidic acid and
CC phosphatidylserine (PubMed:19038970). Negatively regulates ER-Golgi
CC protein transport (By similarity). Probably in association with MTMR9,
CC plays a role in the late stages of macropinocytosis by
CC dephosphorylating phosphatidylinositol 3-phosphate in membrane ruffles
CC (PubMed:24591580). Acts as a negative regulator of KCNN4/KCa3.1 channel
CC activity in CD4(+) T-cells possibly by decreasing intracellular levels
CC of phosphatidylinositol 3-phosphate (PubMed:15831468). Negatively
CC regulates proliferation of reactivated CD4(+) T-cells
CC (PubMed:16847315). In complex with MTMR9, negatively regulates DNA
CC damage-induced apoptosis (PubMed:19038970, PubMed:22647598). The
CC formation of the MTMR6-MTMR9 complex stabilizes both MTMR6 and MTMR9
CC protein levels (PubMed:19038970). {ECO:0000250|UniProtKB:A0A0G2JXT6,
CC ECO:0000269|PubMed:15831468, ECO:0000269|PubMed:16847315,
CC ECO:0000269|PubMed:19038970, ECO:0000269|PubMed:22647598,
CC ECO:0000269|PubMed:24591580, ECO:0000305|PubMed:24591580}.
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:22647598};
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:19038970, ECO:0000269|PubMed:22647598,
CC ECO:0000305|PubMed:24591580};
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-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 -!- ACTIVITY REGULATION: Allosterically activated by phosphatidylserine
CC and/or phosphatidylinositol 4-phosphate (PtdIns(4)P), and
CC phosphatidylinositol 5-phosphate (PtdIns(5)P) (PubMed:19038970).
CC Interaction with MTMR9 increases catalytic activity towards
CC phosphatidylinositol 3,5-bisphosphate (PubMed:19038970).
CC {ECO:0000269|PubMed:19038970}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC pH dependence:
CC Optimum pH is 7. {ECO:0000269|PubMed:19038970};
CC -!- SUBUNIT: Homodimer (PubMed:19038970). Heterodimer (via C-terminus) with
CC MTMR9 (via C-terminus) (PubMed:12890864, PubMed:16787938,
CC PubMed:19038970, PubMed:23188820). Interacts with ALKBH4
CC (PubMed:23145062). Interacts with KCNN4 (PubMed:15831468). Interacts
CC (via GRAM domain) with RAB1B (in GDP-bound form); the interaction
CC regulates MTMR6 recruitment to the endoplasmic reticulum-Golgi
CC intermediate compartment (PubMed:23188820).
CC {ECO:0000269|PubMed:12890864, ECO:0000269|PubMed:15831468,
CC ECO:0000269|PubMed:16787938, ECO:0000269|PubMed:19038970,
CC ECO:0000269|PubMed:23145062, ECO:0000269|PubMed:23188820}.
CC -!- INTERACTION:
CC Q9Y217; Q9Y2J4-4: AMOTL2; NbExp=3; IntAct=EBI-766064, EBI-10187270;
CC Q9Y217; Q96QG7: MTMR9; NbExp=12; IntAct=EBI-766064, EBI-744593;
CC Q9Y217; Q5JR59: MTUS2; NbExp=3; IntAct=EBI-766064, EBI-742948;
CC Q9Y217; Q13287: NMI; NbExp=6; IntAct=EBI-766064, EBI-372942;
CC Q9Y217; P14373: TRIM27; NbExp=3; IntAct=EBI-766064, EBI-719493;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:19038970}.
