MTMR6_CAEEL
ID MTMR6_CAEEL Reviewed; 676 AA.
AC G5ED68; Q69Z15;
DT 11-MAY-2016, integrated into UniProtKB/Swiss-Prot.
DT 14-DEC-2011, sequence version 1.
DT 03-AUG-2022, entry version 81.
DE RecName: Full=Myotubularin-related protein 6 {ECO:0000305};
DE AltName: Full=Phosphatidylinositol-3-phosphate phosphatase {ECO:0000305};
DE EC=3.1.3.64 {ECO:0000305|PubMed:12788949};
GN Name=mtm-6 {ECO:0000312|WormBase:F53A2.8a};
GN Synonyms=cup-6 {ECO:0000312|WormBase:F53A2.8a};
GN ORFNames=F53A2.8 {ECO:0000312|WormBase:F53A2.8a};
OS Caenorhabditis elegans.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6239 {ECO:0000312|Proteomes:UP000001940};
RN [1] {ECO:0000312|EMBL:AAP79302.1}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM A), FUNCTION, INTERACTION WITH MTM-9,
RP SUBCELLULAR LOCATION, DOMAIN, AND MUTAGENESIS OF CYS-335.
RX PubMed=14565969; DOI=10.1091/mbc.e03-08-0605;
RA Dang H., Li Z., Skolnik E.Y., Fares H.;
RT "Disease-related myotubularins function in endocytic traffic in
RT Caenorhabditis elegans.";
RL Mol. Biol. Cell 15:189-196(2004).
RN [2] {ECO:0000312|Proteomes:UP000001940}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Bristol N2 {ECO:0000312|Proteomes:UP000001940};
RX PubMed=9851916; DOI=10.1126/science.282.5396.2012;
RG The C. elegans sequencing consortium;
RT "Genome sequence of the nematode C. elegans: a platform for investigating
RT biology.";
RL Science 282:2012-2018(1998).
RN [3] {ECO:0000305}
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, DOMAIN, AND DISRUPTION
RP PHENOTYPE.
RX PubMed=12788949; DOI=10.1074/jbc.m303259200;
RA Xue Y., Fares H., Grant B., Li Z., Rose A.M., Clark S.G., Skolnik E.Y.;
RT "Genetic analysis of the myotubularin family of phosphatases in
RT Caenorhabditis elegans.";
RL J. Biol. Chem. 278:34380-34386(2003).
RN [4] {ECO:0000305}
RP FUNCTION, AND MUTAGENESIS OF CYS-335 AND ASP-340.
RX PubMed=21076391; DOI=10.1038/emboj.2010.278;
RA Silhankova M., Port F., Harterink M., Basler K., Korswagen H.C.;
RT "Wnt signalling requires MTM-6 and MTM-9 myotubularin lipid-phosphatase
RT function in Wnt-producing cells.";
RL EMBO J. 29:4094-4105(2010).
RN [5] {ECO:0000305}
RP FUNCTION, TISSUE SPECIFICITY, AND MUTAGENESIS OF CYS-335.
RX PubMed=25479419; DOI=10.1371/journal.pone.0114501;
RA Ericson V.R., Spilker K.A., Tugizova M.S., Shen K.;
RT "MTM-6, a phosphoinositide phosphatase, is required to promote synapse
RT formation in Caenorhabditis elegans.";
RL PLoS ONE 9:E114501-E114501(2014).
CC -!- FUNCTION: May dephosphorylate phosphatidylinositol-3-phosphate (PI3P)
CC (PubMed:12788949, PubMed:14565969). In association with mtm-9, plays a
CC role in endosome trafficking probably by regulating
CC phosphatidylinositol-3-phosphate levels (PubMed:14565969,
CC PubMed:21076391). Regulates fluid phase endocytosis in coelomocytes
CC (PubMed:14565969). Controls the endosomal localization of sorting nexin
CC snx-3 and the levels of sorting receptor mig-14 (PubMed:21076391). By
CC regulating the retrograde transport of mig-14, may be involved in the
CC secretion of Wnt ligands such as egl-20 (PubMed:21076391). Regulates
CC posterior migration of QL neuroblast descendants and the anterior
CC migration of QR neuroblast descendants and HSN neurons during larval
CC development (PubMed:21076391). Involved in the formation of correct
CC synapse number in DA9 motor neurons probably in part by regulating the
CC secretion of Wnt ligand egl-20 (PubMed:25479419).
