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{{Infobox_gene}}
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'''Tumor necrosis factor, alpha-induced protein 3''' is a [[protein]] that in humans is encoded by the ''TNFAIP3'' [[gene]].<ref name="pmid2118515">{{cite journal |author1=Opipari AW Jr |author2=Boguski MS |author3=Dixit VM | title = The A20 cDNA induced by tumor necrosis factor alpha encodes a novel type of zinc finger protein | journal = J Biol Chem | volume = 265 | issue = 25 | pages = 14705–8 |date=October 1990 | pmid = 2118515 | pmc =  | doi = }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: TNFAIP3 tumor necrosis factor, alpha-induced protein 3| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=7128| accessdate = }}</ref>
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{{GNF_Protein_box
| image = 
| image_source = 
| PDB =
| Name = Tumor necrosis factor, alpha-induced protein 3
| HGNCid = 11896
| Symbol = TNFAIP3
| AltSymbols =; A20; MGC104522; MGC138687; MGC138688; OTUD7C; TNFA1P2
| OMIM = 191163
| ECnumber = 
| Homologene = 4582
| MGIid = 1196377
| GeneAtlas_image1 = PBB_GE_TNFAIP3_202644_s_at_tn.png
| GeneAtlas_image2 = PBB_GE_TNFAIP3_202643_s_at_tn.png
| Function = {{GNF_GO|id=GO:0003677 |text = DNA binding}} {{GNF_GO|id=GO:0005515 |text = protein binding}} {{GNF_GO|id=GO:0008234 |text = cysteine-type peptidase activity}} {{GNF_GO|id=GO:0008270 |text = zinc ion binding}} {{GNF_GO|id=GO:0046872 |text = metal ion binding}}
| Component = {{GNF_GO|id=GO:0005634 |text = nucleus}} {{GNF_GO|id=GO:0005737 |text = cytoplasm}}
  | Process = {{GNF_GO|id=GO:0006512 |text = ubiquitin cycle}} {{GNF_GO|id=GO:0006915 |text = apoptosis}} {{GNF_GO|id=GO:0006916 |text = anti-apoptosis}} {{GNF_GO|id=GO:0043124 |text = negative regulation of I-kappaB kinase/NF-kappaB cascade}}
| Orthologs = {{GNF_Ortholog_box
    | Hs_EntrezGene = 7128
    | Hs_Ensembl = ENSG00000118503
    | Hs_RefseqProtein = NP_006281
    | Hs_RefseqmRNA = NM_006290
    | Hs_GenLoc_db = 
    | Hs_GenLoc_chr = 6
    | Hs_GenLoc_start = 138230151
    | Hs_GenLoc_end = 138246135
    | Hs_Uniprot = P21580
    | Mm_EntrezGene = 21929
    | Mm_Ensembl = ENSMUSG00000019850
    | Mm_RefseqmRNA = NM_009397
    | Mm_RefseqProtein = NP_033423
    | Mm_GenLoc_db = 
    | Mm_GenLoc_chr = 10
    | Mm_GenLoc_start = 18690335
    | Mm_GenLoc_end = 18704826
    | Mm_Uniprot = Q3T9G9
  }}
}}
'''Tumor necrosis factor, alpha-induced protein 3''', also known as '''TNFAIP3''', is a human [[gene]].<ref name="entrez">{{cite web | title = Entrez Gene: TNFAIP3 tumor necrosis factor, alpha-induced protein 3| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=7128| accessdate = }}</ref>


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{{PBB_Summary
{{PBB_Summary
| section_title =  
| section_title =
| summary_text = 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 has been shown to inhibit NF-kappa B activation as well as TNF-mediated apoptosis. Knockout studies of a similar gene in mice suggested that this gene is critical for limiting inflammation by terminating TNF-induced NF-kappa B responses.<ref name="entrez">{{cite web | title = Entrez Gene: TNFAIP3 tumor necrosis factor, alpha-induced protein 3| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=7128| accessdate = }}</ref>
| summary_text = 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 has been shown to inhibit [[NF-kappa B]] activation as well as TNF-mediated [[apoptosis]]. Knockout studies of a similar gene in mice suggested that this gene is critical for limiting inflammation by terminating TNF-induced NF-kappa B responses.<ref name="entrez"/>
}}
}}
==Interactions==
