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 27-MAR-2024, entry version 138.
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).
RN [5]
RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH NLRP3, AND DISRUPTION
RP PHENOTYPE.
RX PubMed=36178239; DOI=10.15252/embr.202154569;
RA Lin Y., Lv X., Sun C., Sun Y., Yang M., Ma D., Jing W., Zhao Y., Cheng Y.,
RA Xuan H., Han L.;
RT "TRIM50 promotes NLRP3 inflammasome activation by directly inducing NLRP3
RT oligomerization.";
RL EMBO Rep. 23:e54569-e54569(2022).
CC -!- FUNCTION: E3 ubiquitin-protein ligase that ubiquitinates Beclin-1/BECN1
CC in a 'Lys-63'-dependent manner enhancing its binding to ULK1
CC (PubMed:29604308). In turn, promotes starvation-induced autophagy
CC activation. Interacts also with p62/SQSTM1 protein and thereby induces
CC the formation and the autophagy clearance of aggresome-associated
CC polyubiquitinated proteins through HDAC6 interaction (PubMed:22792322).
CC Promotes also NLRP3 inflammasome activation by directly inducing NLRP3
CC oligomerization independent of its E3 ligase function
CC (PubMed:36178239). {ECO:0000269|PubMed:22792322,
CC ECO:0000269|PubMed:29604308, ECO:0000269|PubMed:36178239}.
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 Interacts with NLRP3 (PubMed:36178239). {ECO:0000250|UniProtKB:Q86XT4,
CC ECO:0000269|PubMed:22792322, ECO:0000269|PubMed:29604308,
CC ECO:0000269|PubMed:36178239}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:22792322,
CC ECO:0000269|PubMed:24308962, ECO:0000269|PubMed:29604308,
CC ECO:0000269|PubMed:36178239}. Note=Localizes mainly into discrete
CC cytoplasmic punctuate structures heterogeneous in size and shape
CC containing polyubiquitinated proteins. {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 -!- DISRUPTION PHENOTYPE: TRIM50-deficient mice show a significantly
CC prolonged survival time when LPS-challenged when compared with wild-
CC type mice. TRIM50 deficiency also significantly ameliorates NLRP3-
CC mediated inflammation and tissue damage in vivo.
CC {ECO:0000269|PubMed:36178239}.
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 BioGRID; 229593; 1.
DR STRING; 10090.ENSMUSP00000066662; -.
DR iPTMnet; Q810I2; -.
DR PhosphoSitePlus; Q810I2; -.
DR PaxDb; 10090-ENSMUSP00000106811; -.
DR ProteomicsDB; 298303; -.
DR Antibodypedia; 14287; 150 antibodies from 19 providers.
DR DNASU; 215061; -.
DR Ensembl; ENSMUST00000065785.4; ENSMUSP00000066662.4; ENSMUSG00000053388.11.
DR GeneID; 215061; -.
DR KEGG; mmu:215061; -.
DR UCSC; uc008zyf.1; mouse.
DR AGR; MGI:2664992; -.
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 OrthoDB; 3453019at2759; -.
DR PhylomeDB; Q810I2; -.
DR Reactome; R-MMU-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR BioGRID-ORCS; 215061; 1 hit in 77 CRISPR screens.
DR PRO; PR:Q810I2; -.
DR Proteomes; UP000000589; Chromosome 5.
DR RNAct; Q810I2; Protein.
DR Bgee; ENSMUSG00000053388; Expressed in stomach and 11 other cell types or 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 CDD; cd16605; RING-HC_TRIM50_like_C-IV; 1.
DR CDD; cd13743; SPRY_PRY_TRIM50; 1.
DR Gene3D; 2.60.120.920; -; 1.
DR Gene3D; 3.30.160.60; Classic Zinc Finger; 1.
DR Gene3D; 3.30.40.10; Zinc/RING finger domain, C3HC4 (zinc finger); 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_euk.
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; E3 UBIQUITIN-PROTEIN LIGASE TRIM; 1.
DR PANTHER; PTHR24103:SF326; E3 UBIQUITIN-PROTEIN LIGASE TRIM50-RELATED; 1.
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; SSF57845; B-box zinc-binding domain; 1.
DR SUPFAM; SSF49899; Concanavalin A-like lectins/glucanases; 1.
DR SUPFAM; SSF57850; RING/U-box; 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
//
