MTMR9_MOUSE
ID MTMR9_MOUSE Reviewed; 545 AA.
AC Q9Z2D0; A6H6P1; Q80XL4;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT 19-JUL-2003, sequence version 2.
DT 03-AUG-2022, entry version 148.
DE RecName: Full=Myotubularin-related protein 9;
DE AltName: Full=Inactive phosphatidylinositol 3-phosphatase 9 {ECO:0000305};
GN Name=Mtmr9; Synonyms=Mtmr3;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Brain, and Olfactory epithelium;
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 [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 392-545.
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 [3]
RP FUNCTION, INTERACTION WITH MTMR6 AND MTMR7, SUBUNIT, AND DOMAIN.
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 [4]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Lung, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [5]
RP SUBCELLULAR LOCATION, DOMAIN, AND MUTAGENESIS OF 2-GLU--MET-108.
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: Acts as an adapter for myotubularin-related phosphatases
CC (PubMed:12890864). Increases lipid phosphatase MTMR6 catalytic
CC activity, specifically towards phosphatidylinositol 3,5-bisphosphate,
CC and MTMR6 binding affinity for phosphorylated phosphatidylinositols (By
CC similarity). Positively regulates lipid phosphatase MTMR7 catalytic
CC activity (PubMed:12890864). The formation of the MTMR6-MTMR9 complex,
CC stabilizes both MTMR6 and MTMR9 protein levels (By similarity). Plays a
CC role in the late stages of macropinocytosis possibly by regulating
CC MTMR6-mediated dephosphorylation of phosphatidylinositol 3-phosphate in
CC membrane ruffles (By similarity). Negatively regulates DNA damage-
CC induced apoptosis, in part via its association with MTMR6 (By
CC similarity). Does not bind mono-, di- and tri-phosphorylated
CC phosphatidylinositols, phosphatidic acid and phosphatidylserine (By
CC similarity). {ECO:0000250|UniProtKB:Q96QG7,
CC ECO:0000269|PubMed:12890864}.
CC -!- SUBUNIT: Homodimer (PubMed:12890864). Heterodimer (via C-terminus) with
CC lipid phosphatase MTMR6 (via C-terminus) (PubMed:12890864). Heterodimer
CC (via coiled coil domain) with lipid phosphatase MTMR7 (via C-terminus)
CC (PubMed:12890864). {ECO:0000269|PubMed:12890864}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:24591580}. Cell
CC projection, ruffle membrane {ECO:0000269|PubMed:24591580}; Peripheral
CC membrane protein {ECO:0000305}; Cytoplasmic side {ECO:0000305}.
CC Cytoplasm, perinuclear region {ECO:0000250|UniProtKB:Q96QG7}.
CC Endoplasmic reticulum {ECO:0000250|UniProtKB:Q96QG7}. Note=Localizes to
CC ruffles during EGF-induced macropinocytosis (PubMed:24591580).
CC Colocalizes with MTMR6 to the perinuclear region (By similarity).
CC Partially localizes to the endoplasmic reticulum (By similarity).
CC {ECO:0000250|UniProtKB:Q96QG7, ECO:0000269|PubMed:24591580}.
CC -!- DOMAIN: The GRAM domain is required for cell membrane localization.
CC {ECO:0000269|PubMed:24591580}.
CC -!- DOMAIN: The coiled coil domain mediates interaction with MTMR9.
CC {ECO:0000269|PubMed:12890864}.
CC -!- SIMILARITY: Belongs to the protein-tyrosine phosphatase family. Non-
CC receptor class myotubularin subfamily. {ECO:0000305}.
CC -!- CAUTION: Although it belongs to the non-receptor class myotubularin
CC subfamily, lacks the conserved active site cysteine residue at position
CC 333 in the dsPTPase catalytic loop, suggesting that it has no
CC carboxypeptidase activity. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAC80003.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; BC046275; AAH46275.1; -; mRNA.
DR EMBL; BC145946; AAI45947.1; -; mRNA.
DR EMBL; BC145948; AAI45949.1; -; mRNA.
DR EMBL; AF073881; AAC80003.1; ALT_FRAME; mRNA.
DR CCDS; CCDS27203.1; -.
DR RefSeq; NP_808262.1; NM_177594.1.
DR AlphaFoldDB; Q9Z2D0; -.
DR SMR; Q9Z2D0; -.
DR BioGRID; 229150; 3.
DR IntAct; Q9Z2D0; 1.
DR MINT; Q9Z2D0; -.
DR STRING; 10090.ENSMUSP00000059894; -.
DR iPTMnet; Q9Z2D0; -.
DR PhosphoSitePlus; Q9Z2D0; -.
DR EPD; Q9Z2D0; -.
DR MaxQB; Q9Z2D0; -.
DR PaxDb; Q9Z2D0; -.
DR PRIDE; Q9Z2D0; -.
DR ProteomicsDB; 291455; -.
DR Antibodypedia; 22096; 124 antibodies from 29 providers.
DR DNASU; 210376; -.