TNFAIP3 has been shown to [[Protein-protein interaction|interact]] with [[TNIP1]],<ref name=pmid10385526>{{cite journal |last=Heyninck |first=K |authorlink= |author2=De Valck D |author3=Vanden Berghe W |author4=Van Criekinge W |author5=Contreras R |author6=Fiers W |author7=Haegeman G |author8=Beyaert R  |date=June 1999 |title=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 |journal=J. Cell Biol. |volume=145 |issue=7 |pages=1471–82 |publisher= |location = UNITED STATES| issn = 0021-9525| pmid = 10385526 | bibcode = | oclc =| id = | url = | language = | format = | accessdate = | laysummary = | laysource = | laydate = | quote = |doi=10.1083/jcb.145.7.1471 |pmc=2133159 }}</ref> [[TRAF1]],<ref name=pmid8692885>{{cite journal |last=Song |first=H Y |authorlink= |author2=Rothe M |author3=Goeddel D V  |date=June 1996 |title=The tumor necrosis factor-inducible zinc finger protein A20 interacts with TRAF1/TRAF2 and inhibits NF-kappaB activation |journal=[[PNAS|Proc. Natl. Acad. Sci. U.S.A.]] |volume=93 |issue=13 |pages=6721–5 |publisher= |location = UNITED STATES| issn = 0027-8424| pmid = 8692885 | bibcode =1996PNAS...93.6721S | oclc =| id = | url = | language = | format = | accessdate = | laysummary = | laysource = | laydate = | quote = |doi=10.1073/pnas.93.13.6721 |pmc=39093 }}</ref><ref name=pmid9928991>{{cite journal |last=Heyninck |first=K |authorlink= |author2=Beyaert R  |date=January 1999 |title=The cytokine-inducible zinc finger protein A20 inhibits IL-1-induced NF-kappaB activation at the level of TRAF6 |journal=FEBS Lett. |volume=442 |issue=2–3 |pages=147–50 |publisher= |location = NETHERLANDS| issn = 0014-5793| pmid = 9928991 | bibcode = | oclc =| id = | url = | language = | format = | accessdate = | laysummary = | laysource = | laydate = | quote = |doi=10.1016/S0014-5793(98)01645-7 }}</ref> [[TRAF2]],<ref name=pmid8692885/> [[IKBKG]],<ref name=pmid10755617>{{cite journal |last=Zhang |first=S Q |authorlink= |author2=Kovalenko A |author3=Cantarella G |author4=Wallach D  |date=March 2000 |title=Recruitment of the IKK signalosome to the p55 TNF receptor: RIP and A20 bind to NEMO (IKKgamma) upon receptor stimulation |journal=Immunity |volume=12 |issue=3 |pages=301–11 |publisher= |location = UNITED STATES| issn = 1074-7613| pmid = 10755617 | bibcode = | oclc =| id = | url = | language = | format = | accessdate = | laysummary = | laysource = | laydate = | quote = |doi=10.1016/S1074-7613(00)80183-1 }}</ref> [[TAX1BP1]],<ref name=pmid10435631>{{cite journal |last=De Valck |first=D |authorlink= |author2=Jin D Y |author3=Heyninck K |author4=Van de Craen M |author5=Contreras R |author6=Fiers W |author7=Jeang K T |author8=Beyaert R  |date=July 1999 |title=The zinc finger protein A20 interacts with a novel anti-apoptotic protein which is cleaved by specific caspases |journal=Oncogene |volume=18 |issue=29 |pages=4182–90 |publisher= |location = ENGLAND| issn = 0950-9232| pmid = 10435631 |doi = 10.1038/sj.onc.1202787 | bibcode = | oclc =| id = | url = | language = | format = | accessdate = | laysummary = | laysource = | laydate = | quote = }}</ref> [[YWHAB]],<ref name=pmid8702721>{{cite journal |last=Vincenz |first=C |authorlink= |author2=Dixit V M  |date=August 1996 |title=14-3-3 proteins associate with A20 in an isoform-specific manner and function both as chaperone and adapter molecules |journal=J. Biol. Chem. |volume=271 |issue=33 |pages=20029–34 |publisher= |location = UNITED STATES| issn = 0021-9258| pmid = 8702721 | bibcode = | oclc =| id = | url = | language = | format = | accessdate = | laysummary = | laysource = | laydate = | quote = |doi=10.1074/jbc.271.33.20029 }}</ref> [[YWHAZ]],<ref name=pmid8702721/><ref