ID MTMRC_RAT Reviewed; 748 AA.
AC Q5FVM6;
DT 15-JAN-2008, integrated into UniProtKB/Swiss-Prot.
DT 15-JAN-2008, sequence version 2.
DT 24-JAN-2024, entry version 114.
DE RecName: Full=Myotubularin-related protein 12;
DE AltName: Full=Inactive phosphatidylinositol 3-phosphatase 12 {ECO:0000305};
DE AltName: Full=Phosphatidylinositol 3-phosphatase-associated protein;
GN Name=Mtmr12; Synonyms=Pip3ap;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Brown Norway;
RX PubMed=15057822; DOI=10.1038/nature02426;
RA Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J.,
RA Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G.,
RA Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G.,
RA Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G.,
RA Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S.,
RA Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T.,
RA Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D.,
RA Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L.,
RA Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D.,
RA Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M.,
RA Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C.,
RA Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J.,
RA Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H.,
RA Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X.,
RA Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q.,
RA Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P.,
RA Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A.,
RA Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C.,
RA Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J.,
RA Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J.,
RA Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F.,
RA Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A.,
RA Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A.,
RA Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J.,
RA Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E.,
RA Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M.,
RA Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C.,
RA Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L.,
RA Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W.,
RA Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y.,
RA Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V.,
RA Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M.,
RA Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S.,
RA Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B.,
RA Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R.,
RA Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J.,
RA Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D.,
RA Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S.,
RA Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S.,
RA Mockrin S., Collins F.S.;
RT "Genome sequence of the Brown Norway rat yields insights into mammalian
RT evolution.";
RL Nature 428:493-521(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Liver;
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 project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-602, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
CC -!- FUNCTION: Acts as an adapter for the myotubularin-related phosphatases.
CC Regulates phosphatase MTM1 protein stability and possibly its
CC intracellular location. By stabilizing MTM1 protein levels, required
CC for skeletal muscle maintenance but not for myogenesis.
CC {ECO:0000250|UniProtKB:Q80TA6}.
CC -!- SUBUNIT: Heterodimer with lipid phosphatase MTM1 (By similarity).
CC Heterodimer with lipid phosphatase MTMR2 (By similarity).
CC {ECO:0000250|UniProtKB:Q80TA6, ECO:0000250|UniProtKB:Q9C0I1}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q9C0I1}.
CC Sarcoplasmic reticulum {ECO:0000250|UniProtKB:Q80TA6}. Cytoplasm,
CC myofibril, sarcomere {ECO:0000250|UniProtKB:Q80TA6}. Note=Localizes to
CC punctate vesicles when associated with MTM1 (By similarity). Localizes
CC to triads, a structure formed by a T tubule and two sarcoplasmic
CC reticulum terminal cisterna. In skeletal muscles, co-localizes with
CC MTM1 in the sarcomere. Partially localizes to the sarcoplasmic
CC reticulum in skeletal muscles (By similarity).
CC {ECO:0000250|UniProtKB:Q80TA6, ECO:0000250|UniProtKB:Q9C0I1}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q5FVM6-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q5FVM6-2; Sequence=VSP_030724, VSP_030725;
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 392 in the dsPTPase catalytic loop and does not have phosphatase
CC activity. {ECO:0000250|UniProtKB:Q9C0I1}.
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DR EMBL; AABR03012204; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC089876; AAH89876.1; -; mRNA.
DR RefSeq; NP_001012077.1; NM_001012077.1. [Q5FVM6-2]
DR RefSeq; XP_006232108.1; XM_006232046.3.
DR AlphaFoldDB; Q5FVM6; -.
DR SMR; Q5FVM6; -.
DR BioGRID; 259560; 1.
DR STRING; 10116.ENSRNOP00000036677; -.
DR iPTMnet; Q5FVM6; -.
DR PhosphoSitePlus; Q5FVM6; -.
DR jPOST; Q5FVM6; -.
DR PaxDb; 10116-ENSRNOP00000036677; -.
DR GeneID; 310155; -.
DR KEGG; rno:310155; -.
