MTMR1_CAEEL
ID MTMR1_CAEEL Reviewed; 588 AA.
AC Q9N589;
DT 11-MAY-2016, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2002, sequence version 2.
DT 03-AUG-2022, entry version 137.
DE RecName: Full=Myotubularin-related protein 1 {ECO:0000305};
DE AltName: Full=Phosphatidylinositol-3,5-bisphosphate 3-phosphatase {ECO:0000303|PubMed:21490059};
DE EC=3.1.3.95 {ECO:0000269|PubMed:21490059};
DE AltName: Full=Phosphatidylinositol-3-phosphate phosphatase {ECO:0000303|PubMed:21490059};
DE EC=3.1.3.64 {ECO:0000269|PubMed:21490059};
GN Name=mtm-1 {ECO:0000312|WormBase:Y110A7A.5};
GN ORFNames=Y110A7A.5 {ECO:0000312|WormBase:Y110A7A.5};
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|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 [2] {ECO:0000305}
RP TISSUE SPECIFICITY.
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 [3] {ECO:0000305}
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, DOMAIN, AND DISRUPTION
RP PHENOTYPE.
RX PubMed=19816564; DOI=10.1371/journal.pgen.1000679;
RA Zou W., Lu Q., Zhao D., Li W., Mapes J., Xie Y., Wang X.;
RT "Caenorhabditis elegans myotubularin MTM-1 negatively regulates the
RT engulfment of apoptotic cells.";
RL PLoS Genet. 5:E1000679-E1000679(2009).
RN [4] {ECO:0000305}
RP FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, TISSUE SPECIFICITY,
RP DISRUPTION PHENOTYPE, AND MUTAGENESIS OF GLY-106.
RX PubMed=21490059; DOI=10.1242/dev.060012;
RA Neukomm L.J., Nicot A.S., Kinchen J.M., Almendinger J., Pinto S.M.,
RA Zeng S., Doukoumetzidis K., Tronchere H., Payrastre B., Laporte J.F.,
RA Hengartner M.O.;
RT "The phosphoinositide phosphatase MTM-1 regulates apoptotic cell corpse
RT clearance through CED-5-CED-12 in C. elegans.";
RL Development 138:2003-2014(2011).
CC -!- FUNCTION: Dephosphorylates phosphatidylinositol 3-phosphate (PI3P) and
CC phosphatidylinositol 3,5-bisphosphate (PI(3,5)P2). Negatively regulates
CC accumulation of PI3P on intracellular vesicles (PubMed:19816564,
CC PubMed:21490059). Negatively regulates phagocytosis of apoptotic cells
CC probably by limiting the recruitment and/or the activation of ced-5,
CC ced-2 and ced-12 complex (PubMed:19816564, PubMed:21490059). In
CC addition, may positively regulate phagosome maturation by promoting
CC recycling of apoptotic receptor ced-1 back to the plasma membrane
CC (PubMed:21490059). Essential for embryonic and larval development
CC (PubMed:19816564). May promote migration of distal tip cells
CC (PubMed:19816564). {ECO:0000269|PubMed:19816564,
CC ECO:0000269|PubMed:21490059}.
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:0000269|PubMed:21490059};
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:0000269|PubMed:21490059};
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:Q13613};
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:19816564};
CC Peripheral membrane protein {ECO:0000269|PubMed:19816564}. Cell
CC projection, phagocytic cup {ECO:0000269|PubMed:19816564}. Apical cell
CC membrane {ECO:0000269|PubMed:21490059}; Peripheral membrane protein
CC {ECO:0000269|PubMed:21490059}. Cytoplasmic granule membrane
CC {ECO:0000269|PubMed:21490059}. Note=Transiently co-localizes with
CC phagocytic receptor ced-1 at the pseudopods during phagocytosis of
CC apoptotic cells. {ECO:0000269|PubMed:19816564}.
CC -!- TISSUE SPECIFICITY: Expressed in embryo, larva and in adults
CC (PubMed:19816564, PubMed:21490059). Expressed in a few head and tail
CC neurons (PubMed:12788949). Expressed in hypodermis, body wall and
CC pharyngeal muscles, sheath cells, vulva, distal tip cells and
CC coelomocytes (PubMed:19816564, PubMed:21490059).
CC {ECO:0000269|PubMed:12788949, ECO:0000269|PubMed:19816564,
CC ECO:0000269|PubMed:21490059}.
CC -!- DOMAIN: The GRAM domain is required for localization to the plasma
CC membrane. {ECO:0000269|PubMed:19816564}.
CC -!- DOMAIN: The myotubularin phosphatase domain is required for
CC localization to the plasma membrane. {ECO:0000269|PubMed:19816564}.
CC -!- DISRUPTION PHENOTYPE: RNAi-mediated knockdown causes an increase in
CC PI3P levels in intracellular vesicles. Also causes an increase in
CC germline cell corpse engulfment, although corpses fail to be cleared.
CC RNAi-mediated knockdown in ced-1, ced-6, ced-2, ced-10 or ced-7 mutant
CC background partially restores cell corpses engulfment.
CC {ECO:0000269|PubMed:19816564, ECO:0000269|PubMed:21490059}.
CC -!- SIMILARITY: Belongs to the protein-tyrosine phosphatase family. Non-
CC receptor class myotubularin subfamily. {ECO:0000305}.
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DR EMBL; BX284601; CCD66194.1; -; Genomic_DNA.
DR RefSeq; NP_491531.2; NM_059130.4.
DR AlphaFoldDB; Q9N589; -.
DR SMR; Q9N589; -.
