TRI25_HUMAN
ID TRI25_HUMAN Reviewed; 630 AA.
AC Q14258;
DT 24-JAN-2001, integrated into UniProtKB/Swiss-Prot.
DT 30-NOV-2010, sequence version 2.
DT 03-AUG-2022, entry version 217.
DE RecName: Full=E3 ubiquitin/ISG15 ligase TRIM25;
DE EC=6.3.2.n3 {ECO:0000269|PubMed:16352599};
DE AltName: Full=Estrogen-responsive finger protein {ECO:0000303|PubMed:8248217};
DE AltName: Full=RING finger protein 147;
DE AltName: Full=RING-type E3 ubiquitin transferase;
DE EC=2.3.2.27 {ECO:0000269|PubMed:17392790};
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:8248217}, RNF147, ZNF147;
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], AND VARIANT LEU-358.
RC TISSUE=Placenta;
RX PubMed=8248217; DOI=10.1073/pnas.90.23.11117;
RA Inoue S., Orimo A., Hosoi T., Kondo S., Toyoshima H., Kondo T., Ikegami A.,
RA Ouchi Y., Orimo H., Muramatsu M.;
RT "Genomic binding-site cloning reveals an estrogen-responsive gene that
RT encodes a RING finger protein.";
RL Proc. Natl. Acad. Sci. U.S.A. 90:11117-11121(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16625196; DOI=10.1038/nature04689;
RA Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R.,
RA Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A.,
RA Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J.,
RA Chang J.L., Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J.,
RA DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S.,
RA Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E.,
RA Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K.,
RA LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J.,
RA Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A.,
RA Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K.,
RA Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D.,
RA Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A.,
RA Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.;
RT "DNA sequence of human chromosome 17 and analysis of rearrangement in the
RT human lineage.";
RL Nature 440:1045-1049(2006).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT LEU-358.
RC TISSUE=Lymph;
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 TISSUE SPECIFICITY.
RX PubMed=15130519; DOI=10.1016/j.mce.2003.12.008;
RA Shimada N., Suzuki T., Inoue S., Kato K., Imatani A., Sekine H., Ohara S.,
RA Shimosegawa T., Sasano H.;
RT "Systemic distribution of estrogen-responsive finger protein (Efp) in human
RT tissues.";
RL Mol. Cell. Endocrinol. 218:147-153(2004).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=15592455; DOI=10.1038/nbt1046;
RA Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H.,
RA Zha X.-M., Polakiewicz R.D., Comb M.J.;
RT "Immunoaffinity profiling of tyrosine phosphorylation in cancer cells.";
RL Nat. Biotechnol. 23:94-101(2005).
RN [6]
RP INDUCTION, AND FUNCTION.
RX PubMed=17069755; DOI=10.1016/j.bbrc.2006.10.061;
RA Nakasato N., Ikeda K., Urano T., Horie-Inoue K., Takeda S., Inoue S.;
RT "A ubiquitin E3 ligase Efp is up-regulated by interferons and conjugated
RT with ISG15.";
RL Biochem. Biophys. Res. Commun. 351:540-546(2006).
RN [7]
RP FUNCTION AS A ISG15 E3 LIGASE, CATALYTIC ACTIVITY, AND INDUCTION.
RX PubMed=16352599; DOI=10.1074/jbc.m510787200;
RA Zou W., Zhang D.-E.;
RT "The interferon-inducible ubiquitin-protein isopeptide ligase (E3) EFP also
RT functions as an ISG15 E3 ligase.";
RL J. Biol. Chem. 281:3989-3994(2006).
RN [8]
RP ISGYLATION AT LYS-117, MUTAGENESIS OF LYS-21; LYS-65; LYS-112 AND LYS-117,
RP AND AUTOISGYLATION.
RX PubMed=17222803; DOI=10.1016/j.bbrc.2006.12.210;
RA Zou W., Wang J., Zhang D.-E.;
RT "Negative regulation of ISG15 E3 ligase EFP through its autoISGylation.";
RL Biochem. Biophys. Res. Commun. 354:321-327(2007).
RN [9]
RP FUNCTION AS AN UBIQUITIN LIGASE, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION,
RP AND INTERACTION WITH DDX58.
