MTMR2_PONAB
ID MTMR2_PONAB Reviewed; 643 AA.
AC Q5REB9;
DT 16-DEC-2008, integrated into UniProtKB/Swiss-Prot.
DT 21-DEC-2004, sequence version 1.
DT 03-AUG-2022, entry version 92.
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 Pongo abelii (Sumatran orangutan) (Pongo pygmaeus abelii).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Pongo.
OX NCBI_TaxID=9601;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain cortex;
RG The German cDNA consortium;
RL Submitted (NOV-2004) 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}.
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DR EMBL; CR857613; CAH89888.1; -; mRNA.
DR RefSeq; NP_001127209.1; NM_001133737.1.
DR AlphaFoldDB; Q5REB9; -.
DR SMR; Q5REB9; -.
DR STRING; 9601.ENSPPYP00000004337; -.
DR GeneID; 100174264; -.
DR KEGG; pon:100174264; -.
DR CTD; 8898; -.
DR eggNOG; KOG4471; Eukaryota.
DR InParanoid; Q5REB9; -.
DR OrthoDB; 824298at2759; -.
DR Proteomes; UP000001595; Unplaced.
DR GO; GO:0030424; C:axon; IEA:UniProtKB-SubCell.
DR GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR GO; GO:0031901; C:early endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:UniProtKB-SubCell.
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:0006661; P:phosphatidylinositol biosynthetic process; IEA:UniProt.
DR GO; GO:0046856; P:phosphatidylinositol dephosphorylation; ISS:UniProtKB.
DR Gene3D; 2.30.29.30; -; 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; PTHR10807; 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; SSF52799; 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_0000356228"
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..56
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 615..643
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 593..627
FT /evidence="ECO:0000255"
FT COMPBIAS 19..56
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; 73384 MW; 065A2F653D40A71F CRC64;
MEKSSSCESL GSQPAAARPP SVDSLSSAST SHSENSVHTK SASVVSSDSI STSADNFSPD
LRVLRESNKL AEMEEPPLLP GENIKDMAKD VTYICPFTGA VRGTLTVTNY RLYFKSMERD
PPFVLDASLG VINRVEKIGG ASSRGENSYG LETVCKDIRN LRFAHKPEGR TRRSIFENLM
KYAFPVSNNL PLFAFEYKEV FPENGWKLYD PLLEYRRQGI PNESWRITKI NERYELCDTY
PALLVVPANI PDEELKRVAS FRSRGRIPVL SWIHPESQAT ITRCSQPMVG VSGKRSKEDE
KYLQAIMDSN AQSHEIFIFD ARPSVNAVAN KAKGGGYESE DAYQNAELVF LDIHNIHVMR
ESLRKLKEIV YPNIEETHWL SNLESTHWLE HIKLILAGAL RIADKVESGK TSVIVHCSDG
WDRTAQLTSL AMLMLDGYYR TTRGFEVLVE KEWLSFGHRF QLRVGHGDKN HADADRSPVF
LQFIDCVWQM TRQFPTAFEF NEYFLITILD HLYSCLFGTF LCNSEQQRGK ENLPKRTVSL
WSYINSQLED FTNPLYGSYS NHVLYPVASM RHLELWVGYY IRWNPRMKPQ EPIHNRYKEL
LAKRAELQKK VEELQREISN RSTSSSERAS SPAQCVTPVQ TVV
