TRI50_HUMAN
ID TRI50_HUMAN Reviewed; 487 AA.
AC Q86XT4; Q2M204; Q86XT3;
DT 07-DEC-2004, integrated into UniProtKB/Swiss-Prot.
DT 23-FEB-2022, sequence version 2.
DT 03-AUG-2022, entry version 154.
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 {ECO:0000312|HGNC:HGNC:19017}; Synonyms=TRIM50A;
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 (ISOFORMS ALPHA AND BETA), FUNCTION, SUBCELLULAR
RP LOCATION, AUTOUBIQUITINATION, DIMERIZATION, TRIMERIZATION, INTERACTION WITH
RP UBE2L6; UBE2E1 AND UBE2E3, AND VARIANTS LEU-8 AND TRP-13.
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] {ECO:0000312|EMBL:BAF84763.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Stomach {ECO:0000312|EMBL:BAF84763.1};
RA Wakamatsu A., Yamamoto J., Kimura K., Ishii S., Watanabe K., Sugiyama A.,
RA Murakawa K., Kaida T., Tsuchiya K., Fukuzumi Y., Kumagai A., Oishi Y.,
RA Yamamoto S., Ono Y., Komori Y., Yamazaki M., Kisu Y., Nishikawa T.,
RA Sugano S., Nomura N., Isogai T.;
RT "NEDO human cDNA sequencing project.";
RL Submitted (OCT-2007) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12853948; DOI=10.1038/nature01782;
RA Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H.,
RA Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K.,
RA Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A.,
RA Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H., Sun H.,
RA Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A.,
RA Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P.,
RA Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M.,
RA Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S.,
RA Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R.,
RA Strowmatt C., Latreille P., Miller N., Johnson D., Murray J.,
RA Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W.,
RA Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A.,
RA Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E.,
RA Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E.,
RA Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A.,
RA Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A.,
RA Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R.,
RA McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H.,
RA Wilson R.K.;
RT "The DNA sequence of human chromosome 7.";
RL Nature 424:157-164(2003).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [5] {ECO:0000312|EMBL:AAI12155.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 [6]
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 [7]
RP SUBCELLULAR LOCATION, AND ACETYLATION.
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 [8]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH BECN1.
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:18398435,
CC ECO:0000269|PubMed:22792322, 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:0000269|PubMed:18398435, ECO:0000269|PubMed:22792322,
CC ECO:0000269|PubMed:29604308}.
CC -!- INTERACTION:
CC Q86XT4; Q92619: ARHGAP45; NbExp=3; IntAct=EBI-9867283, EBI-2825900;
CC Q86XT4; Q07002: CDK18; NbExp=3; IntAct=EBI-9867283, EBI-746238;
CC Q86XT4; P49760: CLK2; NbExp=3; IntAct=EBI-9867283, EBI-750020;
CC Q86XT4; Q5JST6: EFHC2; NbExp=3; IntAct=EBI-9867283, EBI-2349927;
CC Q86XT4; Q7L775: EPM2AIP1; NbExp=3; IntAct=EBI-9867283, EBI-6255981;
CC Q86XT4; A6H8Z2: FAM221B; NbExp=3; IntAct=EBI-9867283, EBI-12006844;
CC Q86XT4; Q96CN9: GCC1; NbExp=3; IntAct=EBI-9867283, EBI-746252;