name=pmid9299557>{{cite journal |last=De Valck |first=D |authorlink= |author2=Heyninck K |author3=Van Criekinge W |author4=Vandenabeele P |author5=Fiers W |author6=Beyaert R  |date=September 1997 |title=A20 inhibits NF-kappaB activation independently of binding to 14-3-3 proteins |journal=Biochem. Biophys. Res. Commun. |volume=238 |issue=2 |pages=590–4 |publisher= |location = UNITED STATES| issn = 0006-291X| pmid = 9299557 |doi = 10.1006/bbrc.1997.7343 | bibcode = | oclc =| id = | url = | language = | format = | accessdate = | laysummary = | laysource = | laydate = | quote = }}</ref> [[TRAF6]]<ref name=pmid9928991/><ref name=pmid11463333>{{cite journal |last=Evans |first=P C |authorlink= |author2=Taylor E R |author3=Coadwell J |author4=Heyninck K |author5=Beyaert R |author6=Kilshaw P J  |date=August 2001 |title=Isolation and characterization of two novel A20-like proteins |journal=Biochem. J. |volume=357 |issue=Pt 3 |pages=617–23 |publisher= |location = England| issn = 0264-6021| pmid = 11463333 | bibcode = | oclc =| id = | url = | language = | format = | accessdate = | laysummary = | laysource = | laydate = | quote = |doi=10.1042/0264-6021:3570617 |pmc=1221992 }}</ref> and [[YWHAH]].<ref name=pmid8702721/><ref name=pmid9299557/>
==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) [[single-nucleotide polymorphism|SNPs]] increase risk of RA by 20 to 40% respectively.<ref name="pmid20453842">{{cite journal  |vauthors=Stahl EA, Raychaudhuri S, Remmers EF, etal | title = Genome-wide association study meta-analysis identifies seven new rheumatoid arthritis risk loci | journal = Nat. Genet. | volume = 42 | issue = 6 | pages = 508–14 |date=June 2010 | pmid = 20453842 | doi = 10.1038/ng.582 | url = | issn = | pmc = 4243840 }}</ref> 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.<ref name=Zheng2018>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 </ref>


==References==
==References==
{{reflist|2}}
{{Reflist}}
 
==Further reading==
==Further reading==
{{refbegin | 2}}
{{Refbegin | 2}}
{{PBB_Further_reading  
{{PBB_Further_reading
| citations =  
| citations =
*{{cite journal | author=Opipari AW, Boguski MS, Dixit VM |title=The A20 cDNA induced by tumor necrosis factor alpha encodes a novel type of zinc finger protein. |journal=J. Biol. Chem. |volume=265 |issue= 25 |pages= 14705-8 |year= 1990 |pmid= 2118515 |doi=  }}
*{{cite journal   |vauthors=Dixit VM, Green S, Sarma V, etal |title=Tumor necrosis factor-alpha induction of novel gene products in human endothelial cells including a macrophage-specific chemotaxin |journal=J. Biol. Chem. |volume=265 |issue= 5 |pages= 2973–8 |year= 1990 |pmid= 2406243 |doi=  }}
*{{cite journal | author=Dixit VM, Green S, Sarma V, ''et al.'' |title=Tumor necrosis factor-alpha induction of novel gene products in human endothelial cells including a macrophage-specific chemotaxin. |journal=J. Biol. Chem. |volume=265 |issue= 5 |pages= 2973-8 |year= 1990 |pmid= 2406243 |doi=  }}
*{{cite journal   |vauthors=Cooper JT, Stroka DM, Brostjan C, etal |title=A20 blocks endothelial cell activation through a NF-kappaB-dependent mechanism |journal=J. Biol. Chem. |volume=271 |issue= 30 |pages= 18068–73 |year= 1996 |pmid= 8663499 |doi=10.1074/jbc.271.30.18068 }}
*{{cite journal | author=Cooper JT, Stroka DM, Brostjan C, ''et al.'' |title=A20 blocks endothelial cell activation through a NF-kappaB-dependent mechanism. |journal=J. Biol. Chem. |volume=271 |issue= 30 |pages= 18068-73 |year= 1996 |pmid= 8663499 |doi= }}
*{{cite journal   |vauthors=Meng Z, Zhao T, Zhou K, etal |title=A20 Ameliorates Intracerebral Hemorrhage-Induced Inflammatory Injury by Regulating TRAF6 Polyubiquitination |journal=J. Immunol. |volume=198 |issue= 2 |pages= 820–31 |year= 2017 |pmid= 27986908 |doi=10.4049/jimmunol.1600334 |pmc=5220121}}
