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ABIN-2, TNFAIP3 interacting protein 2, binds to the COOH-terminal zinc finger domain of A20. NF-kB activation induced by TNF and interleukin-1 is inhibited by overexpression of ABIN-2. The latter also inhibits NF-kB activation induced by overexpression of receptor-interacting protein or TNF receptor-associated factor 2. A-20 binding Inhibitor of Nuclear Factor-kappaB (NF-kB)Activation (ABIN-2) binds to A-20. ABIN-2 interferes with NF-kB activation upstream of the IKK complex and might contribute to NF-kB inhibitory function of A-20.