ID MTMRC_DANRE Reviewed; 736 AA.
AC A2BGG1;
DT 15-JAN-2008, integrated into UniProtKB/Swiss-Prot.
DT 20-FEB-2007, sequence version 1.
DT 27-MAR-2024, entry version 97.
DE RecName: Full=Myotubularin-related protein 12;
DE AltName: Full=Inactive phosphatidylinositol 3-phosphatase 12 {ECO:0000305};
GN Name=mtmr12; ORFNames=si:dkey-207e22.3;
OS Danio rerio (Zebrafish) (Brachydanio rerio).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC Danionidae; Danioninae; Danio.
OX NCBI_TaxID=7955;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Tuebingen;
RX PubMed=23594743; DOI=10.1038/nature12111;
RA Howe K., Clark M.D., Torroja C.F., Torrance J., Berthelot C., Muffato M.,
RA Collins J.E., Humphray S., McLaren K., Matthews L., McLaren S., Sealy I.,
RA Caccamo M., Churcher C., Scott C., Barrett J.C., Koch R., Rauch G.J.,
RA White S., Chow W., Kilian B., Quintais L.T., Guerra-Assuncao J.A., Zhou Y.,
RA Gu Y., Yen J., Vogel J.H., Eyre T., Redmond S., Banerjee R., Chi J., Fu B.,
RA Langley E., Maguire S.F., Laird G.K., Lloyd D., Kenyon E., Donaldson S.,
RA Sehra H., Almeida-King J., Loveland J., Trevanion S., Jones M., Quail M.,
RA Willey D., Hunt A., Burton J., Sims S., McLay K., Plumb B., Davis J.,
RA Clee C., Oliver K., Clark R., Riddle C., Elliot D., Threadgold G.,
RA Harden G., Ware D., Begum S., Mortimore B., Kerry G., Heath P.,
RA Phillimore B., Tracey A., Corby N., Dunn M., Johnson C., Wood J., Clark S.,
RA Pelan S., Griffiths G., Smith M., Glithero R., Howden P., Barker N.,
RA Lloyd C., Stevens C., Harley J., Holt K., Panagiotidis G., Lovell J.,
RA Beasley H., Henderson C., Gordon D., Auger K., Wright D., Collins J.,
RA Raisen C., Dyer L., Leung K., Robertson L., Ambridge K., Leongamornlert D.,
RA McGuire S., Gilderthorp R., Griffiths C., Manthravadi D., Nichol S.,
RA Barker G., Whitehead S., Kay M., Brown J., Murnane C., Gray E.,
RA Humphries M., Sycamore N., Barker D., Saunders D., Wallis J., Babbage A.,
RA Hammond S., Mashreghi-Mohammadi M., Barr L., Martin S., Wray P.,
RA Ellington A., Matthews N., Ellwood M., Woodmansey R., Clark G., Cooper J.,
RA Tromans A., Grafham D., Skuce C., Pandian R., Andrews R., Harrison E.,
RA Kimberley A., Garnett J., Fosker N., Hall R., Garner P., Kelly D., Bird C.,
RA Palmer S., Gehring I., Berger A., Dooley C.M., Ersan-Urun Z., Eser C.,
RA Geiger H., Geisler M., Karotki L., Kirn A., Konantz J., Konantz M.,
RA Oberlander M., Rudolph-Geiger S., Teucke M., Lanz C., Raddatz G.,
RA Osoegawa K., Zhu B., Rapp A., Widaa S., Langford C., Yang F.,
RA Schuster S.C., Carter N.P., Harrow J., Ning Z., Herrero J., Searle S.M.,
RA Enright A., Geisler R., Plasterk R.H., Lee C., Westerfield M.,
RA de Jong P.J., Zon L.I., Postlethwait J.H., Nusslein-Volhard C.,
RA Hubbard T.J., Roest Crollius H., Rogers J., Stemple D.L.;
RT "The zebrafish reference genome sequence and its relationship to the human
RT genome.";
RL Nature 496:498-503(2013).
RN [2]
RP FUNCTION, SUBUNIT, DEVELOPMENTAL STAGE, AND DISRUPTION PHENOTYPE.
