Regulates pathways leading to the activation of NF- kappa-B and MAP kinases, and plays a central role in the regulation of B-cell survival. Part of signaling pathways leading to the production of cytokines and interferon. Required for normal antibody isotype switching from IgM to IgG. Plays a role T-cell dependent immune responses. Plays a role in the regulation of antiviral responses. Is an essential constituent of several E3 ubiquitin-protein ligase complexes. May have E3 ubiquitin-protein ligase activity and promote 'Lys-63'-linked ubiquitination of target proteins. Inhibits activation of NF-kappa-B in response to LTBR stimulation. Inhibits TRAF2-mediated activation of NF-kappa- B. Down-regulates proteolytic processing of NFKB2, and thereby inhibits non-canonical activation of NF-kappa-B. Promotes ubiquitination and proteasomal degradation of MAP3K14. Homotrimer. Heterotrimer with TRAF2 and TRAF5. Interacts with LTBR/TNFRSF3, TNFRSF4, TNFRSF5/CD40, TNFRSF8/CD30, TNFRSF13C TNFRSF17/BCMA, TLR4 and EDAR. Interacts with MAP3K5, MAP3K14, TRAIP/TRIP, TDP2/TTRAP, TANK/ITRAF and TRAF3IP1. Interaction with TNFRSF5/CD40 is modulated by TANK/ITRAF, which competes for the same binding site. Interacts with TICAM1. Interacts with TRAFD1. Interacts with OTUB1, OTUB2 and OTUD5. Interacts with RNF216, MAVS, OPTN and TBK1. Identified in a complex with TRAF2, MAP3K14 and BIRC3. Interacts with BIRC2 and BIRC3. Upon exposure to bacterial lipopolysaccharide (LPS), recruited to a transient complex containing TLR4, TRAF3, TRAF6, IKBKG, MAP3K7, MYD88, TICAM1, BIRC2, BIRC3 and UBE2N. Interacts with Epstein-Barr virus protein LMP1. Interacts (via RING-type zinc finger domain) with SRC. Belongs to the TNF receptor-associated factor family. A subfamily. 2 isoforms of the human protein are produced by alternative splicing. Note: This description may include information from UniProtKB.
Protein type: Ubiquitin conjugating system
Chromosomal Location of Human Ortholog: 14q32.32
Cellular Component: internal side of plasma membrane; mitochondrion; cytosol; endosome
Molecular Function: signal transducer activity; protein binding; zinc ion binding; thioesterase binding; ubiquitin protein ligase binding; ubiquitin-protein ligase activity; protein kinase binding; tumor necrosis factor receptor binding; ligase activity
Biological Process: apoptosis; MyD88-independent toll-like receptor signaling pathway; regulation of defense response to virus; protein ubiquitination; toll-like receptor 3 signaling pathway; signal transduction; Toll signaling pathway; regulation of cytokine production; regulation of apoptosis; tumor necrosis factor-mediated signaling pathway; inhibition of NF-kappaB transcription factor; regulation of proteolysis; toll-like receptor signaling pathway; innate immune response; regulation of interferon-beta production; negative regulation of interferon type I production; toll-like receptor 4 signaling pathway
SS: The number of records in which this modification site was determined using site-specific methods. SS methods include amino acid sequencing, site-directed mutagenesis, modification site-specific antibodies, specific MS strategies, etc.