CC Endoplasmic reticulum-Golgi intermediate compartment
CC {ECO:0000269|PubMed:16787938, ECO:0000269|PubMed:19038970}. Endoplasmic
CC reticulum {ECO:0000269|PubMed:19038970}. Cell projection, ruffle
CC membrane {ECO:0000250|UniProtKB:Q8VE11}; Peripheral membrane protein
CC {ECO:0000305}; Cytoplasmic side {ECO:0000305}. Cytoplasm, perinuclear
CC region {ECO:0000269|PubMed:19038970}. Note=Localizes to ruffles during
CC EGF-induced macropinocytosis (By similarity). Colocalizes with MTMR9 to
CC the perinuclear region (PubMed:19038970). Partially localizes to the
CC endoplasmic reticulum (PubMed:19038970). Co-localizes with RAB1B to the
CC endoplasmic reticulum-Golgi intermediate compartment and to the peri-
CC Golgi region (By similarity). {ECO:0000250|UniProtKB:A0A0G2JXT6,
CC ECO:0000250|UniProtKB:Q8VE11, ECO:0000269|PubMed:19038970}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9Y217-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9Y217-2; Sequence=VSP_036614, VSP_036615;
CC -!- TISSUE SPECIFICITY: Expressed in CD4+ T-cells.
CC {ECO:0000269|PubMed:16847315}.
CC -!- DOMAIN: The GRAM domain is required for cell membrane localization.
CC {ECO:0000250|UniProtKB:Q8VE11}.
CC -!- DOMAIN: The C-terminus domain (aa 502-621) mediates interaction with
CC MTMR9. {ECO:0000250|UniProtKB:Q8VE11}.
CC -!- SIMILARITY: Belongs to the protein-tyrosine phosphatase family. Non-
CC receptor class myotubularin subfamily. {ECO:0000305}.
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DR EMBL; AF406619; AAL01037.1; -; mRNA.
DR EMBL; AK093237; BAG52676.1; -; mRNA.
DR EMBL; AK314587; BAG37162.1; -; mRNA.
DR EMBL; AL832017; CAD89918.1; -; mRNA.
DR EMBL; AL590787; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC040012; AAH40012.1; -; mRNA.
DR EMBL; AF072928; AAC78841.1; -; mRNA.
DR CCDS; CCDS9313.1; -. [Q9Y217-1]
DR RefSeq; NP_004676.3; NM_004685.3. [Q9Y217-1]
DR PDB; 2YF0; X-ray; 2.65 A; A=1-505.
DR PDBsum; 2YF0; -.
DR AlphaFoldDB; Q9Y217; -.
DR SMR; Q9Y217; -.
DR BioGRID; 114558; 77.
DR IntAct; Q9Y217; 33.
DR MINT; Q9Y217; -.
DR STRING; 9606.ENSP00000371221; -.
DR SwissLipids; SLP:000001133; -.
DR DEPOD; MTMR6; -.
DR GlyGen; Q9Y217; 2 sites, 1 O-linked glycan (2 sites).
DR iPTMnet; Q9Y217; -.
DR PhosphoSitePlus; Q9Y217; -.
DR BioMuta; MTMR6; -.
DR DMDM; 317373414; -.
DR EPD; Q9Y217; -.
DR jPOST; Q9Y217; -.
DR MassIVE; Q9Y217; -.
DR MaxQB; Q9Y217; -.
DR PaxDb; Q9Y217; -.
DR PeptideAtlas; Q9Y217; -.
DR PRIDE; Q9Y217; -.
DR ProteomicsDB; 85593; -. [Q9Y217-1]
DR ProteomicsDB; 85594; -. [Q9Y217-2]
DR TopDownProteomics; Q9Y217-1; -. [Q9Y217-1]
DR Antibodypedia; 22544; 143 antibodies from 24 providers.
DR DNASU; 9107; -.
DR Ensembl; ENST00000381801.6; ENSP00000371221.5; ENSG00000139505.12. [Q9Y217-1]
DR GeneID; 9107; -.
DR KEGG; hsa:9107; -.
DR MANE-Select; ENST00000381801.6; ENSP00000371221.5; NM_004685.5; NP_004676.3.
DR UCSC; uc001uqf.6; human. [Q9Y217-1]
DR CTD; 9107; -.
DR DisGeNET; 9107; -.
DR GeneCards; MTMR6; -.
DR HGNC; HGNC:7453; MTMR6.
DR HPA; ENSG00000139505; Low tissue specificity.
DR MIM; 603561; gene.
DR neXtProt; NX_Q9Y217; -.
