TNFAIP3
Lua error in Module:Infobox_gene at line 53: attempt to index field 'wikibase' (a nil value). Tumor necrosis factor, alpha-induced protein 3 or A20 is a protein that in humans is encoded by the TNFAIP3 gene.[1][2]
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.[3] 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.[4][5][6] 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.[5]
Interactions
[edit | edit source]TNFAIP3 has been shown to interact with TNIP1,[7] TRAF1,[8][9] TRAF2,[8] IKBKG,[10] TAX1BP1,[11] YWHAB,[12] YWHAZ,[12][13] TRAF6[9][14] and YWHAH.[12][13]
Association with rheumatoid arthritis
[edit | edit source]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.[15] A third SNP, rs10499194 (T) is found less often in rheumatoid arthritis but this negative association may not be statistically meaningful.
Other diseases
[edit | edit source]An association with infantile onset intractable inflammatory bowel disease has also been reported.[16]
See also
[edit | edit source]References
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- ^ Zheng C, Huang Y, Ye Z, Wang Y, Tang Z, Lu J, Wu J, Zhou Y, Wang L, Huang Z, Yang H, Xue A (2018) Infantile onset intractable inflammatory bowel disease due to novel heterozygous mutations in TNFAIP3 (A20). Inflamm Bowel Dis doi: 10.1093/ibd/izy165
Further reading
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