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 apparatus; extracellular space; protein complex; cell surface; mitochondrion; integral to membrane; cytosol; lipid raft; Golgi membrane; membrane; axon; plasma membrane; synapse; intracellular; nucleus; receptor complex
Molecular Function: protein binding; tumor necrosis factor receptor activity; protease binding; protein complex binding; tumor necrosis factor binding
Biological Process: positive regulation of protein import into nucleus, translocation; apoptosis; protein heterooligomerization; cytokine and chemokine mediated signaling pathway; programmed cell death; defense response; signal transduction; positive regulation of tumor necrosis factor production; prostaglandin metabolic process; regulation of apoptosis; positive regulation of angiogenesis; positive regulation of tyrosine phosphorylation of Stat1 protein; cell surface receptor linked signal transduction; DNA damage response, signal transduction resulting in induction of apoptosis; tumor necrosis factor-mediated signaling pathway; positive regulation of neuron apoptosis; negative regulation of inflammatory response; defense response to bacterium; negative regulation of interleukin-6 production; positive regulation of transcription from RNA polymerase II promoter; inflammatory response; positive regulation of inflammatory response; negative regulation of apoptosis
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.