{PDOC00561} {PS00652; TNFR_NGFR_1} {PS50050; TNFR_NGFR_2} {BEGIN} *************************************************************** * 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-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 -------------------------------------------------------------------------------- PROSITE is copyrighted by the SIB Swiss Institute of Bioinformatics and distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives (CC BY-NC-ND 4.0) License, see https://prosite.expasy.org/prosite_license.html -------------------------------------------------------------------------------- {END}