TRAF Domain

Domain Binding and Function

The approximately 150 amino acid TRAF domain is found in Tumor Necrosis Factor (TNF) receptor-associated factors. TRAF proteins appear to be a relatively recent evolutionary development as there is just one C. elegans TRAF protein and only two Drosophila, and six mammalian TRAF proteins. All mammalian TRAFs localize to the cytoplasm except TRAF4 which is found in the nucleus. TRAF proteins are recruited to the membrane through interactions of their TRAF domains with activated TNF receptors, IL-1/Toll receptors or through intermediate proteins such as the TRADDs. TRAFs primarily act in cell survival upon interacting with TNF receptors by activating the NFkB and AP-1 transcription factors. The six mammalian TRAF proteins have distinct functions. For example, TRAF3 regulates T-cell dependent antigen responses, TRAF4 is required for formation of the trachea and TRAF6 modulates IL-1, CD40, and LPS signaling. TRAFs are also important in Epstein-Barr Virus replication by binding to LMP1 and subsequently potentiating growth and transformation.

Structure Reference

1. Park, Y.C. et al. (2000) Cell 101 (7), 777–787.

Examples of Domain Proteins

Binding Examples

TRAF Domain Proteins	Binding Partners
TRAF 1,2,3,5	CD40
TRAF 1,2	TRADD
TRAF6	IRAK
TRAF 2	TNFR1
TRAF 6	IL-1