DR OpenTargets; ENSG00000139505; -.
DR PharmGKB; PA31256; -.
DR VEuPathDB; HostDB:ENSG00000139505; -.
DR eggNOG; KOG1089; Eukaryota.
DR GeneTree; ENSGT00940000158055; -.
DR HOGENOM; CLU_001839_3_2_1; -.
DR InParanoid; Q9Y217; -.
DR OMA; PNTDYMY; -.
DR OrthoDB; 824298at2759; -.
DR PhylomeDB; Q9Y217; -.
DR TreeFam; TF315197; -.
DR BRENDA; 3.1.3.95; 2681.
DR PathwayCommons; Q9Y217; -.
DR Reactome; R-HSA-1660499; Synthesis of PIPs at the plasma membrane.
DR SignaLink; Q9Y217; -.
DR BioGRID-ORCS; 9107; 27 hits in 1082 CRISPR screens.
DR ChiTaRS; MTMR6; human.
DR GeneWiki; MTMR6; -.
DR GenomeRNAi; 9107; -.
DR Pharos; Q9Y217; Tbio.
DR PRO; PR:Q9Y217; -.
DR Proteomes; UP000005640; Chromosome 13.
DR RNAct; Q9Y217; protein.
DR Bgee; ENSG00000139505; Expressed in endothelial cell and 204 other tissues.
DR Genevisible; Q9Y217; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005783; C:endoplasmic reticulum; IEA:UniProtKB-SubCell.
DR GO; GO:0005793; C:endoplasmic reticulum-Golgi intermediate compartment; IEA:UniProtKB-SubCell.
DR GO; GO:0005635; C:nuclear envelope; IDA:UniProtKB.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0032587; C:ruffle membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0052629; F:phosphatidylinositol-3,5-bisphosphate 3-phosphatase activity; TAS:Reactome.
DR GO; GO:0106018; F:phosphatidylinositol-3,5-bisphosphate phosphatase activity; IDA:UniProtKB.
DR GO; GO:0004438; F:phosphatidylinositol-3-phosphatase activity; IDA:UniProtKB.
DR GO; GO:0004722; F:protein serine/threonine phosphatase activity; NAS:UniProtKB.
DR GO; GO:0004725; F:protein tyrosine phosphatase activity; NAS:UniProtKB.
DR GO; GO:0006897; P:endocytosis; IEA:UniProtKB-KW.
DR GO; GO:0006661; P:phosphatidylinositol biosynthetic process; TAS:Reactome.
DR GO; GO:0046856; P:phosphatidylinositol dephosphorylation; IDA:UniProtKB.
DR GO; GO:0006470; P:protein dephosphorylation; NAS:UniProtKB.
DR CDD; cd13343; PH-GRAM_MTMR6; 1.
DR Gene3D; 2.30.29.30; -; 1.
DR InterPro; IPR030581; MTMR6.
DR InterPro; IPR035998; MTMR6_PH-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 PANTHER; PTHR10807; PTHR10807; 1.
DR PANTHER; PTHR10807:SF34; PTHR10807:SF34; 1.
DR Pfam; PF06602; Myotub-related; 1.
DR SMART; SM00404; PTPc_motif; 1.
DR SUPFAM; SSF52799; SSF52799; 1.
DR PROSITE; PS51339; PPASE_MYOTUBULARIN; 1.
DR PROSITE; PS00383; TYR_PHOSPHATASE_1; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cell membrane; Cell projection;
KW Cytoplasm; Endocytosis; Endoplasmic reticulum; Hydrolase; Lipid metabolism;
KW Membrane; Phosphoprotein; Reference proteome.
