E3 ubiquitin-protein ligase that plays several important roles in innate immunity and adaptive immunity ( ). Mediates ubiquitination of CD86 and MHC class II proteins, such as HLA-DR alpha and beta, and promotes their subsequent endocytosis and sorting to lysosomes via multivesicular bodies (, ). Possesses a very broad antiviral activity by specifically inactivating different viral fusion proteins . Targets and ubiquitinates cytoplasmic lysine residues of viral envelope glycoproteins with single transmembrane domains leading to their lysosomal degradation . Therefore, shows broad-spectrum inhibition against many viruses including retroviruses, rhabdoviruses, arenaviruses, sarbecoviruses or influenzaviruses (, ). Strongly blocks human immunodeficiency virus type 1 envelope glycoprotein incorporation into virions by down-regulating its cell surface expression. Blocks also ebola virus glycoprotein/GP incorporation via surface down-regulation . Mediates 'Lys-63'-linked polyubiquitination of influenza M2 to target it to lysosome for degradation . Mediates the regulation of constitutive ubiquitination and trafficking of the viral restriction factor BST2 within the endocytic pathway . Plays a role in maintenance of immune tolerance to self by promoting the turnover and proteasomal degradation of PD-L1/CD274 via ubiquitination . Catalyzes the 'Lys-63'-linked polyubiquitylation of cGAS thereby inhibiting its DNA binding ability and impairing its antiviral innate immunity .
(Microbial infection) Mediates 'Lys-63'-linked polyubiquitination of hepatitis C virus/HCV protein NS2 which allows its binding to HGS, an ESCRT-0 complex component, and this interaction is essential for HCV envelopment.
Subcellular locations: Golgi apparatus membrane, Endoplasmic reticulum membrane, Cytoplasmic vesicle membrane, Lysosome membrane, Early endosome membrane
Broadly expressed. Present in immature dendritic cells (at protein level).