Home ScanProsite ProRule Documents Downloads Links Funding
	PROSITE documentation PDOC00561 [for PROSITE entry PS00652]

TNFR/NGFR family cysteine-rich region signature and profile

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. Proteins known to belong to this family [1,2,3,4] are listed below:

• Tumor Necrosis Factor type I and type II receptors (TNFR). Both receptors bind TNF-α and TNF-β, but are only similar in the cysteine-rich region.
• Shope fibroma virus soluble TNF receptor (protein T2).
• Lymphotoxin α/β 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 [5] that the six cysteines all involved in intrachain disulfide 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 disulfide bond.

We have developed a signature pattern for the cysteine-rich region. It is based mainly on the position of the six conserved cysteines in each of the repeats. The profile spans the complete domain.

Last update:

December 2004 / Pattern and text revised.

PROSITE methods (with tools and information) covered by this documentation:

TNFR_NGFR_1, PS00652; TNFR/NGFR family cysteine-rich region signature  (PATTERN)

• Consensus pattern:
  C-x(4,6)-[FYH]-x(5,10)-C-x(0,2)-C-x(2,3)-C-x(7,11)-C-x(4,6)-[DNEQSKP]-{PD}-{CP}-C
  The 6 C's are involved in disulfide bonds
• Sequences in UniProtKB/Swiss-Prot known to belong to this class: 94
  • detected by PS00652: 74 (true positives)
  • undetected by PS00652: 20 (20 false negatives and 0 'partial')
• Other sequence(s) in UniProtKB/Swiss-Prot detected by PS00652:
  28 false positives.
• Retrieve an alignment of UniProtKB/Swiss-Prot true positive hits:
  Clustal format, color, condensed view  /  Clustal format, color  /  Clustal format, plain text  /  Fasta format
• Retrieve the sequence logo from the alignment
• Taxonomic distribution of all UniProtKB (Swiss-Prot + TrEMBL) entries matching PS00652
• Retrieve a list of all UniProtKB (Swiss-Prot + TrEMBL) entries matching PS00652
• Scan UniProtKB (Swiss-Prot and/or TrEMBL) entries against PS00652
• View ligand binding statistics of PS00652
• Matching PDB structures: 1D0G 1D4V 1DU3 1EXT ... [ALL]

TNFR_NGFR_2, PS50050; TNFR/NGFR family cysteine-rich region domain profile  (MATRIX)

• Sequences in UniProtKB/Swiss-Prot known to belong to this class: 97
  • detected by PS50050: 78 (true positives)
  • undetected by PS50050: 19 (19 false negatives and 0 'partial')
• Other sequence(s) in UniProtKB/Swiss-Prot detected by PS50050:
  1 false positive.
• Domain architecture view of Swiss-Prot proteins matching PS50050
  
• Retrieve an alignment of UniProtKB/Swiss-Prot true positive hits:
  Clustal format, color, condensed view  /  Clustal format, color  /  Clustal format, plain text  /  Fasta format
• Retrieve the sequence logo from the alignment
• Taxonomic distribution of all UniProtKB (Swiss-Prot + TrEMBL) entries matching PS50050
• Retrieve a list of all UniProtKB (Swiss-Prot + TrEMBL) entries matching PS50050
• Scan UniProtKB (Swiss-Prot and/or TrEMBL) entries against PS50050
• View ligand binding statistics of PS50050
• Matching PDB structures: 1D0G 1D4V 1DU3 1EXT ... [ALL]

1	Authors	Mallet S., Barclay A.N.
	Source	Immunol. Today 12:220-223(1991).

2	Authors	Sprang S.R.
	Title	The divergent receptors for TNF.
	Source	Trends Biochem. Sci. 15:366-368(1990).
	PubMed ID	2174582

3	Authors	Krammer P.H., Debatin K.-M.
	Title	When apoptosis fails.
	Source	Curr. Biol. 2:383-385(1992).
	PubMed ID	15335933

4	Authors	Bazan J.F.
	Title	Emerging families of cytokines and receptors.
	Source	Curr. Biol. 3:603-606(1993).
	PubMed ID	15335677

5	Authors	Banner D.W., D'Arcy A., Janes W., Gentz R., Schoenfeld H.-J., Broger C., Loetscher H., Lesslauer W.
	Title	Crystal structure of the soluble human 55 kd TNF receptor-human TNF beta complex: implications for TNF receptor activation.
	Source	Cell 73:431-445(1993).
	PubMed ID	8387891

PROSITE is copyright. It is produced by the SIB Swiss Institute Bioinformatics. There are no restrictions on its use by non-profit institutions as long as its content is in no way modified. Usage by and for commercial entities requires a license agreement. For information about the licensing scheme send an email to

Prosite License or see: prosite_license.html.


View entry in original PROSITE document format
View entry in raw text format (no links)