TRIM25

The RING-type zinc finger is important for ISG15 E3 ligase activity and autoISGylation. AutoISGylation negatively regulates ISG15 E3 ligase activity.

The C-terminal B30.2/SPRY domain interacts with the first N-terminal CARD domain of RIGI.

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). Mediates also the ubiquitination of various substrates implicated in stress granule formation, nonsense-mediated mRNA decay, nucleoside synthesis and mRNA translation and stability (PubMed:36067236).

Protein modification; protein ubiquitination.

Auto-ISGylated.

(Microbial infection) Autoubiquitinated; promoted by Epstein-Barr virus protein BPLF1.

Expressed in breast tumors (at protein level). Ubiquitous.

• Cytoplasm
• Cytoplasm
• Stress granule
• Nucleus

EFP, RNF147, ZNF147, TRIM25, E3 ubiquitin/ISG15 ligase TRIM25, Estrogen-responsive finger protein, RING finger protein 147, RING-type E3 ubiquitin transferase, RING-type E3 ubiquitin transferase TRIM25, Tripartite motif-containing protein 25, Ubiquitin/ISG15-conjugating enzyme TRIM25, Zinc finger protein 147

• entrezGene:7706
• omim:600453
• swissprot:Q14258

Proteins

Oncology

70973Da