RX PubMed=17392790; DOI=10.1038/nature05732;
RA Gack M.U., Shin Y.C., Joo C.H., Urano T., Liang C., Sun L., Takeuchi O.,
RA Akira S., Chen Z., Inoue S., Jung J.U.;
RT "TRIM25 RING-finger E3 ubiquitin ligase is essential for RIG-I-mediated
RT antiviral activity.";
RL Nature 446:916-920(2007).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-100, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [11]
RP INTERACTION WITH INFLUENZA VIRUS PROTEIN NS1 (MICROBIAL INFECTION).
RX PubMed=19454348; DOI=10.1016/j.chom.2009.04.006;
RA Gack M.U., Albrecht R.A., Urano T., Inn K.-S., Huang I.-C., Carnero E.,
RA Farzan M., Inoue S., Jung J.U., Garcia-Sastre A.;
RT "Influenza A virus NS1 targets the ubiquitin ligase TRIM25 to evade
RT recognition by the host viral RNA sensor RIG-I.";
RL Cell Host Microbe 5:439-449(2009).
RN [12]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-273 AND LYS-567, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C.,
RA Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [13]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [14]
RP IDENTIFICATION BY MASS SPECTROMETRY [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 [15]
RP FUNCTION, INTERACTION WITH ZFHX3, AND TISSUE SPECIFICITY.
RX PubMed=22452784; DOI=10.1042/bj20111890;
RA Dong X.Y., Fu X., Fan S., Guo P., Su D., Dong J.T.;
RT "Oestrogen causes ATBF1 protein degradation through the oestrogen-
RT responsive E3 ubiquitin ligase EFP.";
RL Biochem. J. 444:581-590(2012).
RN [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-91 AND SER-100, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and 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 [17]
RP FUNCTION, INTERACTION WITH DDX58, AND SUBCELLULAR LOCATION.
RX PubMed=23950712; DOI=10.1371/journal.ppat.1003533;
RA Oshiumi H., Miyashita M., Matsumoto M., Seya T.;
RT "A distinct role of Riplet-mediated K63-Linked polyubiquitination of the
RT RIG-I repressor domain in human antiviral innate immune responses.";
RL PLoS Pathog. 9:E1003533-E1003533(2013).
RN [18]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-278, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [19]
RP INTERACTION WITH SFTSV NSS (MICROBIAL INFECTION).
RX PubMed=24478431; DOI=10.1128/jvi.03021-13;
RA Santiago F.W., Covaleda L.M., Sanchez-Aparicio M.T., Silvas J.A.,
RA Diaz-Vizarreta A.C., Patel J.R., Popov V., Yu X.J., Garcia-Sastre A.,
RA Aguilar P.V.;
RT "Hijacking of RIG-I signaling proteins into virus-induced cytoplasmic
RT structures correlates with the inhibition of type I interferon responses.";
RL J. Virol. 88:4572-4585(2014).
RN [20]
RP FUNCTION.
RX PubMed=30193849; DOI=10.1016/j.immuni.2018.08.014;
RA Lian H., Zang R., Wei J., Ye W., Hu M.M., Chen Y.D., Zhang X.N., Guo Y.,
RA Lei C.Q., Yang Q., Luo W.W., Li S., Shu H.B.;
RT "The zinc-finger protein ZCCHC3 binds RNA and facilitates viral RNA sensing
RT and activation of the RIG-I-like receptors.";
RL Immunity 49:438-448(2018).
RN [21]
RP INTERACTION WITH HRSV NON-STRUCTURAL PROTEIN 1 (MICROBIAL INFECTION).
RX PubMed=30558248; DOI=10.3390/v10120716;
RA Ban J., Lee N.R., Lee N.J., Lee J.K., Quan F.S., Inn K.S.;
RT "Human Respiratory Syncytial Virus NS 1 Targets TRIM25 to Suppress RIG-I
RT Ubiquitination and Subsequent RIG-I-Mediated Antiviral Signaling.";
RL Viruses 10:0-0(2018).
RN [22]
RP INTERACTION WITH NLRP12.
