TRI50_MOUSE
ID TRI50_MOUSE Reviewed; 483 AA.
AC Q810I2;
DT 07-DEC-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2003, sequence version 1.
DT 03-AUG-2022, entry version 130.
DE RecName: Full=E3 ubiquitin-protein ligase TRIM50;
DE EC=2.3.2.27 {ECO:0000269|PubMed:29604308};
DE AltName: Full=RING-type E3 ubiquitin transferase TRIM50 {ECO:0000305};
DE AltName: Full=Tripartite motif-containing protein 50;
GN Name=Trim50;
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], AND TISSUE SPECIFICITY.
RX PubMed=18398435; DOI=10.1038/ejhg.2008.68;
RA Micale L., Fusco C., Augello B., Napolitano L.M.R., Dermitzakis E.T.,
RA Meroni G., Merla G., Reymond A.;
RT "Williams-Beuren syndrome TRIM50 encodes an E3 ubiquitin ligase.";
RL Eur. J. Hum. Genet. 16:1038-1049(2008).
RN [2]
RP FUNCTION, INTERACTION WITH SQSTM1, AND SUBCELLULAR LOCATION.
RX PubMed=22792322; DOI=10.1371/journal.pone.0040440;
RA Fusco C., Micale L., Egorov M., Monti M., D'Addetta E.V., Augello B.,
RA Cozzolino F., Calcagni A., Fontana A., Polishchuk R.S., Didelot G.,
RA Reymond A., Pucci P., Merla G.;
RT "The E3-ubiquitin ligase TRIM50 interacts with HDAC6 and p62, and promotes
RT the sequestration and clearance of ubiquitinated proteins into the
RT aggresome.";
RL PLoS ONE 7:E40440-E40440(2012).
RN [3]
RP SUBCELLULAR LOCATION, ACETYLATION AT LYS-372, AND MUTAGENESIS OF LYS-372.
RX PubMed=24308962; DOI=10.1016/j.cellsig.2013.11.036;
RA Fusco C., Micale L., Augello B., Mandriani B., Pellico M.T., De Nittis P.,
RA Calcagni A., Monti M., Cozzolino F., Pucci P., Merla G.;
RT "HDAC6 mediates the acetylation of TRIM50.";
RL Cell. Signal. 26:363-369(2014).
RN [4]
RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH BECN1, AND CATALYTIC
RP ACTIVITY.
RX PubMed=29604308; DOI=10.1016/j.bbamcr.2018.03.011;
RA Fusco C., Mandriani B., Di Rienzo M., Micale L., Malerba N.,
RA Cocciadiferro D., Sjoettem E., Augello B., Squeo G.M., Pellico M.T.,
RA Jain A., Johansen T., Fimia G.M., Merla G.;
RT "TRIM50 regulates Beclin 1 proautophagic activity.";
RL Biochim. Biophys. Acta 1865:908-919(2018).
CC -!- FUNCTION: E3 ubiquitin-protein ligase that ubiquitinates Beclin-1/BECN1
CC in a 'Lys-63'-dependent manner enhancing its binding to ULK1. In turn,
CC promotes starvation-induced autophagy activation. Interacts also with
CC p62/SQSTM1 protein and thereby induces the formation and the autophagy
CC clearance of aggresome-associated polyubiquitinated proteins through
CC HDAC6 interaction. {ECO:0000269|PubMed:22792322,
CC ECO:0000269|PubMed:29604308}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine +
CC [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-
CC cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine.;
CC EC=2.3.2.27; Evidence={ECO:0000269|PubMed:29604308};
CC -!- SUBUNIT: Can form dimers and trimers. Interacts with several E2
CC ubiquitin-conjugating enzymes, including UBE2L6, UBE2E1, UBE2E3. No
CC interaction with UBE2H. Interacts with BECN1. Interacts with SQSTM1.
CC {ECO:0000250|UniProtKB:Q86XT4, ECO:0000269|PubMed:22792322,
CC ECO:0000269|PubMed:29604308}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:22792322,
CC ECO:0000269|PubMed:24308962, ECO:0000269|PubMed:29604308}.
CC Note=Localizes mainly into discrete cytoplasmic punctuate structures
CC heterogeneous in size and shape containing polyubiquitinated proteins.
CC {ECO:0000269|PubMed:22792322}.
CC -!- TISSUE SPECIFICITY: Expressed in the stomach.
CC {ECO:0000269|PubMed:18398435}.
CC -!- PTM: Auto-ubiquitinated. {ECO:0000250|UniProtKB:Q86XT4}.
CC -!- PTM: Acetylated by EP300 and KAT2B. HDAC6 drives TRIM50 deacetylation.
CC Acetylation antagonizes with TRIM50 ubiquitination.
CC {ECO:0000269|PubMed:24308962}.
