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{PDOC00561}
{PS00652; TNFR_NGFR_1}
{PS50050; TNFR_NGFR_2}
{BEGIN}
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* TNFR/NGFR family cysteine-rich region signature and profile *
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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-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  [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.

-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 known to belong to this class detected by the pattern: ALL.
-Other sequence(s) detected in Swiss-Prot: 10.

-Sequences known to belong to this class detected by the profile: ALL.
-Other sequence(s) detected in Swiss-Prot: 1.

-Last update: December 2004 / Pattern and text revised.

[ 1] Mallet S., Barclay A.N.
     Immunol. Today 12:220-223(1991).
[ 2] Sprang S.R.
     "The divergent receptors for TNF."
     Trends Biochem. Sci. 15:366-368(1990).
     PubMed=2174582
[ 3] Krammer P.H., Debatin K.-M.
     "When apoptosis fails."
     Curr. Biol. 2:383-385(1992).
     PubMed=15335933
[ 4] Bazan J.F.
     "Emerging families of cytokines and receptors."
     Curr. Biol. 3:603-606(1993).
     PubMed=15335677
[ 5] Banner D.W., D'Arcy A., Janes W., Gentz R., Schoenfeld H.-J., Broger C.,
     Loetscher H., Lesslauer W.
     "Crystal structure of the soluble human 55 kd TNF receptor-human TNF
     beta complex: implications for TNF receptor activation."
     Cell 73:431-445(1993).
     PubMed=8387891

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