RX PubMed=23818870; DOI=10.1371/journal.pgen.1003583;
RA Gupta V.A., Hnia K., Smith L.L., Gundry S.R., McIntire J.E., Shimazu J.,
RA Bass J.R., Talbot E.A., Amoasii L., Goldman N.E., Laporte J., Beggs A.H.;
RT "Loss of catalytically inactive lipid phosphatase myotubularin-related
RT protein 12 impairs myotubularin stability and promotes centronuclear
RT myopathy in zebrafish.";
RL PLoS Genet. 9:E1003583-E1003583(2013).
CC -!- FUNCTION: Acts as an adapter for the myotubularin phosphatase mtm1 to
CC regulate mtm1 protein stability and possibly its intracellular location
CC (PubMed:23818870). By stabilizing mtm1 protein levels, required for
CC skeletal muscle maintenance but not for myogenesis (PubMed:23818870).
CC In skeletal muscle cells, does not regulate mtm1 subcellular
CC localization (PubMed:23818870). {ECO:0000269|PubMed:23818870}.
CC -!- SUBUNIT: Heterodimer with lipid phosphatase mtm1 (By similarity). In
CC skeletal muscles, the interaction stabilizes both mtmr12 and mtm1
CC protein levels (PubMed:23818870). {ECO:0000250|UniProtKB:Q80TA6,
CC ECO:0000269|PubMed:23818870}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q9C0I1}.
CC Sarcoplasmic reticulum {ECO:0000250|UniProtKB:Q80TA6}. Cytoplasm,
CC myofibril, sarcomere {ECO:0000250|UniProtKB:Q80TA6}.
CC -!- DEVELOPMENTAL STAGE: At 1 day post fertilization (dpf), expressed
CC ubiquitously in developing eyes, brain, heart and skeletal muscles.
CC Maternally expressed up to 8 hour post fertilization and zygotic
CC expression starts at 1 dpf and continues until 5 dpf.
CC {ECO:0000269|PubMed:23818870}.
CC -!- DISRUPTION PHENOTYPE: Morpholino knockdown results in early embryonic
CC mortality between 3 to 5 days post fertilization. Causes a reduction in
CC size with an abnormal dorsal curvature through the back and tail.
CC Impaired motor function characterized by a delay in chorion hatching
CC and a reduced motility. Some animals have pericardial edema. Defects in
CC skeletal muscles including sarcomeric disorganization often with
CC central nucleation and triad disorganization. In skeletal muscles,
CC increased phosphatidylinositol 3-phosphate levels and severe reduction
CC of mtm1 levels without affecting mtm1 subcellular localization. Double
CC morpholino knockdown of mtmr12 and mtm1 results in a more severe
CC phenotype. {ECO:0000269|PubMed:23818870}.
CC -!- SIMILARITY: Belongs to the protein-tyrosine phosphatase family. Non-
CC receptor class myotubularin subfamily. {ECO:0000305}.
CC -!- CAUTION: Although it belongs to the non-receptor class myotubularin
CC subfamily, lacks the conserved active site cysteine residue at position
CC 378 in the dsPTPase catalytic loop and does not have phosphatase
CC activity. {ECO:0000250|UniProtKB:Q80TA6}.
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DR EMBL; BX470118; CAM15354.1; -; Genomic_DNA.
DR RefSeq; NP_001107085.1; NM_001113613.1.
DR AlphaFoldDB; A2BGG1; -.
DR SMR; A2BGG1; -.
DR STRING; 7955.ENSDARP00000077996; -.
DR PaxDb; 7955-ENSDARP00000077996; -.
DR PeptideAtlas; A2BGG1; -.
DR GeneID; 569130; -.
DR KEGG; dre:569130; -.
DR AGR; ZFIN:ZDB-GENE-050401-1; -.
DR CTD; 54545; -.
DR ZFIN; ZDB-GENE-050401-1; mtmr12.
DR eggNOG; KOG1089; Eukaryota.
DR HOGENOM; CLU_021912_1_0_1; -.