DR Ensembl; ENSMUST00000058679; ENSMUSP00000059894; ENSMUSG00000035078.
DR GeneID; 210376; -.
DR KEGG; mmu:210376; -.
DR UCSC; uc007uht.1; mouse.
DR CTD; 66036; -.
DR MGI; MGI:2442842; Mtmr9.
DR VEuPathDB; HostDB:ENSMUSG00000035078; -.
DR eggNOG; KOG1089; Eukaryota.
DR GeneTree; ENSGT00940000157818; -.
DR HOGENOM; CLU_001839_3_1_1; -.
DR InParanoid; Q9Z2D0; -.
DR OMA; RHENGAT; -.
DR OrthoDB; 824298at2759; -.
DR PhylomeDB; Q9Z2D0; -.
DR TreeFam; TF315197; -.
DR Reactome; R-MMU-1660499; Synthesis of PIPs at the plasma membrane.
DR BioGRID-ORCS; 210376; 6 hits in 76 CRISPR screens.
DR ChiTaRS; Mtmr3; mouse.
DR PRO; PR:Q9Z2D0; -.
DR Proteomes; UP000000589; Chromosome 14.
DR RNAct; Q9Z2D0; protein.
DR Bgee; ENSMUSG00000035078; Expressed in cortical plate and 259 other tissues.
DR ExpressionAtlas; Q9Z2D0; baseline and differential.
DR Genevisible; Q9Z2D0; MM.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005783; C:endoplasmic reticulum; IEA:UniProtKB-SubCell.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0032991; C:protein-containing complex; ISO:MGI.
DR GO; GO:0032587; C:ruffle membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0030234; F:enzyme regulator activity; IDA:MGI.
DR GO; GO:0004438; F:phosphatidylinositol-3-phosphatase activity; IBA:GO_Central.
DR GO; GO:0019903; F:protein phosphatase binding; ISO:MGI.
DR GO; GO:0006897; P:endocytosis; IEA:UniProtKB-KW.
DR GO; GO:0010507; P:negative regulation of autophagy; ISO:MGI.
DR GO; GO:0046856; P:phosphatidylinositol dephosphorylation; IBA:GO_Central.
DR GO; GO:0010922; P:positive regulation of phosphatase activity; ISO:MGI.
DR GO; GO:0050821; P:protein stabilization; ISO:MGI.
DR GO; GO:0060304; P:regulation of phosphatidylinositol dephosphorylation; ISO:MGI.
DR Gene3D; 2.30.29.30; -; 1.
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 PANTHER; PTHR10807; PTHR10807; 1.
DR Pfam; PF06602; Myotub-related; 1.
DR SUPFAM; SSF52799; SSF52799; 1.
DR PROSITE; PS51339; PPASE_MYOTUBULARIN; 1.
PE 1: Evidence at protein level;
KW Acetylation; Cell membrane; Cell projection; Coiled coil; Cytoplasm;
KW Endocytosis; Endoplasmic reticulum; Membrane; Reference proteome.
FT CHAIN 1..545
FT /note="Myotubularin-related protein 9"
FT /id="PRO_0000094944"
FT DOMAIN 4..99
FT /note="GRAM"
FT /evidence="ECO:0000255"
FT DOMAIN 123..498
FT /note="Myotubularin phosphatase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00669"
FT COILED 508..542
FT /evidence="ECO:0000255"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0000250|UniProtKB:Q96QG7"
FT MUTAGEN 2..108
FT /note="Missing: Loss of cell membrane recruitment following
FT EGF stimulation."
FT /evidence="ECO:0000269|PubMed:24591580"
SQ SEQUENCE 545 AA; 62908 MW; 1A6F21023BA04AD5 CRC64;
MEFAELIKTP RVDNVVLHRP FYTAVEGTLC LTGHHLILSS RQDNTEELWL LHSNIDAIDK
RFVGSLGTII IKCKDFRIIQ LDIPGMEECL NIASSIEALS TLDSVTLMYP FFYRPMFEVI
EDGWHSFLPE QEFEFYSSAT SEWRLSYINK DFSICPSYPP TVIVPKSVDD EALRKVAAFR
HGGRFPVLSY YHKKNGMVIM RSGQPLTGTN GRRCKEDEKL INATLRAGKR GYLIDTRSLN
VAQQARAKGG GFEQEAHYPQ WRRIHKSIER YHVLQESLIK LVEACNEQTH NMDRWLGKLE
ASNWLTHIKE ILTTACLAAQ CIDREGASVL IHGTEGTDST LQVTSLAQII LEPRSRTIRG
FEALIEREWL QAGHPFQQRC AQSAYCSSKQ KWEAPVFLLF LDCVWQILRQ FPCSFEFNEH
FLIMLFEHAY ASQFGTFLGN NESERCKLKL QQKTMSLWSW VNRPGELSKF TNPLFEANNL
VIWPSVAPQS LQLWEGIFLR WSRSSKYLDE AYEEMVNIIE YNKELQAKVN VLRRQLAELE
TEDGL
