TNF-R1: 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.
Protein type: Receptor, cytokine; Membrane protein, integral
Chromosomal Location of Human Ortholog: 12p13.2
Cellular Component: Golgi membrane; extracellular space; cell surface; mitochondrion; axon; integral to plasma membrane; extracellular region; plasma membrane; synapse; nucleus; cytosol; receptor complex; lipid raft
Molecular Function: protein binding; tumor necrosis factor receptor activity; protease binding; protein complex binding; tumor necrosis factor binding
Biological Process: response to alkaloid; positive regulation of I-kappaB kinase/NF-kappaB cascade; positive regulation of protein import into nucleus, translocation; viral reproduction; protein heterooligomerization; cytokine and chemokine mediated signaling pathway; response to lipopolysaccharide; response to amino acid stimulus; positive regulation of tumor necrosis factor production; prostaglandin metabolic process; positive regulation of angiogenesis; positive regulation of tyrosine phosphorylation of Stat1 protein; response to ethanol; DNA damage response, signal transduction resulting in induction of apoptosis; tumor necrosis factor-mediated signaling pathway; induction of apoptosis via death domain receptors; positive regulation of neuron apoptosis; negative regulation of inflammatory response; defense response to bacterium; response to wounding; negative regulation of interleukin-6 production; response to hypoxia; tetrapyrrole metabolic process; positive regulation of transcription from RNA polymerase II promoter; inflammatory response; positive regulation of inflammatory response; negative regulation of apoptosis
Disease: Periodic Fever, Familial, Autosomal Dominant; Multiple Sclerosis, Susceptibility To, 5
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