TRIM8_MOUSE
ID TRIM8_MOUSE Reviewed; 551 AA.
AC Q99PJ2; Q3U2G3; Q8C508; Q8C700; Q8CGI2; Q99PQ4;
DT 26-SEP-2001, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 3.
DT 03-AUG-2022, entry version 174.
DE RecName: Full=E3 ubiquitin-protein ligase TRIM8;
DE EC=2.3.2.27;
DE AltName: Full=Glioblastoma-expressed RING finger protein;
DE AltName: Full=RING finger protein 27;
DE AltName: Full=RING-type E3 ubiquitin transferase TRIM8 {ECO:0000305};
DE AltName: Full=Tripartite motif-containing protein 8;
GN Name=Trim8; Synonyms=Gerp, Rnf27;
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].
RC TISSUE=Brain;
RX PubMed=11118312; DOI=10.1006/bbrc.2000.3984;
RA Vincent S.R., Kwasnicka D.A., Fretier P.;
RT "A novel RING finger-B box-coiled-coil protein, GERP.";
RL Biochem. Biophys. Res. Commun. 279:482-486(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J, and NOD; TISSUE=Kidney;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Colon;
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 NUCLEOTIDE SEQUENCE [MRNA] OF 196-463, AND TISSUE SPECIFICITY.
RX PubMed=11331580; DOI=10.1093/emboj/20.9.2140;
RA Reymond A., Meroni G., Fantozzi A., Merla G., Cairo S., Luzi L.,
RA Riganelli D., Zanaria E., Messali S., Cainarca S., Guffanti A., Minucci S.,
RA Pelicci P.G., Ballabio A.;
RT "The tripartite motif family identifies cell compartments.";
RL EMBO J. 20:2140-2151(2001).
RN [5]
RP FUNCTION, INTERACTION WITH SOCS1, TISSUE SPECIFICITY, INDUCTION, AND
RP C-TERMINAL DOMAIN.
RX PubMed=12163497; DOI=10.1074/jbc.m205900200;
RA Toniato E., Chen X.P., Losman J., Flati V., Donahue L., Rothman P.;
RT "TRIM8/GERP RING finger protein interacts with SOCS-1.";
RL J. Biol. Chem. 277:37315-37322(2002).
RN [6]
RP INTERACTION WITH HSP90AB1.
RX PubMed=21689689; DOI=10.1016/j.bbamcr.2011.05.013;
RA Okumura F., Okumura A.J., Matsumoto M., Nakayama K.I., Hatakeyama S.;
RT "TRIM8 regulates Nanog via Hsp90beta-mediated nuclear translocation of
RT STAT3 in embryonic stem cells.";
RL Biochim. Biophys. Acta 1813:1784-1792(2011).
RN [7]
RP FUNCTION, INTERACTION WITH TAK1, AND TISSUE SPECIFICITY.
RX PubMed=27995356; DOI=10.1007/s10753-016-0491-3;
RA Guo L., Dong W., Fu X., Lin J., Dong Z., Tan X., Zhang T.;
RT "Tripartite Motif 8 (TRIM8) positively regulates pro-inflammatory responses
RT in Pseudomonas aeruginosa-induced keratitis through promoting K63-Linked
RT polyubiquitination of TAK1 protein.";
RL Inflammation 40:454-463(2017).
RN [8]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=28747347; DOI=10.4049/jimmunol.1601647;
RA Ye W., Hu M.M., Lei C.Q., Zhou Q., Lin H., Sun M.S., Shu H.B.;
RT "TRIM8 Negatively Regulates TLR3/4-Mediated Innate Immune Response by
RT Blocking TRIF-TBK1 Interaction.";
RL J. Immunol. 199:1856-1864(2017).
RN [9]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=31360105; DOI=10.7150/ijbs.33323;
RA Tao Q., Tianyu W., Jiangqiao Z., Zhongbao C., Xiaoxiong M., Long Z.,
RA Jilin Z.;
RT "Tripartite Motif 8 Deficiency Relieves Hepatic Ischaemia/reperfusion
RT Injury via TAK1-dependent Signalling Pathways.";
RL Int. J. Biol. Sci. 15:1618-1629(2019).
