TRI72_MOUSE
ID TRI72_MOUSE Reviewed; 477 AA.
AC Q1XH17; B2RWH7; Q6NX76;
DT 20-FEB-2007, integrated into UniProtKB/Swiss-Prot.
DT 02-MAY-2006, sequence version 1.
DT 03-AUG-2022, entry version 126.
DE RecName: Full=Tripartite motif-containing protein 72;
DE AltName: Full=Mitsugumin-53;
DE Short=Mg53;
GN Name=Trim72 {ECO:0000312|MGI:MGI:3612190};
GN Synonyms=Mg53 {ECO:0000312|EMBL:BAE93014.1};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, SUBUNIT,
RP PHOSPHATIDYLSERINE-BINDING, DISRUPTION PHENOTYPE, TISSUE SPECIFICITY,
RP DISULFIDE BOND AT CYS-242, AND MUTAGENESIS OF CYS-14; CYS-17; CYS-29;
RP CYS-34; CYS-37; CYS-53; CYS-55; CYS-56; CYS-86; CYS-97; CYS-105; CYS-108;
RP CYS-144; CYS-242; CYS-313 AND CYS-456.
RC STRAIN=C57BL/6J; TISSUE=Skeletal muscle;
RX PubMed=19043407; DOI=10.1038/ncb1812;
RA Cai C., Masumiya H., Weisleder N., Matsuda N., Nishi M., Hwang M.,
RA Ko J.-K., Lin P., Thornton A., Zhao X., Pan Z., Komazaki S., Brotto M.,
RA Takeshima H., Ma J.;
RT "MG53 nucleates assembly of cell membrane repair machinery.";
RL Nat. Cell Biol. 11:56-64(2009).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain, Jaw, and Limb;
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 FUNCTION.
RX PubMed=19202355; DOI=10.4161/chan.3.1.7571;
RA Masumiya H., Asaumi Y., Nishi M., Minamisawa S., Adachi-Akahane S.,
RA Yoshida M., Kangawa K., Ito K., Kagaya Y., Yanagisawa T., Yamazaki T.,
RA Ma J., Takeshima H.;
RT "Mitsugumin 53-mediated maintenance of K+ currents in cardiac myocytes.";
RL Channels 3:6-11(2009).
RN [4]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=19029292; DOI=10.1074/jbc.m808866200;
RA Cai C., Masumiya H., Weisleder N., Pan Z., Nishi M., Komazaki S.,
RA Takeshima H., Ma J.;
RT "MG53 regulates membrane budding and exocytosis in muscle cells.";
RL J. Biol. Chem. 284:3314-3322(2009).
RN [5]
RP FUNCTION, AND INTERACTION WITH DYSF AND CAV3.
RX PubMed=19380584; DOI=10.1074/jbc.m109.009589;
RA Cai C., Weisleder N., Ko J.-K., Komazaki S., Sunada Y., Nishi M.,
RA Takeshima H., Ma J.;
RT "Membrane repair defects in muscular dystrophy are linked to altered
RT interaction between MG53, caveolin-3, and dysferlin.";
RL J. Biol. Chem. 284:15894-15902(2009).
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brown adipose tissue, Heart, and Lung;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
CC -!- FUNCTION: Muscle-specific protein that plays a central role in cell
CC membrane repair by nucleating the assembly of the repair machinery at
CC injury sites. Specifically binds phosphatidylserine. Acts as a sensor
CC of oxidation: upon membrane damage, entry of extracellular oxidative
CC environment results in disulfide bond formation and homooligomerization
CC at the injury site. This oligomerization acts as a nucleation site for
CC recruitment of TRIM72-containing vesicles to the injury site, leading
CC to membrane patch formation. Probably acts upstream of the Ca(2+)-
CC dependent membrane resealing process. Required for transport of DYSF to
CC sites of cell injury during repair patch formation. Regulates membrane
CC budding and exocytosis. May be involved in the regulation of the
CC mobility of KCNB1-containing endocytic vesicles.
CC {ECO:0000269|PubMed:19029292, ECO:0000269|PubMed:19043407,
CC ECO:0000269|PubMed:19202355, ECO:0000269|PubMed:19380584}.