DR AGR; RGD:1307902; -.
DR CTD; 54545; -.
DR RGD; 1307902; Mtmr12.
DR VEuPathDB; HostDB:ENSRNOG00000022929; -.
DR eggNOG; KOG1089; Eukaryota.
DR HOGENOM; CLU_021912_2_0_1; -.
DR InParanoid; Q5FVM6; -.
DR OrthoDB; 5474662at2759; -.
DR PhylomeDB; Q5FVM6; -.
DR TreeFam; TF315197; -.
DR Reactome; R-RNO-1660516; Synthesis of PIPs at the early endosome membrane.
DR PRO; PR:Q5FVM6; -.
DR Proteomes; UP000002494; Chromosome 2.
DR Bgee; ENSRNOG00000022929; Expressed in lung and 18 other cell types or tissues.
DR GO; GO:0005737; C:cytoplasm; ISO:RGD.
DR GO; GO:0030017; C:sarcomere; IEA:UniProtKB-SubCell.
DR GO; GO:0016529; C:sarcoplasmic reticulum; IEA:UniProtKB-SubCell.
DR CDD; cd14594; PTP-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; IPR030576; MTMR12_PTP.
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 Alternative splicing; Cytoplasm; Phosphoprotein; Reference proteome;
KW Sarcoplasmic reticulum.
FT CHAIN 1..748
FT /note="Myotubularin-related protein 12"
FT /id="PRO_0000315827"
FT DOMAIN 206..644
FT /note="Myotubularin phosphatase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00669"
FT REGION 450..559
FT /note="Interaction with MTM1"
FT /evidence="ECO:0000250"
FT REGION 549..576
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 565
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9C0I1"
FT MOD_RES 602
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT VAR_SEQ 560..587
FT /note="HQRQLSLPLTQSKSSPKRGFFREETDHL -> VRCAVLTPPHPHLHQLLHPV
FT YVRTKATL (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_030724"
FT VAR_SEQ 588..748
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_030725"
SQ SEQUENCE 748 AA; 85686 MW; 3001DA217CB3DC7D CRC64;
MLGKGGVGGG GGTKAPKPSF VSYVRPEEIH TNEKEVTEKE EVTLHLLPGE QLLCEASTVL
KYVQEDSCQL GICGRLVCTD FRISFLGDEG SAVDNGAETH FKNKIIGVND IPLHCVDQIY
GVFDEKKKPL FGQLKKYPEK LVIHCKDLRV LHFCLRYTKE EEVKRIVSGI IHHTQSPKLL
KRLFLFSYAA AVHGTAADPR NCTVMFDTPK DWCWELERTK GSVKYKTVSV NEGYRVCDRL
PAYFVVPTPL LEDDVKRFQG RGIPIWCWSC HNGSALLKMS ALPKEQDDSA LQIQKSFLDG
IYKTIHRPPY EMVKTEDLSS NFLSLQEIQS SYCKFKQLFL IDSSSEFWDT DVKWFSLLES
SGWLDIIRRC LKRAIEIIEC LEAQNMNVLL LEENASDLCC LLSSLVQVMM DAHCRTWTGF
QSLIQKEWVM GGHSFLDRCN HLHQSDKEEV PVFLLFLDCV WQLVHQHPPA FEFTETYLTV
LSDSLYIPIF STFFFNSPHQ KDTNMGRESL DAQSKPLTLL TVWDWSVQFE PKAQTLLRNP
LYVEKPKLDK GQRKGSRFKH QRQLSLPLTQ SKSSPKRGFF REETDHLIKN LLGKRISKLI
NSSDDLQDNS REFYDNWHSK PTDYHGLLLP HIEGPEIKVW AQRYLRWIPE AQILGGGRVA
TMGKLLEMME EVQSLQEKIE ARHHRQEAIH VQAPGLLRNS ARLSSLFPFA MHQRHSAKPV
LPTSGWKALG GEDDLAKRED EFVDLGDV
//
