TRI25_MOUSE
ID TRI25_MOUSE Reviewed; 634 AA.
AC Q61510; Q5SU70;
DT 24-JAN-2001, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 2.
DT 03-AUG-2022, entry version 186.
DE RecName: Full=E3 ubiquitin/ISG15 ligase TRIM25;
DE EC=6.3.2.n3 {ECO:0000250|UniProtKB:Q14258};
DE AltName: Full=Estrogen-responsive finger protein {ECO:0000303|PubMed:7592654};
DE AltName: Full=RING-type E3 ubiquitin transferase;
DE EC=2.3.2.27 {ECO:0000250|UniProtKB:Q14258};
DE AltName: Full=RING-type E3 ubiquitin transferase TRIM25 {ECO:0000305};
DE AltName: Full=Tripartite motif-containing protein 25;
DE AltName: Full=Ubiquitin/ISG15-conjugating enzyme TRIM25;
DE AltName: Full=Zinc finger protein 147;
GN Name=Trim25; Synonyms=Efp {ECO:0000303|PubMed:7592654}, Zfp147, Znf147;
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.
RC TISSUE=Ovary, Placenta, and Uterus;
RX PubMed=7592654; DOI=10.1074/jbc.270.41.24406;
RA Orimo A., Inoue S., Ikeda K., Noji S., Muramatsu M.;
RT "Molecular cloning, structure, and expression of mouse estrogen-responsive
RT finger protein Efp. Co-localization with estrogen receptor mRNA in target
RT organs.";
RL J. Biol. Chem. 270:24406-24413(1995).
RN [2]
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [4]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Kidney, Liver, 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 [5]
RP FUNCTION, INTERACTION WITH OOEP; KHDC3 AND BLM, AND SUBCELLULAR LOCATION.
RX PubMed=29125140; DOI=10.1038/cr.2017.139;
RA Zhao B., Zhang W., Cun Y., Li J., Liu Y., Gao J., Zhu H., Zhou H.,
RA Zhang R., Zheng P.;
RT "Mouse embryonic stem cells have increased capacity for replication fork
RT restart driven by the specific Filia-Floped protein complex.";
RL Cell Res. 28:69-89(2018).
CC -!- FUNCTION: Functions as a ubiquitin E3 ligase and as an ISG15 E3 ligase.
CC Involved in innate immune defense against viruses by mediating
CC ubiquitination of DDX58 and IFIH1 (By similarity). Mediates 'Lys-63'-
CC linked polyubiquitination of the DDX58 N-terminal CARD-like region and
CC may play a role in signal transduction that leads to the production of
CC interferons in response to viral infection (By similarity). Mediates
CC 'Lys-63'-linked polyubiquitination of IFIH1 (By similarity). Promotes
CC ISGylation of 14-3-3 sigma (SFN), an adapter protein implicated in the
CC regulation of a large spectrum signaling pathway. Mediates estrogen
CC action in various target organs (By similarity). Mediates the
CC ubiquitination and subsequent proteasomal degradation of ZFHX3 (By
CC similarity). Plays a role in promoting the restart of stalled
CC replication forks via interaction with the KHDC3-OOEP scaffold and
CC subsequent ubiquitination of BLM, resulting in the recruitment and
CC retainment of BLM at DNA replication forks (PubMed:29125140).
CC {ECO:0000250|UniProtKB:Q14258, ECO:0000269|PubMed:29125140}.
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:0000250|UniProtKB:Q14258};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + [ISG15] + [protein]-lysine = AMP + diphosphate +
CC [protein]-N-ISGyllysine.; EC=6.3.2.n3;
CC Evidence={ECO:0000250|UniProtKB:Q14258};
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC -!- SUBUNIT: Interacts (via SPRY domain) with DDX58 (via CARD domain).
CC Interacts with ZFHX3. Interacts with NLRP12; this interaction reduces
CC the E3 ubiquitin ligase TRIM25-mediated 'Lys-63'-linked DDX58
CC activation. Interacts with the KHDC3/FILIA-OOEP/FLOPED scaffold complex
CC and BLM at DNA replication forks (PubMed:29125140). Interacts with
CC RTN3; this interaction prevents DDX58 ubiquitination (By similarity).
CC {ECO:0000250|UniProtKB:Q14258, ECO:0000269|PubMed:29125140}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q14258}.
CC Cytoplasm, Stress granule {ECO:0000250|UniProtKB:Q14258}. Nucleus
CC {ECO:0000269|PubMed:29125140}. Note=Localized to DNA replication forks.
CC {ECO:0000269|PubMed:29125140}.
CC -!- TISSUE SPECIFICITY: Ubiquitous. {ECO:0000269|PubMed:7592654}.