CC -!- SUBUNIT: Homooligomer; disulfide-linked. Interacts with DYSF and CAV3.
CC {ECO:0000269|PubMed:19043407, ECO:0000269|PubMed:19380584}.
CC -!- INTERACTION:
CC Q1XH17; P15208: Insr; NbExp=2; IntAct=EBI-16034016, EBI-6999015;
CC Q1XH17; P35569: Irs1; NbExp=4; IntAct=EBI-16034016, EBI-400825;
CC Q1XH17; P06213-1: INSR; Xeno; NbExp=2; IntAct=EBI-16034016, EBI-15558981;
CC -!- SUBCELLULAR LOCATION: Cell membrane, sarcolemma. Cytoplasmic vesicle
CC membrane. Note=Tethered to plasma membrane and cytoplasmic vesicles via
CC its interaction with phosphatidylserine.
CC -!- TISSUE SPECIFICITY: Muscle-specific. Exclusively expressed in cardiac
CC and skeletal muscle. {ECO:0000269|PubMed:19043407}.
CC -!- PTM: Disulfide bond formation at Cys-242 occurs in case of membrane
CC damage that cause the entry of the oxidized milieu of the extracellular
CC space, resulting in homooligomerization.
CC -!- PTM: S-nitrosylation at Cys-144 stabilizes TRIM72 and protects against
CC oxidation-induced protein degradation and cell death.
CC {ECO:0000250|UniProtKB:Q6ZMU5}.
CC -!- DISRUPTION PHENOTYPE: Viable until at least 11 months of age under
CC unstressed conditions, and develop progressive muscle pathology with
CC age. Mice show progressive myopathy and reduced exercise capability,
CC associated with defective membrane-repair capacity.
CC {ECO:0000269|PubMed:19043407}.
CC -!- SIMILARITY: Belongs to the TRIM/RBCC family. {ECO:0000255}.
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DR EMBL; AB231474; BAE93014.1; -; mRNA.
DR EMBL; BC067209; AAH67209.1; -; mRNA.
DR EMBL; BC147789; AAI47790.1; -; mRNA.
DR EMBL; BC158111; AAI58112.1; -; mRNA.
DR EMBL; BC158120; AAI58121.1; -; mRNA.
DR CCDS; CCDS40148.1; -.
DR RefSeq; NP_001073401.1; NM_001079932.3.
DR RefSeq; XP_006508065.1; XM_006508002.3.
DR AlphaFoldDB; Q1XH17; -.
DR SMR; Q1XH17; -.
DR BioGRID; 241694; 2.
DR DIP; DIP-60129N; -.
DR IntAct; Q1XH17; 4.
DR STRING; 10090.ENSMUSP00000079832; -.
DR iPTMnet; Q1XH17; -.
DR PhosphoSitePlus; Q1XH17; -.
DR MaxQB; Q1XH17; -.
DR PaxDb; Q1XH17; -.
DR PeptideAtlas; Q1XH17; -.
DR PRIDE; Q1XH17; -.
DR ProteomicsDB; 298305; -.
DR Antibodypedia; 14026; 210 antibodies from 31 providers.
DR Ensembl; ENSMUST00000081042; ENSMUSP00000079832; ENSMUSG00000042828.
DR Ensembl; ENSMUST00000106248; ENSMUSP00000101855; ENSMUSG00000042828.
DR GeneID; 434246; -.
DR KEGG; mmu:434246; -.
DR UCSC; uc009jxv.2; mouse.
DR CTD; 493829; -.
DR MGI; MGI:3612190; Trim72.
DR VEuPathDB; HostDB:ENSMUSG00000042828; -.
DR eggNOG; KOG2177; Eukaryota.
DR GeneTree; ENSGT00940000161791; -.
DR HOGENOM; CLU_013137_0_3_1; -.
DR InParanoid; Q1XH17; -.
DR OMA; VECVEHK; -.
DR OrthoDB; 574602at2759; -.
DR PhylomeDB; Q1XH17; -.
DR TreeFam; TF342569; -.