*{{cite journal  | author=Song HY, Rothe M, Goeddel DV |title=The tumor necrosis factor-inducible zinc finger protein A20 interacts with TRAF1/TRAF2 and inhibits NF-kappaB activation. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=93 |issue= 13 |pages= 6721-5 |year= 1996 |pmid= 8692885 |doi=  }}
*{{cite journal  |vauthors=Song HY, Rothe M, Goeddel DV |title=The tumor necrosis factor-inducible zinc finger protein A20 interacts with TRAF1/TRAF2 and inhibits NF-kappaB activation |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=93 |issue= 13 |pages= 6721–5 |year= 1996 |pmid= 8692885 |doi=10.1073/pnas.93.13.6721 | pmc=39093  |bibcode=1996PNAS...93.6721S }}
*{{cite journal  | author=Vincenz C, Dixit VM |title=14-3-3 proteins associate with A20 in an isoform-specific manner and function both as chaperone and adapter molecules. |journal=J. Biol. Chem. |volume=271 |issue= 33 |pages= 20029-34 |year= 1996 |pmid= 8702721 |doi=  }}
*{{cite journal  |vauthors=Vincenz C, Dixit VM |title=14-3-3 proteins associate with A20 in an isoform-specific manner and function both as chaperone and adapter molecules |journal=J. Biol. Chem. |volume=271 |issue= 33 |pages= 20029–34 |year= 1996 |pmid= 8702721 |doi=10.1074/jbc.271.33.20029 }}
*{{cite journal | author=De Valck D, Heyninck K, Van Criekinge W, ''et al.'' |title=A20, an inhibitor of cell death, self-associates by its zinc finger domain. |journal=FEBS Lett. |volume=384 |issue= 1 |pages= 61-4 |year= 1996 |pmid= 8797804 |doi=  }}
*{{cite journal   |vauthors=De Valck D, Heyninck K, Van Criekinge W, etal |title=A20, an inhibitor of cell death, self-associates by its zinc finger domain |journal=FEBS Lett. |volume=384 |issue= 1 |pages= 61–4 |year= 1996 |pmid= 8797804 |doi=10.1016/0014-5793(96)00283-9 }}
*{{cite journal | author=De Valck D, Heyninck K, Van Criekinge W, ''et al.'' |title=A20 inhibits NF-kappaB activation independently of binding to 14-3-3 proteins. |journal=Biochem. Biophys. Res. Commun. |volume=238 |issue= 2 |pages= 590-4 |year= 1997 |pmid= 9299557 |doi= 10.1006/bbrc.1997.7343 }}
*{{cite journal   |vauthors=De Valck D, Heyninck K, Van Criekinge W, etal |title=A20 inhibits NF-kappaB activation independently of binding to 14-3-3 proteins |journal=Biochem. Biophys. Res. Commun. |volume=238 |issue= 2 |pages= 590–4 |year= 1997 |pmid= 9299557 |doi= 10.1006/bbrc.1997.7343 }}
*{{cite journal | author=Eliopoulos AG, Blake SM, Floettmann JE, ''et al.'' |title=Epstein-Barr virus-encoded latent membrane protein 1 activates the JNK pathway through its extreme C terminus via a mechanism involving TRADD and TRAF2. |journal=J. Virol. |volume=73 |issue= 2 |pages= 1023-35 |year= 1999 |pmid= 9882303 |doi=  }}
*{{cite journal   |vauthors=Eliopoulos AG, Blake SM, Floettmann JE, etal |title=Epstein-Barr virus-encoded latent membrane protein 1 activates the JNK pathway through its extreme C terminus via a mechanism involving TRADD and TRAF2 |journal=J. Virol. |volume=73 |issue= 2 |pages= 1023–35 |year= 1999 |pmid= 9882303 |doi= | pmc=103922 }}
*{{cite journal  | author=Heyninck K, Beyaert R |title=The cytokine-inducible zinc finger protein A20 inhibits IL-1-induced NF-kappaB activation at the level of TRAF6. |journal=FEBS Lett. |volume=442 |issue= 2-3 |pages= 147-50 |year= 1999 |pmid= 9928991 |doi=  }}
*{{cite journal  |vauthors=Heyninck K, Beyaert R |title=The cytokine-inducible zinc finger protein A20 inhibits IL-1-induced NF-kappaB activation at the level of TRAF6 |journal=FEBS Lett. |volume=442 |issue= 2–3 |pages= 147–50 |year= 1999 |pmid= 9928991 |doi=10.1016/S0014-5793(98)01645-7 }}
