TNFAIP3 is a functioning gene of 15869 bp comprising 9 exons and 8 introns. Exon 1, the 5 part of exon 2 and the 3 part of exon 9 are non coding.

Length of the transcript is 4446 bp.
Coding sequence: CDS 67-2439.
mRNA is expressed at high levels in lymph nodes, respiratory tract, larynx, trachea and kidney.

Protein length of the unprocessed precursor: 790 amino acids.
Molecular weight of the unprocessed precursor: 89614 Da.
TNFAIP3 is a zinc finger protein containing seven A20-type finger motifs (E3 ubiquitin ligase domain) in its C-terminal region and a deubiquitinating enzyme domain, termed ovarian tumor (OTU) domain, in its N-terminal region. TNFAIP3 belongs to the peptidase C64 family. It is a homodimer that interacts with:
-TNIP1 (TNFAIP3 interacting protein 1, also known as Naf1 or ABIN-1),
-TAX1BP1 (Tax1 binding protein 1, also known as TXBP151 or T6BP),
-ITCH (itchy E3 ubiquitin protein ligase homolog (mouse)),
-RNF11 (ring finger protein 11),
-TRAF1, TRAF2, TRAF6 (TNF receptor-associated factor 1, 2 and 6).

Expression of TNFAIP3 is induced by TNF and is repressed by PML (promyelocytic leukemia) protein.

Cytoplasm and nucleus.

TNFAIP3 inhibits activation of NFKB and AP-1 transcription factors, and TNF- and IL-1beta (interleukin-1beta)- induced apoptosis.
TNFAIP3 is critical for limiting inflammatory processes by terminating TNF-induced NFKB responses, and contributes to the in vivo effects of TNF.
TNFAIP3 also restricts NFKB signaling in response to stimulation of TLR (toll-like receptor) and NOD (nuclear-binding and oligomerization domain) pathways.
TNFAIP3 possesses dual ubiquitin-editing functions. In particular, the N-terminal domain of TNFAIP3 is a deubiquitinating enzyme (DUB) for Lys63-linked polyubiquitinated signaling mediators such as TRAF2/6 and RIP1 (receptor interacting protein 1). Instead, the C-terminal domain of TNFAIP3 is a ubiquitin ligase (E3) for Lys48-linked degradative polyubiquitination of the same substrates. TNFAIP3 has a specificity for particular polyubiquitinated substrates to regulate NFKB activation in the TNF, IL-1beta and TLR pathways.
TNFAIP3 has a role in the function of the lymphoid system because it inhibits NFKB signaling and may play an important role in lymphomagenesis. TNFAIP3 also negatively regulates the activity of CARD10 (caspase recruitment domain family, member 10) and BCL10 (B-cell CLL/lymphoma 10) in lymphoid and non-lymphoid cells.
A TNFAIP3-mediated inhibition of TNF-induced apoptosis is associated with the inhibition of caspase-8.
TNFAIP3 acts forming a multiprotein complex with other proteins, in particular ABIN-1, TAX1BP1, ITCH, RNF11, TRAF1, TRAF2, TRAF6, to regulate NFKB signaling cascade and TNF-induced cell death.
TNFAIP3 negatively regulates the maturation, inflammatory cytokine production and immunostimulatory potency of dendritic cells.

Interspecies: ortholog to murine TNFAIP3 and homolog to Caenorhabditis elegans F21C3.2.

Deletions and bi-allelic somatic mutations involving TNFAIP3 gene have been identified in different subtypes of B-cell lymphomas. Most of the TNFAIP3 mutations are nonsense or frameshift that prevent production of full-length TNFAIP3 protein.