CC -!- FUNCTION: E3 ubiquitin-protein ligase that participates in multiple
CC biological processes including cell survival, differentiation,
CC apoptosis, and in particular, the innate immune response
CC (PubMed:28747347, PubMed:31360105). Participates in the activation of
CC interferon-gamma signaling by promoting proteasomal degradation of the
CC repressor SOCS1 (PubMed:12163497). Plays a positive role in the
CC TNFalpha and IL-1beta signaling pathways. Mechanistically, induces the
CC 'Lys-63'-linked polyubiquitination of MAP3K7/TAK1 component leading to
CC the activation of NF-kappa-B (By similarity). Modulates also STAT3
CC activity through negative regulation of PIAS3, either by degradation of
CC PIAS3 through the ubiquitin-proteasome pathway or exclusion of PIAS3
CC from the nucleus (By similarity). Negatively regulates TLR3/4-mediated
CC innate immune response by catalyzing 'Lys-6'- and 'Lys-33'-linked
CC polyubiquitination of TICAM1 and thereby disrupting the TICAM1-TBK1
CC interaction (PubMed:28747347). {ECO:0000250|UniProtKB:Q9BZR9,
CC ECO:0000269|PubMed:12163497, ECO:0000269|PubMed:28747347,
CC ECO:0000269|PubMed:31360105}.
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: Homodimer. Interacts with SOCS1 (via) SH2 domain and SOCS box.
CC Interacts with HSP90AB1; prevents nucleus translocation of
CC phosphorylated STAT3 and HSP90AB1 (PubMed:21689689). Interacts with
CC MAP3K7/TAK1 (By similarity). Interacts with PIAS3 (By similarity).
CC Interacts with TICAM1 (PubMed:28747347). {ECO:0000250|UniProtKB:Q9BZR9,
CC ECO:0000269|PubMed:12163497, ECO:0000269|PubMed:21689689,
CC ECO:0000269|PubMed:28747347}.
CC -!- TISSUE SPECIFICITY: High expression in heart, liver, and thymus.
CC Expressed in embryonic CNS, kidney, lens and gut.
CC {ECO:0000269|PubMed:11331580, ECO:0000269|PubMed:12163497}.
CC -!- DEVELOPMENTAL STAGE: At 10.5 and 12.5 dpc, expressed in the central
CC nervous system. At 14.5 dpc, expressed in the eye (lens and inner
CC neural layer of the retina), in the primitive glomeruli of the
CC developing kidney, in the villi of the gut and in the dorsal root
CC ganglia.
CC -!- DOMAIN: The coiled coil domain is required for homodimerization.
CC {ECO:0000250}.
CC -!- DOMAIN: The region immediately C-terminal to the RING motif is
CC sufficient to mediate the interaction with SOCS1.
CC -!- DISRUPTION PHENOTYPE: Mice are more susceptible to LPS and bacterial-
CC induced death (PubMed:28747347). In addition, TRIM8 deletion plays a
CC protective role in hepatocyte injury triggered by hepatic
CC ischaemia/reperfusion (I/R) injury (PubMed:31360105).
CC {ECO:0000269|PubMed:28747347, ECO:0000269|PubMed:31360105}.
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; AF281047; AAG53088.1; -; mRNA.
DR EMBL; AK052763; BAC35138.1; -; mRNA.
DR EMBL; AK079847; BAC37764.1; -; mRNA.
DR EMBL; AK155303; BAE33177.1; -; mRNA.
DR EMBL; BC037065; AAH37065.1; -; mRNA.
DR EMBL; BC152343; AAI52344.1; -; mRNA.
DR EMBL; BC152344; AAI52345.1; -; mRNA.
DR EMBL; AF220035; AAG53489.1; -; mRNA.
DR CCDS; CCDS38009.1; -.
DR RefSeq; NP_444330.2; NM_053100.2.
DR AlphaFoldDB; Q99PJ2; -.
DR SMR; Q99PJ2; -.
DR BioGRID; 220231; 13.
DR IntAct; Q99PJ2; 1.
DR STRING; 10090.ENSMUSP00000026008; -.
DR PhosphoSitePlus; Q99PJ2; -.
DR EPD; Q99PJ2; -.
DR MaxQB; Q99PJ2; -.
DR PaxDb; Q99PJ2; -.
DR PRIDE; Q99PJ2; -.
DR ProteomicsDB; 298227; -.
DR TopDownProteomics; Q99PJ2; -.
DR Antibodypedia; 31471; 175 antibodies from 29 providers.
DR DNASU; 93679; -.
DR Ensembl; ENSMUST00000026008; ENSMUSP00000026008; ENSMUSG00000025034.
DR GeneID; 93679; -.
DR KEGG; mmu:93679; -.
DR UCSC; uc008hts.1; mouse.
DR CTD; 81603; -.
DR MGI; MGI:1933302; Trim8.
DR VEuPathDB; HostDB:ENSMUSG00000025034; -.
DR eggNOG; KOG2177; Eukaryota.
DR GeneTree; ENSGT00940000157919; -.
DR HOGENOM; CLU_036491_0_0_1; -.
DR InParanoid; Q99PJ2; -.
DR OMA; YPCGVNS; -.
