MTMR3_MOUSE
ID MTMR3_MOUSE Reviewed; 1196 AA.
AC Q8K296; Q5NCA4;
DT 19-JUL-2003, integrated into UniProtKB/Swiss-Prot.
DT 29-MAY-2007, sequence version 2.
DT 03-AUG-2022, entry version 143.
DE RecName: Full=Myotubularin-related protein 3;
DE EC=3.1.3.48;
DE AltName: Full=Phosphatidylinositol-3,5-bisphosphate 3-phosphatase;
DE EC=3.1.3.95 {ECO:0000250|UniProtKB:Q13615};
DE AltName: Full=Phosphatidylinositol-3-phosphate phosphatase;
DE EC=3.1.3.64 {ECO:0000250|UniProtKB:Q13615};
GN Name=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 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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
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 [3]
RP IDENTIFICATION BY 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 [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-8; SER-613 AND SER-1062, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
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: Phosphatase that acts on lipids with a phosphoinositol
CC headgroup. Has phosphatase activity towards phosphatidylinositol 3-
CC phosphate and phosphatidylinositol 3,5-bisphosphate. May also
CC dephosphorylate proteins phosphorylated on Ser, Thr, and Tyr residues
CC (By similarity). {ECO:0000250|UniProtKB:Q13615}.
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;
CC Evidence={ECO:0000250|UniProtKB:Q13615, ECO:0000255|PROSITE-
CC ProRule:PRU10044};
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:0000250|UniProtKB:Q13615};
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:0000250|UniProtKB:Q13615};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1,2-dihexadecanoyl-sn-glycero-3-phospho-(1D-myo-inositol-3-
CC phosphate) + H2O = 1,2-dihexadecanoyl-sn-glycero-3-phospho-(1D-myo-
CC inositol) + phosphate; Xref=Rhea:RHEA:45640, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:72835, ChEBI:CHEBI:78995;
CC Evidence={ECO:0000250|UniProtKB:Q13615};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1,2-dihexadecanoyl-sn-glycero-3-phospho-(1D-myo-inositol-3,5-
CC phosphate) + H2O = 1,2-dihexadecanoyl-sn-glycero-3-phospho-(1D-myo-
CC inositol-5-phosphate) + phosphate; Xref=Rhea:RHEA:45636,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:43474, ChEBI:CHEBI:78994,
CC ChEBI:CHEBI:84968; Evidence={ECO:0000250|UniProtKB:Q13615};
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:0000250|UniProtKB:Q13615};
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q13615}.
CC Membrane {ECO:0000250|UniProtKB:Q13615}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:Q13615}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q8K296-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8K296-2; Sequence=VSP_026027;
CC -!- SIMILARITY: Belongs to the protein-tyrosine phosphatase family. Non-
CC receptor class myotubularin subfamily. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=CAI35184.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
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; AL645910; CAI35184.1; ALT_SEQ; Genomic_DNA.
DR EMBL; BC032166; AAH32166.1; -; mRNA.
DR RefSeq; XP_006514910.1; XM_006514847.3.
DR AlphaFoldDB; Q8K296; -.
DR SMR; Q8K296; -.
DR BioGRID; 216649; 7.
DR IntAct; Q8K296; 1.
DR MINT; Q8K296; -.
DR STRING; 10090.ENSMUSP00000122422; -.
DR iPTMnet; Q8K296; -.
DR PhosphoSitePlus; Q8K296; -.
DR EPD; Q8K296; -.
DR jPOST; Q8K296; -.
DR MaxQB; Q8K296; -.
DR PaxDb; Q8K296; -.
DR PRIDE; Q8K296; -.
DR ProteomicsDB; 286075; -. [Q8K296-1]
DR ProteomicsDB; 286076; -. [Q8K296-2]
DR DNASU; 74302; -.
DR GeneID; 74302; -.
DR UCSC; uc007huy.1; mouse. [Q8K296-1]
DR CTD; 8897; -.
