ID   MTMR4_MOUSE             Reviewed;        1190 AA.
AC   Q91XS1; Q5ND06; Q5ND08;
DT   11-SEP-2007, integrated into UniProtKB/Swiss-Prot.
DT   01-DEC-2001, sequence version 1.
DT   24-JAN-2024, entry version 160.
DE   RecName: Full=Myotubularin-related protein 4;
DE            EC=3.1.3.48;
GN   Name=Mtmr4;
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 [MRNA] (ISOFORM 1).
RC   STRAIN=BALB/cJ; TISSUE=Bone marrow;
RA   Gorski K.S., Shin T., Otuji M., Suyi T., Pardoll D., Tsuchiya H.;
RT   "Isolation of a FYVE zinc finger containing phosphatase expressed in mouse
RT   bone marrow derived dendritic cells.";
RL   Submitted (MAY-2000) to the EMBL/GenBank/DDBJ databases.
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC   STRAIN=C57BL/6J; TISSUE=Amnion;
RX   PubMed=16141072; DOI=10.1126/science.1112014;
RA   Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA   Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA   Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA   Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA   Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA   Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA   Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA   Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA   Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA   Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA   Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA   Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA   Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA   Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA   Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA   Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA   Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA   Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA   Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA   Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA   Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA   Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA   Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA   Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA   Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA   van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA   Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA   Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA   Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA   Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA   Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA   Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA   Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA   Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT   "The transcriptional landscape of the mammalian genome.";
RL   Science 309:1559-1563(2005).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=C57BL/6J;
RX   PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA   Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA   Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA   Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA   Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA   Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA   Eichler E.E., Ponting C.P.;
RT   "Lineage-specific biology revealed by a finished genome assembly of the
RT   mouse.";
RL   PLoS Biol. 7:E1000112-E1000112(2009).
RN   [4]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-610, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Liver;
RX   PubMed=17242355; DOI=10.1073/pnas.0609836104;
RA   Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.;
RT   "Large-scale phosphorylation analysis of mouse liver.";
RL   Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007).
RN   [5]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-610, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung,
RC   Spleen, 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).
CC   -!- FUNCTION: Dephosphorylates proteins phosphorylated on Ser, Thr, and Tyr
CC       residues and low molecular weight phosphatase substrate para-
CC       nitrophenylphosphate. Phosphorylates phosphatidylinositol 3,4,5-
CC       trisphosphate (PIP3) (By similarity). {ECO:0000250}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=H2O + O-phospho-L-tyrosyl-[protein] = L-tyrosyl-[protein] +
CC         phosphate; Xref=Rhea:RHEA:10684, Rhea:RHEA-COMP:10136, Rhea:RHEA-
CC         COMP:10137, ChEBI:CHEBI:15377, ChEBI:CHEBI:43474, ChEBI:CHEBI:46858,
CC         ChEBI:CHEBI:82620; EC=3.1.3.48; Evidence={ECO:0000255|PROSITE-
CC         ProRule:PRU10044};
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Membrane {ECO:0000250};
CC       Peripheral membrane protein {ECO:0000250}. Note=Localized to
CC       perinuclear region. {ECO:0000250}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1;
CC         IsoId=Q91XS1-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=Q91XS1-2; Sequence=VSP_028126;
CC   -!- SIMILARITY: Belongs to the protein-tyrosine phosphatase family. Non-
CC       receptor class myotubularin subfamily. {ECO:0000305}.
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DR   EMBL; AF262986; AAK58180.1; -; mRNA.
DR   EMBL; AK146641; BAE27324.1; -; mRNA.
DR   EMBL; AL596086; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   CCDS; CCDS25214.1; -. [Q91XS1-1]
DR   CCDS; CCDS88215.1; -. [Q91XS1-2]
DR   RefSeq; NP_573478.1; NM_133215.1. [Q91XS1-1]
DR   RefSeq; XP_006532447.1; XM_006532384.3.
DR   RefSeq; XP_006532448.1; XM_006532385.3.
DR   RefSeq; XP_011247082.1; XM_011248780.2.
DR   AlphaFoldDB; Q91XS1; -.
DR   SMR; Q91XS1; -.
DR   BioGRID; 228413; 4.
DR   STRING; 10090.ENSMUSP00000099468; -.
DR   iPTMnet; Q91XS1; -.
DR   PhosphoSitePlus; Q91XS1; -.
DR   EPD; Q91XS1; -.
DR   MaxQB; Q91XS1; -.
DR   PaxDb; 10090-ENSMUSP00000099468; -.
DR   ProteomicsDB; 286077; -. [Q91XS1-1]
DR   ProteomicsDB; 286078; -. [Q91XS1-2]
DR   Pumba; Q91XS1; -.
DR   Antibodypedia; 30984; 219 antibodies from 26 providers.
DR   DNASU; 170749; -.
