TNFAIP3

Tumor necrosis factor, alpha-induced protein 3

Rendering based on PDB 2EQE.

Available structures

Ortholog search: PDBe, RCSB

List of PDB id codes
2EQE, 2EQF, 2EQG, 2VFJ, 3DKB, 3OJ3, 3OJ4, 3VUW, 3VUX, 3VUY, 3ZJD, 3ZJE, 3ZJF, 3ZJG

Identifiers

Symbols

TNFAIP3 ; A20; OTUD7C; TNFA1P2

External IDs

OMIM: 191163 MGI: 1196377 HomoloGene: 4582 GeneCards: TNFAIP3 Gene

EC number

3.4.19.12

Gene ontology
Molecular function	• protease binding • DNA binding • ubiquitin-protein transferase activity • ubiquitin-specific protease activity • protein binding • zinc ion binding • ligase activity • kinase binding • ubiquitin binding • protein self-association • K63-linked polyubiquitin binding
Cellular component	• nucleus • cytoplasm • lysosome • centrosome • cytosol • extracellular exosome
Biological process	• B-1 B cell homeostasis • response to molecule of bacterial origin • regulation of germinal center formation • negative regulation of chronic inflammatory response • apoptotic process • inflammatory response • protein deubiquitination • negative regulation of protein ubiquitination • negative regulation of NF-kappaB transcription factor activity • negative regulation of type I interferon production • response to muramyl dipeptide • negative regulation of interleukin-1 beta production • negative regulation of interleukin-2 production • negative regulation of interleukin-6 production • negative regulation of tumor necrosis factor production • negative regulation of toll-like receptor 2 signaling pathway • negative regulation of toll-like receptor 3 signaling pathway • negative regulation of toll-like receptor 4 signaling pathway • negative regulation of toll-like receptor 5 signaling pathway • protein K11-linked deubiquitination • nucleotide-binding domain, leucine rich repeat containing receptor signaling pathway • negative regulation of I-kappaB kinase/NF-kappaB signaling • innate immune response • positive regulation of protein catabolic process • negative regulation of cyclin-dependent protein serine/threonine kinase activity • negative regulation of bone resorption • negative regulation of innate immune response • negative regulation of smooth muscle cell proliferation • regulation of defense response to virus by host • regulation of inflammatory response • negative regulation of inflammatory response • negative regulation of B cell activation • protein oligomerization • regulation of vascular wound healing • cellular response to hydrogen peroxide • nucleotide-binding oligomerization domain containing signaling pathway • negative regulation of nucleotide-binding oligomerization domain containing 1 signaling pathway • negative regulation of nucleotide-binding oligomerization domain containing 2 signaling pathway • protein K63-linked deubiquitination • protein K48-linked ubiquitination • protein K48-linked deubiquitination • cellular response to lipopolysaccharide • protein deubiquitination involved in ubiquitin-dependent protein catabolic process • tolerance induction to lipopolysaccharide • establishment of protein localization to vacuole • negative regulation of osteoclast proliferation • negative regulation of extrinsic apoptotic signaling pathway via death domain receptors • positive regulation of cellular protein catabolic process • positive regulation of hepatocyte proliferation • negative regulation of CD40 signaling pathway • negative regulation of endothelial cell apoptotic process
Sources: Amigo / QuickGO

RNA expression pattern

More reference expression data

Orthologs

Species

Human

Mouse

RefSeq (mRNA)

RefSeq (protein)

Location (UCSC)

Chr 6:
137.87 – 137.88 Mb

Chr 10:
19 – 19.02 Mb

PubMed search

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.

References

↑ 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.
1 2 "Entrez Gene: TNFAIP3 tumor necrosis factor, alpha-induced protein 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.
1 2 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. doi:10.1073/pnas.93.13.6721. ISSN 0027-8424. PMC 39093. PMID 8692885.
1 2 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.
↑ 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.
↑ 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.
1 2 3 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.
1 2 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.
↑ 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.
↑ 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. PMID 20453842.

TNFAIP3

Interactions

Association with rheumatoid arthritis

References

Further reading