FT CHAIN 1..621
FT /note="Myotubularin-related protein 6"
FT /id="PRO_0000094939"
FT DOMAIN 1..101
FT /note="GRAM"
FT /evidence="ECO:0000255"
FT DOMAIN 124..499
FT /note="Myotubularin phosphatase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00669"
FT REGION 2..141
FT /note="Interaction with RAB1B"
FT /evidence="ECO:0000250|UniProtKB:Q8VE11"
FT ACT_SITE 336
FT /note="Phosphocysteine intermediate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10044"
FT BINDING 248..251
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q13614"
FT BINDING 273..274
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q13614"
FT BINDING 336..342
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q13614"
FT BINDING 382
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q13614"
FT MOD_RES 108
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q8VE11"
FT MOD_RES 556
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 561
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569"
FT MOD_RES 589
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 611
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT VAR_SEQ 536..548
FT /note="KIKQRKNKQTDGI -> LTSYSSFKIIVGQ (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_036614"
FT VAR_SEQ 549..621
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_036615"
FT VARIANT 131
FT /note="A -> T (in dbSNP:rs34885345)"
FT /id="VAR_057143"
FT VARIANT 319
FT /note="I -> V (in dbSNP:rs7995033)"
FT /evidence="ECO:0000269|PubMed:14702039,
FT ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:17974005,
FT ECO:0000269|PubMed:9736772, ECO:0000269|Ref.2"
FT /id="VAR_024583"
FT CONFLICT 89
FT /note="H -> R (in Ref. 4; CAD89918)"
FT /evidence="ECO:0000305"
FT CONFLICT 114
FT /note="P -> S (in Ref. 3; BAG37162)"
FT /evidence="ECO:0000305"
FT CONFLICT 125
FT /note="W -> R (in Ref. 4; CAD89918)"
FT /evidence="ECO:0000305"
FT CONFLICT 333
FT /note="L -> S (in Ref. 2; AAL01037 and 7; AAC78841)"
FT /evidence="ECO:0000305"
FT CONFLICT 368
FT /note="I -> T (in Ref. 3; BAG37162)"
FT /evidence="ECO:0000305"
FT CONFLICT 430
FT /note="H -> D (in Ref. 3; BAG52676)"
FT /evidence="ECO:0000305"
FT CONFLICT 442
FT /note="Q -> P (in Ref. 2; AAL01037 and 7; AAC78841)"
FT /evidence="ECO:0000305"
FT STRAND 5..11
FT /evidence="ECO:0007829|PDB:2YF0"
FT STRAND 26..31
FT /evidence="ECO:0007829|PDB:2YF0"
FT STRAND 33..43
FT /evidence="ECO:0007829|PDB:2YF0"
FT STRAND 45..49
FT /evidence="ECO:0007829|PDB:2YF0"
FT HELIX 50..52
FT /evidence="ECO:0007829|PDB:2YF0"
FT STRAND 53..58
FT /evidence="ECO:0007829|PDB:2YF0"
FT STRAND 65..72
FT /evidence="ECO:0007829|PDB:2YF0"
FT STRAND 77..83
FT /evidence="ECO:0007829|PDB:2YF0"
FT HELIX 85..98
FT /evidence="ECO:0007829|PDB:2YF0"
FT HELIX 108..110
FT /evidence="ECO:0007829|PDB:2YF0"
FT HELIX 119..125
FT /evidence="ECO:0007829|PDB:2YF0"