DR MGI; MGI:1921552; Mtmr3.
DR eggNOG; KOG4471; Eukaryota.
DR InParanoid; Q8K296; -.
DR OrthoDB; 824298at2759; -.
DR PhylomeDB; Q8K296; -.
DR TreeFam; TF315197; -.
DR Reactome; R-MMU-1632852; Macroautophagy.
DR Reactome; R-MMU-1660499; Synthesis of PIPs at the plasma membrane.
DR BioGRID-ORCS; 74302; 6 hits in 76 CRISPR screens.
DR ChiTaRS; Mtmr3; mouse.
DR PRO; PR:Q8K296; -.
DR Proteomes; UP000000589; Unplaced.
DR RNAct; Q8K296; protein.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0019898; C:extrinsic component of membrane; ISS:UniProtKB.
DR GO; GO:0016020; C:membrane; ISO:MGI.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0052629; F:phosphatidylinositol-3,5-bisphosphate 3-phosphatase activity; ISS:UniProtKB.
DR GO; GO:0004438; F:phosphatidylinositol-3-phosphatase activity; ISS:UniProtKB.
DR GO; GO:0019903; F:protein phosphatase binding; ISO:MGI.
DR GO; GO:0004722; F:protein serine/threonine phosphatase activity; ISO:MGI.
DR GO; GO:0004725; F:protein tyrosine phosphatase activity; ISO:MGI.
DR GO; GO:0008138; F:protein tyrosine/serine/threonine phosphatase activity; ISO:MGI.
DR GO; GO:0042149; P:cellular response to glucose starvation; ISO:MGI.
DR GO; GO:1904562; P:phosphatidylinositol 5-phosphate metabolic process; ISO:MGI.
DR GO; GO:0046856; P:phosphatidylinositol dephosphorylation; ISS:UniProtKB.
DR GO; GO:0006470; P:protein dephosphorylation; ISO:MGI.
DR GO; GO:2000785; P:regulation of autophagosome assembly; ISO:MGI.
DR GO; GO:0010506; P:regulation of autophagy; IBA:GO_Central.
DR GO; GO:0060304; P:regulation of phosphatidylinositol dephosphorylation; ISO:MGI.
DR CDD; cd13341; PH-GRAM_MTMR3; 1.
DR CDD; cd14586; PTP-MTMR3; 1.
DR Gene3D; 3.30.40.10; -; 1.
DR Gene3D; 3.90.190.10; -; 1.
DR InterPro; IPR046352; MTMR3_Pase_dom.
DR InterPro; IPR035888; MTMR3_PH-GRAM.
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; IPR003595; Tyr_Pase_cat.
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; PTHR10807; 1.
DR Pfam; PF01363; FYVE; 1.
DR Pfam; PF06602; Myotub-related; 1.
DR SMART; SM00064; FYVE; 1.
DR SMART; SM00404; PTPc_motif; 1.
DR SUPFAM; SSF52799; SSF52799; 1.
DR SUPFAM; SSF57903; SSF57903; 1.
DR PROSITE; PS51339; PPASE_MYOTUBULARIN; 1.
DR PROSITE; PS00383; TYR_PHOSPHATASE_1; 1.
DR PROSITE; PS50178; ZF_FYVE; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Coiled coil; Cytoplasm; Hydrolase; Lipid metabolism;
KW Membrane; Metal-binding; Phosphoprotein; Protein phosphatase;
KW Reference proteome; Zinc; Zinc-finger.
