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   03-AUG-2022, entry version 90.
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; A2BGG1; -.
DR   PeptideAtlas; A2BGG1; -.
DR   PRIDE; A2BGG1; -.
DR   Ensembl; ENSDART00000083561; ENSDARP00000077996; ENSDARG00000059817.
DR   GeneID; 569130; -.
DR   KEGG; dre:569130; -.
DR   CTD; 54545; -.
DR   ZFIN; ZDB-GENE-050401-1; mtmr12.
DR   eggNOG; KOG1089; Eukaryota.
DR   GeneTree; ENSGT00940000160263; -.
DR   HOGENOM; CLU_021912_1_0_1; -.
DR   InParanoid; A2BGG1; -.
DR   OMA; LRFQGHG; -.
DR   OrthoDB; 620702at2759; -.
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; Genome assembly.
DR   Proteomes; UP000814640; Chromosome 5.
DR   Bgee; ENSDARG00000059817; Expressed in intestine and 19 other tissues.
DR   GO; GO:0030017; C:sarcomere; IEA:UniProtKB-SubCell.
DR   GO; GO:0016529; C:sarcoplasmic reticulum; IEA:UniProtKB-SubCell.
DR   GO; GO:0019208; F:phosphatase regulator activity; IEA:InterPro.
DR   GO; GO:0004438; F:phosphatidylinositol-3-phosphatase activity; IBA:GO_Central.
DR   GO; GO:0007626; P:locomotory behavior; IMP:ZFIN.
DR   GO; GO:0046856; P:phosphatidylinositol dephosphorylation; IBA:GO_Central.
DR   GO; GO:0048741; P:skeletal muscle fiber development; IMP:ZFIN.
DR   Gene3D; 2.30.29.30; -; 1.
DR   InterPro; IPR030576; MTMR12.
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; PTHR10807; 1.
DR   PANTHER; PTHR10807:SF37; PTHR10807:SF37; 1.
DR   Pfam; PF12578; 3-PAP; 1.
DR   Pfam; PF06602; Myotub-related; 1.
DR   SUPFAM; SSF52799; SSF52799; 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