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- ***************************************************
- * TNFR/NGFR family cysteine-rich region signature *
- ***************************************************
-
- 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] 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) [3].
- - Low-affinity nerve growth factor receptor (LA-NGFR).
- - Mammalian CD40 (Bp50), the receptor for the CD40L (or TRAP) cytokine.
- - Human T-cell activation antigen CD27, the receptor for CD27L.
- - Human lymphocyte activation antigen CD30, the receptor for CD30L.
- - FAS antigen [4] (or APO-1), the receptor for FASL, a protein involved in
- apoptosis (programmed cell death).
- - Rat T-cell antigen OX40.
- - Mouse T-cell protein 4-1BB which may function as a receptor specifically
- required during T cell activation [5].
- - Vaccinia virus protein A53 (SalF19R).
-
- It has been shown [6] 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.
-
- -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)-[DNEQSP]-x(2)-C
- [The six 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: a sheep keratin and fission yeast
- PCK1.
-
- -Note: this pattern is found from 1 to 4 times in the proteins listed above.
-
- -Last update: June 1994 / Text revised.
-
- [ 1] Mallet S., Barclay A.N.
- Immunol. Today 12:220-223(1991).
- [ 2] Sprang S.R.
- Trends Biochem. Sci. 15:366-368(1990).
- [ 3] Smith C.A., Davis T., Wignall J.M., Din W.S., Farrah T., Upton C.,
- McFadden G., Goodwin R.G.
- Biochem. Biophys. Res. Commun. 176:335-342(1991).
- [ 4] Krammer P.H., Debatin K.-M.
- Curr. Biol. 2:383-385(1992).
- [ 5] Pollok K.E., Kim Y.-J., Zhou Z., Hurtado J., Kin K.K., Pickard R.T.,
- Kwon B.S.
- J. Immunol. 150:771-781(1993).
- [ 6] Banner D.W., d'Arcy A., Janes W., Gentz R., Schoenfeld H.-J., Broger C.,
- Loetscher H., Lesslauer W.
- Cell 73:431-445(1993).
-