TNFAIP3

Tumor necrosis factor alpha-induced protein 3
Identifiers
Symbol	?
NCBI gene	7128
HGNC	11905
OMIM	191163
RefSeq	NM_006290
UniProt	P21580
Search for Structures Swiss-model Domains InterPro

Tumor necrosis factor alpha-induced protein 3 (TNFAIP3), also known as A20, is a human gene that encodes a protein involved in the negative feedback regulation of inflammation. TNFAIP3 is a critical regulator of the NF-kB signaling pathway, which plays a key role in immune responses, inflammation, and cell survival.

Structure

The TNFAIP3 gene is located on chromosome 6q23.3 and spans approximately 95 kilobases. It consists of 9 exons and encodes a protein of 790 amino acids. The TNFAIP3 protein contains several functional domains, including an N-terminal ovarian tumor (OTU) domain with deubiquitinating activity and seven C-terminal zinc finger domains that mediate interactions with other proteins.

Function

TNFAIP3 acts as a ubiquitin-editing enzyme that removes ubiquitin moieties from specific substrates, thereby regulating their stability and activity. It is primarily involved in the termination of NF-kB signaling by deubiquitinating key signaling molecules such as RIPK1 and TRAF6. This action prevents excessive inflammatory responses and maintains immune homeostasis.

Clinical Significance

Mutations and dysregulation of TNFAIP3 have been implicated in a variety of autoimmune and inflammatory diseases, including systemic lupus erythematosus, rheumatoid arthritis, and Crohn's disease. Loss-of-function mutations in TNFAIP3 can lead to uncontrolled activation of the NF-kB pathway, resulting in chronic inflammation and tissue damage.

Research and Therapeutic Potential

Given its central role in regulating inflammation, TNFAIP3 is a potential therapeutic target for treating inflammatory and autoimmune diseases. Strategies to enhance TNFAIP3 activity or mimic its function are being explored to develop new treatments for these conditions.

Also see

• NF-kB
• Ubiquitination
• Autoimmune diseases
• Inflammation