RX PubMed=30902577; DOI=10.1016/j.chom.2019.02.013;
RA Chen S.T., Chen L., Lin D.S., Chen S.Y., Tsao Y.P., Guo H., Li F.J.,
RA Tseng W.T., Tam J.W., Chao C.W., Brickey W.J., Dzhagalov I., Song M.J.,
RA Kang H.R., Jung J.U., Ting J.P.;
RT "NLRP12 Regulates Anti-viral RIG-I Activation via Interaction with
RT TRIM25.";
RL Cell Host Microbe 0:0-0(2019).
RN [23]
RP FUNCTION, AND INTERACTION WITH JC VIRUS SMALL T ANTIGEN (MICROBIAL
RP INFECTION).
RX PubMed=33849980; DOI=10.1128/mbio.00620-21;
RA Chiang C., Dvorkin S., Chiang J.J., Potter R.B., Gack M.U.;
RT "The Small t Antigen of JC Virus Antagonizes RIG-I-Mediated Innate Immunity
RT by Inhibiting TRIM25's RNA Binding Ability.";
RL MBio 12:0-0(2021).
RN [24]
RP INTERACTION WITH RTN3.
RX PubMed=34313226; DOI=10.7554/elife.68958;
RA Yang Z., Wang J., He B., Zhang X., Li X., Kuang E.;
RT "RTN3 inhibits RIG-I-mediated antiviral responses by impairing TRIM25-
RT mediated K63-linked polyubiquitination.";
RL Elife 10:0-0(2021).
RN [25]
RP VARIANT [LARGE SCALE ANALYSIS] LEU-358, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
CC -!- FUNCTION: Functions as a ubiquitin E3 ligase and as an ISG15 E3 ligase
CC (PubMed:16352599). Involved in innate immune defense against viruses by
CC mediating ubiquitination of DDX58 and IFIH1 (PubMed:17392790,
CC PubMed:30193849, PubMed:33849980). Mediates 'Lys-63'-linked
CC polyubiquitination of the DDX58 N-terminal CARD-like region and may
CC play a role in signal transduction that leads to the production of
CC interferons in response to viral infection (PubMed:17392790,
CC PubMed:23950712). Mediates 'Lys-63'-linked polyubiquitination of IFIH1
CC (PubMed:30193849). Promotes ISGylation of 14-3-3 sigma (SFN), an
CC adapter protein implicated in the regulation of a large spectrum
CC signaling pathway (PubMed:16352599, PubMed:17069755). Mediates estrogen
CC action in various target organs (PubMed:22452784). Mediates the
CC ubiquitination and subsequent proteasomal degradation of ZFHX3
CC (PubMed:22452784). Plays a role in promoting the restart of stalled
CC replication forks via interaction with the KHDC3L-OOEP scaffold and
CC subsequent ubiquitination of BLM, resulting in the recruitment and
CC retainment of BLM at DNA replication forks (By similarity).
CC {ECO:0000250|UniProtKB:Q61510, ECO:0000269|PubMed:16352599,
CC ECO:0000269|PubMed:17069755, ECO:0000269|PubMed:17392790,
CC ECO:0000269|PubMed:22452784, ECO:0000269|PubMed:23950712,
CC ECO:0000269|PubMed:30193849, ECO:0000269|PubMed:33849980}.
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:17392790};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + [ISG15] + [protein]-lysine = AMP + diphosphate +
CC [protein]-N-ISGyllysine.; EC=6.3.2.n3;
CC Evidence={ECO:0000269|PubMed:16352599};
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 KHDC3L/FILIA-OOEP/FLOPED scaffold
CC complex and BLM at DNA replication forks (By similarity). Interacts
CC with RTN3; this interaction prevents DDX58 ubiquitination
CC (PubMed:34313226). {ECO:0000250|UniProtKB:Q61510,
CC ECO:0000269|PubMed:17392790, ECO:0000269|PubMed:22452784,
CC ECO:0000269|PubMed:23950712, ECO:0000269|PubMed:30902577,
CC ECO:0000269|PubMed:34313226}.
