InterPro domain: IPR008974

The tumour necrosis factor receptor (TNFR) associated factors (TRAFs) act as signal transducers for both TNFRs and interleukin-1/Toll-like receptors. TRAFs function in immunity, embryonic development, stress response and bone metabolism through their induction of cell proliferation, differentiation, and apoptosis [ 1 ]. TRAFs are characterised by two domains: an N-terminal domain containing RING and zinc finger motifs that is essential for the activation of downstream effectors, and a C-terminal TRAF domain that is essential for self-association and receptor interaction [ 2 ]. The TRAF-domain like fold is a beta-sandwich consisting of 8 strands in 2 beta sheets and has a circularly permuted greek-key immunoglobulin-fold topology that contains an extra strand.

The substrate-binding domain (SBD) of the SIAH (seven in absentia homologue) family of proteins is structurally highly similar to the TRAF domain. The SIAH SBD interacts with a number of proteins, and is involved in TNF-alpha-mediated NFkappaB activation [ 3 ].

1. All TRAFs are not created equal: common and distinct molecular mechanisms of TRAF-mediated signal transduction. J. Cell. Sci. 115, 679-88
2. The structural basis for the recognition of diverse receptor sequences by TRAF2. Mol. Cell 4, 321-30
3. Siah ubiquitin ligase is structurally related to TRAF and modulates TNF-alpha signaling. Nat. Struct. Biol. 9, 68-75