ID MTMR3_HUMAN Reviewed; 1198 AA.
AC Q13615; A5PL26; A7MD32; Q9NYN5; Q9NYN6; Q9UDX6; Q9UEG3;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 19-JUL-2003, sequence version 3.
DT 01-MAY-2013, entry version 124.
DE RecName: Full=Myotubularin-related protein 3;
DE EC=3.1.3.48;
DE AltName: Full=FYVE domain-containing dual specificity protein phosphatase 1;
DE Short=FYVE-DSP1;
DE AltName: Full=Zinc finger FYVE domain-containing protein 10;
GN Name=MTMR3; Synonyms=KIAA0371, ZFYVE10;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE (ISOFORMS A; B AND C), AND CHARACTERIZATION.
RX PubMed=10733931; DOI=10.1006/bbrc.2000.2417;
RA Zhao R., Qi Y., Zhao Z.J.;
RT "FYVE-DSP1, a dual-specificity protein phosphatase containing an FYVE
RT domain.";
RL Biochem. Biophys. Res. Commun. 270:222-229(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM B).
RC TISSUE=Brain;
RX PubMed=9205841; DOI=10.1093/dnares/4.2.141;
RA Nagase T., Ishikawa K., Nakajima D., Ohira M., Seki N., Miyajima N.,
RA Tanaka A., Kotani H., Nomura N., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. VII.
RT The complete sequences of 100 new cDNA clones from brain which can
RT code for large proteins in vitro.";
RL DNA Res. 4:141-150(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM B).
RX PubMed=15461802; DOI=10.1186/gb-2004-5-10-r84;
RA Collins J.E., Wright C.L., Edwards C.A., Davis M.P., Grinham J.A.,
RA Cole C.G., Goward M.E., Aguado B., Mallya M., Mokrab Y., Huckle E.J.,
RA Beare D.M., Dunham I.;
RT "A genome annotation-driven approach to cloning the human ORFeome.";
RL Genome Biol. 5:R84.1-R84.11(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=10591208; DOI=10.1038/990031;
RA Dunham I., Hunt A.R., Collins J.E., Bruskiewich R., Beare D.M.,
RA Clamp M., Smink L.J., Ainscough R., Almeida J.P., Babbage A.K.,
RA Bagguley C., Bailey J., Barlow K.F., Bates K.N., Beasley O.P.,
RA Bird C.P., Blakey S.E., Bridgeman A.M., Buck D., Burgess J.,
RA Burrill W.D., Burton J., Carder C., Carter N.P., Chen Y., Clark G.,
RA Clegg S.M., Cobley V.E., Cole C.G., Collier R.E., Connor R.,
RA Conroy D., Corby N.R., Coville G.J., Cox A.V., Davis J., Dawson E.,
RA Dhami P.D., Dockree C., Dodsworth S.J., Durbin R.M., Ellington A.G.,
RA Evans K.L., Fey J.M., Fleming K., French L., Garner A.A.,
RA Gilbert J.G.R., Goward M.E., Grafham D.V., Griffiths M.N.D., Hall C.,
RA Hall R.E., Hall-Tamlyn G., Heathcott R.W., Ho S., Holmes S.,
RA Hunt S.E., Jones M.C., Kershaw J., Kimberley A.M., King A.,
RA Laird G.K., Langford C.F., Leversha M.A., Lloyd C., Lloyd D.M.,
RA Martyn I.D., Mashreghi-Mohammadi M., Matthews L.H., Mccann O.T.,
RA Mcclay J., Mclaren S., McMurray A.A., Milne S.A., Mortimore B.J.,