DR   Ensembl; ENSMUST00000092802.12; ENSMUSP00000090478.6; ENSMUSG00000018401.18. [Q91XS1-2]
DR   Ensembl; ENSMUST00000103179.10; ENSMUSP00000099468.4; ENSMUSG00000018401.18. [Q91XS1-1]
DR   Ensembl; ENSMUST00000119628.8; ENSMUSP00000112902.2; ENSMUSG00000018401.18. [Q91XS1-1]
DR   GeneID; 170749; -.
DR   KEGG; mmu:170749; -.
DR   UCSC; uc007ktz.1; mouse. [Q91XS1-1]
DR   UCSC; uc007kua.1; mouse. [Q91XS1-2]
DR   AGR; MGI:2180699; -.
DR   CTD; 9110; -.
DR   MGI; MGI:2180699; Mtmr4.
DR   VEuPathDB; HostDB:ENSMUSG00000018401; -.
DR   eggNOG; KOG4471; Eukaryota.
DR   GeneTree; ENSGT00940000158976; -.
DR   HOGENOM; CLU_001839_2_2_1; -.
DR   InParanoid; Q91XS1; -.
DR   OMA; TRWLQHM; -.
DR   OrthoDB; 5474662at2759; -.
DR   PhylomeDB; Q91XS1; -.
DR   TreeFam; TF315197; -.
DR   Reactome; R-MMU-1660516; Synthesis of PIPs at the early endosome membrane.
DR   Reactome; R-MMU-1660517; Synthesis of PIPs at the late endosome membrane.
DR   Reactome; R-MMU-2173788; Downregulation of TGF-beta receptor signaling.
DR   BioGRID-ORCS; 170749; 3 hits in 82 CRISPR screens.
DR   ChiTaRS; Mtmr4; mouse.
DR   PRO; PR:Q91XS1; -.
DR   Proteomes; UP000000589; Chromosome 11.
DR   RNAct; Q91XS1; Protein.
DR   Bgee; ENSMUSG00000018401; Expressed in urogenital fold and 240 other cell types or tissues.
DR   ExpressionAtlas; Q91XS1; baseline and differential.
DR   GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR   GO; GO:0005768; C:endosome; ISO:MGI.
DR   GO; GO:0016020; C:membrane; IBA:GO_Central.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0052629; F:phosphatidylinositol-3,5-bisphosphate 3-phosphatase activity; IBA:GO_Central.
DR   GO; GO:0004438; F:phosphatidylinositol-3-phosphate phosphatase activity; IBA:GO_Central.
DR   GO; GO:0019903; F:protein phosphatase binding; ISO:MGI.
DR   GO; GO:0004725; F:protein tyrosine phosphatase activity; IEA:UniProtKB-EC.
DR   GO; GO:0046856; P:phosphatidylinositol dephosphorylation; IBA:GO_Central.
DR   GO; GO:0010506; P:regulation of autophagy; IBA:GO_Central.
DR   GO; GO:0060304; P:regulation of phosphatidylinositol dephosphorylation; ISO:MGI.
DR   GO; GO:0014894; P:response to denervation involved in regulation of muscle adaptation; IEA:Ensembl.
DR   CDD; cd15733; FYVE_MTMR4; 1.
DR   CDD; cd13342; PH-GRAM_MTMR4; 1.
DR   CDD; cd14587; PTP-MTMR4; 1.
DR   Gene3D; 3.30.40.10; Zinc/RING finger domain, C3HC4 (zinc finger); 1.
DR   InterPro; IPR046978; MTMR4_FYVE.
DR   InterPro; IPR035997; MTMR4_PH-GRAM.
DR   InterPro; IPR030590; MTMR4_PTP.
DR   InterPro; IPR010569; Myotubularin-like_Pase_dom.
DR   InterPro; IPR030564; Myotubularin_fam.
DR   InterPro; IPR029021; Prot-tyrosine_phosphatase-like.
DR   InterPro; IPR016130; Tyr_Pase_AS.
DR   InterPro; IPR000387; Tyr_Pase_dom.
DR   InterPro; IPR000306; Znf_FYVE.
DR   InterPro; IPR017455; Znf_FYVE-rel.
DR   InterPro; IPR011011; Znf_FYVE_PHD.
DR   InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR   PANTHER; PTHR10807; MYOTUBULARIN-RELATED; 1.
DR   PANTHER; PTHR10807:SF64; MYOTUBULARIN-RELATED PROTEIN 4; 1.
DR   Pfam; PF01363; FYVE; 1.
DR   Pfam; PF06602; Myotub-related; 1.
DR   SMART; SM00064; FYVE; 1.
DR   SUPFAM; SSF52799; (Phosphotyrosine protein) phosphatases II; 1.
DR   SUPFAM; SSF57903; FYVE/PHD zinc finger; 1.
DR   SUPFAM; SSF50729; PH domain-like; 1.
DR   PROSITE; PS51339; PPASE_MYOTUBULARIN; 1.
DR   PROSITE; PS00383; TYR_PHOSPHATASE_1; 1.