CC -!- DOMAIN: The RING-type zinc finger is important for ISG15 E3 ligase
CC activity and autoISGylation. AutoISGylation negatively regulates ISG15
CC E3 ligase activity. {ECO:0000250|UniProtKB:Q14258}.
CC -!- DOMAIN: The C-terminal B30.2/SPRY domain interacts with the first N-
CC terminal CARD domain of DDX58. {ECO:0000250|UniProtKB:Q14258}.
CC -!- PTM: Auto-ISGylated. {ECO:0000250|UniProtKB:Q14258}.
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DR EMBL; D63902; BAA09941.1; -; mRNA.
DR EMBL; AK169562; BAE41230.1; -; mRNA.
DR EMBL; AL646096; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS36278.1; -.
DR PIR; I49642; I49642.
DR RefSeq; NP_033572.2; NM_009546.2.
DR PDB; 4B8E; X-ray; 1.78 A; A/B=440-634.
DR PDBsum; 4B8E; -.
DR AlphaFoldDB; Q61510; -.
DR SMR; Q61510; -.
DR BioGRID; 229840; 5.
DR IntAct; Q61510; 1.
DR MINT; Q61510; -.
DR STRING; 10090.ENSMUSP00000103528; -.
DR iPTMnet; Q61510; -.
DR PhosphoSitePlus; Q61510; -.
DR SwissPalm; Q61510; -.
DR EPD; Q61510; -.
DR MaxQB; Q61510; -.
DR PaxDb; Q61510; -.
DR PeptideAtlas; Q61510; -.
DR PRIDE; Q61510; -.
DR ProteomicsDB; 258975; -.
DR Antibodypedia; 1778; 541 antibodies from 38 providers.
DR DNASU; 217069; -.
DR Ensembl; ENSMUST00000107896; ENSMUSP00000103528; ENSMUSG00000000275.
DR GeneID; 217069; -.
DR KEGG; mmu:217069; -.
DR UCSC; uc007kwc.1; mouse.
DR CTD; 7706; -.
DR MGI; MGI:102749; Trim25.
DR VEuPathDB; HostDB:ENSMUSG00000000275; -.
DR eggNOG; KOG2177; Eukaryota.
DR GeneTree; ENSGT00940000160741; -.
DR InParanoid; Q61510; -.
DR OMA; CYGSMPR; -.
DR OrthoDB; 209218at2759; -.
DR PhylomeDB; Q61510; -.
DR TreeFam; TF351086; -.
DR Reactome; R-MMU-1169408; ISG15 antiviral mechanism.
DR Reactome; R-MMU-5656169; Termination of translesion DNA synthesis.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 217069; 3 hits in 75 CRISPR screens.
DR ChiTaRS; Trim25; mouse.
DR PRO; PR:Q61510; -.
DR Proteomes; UP000000589; Chromosome 11.
DR RNAct; Q61510; protein.
DR Bgee; ENSMUSG00000000275; Expressed in paneth cell and 262 other tissues.
DR ExpressionAtlas; Q61510; baseline and differential.
DR Genevisible; Q61510; MM.
DR GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR GO; GO:0010494; C:cytoplasmic stress granule; ISO:MGI.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0016604; C:nuclear body; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0016874; F:ligase activity; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0039552; F:RIG-I binding; ISO:MGI.
DR GO; GO:0003713; F:transcription coactivator activity; ISO:MGI.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; ISO:MGI.
DR GO; GO:0004842; F:ubiquitin-protein transferase activity; ISO:MGI.
DR GO; GO:1990830; P:cellular response to leukemia inhibitory factor; IEP:MGI.
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: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:0006513; P:protein monoubiquitination; ISO:MGI.
DR GO; GO:0032880; P:regulation of protein localization; IMP:UniProtKB.
DR GO; GO:0046596; P:regulation of viral entry into host cell; ISO:MGI.
DR GO; GO:0043627; P:response to estrogen; ISO:MGI.
DR GO; GO:0033280; P:response to vitamin D; IEA:Ensembl.
DR GO; GO:0044790; P:suppression of viral release by host; IDA:UniProtKB.
DR GO; GO:0030433; P:ubiquitin-dependent ERAD pathway; ISO:MGI.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; ISO:MGI.
DR GO; GO:0019076; P:viral release from host cell; ISO:MGI.
DR CDD; cd13736; SPRY_PRY_TRIM25; 1.
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; IPR042753; TRIM25_SPRY_PRY.
DR InterPro; IPR027370; Znf-RING_LisH.
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; PF13445; zf-RING_UBOX; 1.
DR PRINTS; PR01407; BUTYPHLNCDUF.
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; PS00518; ZF_RING_1; 1.
DR PROSITE; PS50089; ZF_RING_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Antiviral defense; Coiled coil; Cytoplasm;
KW Immunity; Innate immunity; Isopeptide bond; Ligase; Metal-binding; Nucleus;
KW Phosphoprotein; Reference proteome; Transferase; Ubl conjugation;
KW Ubl conjugation pathway; Zinc; Zinc-finger.