RA Odell C.N., Pavitt R., Pearce A.V., Pearson D., Phillimore B.J.C.T.,
RA Phillips S.H., Plumb R.W., Ramsay H., Ramsey Y., Rogers L., Ross M.T.,
RA Scott C.E., Sehra H.K., Skuce C.D., Smalley S., Smith M.L.,
RA Soderlund C., Spragon L., Steward C.A., Sulston J.E., Swann R.M.,
RA Vaudin M., Wall M., Wallis J.M., Whiteley M.N., Willey D.L.,
RA Williams L., Williams S.A., Williamson H., Wilmer T.E., Wilming L.,
RA Wright C.L., Hubbard T., Bentley D.R., Beck S., Rogers J., Shimizu N.,
RA Minoshima S., Kawasaki K., Sasaki T., Asakawa S., Kudoh J.,
RA Shintani A., Shibuya K., Yoshizaki Y., Aoki N., Mitsuyama S.,
RA Roe B.A., Chen F., Chu L., Crabtree J., Deschamps S., Do A., Do T.,
RA Dorman A., Fang F., Fu Y., Hu P., Hua A., Kenton S., Lai H., Lao H.I.,
RA Lewis J., Lewis S., Lin S.-P., Loh P., Malaj E., Nguyen T., Pan H.,
RA Phan S., Qi S., Qian Y., Ray L., Ren Q., Shaull S., Sloan D., Song L.,
RA Wang Q., Wang Y., Wang Z., White J., Willingham D., Wu H., Yao Z.,
RA Zhan M., Zhang G., Chissoe S., Murray J., Miller N., Minx P.,
RA Fulton R., Johnson D., Bemis G., Bentley D., Bradshaw H., Bourne S.,
RA Cordes M., Du Z., Fulton L., Goela D., Graves T., Hawkins J.,
RA Hinds K., Kemp K., Latreille P., Layman D., Ozersky P., Rohlfing T.,
RA Scheet P., Walker C., Wamsley A., Wohldmann P., Pepin K., Nelson J.,
RA Korf I., Bedell J.A., Hillier L.W., Mardis E., Waterston R.,
RA Wilson R., Emanuel B.S., Shaikh T., Kurahashi H., Saitta S.,
RA Budarf M.L., McDermid H.E., Johnson A., Wong A.C.C., Morrow B.E.,
RA Edelmann L., Kim U.J., Shizuya H., Simon M.I., Dumanski J.P.,
RA Peyrard M., Kedra D., Seroussi E., Fransson I., Tapia I., Bruder C.E.,
RA O'Brien K.P., Wilkinson P., Bodenteich A., Hartman K., Hu X.,
RA Khan A.S., Lane L., Tilahun Y., Wright H.;
RT "The DNA sequence of human chromosome 22.";
RL Nature 402:489-495(1999).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS B AND C).
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP NUCLEOTIDE SEQUENCE OF 374-578.
RX PubMed=9736772; DOI=10.1093/hmg/7.11.1703;
RA Laporte J., Blondeau F., Buj-Bello A., Tentler D., Kretz C., Dahl N.,
RA Mandel J.-L.;
RT "Characterization of the myotubularin dual specificity phosphatase
RT gene family from yeast to human.";
RL Hum. Mol. Genet. 7:1703-1712(1998).
RN [8]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 381-463.
RX PubMed=8640223; DOI=10.1038/ng0696-175;
RA Laporte J., Hu L.-J., Kretz C., Mandel J.-L., Kioschis P., Coy J.,
RA Klauck S.M., Poutska A., Dahl N.;
RT "A gene mutated in X-linked myotubular myopathy defines a new putative
RT tyrosine phosphatase family conserved in yeast.";
RL Nat. Genet. 13:175-182(1996).
RN [9]
RP FUNCTION, AND MUTAGENESIS OF CYS-413.
