ID MTMR2_BOVIN Reviewed; 643 AA. AC A6QLT2; DT 16-DEC-2008, integrated into UniProtKB/Swiss-Prot. DT 21-AUG-2007, sequence version 1. DT 24-JAN-2024, entry version 103. DE RecName: Full=Myotubularin-related protein 2; DE AltName: Full=Phosphatidylinositol-3,5-bisphosphate 3-phosphatase; DE EC=3.1.3.95 {ECO:0000250|UniProtKB:Q13614}; DE AltName: Full=Phosphatidylinositol-3-phosphate phosphatase; DE EC=3.1.3.64 {ECO:0000250|UniProtKB:Q13614}; GN Name=MTMR2; OS Bos taurus (Bovine). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae; OC Bovinae; Bos. OX NCBI_TaxID=9913; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC STRAIN=Hereford; TISSUE=Basal ganglia; RG NIH - Mammalian Gene Collection (MGC) project; RL Submitted (JUN-2007) to the EMBL/GenBank/DDBJ databases. 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 (By similarity). CC Binds phosphatidylinositol 4-phosphate, phosphatidylinositol 5- CC phosphate, phosphatidylinositol 3,5-bisphosphate and CC phosphatidylinositol 3,4,5-trisphosphate. Stabilizes SBF2/MTMR13 at the CC membranes. Specifically in peripheral nerves, stabilizes SBF2/MTMR13 CC protein (By similarity). {ECO:0000250|UniProtKB:Q13614, CC ECO:0000250|UniProtKB:Q9Z2D1}. 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:Q13614}; 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:Q13614}; 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:Q13614}; 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:0000250|UniProtKB:Q13614}; CC -!- ACTIVITY REGULATION: Interaction with SBF1/MTMR5 increases phosphatase CC activity. {ECO:0000250|UniProtKB:Q13614}. CC -!- SUBUNIT: Homodimer (via coiled-coil domain). Heterotetramer consisting CC of one MTMR2 dimer and one SBF2/MTMR13 dimer. Heterodimer with CC SBF1/MTMR5. Heterodimer with MTMR12. {ECO:0000250|UniProtKB:Q13614}. CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q13614}. Early CC endosome membrane {ECO:0000250|UniProtKB:Q13614}; Peripheral membrane CC protein {ECO:0000250|UniProtKB:Q13614}. Cytoplasm, perinuclear region CC {ECO:0000250|UniProtKB:Q13614}. Cell projection, axon CC {ECO:0000250|UniProtKB:Q9Z2D1}. Endosome membrane CC {ECO:0000250|UniProtKB:Q9Z2D1}; Peripheral membrane protein CC {ECO:0000250|UniProtKB:Q13614}. Note=Partly associated with membranes CC (By similarity). Localizes to vacuoles in hypo-osmotic conditions (By CC similarity). {ECO:0000250|UniProtKB:Q13614, CC ECO:0000250|UniProtKB:Q9Z2D1}. CC -!- DOMAIN: The coiled-coil domain mediates homodimerization. Also mediates CC interaction with SBF1/MTMR5 (By similarity). By mediating MTMR2 CC homodimerization, indirectly involved in SBF2/MTMR13 and MTMR2 CC heterotetramerization (By similarity). {ECO:0000250|UniProtKB:Q13614, CC ECO:0000250|UniProtKB:Q9Z2D1}. 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:0000250|UniProtKB:Q13614}. CC -!- SIMILARITY: Belongs to the protein-tyrosine phosphatase family. Non- CC receptor class myotubularin subfamily. {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; BC148076; AAI48077.1; -; mRNA. DR RefSeq; NP_001095664.1; NM_001102194.1. DR AlphaFoldDB; A6QLT2; -. DR SMR; A6QLT2; -. DR STRING; 9913.ENSBTAP00000073339; -. DR PaxDb; 9913-ENSBTAP00000022028; -. DR Ensembl; ENSBTAT00000071612.1; ENSBTAP00000073339.1; ENSBTAG00000016557.6. DR GeneID; 536810; -. DR KEGG; bta:536810; -. DR CTD; 8898; -. DR VEuPathDB; HostDB:ENSBTAG00000016557; -. DR VGNC; VGNC:31741; MTMR2. DR eggNOG; KOG4471; Eukaryota. DR GeneTree; ENSGT00940000153669; -. DR HOGENOM; CLU_001839_4_1_1; -. DR InParanoid; A6QLT2; -. DR