Acts as an E3 ubiquitin-protein ligase which accepts ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfers the ubiquitin to targeted substrates (       , ). Catalyzes 'Lys-29'-, 'Lys-48'- and 'Lys-63'-linked ubiquitin conjugation ( , ). Involved in the control of inflammatory signaling pathways . Essential component of a ubiquitin-editing protein complex, comprising also TNFAIP3, TAX1BP1 and RNF11, that ensures the transient nature of inflammatory signaling pathways . Promotes the association of the complex after TNF stimulation . Once the complex is formed, TNFAIP3 deubiquitinates 'Lys-63' polyubiquitin chains on RIPK1 and catalyzes the formation of 'Lys-48'-polyubiquitin chains . This leads to RIPK1 proteasomal degradation and consequently termination of the TNF- or LPS-mediated activation of NFKB1 . Ubiquitinates RIPK2 by 'Lys-63'-linked conjugation and influences NOD2-dependent signal transduction pathways . Regulates the transcriptional activity of several transcription factors, and probably plays an important role in the regulation of immune response (, ). Ubiquitinates NFE2 by 'Lys-63' linkages and is implicated in the control of the development of hematopoietic lineages . Mediates JUN ubiquitination and degradation (By similarity). Mediates JUNB ubiquitination and degradation . Critical regulator of type 2 helper T (Th2) cell cytokine production by inducing JUNB ubiquitination and degradation (By similarity). Involved in the negative regulation of MAVS-dependent cellular antiviral responses . Ubiquitinates MAVS through 'Lys-48'-linked conjugation resulting in MAVS proteasomal degradation . Following ligand stimulation, regulates sorting of Wnt receptor FZD4 to the degradative endocytic pathway probably by modulating PI42KA activity . Ubiquitinates PI4K2A and negatively regulates its catalytic activity . Ubiquitinates chemokine receptor CXCR4 and regulates sorting of CXCR4 to the degradative endocytic pathway following ligand stimulation by ubiquitinating endosomal sorting complex required for transport ESCRT-0 components HGS and STAM ( ). Targets DTX1 for lysosomal degradation and controls NOTCH1 degradation, in the absence of ligand, through 'Lys-29'-linked polyubiquitination ( ). Ubiquitinates SNX9 . Ubiquitinates MAP3K7 through 'Lys-48'-linked conjugation (By similarity). Involved in the regulation of apoptosis and reactive oxygen species levels through the ubiquitination and proteasomal degradation of TXNIP . Mediates the antiapoptotic activity of epidermal growth factor through the ubiquitination and proteasomal degradation of p15 BID . Ubiquitinates BRAT1 and this ubiquitination is enhanced in the presence of NDFIP1 . Inhibits the replication of influenza A virus (IAV) via ubiquitination of IAV matrix protein 1 (M1) through 'Lys-48'-linked conjugation resulting in M1 proteasomal degradation . Ubiquitinates NEDD9/HEF1, resulting in proteasomal degradation of NEDD9/HEF1 .
Subcellular locations: Cell membrane, Cytoplasm, Nucleus, Early endosome membrane, Endosome membrane
May be recruited to exosomes by NDFIP1 . Localizes to plasma membrane upon CXCL12 stimulation where it co-localizes with CXCL4 . Localization to early endosomes is increased upon CXCL12 stimulation where it co-localizes with DTX3L and CXCL4 .
Widely expressed.