*{{cite journal | author=Heyninck K, De Valck D, Vanden Berghe W, ''et al.'' |title=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. |journal=J. Cell Biol. |volume=145 |issue= 7 |pages= 1471-82 |year= 1999 |pmid= 10385526 |doi=  }}
*{{cite journal   |vauthors=Heyninck K, De Valck D, Vanden Berghe W, etal |title=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 |journal=J. Cell Biol. |volume=145 |issue= 7 |pages= 1471–82 |year= 1999 |pmid= 10385526 |doi=10.1083/jcb.145.7.1471  | pmc=2133159 |hdl=1854/LU-113881 }}
*{{cite journal | author=De Valck D, Jin DY, Heyninck K, ''et al.'' |title=The zinc finger protein A20 interacts with a novel anti-apoptotic protein which is cleaved by specific caspases. |journal=Oncogene |volume=18 |issue= 29 |pages= 4182-90 |year= 1999 |pmid= 10435631 |doi= 10.1038/sj.onc.1202787 }}
*{{cite journal   |vauthors=De Valck D, Jin DY, Heyninck K, etal |title=The zinc finger protein A20 interacts with a novel anti-apoptotic protein which is cleaved by specific caspases |journal=Oncogene |volume=18 |issue= 29 |pages= 4182–90 |year= 1999 |pmid= 10435631 |doi= 10.1038/sj.onc.1202787 }}
*{{cite journal  | author=Zhang SQ, Kovalenko A, Cantarella G, Wallach D |title=Recruitment of the IKK signalosome to the p55 TNF receptor: RIP and A20 bind to NEMO (IKKgamma) upon receptor stimulation. |journal=Immunity |volume=12 |issue= 3 |pages= 301-11 |year= 2000 |pmid= 10755617 |doi=  }}
*{{cite journal  |vauthors=Zhang SQ, Kovalenko A, Cantarella G, Wallach D |title=Recruitment of the IKK signalosome to the p55 TNF receptor: RIP and A20 bind to NEMO (IKKgamma) upon receptor stimulation |journal=Immunity |volume=12 |issue= 3 |pages= 301–11 |year= 2000 |pmid= 10755617 |doi=10.1016/S1074-7613(00)80183-1 }}
*{{cite journal | author=Lee EG, Boone DL, Chai S, ''et al.'' |title=Failure to regulate TNF-induced NF-kappaB and cell death responses in A20-deficient mice. |journal=Science |volume=289 |issue= 5488 |pages= 2350-4 |year= 2000 |pmid= 11009421 |doi= }}
*{{cite journal   |vauthors=Lee EG, Boone DL, Chai S, etal |title=Failure to regulate TNF-induced NF-kappaB and cell death responses in A20-deficient mice |journal=Science |volume=289 |issue= 5488 |pages= 2350–4 |year= 2000 |pmid= 11009421 |doi=10.1126/science.289.5488.2350 |pmc=3582399|bibcode=2000Sci...289.2350L }}
*{{cite journal  | author=Klinkenberg M, Van Huffel S, Heyninck K, Beyaert R |title=Functional redundancy of the zinc fingers of A20 for inhibition of NF-kappaB activation and protein-protein interactions. |journal=FEBS Lett. |volume=498 |issue= 1 |pages= 93-7 |year= 2001 |pmid= 11389905 |doi= }}
*{{cite journal  |vauthors=Klinkenberg M, Van Huffel S, Heyninck K, Beyaert R |title=Functional redundancy of the zinc fingers of A20 for inhibition of NF-kappaB activation and protein-protein interactions |journal=FEBS Lett. |volume=498 |issue= 1 |pages= 93–7 |year= 2001 |pmid= 11389905 |doi=10.1016/S0014-5793(01)02504-2  }}
*{{cite journal | author=Van Huffel S, Delaei F, Heyninck K, ''et al.'' |title=Identification of a novel A20-binding inhibitor of nuclear factor-kappa B activation termed ABIN-2. |journal=J. Biol. Chem. |volume=276 |issue= 32 |pages= 30216-23 |year= 2001 |pmid= 11390377 |doi= 10.1074/jbc.M100048200 }}
*{{cite journal   |vauthors=Van Huffel S, Delaei F, Heyninck K, etal |title=Identification of a novel A20-binding inhibitor of nuclear factor-kappa B activation termed ABIN-2 |journal=J. Biol. Chem. |volume=276 |issue= 32 |pages= 30216–23 |year= 2001 |pmid= 11390377 |doi= 10.1074/jbc.M100048200 }}
*{{cite journal | author=Evans PC, Taylor ER, Coadwell J, ''et al.'' |title=Isolation and characterization of two novel A20-like proteins. |journal=Biochem. J. |volume=357 |issue= Pt 3 |pages= 617-23 |year= 2001 |pmid= 11463333 |doi=  }}
