TNFAIP3

Tumor necrosis factor, alpha-induced protein 3 or A20 is a protein that in humans is encoded by the TNFAIP3 gene.^[5][6]

TNFAIP3
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2EQF, 2EQG, 2VFJ, 3DKB, 3OJ3, 3OJ4, 3VUW, 3VUX, 3VUY, 3ZJD, 3ZJE, 3ZJF, 3ZJG, 4ZRH, 4ZS5
Identifiers
Aliases	TNFAIP3, A20, OTUD7C, TNFA1P2, AISBL, TNF alpha induced protein 3, AIFBL1
External IDs	OMIM: 191163; MGI: 1196377; HomoloGene: 4582; GeneCards: TNFAIP3; OMA:TNFAIP3 - orthologs
Gene location (Human) Chr. Chromosome 6 (human)[1] Band 6q23.3 Start 137,867,214 bp[1] End 137,883,312 bp[1]
Gene location (Mouse) Chr. Chromosome 10 (mouse)[2] Band 10 A3|10 8.08 cM Start 18,876,658 bp[2] End 18,891,405 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in vena cava mucosa of paranasal sinus appendix epithelium of nasopharynx pericardium mucosa of urinary bladder skin of thigh thymus lymph node cartilage tissue Top expressed in neural layer of retina retinal pigment epithelium mesenteric lymph nodes thymus epithelium of lens granulocyte Paneth cell jejunum left colon stroma of bone marrow More reference expression data BioGPS More reference expression data
Gene ontology Molecular function DNA binding cysteine-type peptidase activity zinc ion binding metal ion binding ubiquitin-protein transferase activity protease binding protein self-association peptidase activity ligase activity kinase binding K63-linked polyubiquitin modification-dependent protein binding ubiquitin binding protein binding catalytic activity thiol-dependent deubiquitinase hydrolase activity identical protein binding Lys63-specific deubiquitinase activity transferase activity Cellular component cytoplasm cytosol lysosome extracellular exosome nucleus intracellular membrane-bounded organelle Biological process regulation of germinal center formation positive regulation of hepatocyte proliferation negative regulation of endothelial cell apoptotic process negative regulation of interleukin-1 beta production negative regulation of smooth muscle cell proliferation regulation of vascular wound healing B-1 B cell homeostasis protein K48-linked deubiquitination positive regulation of protein catabolic process negative regulation of cyclin-dependent protein serine/threonine kinase activity regulation of defense response to virus by host protein deubiquitination involved in ubiquitin-dependent protein catabolic process negative regulation of toll-like receptor 2 signaling pathway negative regulation of nucleotide-binding oligomerization domain containing 2 signaling pathway regulation of tumor necrosis factor-mediated signaling pathway negative regulation of interleukin-6 production negative regulation of B cell activation negative regulation of toll-like receptor 5 signaling pathway tolerance induction to lipopolysaccharide response to muramyl dipeptide negative regulation of chronic inflammatory response negative regulation of cell death negative regulation of I-kappaB kinase/NF-kappaB signaling proteolysis establishment of protein localization to vacuole protein deubiquitination negative regulation of protein ubiquitination protein K48-linked ubiquitination protein K63-linked deubiquitination negative regulation of CD40 signaling pathway negative regulation of extrinsic apoptotic signaling pathway via death domain receptors protein complex oligomerization protein K11-linked deubiquitination regulation of inflammatory response negative regulation of nucleotide-binding oligomerization domain containing 1 signaling pathway negative regulation of innate immune response negative regulation of osteoclast proliferation negative regulation of tumor necrosis factor production negative regulation of type I interferon production metabolism inflammatory response response to molecule of bacterial origin negative regulation of NF-kappaB transcription factor activity negative regulation of interleukin-2 production negative regulation of inflammatory response negative regulation of toll-like receptor 3 signaling pathway nucleotide-binding oligomerization domain containing signaling pathway cellular response to lipopolysaccharide negative regulation of toll-like receptor 4 signaling pathway negative regulation of bone resorption cellular response to hydrogen peroxide apoptotic process protein ubiquitination cytoskeleton organization cell migration positive regulation of Wnt signaling pathway protein K29-linked deubiquitination protein K33-linked deubiquitination Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 7128 21929 Ensembl ENSG00000118503 ENSMUSG00000019850 UniProt P21580 Q60769 RefSeq (mRNA) NM_001270507 NM_001270508 NM_006290 NM_001166402 NM_009397 RefSeq (protein) NP_001257436 NP_001257437 NP_006281 NP_001159874 NP_033423 Location (UCSC) Chr 6: 137.87 – 137.88 Mb Chr 10: 18.88 – 18.89 Mb PubMed search [3] [4]
Wikidata
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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 a deubiquitinating enzyme, and has been shown to inhibit NF-kappa B activation as well as TNF-mediated apoptosis. The A20 protein is ancient, and protein homolog can be found as far back as cnidaria (corals, jellyfish, anemones) with a conserved protein domain composition.^[7] Using knockout mouse models of TNFAIP3 and its transcriptional repressor (i.e. KCHIP3), TNFAIP3 has been shown to be critical for limiting inflammation by terminating endotoxin- and TNF-induced NF-kappa B responses.^[8][9][10] In brief, deubiquitinase function of TNFAIP3 was shown to remove ubiquitin chains from VE-cadherin to prevent loss of VE-cadherin at the endothelial adherens junctions.^[9]

Interactions

TNFAIP3 has been shown to interact with TNIP1,^[11] TRAF1,^[12][13] TRAF2,^[12] IKBKG,^[14] TAX1BP1,^[15] YWHAB,^[16] YWHAZ,^[16][17] TRAF6^[13][18] and YWHAH.^[16][17]

Association with rheumatoid arthritis

The TNFAIP3 locus is implicated as a positively associated factor in rheumatoid arthritis (RA). The rs5029937 (T) and the rs6920220 (A) SNPs increase risk of RA by 20 to 40% respectively.^[19] A third SNP, rs10499194 (T) is found less often in rheumatoid arthritis but this negative association may not be statistically meaningful.

Other diseases

An association with infantile onset intractable inflammatory bowel disease has also been reported.^[20]

See also

• Haploinsufficiency of A20