The domain within your query sequence starts at position 107 and ends at position 146; the E-value for the TNFR domain shown below is 2.87e-5.

CQPGMHCCTPAVNSCARCKLHCSGEEVVKSPGTAKKDTIC

TNFR

Tumor necrosis factor receptor / nerve growth factor receptor repeats.

• SMART accession number: SM00208
• Description: Repeats in growth factor receptors that are involved in growth factor binding. TNF/TNFR
• Interpro abstract (IPR001368):

  A number of proteins, some of which are known to be receptors for growth factors, have been found to contain a cysteine-rich domain of about 110 to 160 amino acids in their N-terminal part, that can be subdivided into four (or in some cases, three) modules of about 40 residues containing 6 conserved cysteines. Some of the proteins containing this domain are listed below [ (PUBMED:2174582) (PUBMED:15335933) (PUBMED:15335677) ]:

  • Tumor Necrosis Factor type I and type II receptors (TNFR). Both receptors bind TNF-alpha and TNF-beta, but are only similar in the cysteine-rich region. TNFR contains four cysteine-rich domain modules (CRDs), termed CRD1 through CRD4. CRD2 and CRD3 are known as TNF-binding domains [ (PUBMED:8387891) ].
  • Shope fibroma virus soluble TNF receptor (protein T2)
  • Lymphotoxin alpha/beta receptor
  • Low-affinity nerve growth factor receptor (LA-NGFR) (p75)
  • CD40 (Bp50), the receptor for the CD40L (or TRAP) cytokine
  • CD27, the receptor for the CD27L cytokine
  • CD30, the receptor for the CD30L cytokine
  • T-cell protein 4-1BB, the receptor for the 4-1BBL putative cytokine
  • FAS antigen (or APO-1), the receptor for FASL, a protein involved in apoptosis (programmed cell death)
  • T-cell antigen OX40, the receptor for the OX40L cytokine
  • Wsl-1, a receptor (for a yet undefined ligand) that mediates apoptosis
  • Vaccinia virus protein A53 (SalF19R)

  It has been shown [ (PUBMED:8387891) ] that the six cysteines all involved in intrachain disulphide bonds. A schematic representation of the structure of the 40 residue module of these receptors is shown below:

                    +-------------+    +--------------+
                    |             |    |              |
                   xCxxxxxxxxxxxxxCxCxxCxxxxxxxxxCxxxxCxx
                                    |            |
                                    +------------+
  

  'C': conserved cysteine involved in a disulphide bond.

• GO function: protein binding (GO:0005515)

There are 32859 TNFR domains in 11619 proteins in SMART's nrdb database.

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

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

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

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)

% 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	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
3alq	Crystal structure of TNF-TNFR2 complex
3buk	Crystal Structure of the Neurotrophin-3 and p75NTR Symmetrical Complex
3ij2	Ligand-receptor structure
3k51	Crystal Structure of DcR3-TL1A complex
3me2	Crystal structure of mouse RANKL-RANK complex
3me4	Crystal structure of mouse RANK
3mhd	Crystal structure of DCR3
3mi8	The structure of TL1A-DCR3 COMPLEX
3qbq	Crystal structure of extracellular domains of mouse RANK-RANKL complex
3qd6	Crystal structure of the CD40 and CD154 (CD40L) complex
3qo4	The Crystal Structure of Death Receptor 6
3thm	Crystal structure of Fas receptor extracellular domain in complex with Fab EP6b_B01
3tje	Crystal structure of Fas receptor extracellular domain in complex with Fab E09
3u3p	The S-SAD phased crystal structure of the ecto-domain of Death Receptor 6 (DR6)
3u3q	The S-SAD phased crystal structure of the ecto-domain of Death Receptor 6 (DR6)
3u3s	The S-SAD phased crystal structure of the ecto-domain of Death Receptor 6 (DR6)
3u3t	The S-SAD phased crystal structure of the ecto-domain of Death Receptor 6 (DR6)
3u3v	The S-SAD phased crystal structure of the ecto-domain of Death Receptor 6 (DR6)
3urf	Human RANKL/OPG complex
3wvt	3WVT
3x3f	3X3F
4e4d	Crystal structure of mouse RANKL-OPG complex
4fhq	Crystal Structure of HVEM
4giq	Crystal Structure of mouse RANK bound to RANKL
4i9x	Crystal structure of human cytomegalovirus glycoprotein UL141 targeting the death receptor TRAIL-R2
4j6g	CRYSTAL STRUCTURE OF LIGHT AND DcR3 COMPLEX
4kgg	Crystal structure of light mutant2 and dcr3 complex
4kgq	Crystal structure of a human light loop mutant in complex with dcr3
4msv	Crystal structure of FASL and DcR3 complex
4mxw	Structure of heterotrimeric lymphotoxin LTa1b2 bound to lymphotoxin beta receptor LTbR and anti-LTa Fab
4n90	4N90
4od2	Crystal structure of the Fab fragment of an anti-DR5 antibody bound to DR5
4rsu	4RSU
4yn0	4YN0
5bnq	5BNQ
5dmi	5DMI
5dmj	5DMJ
5ihl	5IHL
5l36	5L36

Links (links to other resources describing this domain)

• INTERPRO: IPR001368
• PFAM: TNFR_c6
• PROSITE: TNFR_DOMAIN