UniProt:Q14258 TRIM25

chain
  • chain:1-630
checksum EB0AB353F0AD4C80
comment
  • FUNCTION Functions as a ubiquitin E3 ligase and as an ISG15 E3 ligase (PubMed:16352599). Involved in innate immune defense against viruses by mediating ubiquitination of RIGI and IFIH1 (PubMed:17392790, PubMed:29357390, PubMed:30193849, PubMed:31710640, PubMed:33849980, PubMed:36045682). Mediates 'Lys-63'-linked polyubiquitination of the RIGI N-terminal CARD-like region and may play a role in signal transduction that leads to the production of interferons in response to viral infection (PubMed:17392790, PubMed:23950712). Mediates 'Lys-63'-linked polyubiquitination of IFIH1 (PubMed:30193849). Promotes ISGylation of 14-3-3 sigma (SFN), an adapter protein implicated in the regulation of a large spectrum signaling pathway (PubMed:16352599, PubMed:17069755). Mediates estrogen action in various target organs (PubMed:22452784). Mediates the ubiquitination and subsequent proteasomal degradation of ZFHX3 (PubMed:22452784). Plays a role in promoting the restart of stalled replication forks via interaction with the KHDC3L-OOEP scaffold and subsequent ubiquitination of BLM, resulting in the recruitment and retainment of BLM at DNA replication forks (By similarity). Plays an essential role in the antiviral activity of ZAP/ZC3HAV1; an antiviral protein which inhibits the replication of certain viruses. Mechanistically, mediates 'Lys-63'-linked polyubiquitination of ZAP/ZC3HAV1 that is required for its optimal binding to target mRNA (PubMed:28060952, PubMed:28202764). Also mediates the ubiquitination of various substrates implicated in stress granule formation, nonsense-mediated mRNA decay, nucleoside synthesis and mRNA translation and stability (PubMed:36067236).CATALYTIC ACTIVITY S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine.CATALYTIC ACTIVITY ATP + [ISG15] + [protein]-lysine = AMP + diphosphate + [protein]-N-ISGyllysine.ACTIVITY REGULATION RING domain dimerization is required for catalysis, TRIM25-mediated RIG-I ubiquitination, interferon induction, and antiviral activity.PATHWAY Protein modification; protein ubiquitination.SUBUNIT Forms homodimers (PubMed:27154206, PubMed:27425606, PubMed:29357390, PubMed:31710640). Interacts (via SPRY domain) with RIGI (via CARD domain). Interacts with ZFHX3. Interacts with NLRP12; this interaction reduces the E3 ubiquitin ligase TRIM25-mediated 'Lys-63'-linked RIGI activation. Interacts with the KHDC3L/FILIA-OOEP/FLOPED scaffold complex and BLM at DNA replication forks (By similarity). Interacts with RTN3; this interaction prevents RIGI ubiquitination (PubMed:34313226). Interacts with YWHAE (PubMed:22607805).SUBUNIT (Microbial infection) Interacts (via coiled coil) with influenza A virus NS1 protein; this interaction specifically inhibits TRIM25 multimerization and TRIM25-mediated RIGI CARD ubiquitination, thereby suppressing RIGI signal transduction.SUBUNIT (Microbial infection) Interacts (via SPRY domain) with human respiratory syncytial virus (HRSV) non-structural protein 1; this interaction suppresses RIGI ubiquitination and results in decreased interaction between RIGI and MAVS.SUBUNIT (Microbial infection) Interacts with JC virus small t antigen; this interaction suppresses RIGI ubiquitination thereby suppressing RIGI signal transduction.SUBUNIT (Microbial infection) Interacts with paramyxoviruses (Sendai virus, Nipah virus, Measles virus and Parainfluenza virus 5) protein V; this interaction inhibits TRIM25-mediated ubiquitination of RIG-I and prevents downstream RIG-I signaling thereby inhibiting the IFN responses.SUBUNIT (Microbial infection) Interacts with Severe fever with thrombocytopenia virus (SFTSV) NSs; this interaction this interaction sequesters TRIM25 in NSs-induced cytoplasmic inclusion bodies thereby inhibiting the IFN responses.SUBUNIT (Microbial infection) Interacts with Epstein-Barr virus protein BPLF1 and YWHAZ; leading to inhibition of the type-I IFN response.SUBUNIT (Microbial infection) Interacts with human metapneumovirus protein M2-2; this interaction suppresses RIGI ubiquitination thereby suppressing RIGI signal transduction.INTERACTION Expressed in breast tumors (at protein level). 