*{{cite journal   |vauthors=Evans PC, Taylor ER, Coadwell J, etal |title=Isolation and characterization of two novel A20-like proteins |journal=Biochem. J. |volume=357 |issue= Pt 3 |pages= 617–23 |year= 2001 |pmid= 11463333 |doi=10.1042/0264-6021:3570617  | pmc=1221992 }}
*{{cite journal  | author=Baltathakis I, Alcantara O, Boldt DH |title=Expression of different NF-kappaB pathway genes in dendritic cells (DCs) or macrophages assessed by gene expression profiling. |journal=J. Cell. Biochem. |volume=83 |issue= 2 |pages= 281-90 |year= 2001 |pmid= 11573245 |doi=  }}
*{{cite journal  |vauthors=Baltathakis I, Alcantara O, Boldt DH |title=Expression of different NF-kappaB pathway genes in dendritic cells (DCs) or macrophages assessed by gene expression profiling |journal=J. Cell. Biochem. |volume=83 |issue= 2 |pages= 281–90 |year= 2001 |pmid= 11573245 |doi=10.1002/jcb.1231 }}
*{{cite journal | author=Zetoune FS, Murthy AR, Shao Z, ''et al.'' |title=A20 inhibits NF-kappa B activation downstream of multiple Map3 kinases and interacts with the I kappa B signalosome. |journal=Cytokine |volume=15 |issue= 6 |pages= 282-98 |year= 2002 |pmid= 11594795 |doi= 10.1006/cyto.2001.0921 }}
*{{cite journal   |vauthors=Zetoune FS, Murthy AR, Shao Z, etal |title=A20 inhibits NF-kappa B activation downstream of multiple Map3 kinases and interacts with the I kappa B signalosome |journal=Cytokine |volume=15 |issue= 6 |pages= 282–98 |year= 2002 |pmid= 11594795 |doi= 10.1006/cyto.2001.0921 }}
*{{cite journal  | author=Wu WS, Xu ZX, Chang KS |title=The promyelocytic leukemia protein represses A20-mediated transcription. |journal=J. Biol. Chem. |volume=277 |issue= 35 |pages= 31734-9 |year= 2002 |pmid= 12080044 |doi= 10.1074/jbc.M201648200 }}
*{{cite journal  |vauthors=Wu WS, Xu ZX, Chang KS |title=The promyelocytic leukemia protein represses A20-mediated transcription |journal=J. Biol. Chem. |volume=277 |issue= 35 |pages= 31734–9 |year= 2002 |pmid= 12080044 |doi= 10.1074/jbc.M201648200 }}
*{{cite journal  | author=He KL, Ting AT |title=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. |journal=Mol. Cell. Biol. |volume=22 |issue= 17 |pages= 6034-45 |year= 2002 |pmid= 12167698 |doi=  }}
*{{cite journal  |vauthors=He KL, Ting AT |title=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 |journal=Mol. Cell. Biol. |volume=22 |issue= 17 |pages= 6034–45 |year= 2002 |pmid= 12167698 |doi=10.1128/MCB.22.17.6034-6045.2002  | pmc=133997 }}
}}
}}
{{refend}}
{{Refend}}


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Latest revision as of 14:17, 4 November 2018

VALUE_ERROR (nil)
Identifiers
Aliases
External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
Entrez

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Tumor necrosis factor, alpha-induced protein 3 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 has been shown to inhibit NF-kappa B activation as well as TNF-mediated apoptosis. Knockout studies of a similar gene in mice suggested that this gene is critical for limiting inflammation by terminating TNF-induced NF-kappa B responses.[2]

Interactions

TNFAIP3 has been shown to interact with TNIP1,[3] TRAF1,[4][5] TRAF2,[4] IKBKG,[6] TAX1BP1,[7] YWHAB,[8] YWHAZ,[8][9] TRAF6[5][10] and YWHAH.[8][9]

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.[11] 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.[12]

References

  1. ↑ Opipari AW Jr; Boguski MS; Dixit VM (October 1990). "The A20 cDNA induced by tumor necrosis factor alpha encodes a novel type of zinc finger protein". J Biol Chem. 265 (25): 14705–8. PMID 2118515.