FT CHAIN 1..1196
FT /note="Myotubularin-related protein 3"
FT /id="PRO_0000094937"
FT DOMAIN 155..576
FT /note="Myotubularin phosphatase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00669"
FT ZN_FING 1117..1177
FT /note="FYVE-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00091"
FT REGION 587..612
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 697..719
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 855..900
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 993..1019
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 1027..1060
FT /evidence="ECO:0000255"
FT COMPBIAS 993..1008
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 413
FT /note="Phosphocysteine intermediate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10044"
FT BINDING 326..329
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 351..352
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 413..419
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 459
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 1123
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00091"
FT BINDING 1126
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00091"
FT BINDING 1139
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00091"
FT BINDING 1142
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00091"
FT BINDING 1147
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00091"
FT BINDING 1150
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00091"
FT BINDING 1169
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00091"
FT BINDING 1172
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:0007744|PubMed:21183079"
FT MOD_RES 613
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 633
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q13615"
FT MOD_RES 647
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q13615"
FT MOD_RES 651
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q13615"
FT MOD_RES 907
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q13615"
FT MOD_RES 1062
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT VAR_SEQ 1076..1196
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_026027"
FT CONFLICT 782
FT /note="R -> S (in Ref. 2; AAH32166)"
FT /evidence="ECO:0000305"
FT CONFLICT 1074
FT /note="T -> V (in Ref. 2; AAH32166)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1196 AA; 133840 MW; 409D23ABBEABAC7D CRC64;
MDEEMRHSLE CIQANQIFPR KQLIREDENL QVPFLELHGE STEYVGRAEE AIIALSNYRL
HIKFKESLVN VPLQLIESVE CRDIFQLHLT CKDCKVIRCQ FPTFEQCQDW LKRLNNAIRP
PGKIEDLFSF AYHAWCMEVY ASEKEQHGDL CRPGEHVTSR FKNEVERMGF DMNNAWRISN
INEKYKLCGS YPQELIVPAW ITDKELESVA GFRSWKRIPA VIYRHQSNGA VIARCGQPEV
SWWGWRNADD EHLVQSVARA CASDSQSSIS KVSTRNSCRD FPNAGDLSDV EFDSSLSNTS
GAESLALQPQ KLLILDARSY AAAVANRAKG GGCECPEYYP NCEVVFMGMA NIHSIRRSFQ
SLRLLCTQMP DPGNWLSALE STKWLHHLSV LLKSALLVVH AVDRDQRPVL VHCSDGWDRT
PQIVALAKLL LDPYYRTIEG FQVLVEMEWL DFGHKFADRC GHGEDSDDLN ERCPVFLQWL
DCVHQLQRQF PCSFEFNEAF LVKLVQHTYS CLFGTFLCNN AKERGEKQTQ ERTCSVWSLL
RAGNKAFKNL LYSSQSEAVL YPVCHVRNLM LWSAVYLPCP SPSTPTDDSC APYPVPGTSP
DEPPLSRLPK TRSFDNLTTT CENMVPLASR RSSDPSLNEK WQEHGRSLEL SSFASAGEEV
PAMDSLRKPS RLLGGAELSV AAGVAEGQME NILQEATKEE SGVEEPTHRG HTEVPEVKEE
APLAKESSMA AEGPVVLYQE PQLDDATLRS HQGPSLSLFS QGIPEHQDGH NVLSSSLQAP
LRGEDSQEVP VEQPQVENIA EDRENVAPAV PVDAKVGLGI SQSSSLLPSQ VPFETRGPHI
NNSVHMLLED KVKSESGPQL HHRPCPASSG RFSGKDMLPV APEPRSAERP QWDSVLHRTS
SPGNTLSLLQ APCALPLDKC RQGIVCNGAL ETENKASEQP AGFDTLQKYP TPNGHCANWE
AGRSKDSLSH QLSATSCSSA HLYSRNLHHK WLNSHSGRPS TTSSPDQPSR SHLDDDGMPV
YTDTIQQRLR QIESGHQQEV ETLKKQVQEL KSRLESQYLT SSLRFNGDFG DEVTSIPDSE
SNLDQNCVSR CSTEIFSEAS WEQVDKQDTE MTRWLPDHLA AHCYACDSAF WLASRKHHCR
NCGNVFCSSC CNQKVPVPSQ QLFEPSRVCK SCYSSLHPTS SSIDLELDKP IAATSN