DR STRING; 6239.Y110A7A.5; -.
DR EPD; Q9N589; -.
DR PaxDb; Q9N589; -.
DR PeptideAtlas; Q9N589; -.
DR EnsemblMetazoa; Y110A7A.5.1; Y110A7A.5.1; WBGene00003475.
DR GeneID; 172148; -.
DR KEGG; cel:CELE_Y110A7A.5; -.
DR UCSC; Y110A7A.5; c. elegans.
DR CTD; 172148; -.
DR WormBase; Y110A7A.5; CE30707; WBGene00003475; mtm-1.
DR eggNOG; KOG4471; Eukaryota.
DR GeneTree; ENSGT00940000167774; -.
DR HOGENOM; CLU_001839_4_1_1; -.
DR InParanoid; Q9N589; -.
DR OMA; ESYAICD; -.
DR OrthoDB; 824298at2759; -.
DR PhylomeDB; Q9N589; -.
DR Reactome; R-CEL-1483248; Synthesis of PIPs at the ER membrane.
DR Reactome; R-CEL-1660499; Synthesis of PIPs at the plasma membrane.
DR Reactome; R-CEL-1660516; Synthesis of PIPs at the early endosome membrane.
DR Reactome; R-CEL-1660517; Synthesis of PIPs at the late endosome membrane.
DR Reactome; R-CEL-9035034; RHOF GTPase cycle.
DR PRO; PR:Q9N589; -.
DR Proteomes; UP000001940; Chromosome I.
DR Bgee; WBGene00003475; Expressed in germ line (C elegans) and 4 other tissues.
DR GO; GO:0045179; C:apical cortex; IDA:WormBase.
DR GO; GO:0016324; C:apical plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005938; C:cell cortex; IDA:WormBase.
DR GO; GO:0042995; C:cell projection; IEA:UniProtKB-KW.
DR GO; GO:0005829; C:cytosol; IDA:WormBase.
DR GO; GO:0001891; C:phagocytic cup; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; IDA:WormBase.
DR GO; GO:0052629; F:phosphatidylinositol-3,5-bisphosphate 3-phosphatase activity; IDA:WormBase.
DR GO; GO:0004438; F:phosphatidylinositol-3-phosphatase activity; IDA:WormBase.
DR GO; GO:0005546; F:phosphatidylinositol-4,5-bisphosphate binding; IDA:WormBase.
DR GO; GO:0045806; P:negative regulation of endocytosis; IGI:WormBase.
DR GO; GO:1901075; P:negative regulation of engulfment of apoptotic cell; IGI:WormBase.
DR GO; GO:0006909; P:phagocytosis; IEA:UniProtKB-KW.
DR GO; GO:0046856; P:phosphatidylinositol dephosphorylation; IBA:GO_Central.
DR GO; GO:0046839; P:phospholipid dephosphorylation; IDA:WormBase.
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 PANTHER; PTHR10807; PTHR10807; 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.
PE 1: Evidence at protein level;
KW Cell membrane; Cell projection; Coiled coil; Hydrolase; Lipid metabolism;
KW Membrane; Phagocytosis; Reference proteome.
FT CHAIN 1..588
FT /note="Myotubularin-related protein 1"
FT /evidence="ECO:0000305"
FT /id="PRO_0000436175"
FT DOMAIN 20..91
FT /note="GRAM"
FT /evidence="ECO:0000255"
FT DOMAIN 164..543
FT /note="Myotubularin phosphatase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00669"
FT COILED 563..588
FT /evidence="ECO:0000255"
FT ACT_SITE 378
FT /note="Phosphocysteine intermediate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10044"
FT BINDING 293..296
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q13614"
FT BINDING 316..317
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q13614"
FT BINDING 378..384
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q13614"
FT MUTAGEN 106
FT /note="G->E: In op309; severe reduction in PI3P and
FT PI(3,5)P2 dephosphorylation. Increased levels of PI3P in
FT intracellular vesicles. Restores the engulfment of cell
FT corpses in a ced-6 n1813 mutant background."
FT /evidence="ECO:0000269|PubMed:21490059"
SQ SEQUENCE 588 AA; 67593 MW; 99D74883745D2A28 CRC64;
MDDRGNNSGE VGEFASSSMI QESIDLKLLA AESLIWTEKN VTYFGPLGKF PGKIVITRYR
MVFLVGDGGK MYEQWKLDIP LGQVSRIEKV GRKTTSVAKR GDDNYGFTIY CKDYRVYRFT
CNPASSDRKN VCDSLNRYAF PLSHNLPMFA SVHAAETPRL MKDGWKIYSA EKEYERLGIP
NSRLWKEVDI NKDYKFSETY PRTFVIPTVS WEEGKPFVKK LGEFRSKERI PVLSWINQTT
LASISRCSQP MTGISGKRSA EDERHLTNIM NANANCRELL ILDARPAVNA KLNKAKGGGY
EENYVNAPLT FLNIHNIHVV RDSLKRLLAA LIPRVDEKGY YKALDESKWL NHVQSILEGA
VKAVFNVDTE KQSVLIHCSD GWDRTAQLTS LAMIQLDSYY RTIEGFIVLI EKEWCSFGHK
FGERIGHGDD NYSDGERSPV FVQFCDCLWQ IMRQFPWAFE FTQELLICML DELYACRYGT
FLYNSEKIRL KDKKCDETTI SFWSYVLENK KKFRNPMFKH GKSNKVINVN PSLCGLHVWI
DYYARSNPYV VTPNHEDVQQ PGAQFVDEKK QLLDEIMALD DAAQKLTA
