Deubiquitinating enzyme that plays various roles in the regulation of the immune response and inflammation (, ). In complex with WDR48, acts as a potential tumor suppressor by positively regulating PHLPP1 stability . During TCR engagement and activation, translocates into the cytoplasm and deubiquitinates its substrates LAT and TRAT1 and prevents their lysosome-dependent degradation to stabilize the TCR signaling complex at the plasma membrane . Plays an essential role in the selective LPS-induced macrophage response through the activation of NF-kappa-B pathway . In addition, promotes that antiviral immune response through targeting DNA sensor IFI16 to inhibit its proteasome-dependent degradation . Participates in the interferon signaling pathway and antiviral response independently of its deubiquitinase activity by maintaining nuclear phosphorylated STAT1 levels via inhibition of its CREBBP-mediated acetylation and subsequent dephosphorylation . Plays an intrinsic role in promoting the differentiation, activation and proliferation of CD4(+) T-cell by activating the NF-kappa-B signaling pathway through deubiquitinating and stabilizing B-cell lymphoma/leukemia 10/BCL10 (By similarity). In myeloid-derived suppressor cells promotes the activation of the NF-kappa-B via deubiquitination and stabilization of RELA (By similarity). Regulates the 'Lys-63'-linked polyubiquitin chains of BAX and thereby modulates the mitochondrial apoptotic process .
(Microbial infection) Forms a complex with Epstein-Barr virus protein EBNA3 which is an active deubiquitinase activity that may select specific substrates to promote B-lymphocyte transformation.
Subcellular locations: Nucleus, Cytoplasm, Cell membrane
Translocates from the nucleus to the cytosol on TCR stimulation, while it translocates into the nucleus in IFN signaling. USP12/WDR20/WDR48 complex is localized mainly to the plasma membrane .