CC Q86XT4; Q8NA54: IQUB; NbExp=3; IntAct=EBI-9867283, EBI-10220600;
CC Q86XT4; O95198: KLHL2; NbExp=3; IntAct=EBI-9867283, EBI-746999;
CC Q86XT4; Q969R5: L3MBTL2; NbExp=3; IntAct=EBI-9867283, EBI-739909;
CC Q86XT4; Q8TBB1: LNX1; NbExp=5; IntAct=EBI-9867283, EBI-739832;
CC Q86XT4; Q6FHY5: MEOX2; NbExp=3; IntAct=EBI-9867283, EBI-16439278;
CC Q86XT4; O75928-2: PIAS2; NbExp=3; IntAct=EBI-9867283, EBI-348567;
CC Q86XT4; O60733: PLA2G6; NbExp=3; IntAct=EBI-9867283, EBI-12089905;
CC Q86XT4; P54725: RAD23A; NbExp=3; IntAct=EBI-9867283, EBI-746453;
CC Q86XT4; Q9UHP6: RSPH14; NbExp=3; IntAct=EBI-9867283, EBI-748350;
CC Q86XT4; Q9NZD8: SPG21; NbExp=3; IntAct=EBI-9867283, EBI-742688;
CC Q86XT4; Q96N21: TEPSIN; NbExp=3; IntAct=EBI-9867283, EBI-11139477;
CC Q86XT4; Q12933: TRAF2; NbExp=3; IntAct=EBI-9867283, EBI-355744;
CC Q86XT4; P14373: TRIM27; NbExp=3; IntAct=EBI-9867283, EBI-719493;
CC Q86XT4; Q86XT4: TRIM50; NbExp=6; IntAct=EBI-9867283, EBI-9867283;
CC Q86XT4; Q3SY00: TSGA10IP; NbExp=3; IntAct=EBI-9867283, EBI-10241197;
CC Q86XT4; Q96PN8: TSSK3; NbExp=6; IntAct=EBI-9867283, EBI-3918381;
CC Q86XT4; P57075-2: UBASH3A; NbExp=3; IntAct=EBI-9867283, EBI-7353612;
CC Q86XT4; P51668: UBE2D1; NbExp=5; IntAct=EBI-9867283, EBI-743540;
CC Q86XT4; P62837: UBE2D2; NbExp=3; IntAct=EBI-9867283, EBI-347677;
CC Q86XT4; Q9Y2X8: UBE2D4; NbExp=3; IntAct=EBI-9867283, EBI-745527;
CC Q86XT4; Q96LR5: UBE2E2; NbExp=6; IntAct=EBI-9867283, EBI-2129763;
CC Q86XT4; Q969T4: UBE2E3; NbExp=3; IntAct=EBI-9867283, EBI-348496;
CC Q86XT4; P61086: UBE2K; NbExp=3; IntAct=EBI-9867283, EBI-473850;
CC Q86XT4; Q9HAC8: UBTD1; NbExp=3; IntAct=EBI-9867283, EBI-745871;
CC Q86XT4; O75604: USP2; NbExp=3; IntAct=EBI-9867283, EBI-743272;
CC Q86XT4; Q6GPH4: XAF1; NbExp=3; IntAct=EBI-9867283, EBI-2815120;
CC Q86XT4; Q7Z4V0: ZNF438; NbExp=3; IntAct=EBI-9867283, EBI-11962468;
CC Q86XT4; Q6ZNG0: ZNF620; NbExp=3; IntAct=EBI-9867283, EBI-4395669;
CC Q86XT4; PRO_0000449631 [P0DTD1]: rep; Xeno; NbExp=3; IntAct=EBI-9867283, EBI-25475920;
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 -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=Alpha;
CC IsoId=Q86XT4-1; Sequence=Displayed;
CC Name=Beta;
CC IsoId=Q86XT4-2; Sequence=VSP_012088;
CC -!- PTM: Auto-ubiquitinated. {ECO:0000269|PubMed:18398435}.
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}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AY081948; AAL91071.1; -; mRNA.
DR EMBL; AY081949; AAL91072.1; -; mRNA.
DR EMBL; AK292074; BAF84763.1; -; mRNA.
DR EMBL; AC073841; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471200; EAW69688.1; -; Genomic_DNA.
DR EMBL; CH471200; EAW69691.1; -; Genomic_DNA.
DR EMBL; BC112152; AAI12153.1; -; mRNA.
DR EMBL; BC112154; AAI12155.1; -; mRNA.
DR CCDS; CCDS34654.1; -. [Q86XT4-1]
DR RefSeq; NP_001268379.1; NM_001281450.1.
DR RefSeq; NP_001268380.1; NM_001281451.1.
DR RefSeq; NP_835226.2; NM_178125.3.
DR AlphaFoldDB; Q86XT4; -.
DR SMR; Q86XT4; -.
DR BioGRID; 126435; 46.
DR IntAct; Q86XT4; 36.
DR STRING; 9606.ENSP00000327994; -.
DR iPTMnet; Q86XT4; -.
DR PhosphoSitePlus; Q86XT4; -.
DR BioMuta; TRIM50; -.
DR DMDM; 56404881; -.
DR jPOST; Q86XT4; -.
DR MassIVE; Q86XT4; -.
DR PaxDb; Q86XT4; -.
DR PeptideAtlas; Q86XT4; -.
DR PRIDE; Q86XT4; -.
DR ProteomicsDB; 70331; -. [Q86XT4-1]
DR ProteomicsDB; 70332; -. [Q86XT4-2]
DR Antibodypedia; 14287; 131 antibodies from 18 providers.
DR DNASU; 135892; -.
