TNFAIP3 Protein, Human (Active, GST, His)

TNFAIP3 is a ubiquitin-editing enzyme with both ubiquitin ligase and deubiquitinase activities, involved in immune and inflammatory responses triggered by cytokines such as TNF-alpha and IL-1 beta or pathogens via Toll-like receptors (TLRs) by terminating NF-kappa-B activity. It is an essential component of a ubiquitin-editing protein complex, including RNF11, ITCH, and TAX1BP1, ensuring the transient nature of inflammatory signaling pathways. In cooperation with TAX1BP1, it promotes disassembly of E2-E3 ubiquitin protein ligase complexes in IL-1R and TNFR-1 pathways, affecting at least E3 ligases TRAF6, TRAF2, and BIRC2, as well as E2 ubiquitin-conjugating enzymes UBE2N and UBE2D3. Upon TNF stimulation, it deubiquitinates 'Lys-63'-polyubiquitin chains on RIPK1 and catalyzes 'Lys-48'-polyubiquitin chain formation, leading to RIPK1 proteasomal degradation and termination of TNF- or LPS-mediated NF-kappa-B activation. It also deubiquitinates TRAF6, likely acting on 'Lys-63'-linked polyubiquitin. During TCR-mediated T-cell activation, it deubiquitinates 'Lys-63'-polyubiquitin chains on MALT1, mediating disassociation of the CBM (CARD11:BCL10:MALT1) and IKK complexes to prevent sustained IKK activation. Additionally, it deubiquitinates NEMO/IKBKG, facilitated by TNIP1, inhibiting NF-kappa-B activation. Upon bacterial peptidoglycan stimulation, it likely deubiquitinates RIPK2. It can also inhibit I-kappa-B-kinase (IKK) non-catalytically via polyubiquitin, which promotes association with IKBKG and blocks IKK MAP3K7-mediated phosphorylation. It targets TRAF2 for lysosomal degradation and, in vitro, deubiquitinates 'Lys-11'-, 'Lys-48'-, and 'Lys-63'-polyubiquitin chains. As an inhibitor of programmed cell death, it plays a role in lymphoid system function and is required for LPS-induced pro-inflammatory cytokine and IFN beta production in LPS-tolerized macrophages.