DR   PROSITE; PS50056; TYR_PHOSPHATASE_2; 1.
DR   PROSITE; PS50178; ZF_FYVE; 1.
DR   Genevisible; Q91XS1; MM.
PE   1: Evidence at protein level;
KW   Alternative splicing; Coiled coil; Cytoplasm; Hydrolase; Membrane;
KW   Metal-binding; Phosphoprotein; Protein phosphatase; Reference proteome;
KW   Zinc; Zinc-finger.
FT   CHAIN           1..1190
FT                   /note="Myotubularin-related protein 4"
FT                   /id="PRO_0000304810"
FT   DOMAIN          153..570
FT                   /note="Myotubularin phosphatase"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00669"
FT   ZN_FING         1109..1169
FT                   /note="FYVE-type"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00091"
FT   REGION          616..694
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          724..749
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          773..848
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COILED          1020..1052
FT                   /evidence="ECO:0000255"
FT   COMPBIAS        616..644
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        785..847
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   ACT_SITE        407
FT                   /note="Phosphocysteine intermediate"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10044"
FT   BINDING         320..323
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250"
FT   BINDING         345..346
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250"
FT   BINDING         407..413
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250"
FT   BINDING         453
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250"
FT   BINDING         1115
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00091"
FT   BINDING         1118
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00091"
FT   BINDING         1131
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00091"
FT   BINDING         1134
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00091"
FT   BINDING         1139
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00091"
FT   BINDING         1142
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00091"
FT   BINDING         1161
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00091"
FT   BINDING         1164
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00091"
FT   MOD_RES         8
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q9NYA4"
FT   MOD_RES         610
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:17242355,
FT                   ECO:0007744|PubMed:21183079"
FT   MOD_RES         629
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q9NYA4"
FT   VAR_SEQ         497..553
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000305"
FT                   /id="VSP_028126"
SQ   SEQUENCE   1190 AA;  132885 MW;  37E6741227E9DBFF CRC64;
     MGEEGPPSLE YIQAKDLFPP KELVKEEENL QVPFTVLQGE GVEFLGRATD ALIAISNYRL
     HIKFKDSVIN VPLRMIDSVE SRDMFQLHIA CKDSKVVRCH FSTFKQCQEW LSRLSRATAR
     PAKPEDLFAF AYHAWCLGLT EEDQHTHLCQ PGEHIRCRQE AELARMGFDL QNVWRVSHIN
     SNYKLCPSYP QKLLVPVWIT DKELENVASF RSWKRIPVVV YRHLRNGAAI ARCSQPEISW
     WGWRNADDEY LVTSIAKACA LDPGTRASGG SLSTGTNDAS EACDTDFDSS LTACSGVEST
     AAPQKLLILD ARSYTAAVAN RAKGGGCECE EYYPNCEVLF MGMANIHAIR NSFQYLRAVC
     SQMPDPSNWL SALESTKWLQ HLSVMLKAAV LVANTVDREG RPVLVHCSDG WDRTPQIVAL
     AKILLDPYYR TLEGFQVLVE SDWLDFGHKF GDRCGHQENA EDQNEQCPVF LQWLDSVHQL
     LKQFPCLFEF NEAFLVKLVQ HTYSCLYGTF LANNPCEREK RNIYKRTCSV WALLRAGNKN
     FHNFLYTPGS DVVLHPVCHV RALHLWTAVY LPASSPCTLG EENMDLYLSP VAQSQEFSGR
     SLDRLPKTRS MDDLLSACDT SSPLTRTSSD PNLNNHSQEV RGSLEPWHSS PEGAETVIDS
     GVGSPQLTVG EMGLPPPLPS SQKEYLSNKP FKGHKSCSLS YKLLNTSVSW EMKSNTSDIK
     VLEETEALAP DPSAQEEQGR TSDGLGKPPE QFLEKEAVSS LCSVSSKCGG ACDFPEPPQD
     PLTGTPQQPH LDSMQISPSR CTPDHSQGSL CNPPSVASQT PEPNTDLLSQ DPPGSTASIS
     HQEQPSSVPD LIYKKEDAGK RGSKNGQLLE NPRFGKMPLE LARKPISQSQ ISEFSFLGSN
     WDSFQGMMTS FPSGETTPRR LLAYGCCSKR PSNKHIRAAG PCLGGQWAQR EGMKSPVCSS
     HSNGHCTGPG GKNNRMWFSS HPKQVSSTKP SLLSCPSPVP PLYLDDDGLP FPTDVIQHRL
     RQIEAGYRQE VEQLRRQVRE LQMRLDIRHC CAPPAEPPMD YEDDFTCLKE SDGSDTEDFG
     SDHSEDCLSE ASWEPVDKKE TEVTRWVPDH MASHCFNCDC EFWLAKRRHH CRNCGNVFCA
     GCCHLKLPIP DQQLYDPVLV CNSCYEHIQV SRARELMSQH LKKPIATASS
//