1kzz
From Proteopedia
DOWNSTREAM REGULATOR TANK BINDS TO THE CD40 RECOGNITION SITE ON TRAF3
Structural highlights
Disease[TRAF3_HUMAN] Defects in TRAF3 are the cause of susceptibility to herpes simplex encephalitis 3 (HSE3) [MIM:614849]. A rare complication of human herpesvirus 1 (HHV-1) infection, occurring in only a small minority of HHV-1 infected individuals. HSE is characterized by hemorrhagic necrosis of parts of the temporal and frontal lobes. Onset is over several days and involves fever, headache, seizures, stupor, and often coma, frequently with a fatal outcome.[1] Function[TRAF3_HUMAN] Regulates pathways leading to the activation of NF-kappa-B and MAP kinases, and plays a central role in the regulation of B-cell survival. Part of signaling pathways leading to the production of cytokines and interferon. Required for normal antibody isotype switching from IgM to IgG. Plays a role T-cell dependent immune responses. Plays a role in the regulation of antiviral responses. Is an essential constituent of several E3 ubiquitin-protein ligase complexes. May have E3 ubiquitin-protein ligase activity and promote 'Lys-63'-linked ubiquitination of target proteins. Inhibits activation of NF-kappa-B in response to LTBR stimulation. Inhibits TRAF2-mediated activation of NF-kappa-B. Down-regulates proteolytic processing of NFKB2, and thereby inhibits non-canonical activation of NF-kappa-B. Promotes ubiquitination and proteasomal degradation of MAP3K14.[2] [3] [4] [5] [6] [7] [TANK_HUMAN] Acts as a regulator of TRAF function by maintaining them in a latent state. Overexpression inhibits TRAF2-mediated NF-kappa-B activation signaled by CD40, TNFR1 and TNFR2. Blocks TRAF2 binding to LMP1 and inhibits LMP1-mediated NF-kappa-B activation. May be involved in I-kappa-B-kinase (IKK) regulation; may function as an adapter for kinases such as TBK1 or IKBKE that can modulate IKK activity.[8] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedTRAFs (tumor necrosis factor receptor [TNFR]-associated factors) bind to the cytoplasmic portion of liganded TNFRs and stimulate activation of NF-kappaB or JNK pathways. A modulator of TRAF signaling, TANK, serves as either an enhancer or an inhibitor of TRAF-mediated signaling pathways. The crystal structure of a region of TANK bound to TRAF3 has been determined and compared to a similar CD40/TRAF3 complex. TANK and CD40 bind to the same crevice on TRAF3. The recognition motif PxQxT is presented in a boomerang-like structure in TANK that is markedly different from the hairpin loop that forms in CD40 upon binding to TRAF3. Critical TANK contact residues were confirmed by mutagenesis to be required for binding to TRAF3 or TRAF2. Binding affinity, measured by isothermal titration calorimetry and competition assays, demonstrated that TANK competes with CD40 for the TRAF binding site. Downstream regulator TANK binds to the CD40 recognition site on TRAF3.,Li C, Ni CZ, Havert ML, Cabezas E, He J, Kaiser D, Reed JC, Satterthwait AC, Cheng G, Ely KR Structure. 2002 Mar;10(3):403-11. PMID:12005438[9] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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Categories: Human | Cabezas, E | Cheng, G | Ely, K R | Havert, M L | He, J | Kaiser, D | Li, C | Ni, C Z | Reed, J C | Satterthwait, A C | Cd40 | Nf-kb signaling | Signaling protein | Tank | Tnf receptor | Traf3