OMA; WRATKIN; -. DR OrthoDB; 5474662at2759; -. DR Reactome; R-BTA-1483248; Synthesis of PIPs at the ER membrane. DR Reactome; R-BTA-1660516; Synthesis of PIPs at the early endosome membrane. DR Reactome; R-BTA-1660517; Synthesis of PIPs at the late endosome membrane. DR Proteomes; UP000009136; Chromosome 15. DR Bgee; ENSBTAG00000016557; Expressed in spermatocyte and 108 other cell types or tissues. DR ExpressionAtlas; A6QLT2; baseline and differential. DR GO; GO:0030424; C:axon; IEA:UniProtKB-SubCell. DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central. DR GO; GO:0005829; C:cytosol; ISS:UniProtKB. DR GO; GO:0031901; C:early endosome membrane; IEA:UniProtKB-SubCell. DR GO; GO:0016020; C:membrane; IBA:GO_Central. DR GO; GO:0005634; C:nucleus; IEA:Ensembl. DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:UniProtKB-SubCell. 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; ISS:UniProtKB. DR GO; GO:0004438; F:phosphatidylinositol-3-phosphate phosphatase activity; ISS:UniProtKB. DR GO; GO:0032288; P:myelin assembly; IEA:Ensembl. DR GO; GO:0031642; P:negative regulation of myelination; IEA:Ensembl. DR GO; GO:0048666; P:neuron development; IEA:Ensembl. DR GO; GO:0046856; P:phosphatidylinositol dephosphorylation; ISS:UniProtKB. DR GO; GO:0060304; P:regulation of phosphatidylinositol dephosphorylation; IEA:Ensembl. DR CDD; cd14590; PTP-MTMR2; 1. DR Gene3D; 2.30.29.30; Pleckstrin-homology domain (PH domain)/Phosphotyrosine-binding domain (PTB); 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; MYOTUBULARIN-RELATED; 1. DR PANTHER; PTHR10807:SF42; MYOTUBULARIN-RELATED PROTEIN 2; 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; (Phosphotyrosine protein) phosphatases II; 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. PE 2: Evidence at transcript level; KW Cell projection; Coiled coil; Cytoplasm; Endosome; Hydrolase; KW Lipid metabolism; Membrane; Phosphoprotein; Reference proteome. FT CHAIN 1..643 FT /note="Myotubularin-related protein 2" FT /id="PRO_0000356227" 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..54 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 614..643 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COILED 593..627 FT /evidence="ECO:0000255" FT COMPBIAS 19..54 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:0000255|PROSITE-ProRule:PRU10044" FT BINDING 330..333 FT /ligand="substrate" FT /evidence="ECO:0000250|UniProtKB:Q13614" FT BINDING 355..356 FT /ligand="substrate" FT /evidence="ECO:0000250|UniProtKB:Q13614" FT BINDING 417..423 FT /ligand="substrate" FT /evidence="ECO:0000250|UniProtKB:Q13614" FT BINDING 463 FT /ligand="substrate" FT /evidence="ECO:0000250|UniProtKB:Q13614" 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:0000250|UniProtKB:Q13614" SQ SEQUENCE 643 AA; 73348 MW; 0BF63C1A07DA9895 CRC64; MEKSSSCESL GSQPAVARPP SVDSLSSAST SHSENSVHTK SASVVSSDSI STSAENFSPD LRVLRESNKL AEMEEPPLLP GENIKDMAKD VTYICPFTGA VRGTLTVTNY RLYFKSMERD PPFVLDASLG VISRVEKIGG ASSRGENSYG LETVCKDIRN LRFAHKPEGR TRRSIFENLM KYAFPVSNNL SLFAFEYKEV FPENGWKLYD SLSEYRRQGI PNESWRITKV NERYELCDTY PALLVVPANI PDEELKRVAS FRSRGRIPVL SWIHPESQAT ITRCSQPMVG VSGKRSKEDE KYLQAIMDSN AQSHKIFIFD ARPSVNAVAN KAKGGGYESE DAYQNAELVF LDIHNIHVMR ESLRKLKEIV YPNIEETHWL SNLESTHWLE HIKLILAGAL RIADRVESGK TSVVVHCSDG WDRTAQLTSL AMLMLDGYYR TIRGFEVLVE KEWLSFGHRF QLRVGHGDKN HADADRSPVF LQFIDCVWQM TRQFPTAFEF NEYFLITILD HLYSCLFGTF LCNSEQQRGK ENLPRRTVSL WSYINSQLED FTNPLYGSYS NHVLYPVASM RHLELWVGYY VRWNPRMKPQ EPIHNRYKEL LAKRAELQKK VEELQREISN RSTSSSERAG SPAQCVTPVQ TVV //