TRIM25
Description
The TRIM25 (tripartite motif containing 25) is a protein-coding gene located on chromosome 17.
Tripartite motif-containing protein 25 is a protein that in humans is encoded by the TRIM25 gene.
== Function == The protein encoded by this gene is a member of the tripartite motif (TRIM) family grouping more than 70 TRIMs. TRIM proteins primarily function as ubiquitin ligases that regulate the innate response to infection. TRIM25 localizes to the cytoplasm. The presence of potential DNA-binding and dimerization-transactivation domains suggests that this protein may act as a transcription factor, similar to several other members of the TRIM family. Expression of the gene is upregulated in response to estrogen, and it is thought to mediate estrogen actions in breast cancer as a primary response gene.
== Domain Architecture == TRIM25 has an N-terminal RING domain, followed by a B-box type 1 domain, a B-box type 2 domain, a coiled-coil domain (CCD) and a C-terminal SPRY domain. The RING domain coordinates two zinc atoms and is essential for recruiting ubiquitin-conjugating enzymes. The function of the B-box domains is unknown. The CCD domain has been implicated in multimerization and other protein-protein interactions.
TRIM25 acts as a ubiquitin E3 ligase and an ISG15 E3 ligase, playing a crucial role in the innate immune defense against viruses. It mediates the ubiquitination of RIGI and IFIH1, two key proteins involved in viral recognition and signaling. Specifically, TRIM25 catalyzes 'Lys-63'-linked polyubiquitination of the RIGI N-terminal CARD-like region, potentially triggering the production of interferons in response to viral infection. Furthermore, TRIM25 promotes ISGylation of 14-3-3 sigma (SFN), an adapter protein involved in various signaling pathways. TRIM25 also mediates estrogen action in various target organs, ubiquitinates and degrades ZFHX3, and plays a role in restarting stalled DNA replication forks by interacting with the KHDC3L-OOEP scaffold and ubiquitinating BLM. Notably, TRIM25 is essential for the antiviral activity of ZAP/ZC3HAV1, a protein that inhibits viral replication. TRIM25 mediates 'Lys-63'-linked polyubiquitination of ZAP/ZC3HAV1, facilitating its binding to target mRNA. Additionally, TRIM25 ubiquitinates various substrates implicated in stress granule formation, nonsense-mediated mRNA decay, nucleoside synthesis, and mRNA translation and stability.
TRIM25 is also known as EFP, RNF147, Z147, ZNF147.