FT HELIX 130..136
FT /evidence="ECO:0007829|PDB:2YF0"
FT STRAND 140..147
FT /evidence="ECO:0007829|PDB:2YF0"
FT HELIX 148..150
FT /evidence="ECO:0007829|PDB:2YF0"
FT STRAND 157..159
FT /evidence="ECO:0007829|PDB:2YF0"
FT STRAND 161..169
FT /evidence="ECO:0007829|PDB:2YF0"
FT HELIX 171..180
FT /evidence="ECO:0007829|PDB:2YF0"
FT HELIX 182..184
FT /evidence="ECO:0007829|PDB:2YF0"
FT STRAND 188..192
FT /evidence="ECO:0007829|PDB:2YF0"
FT TURN 194..196
FT /evidence="ECO:0007829|PDB:2YF0"
FT STRAND 199..202
FT /evidence="ECO:0007829|PDB:2YF0"
FT HELIX 215..227
FT /evidence="ECO:0007829|PDB:2YF0"
FT STRAND 234..238
FT /evidence="ECO:0007829|PDB:2YF0"
FT TURN 258..260
FT /evidence="ECO:0007829|PDB:2YF0"
FT STRAND 264..268
FT /evidence="ECO:0007829|PDB:2YF0"
FT HELIX 274..288
FT /evidence="ECO:0007829|PDB:2YF0"
FT HELIX 295..304
FT /evidence="ECO:0007829|PDB:2YF0"
FT HELIX 307..326
FT /evidence="ECO:0007829|PDB:2YF0"
FT STRAND 332..334
FT /evidence="ECO:0007829|PDB:2YF0"
FT TURN 336..338
FT /evidence="ECO:0007829|PDB:2YF0"
FT STRAND 339..341
FT /evidence="ECO:0007829|PDB:2YF0"
FT HELIX 342..354
FT /evidence="ECO:0007829|PDB:2YF0"
FT HELIX 357..359
FT /evidence="ECO:0007829|PDB:2YF0"
FT HELIX 361..371
FT /evidence="ECO:0007829|PDB:2YF0"
FT TURN 372..376
FT /evidence="ECO:0007829|PDB:2YF0"
FT HELIX 379..383
FT /evidence="ECO:0007829|PDB:2YF0"
FT STRAND 385..387
FT /evidence="ECO:0007829|PDB:2YF0"
FT HELIX 390..392
FT /evidence="ECO:0007829|PDB:2YF0"
FT HELIX 396..410
FT /evidence="ECO:0007829|PDB:2YF0"
FT TURN 412..414
FT /evidence="ECO:0007829|PDB:2YF0"
FT HELIX 419..429
FT /evidence="ECO:0007829|PDB:2YF0"
FT TURN 430..432
FT /evidence="ECO:0007829|PDB:2YF0"
FT STRAND 439..441
FT /evidence="ECO:0007829|PDB:2YF0"
FT HELIX 442..447
FT /evidence="ECO:0007829|PDB:2YF0"
FT HELIX 450..453
FT /evidence="ECO:0007829|PDB:2YF0"
FT HELIX 458..461
FT /evidence="ECO:0007829|PDB:2YF0"
FT HELIX 465..468
FT /evidence="ECO:0007829|PDB:2YF0"
FT STRAND 488..491
FT /evidence="ECO:0007829|PDB:2YF0"
FT HELIX 496..502
FT /evidence="ECO:0007829|PDB:2YF0"
SQ SEQUENCE 621 AA; 71968 MW; 1F34608F99DCEA39 CRC64;
MEHIRTTKVE QVKLLDRFST SNKSLTGTLY LTATHLLFID SHQKETWILH HHIASVEKLA
LTTSGCPLVI QCKNFRTVHF IVPRERDCHD IYNSLLQLSK QAKYEDLYAF SYNPKQNDSE
RLQGWQLIDL AEEYKRMGVP NSHWQLSDAN RDYKICETYP RELYVPRIAS KPIIVGSSKF
RSKGRFPVLS YYHQDKEAAI CRCSQPLSGF SARCLEDEHL LQAISKANPV NRYMYVMDTR
PKLNAMANRA AGKGYENEDN YSNIRFQFVG IENIHVMRSS LQKLLEVNGT KGLSVNDFYS
GLESSGWLRH IKAVMDAAIF LAKAITVENA SVLVHCSDGW DRTSQVCSLG SLLLDSYYRT
IKGFMVLIEK DWISFGHKFS ERCGQLDGDP KEVSPVFTQF LECVWHLTEQ FPQAFEFSEA
FLLQIHEHIH SCQFGNFLGN CQKEREELKL KEKTYSLWPF LLEDQKKYLN PLYSSESHRF
TVLEPNTVSF NFKFWRNMYH QFDRTLHPRQ SVFNIIMNMN EQNKQLEKDI KDLESKIKQR
KNKQTDGILT KELLHSVHPE SPNLKTSLCF KEQTLLPVND ALRTIEGSSP ADNRYSEYAE
EFSKSEPAVV SLEYGVARMT C
