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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:

                  +-------------+    +--------------+
                  |             |    |              |
                                  |            |
'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.

Technical section

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

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

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


1AuthorsMallet S., Barclay A.N.
SourceImmunol. Today 12:220-223(1991).

2AuthorsSprang S.R.
TitleThe divergent receptors for TNF.
SourceTrends Biochem. Sci. 15:366-368(1990).
PubMed ID2174582

3AuthorsKrammer P.H., Debatin K.-M.
TitleWhen apoptosis fails.
SourceCurr. Biol. 2:383-385(1992).
PubMed ID15335933

4AuthorsBazan J.F.
TitleEmerging families of cytokines and receptors.
SourceCurr. Biol. 3:603-606(1993).
PubMed ID15335677

5AuthorsBanner D.W., D'Arcy A., Janes W., Gentz R., Schoenfeld H.-J., Broger C., Loetscher H., Lesslauer W.
TitleCrystal structure of the soluble human 55 kd TNF receptor-human TNF beta complex: implications for TNF receptor activation.
SourceCell 73:431-445(1993).
PubMed ID8387891

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