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                                          Protein Interaction Domains
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                                      Image Not Available The TRAF Domain
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                                                   Structure
                                              Image Not Available

      TRAF domains are composed of a highly conserved coiled-coil domain followed by a TRAF-C domain. The
    N-terminal coiled-coil domain is comprised of a single alpha helix while the TRAF-C domain folds into a
    beta-sandwich structure. TRAF domains oligomerize as dimers, trimers and/or heterotrimers. The structure
      of the TRAF domain of TRAF-2 reveals a trimer where the coiled-coil region forms a single stalk-like
   structure and the TRAF-C domains form three separate lobed structures below this stalk. The monomeric form
           of the TRAF 2 domain is shown. Reference: Park, Y.C. et al. (2000) Cell 101 (7), 777-787.
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                                          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.
                                              Image Not Available
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                                                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
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             Copyright of the authors and Cell Signaling Techology, a New England Biolabs company.
               Reference Cell Signaling Technology Catalog, Reference Section on Protein Domains
                 Dan Lin, Kathleen Binns, Neil Warner, Piers Nash, Ian Donaldson, Jim Fawcett,
                             Berri Baskin, Terry Kubiseski, and Tony Pawson (2000)

                        Copyright 2000-2003, Pawson Lab, Samuel Lunenfeld Research Institute, Toronto, Canada
