TNFAIP3 information

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)
End	137,883,312 bp
Gene location (Mouse)
Chr.	Chromosome 10 (mouse)
End	18,891,405 bp
RNA expression pattern
	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
	retinal pigment epithelium; ; thymus; ; Paneth cell; ; jejunum; ; left colon; ; spleen; ; subcutaneous adipose tissue; ; carotid body; ; urethra; ; female urethra;
	More reference expression data
	; ;
	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
	7128
	21929
	ENSG00000118503
	ENSMUSG00000019850
	P21580
	Q60769
	NM_001270507; NM_001270508; NM_006290
	NM_001166402; NM_009397
	NP_001257436; NP_001257437; NP_006281
	NP_001159874; NP_033423
	Wikidata
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 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]

^ ^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.
^ 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. doi:10.1016/S0021-9258(18)77165-2. PMID 2118515.
^ "Entrez Gene: TNFAIP3 tumor necrosis factor, alpha-induced protein 3".
^ Staal J, Driege Y, Haegman M, Borghi A, Hulpiau P, Lievens L, et al. (2018). "Ancient Origin of the CARD-Coiled Coil/Bcl10/MALT1-Like Paracaspase Signaling Complex Indicates Unknown Critical Functions". Frontiers in Immunology. 9: 1136. doi:10.3389/fimmu.2018.01136. PMC 5978004. PMID 29881386.
^ Lee EG, Boone DL, Chai S, Libby SL, Chien M, Lodolce JP, Ma A (September 2000). "Failure to regulate TNF-induced NF-kappaB and cell death responses in A20-deficient mice". Science. 289 (5488): 2350–2354. Bibcode:2000Sci...289.2350L. doi:10.1126/science.289.5488.2350. PMC 3582399. PMID 11009421.
^ ^a ^b 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. doi:10.1038/s41420-018-0056-3. PMC 5955943. PMID 29796309.
^ Tiruppathi C, Soni D, Wang DM, et al. (March 2014). "The transcription factor DREAM represses A20 and mediates inflammation". Nat Immunol. 15 (3): 239–247. doi:10.1038/ni.2823. PMC 4005385. PMID 24487321.

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000118503 – Ensembl, May 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000019850 – Ensembl, May 2017

[3] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[4] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[pmid2118515-5] 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. doi:10.1016/S0021-9258(18)77165-2. PMID 2118515.

[entrez-6] "Entrez Gene: TNFAIP3 tumor necrosis factor, alpha-induced protein 3".

[7] Staal J, Driege Y, Haegman M, Borghi A, Hulpiau P, Lievens L, et al. (2018). "Ancient Origin of the CARD-Coiled Coil/Bcl10/MALT1-Like Paracaspase Signaling Complex Indicates Unknown Critical Functions". Frontiers in Immunology. 9: 1136. doi:10.3389/fimmu.2018.01136. PMC 5978004. PMID 29881386.

[Lee_2001-8] Lee EG, Boone DL, Chai S, Libby SL, Chien M, Lodolce JP, Ma A (September 2000). "Failure to regulate TNF-induced NF-kappaB and cell death responses in A20-deficient mice". Science. 289 (5488): 2350–2354. Bibcode:2000Sci...289.2350L. doi:10.1126/science.289.5488.2350. PMC 3582399. PMID 11009421.

[Soni_2018-9] 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. doi:10.1038/s41420-018-0056-3. PMC 5955943. PMID 29796309.

[PMC4005385-10] Tiruppathi C, Soni D, Wang DM, et al. (March 2014). "The transcription factor DREAM represses A20 and mediates inflammation". Nat Immunol. 15 (3): 239–247. doi:10.1038/ni.2823. PMC 4005385. PMID 24487321.

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