DR Ensembl; ENST00000333149.7; ENSP00000327994.2; ENSG00000146755.11. [Q86XT4-1]
DR Ensembl; ENST00000453152.1; ENSP00000413875.1; ENSG00000146755.11. [Q86XT4-1]
DR GeneID; 135892; -.
DR KEGG; hsa:135892; -.
DR MANE-Select; ENST00000333149.7; ENSP00000327994.2; NM_178125.3; NP_835226.2.
DR UCSC; uc032zrf.2; human. [Q86XT4-1]
DR CTD; 135892; -.
DR DisGeNET; 135892; -.
DR GeneCards; TRIM50; -.
DR HGNC; HGNC:19017; TRIM50.
DR HPA; ENSG00000146755; Group enriched (pancreas, parathyroid gland, stomach).
DR MIM; 612548; gene.
DR neXtProt; NX_Q86XT4; -.
DR OpenTargets; ENSG00000146755; -.
DR PharmGKB; PA38778; -.
DR VEuPathDB; HostDB:ENSG00000146755; -.
DR eggNOG; KOG2177; Eukaryota.
DR GeneTree; ENSGT00940000161467; -.
DR HOGENOM; CLU_013137_0_3_1; -.
DR InParanoid; Q86XT4; -.
DR OMA; DVCWHER; -.
DR OrthoDB; 574602at2759; -.
DR PhylomeDB; Q86XT4; -.
DR TreeFam; TF342569; -.
DR PathwayCommons; Q86XT4; -.
DR Reactome; R-HSA-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR SignaLink; Q86XT4; -.
DR BioGRID-ORCS; 135892; 11 hits in 1100 CRISPR screens.
DR ChiTaRS; TRIM50; human.
DR GenomeRNAi; 135892; -.
DR Pharos; Q86XT4; Tbio.
DR PRO; PR:Q86XT4; -.
DR Proteomes; UP000005640; Chromosome 7.
DR RNAct; Q86XT4; protein.
DR Bgee; ENSG00000146755; Expressed in body of pancreas and 100 other tissues.
DR ExpressionAtlas; Q86XT4; baseline and differential.
DR Genevisible; Q86XT4; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
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 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; Alternative splicing; Coiled coil; Cytoplasm; Metal-binding;
KW Reference proteome; Transferase; Ubl conjugation; Ubl conjugation pathway;
KW Zinc; Zinc-finger.
FT CHAIN 1..487
FT /note="E3 ubiquitin-protein ligase TRIM50"
FT /id="PRO_0000056274"
FT DOMAIN 276..475
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 REGION 468..487
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 125..169
FT /evidence="ECO:0000255"
FT COILED 204..235
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 373
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q810I2"
FT VAR_SEQ 243
FT /note="Missing (in isoform Beta)"
FT /evidence="ECO:0000305"
FT /id="VSP_012088"
FT VARIANT 8
FT /note="P -> L (in dbSNP:rs6980124)"
FT /evidence="ECO:0000269|PubMed:18398435"
FT /id="VAR_020491"
FT VARIANT 13
FT /note="R -> W"
FT /evidence="ECO:0000269|PubMed:18398435"
FT /id="VAR_085709"
SQ SEQUENCE 487 AA; 54728 MW; 00E417623E5287C6 CRC64;
MAWQVSLPEL EDRLQCPICL EVFKEPLMLQ CGHSYCKGCL VSLSCHLDAE LRCPVCRQAV
DGSSSLPNVS LARVIEALRL PGDPEPKVCV HHRNPLSLFC EKDQELICGL CGLLGSHQHH
PVTPVSTVYS RMKEELAALI SELKQEQKKV DELIAKLVNN RTRIVNESDV FSWVIRREFQ
ELHHLVDEEK ARCLEGIGGH TRGLVASLDM QLEQAQGTRE RLAQAECVLE QFGNEDHHKF
IRKFHSMASR AEMPQARPLE GAFSPISFKP GLHQADIKLT VWKRLFRKVL PAPEPLKLDP
ATAHPLLELS KGNTVVQCGL LAQRRASQPE RFDYSTCVLA SRGFSCGRHY WEVVVGSKSD
WRLGVIKGTA SRKGKLNRSP EHGVWLIGLK EGRVYEAFAC PRVPLPVAGH PHRIGLYLHY
EQGELTFFDA DRPDDLRPLY TFQADFQGKL YPILDTCWHE RGSNSLPMVL PPPSGPGPLS
PEQPTKL
