TRIM25 Gene - Function, Mutations, and Disease Associations

TRIM25 (tripartite motif containing 25) encodes a member of the tripartite motif (TRIM) family. The protein functions as an E3 ubiquitin-protein ligase, catalyzing the ubiquitination of target proteins. It is best known for its role in innate antiviral immunity by mediating the ubiquitination of the cytosolic RNA sensor RIG-I (DDX58), which is essential for RIG-I activation and downstream interferon signaling. TRIM25 also participates in estrogen receptor signaling and has been implicated in various cancers, including breast cancer, where it can act as an oncogene or tumor suppressor depending on context.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• RIG-I/MDA5 mediated induction of interferon-alpha/beta (Reactome: R-HSA-936440)

• Antiviral mechanism by IFN-stimulated genes (Reactome: R-HSA-1169410)

• Estrogen-dependent gene expression (Reactome: R-HSA-8939211)

TRIM25 is a 72 kDa protein containing an N-terminal RING finger domain, two B-box domains, a coiled-coil region, and a C-terminal SPRY domain. The RING domain confers E3 ubiquitin ligase activity, while the SPRY domain mediates substrate recognition. TRIM25 is primarily cytoplasmic and undergoes self-ubiquitination. Its best-characterized substrate is RIG-I, where TRIM25 attaches K63-linked polyubiquitin chains to the CARD domains, enabling RIG-I to activate MAVS and trigger interferon production. TRIM25 also ubiquitinates other targets including p53, ZAP, and ERα, linking it to both antiviral defense and cancer biology.