TRI35_HUMAN
ID TRI35_HUMAN Reviewed; 493 AA.
AC Q9UPQ4; Q86XQ0; Q8WVA4;
DT 07-DEC-2004, integrated into UniProtKB/Swiss-Prot.
DT 07-DEC-2004, sequence version 2.
DT 03-AUG-2022, entry version 173.
DE RecName: Full=E3 ubiquitin-protein ligase TRIM35 {ECO:0000303|PubMed:32562145};
DE EC=2.3.2.27;
DE AltName: Full=Hemopoietic lineage switch protein 5;
GN Name=TRIM35; Synonyms=HLS5, KIAA1098;
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).
RC TISSUE=Liver;
RX PubMed=14662771; DOI=10.1074/jbc.m306751200;
RA Lalonde J.-P., Lim R., Ingley E., Tilbrook P.A., Thompson M.J.,
RA McCulloch R., Beaumont J.G., Wicking C., Eyre H.J., Sutherland G.R.,
RA Howe K., Solomon E., Williams J.H., Klinken S.P.;
RT "HLS5, a novel RBCC (ring finger, B box, coiled-coil) family member
RT isolated from a hemopoietic lineage switch, is a candidate tumor
RT suppressor.";
RL J. Biol. Chem. 279:8181-8189(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=10470851; DOI=10.1093/dnares/6.3.197;
RA Kikuno R., Nagase T., Ishikawa K., Hirosawa M., Miyajima N., Tanaka A.,
RA Kotani H., Nomura N., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XIV. The
RT complete sequences of 100 new cDNA clones from brain which code for large
RT proteins in vitro.";
RL DNA Res. 6:197-205(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Brain, and Lung;
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 [4]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, PHOSPHORYLATION [LARGE SCALE
RP ANALYSIS] AT SER-4 AND SER-8, AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-4, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=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 [6]
RP FUNCTION, INTERACTION WITH PKM, AND SUBCELLULAR LOCATION.
RX PubMed=25263439; DOI=10.1038/onc.2014.325;
RA Chen Z., Wang Z., Guo W., Zhang Z., Zhao F., Zhao Y., Jia D., Ding J.,
RA Wang H., Yao M., He X.;
RT "TRIM35 Interacts with pyruvate kinase isoform M2 to suppress the Warburg
RT effect and tumorigenicity in hepatocellular carcinoma.";
RL Oncogene 34:3946-3956(2015).
RN [7]
RP FUNCTION, INDUCTION BY TLR5 AND TLR7, AND INTERACTION WITH IRF7.
RX PubMed=25907537; DOI=10.1016/j.febslet.2015.04.019;
RA Wang Y., Yan S., Yang B., Wang Y., Zhou H., Lian Q., Sun B.;
RT "TRIM35 negatively regulates TLR7- and TLR9-mediated type I interferon
RT production by targeting IRF7.";
RL FEBS Lett. 589:1322-1330(2015).
RN [8]
RP FUNCTION, AND INTERACTION WITH TRAF3.
RX PubMed=32562145; DOI=10.1007/s13238-020-00734-6;
RA Sun N., Jiang L., Ye M., Wang Y., Wang G., Wan X., Zhao Y., Wen X.,
RA Liang L., Ma S., Liu L., Bu Z., Chen H., Li C.;
RT "TRIM35 mediates protection against influenza infection by activating TRAF3
RT and degrading viral PB2.";
RL Protein Cell 11:894-914(2020).
CC -!- FUNCTION: E3 ubiquitin-protein ligase that participates in multiple
CC biological processes including cell death, glucose metabolism, and in
CC particular, the innate immune response. Mediates 'Lys-63'-linked
CC polyubiquitination of TRAF3 thereby promoting type I interferon
CC production via DDX58/RIG-I signaling pathway (PubMed:32562145). Can
CC also catalyze 'Lys-48'-linked polyubiquitination and proteasomal
CC degradation of viral proteins such as influenza virus PB2
CC (PubMed:32562145). Acts as a negative feedback regulator of TLR7- and
CC TLR9-triggered signaling. Mechanistically, promotes the 'Lys-48'-linked
CC ubiquitination of IRF7 and induces its degradation via a proteasome-
CC dependent pathway (PubMed:25907537). Reduces FGFR1-dependent tyrosine
CC phosphorylation of PKM, inhibiting PKM-dependent lactate production,
CC glucose metabolism, and cell growth (PubMed:25263439).
