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