TNFAIP3

1. 본문

TNFAIP3 (Tumor necrosis factor, alpha-induced protein 3), also known as A20, is a protein encoded by the *TNFAIP3* gene in humans. It plays a crucial role in regulating immune and inflammatory responses. Here's a breakdown of its key aspects:
Function:

• Ubiquitin-editing enzyme: TNFAIP3 has both ubiquitin ligase and deubiquitinase activities, meaning it can both add and remove ubiquitin tags from other proteins.
• NF-κB inhibitor: It is a critical negative regulator of the NF-κB signaling pathway, a pathway crucial for inflammation and immune responses. TNFAIP3 terminates NF-κB activity induced by cytokines like TNF-alpha and IL-1 beta, and by pathogens through Toll-like receptors (TLRs).
• Apoptosis inhibitor: TNFAIP3 can inhibit TNF-mediated apoptosis (programmed cell death).
• Immune and inflammatory response regulation: It is involved in immune and inflammatory responses signaled by cytokines or pathogens. It ensures the transient nature of inflammatory signaling pathways.

• Deubiquitination: Upon TNF stimulation, TNFAIP3 deubiquitinates 'Lys-63'-polyubiquitin chains on RIPK1, leading to its proteasomal degradation and termination of NF-κB activation. It also deubiquitinates TRAF6 and MALT1.
• Ubiquitination: It catalyzes the formation of 'Lys-48'-polyubiquitin chains on RIPK1.
• Protein complex interactions: TNFAIP3 forms a complex with other proteins, including RNF11, ITCH, and TAX1BP1, to regulate NF-κB signaling.

• Zinc finger protein: TNFAIP3 contains zinc finger motifs.
• Domains: It has an ovarian tumor (OTU) domain (deubiquitinating enzyme domain) in its N-terminal region and A20-type finger motifs (E3 ubiquitin ligase domain) in its C-terminal region.
• It is a homodimer and interacts with proteins such as TNIP1, TAX1BP1, ITCH, RNF11, TRAF1, TRAF2, and TRAF6.

• *TNFAIP3* is a functioning gene of 15869 base pairs, comprising 9 exons and 8 introns.
• Somatic mutations in the *TNFAIP3* gene have been found in certain types of lymphomas.

• Mutations or deletions in TNFAIP3 can lead to constitutive NF-κB activation and are associated with various diseases, including lymphomas, autoinflammatory syndromes and inflammatory arthritis.
• TNFAIP3 has been identified as a potential locus for type 1 diabetes.
• Mice deficient in A20 (TNFAIP3) in their B cells are prone to food allergies.