Schultz et al. (1998) Proc. Natl. Acad. Sci. USA 95, 5857-5864
Letunic et al. (2012) Nucleic Acids Res , doi:10.1093/nar/gkr931

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TNFR Tumor necrosis factor receptor / nerve growth factor receptor repeats.

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There are 3265 TNFR domains in 1106 proteins in SMART's nrdb database.

Click on the following links for more information.

• Evolution (species in which this domain is found)

• Click on to expand nodes. To display all proteins with a TNFR domain in a specific node, click on it.

  This tree shows only several representative species. The complete taxonomic breakdown of all proteins with TNFR domain is also avaliable.

  Useful shortcuts: Expand all nodes or Collapse tree
  Go to specific node: Anopheles gambiae, Arabidopsis thaliana, Caenorhabditis elegans, Drosophila melanogaster, Homo sapiens, Mus musculus, Rattus norvegicus, Takifugu rubripes

• Literature (relevant references for this domain)

• Primary literature is listed below; Automatically-derived, secondary literature is also avaliable.

  • Lotz M, Setareh M, vonKempis J, Schwarz H
  • The nerve growth factor/tumor necrosis factor receptor family.
  • J Leukoc Biol. 1996; 60: 1-7
  • Display abstract

  • Receptors in the nerve growth factor/tumor necrosis factor receptor family are characterized by the presence of cysteine-rich motifs of approximately 40 amino acids in the extracellular domain. The ligands are type II transmembrane proteins with beta-strands that form a jelly-roll beta-sandwich. The receptors recognize soluble or cell-surface-bound ligands and mediate diverse cellular responses. Activation of intracellular signals is mediated at least in part by the association of proteins with a RING finger motif or a death domain to the cytoplasmic domains of the receptors. In addition to cell-membrane-bound receptors soluble forms have been described for most of the receptors. Activation of intracellular signals not only occurs through ligand binding to the receptors but cross-linking of at least some members of the ligand family can regulate cell functions.

  • Armitage RJ
  • Tumor necrosis factor receptor superfamily members and their ligands.
  • Curr Opin Immunol. 1994; 6: 407-13
  • Display abstract

  • The tumor necrosis factor (TNF) receptor family comprises a number of type I integral membrane glycoproteins which exhibit sequence homology in their cysteine-rich extracellular domains. Recently, ligands for many of these receptors have been identified. These molecules all display sequence identity with TNF and lymphotoxin beta, prototype ligands for this receptor family, and have the conformation of type II transmembrane molecules. While certain biological activities are common to many members of this TNF-like family, other activities appear to be shared only by some ligands, or are unique. The identification of the TNF superfamily of ligands has provided the opportunity to compare and contrast the diverse biological effects mediated through the interaction of these related molecules with their receptors.

  • Tartaglia LA, Rothe M, Hu YF, Goeddel DV
  • Tumor necrosis factor's cytotoxic activity is signaled by the p55 TNF receptor.
  • Cell. 1993; 73: 213-6

  • Schall TJ et al.
  • Molecular cloning and expression of a receptor for human tumor necrosis factor.
  • Cell. 1990; 61: 361-70
  • Display abstract

  • A human tumor necrosis factor (TNF) binding protein from serum of cancer patients was purified to homogeneity and partially sequenced. Synthetic DNA probes based on amino acid sequence information were used to isolate cDNA clones encoding a receptor for TNF. The TNF receptor (TNF-R) is a 415 amino acid polypeptide with a single membrane-spanning region. The extracellular cysteine-rich domain of the TNF-R is homologous to the nerve growth factor receptor and the B cell activation protein Bp50. Human embryonic kidney cells transfected with a TNF-R expression vector specifically bind both 125I-labeled and biotinylated TNF-alpha. Unlabeled TNF-alpha and TNF-beta were equally effective at displacing the binding of labeled TNF-alpha to TNF-R expressing cells. Northern analysis indicates a single species of mRNA for the TNF-R in a variety of cell types. Therefore, the soluble TNF binding protein found in human serum is probably proteolytically derived from the TNF-R.

  • Sprang SR
  • The divergent receptors for TNF.
  • Trends Biochem Sci. 1990; 15: 366-8
• Metabolism (metabolic pathways involving proteins which contain this domain)

• Click the image to view the interactive version of the map in iPath

  % proteins involved KEGG pathway ID Description 54.78 map04060 Cytokine-cytokine receptor interaction 11.40 map04210 Apoptosis 8.09 map04650 Natural killer cell mediated cytotoxicity 6.62 map04010 MAPK signaling pathway 6.62 map04920 Adipocytokine signaling pathway 3.31 map04940 Type I diabetes mellitus 3.31 map04115 p53 signaling pathway 2.57 map04620 Toll-like receptor signaling pathway 2.57 map04514 Cell adhesion molecules (CAMs) 0.37 map00562 Inositol phosphate metabolism 0.37 map00632 Benzoate degradation via CoA ligation This information is based on mapping of SMART genomic protein database to KEGG orthologous groups. Percentage points are related to the number of proteins with TNFR domain which could be assigned to a KEGG orthologous group, and not all proteins containing TNFR domain. Please note that proteins can be included in multiple pathways, ie. the numbers above will not always add up to 100%.

• Structure (3D structures containing this domain)

• 3D Structures of TNFR domains in PDB

  PDB code	Main view	Title
  1d0g		Crystal structure of death receptor 5 (dr5) bound to apo2l/trail
  1d4v		Crystal structure of trail-dr5 complex
  1du3		Crystal structure of trail-sdr5
  1ext		Extracellular domain of the 55kda tumor necrosis factor receptor. crystallized at ph3.7 in p 21 21 21.
  1ft4		Photochemically-enhanced binding of small molecules to the tumor necrosis factor receptor-1
  1jma		Crystal structure of the herpes simplex virus glycoprotein d bound to the cellular receptor hvea/hvem
  1ncf		A new paradigm for tumor necrosis factor signalling
  1sg1		Crystal structure of the receptor-ligand complex between nerve growth factor and the common neurotrophin receptor p75
  1tnr		Crystal structure of the soluble human 55 kd tnf receptor- human tnf-beta complex: implications for tnf receptor activation
  1za3		The crystal structure of the ysd1 fab bound to dr5
  2aw2		Crystal structure of the human btla-hvem complex
  2h9g		Crystal structure of phage derived fab bdf1 with human death receptor 5 (dr5)
  2hev		Crystal structure of the complex between ox40l and ox40
  2hey		Crystal structure of murine ox40l bound to human ox40
  2uwi		Structure of crme, a poxvirus tnf receptor
  3buk		Crystal structure of the neurotrophin-3 and p75ntr symmetrical complex

• Links (links to other resources describing this domain)

• BLOCKS	TNFR_NGFR_1
  PFAM	TNFR_c6
  INTERPRO	IPR001368
  PROSITE	TNFR_DOMAIN