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88  structures 156  species 4  interactions 2327  sequences 54  architectures

Family: TNFR_c6 (PF00020)

Summary: TNFR/NGFR cysteine-rich region

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This is the Wikipedia entry entitled "Tumor necrosis factor receptor". More...

Tumor necrosis factor receptor Edit Wikipedia article

TNFR/NGFR cysteine-rich region
PDB 1tnr EBI.jpg
Structure of the soluble human 55 kd TNF receptor-human TNF beta complex.[1]
Identifiers
Symbol TNFR_c6
Pfam PF00020
InterPro IPR011614
PROSITE PDOC00561
SCOP 1tnr
SUPERFAMILY 1tnr

A tumor necrosis factor receptor (TNFR), or death receptor, is a trimeric[2] cytokine receptor that binds tumor necrosis factors (TNF). The receptor cooperates with an adaptor protein (such as TRADD, TRAF, RIP), which is important in determining the outcome of the response (e.g. apoptosis, inflammation).

Because "TNF" is often used to describe TNF alpha, "TNFR" is often used to describe the receptors that bind to TNF alpha - namely, CD120. However, there are several other members of this family that bind to the other TNFs.[3][4]

Members[edit]

Family members include:[3]

Type Protein Aliases Gene
1 (CD120) CD120a TNFRSF1A
CD120b TNFRSF1B
3 Lymphotoxin β receptor TNFRSF3 LTBR
4 CD134 TNFRSF4
5 CD40 TNFRSF5 CD40
6 FAS TNFRSF6 FAS
TNFRSF6B TNFRSF6B
7 CD27 TNFRSF7 CD27
8 CD30 TNFRSF8
9 CD137 TNFRSF9
10 TNFRSF10A DR4 TNFRSF10A
TNFRSF10B DR5 TNFRSF10B
TNFRSF10C TNFRSF10C
TNFRSF10D TNFRSF10D
11 RANK TNFRSF11A
Osteoprotegerin TNFRSF11B
12 TNFRSF12A Fn14 TNFRSF12A
13 TNFRSF13B TNFRSF13B
TNFRSF13C TNFRSF13C
14 TNFRSF14 TNFRSF14
16 Nerve growth factor receptor TNFRSF16 NGFR
17 TNFRSF17 TNFRSF17
18 TNFRSF18 TNFRSF18
19 TNFRSF19 TNFRSF19
21 TNFRSF21 DR6 TNFRSF21
25 TNFRSF25 DR3 TRAMP LARD WS-1[5] TNFRSF25
27 Ectodysplasin A2 receptor TNFRSF27 EDA2R

References[edit]

  1. ^ Banner DW, D'Arcy A, Janes W et al. (May 1993). "Crystal structure of the soluble human 55 kd TNF receptor-human TNF beta complex: implications for TNF receptor activation". Cell 73 (3): 431–45. doi:10.1016/0092-8674(93)90132-A. PMID 8387891. 
  2. ^ Ashkenazi, A.; Dixit, VM (1998). "Death Receptors: Signaling and Modulation". Science 281 (5381): 1305–8. doi:10.1126/science.281.5381.1305. PMID 9721089. 
  3. ^ a b Locksley RM, Killeen N, Lenardo MJ (2001). "The TNF and TNF receptor superfamilies: integrating mammalian biology". Cell 104 (4): 487–501. doi:10.1016/S0092-8674(01)00237-9. PMID 11239407. 
  4. ^ Hehlgans T, Pfeffer K (2005). "The intriguing biology of the tumour necrosis factor/tumour necrosis factor receptor superfamily: players, rules and the games". Immunology 115 (1): 1–20. doi:10.1111/j.1365-2567.2005.02143.x. PMC 1782125. PMID 15819693. 
  5. ^ Marsters. "Identification of a ligand for the death-domain-containing receptor Apo3". current biology. Retrieved 4 December 2013. 

Further reading[edit]

External links[edit]


This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.

This tab holds the annotation information that is stored in the Pfam database. As we move to using Wikipedia as our main source of annotation, the contents of this tab will be gradually replaced by the Wikipedia tab.

TNFR/NGFR cysteine-rich region Provide feedback

No Pfam abstract.

Internal database links

External database links

This tab holds annotation information from the InterPro database.

InterPro entry 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
  • 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.

Gene Ontology

The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.

Domain organisation

Below is a listing of the unique domain organisations or architectures in which this domain is found. More...

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Alignments

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We make a range of alignments for each Pfam-A family. You can see a description of each above. You can view these alignments in various ways but please note that some types of alignment are never generated while others may not be available for all families, most commonly because the alignments are too large to handle.

  Seed
(37)
Full
(2327)
Representative proteomes NCBI
(2043)
Meta
(25)
RP15
(184)
RP35
(248)
RP55
(442)
RP75
(889)
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  Seed
(37)
Full
(2327)
Representative proteomes NCBI
(2043)
Meta
(25)
RP15
(184)
RP35
(248)
RP55
(442)
RP75
(889)
Alignment:
Format:
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Sequence:
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  Seed
(37)
Full
(2327)
Representative proteomes NCBI
(2043)
Meta
(25)
RP15
(184)
RP35
(248)
RP55
(442)
RP75
(889)
Raw Stockholm Download   Download   Download   Download   Download   Download   Download   Download  
Gzipped Download   Download   Download   Download   Download   Download   Download   Download  

You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.

External links

MyHits provides a collection of tools to handle multiple sequence alignments. For example, one can refine a seed alignment (sequence addition or removal, re-alignment or manual edition) and then search databases for remote homologs using HMMER3.

HMM logo

HMM logos is one way of visualising profile HMMs. Logos provide a quick overview of the properties of an HMM in a graphical form. You can see a more detailed description of HMM logos and find out how you can interpret them here. More...

Trees

This page displays the phylogenetic tree for this family's seed alignment. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed alignment.

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Curation and family details

This section shows the detailed information about the Pfam family. You can see the definitions of many of the terms in this section in the glossary and a fuller explanation of the scoring system that we use in the scores section of the help pages.

Curation View help on the curation process

Seed source: Swissprot_feature_table
Previous IDs: none
Type: Domain
Author: Sonnhammer ELL
Number in seed: 37
Number in full: 2327
Average length of the domain: 38.90 aa
Average identity of full alignment: 30 %
Average coverage of the sequence by the domain: 15.97 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 23193494 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 20.6 20.6
Trusted cut-off 20.6 20.6
Noise cut-off 20.5 20.5
Model length: 39
Family (HMM) version: 13
Download: download the raw HMM for this family

Species distribution

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Interactions

There are 4 interactions for this family. More...

TNFR_c6 NGF TNF V-set

Structures

For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the TNFR_c6 domain has been found. There are 88 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein seqence.

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