CC -!- SIMILARITY: Belongs to the TRIM/RBCC family. {ECO:0000305}.
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DR EMBL; AY081947; AAL91070.1; -; mRNA.
DR CCDS; CCDS19739.1; -.
DR RefSeq; NP_839971.1; NM_178240.2.
DR RefSeq; XP_006504475.1; XM_006504412.3.
DR AlphaFoldDB; Q810I2; -.
DR SMR; Q810I2; -.
DR STRING; 10090.ENSMUSP00000106811; -.
DR iPTMnet; Q810I2; -.
DR PhosphoSitePlus; Q810I2; -.
DR PaxDb; Q810I2; -.
DR PRIDE; Q810I2; -.
DR ProteomicsDB; 298303; -.
DR Antibodypedia; 14287; 131 antibodies from 18 providers.
DR DNASU; 215061; -.
DR Ensembl; ENSMUST00000065785; ENSMUSP00000066662; ENSMUSG00000053388.
DR GeneID; 215061; -.
DR KEGG; mmu:215061; -.
DR UCSC; uc008zyf.1; mouse.
DR CTD; 135892; -.
DR MGI; MGI:2664992; Trim50.
DR VEuPathDB; HostDB:ENSMUSG00000053388; -.
DR eggNOG; KOG2177; Eukaryota.
DR GeneTree; ENSGT00940000161467; -.
DR HOGENOM; CLU_013137_0_3_1; -.
DR InParanoid; Q810I2; -.
DR PhylomeDB; Q810I2; -.
DR Reactome; R-MMU-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR BioGRID-ORCS; 215061; 1 hit in 72 CRISPR screens.
DR PRO; PR:Q810I2; -.
DR Proteomes; UP000000589; Chromosome 5.
DR RNAct; Q810I2; protein.
DR Bgee; ENSMUSG00000053388; Expressed in stomach and 8 other tissues.
DR ExpressionAtlas; Q810I2; baseline and differential.
DR GO; GO:0016235; C:aggresome; IDA:MGI.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; IBA:GO_Central.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0016567; P:protein ubiquitination; IBA:GO_Central.
DR GO; GO:0070201; P:regulation of establishment of protein localization; IDA:MGI.
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; IPR027370; Znf-RING_LisH.
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 Pfam; PF13765; PRY; 1.
DR Pfam; PF00622; SPRY; 1.
DR Pfam; PF00643; zf-B_box; 1.
DR Pfam; PF13445; zf-RING_UBOX; 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 Acetylation; Coiled coil; Cytoplasm; Metal-binding; Reference proteome;
KW Transferase; Ubl conjugation; Ubl conjugation pathway; Zinc; Zinc-finger.
FT CHAIN 1..483
FT /note="E3 ubiquitin-protein ligase TRIM50"
FT /id="PRO_0000056275"
FT DOMAIN 275..474
FT /note="B30.2/SPRY"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00548"
FT ZN_FING 16..57
FT /note="RING-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00175"
FT ZN_FING 84..125
FT /note="B box-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00024"
FT COILED 127..169
FT /evidence="ECO:0000255"
FT COILED 203..236
FT /evidence="ECO:0000255"
FT BINDING 89
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00024"
FT BINDING 92
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00024"
FT BINDING 111
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00024"
FT BINDING 117
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00024"
FT MOD_RES 372
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000269|PubMed:24308962"
FT MUTAGEN 372
FT /note="K->R: Complete loss of acetylation."
FT /evidence="ECO:0000269|PubMed:24308962"
SQ SEQUENCE 483 AA; 54607 MW; DA3A7234C1A8145B CRC64;
MAWRLTVPEL QDQLQCPICL EVFKEPLMLQ CGHSYCKDCL DNLSQHLDSE LCCPVCRQSV
DCSSSPPNVS LARVIDALRL PGDIEPTVCV HHRNPLSLFC EKDQEFICGL CGLLGSHQHH
RVTPVSTVYS RMKEELAGRI SELKEEHRNV EEHIGKLVNN RTRIINESDV FSWVIRREFQ
ELHHLVDEEK ARCLEGLEGH TRGLVASLDM QLEQAQGTQE RLAQAEQVLE QFGNESHHEF
IRFHSVASRA EVQQARPLEG VFSPISFKPA LHQADIKLTV WKRLFRKVLP APASLKLDPA
TAHPLLELSK GNTVVHCGLL AQRRASQPER FDYSTCVLAS KGFSWGRHYW EVVVGSKSDW
RLGVIKGTAS RKGKLNKSPE HGVWLIGLKE GRVYEAFGCP RLPLPVAGHP HRIGVYLHYE
QGELTFFDAD RPDDLRTLYT FQADFQGKLY PILDTCWHER GSNSLPMVLP PPSGPGHFTL
GQV