CC {ECO:0000269|PubMed:25263439, ECO:0000269|PubMed:25907537,
CC ECO:0000269|PubMed:32562145}.
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;
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC -!- SUBUNIT: Interacts with PKM isoform M2, but not isoform M1; this
CC interaction may compete with that between PKM and FGFR1, and hence
CC reduces FGFR1-dependent tyrosine phosphorylation of PKM
CC (PubMed:25263439). Interacts with IRF7; this interaction promotes IRF7
CC proteasomal degradation (PubMed:25907537). Interacts with TRAF3; this
CC interaction promotes TRAF3 activation (PubMed:32562145).
CC {ECO:0000269|PubMed:25263439, ECO:0000269|PubMed:25907537,
CC ECO:0000269|PubMed:32562145}.
CC -!- INTERACTION:
CC Q9UPQ4-2; Q15848: ADIPOQ; NbExp=3; IntAct=EBI-17716262, EBI-10827839;
CC Q9UPQ4-2; Q8N9N5-2: BANP; NbExp=3; IntAct=EBI-17716262, EBI-11524452;
CC Q9UPQ4-2; Q9NPB3: CABP2; NbExp=3; IntAct=EBI-17716262, EBI-12011224;
CC Q9UPQ4-2; P27658: COL8A1; NbExp=3; IntAct=EBI-17716262, EBI-747133;
CC Q9UPQ4-2; Q86UW9: DTX2; NbExp=3; IntAct=EBI-17716262, EBI-740376;
CC Q9UPQ4-2; Q9H0I2: ENKD1; NbExp=3; IntAct=EBI-17716262, EBI-744099;
CC Q9UPQ4-2; P22607: FGFR3; NbExp=3; IntAct=EBI-17716262, EBI-348399;
CC Q9UPQ4-2; Q53EP0-3: FNDC3B; NbExp=3; IntAct=EBI-17716262, EBI-10242151;
CC Q9UPQ4-2; Q14749: GNMT; NbExp=3; IntAct=EBI-17716262, EBI-744239;
CC Q9UPQ4-2; Q14957: GRIN2C; NbExp=3; IntAct=EBI-17716262, EBI-8285963;
CC Q9UPQ4-2; P28799: GRN; NbExp=3; IntAct=EBI-17716262, EBI-747754;
CC Q9UPQ4-2; I6L957: HNRNPA2B1; NbExp=3; IntAct=EBI-17716262, EBI-1642515;
CC Q9UPQ4-2; P42858: HTT; NbExp=9; IntAct=EBI-17716262, EBI-466029;
CC Q9UPQ4-2; Q86VF2-5: IGFN1; NbExp=3; IntAct=EBI-17716262, EBI-11955401;
CC Q9UPQ4-2; Q63ZY3: KANK2; NbExp=3; IntAct=EBI-17716262, EBI-2556193;
CC Q9UPQ4-2; O60333-2: KIF1B; NbExp=3; IntAct=EBI-17716262, EBI-10975473;
CC Q9UPQ4-2; P06239-3: LCK; NbExp=3; IntAct=EBI-17716262, EBI-13287659;
CC Q9UPQ4-2; P25800: LMO1; NbExp=3; IntAct=EBI-17716262, EBI-8639312;
CC Q9UPQ4-2; Q16656-4: NRF1; NbExp=3; IntAct=EBI-17716262, EBI-11742836;
CC Q9UPQ4-2; Q9BYG5: PARD6B; NbExp=3; IntAct=EBI-17716262, EBI-295391;
CC Q9UPQ4-2; O14737: PDCD5; NbExp=3; IntAct=EBI-17716262, EBI-712290;
CC Q9UPQ4-2; Q9UPV7: PHF24; NbExp=3; IntAct=EBI-17716262, EBI-17717171;
CC Q9UPQ4-2; P67775: PPP2CA; NbExp=3; IntAct=EBI-17716262, EBI-712311;
CC Q9UPQ4-2; O43741: PRKAB2; NbExp=3; IntAct=EBI-17716262, EBI-1053424;
CC Q9UPQ4-2; O60260-5: PRKN; NbExp=3; IntAct=EBI-17716262, EBI-21251460;
CC Q9UPQ4-2; P86480: PRR20D; NbExp=3; IntAct=EBI-17716262, EBI-12754095;
CC Q9UPQ4-2; P47897: QARS1; NbExp=4; IntAct=EBI-17716262, EBI-347462;
CC Q9UPQ4-2; Q9Y3C5: RNF11; NbExp=3; IntAct=EBI-17716262, EBI-396669;
