TRI56_MOUSE
ID TRI56_MOUSE Reviewed; 734 AA.
AC Q80VI1; Q8CAY0;
DT 21-DEC-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2003, sequence version 1.
DT 03-AUG-2022, entry version 142.
DE RecName: Full=E3 ubiquitin-protein ligase TRIM56 {ECO:0000305};
DE EC=2.3.2.27 {ECO:0000269|PubMed:21074459};
DE AltName: Full=Tripartite motif-containing protein 56;
GN Name=Trim56 {ECO:0000303|PubMed:21074459, ECO:0000312|MGI:MGI:2685298};
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 [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Thymus;
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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Mammary tumor;
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 [3]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Lung, Pancreas, and Spleen;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [4]
RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH STING1, AND INDUCTION.
RX PubMed=21074459; DOI=10.1016/j.immuni.2010.10.013;
RA Tsuchida T., Zou J., Saitoh T., Kumar H., Abe T., Matsuura Y., Kawai T.,
RA Akira S.;
RT "The ubiquitin ligase TRIM56 regulates innate immune responses to
RT intracellular double-stranded DNA.";
RL Immunity 33:765-776(2010).
RN [5]
RP FUNCTION, CATALYTIC ACTIVITY, PATHWAY, AND DISRUPTION PHENOTYPE.
RX PubMed=29426904; DOI=10.1038/s41467-018-02936-3;
RA Seo G.J., Kim C., Shin W.J., Sklan E.H., Eoh H., Jung J.U.;
RT "TRIM56-mediated monoubiquitination of cGAS for cytosolic DNA sensing.";
RL Nat. Commun. 9:613-613(2018).
CC -!- FUNCTION: E3 ubiquitin-protein ligase that plays a key role in innate
CC antiviral immunity by mediating ubiquitination of CGAS and STING1
CC (PubMed:21074459, PubMed:29426904). In response to pathogen- and host-
CC derived double-stranded DNA (dsDNA), targets STING1 to 'Lys-63'-linked
CC ubiquitination, thereby promoting its homodimerization, a step required
CC for the production of type I interferon IFN-beta (PubMed:21074459).
CC Also mediates monoubiquitination of CGAS, thereby promoting CGAS
CC oligomerization and subsequent activation (PubMed:29426904).
CC Independently of its E3 ubiquitin ligase activity, positive regulator
CC of TLR3 signaling (By similarity). Potentiates extracellular double
CC stranded RNA (dsRNA)-induced expression of IFNB1 and interferon-
CC stimulated genes ISG15, IFIT1/ISG56, CXCL10, OASL and CCL5/RANTES (By
CC similarity). {ECO:0000250|UniProtKB:Q9BRZ2,
CC ECO:0000269|PubMed:21074459, ECO:0000269|PubMed:29426904}.
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:21074459,
CC ECO:0000269|PubMed:29426904};
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC {ECO:0000269|PubMed:21074459, ECO:0000269|PubMed:29426904}.
CC -!- SUBUNIT: Interacts with STING1 (PubMed:21074459). Interacts with TICAM1
CC (By similarity). {ECO:0000250|UniProtKB:Q9BRZ2,
CC ECO:0000269|PubMed:21074459}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:21074459}.
CC -!- INDUCTION: By interferon. {ECO:0000269|PubMed:21074459}.
CC -!- DISRUPTION PHENOTYPE: High susceptibility to DNA virus infection, such
CC as lethal herpes simplex virus-1 (HSV-1) (PubMed:29426904). Cells are
CC defective in CGAS-mediated type I interferon IFN-beta production upon
CC HSV-1 infection (PubMed:29426904). No susceptibility to RNA virus
CC infection, such as influenza A virus (PubMed:29426904). No visible
CC phenotype in normal conditions (PubMed:29426904).
CC {ECO:0000269|PubMed:29426904}.
CC -!- SIMILARITY: Belongs to the TRIM/RBCC family. {ECO:0000305}.
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DR EMBL; AK037350; BAC29792.1; -; mRNA.
DR EMBL; BC045615; AAH45615.1; -; mRNA.
DR CCDS; CCDS19762.1; -.
DR RefSeq; NP_958761.1; NM_201373.4.
DR RefSeq; XP_006504504.1; XM_006504441.3.
DR RefSeq; XP_011239185.1; XM_011240883.1.
DR AlphaFoldDB; Q80VI1; -.
DR SMR; Q80VI1; -.
DR BioGRID; 239120; 9.
DR IntAct; Q80VI1; 2.
DR MINT; Q80VI1; -.
DR STRING; 10090.ENSMUSP00000058109; -.
DR iPTMnet; Q80VI1; -.
DR PhosphoSitePlus; Q80VI1; -.
DR EPD; Q80VI1; -.
DR jPOST; Q80VI1; -.
DR MaxQB; Q80VI1; -.
DR PaxDb; Q80VI1; -.
DR PeptideAtlas; Q80VI1; -.
DR PRIDE; Q80VI1; -.
DR ProteomicsDB; 259323; -.