CC -!- SUBUNIT: (Microbial infection) Interacts (via coiled coil) with
CC influenza A virus NS1 protein; this interaction specifically inhibits
CC TRIM25 multimerization and TRIM25-mediated DDX58 CARD ubiquitination,
CC thereby suppressing DDX58 signal transduction.
CC {ECO:0000269|PubMed:19454348}.
CC -!- SUBUNIT: (Microbial infection) Interacts (via SPRY domain) with human
CC respiratory syncytial virus (HRSV) non-structural protein 1; this
CC interaction suppresses DDX58 ubiquitination and results in decreased
CC interaction between DDX58 and MAVS. {ECO:0000269|PubMed:30558248}.
CC -!- SUBUNIT: (Microbial infection) Interacts with JC virus small t antigen;
CC this interaction suppresses DDX58 ubiquitination thereby suppressing
CC DDX58 signal transduction. {ECO:0000269|PubMed:33849980}.
CC -!- SUBUNIT: (Microbial infection) Interacts with Severe fever with
CC thrombocytopenia virus (SFTSV) NSs; this interaction this interaction
CC sequesters TRIM25 in NSs-induced cytoplasmic inclusion bodies thereby
CC inhibiting the IFN responses. {ECO:0000269|PubMed:24478431}.
CC -!- INTERACTION:
CC Q14258; O95786: DDX58; NbExp=10; IntAct=EBI-2341129, EBI-995350;
CC Q14258; Q13283: G3BP1; NbExp=2; IntAct=EBI-2341129, EBI-1047359;
CC Q14258; K9N4V7: N; Xeno; NbExp=2; IntAct=EBI-2341129, EBI-25592177;
CC Q14258; P0DTC9: N; Xeno; NbExp=13; IntAct=EBI-2341129, EBI-25475856;
CC Q14258; P03496: NS; Xeno; NbExp=3; IntAct=EBI-2341129, EBI-2547442;
CC Q14258; F1BA49; Xeno; NbExp=5; IntAct=EBI-2341129, EBI-9687469;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:17392790}.
CC Cytoplasm, Stress granule {ECO:0000269|PubMed:23950712}. Nucleus
CC {ECO:0000250|UniProtKB:Q61510}.
CC -!- TISSUE SPECIFICITY: Expressed in breast tumors (at protein level).
CC Ubiquitous. {ECO:0000269|PubMed:15130519, ECO:0000269|PubMed:22452784}.
CC -!- INDUCTION: By interferons. {ECO:0000269|PubMed:16352599,
CC ECO:0000269|PubMed:17069755}.
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.
CC -!- DOMAIN: The C-terminal B30.2/SPRY domain interacts with the first N-
CC terminal CARD domain of DDX58.
CC -!- PTM: Auto-ISGylated. {ECO:0000269|PubMed:17222803}.
CC -!- WEB RESOURCE: Name=Wikipedia; Note=TRIM25 entry;
CC URL="https://en.wikipedia.org/wiki/TRIM25";
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DR EMBL; D21205; BAA04747.1; -; mRNA.
DR EMBL; AC015912; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC016924; AAH16924.1; -; mRNA.
DR EMBL; BC042541; AAH42541.1; -; mRNA.
DR CCDS; CCDS11591.1; -.
DR PIR; A49656; A49656.
DR RefSeq; NP_005073.2; NM_005082.4.
DR PDB; 4CFG; X-ray; 2.80 A; A/B=1-630.
DR PDB; 4LTB; X-ray; 2.59 A; A/B=189-379.
DR PDB; 5EYA; X-ray; 2.40 A; F/G=1-83.
DR PDB; 5FER; X-ray; 2.34 A; A/D=1-82.
DR PDB; 5NT1; X-ray; 2.82 A; A/E/I=190-379.
DR PDB; 5NT2; X-ray; 4.26 A; A/I/N/V=190-379.
DR PDB; 6FLM; X-ray; 2.01 A; A/B/C=435-630.
DR PDB; 6FLN; X-ray; 3.60 A; A/B/E=189-630.
DR PDBsum; 4CFG; -.
DR PDBsum; 4LTB; -.
DR PDBsum; 5EYA; -.