CC Q9UPQ4-2; Q92529: SHC3; NbExp=3; IntAct=EBI-17716262, EBI-79084;
CC Q9UPQ4-2; Q12824-2: SMARCB1; NbExp=3; IntAct=EBI-17716262, EBI-358436;
CC Q9UPQ4-2; Q7Z699: SPRED1; NbExp=3; IntAct=EBI-17716262, EBI-5235340;
CC Q9UPQ4-2; Q8N8B7-2: TCEANC; NbExp=3; IntAct=EBI-17716262, EBI-11955057;
CC Q9UPQ4-2; O75865-2: TRAPPC6A; NbExp=3; IntAct=EBI-17716262, EBI-8451480;
CC Q9UPQ4-2; Q9UDY6-2: TRIM10; NbExp=3; IntAct=EBI-17716262, EBI-11981577;
CC Q9UPQ4-2; Q96PN8: TSSK3; NbExp=3; IntAct=EBI-17716262, EBI-3918381;
CC Q9UPQ4-2; P61086: UBE2K; NbExp=6; IntAct=EBI-17716262, EBI-473850;
CC Q9UPQ4-2; Q9UMX0: UBQLN1; NbExp=3; IntAct=EBI-17716262, EBI-741480;
CC Q9UPQ4-2; O76024: WFS1; NbExp=3; IntAct=EBI-17716262, EBI-720609;
CC Q9UPQ4-2; Q86VK4-3: ZNF410; NbExp=3; IntAct=EBI-17716262, EBI-11741890;
CC Q9UPQ4-2; Q9Y649; NbExp=3; IntAct=EBI-17716262, EBI-25900580;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:25263439}. Nucleus
CC {ECO:0000250}. Note=Found predominantly in cytoplasm with a granular
CC distribution. Found in punctuate nuclear bodies (By similarity).
CC {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9UPQ4-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9UPQ4-2; Sequence=VSP_012061;
CC -!- INDUCTION: By TLR7 and TLR9 stimulation. {ECO:0000269|PubMed:25907537}.
CC -!- DOMAIN: The RING finger domain and the coiled-coil region are required
CC for the apoptosis-inducing activity. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the TRIM/RBCC family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA83050.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AF492463; AAO85480.1; -; mRNA.
DR EMBL; AB029021; BAA83050.1; ALT_INIT; mRNA.
DR EMBL; BC018337; AAH18337.1; -; mRNA.
DR EMBL; BC069226; AAH69226.1; -; mRNA.
DR CCDS; CCDS6056.2; -. [Q9UPQ4-1]
DR RefSeq; NP_741983.2; NM_171982.4. [Q9UPQ4-1]
DR AlphaFoldDB; Q9UPQ4; -.
DR SMR; Q9UPQ4; -.
DR BioGRID; 116716; 104.
DR IntAct; Q9UPQ4; 68.
DR STRING; 9606.ENSP00000301924; -.
DR iPTMnet; Q9UPQ4; -.
DR PhosphoSitePlus; Q9UPQ4; -.
DR BioMuta; TRIM35; -.
DR DMDM; 56404980; -.
DR EPD; Q9UPQ4; -.
DR jPOST; Q9UPQ4; -.
DR MassIVE; Q9UPQ4; -.
DR MaxQB; Q9UPQ4; -.
DR PaxDb; Q9UPQ4; -.
DR PeptideAtlas; Q9UPQ4; -.
DR PRIDE; Q9UPQ4; -.
DR ProteomicsDB; 85414; -. [Q9UPQ4-1]
DR ProteomicsDB; 85415; -. [Q9UPQ4-2]
DR Antibodypedia; 10095; 304 antibodies from 33 providers.
DR DNASU; 23087; -.
DR Ensembl; ENST00000305364.9; ENSP00000301924.4; ENSG00000104228.13. [Q9UPQ4-1]
DR GeneID; 23087; -.
DR KEGG; hsa:23087; -.
DR MANE-Select; ENST00000305364.9; ENSP00000301924.4; NM_171982.5; NP_741983.2.
DR UCSC; uc003xfl.2; human. [Q9UPQ4-1]
DR CTD; 23087; -.
DR DisGeNET; 23087; -.
DR GeneCards; TRIM35; -.
DR HGNC; HGNC:16285; TRIM35.
DR HPA; ENSG00000104228; Low tissue specificity.
