MTMRC_HUMAN
ID MTMRC_HUMAN Reviewed; 747 AA.
AC Q9C0I1; Q69YJ4; Q6PFW3; Q96QU2; Q9NX27;
DT 15-JAN-2008, integrated into UniProtKB/Swiss-Prot.
DT 15-JAN-2008, sequence version 2.
DT 03-AUG-2022, entry version 136.
DE RecName: Full=Myotubularin-related protein 12;
DE AltName: Full=Inactive phosphatidylinositol 3-phosphatase 12 {ECO:0000305};
DE AltName: Full=Phosphatidylinositol 3 phosphate 3-phosphatase adapter subunit;
DE Short=3-PAP;
DE Short=3-phosphatase adapter protein;
GN Name=MTMR12; Synonyms=KIAA1682, PIP3AP;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, LACK OF CATALYTIC
RP ACTIVITY, AND TISSUE SPECIFICITY.
RX PubMed=11504939; DOI=10.1073/pnas.171306098;
RA Nandurkar H.H., Caldwell K.K., Whisstock J.C., Layton M.J., Gaudet E.A.,
RA Norris F.A., Majerus P.W., Mitchell C.A.;
RT "Characterization of an adapter subunit to a phosphatidylinositol (3)P 3-
RT phosphatase: identification of a myotubularin-related protein lacking
RT catalytic activity.";
RL Proc. Natl. Acad. Sci. U.S.A. 98:9499-9504(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RX PubMed=11214970; DOI=10.1093/dnares/7.6.347;
RA Nagase T., Kikuno R., Hattori A., Kondo Y., Okumura K., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XIX. The
RT complete sequences of 100 new cDNA clones from brain which code for large
RT proteins in vitro.";
RL DNA Res. 7:347-355(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 354-747 (ISOFORM 1).
RC TISSUE=Melanoma;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [6]
RP FUNCTION, IDENTIFICATION IN A COMPLEX WITH MTM1, IDENTIFICATION IN A
RP COMPLEX WITH MTMR2, SUBCELLULAR LOCATION, AND REGION.
RX PubMed=12847286; DOI=10.1073/pnas.1033097100;
RA Nandurkar H.H., Layton M., Laporte J., Selan C., Corcoran L.,
RA Caldwell K.K., Mochizuki Y., Majerus P.W., Mitchell C.A.;
RT "Identification of myotubularin as the lipid phosphatase catalytic subunit
RT associated with the 3-phosphatase adapter protein, 3-PAP.";
RL Proc. Natl. Acad. Sci. U.S.A. 100:8660-8665(2003).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-564 AND SER-716, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [8]
RP FUNCTION, INTERACTION WITH MTM1, AND TISSUE SPECIFICITY.
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).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
CC -!- FUNCTION: Acts as an adapter for the myotubularin-related phosphatases
CC (PubMed:11504939, PubMed:12847286, PubMed:23818870). Regulates
CC phosphatase MTM1 protein stability and possibly its intracellular
CC location (PubMed:23818870). By stabilizing MTM1 protein levels,
CC required for skeletal muscle maintenance but not for myogenesis (By
CC similarity). {ECO:0000250|UniProtKB:Q80TA6,
CC ECO:0000269|PubMed:11504939, ECO:0000269|PubMed:12847286,
CC ECO:0000269|PubMed:23818870}.
CC -!- SUBUNIT: Heterodimer with lipid phosphatase MTM1 (PubMed:12847286,
CC PubMed:23818870). Heterodimer with lipid phosphatase MTMR2
CC (PubMed:12847286). {ECO:0000269|PubMed:12847286,
CC ECO:0000269|PubMed:23818870}.
CC -!- INTERACTION:
CC Q9C0I1; Q13496: MTM1; NbExp=4; IntAct=EBI-2829520, EBI-2864109;
CC Q9C0I1; Q13614: MTMR2; NbExp=2; IntAct=EBI-2829520, EBI-475631;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:12847286}.
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 (PubMed:12847286).
CC Localizes to triads, a structure formed by a T tubule and two
CC sarcoplasmic reticulum terminal cisterna (By similarity). In skeletal
CC muscles, co-localizes with MTM1 in the sarcomere (By similarity).
