TNFAIP3 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. Belongs to the peptidase C64 family. Note: This description may include information from UniProtKB.
Protein type: Apoptosis; EC; Protease; Ubiquitin conjugating system; Ubiquitin ligase
Chromosomal Location of Human Ortholog: 6q23.3
Cellular Component:  cytosol; intracellular membrane-bounded organelle; lysosome; nucleus
Molecular Function:  DNA binding; identical protein binding; kinase binding; Lys63-specific deubiquitinase activity; protease binding; protein binding; protein self-association; thiol-dependent ubiquitin-specific protease activity; thiol-dependent ubiquitinyl hydrolase activity; ubiquitin binding; ubiquitin-protein transferase activity; zinc ion binding
Biological Process:  apoptotic process; B-1 B cell homeostasis; cellular response to hydrogen peroxide; cellular response to lipopolysaccharide; establishment of protein localization to vacuole; inflammatory response; negative regulation of B cell activation; negative regulation of bone resorption; negative regulation of CD40 signaling pathway; negative regulation of chronic inflammatory response; negative regulation of cyclin-dependent protein serine/threonine kinase activity; negative regulation of endothelial cell apoptotic process; negative regulation of extrinsic apoptotic signaling pathway via death domain receptors; negative regulation of I-kappaB kinase/NF-kappaB signaling; negative regulation of inflammatory response; negative regulation of innate immune response; negative regulation of interleukin-1 beta secretion; negative regulation of interleukin-2 production; negative regulation of interleukin-6 production; negative regulation of NF-kappaB transcription factor activity; negative regulation of nucleotide-binding oligomerization domain containing 1 signaling pathway; negative regulation of nucleotide-binding oligomerization domain containing 2 signaling pathway; negative regulation of osteoclast proliferation; negative regulation of protein ubiquitination; negative regulation of smooth muscle cell proliferation; negative regulation of toll-like receptor 2 signaling pathway; negative regulation of toll-like receptor 3 signaling pathway; negative regulation of toll-like receptor 4 signaling pathway; negative regulation of toll-like receptor 5 signaling pathway; negative regulation of tumor necrosis factor production; negative regulation of type I interferon production; nucleotide-binding oligomerization domain containing signaling pathway; positive regulation of cellular protein catabolic process; positive regulation of hepatocyte proliferation; positive regulation of protein catabolic process; protein complex oligomerization; protein deubiquitination; protein K11-linked deubiquitination; protein K48-linked deubiquitination; protein K48-linked ubiquitination; protein K63-linked deubiquitination; regulation of defense response to virus by host; regulation of germinal center formation; regulation of tumor necrosis factor-mediated signaling pathway; regulation of vascular wound healing; response to molecule of bacterial origin; response to muramyl dipeptide; tolerance induction to lipopolysaccharide
Disease: Autoinflammatory Syndrome, Familial, Behcet-like
Reference #:  P21580 (UniProtKB)
Alt. Names/Synonyms: A20; A20p37; A20p50; AISBL; MGC104522; MGC138687; MGC138688; OTU domain-containing protein 7C; OTUD7C; Putative DNA-binding protein A20; TNAP3; TNF alpha induced protein 3; TNF alpha-induced protein 3; TNFA1P2; TNFAIP3; Tumor necrosis factor alpha-induced protein 3; tumor necrosis factor inducible protein A20; tumor necrosis factor, alpha induced protein 3; tumor necrosis factor, alpha-induced protein 3; Zinc finger protein A20
Gene Symbols: TNFAIP3
Molecular weight: 89,614 Da
Basal Isoelectric point: 8.61  Predict pI for various phosphorylation states
CST Pathways:  Inhibition of Apoptosis  |  NF-kB Signaling  |  Toll-Like Receptor Signaling
Protein-Specific Antibodies, siRNAs or Recombinant Proteins from Cell Signaling Technology® Total Proteins
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Protein Structure Not Found.

Cross-references to other databases:  STRING  |  cBioPortal  |  Wikipedia  |  Reactome  |  neXtProt  |  Protein Atlas  |  BioGPS  |  Pfam  |  RCSB PDB  |  ENZYME  |  Phospho3D  |  Phospho.ELM  |  NetworKIN  |  GeneCards  |  UniProtKB  |  Entrez-Gene  |  GenPept  |  Ensembl Gene