CC {ECO:0000269|PubMed:12788949, ECO:0000269|PubMed:14565969,
CC ECO:0000269|PubMed:21076391, ECO:0000269|PubMed:25479419}.
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:0000305|PubMed:12788949};
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:Q9Y217};
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:Q9Y217};
CC -!- SUBUNIT: Heterodimer with mtm-9. {ECO:0000269|PubMed:14565969}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:14565969}. Membrane
CC {ECO:0000269|PubMed:14565969}; Peripheral membrane protein
CC {ECO:0000269|PubMed:14565969}. Apical cell membrane
CC {ECO:0000269|PubMed:12788949}; Peripheral membrane protein
CC {ECO:0000269|PubMed:12788949}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=a {ECO:0000312|WormBase:F53A2.8a};
CC IsoId=G5ED68-1; Sequence=Displayed;
CC Name=c {ECO:0000312|WormBase:F53A2.8c};
CC IsoId=G5ED68-2; Sequence=VSP_058287;
CC -!- TISSUE SPECIFICITY: Expressed in intestinal cells (PubMed:12788949).
CC Expressed in head neurons, pre-anal ganglion, hypodermal cells, anal
CC depressor muscle and non-neuronal cells in the tail (PubMed:25479419).
CC {ECO:0000269|PubMed:12788949, ECO:0000269|PubMed:25479419}.
CC -!- DOMAIN: The FYVE domain appears to be dispensable for membrane
CC targeting and activity but may be important to increase avidity to
CC membrane. {ECO:0000269|PubMed:12788949, ECO:0000269|PubMed:14565969}.
CC -!- DISRUPTION PHENOTYPE: RNAi-mediated knockdown causes an increase in
CC phosphatidylinositol-3-phosphate at the apical plasma membrane of
CC intestinal cells. {ECO:0000269|PubMed:12788949}.
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; AY313177; AAP79302.1; -; mRNA.
DR EMBL; BX284603; CAB04456.1; -; Genomic_DNA.
DR EMBL; BX284603; CAH10812.1; -; Genomic_DNA.
DR PIR; T22532; T22532.
DR RefSeq; NP_001022602.1; NM_001027431.3. [G5ED68-2]
DR RefSeq; NP_499753.1; NM_067352.4. [G5ED68-1]
DR AlphaFoldDB; G5ED68; -.
DR SMR; G5ED68; -.
DR ComplexPortal; CPX-4024; MTM6-MTM9 myotubularin lipid phosphatase complex.
DR STRING; 6239.F53A2.8b.2; -.
DR EPD; G5ED68; -.
DR PaxDb; G5ED68; -.
DR PeptideAtlas; G5ED68; -.
DR EnsemblMetazoa; F53A2.8a.1; F53A2.8a.1; WBGene00003478. [G5ED68-1]
DR EnsemblMetazoa; F53A2.8c.1; F53A2.8c.1; WBGene00003478. [G5ED68-2]
DR GeneID; 176757; -.
DR KEGG; cel:CELE_F53A2.8; -.
DR CTD; 176757; -.
DR WormBase; F53A2.8a; CE16100; WBGene00003478; mtm-6. [G5ED68-1]
DR WormBase; F53A2.8c; CE37116; WBGene00003478; mtm-6. [G5ED68-2]
DR eggNOG; KOG1089; Eukaryota.
DR GeneTree; ENSGT00940000172348; -.
DR Reactome; R-CEL-1660499; Synthesis of PIPs at the plasma membrane.
DR Reactome; R-CEL-1660517; Synthesis of PIPs at the late endosome membrane.
DR PRO; PR:G5ED68; -.
DR Proteomes; UP000001940; Chromosome III.
DR Bgee; WBGene00003478; Expressed in germ line (C elegans) and 4 other tissues.
DR ExpressionAtlas; G5ED68; baseline and differential.
DR GO; GO:0016324; C:apical plasma membrane; IDA:WormBase.
DR GO; GO:0005829; C:cytosol; IDA:WormBase.
DR GO; GO:1904144; C:phosphatidylinositol phosphate phosphatase complex; IC:ComplexPortal.
DR GO; GO:0005886; C:plasma membrane; IDA:WormBase.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0019902; F:phosphatase binding; IPI:WormBase.
DR GO; GO:0004438; F:phosphatidylinositol-3-phosphatase activity; IEA:UniProtKB-EC.
DR GO; GO:0006897; P:endocytosis; IMP:WormBase.
