TRIM56
Function
E3 ubiquitin-protein ligase that plays a key role in innate antiviral immunity by mediating ubiquitination of CGAS and STING1 (PubMed:21289118, PubMed:29426904). In response to pathogen- and host-derived double-stranded DNA (dsDNA), targets STING1 to 'Lys-63'-linked ubiquitination, thereby promoting its homodimerization, a step required for the production of type I interferon IFN-beta (By similarity). Also mediate monoubiquitination of CGAS, thereby promoting CGAS oligomerization and subsequent activation (PubMed:29426904). Promotes also TNFalpha-induced NF-kappa-B signaling by mediating 'Lys-63'-linked ubiquitination TAK1, leading to enhanced interaction between TAK1 and CHUK/IKKalpha (PubMed:35952808). Independently of its E3 ubiquitin ligase activity, positive regulator of TLR3 signaling. Potentiates extracellular double stranded RNA (dsRNA)-induced expression of IFNB1 and interferon-stimulated genes ISG15, IFIT1/ISG56, CXCL10, OASL and CCL5/RANTES (PubMed:22948160). Promotes establishment of an antiviral state by TLR3 ligand and TLR3-mediated chemokine induction following infection by hepatitis C virus (PubMed:22948160). Acts as a restriction factor of Zika virus through direct interaction with the viral RNA via its C-terminal region (PubMed:31251739).
Pathway
Protein modification; protein ubiquitination.
Post-translational modifications
(Microbial infection) Preferentially ubiquitinated with 'Lys-48' and 'Lys-11'-linked ubiquitin chains by Salmonella effector SopA leading to proteasomal targeting and degradation.
Autoubiquitinated.
Sequence Similarities
Belongs to the TRIM/RBCC family.
Tissue Specificity
Widely expressed (at protein level).
Cellular localization
- Cytoplasm
Alternative names
RNF109, TRIM56, E3 ubiquitin-protein ligase TRIM56, RING finger protein 109, Tripartite motif-containing protein 56