RX PubMed=11676921; DOI=10.1016/S0960-9822(01)00501-2;
RA Walker D.M., Urbe S., Dove S.K., Tenza D., Raposo G., Clague M.J.;
RT "Characterization of MTMR3. an inositol lipid 3-phosphatase with novel
RT substrate specificity.";
RL Curr. Biol. 11:1600-1605(2001).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-647, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=18220336; DOI=10.1021/pr0705441;
RA Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D.,
RA Yates J.R. III;
RT "Combining protein-based IMAC, peptide-based IMAC, and MudPIT for
RT efficient phosphoproteomic analysis.";
RL J. Proteome Res. 7:1346-1351(2008).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-633; SER-647 AND
RP THR-731, AND MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [12]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [13]
RP VARIANT [LARGE SCALE ANALYSIS] LEU-221.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S.,
RA Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J.,
RA Dawson D., Willson J.K.V., Gazdar A.F., Hartigan J., Wu L., Liu C.,
RA Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N.,
RA Vogelstein B., Kinzler K.W., Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal
RT cancers.";
RL Science 314:268-274(2006).
CC -!- FUNCTION: Phosphatase that acts on lipids with a phosphoinositol
CC headgroup. Has phosphatase activity towards phosphatidylinositol
CC 3-phosphate and phosphatidylinositol 3,5-bisphosphate. May also
CC dephosphorylate proteins phosphorylated on Ser, Thr, and Tyr
CC residues.
CC -!- CATALYTIC ACTIVITY: Protein tyrosine phosphate + H(2)O = protein
CC tyrosine + phosphate.
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Membrane; Peripheral membrane
CC protein.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=B; Synonyms=FYVE-DSP1b;
CC IsoId=Q13615-1; Sequence=Displayed;
CC Name=A; Synonyms=FYVE-DSP1a;
CC IsoId=Q13615-2; Sequence=VSP_007781, VSP_007782;
CC Name=C; Synonyms=FYVE-DSP1c;
CC IsoId=Q13615-3; Sequence=VSP_007781;
CC -!- SIMILARITY: Belongs to the protein-tyrosine phosphatase family.
CC Non-receptor class myotubularin subfamily.
CC -!- SIMILARITY: Contains 1 FYVE-type zinc finger.
CC -!- SIMILARITY: Contains 1 myotubularin phosphatase domain.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA20826.2; Type=Erroneous initiation;
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DR EMBL; AF233436; AAF40203.2; -; mRNA.
DR EMBL; AF233437; AAF40204.1; -; mRNA.
DR EMBL; AF233438; AAF40205.1; -; mRNA.
DR EMBL; AB002369; BAA20826.2; ALT_INIT; mRNA.
DR EMBL; CR456525; CAG30411.1; -; mRNA.
DR EMBL; CH471095; EAW59852.1; -; Genomic_DNA.
DR EMBL; CH471095; EAW59855.1; -; Genomic_DNA.
DR EMBL; BC142713; AAI42714.1; -; mRNA.
DR EMBL; BC148216; AAI48217.1; -; mRNA.
DR EMBL; BC152455; AAI52456.1; -; mRNA.
DR EMBL; AC003071; AAB83949.1; -; Genomic_DNA.
DR EMBL; U58034; AAC79119.1; -; Genomic_DNA.
DR IPI; IPI00171273; -.
DR IPI; IPI00171274; -.
DR IPI; IPI00185018; -.
DR RefSeq; NP_066576.1; NM_021090.3.
DR RefSeq; NP_694690.1; NM_153050.2.
DR RefSeq; NP_694691.1; NM_153051.2.
DR UniGene; Hs.474536; -.
DR ProteinModelPortal; Q13615; -.
DR IntAct; Q13615; 5.
DR STRING; 9606.ENSP00000384651; -.
DR PhosphoSite; Q13615; -.
DR DMDM; 33112668; -.
DR PaxDb; Q13615; -.
DR PRIDE; Q13615; -.
DR DNASU; 8897; -.
DR Ensembl; ENST00000333027; ENSP00000331649; ENSG00000100330.
DR Ensembl; ENST00000351488; ENSP00000307271; ENSG00000100330.
DR Ensembl; ENST00000401950; ENSP00000384651; ENSG00000100330.
