Receptor for TNFSF2/TNF-alpha and homotrimeric TNFSF1/lymphotoxin-alpha. The adapter molecule FADD recruits caspase-8 to the activated receptor. The resulting death-inducing signaling complex (DISC) performs caspase-8 proteolytic activation which initiates the subsequent cascade of caspases (aspartate- specific cysteine proteases) mediating apoptosis. Contributes to the induction of non-cytocidal TNF effects including anti-viral state and activation of the acid sphingomyelinase. Binding of TNF to the extracellular domain leads to homotrimerization. The aggregated death domains provide a novel molecular interface that interacts specifically with the death domain of TRADD. Various TRADD-interacting proteins such as TRAFS, RIPK1 and possibly FADD, are recruited to the complex by their association with TRADD. This complex activates at least two distinct signaling cascades, apoptosis and NF-kappa-B signaling. Interacts with BAG4, BRE, FEM1B, GRB2, SQSTM1 and TRPC4AP. Interacts with HCV core protein. Interacts with human cytomegalovirus/HHV-5 protein UL138. 3 isoforms of the human protein are produced by alternative splicing. Note: This description may include information from UniProtKB.
Protein type: Membrane protein, integral; Receptor, cytokine
Cellular Component: Golgi membrane; extracellular space; protein complex; cell surface; axon; integral to plasma membrane; plasma membrane; extracellular region; nucleus; lipid raft
Biological Process: response to alkaloid; diterpenoid metabolic process; positive regulation of I-kappaB kinase/NF-kappaB cascade; positive regulation of protein import into nucleus, translocation; apoptosis; cytokine and chemokine mediated signaling pathway; response to lipopolysaccharide; response to amino acid stimulus; positive regulation of tumor necrosis factor production; prostaglandin metabolic process; regulation of apoptosis; positive regulation of tyrosine phosphorylation of Stat1 protein; positive regulation of angiogenesis; response to ethanol; flavonoid metabolic process; negative regulation of inflammatory response; virus-host interaction; defense response to bacterium; response to hypoxia; negative regulation of interleukin-6 production; tetrapyrrole metabolic process; positive regulation of transcription from RNA polymerase II promoter; inflammatory response; positive regulation of inflammatory response
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.