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
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:
| | | |
'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.
December 2004 / Pattern and text revised.
PROSITE methods (with tools and information) covered by this documentation:
PS50050; TNFR/NGFR family cysteine-rich region domain profile (MATRIX)
PS00652; TNFR/NGFR family cysteine-rich region signature (PATTERN)
The 6 C's are involved in disulfide bonds
Sequences in UniProtKB/Swiss-Prot known to belong to this class: 96
detected by PS00652:
76 (true positives)
undetected by PS00652: 20 (
20 false negatives and 0 ' partial')
Other sequence(s) in UniProtKB/Swiss-Prot detected by PS00652:
34 false positives and 1 unknown.
Retrieve an alignment of UniProtKB/Swiss-Prot true positive hits:
Clustal format, color, condensed view
Clustal format, color
Clustal format, plain text
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]
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
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