DR Ensembl; ENST00000406629; ENSP00000384077; ENSG00000100330.
DR GeneID; 8897; -.
DR KEGG; hsa:8897; -.
DR UCSC; uc003agu.4; human.
DR UCSC; uc003agv.4; human.
DR UCSC; uc003agw.4; human.
DR CTD; 8897; -.
DR GeneCards; GC22P030279; -.
DR HGNC; HGNC:7451; MTMR3.
DR HPA; HPA034515; -.
DR HPA; HPA034516; -.
DR MIM; 603558; gene.
DR neXtProt; NX_Q13615; -.
DR PharmGKB; PA31254; -.
DR eggNOG; NOG322789; -.
DR HOVERGEN; HBG052526; -.
DR InParanoid; Q13615; -.
DR KO; K01104; -.
DR OMA; TDTIQQR; -.
DR OrthoDB; EOG4H19V0; -.
DR PhylomeDB; Q13615; -.
DR BioCyc; MetaCyc:HS02045-MONOMER; -.
DR Reactome; REACT_111217; Metabolism.
DR ChiTaRS; MTMR3; human.
DR GenomeRNAi; 8897; -.
DR NextBio; 33415; -.
DR ArrayExpress; Q13615; -.
DR Bgee; Q13615; -.
DR CleanEx; HS_MTMR3; -.
DR Genevestigator; Q13615; -.
DR GermOnline; ENSG00000100330; Homo sapiens.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0016020; C:membrane; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:HPA.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004438; F:phosphatidylinositol-3-phosphatase activity; IDA:UniProtKB.
DR GO; GO:0004722; F:protein serine/threonine phosphatase activity; IDA:UniProtKB.
DR GO; GO:0004725; F:protein tyrosine phosphatase activity; IDA:UniProtKB.
DR GO; GO:0006661; P:phosphatidylinositol biosynthetic process; TAS:Reactome.
DR GO; GO:0046856; P:phosphatidylinositol dephosphorylation; IDA:UniProtKB.
DR GO; GO:0044281; P:small molecule metabolic process; TAS:Reactome.
DR Gene3D; 3.30.40.10; -; 1.
DR InterPro; IPR010569; Myotub-related.
DR InterPro; IPR017906; Myotubularin_phosphatase_dom.
DR InterPro; IPR016130; Tyr_Pase_AS.
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 Pfam; PF01363; FYVE; 1.
DR Pfam; PF06602; Myotub-related; 1.
DR SMART; SM00064; FYVE; 1.
DR SUPFAM; SSF57903; FYVE_PHD_ZnF; 1.
DR PROSITE; PS51339; PPASE_MYOTUBULARIN; 1.
DR PROSITE; PS00383; TYR_PHOSPHATASE_1; 1.
DR PROSITE; PS50056; TYR_PHOSPHATASE_2; FALSE_NEG.
DR PROSITE; PS50178; ZF_FYVE; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Coiled coil; Complete proteome; Cytoplasm;
KW Hydrolase; Membrane; Metal-binding; Phosphoprotein; Polymorphism;
KW Protein phosphatase; Reference proteome; Zinc; Zinc-finger.
FT CHAIN 1 1198 Myotubularin-related protein 3.
FT /FTId=PRO_0000094936.
FT DOMAIN 155 576 Myotubularin phosphatase.
FT ZN_FING 1119 1179 FYVE-type.
FT REGION 326 329 Substrate binding (By similarity).
FT REGION 351 352 Substrate binding (By similarity).
FT REGION 413 419 Substrate binding (By similarity).
FT COILED 1029 1062 Potential.
FT ACT_SITE 413 413 Phosphocysteine intermediate (By
FT similarity).
FT BINDING 459 459 Substrate (By similarity).
FT MOD_RES 613 613 Phosphoserine (By similarity).
FT MOD_RES 633 633 Phosphoserine.