DR Reactome; R-MMU-445355; Smooth Muscle Contraction.
DR BioGRID-ORCS; 434246; 2 hits in 76 CRISPR screens.
DR PRO; PR:Q1XH17; -.
DR Proteomes; UP000000589; Chromosome 7.
DR RNAct; Q1XH17; protein.
DR Bgee; ENSMUSG00000042828; Expressed in skeletal muscle tissue and 25 other tissues.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0030659; C:cytoplasmic vesicle membrane; IDA:UniProtKB.
DR GO; GO:0042383; C:sarcolemma; IDA:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0001786; F:phosphatidylserine binding; IDA:UniProtKB.
DR GO; GO:0031624; F:ubiquitin conjugating enzyme binding; IDA:MGI.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; IMP:MGI.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0006887; P:exocytosis; TAS:UniProtKB.
DR GO; GO:0007517; P:muscle organ development; IMP:UniProtKB.
DR GO; GO:0003012; P:muscle system process; IMP:UniProtKB.
DR GO; GO:0046627; P:negative regulation of insulin receptor signaling pathway; IDA:MGI.
DR GO; GO:0043569; P:negative regulation of insulin-like growth factor receptor signaling pathway; IGI:MGI.
DR GO; GO:0010832; P:negative regulation of myotube differentiation; IDA:MGI.
DR GO; GO:0001778; P:plasma membrane repair; IMP:UniProtKB.
DR GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; IMP:MGI.
DR GO; GO:0051260; P:protein homooligomerization; IPI:UniProtKB.
DR GO; GO:0016567; P:protein ubiquitination; IBA:GO_Central.
DR GO; GO:0006900; P:vesicle budding from membrane; TAS:UniProtKB.
DR Gene3D; 2.60.120.920; -; 1.
DR Gene3D; 3.30.40.10; -; 1.
DR InterPro; IPR001870; B30.2/SPRY.
DR InterPro; IPR043136; B30.2/SPRY_sf.
DR InterPro; IPR003879; Butyrophylin_SPRY.
DR InterPro; IPR013320; ConA-like_dom_sf.
DR InterPro; IPR006574; PRY.
DR InterPro; IPR003877; SPRY_dom.
DR InterPro; IPR035038; TRIM72.
DR InterPro; IPR000315; Znf_B-box.
DR InterPro; IPR001841; Znf_RING.
DR InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR InterPro; IPR017907; Znf_RING_CS.
DR PANTHER; PTHR24103:SF11; PTHR24103:SF11; 1.
DR Pfam; PF13765; PRY; 1.
DR Pfam; PF00622; SPRY; 1.
DR Pfam; PF00643; zf-B_box; 1.
DR PRINTS; PR01407; BUTYPHLNCDUF.
DR SMART; SM00336; BBOX; 1.
DR SMART; SM00589; PRY; 1.
DR SMART; SM00184; RING; 1.
DR SMART; SM00449; SPRY; 1.
DR SUPFAM; SSF49899; SSF49899; 1.
DR PROSITE; PS50188; B302_SPRY; 1.
DR PROSITE; PS50119; ZF_BBOX; 1.
DR PROSITE; PS00518; ZF_RING_1; 1.
DR PROSITE; PS50089; ZF_RING_2; 1.
PE 1: Evidence at protein level;
KW Cell membrane; Coiled coil; Cytoplasmic vesicle; Disulfide bond;
KW Exocytosis; Membrane; Metal-binding; Phosphoprotein; Reference proteome;
KW S-nitrosylation; Transport; Zinc; Zinc-finger.
FT CHAIN 1..477
FT /note="Tripartite motif-containing protein 72"
FT /id="PRO_0000278131"
FT DOMAIN 271..475
FT /note="B30.2/SPRY"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00548"
FT ZN_FING 14..57
FT /note="RING-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00175"
FT ZN_FING 81..122
FT /note="B box-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00024"
FT COILED 135..169
FT /evidence="ECO:0000255"
FT COILED 204..232
FT /evidence="ECO:0000255"
FT BINDING 86
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00024"
FT BINDING 89
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00024"
FT BINDING 108
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00024"
FT BINDING 114
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00024"
FT MOD_RES 144
FT /note="S-nitrosocysteine"
FT /evidence="ECO:0000250|UniProtKB:Q6ZMU5"
FT MOD_RES 255
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:A0JPQ4"
FT DISULFID 242
FT /note="Interchain"
FT /evidence="ECO:0000269|PubMed:19043407"
FT MUTAGEN 14
FT /note="C->A: Does not affect homooligomerization."
