E3 ubiquitin-protein ligase which regulates the IFN-beta production and antiviral response downstream of various DNA-encoded pattern-recognition receptors (PRRs). Plays also a central role in determining the response to different forms of oxidative stress by controlling levels of DNA glycosylases NEIL1, NEIL3 and NTH1 that are involved in repair of damaged DNA (, ). Promotes nuclear IRF3 ubiquitination and proteasomal degradation . Bridges together TBK1 and NEMO during the innate response to viral infection leading to the activation of TBK1. Positively regulates LPS-mediated inflammatory innate immune response by catalyzing the 'Lys-11'-linked polyubiquitination of TAB1 to enhance its activation and subsequent NF-kappa-B and MAPK signaling . In a manner independent of its catalytic activity, inhibits WWP2, a SOX2-directed E3 ubiquitin ligase, and thus protects SOX2 from polyubiquitination and proteasomal degradation . Ubiquitinates the histone acetyltransferase protein complex component PHF20 and thereby triggers its degradation in the nucleus after its recruitment by the histone demethylase KDM6B, serving as a scaffold protein . Upon induction by TGF-beta, ubiquitinates the TFIID component TAF7 for proteasomal degradation . Induces ferroptosis by ubiquitinating SLC7A11, a critical protein for lipid reactive oxygen species (ROS) scavenging (By similarity). Inhibits directly hepatitis B virus replication by mediating HBX ubiquitination and subsequent degradation .
(Microbial infection) Promotes herpes simplex virus type 2/HHV-2 infection in vaginal epithelial cells by decreasing the nuclear localization of IRF3, the primary mediator of type I interferon activation.
Subcellular locations: Cytoplasm, Nucleus
Viral infection mediates TRIM26 nuclear translocation.