DR PDBsum; 5FER; -.
DR PDBsum; 5NT1; -.
DR PDBsum; 5NT2; -.
DR PDBsum; 6FLM; -.
DR PDBsum; 6FLN; -.
DR AlphaFoldDB; Q14258; -.
DR BMRB; Q14258; -.
DR SASBDB; Q14258; -.
DR SMR; Q14258; -.
DR BioGRID; 113500; 2470.
DR CORUM; Q14258; -.
DR IntAct; Q14258; 62.
DR MINT; Q14258; -.
DR STRING; 9606.ENSP00000323889; -.
DR GlyGen; Q14258; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q14258; -.
DR PhosphoSitePlus; Q14258; -.
DR SwissPalm; Q14258; -.
DR BioMuta; TRIM25; -.
DR DMDM; 313104033; -.
DR EPD; Q14258; -.
DR jPOST; Q14258; -.
DR MassIVE; Q14258; -.
DR MaxQB; Q14258; -.
DR PaxDb; Q14258; -.
DR PeptideAtlas; Q14258; -.
DR PRIDE; Q14258; -.
DR ProteomicsDB; 59953; -.
DR Antibodypedia; 1778; 541 antibodies from 38 providers.
DR DNASU; 7706; -.
DR Ensembl; ENST00000316881.9; ENSP00000323889.4; ENSG00000121060.19.
DR Ensembl; ENST00000537230.3; ENSP00000445961.1; ENSG00000121060.19.
DR GeneID; 7706; -.
DR KEGG; hsa:7706; -.
DR MANE-Select; ENST00000316881.9; ENSP00000323889.4; NM_005082.5; NP_005073.2.
DR UCSC; uc002iut.4; human.
DR CTD; 7706; -.
DR DisGeNET; 7706; -.
DR GeneCards; TRIM25; -.
DR HGNC; HGNC:12932; TRIM25.
DR HPA; ENSG00000121060; Low tissue specificity.
DR MIM; 600453; gene.
DR neXtProt; NX_Q14258; -.
DR OpenTargets; ENSG00000121060; -.
DR PharmGKB; PA37519; -.
DR VEuPathDB; HostDB:ENSG00000121060; -.
DR eggNOG; KOG2177; Eukaryota.
DR GeneTree; ENSGT00940000160741; -.
DR HOGENOM; CLU_013137_0_2_1; -.
DR InParanoid; Q14258; -.
DR OMA; CYGSMPR; -.
DR OrthoDB; 209218at2759; -.
DR PhylomeDB; Q14258; -.
DR TreeFam; TF351086; -.
DR BRENDA; 2.3.2.27; 2681.
DR PathwayCommons; Q14258; -.
DR Reactome; R-HSA-1169408; ISG15 antiviral mechanism.
DR Reactome; R-HSA-168928; DDX58/IFIH1-mediated induction of interferon-alpha/beta.
DR Reactome; R-HSA-5656169; Termination of translesion DNA synthesis.
DR Reactome; R-HSA-5689896; Ovarian tumor domain proteases.
DR Reactome; R-HSA-877300; Interferon gamma signaling.
DR Reactome; R-HSA-918233; TRAF3-dependent IRF activation pathway.
DR Reactome; R-HSA-933541; TRAF6 mediated IRF7 activation.
DR Reactome; R-HSA-933542; TRAF6 mediated NF-kB activation.
DR Reactome; R-HSA-933543; NF-kB activation through FADD/RIP-1 pathway mediated by caspase-8 and -10.
DR Reactome; R-HSA-936440; Negative regulators of DDX58/IFIH1 signaling.
DR Reactome; R-HSA-9705671; SARS-CoV-2 activates/modulates innate and adaptive immune responses.
DR SignaLink; Q14258; -.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 7706; 17 hits in 1137 CRISPR screens.
DR ChiTaRS; TRIM25; human.
DR GeneWiki; TRIM25; -.
DR GenomeRNAi; 7706; -.
DR Pharos; Q14258; Tbio.
DR PRO; PR:Q14258; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; Q14258; protein.
DR Bgee; ENSG00000121060; Expressed in ileal mucosa and 181 other tissues.
