Tripartite motif-containing protein 25 (TRIM25)

Tripartite motif-containing protein 25 (TRIM25) is a cytoplasmic E3 ubiquitin ligase enzyme that belongs to the TRIM family, characterized by a RING domain, one or two B-box domains, a coiled-coil domain, and a C-terminal PRY/SPRY domain. It plays central roles in antiviral innate immunity primarily through ubiquitination of proteins such as RIG-I, a key sensor of viral RNA, leading to activation of the type I interferon pathway. TRIM25 also acts as an E3 ligase for ISG15, mediates ISGylation, and has RNA-binding activity important for its antiviral function. The protein is upregulated by estrogen and implicated in breast and ovarian cancers, as well as immune responses against viral infection, cancer progression, and inflammation. Viral proteins such as influenza NS1 interact with TRIM25 to evade host immune response by inhibiting RIG-I ubiquitination. TRIM25 is structurally complex: its RING domain enables E3 ligase activity, its CCD promotes dimerization, and the PRY/SPRY domain binds substrates such as RIG-I and MAVS. Its roles in ubiquitination, immune defense, and oncogenesis make it of therapeutic interest, though no approved drugs specifically target TRIM25 in the clinical setting.

Other names

EFP (Estrogen-responsive finger protein)RNF147ZNF147Zinc finger protein 147RING finger protein 147RING-type E3 ubiquitin transferase TRIM25Tripartite motif protein TRIM25Ubiquitin/ISG15-conjugating enzyme TRIM25Z147

Ubiquitination of target proteins (e.g., RIG-I) via Lys63- and Lys48-linked polyubiquitin chains; Conjugation of ISG15 (ISGylation) to target proteins