CC Partially localizes to the sarcoplasmic reticulum in skeletal muscles
CC (By similarity). {ECO:0000250|UniProtKB:Q80TA6,
CC ECO:0000269|PubMed:12847286}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q9C0I1-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9C0I1-2; Sequence=VSP_030722;
CC Name=3;
CC IsoId=Q9C0I1-3; Sequence=VSP_030721;
CC -!- TISSUE SPECIFICITY: Expressed in skeletal muscles (at protein level)
CC (PubMed:23818870). Ubiquitous with prominent expression in brain,
CC heart, kidney, placenta, and lung (PubMed:11504939).
CC {ECO:0000269|PubMed:11504939, 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 391 in the dsPTPase catalytic loop and does not have phosphatase
CC activity. {ECO:0000305|PubMed:11504939}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAB21773.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AY028703; AAK26171.1; -; mRNA.
DR EMBL; AB051469; BAB21773.1; ALT_INIT; mRNA.
DR EMBL; AK000483; BAA91195.1; -; mRNA.
DR EMBL; BC057393; AAH57393.1; -; mRNA.
DR EMBL; AL833231; CAH10604.1; -; mRNA.
DR CCDS; CCDS34138.1; -. [Q9C0I1-1]
DR CCDS; CCDS75230.1; -. [Q9C0I1-3]
DR CCDS; CCDS77998.1; -. [Q9C0I1-2]
DR RefSeq; NP_001035536.1; NM_001040446.2. [Q9C0I1-1]
DR RefSeq; NP_001281272.1; NM_001294343.1. [Q9C0I1-2]
DR RefSeq; NP_001281273.1; NM_001294344.1. [Q9C0I1-3]
DR AlphaFoldDB; Q9C0I1; -.
DR SMR; Q9C0I1; -.
DR BioGRID; 120032; 29.
DR IntAct; Q9C0I1; 9.
DR MINT; Q9C0I1; -.
DR STRING; 9606.ENSP00000371577; -.
DR DEPOD; MTMR12; -.
DR iPTMnet; Q9C0I1; -.
DR PhosphoSitePlus; Q9C0I1; -.
DR BioMuta; MTMR12; -.
DR DMDM; 166199459; -.
DR EPD; Q9C0I1; -.
DR jPOST; Q9C0I1; -.
DR MassIVE; Q9C0I1; -.
DR MaxQB; Q9C0I1; -.
DR PaxDb; Q9C0I1; -.
DR PeptideAtlas; Q9C0I1; -.
DR PRIDE; Q9C0I1; -.
DR ProteomicsDB; 80050; -. [Q9C0I1-1]
DR ProteomicsDB; 80051; -. [Q9C0I1-2]
DR ProteomicsDB; 80052; -. [Q9C0I1-3]
DR Antibodypedia; 9766; 111 antibodies from 21 providers.
DR DNASU; 54545; -.
DR Ensembl; ENST00000264934.5; ENSP00000264934.5; ENSG00000150712.11. [Q9C0I1-3]
DR Ensembl; ENST00000280285.9; ENSP00000280285.5; ENSG00000150712.11. [Q9C0I1-2]
DR Ensembl; ENST00000382142.8; ENSP00000371577.3; ENSG00000150712.11. [Q9C0I1-1]
DR GeneID; 54545; -.
DR KEGG; hsa:54545; -.
DR MANE-Select; ENST00000382142.8; ENSP00000371577.3; NM_001040446.3; NP_001035536.1.
DR UCSC; uc003jhq.4; human. [Q9C0I1-1]
DR CTD; 54545; -.
DR DisGeNET; 54545; -.
DR GeneCards; MTMR12; -.
DR HGNC; HGNC:18191; MTMR12.
DR HPA; ENSG00000150712; Low tissue specificity.
DR MIM; 606501; gene.
DR neXtProt; NX_Q9C0I1; -.
DR OpenTargets; ENSG00000150712; -.
DR PharmGKB; PA128394670; -.
DR VEuPathDB; HostDB:ENSG00000150712; -.
DR eggNOG; KOG1089; Eukaryota.
DR GeneTree; ENSGT00940000160263; -.