DR ExpressionAtlas; Q14258; baseline and differential.
DR Genevisible; Q14258; HS.
DR GO; GO:0010494; C:cytoplasmic stress granule; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0016604; C:nuclear body; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0045296; F:cadherin binding; HDA:BHF-UCL.
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; IPI:UniProtKB.
DR GO; GO:0003723; F:RNA binding; HDA:UniProtKB.
DR GO; GO:0003713; F:transcription coactivator activity; IDA:ARUK-UCL.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; IMP:ParkinsonsUK-UCL.
DR GO; GO:0004842; F:ubiquitin-protein transferase activity; EXP:Reactome.
DR GO; GO:1990830; P:cellular response to leukemia inhibitory factor; IEA:Ensembl.
DR GO; GO:0045087; P:innate immune response; IDA:UniProtKB.
DR GO; GO:0046597; P:negative regulation of viral entry into host cell; IEA:Ensembl.
DR GO; GO:0051091; P:positive regulation of DNA-binding transcription factor activity; IMP:UniProtKB.
DR GO; GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB signaling; IDA:UniProtKB.
DR GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; IMP:UniProtKB.
DR GO; GO:0006513; P:protein monoubiquitination; IMP:ParkinsonsUK-UCL.
DR GO; GO:0032880; P:regulation of protein localization; ISS:UniProtKB.
DR GO; GO:0046596; P:regulation of viral entry into host cell; IDA:UniProtKB.
DR GO; GO:0043627; P:response to estrogen; IDA:UniProtKB.
DR GO; GO:0033280; P:response to vitamin D; IEA:Ensembl.
DR GO; GO:0044790; P:suppression of viral release by host; IEA:Ensembl.
DR GO; GO:0030433; P:ubiquitin-dependent ERAD pathway; IMP:ParkinsonsUK-UCL.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; IMP:UniProtKB.
DR GO; GO:0019076; P:viral release from host cell; IMP:UniProtKB.
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; 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 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 Host-virus interaction; Immunity; Innate immunity; Isopeptide bond; Ligase;
KW Metal-binding; Nucleus; Phosphoprotein; Reference proteome; Transferase;
KW Ubl conjugation; Ubl conjugation pathway; Zinc; Zinc-finger.
FT CHAIN 1..630
FT /note="E3 ubiquitin/ISG15 ligase TRIM25"
FT /id="PRO_0000056233"
FT DOMAIN 439..630
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 180..450
FT /note="Interaction with influenza A virus NS1"
FT REGION 355..403
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 217..307
FT /evidence="ECO:0000255"
FT COMPBIAS 368..393
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 91
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 100
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 273
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 278
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 567
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT CROSSLNK 117
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ISG15)"
FT /evidence="ECO:0000269|PubMed:17222803"
FT VARIANT 89
FT /note="V -> G (in dbSNP:rs7212260)"
FT /id="VAR_024614"
FT VARIANT 358
FT /note="P -> L (in dbSNP:rs205498)"
FT /evidence="ECO:0000269|PubMed:15489334,
FT ECO:0000269|PubMed:8248217, ECO:0007744|PubMed:21269460"
FT /id="VAR_024615"
FT MUTAGEN 21
FT /note="K->R: No effect on ISGylation."
FT /evidence="ECO:0000269|PubMed:17222803"
FT MUTAGEN 65
FT /note="K->R: No effect on ISGylation."
FT /evidence="ECO:0000269|PubMed:17222803"
FT MUTAGEN 112
FT /note="K->R: No effect on ISGylation."
FT /evidence="ECO:0000269|PubMed:17222803"
FT MUTAGEN 117
FT /note="K->R: No ISGylation."