DR OrthoDB; 364341at2759; -.
DR PhylomeDB; Q99PJ2; -.
DR TreeFam; TF333491; -.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 93679; 2 hits in 75 CRISPR screens.
DR ChiTaRS; Trim8; mouse.
DR PRO; PR:Q99PJ2; -.
DR Proteomes; UP000000589; Chromosome 19.
DR RNAct; Q99PJ2; protein.
DR Bgee; ENSMUSG00000025034; Expressed in lacrimal gland and 243 other tissues.
DR Genevisible; Q99PJ2; MM.
DR GO; GO:0005829; C:cytosol; IDA:MGI.
DR GO; GO:0005634; C:nucleus; IDA:MGI.
DR GO; GO:0016605; C:PML body; ISO:MGI.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0042803; F:protein homodimerization activity; ISO:MGI.
DR GO; GO:0003713; F:transcription coactivator activity; ISO:MGI.
DR GO; GO:0004842; F:ubiquitin-protein transferase activity; NAS:UniProtKB.
DR GO; GO:0045087; P:innate immune response; IDA:UniProtKB.
DR GO; GO:0046597; P:negative regulation of viral entry into host cell; IDA:UniProtKB.
DR GO; GO:0032897; P:negative regulation of viral transcription; IDA:UniProtKB.
DR GO; GO:0010508; P:positive regulation of autophagy; ISS:UniProtKB.
DR GO; GO:0051091; P:positive regulation of DNA-binding transcription factor activity; ISO:MGI.
DR GO; GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB signaling; ISO:MGI.
DR GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; ISO:MGI.
DR GO; GO:1900182; P:positive regulation of protein localization to nucleus; IMP:MGI.
DR GO; GO:0019827; P:stem cell population maintenance; IMP:MGI.
DR GO; GO:0044790; P:suppression of viral release by host; IDA:UniProtKB.
DR Gene3D; 3.30.40.10; -; 1.
DR InterPro; IPR001841; Znf_RING.
DR InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR InterPro; IPR017907; Znf_RING_CS.
DR SMART; SM00184; RING; 1.
DR PROSITE; PS00518; ZF_RING_1; 1.
DR PROSITE; PS50089; ZF_RING_2; 1.
PE 1: Evidence at protein level;
KW Coiled coil; Immunity; Innate immunity; Metal-binding; Reference proteome;
KW Repeat; Transferase; Ubl conjugation pathway; Zinc; Zinc-finger.
FT CHAIN 1..551
FT /note="E3 ubiquitin-protein ligase TRIM8"
FT /id="PRO_0000056207"
FT ZN_FING 15..56
FT /note="RING-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00175"
FT ZN_FING 92..132
FT /note="B box-type 1"
FT ZN_FING 140..182
FT /note="B box-type 2"
FT REGION 399..457
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 181..249
FT /evidence="ECO:0000255"
FT COILED 274..295
FT /evidence="ECO:0000255"
FT COMPBIAS 404..428
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 437..457
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CONFLICT 218
FT /note="K -> M (in Ref. 1; AAG53088 and 4; AAG53489)"
FT /evidence="ECO:0000305"
FT CONFLICT 259
FT /note="A -> G (in Ref. 1; AAG53088)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 551 AA; 61602 MW; A5388F450D6566A1 CRC64;
MAENWKNCFE EELICPICLH VFVEPVQLPC KHNFCRGCIG EAWAKDSGLV RCPECNQAYN
QKPGLEKNLK LTNIVEKFNA LHVEKPPTAL HCVFCRRGPP LPAQKVCLRC EAPCCQSHVQ
THLQQPSTAR GHLLVEADDV RAWSCPQHNA YRLYHCEAEQ VAVCQYCCYY SGAHQGHSVC
DVEIRRNEIR KMLMKQQERL EEREQDIEDQ LYKLESDKRL VEEKVSQLKE EVRLQYEKLH
QLLDEDLRQT VEVLDKAQAK FCSENAAQAL HLGERMQEAK KLLGSLQRLF DKTEDVGFMK
NTKSVKILMD RTQTCTGSSL SPPKIGHLNS KLFLNEVAKK EKQLRKMLEG PFSTPVPFLQ
SVPLYPCGVN SSGAEKRKHS TAFPEASFLE TSSGPVGGQY GAAGTASSEG QSGQPLGPCS
STQHLVALPG GTQPVHSSPV FPPSQYPNGS TTQQPMLPQY GGRKILVCSV DNCYCSSVAN
HGGHQPYPRS GHFPWTVPSQ EYSHPLPPTP SVPQSLPGLA VRDWLDASQQ PGHQDFYRVY
GQPSTKHYVT S
