CD120a; TNF receptor-1A; tumor necrosis factor receptor superfamily member 1A; p60; TNF-R1; TNF-RI; TNFR-I; p55;; TBPI (TNFRSF1A, TNFAR, TNFR1)

Function

• receptor for TNFSF2/TNF-alpha & homotrimeric TNFSF1/lymphotoxin-alpha
• TNFR1 activation leads to activation of the ICE family of cysteine proteases & apoptosis, a process inhibited by the viral protein CrmA.
• TNFR1 also activates:
  • endosomal acidic sphingomyelinase; activation may occur via activation of phospholipase A2 & release of arachidonic acid as a second messenger
  • NF-kappa B in a pathway unaffected by crmA; activation may be modulated by ceramide as a 3rd messenger generated by sphingomyelinase; the TNFR1 signal is mediated (at least in part) by TRADD & by ceramide.
• 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 mediating apoptosis
• contributes to the induction of non-cytocidal TNF effects including anti-viral state & activation of endosomal acidic 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 & possibly FADD, are recruited to the complex by their association with TRADD
• this complex activates at least two distinct signaling cascades, apoptosis & NF-kappa-B signaling
• interacts with BAG4, BRE, FEM1B, GRB2, SQSTM1 & TRPC4AP
• interacts with HCV core protein
• the soluble form is produced from the membrane form by proteolytic processing

Structure

• the domain that induces A-SMASE is probably identical to the death domain
• the N-SMASE activation domain (NSD) is both necessary & sufficient for activation of N-SMASE
• both the cytoplasmic membrane-proximal region & the C-terminal region containing the death domain are involved in the interaction with TRPC4AP (putative)
• contains 1 death domain
• contains 4 TNFR-Cys repeats

Compartment

• cell membrane
• secreted

Pathology

• defects in TNFRSF1A are the cause of familial hibernian fever (TNF receptor-associated periodic syndrome (TRAPS)

Laboratory

• TNF receptor superfamily member 1A in serum/plasma

More general terms

• tumor necrosis factor [TNF] receptor family
• CD antigen
• phosphoprotein
• pro apoptotic protein
• glycoprotein

Additional terms

• apoptosis
• casein kinase 1
• CD40 [CDw40], TNF receptor family member 5 (TNFRSF5), Bp50 or B-cell activation protein CD40
• CD95; Fas antigen; tumor necrosis factor receptor superfamily member 6; apo-1 antigen; apoptosis-mediating surface antigen FAS; FASLG receptor (FAS, APT1, FAS1, TNFRSF6)
• tumor necrosis factor receptor type 1-associated DEATH domain protein; TNFR1-associated DEATH domain protein; TNFRSF1A-associated via death domain (TRADD)
• tumor necrosis factor [TNF]-alpha; tumor necrosis factor ligand superfamily member 2; cachectin (TNF, TNFA, TNFSF2)

Database

• Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:7132
• OMIM: https://mirror.omim.org/entry/142680
• OMIM: https://mirror.omim.org/entry/191190
• UniProt: http://www.uniprot.org/uniprot/P19438.html
• Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=7132