Abstract

The cell activation, cell survival, and antiapoptotic functions of the tumor necrosis factor (TNF) receptor superfamily are mostly mediated by the family of the TNF receptor-associated factors (TRAF1-6). The TRAF proteins are found in mammals, drosophila, C.elegans, and Dictyostelium discoideum. Most of the biological effects are mediated by the activation of the transcriptional factor NF-kB and Ap-1 family, which can turn on numerous genes involved in various aspects of cellular and immune functions.
TRAF2 was isolated biochemically from the TNFR-2 signaling complex and is the prototype of the six TRAF family members. Beside TNFR-2, a number of other TNFRs such as CD30, CD40, CD27, Ox40, 4-1BB, and ATAR also recruit TRAF2. In addition, the transforming effect of the Epstein-Barr virus (EBV) oncoprotein latent infection membrane protein-1 (LMP1) is partly TRAF2 mediated. Several linear consensus sequences have been proposed to bind to TRAF2, including PXQX[TSD] motif in LMP1, CD30, CD40, and CD27; the phiSXEE ( phi = large hydrophobic) sequence in TNFR-2 and CD30; and the QEE motif in 4-1BB and Ox40 receptors.
Despite the apparent sequence diversity, the receptor peptides bind to a common site on the surface of the TRAF domain of TRAF2. Crystal structures of the human TRAF2 domain in complex with peptides from the TNFR family members revealed a conserved binding mode and allowed to identify two consensus sequences.

 Selected references

 This ELM has been assigned the following Gene Ontology (GO) terms for biological process, cellular component and molecular function.

Biological Process
signal transduction	GO:0007165
Cellular Component
cytosol	GO:0005829
Molecular Function
signal transducer	GO:0004871