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Background
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A20, also referred to as TNF-α-induced protein 3 (TNFAIP3), is cytokine-inducible protein that functions to inhibit apoptosis and activate NF-κB. It was first identified as a TNF-α inducible primary response gene in human umbilical vein endothelial cells, and encodes a 790-amino acid protein containing seven Cys2/Cys2-zinc finger motifs. Constitutive expression of A20 is observed in lymphoid tissues, but it is transiently expressed in a variety of cell types in response to inflammatory signals such as TNF-α, IL-1, phorbol esters, and LPS. Expression of A20 can confer resistance to apoptosis and NF-κB activation triggered by these signals, probably through interference with TRAF (TNF receptor associated factor) family members, and interaction with the NF-κB inhibiting protein ABIN. Studies also show that A20 contains site-specific ubiquitin modifying activity that can contribute to its biological functions. The amino-terminus of A20 contains de-ubiquitinating (DUB) activity for Lys63 branches, such as those found in TRAF6 and RIP, while the carboxyl-terminus contains ubiquitin ligase (E3) activity for Lys48 branches of the same substrates and leads to their degradation. Synonyms: TNFAIP3, A20, MGC104522, MGC138687, MGC138688, OTUD7C, TNFA1P2
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