UBP12_HUMAN Loading...

Ubiquitin carboxyl-terminal hydrolase 12

Deubiquitinating enzyme that plays various roles in the regulation of the immune response and inflammation^1,2. 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 membrane³. Plays an essential role in the selective LPS-induced macrophage response through the activation of NF-kappa-B pathway⁴. In addition, promotes that antiviral immune response through targeting DNA sensor IFI16 to inhibit its proteasome-dependent degradation⁵. 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 dephosphorylation⁶. 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 process⁷. Negative regulator of NOTCH signaling that specifically deubiquitinates non-activated NOTCH receptors to target them for lysosomal degradation; deubiquitination of NOTCH stimulates its transport form late endosomes to lysosomes⁸. Protects neurons against HTT/huntingtin-induced polyglutamine expansion-dependent neurodegeneration through regulation of autophagic flux⁹. This function is independent of deubiquitinase activity or of other components of the USP12-WDR20-WDR48 deubiquitinating complex (By similarity). In complex with WDR48, acts as a potential tumor suppressor by positively regulating PHLPP1 stability¹⁰. (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.

AlphaFold DB , UniProt , Accession O75317, Species HUMAN (Homo sapiens, Human), Gene USP12, Length 370 aa.