Summary

Name TNFAIP3
Full Name Tumor necrosis factor alpha-induced protein 3
Synonyms TNF alpha-induced protein 3, OTU domain-containing protein 7C, Putative DNA-binding protein A20, Zinc finger protein A20 | OTUD7C
Primary ID P21580
Links - -
Type protein
Relations 5
Pathways NF-KB Canonical
Function Ubiquitin-editing enzyme that contains both ubiquitin ligase and deubiquitinase activities. Involved in immune and inflammatory responses signaled by cytokines, such as TNF-alpha and IL-1 beta, or pathogens via Toll-like receptors (TLRs) through terminating NF-kappa-B activity. Essential component of a ubiquitin-editing protein complex, comprising also RNF11, ITCH and TAX1BP1, that ensures the transient nature of inflammatory signaling pathways. In cooperation with TAX1BP1 promotes disassembly of E2-E3 ubiquitin protein ligase complexes in IL-1R and TNFR-1 pathways; affected are at least E3 ligases TRAF6, TRAF2 and BIRC2, and E2 ubiquitin-conjugating enzymes UBE2N and UBE2D3. In cooperation with TAX1BP1 promotes ubiquitination of UBE2N and proteasomal degradation of UBE2N and UBE2D3. Upon TNF stimulation, deubiquitinates 'Lys-63'-polyubiquitin chains on RIPK1 and catalyzes the formation of 'Lys-48'-polyubiquitin chains. This leads to RIPK1 proteasomal degradation and consequently termination of the TNF- or LPS-mediated activation of NF-kappa-B. Deubiquitinates TRAF6 probably acting on 'Lys-63'-linked polyubiquitin. Upon T-cell receptor (TCR)-mediated T-cell activation, deubiquitinates 'Lys-63'-polyubiquitin chains on MALT1 thereby mediating disassociation of the CBM (CARD11:BCL10:MALT1) and IKK complexes and preventing sustained IKK activation. Deubiquitinates NEMO/IKBKG; the function is facilitated by TNIP1 and leads to inhibition of NF-kappa-B activation. Upon stimulation by bacterial peptidoglycans, probably deubiquitinates RIPK2. Can also inhibit I-kappa-B-kinase (IKK) through a non-catalytic mechanism which involves polyubiquitin; polyubiquitin promotes association with IKBKG and prevents IKK MAP3K7-mediated phosphorylation. Targets TRAF2 for lysosomal degradation. In vitro able to deubiquitinate 'Lys-11'-, 'Lys-48'- and 'Lys-63' polyubiquitin chains. Inhibitor of programmed cell death. Has a role in the function of the lymphoid system. Required for LPS-induced production of proinflammatory cytokines and IFN beta in LPS-tolerized macrophages.

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Relations

Regulator Mechanism target score ℹ
+ TNFAIP3down-regulates activity img/direct_inhibition.png deubiquitination TRAF6 0.69
Publications: 1 Organism: Homo Sapiens
Pathways:IL1 Signaling , NF-KB Canonical
+ ITCHup-regulates activity img/direct-activation.png binding TNFAIP3 0.285
Publications: 1 Organism: Homo Sapiens
Pathways:IL1 Signaling , NF-KB Canonical
+ TNFAIP3down-regulates quantity img/direct_inhibition.png ubiquitination RIPK1 0.64
Publications: 2 Organism: Homo Sapiens
Pathways:NF-KB Canonical
+ TAX1BP1up-regulates activity img/direct-activation.png binding TNFAIP3 0.67
Publications: 1 Organism: Homo Sapiens
Pathways:IL1 Signaling , NF-KB Canonical