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 RIGI.PTM Auto-ISGylated.PTM (Microbial infection) Autoubiquitinated; promoted by Epstein-Barr virus protein BPLF1.ONLINE INFORMATION TRIM25 entry
crossReference
databaseName UniProt
dbId 67862
description
  • recommendedName: E3 ubiquitin/ISG15 ligase TRIM25 ecNumber evidence="8"6.3.2.n3 alternativeName: fullName evidence="30"Estrogen-responsive finger protein alternativeName: RING finger protein 147 alternativeName: RING-type E3 ubiquitin transferase ecNumber evidence="11 17 18 28"2.3.2.27 alternativeName: fullName evidence="31"RING-type E3 ubiquitin transferase TRIM25 alternativeName: Tripartite motif-containing protein 25 alternativeName: Ubiquitin/ISG15-conjugating enzyme TRIM25 alternativeName: Zinc finger protein 147
displayName UniProt:Q14258 TRIM25
geneName
  • TRIM25
  • EFP
  • RNF147
  • ZNF147
identifier Q14258
isSequenceChanged false
keyword
  • 3D-structure
  • Acetylation
  • Antiviral defense
  • Coiled coil
  • Cytoplasm
  • Host-virus interaction
  • Immunity
  • Innate immunity
  • Isopeptide bond
  • Ligase
  • Metal-binding
  • Nucleus
  • Phosphoprotein
  • Proteomics identification
  • Reference proteome
  • Transferase
  • Ubl conjugation
  • Ubl conjugation pathway
  • Zinc
  • Zinc-finger
modified [InstanceEdit:9948485] Weiser, Joel, 2025-05-21
moleculeType Protein
name
  • TRIM25
otherIdentifier
  • 11733885_a_at
  • 11758537_s_at
  • 1617_at
  • 16846913
  • 16846915
  • 17126024
  • 206911_PM_at
  • 206911_at
  • 224806_PM_at
  • 224806_at
  • 2712090
  • 3335347
  • 3763632
  • 3763634
  • 3763647
  • 3763649
  • 3763651
  • 3763653
  • 3763655
  • 3763657
  • 3763658
  • 3763659
  • 3763660
  • 3763661
  • 3763662
  • 3763663
  • 3763664
  • 3763665
  • 3763666
  • 3763667
  • 3763670
  • 3763671
  • 3763672
  • 3763673
  • 3763674
  • 3763677
  • 3763678
  • 3763679
  • 3763680
  • 3763681
  • 3763682
  • 3763683
  • 3763684
  • 3763685
  • 3763686
  • 42053_at
  • 55776_at
  • 70996_at
  • 7706
  • 8016847
  • A_23_P15326
  • A_24_P236680
  • A_24_P936767
  • A_33_P3331366
  • A_33_P3332302
  • D21205_at
  • GE482009
  • GE57111
  • GE87112
  • GO:0002376
  • GO:0002753
  • GO:0003713
  • GO:0003723
  • GO:0003824
  • GO:0004842
  • GO:0005515
  • GO:0005634
  • GO:0005654
  • GO:0005737
  • GO:0005829
  • GO:0006351
  • GO:0006355
  • GO:0006511
  • GO:0006513
  • GO:0006979
  • GO:0008270
  • GO:0009299
  • GO:0010494
  • GO:0016071
  • GO:0016567
  • GO:0016604
  • GO:0016740
  • GO:0016874
  • GO:0019076
  • GO:0030163
  • GO:0032880
  • GO:0033280
  • GO:0034599
  • GO:0036503
  • GO:0039552
  • GO:0043123
  • GO:0043161
  • GO:0043627
  • GO:0044790
  • GO:0045087
  • GO:0045296
  • GO:0045893
  • GO:0046596
  • GO:0046597
  • GO:0046872
  • GO:0051607
  • GO:0061630
  • GO:0070936
  • GO:0098542
  • GO:0140096
  • GO:0140374
  • GO:1990830
  • HMNXSV003019609
  • HMNXSV003052545
  • Hs.10362.0.S1_3p_at
  • ILMN_1808629
  • ILMN_1813625
  • PH_hs_0034857
  • PH_hs_0038946
  • TC17001715.hg
  • TC17001716.hg
  • TC17002717.hg
  • g4827064_3p_at
  • p34438
physicalEntity
referenceDatabase [ReferenceDatabase:2] UniProt
referenceGene
referenceTranscript
schemaClass ReferenceGeneProduct
secondaryIdentifier
  • TRI25_HUMAN
sequenceLength 630
species [Species:48887] Homo sapiens
stId uniprot:Q14258
url http://purl.uniprot.org/uniprot/Q14258
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