DR HOGENOM; CLU_021912_2_0_1; -.
DR InParanoid; Q9C0I1; -.
DR OMA; LRFQGHG; -.
DR OrthoDB; 620702at2759; -.
DR PhylomeDB; Q9C0I1; -.
DR TreeFam; TF315197; -.
DR BRENDA; 3.1.3.64; 2681.
DR PathwayCommons; Q9C0I1; -.
DR Reactome; R-HSA-1660516; Synthesis of PIPs at the early endosome membrane.
DR SignaLink; Q9C0I1; -.
DR BioGRID-ORCS; 54545; 8 hits in 1079 CRISPR screens.
DR ChiTaRS; MTMR12; human.
DR GenomeRNAi; 54545; -.
DR Pharos; Q9C0I1; Tbio.
DR PRO; PR:Q9C0I1; -.
DR Proteomes; UP000005640; Chromosome 5.
DR RNAct; Q9C0I1; protein.
DR Bgee; ENSG00000150712; Expressed in germinal epithelium of ovary and 185 other tissues.
DR ExpressionAtlas; Q9C0I1; baseline and differential.
DR Genevisible; Q9C0I1; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
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:0046856; P:phosphatidylinositol dephosphorylation; IBA:GO_Central.
DR GO; GO:1901998; P:toxin transport; IEA:Ensembl.
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 Alternative splicing; Cytoplasm; Phosphoprotein; Reference proteome;
KW Sarcoplasmic reticulum.
FT CHAIN 1..747
FT /note="Myotubularin-related protein 12"
FT /id="PRO_0000315825"
FT DOMAIN 205..643
FT /note="Myotubularin phosphatase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00669"
FT REGION 449..558
FT /note="Interaction with MTM1"
FT /evidence="ECO:0000269|PubMed:12847286"
FT MOD_RES 564
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 601
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q5FVM6"
FT MOD_RES 716
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT VAR_SEQ 449..558
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_030721"
FT VAR_SEQ 505..558
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_030722"
FT CONFLICT 197
FT /note="D -> V (in Ref. 3; BAA91195)"
FT /evidence="ECO:0000305"
FT CONFLICT 591
FT /note="L -> M (in Ref. 1; AAK26171)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 747 AA; 86148 MW; 1D11A678CC92F70B CRC64;
MLGKGVVGGG GGTKAPKPSF VSYVRPEEIH TNEKEVTEKE VTLHLLPGEQ LLCEASTVLK
YVQEDSCQHG VYGRLVCTDF KIAFLGDDES ALDNDETQFK NKVIGENDIT LHCVDQIYGV
FDEKKKTLFG QLKKYPEKLI IHCKDLRVFQ FCLRYTKEEE VKRIVSGIIH HTQAPKLLKR
LFLFSYATAA QNNTVTDPKN HTVMFDTLKD WCWELERTKG NMKYKAVSVN EGYKVCERLP
AYFVVPTPLP EENVQRFQGH GIPIWCWSCH NGSALLKMSA LPKEQDDGIL QIQKSFLDGI
YKTIHRPPYE IVKTEDLSSN FLSLQEIQTA YSKFKQLFLI DNSTEFWDTD IKWFSLLESS
SWLDIIRRCL KKAIEITECM EAQNMNVLLL EENASDLCCL ISSLVQLMMD PHCRTRIGFQ
SLIQKEWVMG GHCFLDRCNH LRQNDKEEVP VFLLFLDCVW QLVHQHPPAF EFTETYLTVL
SDSLYIPIFS TFFFNSPHQK DTNMGREGQD TQSKPLNLLT VWDWSVQFEP KAQTLLKNPL
YVEKPKLDKG QRKGMRFKHQ RQLSLPLTQS KSSPKRGFFR EETDHLIKNL LGKRISKLIN
SSDELQDNFR EFYDSWHSKS TDYHGLLLPH IEGPEIKVWA QRYLRWIPEA QILGGGQVAT
LSKLLEMMEE VQSLQEKIDE RHHSQQAPQA EAPCLLRNSA RLSSLFPFAL LQRHSSKPVL
PTSGWKALGD EDDLAKREDE FVDLGDV