DR DNASU; 384309; -.
DR GeneID; 384309; -.
DR KEGG; mmu:384309; -.
DR UCSC; uc009abq.2; mouse.
DR CTD; 81844; -.
DR MGI; MGI:2685298; Trim56.
DR eggNOG; KOG2177; Eukaryota.
DR InParanoid; Q80VI1; -.
DR OrthoDB; 489543at2759; -.
DR PhylomeDB; Q80VI1; -.
DR TreeFam; TF338323; -.
DR Reactome; R-MMU-3134975; Regulation of innate immune responses to cytosolic DNA.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 384309; 3 hits in 77 CRISPR screens.
DR ChiTaRS; Trim56; mouse.
DR PRO; PR:Q80VI1; -.
DR Proteomes; UP000000589; Unplaced.
DR RNAct; Q80VI1; protein.
DR GO; GO:0000785; C:chromatin; IBA:GO_Central.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; IBA:GO_Central.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; IDA:UniProtKB.
DR GO; GO:0004842; F:ubiquitin-protein transferase activity; IBA:GO_Central.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0051607; P:defense response to virus; IDA: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:0032728; P:positive regulation of interferon-beta production; IMP:UniProtKB.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IBA:GO_Central.
DR GO; GO:0060340; P:positive regulation of type I interferon-mediated signaling pathway; IDA:UniProtKB.
DR GO; GO:0070534; P:protein K63-linked ubiquitination; IDA:UniProtKB.
DR GO; GO:0006513; P:protein monoubiquitination; IDA:UniProtKB.
DR GO; GO:0034340; P:response to type I interferon; IDA:UniProtKB.
DR GO; GO:0044790; P:suppression of viral release by host; IDA:UniProtKB.
DR Gene3D; 2.120.10.30; -; 1.
DR Gene3D; 3.30.40.10; -; 1.
DR InterPro; IPR011042; 6-blade_b-propeller_TolB-like.
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; PF00643; zf-B_box; 1.
DR Pfam; PF13445; zf-RING_UBOX; 1.
DR SMART; SM00336; BBOX; 1.
DR SMART; SM00184; RING; 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 Antiviral defense; Coiled coil; Cytoplasm; Immunity; Innate immunity;
KW Metal-binding; Phosphoprotein; Reference proteome; Repeat; Transferase;
KW Ubl conjugation pathway; Zinc; Zinc-finger.
FT CHAIN 1..734
FT /note="E3 ubiquitin-protein ligase TRIM56"
FT /id="PRO_0000056289"
FT ZN_FING 21..60
FT /note="RING-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00175"
FT ZN_FING 98..149
FT /note="B box-type 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00024"
FT ZN_FING 164..205
FT /note="B box-type 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00024"
FT REGION 372..463
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 215..303
FT /evidence="ECO:0000255"
FT COMPBIAS 418..435
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 169
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00024"
FT BINDING 172
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00024"
FT BINDING 192
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00024"
FT BINDING 197
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00024"
FT MOD_RES 454
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9BRZ2"
FT CONFLICT 5
FT /note="V -> D (in Ref. 1; BAC29792)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 734 AA; 79513 MW; 3A8192AC7E57BB3C CRC64;
MNSKVSSPTL LEALSSDFLA CKICLEQLHT PKTLPCLHTY CQDCLAQLDI GGQVRCPECR
EIVPVPAEGV AAFKTNFFVN GLLDLVKARA PGDVHSGKPT CALCPLVGGK SSGGPATARC
LDCADDLCQA CADGHRCSRQ THKHRVVDLV GYRAGWYDEE ARERQASQCP QHPGEALCFL
CQPCSQLLCK DCRLGPHIDH PCLPLAEAVR SRKPGLEELL AGVDSNLVEL EATRVAEKEA
LALLREQAAS VGTQVEEAAE RILKSLLAQK QEVLGQLRAL VEAAEEATRE RLTKIERQEQ
VAKAAAAFAR RVLSLGLEAE ILSLEGAITQ RLRQLQDAPW TSGPTRCVLP QLELHPGLED
KNCHLLRLIF EEPKQSPKDS GKGGAGTQGG DEAQGQGDDR TKIGKQGGAQ PLTPKEGKDQ
NPQEDDGVFI ERGNRPNKKK KCKGRGKSVS REPSPILRPN LEGSGLLPRP VFSWSFPTRM
PGDKRSPRIT GLCPYGPQEI LVADEQNRVL KRFSLNGDYK GTVQVPEGCS PCSVAALQNA
VAFSANAKLY LVSPDGEIQW RRSLSLTQSS HAVAAMPCGD RVAVSVAGHV EVYKKDGSLA
TRFIPGGKAS RGQRALVFLT TSPQGNFVGS DWQQNSVVFC DGLGQVIWEY KGPGLHGCQP
GSVSVDKKGY IFLTLREVNK VVILDPKGSL LGDFLTAYHG LEKPRVTTMV DGKYLVVSLS
NGTIHVFRVR FPDS