FT /evidence="ECO:0000269|PubMed:19043407"
FT MUTAGEN 17
FT /note="C->A: Does not affect homooligomerization."
FT /evidence="ECO:0000269|PubMed:19043407"
FT MUTAGEN 29
FT /note="C->A: Does not affect homooligomerization."
FT /evidence="ECO:0000269|PubMed:19043407"
FT MUTAGEN 34
FT /note="C->A: Does not affect homooligomerization."
FT /evidence="ECO:0000269|PubMed:19043407"
FT MUTAGEN 37
FT /note="C->A: Does not affect homooligomerization."
FT /evidence="ECO:0000269|PubMed:19043407"
FT MUTAGEN 53
FT /note="C->A: Does not affect homooligomerization."
FT /evidence="ECO:0000269|PubMed:19043407"
FT MUTAGEN 55
FT /note="C->A: Does not affect homooligomerization."
FT /evidence="ECO:0000269|PubMed:19043407"
FT MUTAGEN 56
FT /note="C->A: Does not affect homooligomerization."
FT /evidence="ECO:0000269|PubMed:19043407"
FT MUTAGEN 86
FT /note="C->A: Does not affect homooligomerization."
FT /evidence="ECO:0000269|PubMed:19043407"
FT MUTAGEN 97
FT /note="C->A: Does not affect homooligomerization."
FT /evidence="ECO:0000269|PubMed:19043407"
FT MUTAGEN 105
FT /note="C->A: Does not affect homooligomerization."
FT /evidence="ECO:0000269|PubMed:19043407"
FT MUTAGEN 108
FT /note="C->A: Does not affect homooligomerization."
FT /evidence="ECO:0000269|PubMed:19043407"
FT MUTAGEN 144
FT /note="C->A: Does not affect homooligomerization."
FT /evidence="ECO:0000269|PubMed:19043407"
FT MUTAGEN 242
FT /note="C->A: Dominant-negative mutant that abolishes
FT homooligomerization and function in membrane repair."
FT /evidence="ECO:0000269|PubMed:19043407"
FT MUTAGEN 313
FT /note="C->A: Does not affect homooligomerization."
FT /evidence="ECO:0000269|PubMed:19043407"
FT MUTAGEN 456
FT /note="C->A: Does not affect homooligomerization."
FT /evidence="ECO:0000269|PubMed:19043407"
SQ SEQUENCE 477 AA; 52817 MW; DFB52299E5FFB66B CRC64;
MSAAPGLLRQ ELSCPLCLQL FDAPVTAECG HSFCRACLIR VAGEPAADGT VACPCCQAPT
RPQALSTNLQ LSRLVEGLAQ VPQGHCEEHL DPLSIYCEQD RTLVCGVCAS LGSHRGHRLL
PAAEAQARLK TQLPQQKMQL QEACMRKEKT VAVLEHQLVE VEETVRQFRG AVGEQLGKMR
MFLAALESSL DREAERVRGD AGVALRRELS SLNSYLEQLR QMEKVLEEVA DKPQTEFLMK
FCLVTSRLQK ILSESPPPAR LDIQLPVISD DFKFQVWKKM FRALMPALEE LTFDPSSAHP
SLVVSSSGRR VECSDQKAPP AGEDTRQFDK AVAVVAQQLL SQGEHYWEVE VGDKPRWALG
VMAADASRRG RLHAVPSQGL WLLGLRDGKI LEAHVEAKEP RALRTPERPP ARIGLYLSFA
DGVLAFYDAS NPDVLTPIFS FHERLPGPVY PIFDVCWHDK GKNAQPLLLV GPEQEQA