DR GO; GO:0002119; P:nematode larval development; IGI:WormBase.
DR GO; GO:0046856; P:phosphatidylinositol dephosphorylation; IC:ComplexPortal.
DR GO; GO:0046488; P:phosphatidylinositol metabolic process; IMP:WormBase.
DR GO; GO:0030334; P:regulation of cell migration; IMP:WormBase.
DR GO; GO:0030111; P:regulation of Wnt signaling pathway; IMP:WormBase.
DR GO; GO:0007416; P:synapse assembly; IC:ComplexPortal.
DR Gene3D; 2.30.29.30; -; 1.
DR Gene3D; 3.30.40.10; -; 1.
DR InterPro; IPR030581; MTMR6.
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; IPR000306; Znf_FYVE.
DR InterPro; IPR011011; Znf_FYVE_PHD.
DR InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR PANTHER; PTHR10807; PTHR10807; 1.
DR PANTHER; PTHR10807:SF34; PTHR10807:SF34; 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.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell membrane; Cytoplasm; Endocytosis; Hydrolase;
KW Lipid metabolism; Membrane; Metal-binding; Reference proteome; Zinc;
KW Zinc-finger.
FT CHAIN 1..676
FT /note="Myotubularin-related protein 6"
FT /evidence="ECO:0000305"
FT /id="PRO_0000436176"
FT DOMAIN 125..501
FT /note="Myotubularin phosphatase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00669"
FT ZN_FING 618..675
FT /note="FYVE-type"
FT /evidence="ECO:0000255"
FT ACT_SITE 335
FT /note="Phosphocysteine intermediate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10044"
FT BINDING 249..252
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q13614"
FT BINDING 274..275
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q13614"
FT BINDING 335..341
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q13614"
FT BINDING 381
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q13614"
FT VAR_SEQ 104..105
FT /note="Missing (in isoform c)"
FT /evidence="ECO:0000305"
FT /id="VSP_058287"
FT MUTAGEN 335
FT /note="C->S: Inhibits fluid uptake endocytosis in
FT coelomocytes. Localizes in aggregates at the plasma
FT membrane and/or to vesicles close to the plasma membrane.
FT Abnormal anterior migration of QL neuroblast descendants.
FT Reduction in the number of synapses formed in DA9 neurons."
FT /evidence="ECO:0000269|PubMed:14565969,
FT ECO:0000269|PubMed:21076391, ECO:0000269|PubMed:25479419"
FT MUTAGEN 340
FT /note="D->N: In ar515; in 25 percent of mutants, abnormal
FT anterior migration of QL neuroblast descendants."
FT /evidence="ECO:0000269|PubMed:21076391"
SQ SEQUENCE 676 AA; 77309 MW; 527494D1443264E9 CRC64;
MRFEDIGISK VDKVCLVDRL GCQENLVGTV HVTTTHIIFR AENGSKELWL ATGLISSVEK
GTLTAAGCML VIRCKHFQVI TLLISRDKSC QDLYETLQRA AKPVSVNVTE LLAFENREPV
EDVRGWRRLD WNSEMTRQGI TKSQWTESNI NEGYTICDTY PNKLWFPTAA STSVLLGSCK
FRSRGRLPVL TYFHQQTEAA LCRCAQPLTG FSARCVEDEK LMELVGKANT NSDNLFLVDT
RPRVNAMVNK VQGKGFEDER NYSNMRFHFF DIENIHVMRA SQARLLDAVT KCRDVTEYWK
TLEASGWLKH VRSVVECSLF LAESISRGTS CVVHCSDGWD RTSQVVALCQ LLLDPYYRTI
HGFQVLIEKD WLGFGHKFDD RCGHVGALND EAGKEVSPIF TQWLDCIWQI MQQKPRAFQF
NERYLIEMHE HVYSCQFGTF IGNCDKDRRD LNLSKRTKSL WTWMDARHDD YMNPFYSPTA
HVALLDLDTR AARFTVWTAM YNRFDNGLQP RERLEDLTMA AMEHVGVLES HVAQLRTRLA
ELKTQQNQQI TSTNTPTNMV DSGMSSATDD LKNLSLSHPL DPLSSTLPIL ERATSQESGV
MDSSLYYPDE ALTKYSLKWQ PLRGADRCSN PACRGEFSST IERRIHCHLC GMIFCRRCLK
VSADERERVC DKCKTD