FT /evidence="ECO:0000269|PubMed:17222803"
FT HELIX 2..5
FT /evidence="ECO:0007829|PDB:5EYA"
FT HELIX 7..10
FT /evidence="ECO:0007829|PDB:5FER"
FT TURN 14..16
FT /evidence="ECO:0007829|PDB:5FER"
FT STRAND 17..19
FT /evidence="ECO:0007829|PDB:5FER"
FT STRAND 21..25
FT /evidence="ECO:0007829|PDB:5FER"
FT STRAND 31..33
FT /evidence="ECO:0007829|PDB:5FER"
FT HELIX 34..43
FT /evidence="ECO:0007829|PDB:5FER"
FT STRAND 46..49
FT /evidence="ECO:0007829|PDB:5FER"
FT TURN 51..53
FT /evidence="ECO:0007829|PDB:5FER"
FT STRAND 56..59
FT /evidence="ECO:0007829|PDB:5FER"
FT HELIX 67..78
FT /evidence="ECO:0007829|PDB:5FER"
FT HELIX 191..300
FT /evidence="ECO:0007829|PDB:4LTB"
FT HELIX 307..316
FT /evidence="ECO:0007829|PDB:4LTB"
FT HELIX 331..358
FT /evidence="ECO:0007829|PDB:4LTB"
FT HELIX 435..445
FT /evidence="ECO:0007829|PDB:6FLM"
FT HELIX 449..453
FT /evidence="ECO:0007829|PDB:6FLM"
FT TURN 463..465
FT /evidence="ECO:0007829|PDB:6FLM"
FT STRAND 470..473
FT /evidence="ECO:0007829|PDB:6FLM"
FT TURN 474..477
FT /evidence="ECO:0007829|PDB:6FLM"
FT STRAND 478..481
FT /evidence="ECO:0007829|PDB:6FLM"
FT STRAND 496..504
FT /evidence="ECO:0007829|PDB:6FLM"
FT STRAND 507..520
FT /evidence="ECO:0007829|PDB:6FLM"
FT STRAND 522..530
FT /evidence="ECO:0007829|PDB:6FLM"
FT HELIX 538..540
FT /evidence="ECO:0007829|PDB:6FLM"
FT STRAND 548..554
FT /evidence="ECO:0007829|PDB:6FLM"
FT STRAND 557..562
FT /evidence="ECO:0007829|PDB:6FLM"
FT STRAND 565..568
FT /evidence="ECO:0007829|PDB:6FLM"
FT STRAND 576..582
FT /evidence="ECO:0007829|PDB:6FLM"
FT TURN 583..586
FT /evidence="ECO:0007829|PDB:6FLM"
FT STRAND 587..604
FT /evidence="ECO:0007829|PDB:6FLM"
FT STRAND 611..617
FT /evidence="ECO:0007829|PDB:6FLM"
FT STRAND 623..626
FT /evidence="ECO:0007829|PDB:6FLM"
SQ SEQUENCE 630 AA; 70973 MW; EB0AB353F0AD4C80 CRC64;
MAELCPLAEE LSCSICLEPF KEPVTTPCGH NFCGSCLNET WAVQGSPYLC PQCRAVYQAR
PQLHKNTVLC NVVEQFLQAD LAREPPADVW TPPARASAPS PNAQVACDHC LKEAAVKTCL
VCMASFCQEH LQPHFDSPAF QDHPLQPPVR DLLRRKCSQH NRLREFFCPE HSECICHICL
VEHKTCSPAS LSQASADLEA TLRHKLTVMY SQINGASRAL DDVRNRQQDV RMTANRKVEQ
LQQEYTEMKA LLDASETTST RKIKEEEKRV NSKFDTIYQI LLKKKSEIQT LKEEIEQSLT
KRDEFEFLEK ASKLRGISTK PVYIPEVELN HKLIKGIHQS TIDLKNELKQ CIGRLQEPTP
SSGDPGEHDP ASTHKSTRPV KKVSKEEKKS KKPPPVPALP SKLPTFGAPE QLVDLKQAGL
EAAAKATSSH PNSTSLKAKV LETFLAKSRP ELLEYYIKVI LDYNTAHNKV ALSECYTVAS
VAEMPQNYRP HPQRFTYCSQ VLGLHCYKKG IHYWEVELQK NNFCGVGICY GSMNRQGPES
RLGRNSASWC VEWFNTKISA WHNNVEKTLP STKATRVGVL LNCDHGFVIF FAVADKVHLM
YKFRVDFTEA LYPAFWVFSA GATLSICSPK