FT CHAIN 1..634
FT /note="E3 ubiquitin/ISG15 ligase TRIM25"
FT /id="PRO_0000056234"
FT DOMAIN 444..634
FT /note="B30.2/SPRY"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00548"
FT ZN_FING 13..54
FT /note="RING-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00175"
FT REGION 353..437
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 215..305
FT /evidence="ECO:0000255"
FT COMPBIAS 365..381
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 90
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q14258"
FT MOD_RES 99
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q14258"
FT MOD_RES 272
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q14258"
FT MOD_RES 277
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q14258"
FT MOD_RES 572
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q14258"
FT CROSSLNK 116
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ISG15)"
FT /evidence="ECO:0000250|UniProtKB:Q14258"
FT CONFLICT 34
FT /note="M -> T (in Ref. 1; BAA09941)"
FT /evidence="ECO:0000305"
FT CONFLICT 165
FT /note="L -> F (in Ref. 1; BAA09941)"
FT /evidence="ECO:0000305"
FT CONFLICT 261
FT /note="K -> R (in Ref. 1; BAA09941)"
FT /evidence="ECO:0000305"
FT CONFLICT 439
FT /note="V -> I (in Ref. 1; BAA09941)"
FT /evidence="ECO:0000305"
FT HELIX 441..450
FT /evidence="ECO:0007829|PDB:4B8E"
FT HELIX 454..457
FT /evidence="ECO:0007829|PDB:4B8E"
FT HELIX 458..460
FT /evidence="ECO:0007829|PDB:4B8E"
FT TURN 468..470
FT /evidence="ECO:0007829|PDB:4B8E"
FT STRAND 475..478
FT /evidence="ECO:0007829|PDB:4B8E"
FT TURN 479..482
FT /evidence="ECO:0007829|PDB:4B8E"
FT STRAND 483..486
FT /evidence="ECO:0007829|PDB:4B8E"
FT STRAND 501..509
FT /evidence="ECO:0007829|PDB:4B8E"
FT STRAND 514..523
FT /evidence="ECO:0007829|PDB:4B8E"
FT STRAND 528..535
FT /evidence="ECO:0007829|PDB:4B8E"
FT STRAND 540..542
FT /evidence="ECO:0007829|PDB:4B8E"
FT HELIX 543..545
FT /evidence="ECO:0007829|PDB:4B8E"
FT STRAND 553..559
FT /evidence="ECO:0007829|PDB:4B8E"
FT STRAND 562..567
FT /evidence="ECO:0007829|PDB:4B8E"
FT STRAND 570..574
FT /evidence="ECO:0007829|PDB:4B8E"
FT STRAND 581..587
FT /evidence="ECO:0007829|PDB:4B8E"
FT TURN 588..591
FT /evidence="ECO:0007829|PDB:4B8E"
FT STRAND 592..609
FT /evidence="ECO:0007829|PDB:4B8E"
FT STRAND 616..624
FT /evidence="ECO:0007829|PDB:4B8E"
FT STRAND 628..631
FT /evidence="ECO:0007829|PDB:4B8E"
SQ SEQUENCE 634 AA; 71726 MW; 3B764531AAE8582E CRC64;
MAELNPLAEE LSCSVCLELF KEPVTTPCGH NFCMSCLDET WVVQGPPYRC PQCRKVYQVR
PQLQKNTVMC AVVEQFLQAE QARTPVDDWT PPARFSASSA ATQVACDHCL TEIAVKTCLV
CMASFCQEHL RPHFDSPAFQ DHPLQSPIRD LLRRKCTQHN RLRELFCPEH GECICHICLV
EHKTCSPTTL SQASADLEYK LRNKLTIMHS HINGATKALE DVRSKQQCVQ DSMKRKMEQL
RQEYMEMKAV IDAAETSSLR KLKEEEKRVY GKFDTIYQVL VKKKSEMQKL KAEVELIMDK
GDEFEFLEKA AKLQGESTKP VYIPKIDLDH DLIMGIYQGA ADLKSELKHS IKKLQKKSEE
HNGSGNKGDQ TQSTFKPVQP SKKTIQEKKT KKTPVAPGPP SHFSPNKLPT FGAPGQSLDS
KATSPDAAPK ASAAQPDSVG VKAKVLENFL TKSRTELLEY FVKVIFDYNT AHNKVSLSNK
YTTASVSDGL QHYRSHPQRF TYCSQVLGLH CYKNGIHYWE VELQKNNFCG VGICYGSMER
QGPESRLGRN PNSWCVEWFN NKISAWHNNV EKTLPSTKAT RVGVLLNCDH GFVIFFAVTE
KVHLMYKFKV DFTEALYPAF WVFSAGTTLS ICSK
