TNFAIP3
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Location (UCSC) | Chr 6: 137.87 – 137.88 Mb | Chr 10: 18.88 – 18.89 Mb | |||||||
PubMed search | [3] | [4] |
View/Edit Human | View/Edit Mouse |
Tumor necrosis factor, alpha-induced protein 3 or A20 is a protein that in humans is encoded by the TNFAIP3 gene.[5][6]
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
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
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000118503 - Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000019850 - Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- PMID 2118515.
- ^ "Entrez Gene: TNFAIP3 tumor necrosis factor, alpha-induced protein 3".
- PMID 29881386.
- PMID 11009421.
- ^ PMID 29796309.
- PMID 24487321.
- PMID 10385526.
- ^ PMID 8692885.
- ^ S2CID 19072203.
- PMID 10755617.
- PMID 10435631.
- ^ PMID 8702721.
- ^ PMID 9299557.
- PMID 11463333.
- PMID 20453842.
- ^ 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
- Dixit VM, Green S, Sarma V, et al. (1990). "Tumor necrosis factor-alpha induction of novel gene products in human endothelial cells including a macrophage-specific chemotaxin". J. Biol. Chem. 265 (5): 2973–8. PMID 2406243.
- Cooper JT, Stroka DM, Brostjan C, et al. (1996). "A20 blocks endothelial cell activation through a NF-kappaB-dependent mechanism". J. Biol. Chem. 271 (30): 18068–73. PMID 8663499.
- Meng Z, Zhao T, Zhou K, et al. (2017). "A20 Ameliorates Intracerebral Hemorrhage-Induced Inflammatory Injury by Regulating TRAF6 Polyubiquitination". J. Immunol. 198 (2): 820–31. PMID 27986908.
- Song HY, Rothe M, Goeddel DV (1996). "The tumor necrosis factor-inducible zinc finger protein A20 interacts with TRAF1/TRAF2 and inhibits NF-kappaB activation". Proc. Natl. Acad. Sci. U.S.A. 93 (13): 6721–5. PMID 8692885.
- Vincenz C, Dixit VM (1996). "14-3-3 proteins associate with A20 in an isoform-specific manner and function both as chaperone and adapter molecules". J. Biol. Chem. 271 (33): 20029–34. PMID 8702721.
- De Valck D, Heyninck K, Van Criekinge W, et al. (1996). "A20, an inhibitor of cell death, self-associates by its zinc finger domain". FEBS Lett. 384 (1): 61–4. S2CID 29040964.
- De Valck D, Heyninck K, Van Criekinge W, et al. (1997). "A20 inhibits NF-kappaB activation independently of binding to 14-3-3 proteins". Biochem. Biophys. Res. Commun. 238 (2): 590–4. PMID 9299557.
- Eliopoulos AG, Blake SM, Floettmann JE, et al. (1999). "Epstein-Barr virus-encoded latent membrane protein 1 activates the JNK pathway through its extreme C terminus via a mechanism involving TRADD and TRAF2". J. Virol. 73 (2): 1023–35. PMID 9882303.
- Heyninck K, Beyaert R (1999). "The cytokine-inducible zinc finger protein A20 inhibits IL-1-induced NF-kappaB activation at the level of TRAF6". FEBS Lett. 442 (2–3): 147–50. S2CID 19072203.
- Heyninck K, De Valck D, Vanden Berghe W, et al. (1999). "The zinc finger protein A20 inhibits TNF-induced NF-kappaB-dependent gene expression by interfering with an RIP- or TRAF2-mediated transactivation signal and directly binds to a novel NF-kappaB-inhibiting protein ABIN". J. Cell Biol. 145 (7): 1471–82. PMID 10385526.
- De Valck D, Jin DY, Heyninck K, et al. (1999). "The zinc finger protein A20 interacts with a novel anti-apoptotic protein which is cleaved by specific caspases". Oncogene. 18 (29): 4182–90. PMID 10435631.
- Zhang SQ, Kovalenko A, Cantarella G, Wallach D (2000). "Recruitment of the IKK signalosome to the p55 TNF receptor: RIP and A20 bind to NEMO (IKKgamma) upon receptor stimulation". Immunity. 12 (3): 301–11. PMID 10755617.
- Lee EG, Boone DL, Chai S, et al. (2000). "Failure to regulate TNF-induced NF-kappaB and cell death responses in A20-deficient mice". Science. 289 (5488): 2350–4. PMID 11009421.
- Klinkenberg M, Van Huffel S, Heyninck K, Beyaert R (2001). "Functional redundancy of the zinc fingers of A20 for inhibition of NF-kappaB activation and protein-protein interactions". FEBS Lett. 498 (1): 93–7. S2CID 32414520.
- Van Huffel S, Delaei F, Heyninck K, et al. (2001). "Identification of a novel A20-binding inhibitor of nuclear factor-kappa B activation termed ABIN-2". J. Biol. Chem. 276 (32): 30216–23. PMID 11390377.
- Evans PC, Taylor ER, Coadwell J, et al. (2001). "Isolation and characterization of two novel A20-like proteins". Biochem. J. 357 (Pt 3): 617–23. PMID 11463333.
- Baltathakis I, Alcantara O, Boldt DH (2001). "Expression of different NF-kappaB pathway genes in dendritic cells (DCs) or macrophages assessed by gene expression profiling". J. Cell. Biochem. 83 (2): 281–90. S2CID 12756967.
- Zetoune FS, Murthy AR, Shao Z, et al. (2002). "A20 inhibits NF-kappa B activation downstream of multiple Map3 kinases and interacts with the I kappa B signalosome". Cytokine. 15 (6): 282–98. PMID 11594795.
- Wu WS, Xu ZX, Chang KS (2002). "The promyelocytic leukemia protein represses A20-mediated transcription". J. Biol. Chem. 277 (35): 31734–9. PMID 12080044.
- Soni D, Wang DM, Regmi SC, Mittal M, Vogel SM, Schlüter D, Tiruppathi C (May 2018). "Deubiquitinase function of A20 maintains and repairs endothelial barrier after lung vascular injury". Cell Death Discovery. 4 (60): 60. PMID 29796309.
- He KL, Ting AT (2002). "A20 inhibits tumor necrosis factor (TNF) alpha-induced apoptosis by disrupting recruitment of TRADD and RIP to the TNF receptor 1 complex in Jurkat T cells". Mol. Cell. Biol. 22 (17): 6034–45. PMID 12167698.
External links
- Overview of all the structural information available in the PDB for UniProt: P21580 (Tumor necrosis factor alpha-induced protein 3) at the PDBe-KB.