Tbio TNFAIP3 Tumor necrosis factor alpha-induced protein 3

Protein Summary

Description

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. This gene was identified as a gene whose expression is rapidly induced by the tumor necrosis factor (TNF). The protein encoded by this gene is a zinc finger protein and ubiqitin-editing enzyme, and has been shown to inhibit NF-kappa B activation as well as TNF-mediated apoptosis. The encoded protein, which has both ubiquitin ligase and deubiquitinase activities, is involved in the cytokine-mediated immune and inflammatory responses. Several transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Jul 2012]

Uniprot Accession IDs

• P21580
• B2R767
• E1P588
• Q2HIX9
• Q5VXQ7
• Q9NSR6
• TNF alpha-induced protein 3

Gene Name

• TNFAIP3

Ensembl ID

• ENST00000237289
• ENSP00000237289
• ENSG00000118503
• ENST00000612899
• ENSP00000481570

Symbol

• OTUD7C
• A20
• AISBL
• OTUD7C
• TNFA1P2

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
biological process	1
virus perturbation	1
gene perturbation	0.99
transcription factor binding site profile	0.96
molecular function	0.93

Protein Classes

PANTHER Classes

Protein / Nucleic Acid Binding / Dna Binding Protein / Tumor Necrosis Factor Alpha-induced Protein 3

Protein / Hydrolase / Tumor Necrosis Factor Alpha-induced Protein 3

Protein / ... / Cysteine Protease / Tumor Necrosis Factor Alpha-induced Protein 3

DTO Classes

Protein / Enzyme / Protease / Cysteine Protease / Tumor Necrosis Factor Alpha-induced Protein 3

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 483.43   (req: < 5)

Gene RIFs: 392   (req: <= 3)

Antibodies: 441   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 483.43   (req: >= 5)

Gene RIFs: 392   (req: > 3)

Antibodies: 441   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 66

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligand: 0

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drug: 0