FT MOD_RES 647 647 Phosphoserine.
FT MOD_RES 731 731 Phosphothreonine.
FT MOD_RES 1181 1181 Phosphothreonine (By similarity).
FT VAR_SEQ 1076 1112 Missing (in isoform A and isoform C).
FT /FTId=VSP_007781.
FT VAR_SEQ 1142 1142 R -> RDTDRVDQTW (in isoform A).
FT /FTId=VSP_007782.
FT VARIANT 221 221 V -> L (in a breast cancer sample;
FT somatic mutation).
FT /FTId=VAR_035656.
FT MUTAGEN 413 413 C->S: Loss of activity.
FT CONFLICT 560 578 LYPVCHVRNLMLWSAVYLP -> CILQPFHCGQQKEFGVGY
FT I (in Ref. 7).
SQ SEQUENCE 1198 AA; 133619 MW; FE6F4B165074D5F8 CRC64;
MDEETRHSLE CIQANQIFPR KQLIREDENL QVPFLELHGE STEFVGRAED AIIALSNYRL
HIKFKESLVN VPLQLIESVE CRDIFQLHLT CKDCKVIRCQ FSTFEQCQEW LKRLNNAIRP
PAKIEDLFSF AYHAWCMEVY ASEKEQHGDL CRPGEHVTSR FKNEVERMGF DMNNAWRISN
INEKYKLCGS YPQELIVPAW ITDKELESVS SFRSWKRIPA VIYRHQSNGA VIARCGQPEV
SWWGWRNADD EHLVQSVAKA CASDSRSSGS KLSTRNTSRD FPNGGDLSDV EFDSSLSNAS
GAESLAIQPQ KLLILDARSY AAAVANRAKG GGCECPEYYP NCEVVFMGMA NIHSIRRSFQ
SLRLLCTQMP DPGNWLSALE STKWLHHLSV LLKSALLVVH AVDQDQRPVL VHCSDGWDRT
PQIVALAKLL LDPYYRTIEG FQVLVEMEWL DFGHKFADRC GHGENSDDLN ERCPVFLQWL
DCVHQLQRQF PCSFEFNEAF LVKLVQHTYS CLFGTFLCNN AKERGEKHTQ ERTCSVWSLL
RAGNKAFKNL LYSSQSEAVL YPVCHVRNLM LWSAVYLPCP SPTTPVDDSC APYPAPGTSP
DDPPLSRLPK TRSYDNLTTA CDNTVPLASR RCSDPSLNEK WQEHRRSLEL SSLAGPGEDP
LSADSLGKPT RVPGGAELSV AAGVAEGQME NILQEATKEE SGVEEPAHRA GIEIQEGKED
PLLEKESRRK TPEASAIGLH QDPELGDAAL RSHLDMSWPL FSQGISEQQS GLSVLLSSLQ
VPPRGEDSLE VPVEQFRIEE IAEGREEAVL PIPVDAKVGY GTSQSCSLLP SQVPFETRGP
NVDSSTDMLV EDKVKSVSGP QGHHRSCLVN SGKDRLPQTM EPSPSETSLV ERPQVGSVVH
RTSLGSTLSL TRSPCALPLA ECKEGLVCNG APETENRASE QPPGLSTLQM YPTPNGHCAN
GEAGRSKDSL SRQLSAMSCS SAHLHSRNLH HKWLHSHSGR PSATSSPDQP SRSHLDDDGM
SVYTDTIQQR LRQIESGHQQ EVETLKKQVQ ELKSRLESQY LTSSLHFNGD FGDEVTSIPD
SESNLDQNCL SRCSTEIFSE ASWEQVDKQD TEMTRWLPDH LAAHCYACDS AFWLASRKHH
CRNCGNVFCS SCCNQKVPVP SQQLFEPSRV CKSCYSSLHP TSSSIDLELD KPIAATSN
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