E3 ubiquitin-protein ligase that mediates ubiquitination of various substrates and thereby plays a role in diffent processes including proliferation, innate immunity, apoptosis, immune response or autophagy ( , ). Ubiquitinates PIK3C2B and inhibits its activity by mediating the formation of 'Lys-48'-linked polyubiquitin chains; the function inhibits CD4 T-cell activation. Acts as a regulator of retrograde transport: together with MAGEL2, mediates the formation of 'Lys-63'-linked polyubiquitin chains at 'Lys-220' of WASHC1, leading to promote endosomal F-actin assembly . Has a transcriptional repressor activity by cooperating with EPC1. Induces apoptosis by activating Jun N-terminal kinase and p38 kinase and also increases caspase-3-like activity independently of mitochondrial events. May function in male germ cell development. Has DNA-binding activity and preferentially bound to double-stranded DNA. Forms a complex with and ubiquitinates the ubiquitin-specific protease USP7, which in turn deubiquitinates RIPK1 resulting in the positive regulation of TNF-alpha-induced apoptosis . In addition, acts with USP7 or PTPN11 as an inhibitor of the antiviral signaling pathway by promoting kinase TBK1 ubiquitination and degradation (, ). Acts as a negative regulator of NOD2 signaling by mediating ubiquitination of NOD2, promoting its degradation by the proteasome . Alternatively, facilitates mitophagy via stabilization of active TBK1 . Negatively regulates autophagy flux under basal conditions by directly polyubiquitinating ULK1 . During starvation-induced autophagy, catalyzes non-degradative ubiquitination of the kinase STK38L promoting its activation and phosphorylation of ULK1 leading to its ubiquitination and degradation to restrain the amplitude and duration of autophagy .
(Microbial infection) Positively regulates hepatitis C virus replication by suppressing type I IFN response during infection.
Subcellular locations: Nucleus, Cytoplasm, Nucleus, PML body, Early endosome, Mitochondrion
Nuclear or cytoplasmic depending on the cell type (By similarity). Colocalized with PML and EIF3S6 in nuclear bodies. Recruited to retromer-containing endosomes via interaction with MAGEL2 . Co-localizes with p62/SQSTM1 and TBK1 in cytoplasmic structures that are closely associated with the mitochondria .
Expressed in testis namely within the seminiferous tubules.