DR InParanoid; A2BGG1; -.
DR OMA; LRFQGHG; -.
DR OrthoDB; 5474662at2759; -.
DR PhylomeDB; A2BGG1; -.
DR TreeFam; TF315197; -.
DR Reactome; R-DRE-1660516; Synthesis of PIPs at the early endosome membrane.
DR PRO; PR:A2BGG1; -.
DR Proteomes; UP000000437; Alternate scaffold 5.
DR Proteomes; UP000000437; Chromosome 5.
DR Bgee; ENSDARG00000059817; Expressed in intestine and 19 other cell types or tissues.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0030017; C:sarcomere; IEA:UniProtKB-SubCell.
DR GO; GO:0016529; C:sarcoplasmic reticulum; IEA:UniProtKB-SubCell.
DR GO; GO:0007626; P:locomotory behavior; IMP:ZFIN.
DR GO; GO:0048741; P:skeletal muscle fiber development; IMP:ZFIN.
DR CDD; cd13348; PH-GRAM_MTMR12; 1.
DR Gene3D; 2.30.29.30; Pleckstrin-homology domain (PH domain)/Phosphotyrosine-binding domain (PTB); 1.
DR InterPro; IPR022587; MTMR12-like_C.
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 PANTHER; PTHR10807; MYOTUBULARIN-RELATED; 1.
DR PANTHER; PTHR10807:SF37; MYOTUBULARIN-RELATED PROTEIN 12; 1.
DR Pfam; PF12578; 3-PAP; 1.
DR Pfam; PF06602; Myotub-related; 1.
DR SUPFAM; SSF52799; (Phosphotyrosine protein) phosphatases II; 1.
DR SUPFAM; SSF50729; PH domain-like; 1.
DR PROSITE; PS51339; PPASE_MYOTUBULARIN; 1.
PE 1: Evidence at protein level;
KW Cytoplasm; Reference proteome; Sarcoplasmic reticulum.
FT CHAIN 1..736
FT /note="Myotubularin-related protein 12"
FT /id="PRO_0000315829"
FT DOMAIN 182..558
FT /note="Myotubularin phosphatase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00669"
FT REGION 672..691
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ SEQUENCE 736 AA; 84796 MW; 964C0BCCE90D7424 CRC64;
MLSLGSGGAK SSKPSFVSYV TPEEIKLEKD PQKKEKHPDL LPGEVVFCSA NPILKYTQDD
LSQRGVFGTL LCTNFRVAFI SDDAPQEEMS KTFKNKLYGE NDIPLMCVDH IYGVYDEKRK
LITGGLVKNK CPSKMIIHCK DLRVFQFCLT FSKEEDAKRI FQGIAHHCLE EKSLKCVFAF
SYLRSTNPEM LRKREAIMFD SPEDWTQEMK RTKAQCRLVT ENENFELSQR LPQYFVIPSA
LGDLFNYQGK GLPIWCWSHH SGCALFKASF PSMTQEDGDF QSHLDTMITA VARNYLYSVK
TEDLSESLPT LQDIQQSYNK FKQYFLIDNT TDFWLSDVKW FSSLESSGWL DIIRQCLQKA
VEVVECLEKD NTNVLITEEE GTDLCCVISS LAQIMLDPYY RTLMGFQSLV QKEWVAGCHA
FLDRCNHLHQ KDKECHSPVF LLFLECVWQL VQQHSPAFQF SETYLTVLSD SVHVPIFSTF
LFNSAHHRES VMKAESPIAQ SRPLSCPTVW DWSVQFDSKA QNFFFNPLYS EKVKHERTVR
RPHKHKHQRQ LSLPSSAFKT PTKKGFFKDE TDSLKKMLRV KRISRWMGSP DSPVVASREF
YESWQQRPLD YHGLLLPSLD GPSVRIWMQR YLRWIPEVHI MGGGSVAIMT KLMELLSQVE
DLKRVLEQRD PSLATQPDHP PPLHHRLPSF GSSGRLSSSF PFTYSRNRSF KPIIPTGLMQ
SLMVADNLAN QEDETS
//
