ID:TRI25_HUMAN DESCRIPTION: RecName: Full=E3 ubiquitin/ISG15 ligase TRIM25; EC=6.3.2.19; EC=6.3.2.n3; AltName: Full=Estrogen-responsive finger protein; AltName: Full=RING finger protein 147; AltName: Full=Tripartite motif-containing protein 25; AltName: Full=Ubiquitin/ISG15-conjugating enzyme TRIM25; AltName: Full=Zinc finger protein 147; FUNCTION: Functions as an ubiquitin E3 ligase and as an ISG15 E3 ligase. Involved in innate immune defense against viruses by mediating ubiquitination of DDX58. Mediates 'Lys-63'-linked polyubiquitination of the DDX58 N-terminal CARD-like region which is crucial for triggering the cytosolic signal transduction that leads to the production of interferons in response to viral infection. Promotes ISGylation of 14-3-3 sigma (SFN), an adapter protein implicated in the regulation of a large spectrum signaling pathway. Mediates estrogen action in various target organs. CATALYTIC ACTIVITY: ATP + ubiquitin + protein lysine = AMP + diphosphate + protein N-ubiquityllysine. CATALYTIC ACTIVITY: ATP + [ISG15] + [protein]-lysine = AMP + diphosphate + [protein]-N-ISGyllysine. PATHWAY: Protein modification; protein ubiquitination. SUBUNIT: Interacts (via SPRY domain) with DDX58 (via CARD domain). Interacts (via coiled coil) with influenza A virus NS1 protein; this interaction specifically inhibits TRIM25 multimerization and TRIM25-mediated DDX58 CARD ubiquitination, thereby suppressing DDX58 signal transduction. INTERACTION: P03496:NS (xeno); NbExp=3; IntAct=EBI-2341129, EBI-2547442; SUBCELLULAR LOCATION: Cytoplasm. Note=Colocalized with DDX58 at cytoplasmic perinuclear bodies. TISSUE SPECIFICITY: Ubiquitous. INDUCTION: By interferons. DOMAIN: The RING-type zinc finger is important for ISG15 E3 ligase activity and autoISGylation. AutoISGylation negatively regulates ISG15 E3 ligase activity. DOMAIN: The C-terminal B30.2/SPRY domain interacts with the first N-terminal CARD domain of DDX58. PTM: Auto-ISGylated. SIMILARITY: Contains 1 B30.2/SPRY domain. SIMILARITY: Contains 1 RING-type zinc finger. WEB RESOURCE: Name=Wikipedia; Note=TRIM25 entry; URL="http://en.wikipedia.org/wiki/TRIM25";
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on Q14258
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Biological Process: GO:0002376 immune system process GO:0006511 ubiquitin-dependent protein catabolic process GO:0006513 protein monoubiquitination GO:0016032 viral process GO:0016567 protein ubiquitination GO:0019985 translesion synthesis GO:0030433 ER-associated ubiquitin-dependent protein catabolic process GO:0032480 negative regulation of type I interferon production GO:0033280 response to vitamin D GO:0043123 positive regulation of I-kappaB kinase/NF-kappaB signaling GO:0043627 response to estrogen GO:0045087 innate immune response GO:0046596 regulation of viral entry into host cell GO:0046597 negative regulation of viral entry into host cell GO:0051091 positive regulation of sequence-specific DNA binding transcription factor activity GO:0051092 positive regulation of NF-kappaB transcription factor activity GO:0051607 defense response to virus GO:0060333 interferon-gamma-mediated signaling pathway GO:1902186 regulation of viral release from host cell GO:1902187 negative regulation of viral release from host cell GO:1990830 cellular response to leukemia inhibitory factor
BX538220 - Homo sapiens mRNA; cDNA DKFZp686D24130 (from clone DKFZp686D24130). LF384795 - JP 2014500723-A/192298: Polycomb-Associated Non-Coding RNAs. LF209253 - JP 2014500723-A/16756: Polycomb-Associated Non-Coding RNAs. BC053605 - Homo sapiens tripartite motif-containing 25, mRNA (cDNA clone IMAGE:6008783). AK024597 - Homo sapiens cDNA: FLJ20944 fis, clone ADSE01780. BC013752 - Homo sapiens tripartite motif-containing 25, mRNA (cDNA clone IMAGE:4525015), with apparent retained intron. LF327291 - JP 2014500723-A/134794: Polycomb-Associated Non-Coding RNAs. BC038247 - Homo sapiens tripartite motif-containing 25, mRNA (cDNA clone IMAGE:4524805). LF327290 - JP 2014500723-A/134793: Polycomb-Associated Non-Coding RNAs. JD023393 - Sequence 4417 from Patent EP1572962. JD035472 - Sequence 16496 from Patent EP1572962. JD034831 - Sequence 15855 from Patent EP1572962. DL492324 - Novel nucleic acids. DL490814 - Novel nucleic acids. AB208994 - Homo sapiens mRNA for tripartite motif-containing 25 variant protein. BC016924 - Homo sapiens tripartite motif-containing 25, mRNA (cDNA clone MGC:21231 IMAGE:4419084), complete cds. BC042541 - Homo sapiens tripartite motif-containing 25, mRNA (cDNA clone MGC:17069 IMAGE:4338818), complete cds. HZ409099 - JP 2015528002-A/1696: CHIRAL CONTROL. LG052433 - KR 1020150036642-A/1699: CHIRAL CONTROL. D21205 - Homo sapiens efp mRNA for estrogen responsive finger protein, complete cds. LF327289 - JP 2014500723-A/134792: Polycomb-Associated Non-Coding RNAs. HZ480257 - JP 2015535430-A/763: TERMINALLY MODIFIED RNA. HZ790188 - JP 2016504050-A/1933: SIGNAL-SENSOR POLYNUCLEOTIDES FOR THE ALTERATION OF CELLULAR PHENOTYPES. JC512920 - Sequence 3173 from Patent WO2014113089. LF161889 - JP 2016513950-A/1955: Oligomers with improved off-target profile. LQ070508 - Sequence 832 from Patent EP2964234. FR772788 - Homo sapiens microRNA hsa-miR-3614-3p. JD328166 - Sequence 309190 from Patent EP1572962. HZ480258 - JP 2015535430-A/764: TERMINALLY MODIFIED RNA. HZ790189 - JP 2016504050-A/1934: SIGNAL-SENSOR POLYNUCLEOTIDES FOR THE ALTERATION OF CELLULAR PHENOTYPES. JC512921 - Sequence 3174 from Patent WO2014113089. LF160521 - JP 2016513950-A/587: Oligomers with improved off-target profile. LQ070509 - Sequence 833 from Patent EP2964234. LQ724871 - Sequence 504 from Patent WO2018096084. LY486545 - KR 1020170014835-A/3: Genetic marker for predicting and detecting development of colorectal cancer. FR772789 - Homo sapiens microRNA hsa-miR-3614-5p. JD474362 - Sequence 455386 from Patent EP1572962. JD465576 - Sequence 446600 from Patent EP1572962. JD525218 - Sequence 506242 from Patent EP1572962. JD305026 - Sequence 286050 from Patent EP1572962. LF327288 - JP 2014500723-A/134791: Polycomb-Associated Non-Coding RNAs. JD477936 - Sequence 458960 from Patent EP1572962. JD278236 - Sequence 259260 from Patent EP1572962. JD446170 - Sequence 427194 from Patent EP1572962. JD096258 - Sequence 77282 from Patent EP1572962. AK310720 - Homo sapiens cDNA, FLJ17762. JD422765 - Sequence 403789 from Patent EP1572962. JD466961 - Sequence 447985 from Patent EP1572962. AB384815 - Synthetic construct DNA, clone: pF1KB3493, Homo sapiens TRIM25 gene for tripartite motif-containing protein 25, complete cds, without stop codon, in Flexi system. LF327283 - JP 2014500723-A/134786: Polycomb-Associated Non-Coding RNAs. LF327282 - JP 2014500723-A/134785: Polycomb-Associated Non-Coding RNAs. LF327281 - JP 2014500723-A/134784: Polycomb-Associated Non-Coding RNAs. LF327280 - JP 2014500723-A/134783: Polycomb-Associated Non-Coding RNAs. MA644009 - JP 2017113010-A/1933: SIGNAL-SENSOR POLYNUCLEOTIDES FOR THE ALTERATION OF CELLULAR PHENOTYPES. MA731893 - JP 2017140048-A/763: TERMINALLY MODIFIED RNA. MA644010 - JP 2017113010-A/1934: SIGNAL-SENSOR POLYNUCLEOTIDES FOR THE ALTERATION OF CELLULAR PHENOTYPES. MA731894 - JP 2017140048-A/764: TERMINALLY MODIFIED RNA. MA405804 - WO 2018155427-A/578: A probe with reduced false positive binding, a method to desing the probe, and the use thereof. MA620372 - JP 2018138019-A/192298: Polycomb-Associated Non-Coding RNAs. MA562868 - JP 2018138019-A/134794: Polycomb-Associated Non-Coding RNAs. MA562867 - JP 2018138019-A/134793: Polycomb-Associated Non-Coding RNAs. MA562866 - JP 2018138019-A/134792: Polycomb-Associated Non-Coding RNAs. MA562865 - JP 2018138019-A/134791: Polycomb-Associated Non-Coding RNAs. MA562860 - JP 2018138019-A/134786: Polycomb-Associated Non-Coding RNAs. MA562859 - JP 2018138019-A/134785: Polycomb-Associated Non-Coding RNAs. MA562858 - JP 2018138019-A/134784: Polycomb-Associated Non-Coding RNAs. MA562857 - JP 2018138019-A/134783: Polycomb-Associated Non-Coding RNAs. MA444830 - JP 2018138019-A/16756: Polycomb-Associated Non-Coding RNAs. MA801062 - JP 2018183181-A/1933: SIGNAL-SENSOR POLYNUCLEOTIDES FOR THE ALTERATION OF CELLULAR PHENOTYPES. MA801063 - JP 2018183181-A/1934: SIGNAL-SENSOR POLYNUCLEOTIDES FOR THE ALTERATION OF CELLULAR PHENOTYPES. MB407069 - WO 2019159884-A/559: Kit, device, and method for detection of dementia. MB406671 - WO 2019159884-A/161: Kit, device, and method for detection of dementia.