DR MIM; 617007; gene.
DR neXtProt; NX_Q9UPQ4; -.
DR OpenTargets; ENSG00000104228; -.
DR PharmGKB; PA38115; -.
DR VEuPathDB; HostDB:ENSG00000104228; -.
DR eggNOG; KOG2177; Eukaryota.
DR GeneTree; ENSGT00940000160868; -.
DR HOGENOM; CLU_013137_0_3_1; -.
DR InParanoid; Q9UPQ4; -.
DR OMA; ICYDPFR; -.
DR OrthoDB; 472443at2759; -.
DR PhylomeDB; Q9UPQ4; -.
DR TreeFam; TF334286; -.
DR PathwayCommons; Q9UPQ4; -.
DR Reactome; R-HSA-877300; Interferon gamma signaling.
DR SignaLink; Q9UPQ4; -.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 23087; 18 hits in 1126 CRISPR screens.
DR ChiTaRS; TRIM35; human.
DR GenomeRNAi; 23087; -.
DR Pharos; Q9UPQ4; Tbio.
DR PRO; PR:Q9UPQ4; -.
DR Proteomes; UP000005640; Chromosome 8.
DR RNAct; Q9UPQ4; protein.
DR Bgee; ENSG00000104228; Expressed in calcaneal tendon and 146 other tissues.
DR ExpressionAtlas; Q9UPQ4; baseline and differential.
DR Genevisible; Q9UPQ4; HS.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
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:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0045087; P:innate immune response; IDA:UniProtKB.
DR GO; GO:0045930; P:negative regulation of mitotic cell cycle; IDA:UniProtKB.
DR GO; GO:0043065; P:positive regulation of apoptotic process; IDA:UniProtKB.
DR GO; GO:0016567; P:protein ubiquitination; IBA:GO_Central.
DR GO; GO:0044790; P:suppression of viral release by host; IDA: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; 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 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; Apoptosis; Coiled coil; Cytoplasm;
KW Metal-binding; Nucleus; Phosphoprotein; Reference proteome; Transferase;
KW Ubl conjugation pathway; Zinc; Zinc-finger.
FT CHAIN 1..493
FT /note="E3 ubiquitin-protein ligase TRIM35"
FT /id="PRO_0000056250"
FT DOMAIN 284..487
FT /note="B30.2/SPRY"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00548"
FT ZN_FING 21..61
FT /note="RING-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00175"
FT ZN_FING 96..137
FT /note="B box-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00024"
FT COILED 210..251
FT /evidence="ECO:0000255"
FT BINDING 101
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00024"
FT BINDING 104
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00024"
FT BINDING 123
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00024"
FT BINDING 129
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00024"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0007744|PubMed:21406692"
FT MOD_RES 4
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 8
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21406692"
FT VAR_SEQ 146..206
FT /note="AKCRNMEHALREKAKAFWAMRRSYEAIAKHNQVEAAWLEGRIRQEFDKLREF
FT LRVEEQAIL -> VRSLIAEERRNFLPTHQWIVTKTRLQTSSPNLQSRRQGQVQEHGAC
FT TAGEGQGLLGHAALL (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_012061"
SQ SEQUENCE 493 AA; 56540 MW; BFB7E5BFD3AD7E2D CRC64;
MERSPDVSPG PSRSFKEELL CAVCYDPFRD AVTLRCGHNF CRGCVSRCWE VQVSPTCPVC
KDRASPADLR TNHTLNNLVE KLLREEAEGA RWTSYRFSRV CRLHRGQLSL FCLEDKELLC
CSCQADPRHQ GHRVQPVKDT AHDFRAKCRN MEHALREKAK AFWAMRRSYE AIAKHNQVEA
AWLEGRIRQE FDKLREFLRV EEQAILDAMA EETRQKQLLA DEKMKQLTEE TEVLAHEIER
LQMEMKEDDV SFLMKHKSRK RRLFCTMEPE PVQPGMLIDV CKYLGSLQYR VWKKMLASVE
SVPFSFDPNT AAGWLSVSDD LTSVTNHGYR VQVENPERFS SAPCLLGSRV FSQGSHAWEV
ALGGLQSWRV GVVRVRQDSG AEGHSHSCYH DTRSGFWYVC RTQGVEGDHC VTSDPATSPL
VLAIPRRLRV ELECEEGELS FYDAERHCHL YTFHARFGEV RPYFYLGGAR GAGPPEPLRI
CPLHISVKEE LDG