  2. ↑ 2.0 2.1 "Entrez Gene: TNFAIP3 tumor necrosis factor, alpha-induced protein 3".
  3. ↑ Heyninck, K; De Valck D; Vanden Berghe W; Van Criekinge W; Contreras R; Fiers W; Haegeman G; Beyaert R (June 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. UNITED STATES. 145 (7): 1471–82. doi:10.1083/jcb.145.7.1471. ISSN 0021-9525. PMC 2133159. PMID 10385526.
  4. ↑ 4.0 4.1 Song, H Y; Rothe M; Goeddel D V (June 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. UNITED STATES. 93 (13): 6721–5. Bibcode:1996PNAS...93.6721S. doi:10.1073/pnas.93.13.6721. ISSN 0027-8424. PMC 39093. PMID 8692885.
  5. ↑ 5.0 5.1 Heyninck, K; Beyaert R (January 1999). "The cytokine-inducible zinc finger protein A20 inhibits IL-1-induced NF-kappaB activation at the level of TRAF6". FEBS Lett. NETHERLANDS. 442 (2–3): 147–50. doi:10.1016/S0014-5793(98)01645-7. ISSN 0014-5793. PMID 9928991.
  6. ↑ Zhang, S Q; Kovalenko A; Cantarella G; Wallach D (March 2000). "Recruitment of the IKK signalosome to the p55 TNF receptor: RIP and A20 bind to NEMO (IKKgamma) upon receptor stimulation". Immunity. UNITED STATES. 12 (3): 301–11. doi:10.1016/S1074-7613(00)80183-1. ISSN 1074-7613. PMID 10755617.
  7. ↑ De Valck, D; Jin D Y; Heyninck K; Van de Craen M; Contreras R; Fiers W; Jeang K T; Beyaert R (July 1999). "The zinc finger protein A20 interacts with a novel anti-apoptotic protein which is cleaved by specific caspases". Oncogene. ENGLAND. 18 (29): 4182–90. doi:10.1038/sj.onc.1202787. ISSN 0950-9232. PMID 10435631.
  8. ↑ 8.0 8.1 8.2 Vincenz, C; Dixit V M (August 1996). "14-3-3 proteins associate with A20 in an isoform-specific manner and function both as chaperone and adapter molecules". J. Biol. Chem. UNITED STATES. 271 (33): 20029–34. doi:10.1074/jbc.271.33.20029. ISSN 0021-9258. PMID 8702721.
  9. ↑ 9.0 9.1 De Valck, D; Heyninck K; Van Criekinge W; Vandenabeele P; Fiers W; Beyaert R (September 1997). "A20 inhibits NF-kappaB activation independently of binding to 14-3-3 proteins". Biochem. Biophys. Res. Commun. UNITED STATES. 238 (2): 590–4. doi:10.1006/bbrc.1997.7343. ISSN 0006-291X. PMID 9299557.
  10. ↑ Evans, P C; Taylor E R; Coadwell J; Heyninck K; Beyaert R; Kilshaw P J (August 2001). "Isolation and characterization of two novel A20-like proteins". Biochem. J. England. 357 (Pt 3): 617–23. doi:10.1042/0264-6021:3570617. ISSN 0264-6021. PMC 1221992. PMID 11463333.
  11. ↑ Stahl EA, Raychaudhuri S, Remmers EF, et al. (June 2010). "Genome-wide association study meta-analysis identifies seven new rheumatoid arthritis risk loci". Nat. Genet. 42 (6): 508–14. doi:10.1038/ng.582. PMC 4243840. PMID 20453842.
  12. ↑ 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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