Biochemical and Signaling Pathways
BioCarta from NCI Cancer Genome Anatomy Project h_EfpPathway - Estrogen-responsive protein Efp controls cell cycle and breast tumors growth
Reactome (by CSHL, EBI, and GO)
Protein Q14258 (Reactome details) participates in the following event(s):
R-HSA-918224 DDX58 is K63 polyubiquitinated R-HSA-1169403 Interaction of E3 ligase with ISG15:E2 complex R-HSA-1169394 ISGylation of IRF3 R-HSA-1169395 ISGylation of viral protein NS1 R-HSA-1169398 ISGylation of host protein filamin B R-HSA-1169402 ISGylation of E2 conjugating enzymes R-HSA-1169405 ISGylation of protein phosphatase 1 beta (PP2CB) R-HSA-1169406 ISGylation of host proteins R-HSA-5653756 TRIM25 binds monoUb:164-PCNA R-HSA-5653754 UBE2L6:TRIM25 ISGylates monoUb:K164-PCNA R-HSA-1678843 ISGylation of protein translation regulator 4EHP R-HSA-168909 viral dsRNA:IFIH1, viral dsRNA:K63polyUb-DDX58 bind MAVS R-HSA-936378 Inhibition of DDX58/IFIH1 signaling by ATG5:ATG12:MAVS R-HSA-937343 NLRC5 interacts with DDX58/IFIH1 R-HSA-1678842 Competitive inhibition of translation initiation by ISGylated 4EHP R-HSA-168934 MAVS interacts with RIPK1 and FADD R-HSA-918227 Recruitment of TRAF3 to MAVS R-HSA-918230 Recruitment of TRAF6/TRAF2 to IPS-1 R-HSA-990528 Interaction of PCBP2 with MAVS R-HSA-933528 Interaction of MEKK1 with TRAF6 R-HSA-933537 Recruitment of TANK to TRAF6 R-HSA-933539 Recruitment of IKK complex R-HSA-918225 TBK1/IKK epsilon complex interacts with MAVS bound TRAF3 R-HSA-936381 OTUD5 deubiquitinates TRAF3 R-HSA-933526 Recruitment of caspase-8 and -10 to FADD complex R-HSA-990526 Recruitment of AIP4 and K48 ubiquitination of MAVS/IPS-1 R-HSA-933527 Recruitment of TBK1/IKK epsilon complex to TANK:TRAF6 R-HSA-918232 Recruitment of IRF3,IRF7 R-HSA-918229 Phosphorylation and release of IRF3/IRF7 R-HSA-933523 Dimerzation of procaspase-8, procaspase-10 R-HSA-933538 Recruitment of IRF7 to TRAF6 R-HSA-933525 Phosphorylation and release of IRF7 R-HSA-933530 Activation of IKK by MEKK1 R-HSA-933532 Processing of caspases R-HSA-168928 DDX58/IFIH1-mediated induction of interferon-alpha/beta R-HSA-877300 Interferon gamma signaling R-HSA-1169408 ISG15 antiviral mechanism R-HSA-5656169 Termination of translesion DNA synthesis R-HSA-168249 Innate Immune System R-HSA-913531 Interferon Signaling R-HSA-1169410 Antiviral mechanism by IFN-stimulated genes R-HSA-110313 Translesion synthesis by Y family DNA polymerases bypasses lesions on DNA template R-HSA-936440 Negative regulators of DDX58/IFIH1 signaling R-HSA-168256 Immune System R-HSA-1280215 Cytokine Signaling in Immune system R-HSA-73893 DNA Damage Bypass R-HSA-933543 NF-kB activation through FADD/RIP-1 pathway mediated by caspase-8 and -10 R-HSA-918233 TRAF3-dependent IRF activation pathway R-HSA-933541 TRAF6 mediated IRF7 activation R-HSA-933542 TRAF6 mediated NF-kB activation R-HSA-73894 DNA Repair R-HSA-5689896 Ovarian tumor domain proteases R-HSA-5688426 Deubiquitination R-HSA-597592 Post-translational protein modification R-HSA-392499 Metabolism of proteins
US Server
Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
