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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: a) endosomal acidic sphingomyelinase; activation may occur via activation of phospholipase A2 & release of arachidonic acid as a second messenger [9] b) NF-kappa B in a pathway unaffected by crmA [8]; activation may be modulated by ceramide as a 3rd messenger generated by sphingomyelinase [9]; 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

Interactions

molecular events

Related

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)

General

cluster-of-differentiation antigen; cluster designation antigen; CD antigen glycoprotein phosphoprotein pro apoptotic protein tumor necrosis factor [TNF] receptor family

Properties

SIZE: entity length = 455 aa MW = 50 kD COMPARTMENT: cellular membrane MOTIF: signal sequence {1-21} TNFR-Cys {43-82} MOTIF: cysteine residue {C44} MODIFICATION: cysteine residue {C58} N-glycosylation site {N54} cysteine residue {C58} MODIFICATION: cysteine residue {C44} cysteine residue {C59} MODIFICATION: cysteine residue {C72} cysteine residue {C62} MODIFICATION: cysteine residue {C81} cysteine residue {C72} MODIFICATION: cysteine residue {C59} cysteine residue {C81} MODIFICATION: cysteine residue {C62} TNFR-Cys {83-125} MOTIF: cysteine residue {C84} MODIFICATION: cysteine residue {C99} cysteine residue {C99} MODIFICATION: cysteine residue {C84} cysteine residue {C102} MODIFICATION: cysteine residue {C117} cysteine residue {C105} MODIFICATION: cysteine residue {C125} cysteine residue {C117} MODIFICATION: cysteine residue {C102} cysteine residue {C125} MODIFICATION: cysteine residue {C105} TNFR-Cys {126-166} MOTIF: cysteine residue {C127} MODIFICATION: cysteine residue {C143} cysteine residue {C143} MODIFICATION: cysteine residue {C127} N-glycosylation site {N145} cysteine residue {C146} MODIFICATION: cysteine residue {C158} cysteine residue {C149} MODIFICATION: cysteine residue {C166} N-glycosylation site {N151} cysteine residue {C158} MODIFICATION: cysteine residue {C146} cysteine residue {C166} MODIFICATION: cysteine residue {C149} TNFR-Cys {167-196} MOTIF: cysteine residue {C168} MODIFICATION: cysteine residue {C179} cysteine residue {C179} MODIFICATION: cysteine residue {C168} cysteine residue {C182} MODIFICATION: cysteine residue {C195} cysteine residue {C185} MODIFICATION: cysteine residue {C191} cysteine residue {C191} MODIFICATION: cysteine residue {C185} cysteine residue {C195} MODIFICATION: cysteine residue {C182} transmembrane domain {212-234} N-SMase activation domain (NSD) {338-348} death domain NAME: death domain SITE: 356-441

References

  1. UniProt :accession P19438
  2. INFEVERS: repertory of FMF & hereditary autoinflammatory disorders mutations http://fmf.igh.cnrs.fr/ISSAID/infevers/disease_menu.php?n=2
  3. GeneReviews https://www.genecards.org/cgi-bin/carddisp.pl?gene=TNFRSF1A
  4. SeattleSNPs http://pga.gs.washington.edu/data/tnfrsf1a/
  5. Taga T & Kishimoto T Cytokine receptors and signal transduction FASEB J 6:3387 1992 PMID: 1334470
  6. Tartaglia LA, Ayres TM, Wong GH, Goeddel DV. A novel domain within the 55 kd TNF receptor signals cell death. Cell. 1993 Sep 10;74(5):845-53. PMID: 8397073
  7. Nagata S, Golstein P. The Fas death factor. Science. 1995 Mar 10;267(5203):1449-56. Review. PMID: 7533326
  8. Hsu et al, The TNF receptor 1-associated protein TRADD signals cell death and NF-kappa B activation. Cell 81:495 1995 PMID: 7758105
  9. Hannun YA, Obeid LM. Ceramide: an intracellular signal for apoptosis. Trends Biochem Sci. 1995 Feb;20(2):73-7. Review. PMID: 7701566

Component-of

molecular complex

Databases & Figures

OMIM correlations MORBIDMAP 191190 UniProt P19438 PFAM correlations Entrez Gene 7132 KEGG correlations Figures/diagrams/slides/tables related to TNF receptor-1A