======= TNFAIP3 =======


== Gene Information ==
  * **<color #00a2e8>Official Symbol</color>**: TNFAIP3
  * **<color #00a2e8>Official Name</color>**: TNF alpha induced protein 3
  * **<color #00a2e8>Aliases and Previous Symbols</color>**: N/A
  * **<color #00a2e8>Entrez ID</color>**: [[https://www.ncbi.nlm.nih.gov/gene/?term=7128|7128]]
  * **<color #00a2e8>UniProt</color>**: [[https://www.uniprot.org/uniprot/P21580|P21580]]
  * **<color #00a2e8>Interactions</color>**: [[https://thebiogrid.org/search.php?search=TNFAIP3&organism=9606|BioGRID]]
  * **<color #00a2e8>PubMed articles</color>**: [[https://www.ncbi.nlm.nih.gov/pubmed/?term=gene%20TNFAIP3|Open PubMed]]
  * **<color #00a2e8>OMIM</color>**: [[https://omim.org/entry/191163|Open OMIM]]

== Function Summary ==
  * **<color #00a2e8>Entrez Summary</color>**:  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 ubiqitin-editing enzyme, and has been shown to inhibit NF-kappa B activation as well as TNF-mediated apoptosis. The encoded protein, which has both ubiquitin ligase and deubiquitinase activities, is involved in the cytokine-mediated immune and inflammatory responses. Several transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Jul 2012]. 
  * **<color #00a2e8>UniProt Summary</color>**:  Ubiquitin-editing enzyme that contains both ubiquitin ligase and deubiquitinase activities. Involved in immune and inflammatory responses signaled by cytokines, such as TNF-alpha and IL-1 beta, or pathogens via Toll-like receptors (TLRs) through terminating NF-kappa-B activity. Essential component of a ubiquitin-editing protein complex, comprising also RNF11, ITCH and TAX1BP1, that ensures the transient nature of inflammatory signaling pathways. In cooperation with TAX1BP1 promotes disassembly of E2-E3 ubiquitin protein ligase complexes in IL-1R and TNFR-1 pathways; affected are at least E3 ligases TRAF6, TRAF2 and BIRC2, and E2 ubiquitin-conjugating enzymes UBE2N and UBE2D3. In cooperation with TAX1BP1 promotes ubiquitination of UBE2N and proteasomal degradation of UBE2N and UBE2D3. Upon TNF stimulation, deubiquitinates 'Lys-63'-polyubiquitin chains on RIPK1 and catalyzes the formation of 'Lys-48'-polyubiquitin chains. This leads to RIPK1 proteasomal degradation and consequently termination of the TNF- or LPS-mediated activation of NF-kappa-B. Deubiquitinates TRAF6 probably acting on 'Lys-63'-linked polyubiquitin. Upon T-cell receptor (TCR)-mediated T-cell activation, deubiquitinates 'Lys-63'-polyubiquitin chains on MALT1 thereby mediating disassociation of the CBM (CARD11:BCL10:MALT1) and IKK complexes and preventing sustained IKK activation. Deubiquitinates NEMO/IKBKG; the function is facilitated by TNIP1 and leads to inhibition of NF-kappa-B activation. Upon stimulation by bacterial peptidoglycans, probably deubiquitinates RIPK2. Can also inhibit I-kappa-B-kinase (IKK) through a non-catalytic mechanism which involves polyubiquitin; polyubiquitin promotes association with IKBKG and prevents IKK MAP3K7-mediated phosphorylation. Targets TRAF2 for lysosomal degradation. In vitro able to deubiquitinate 'Lys-11'-, 'Lys-48'- and 'Lys-63' polyubiquitin chains. Inhibitor of programmed cell death. Has a role in the function of the lymphoid system. Required for LPS- induced production of proinflammatory cytokines and IFN beta in LPS-tolerized macrophages. {ECO:0000269|PubMed:14748687, ECO:0000269|PubMed:15258597, ECO:0000269|PubMed:16684768, ECO:0000269|PubMed:17961127, ECO:0000269|PubMed:18164316, ECO:0000269|PubMed:18952128, ECO:0000269|PubMed:19494296, ECO:0000269|PubMed:22099304, ECO:0000269|PubMed:23827681, ECO:0000269|PubMed:8692885, ECO:0000269|PubMed:9299557, ECO:0000269|PubMed:9882303}.

<button type='primary' size='sm' modal='Pfam_Domains'>Pfam Domains</button>
<button type='primary' size='sm' modal='GO_terms'>GO Terms</button>


<modal id='Pfam_Domains' size='lg' title='Pfam Domains'>
|zf-A20|
|OTU|
</modal>

<modal id='GO_terms' size='lg' title='GO Terms'>
|regulation of toll-like receptor 5 signaling pathway|
|negative regulation of nucleotide-binding oligomerization domain containing 1 signaling pathway|
|negative regulation of toll-like receptor 5 signaling pathway|
|negative regulation of CD40 signaling pathway|
|tolerance induction to lipopolysaccharide|
|regulation of nucleotide-binding oligomerization domain containing 1 signaling pathway|
|negative regulation of osteoclast proliferation|
|negative regulation of toll-like receptor 3 signaling pathway|
|negative regulation of nucleotide-binding oligomerization domain containing signaling pathway|
|negative regulation of nucleotide-binding oligomerization domain containing 2 signaling pathway|
|B-1 B cell homeostasis|
|protein K33-linked deubiquitination|
|negative regulation of chronic inflammatory response|
|protein K29-linked deubiquitination|
|regulation of osteoclast proliferation|
|negative regulation of toll-like receptor 2 signaling pathway|
|regulation of nucleotide-binding oligomerization domain containing 2 signaling pathway|
|regulation of vascular wound healing|
|regulation of CD40 signaling pathway|
|protein deubiquitination involved in ubiquitin-dependent protein catabolic process|
|positive regulation of hepatocyte proliferation|
|regulation of germinal center formation|
|regulation of chronic inflammatory response|
|regulation of nucleotide-binding oligomerization domain containing signaling pathway|
|negative regulation of toll-like receptor 4 signaling pathway|
|regulation of toll-like receptor 3 signaling pathway|
|regulation of toll-like receptor 2 signaling pathway|
|protein K11-linked deubiquitination|
|Lys63-specific deubiquitinase activity|
|tolerance induction|
|negative regulation of lipopolysaccharide-mediated signaling pathway|
|negative regulation of bone resorption|
|regulation of hepatocyte proliferation|
|negative regulation of bone remodeling|
|negative regulation of interleukin-1 beta secretion|
|negative regulation of interleukin-1 secretion|
|response to muramyl dipeptide|
|negative regulation of tissue remodeling|
|regulation of toll-like receptor 4 signaling pathway|
|K63-linked polyubiquitin modification-dependent protein binding|
|negative regulation of interleukin-2 production|
|regulation of lipopolysaccharide-mediated signaling pathway|
|B cell homeostasis|
|nucleotide-binding oligomerization domain containing signaling pathway|
|negative regulation of interleukin-1 beta production|
|nucleotide-binding domain, leucine rich repeat containing receptor signaling pathway|
|negative regulation of cyclin-dependent protein serine/threonine kinase activity|
|negative regulation of cyclin-dependent protein kinase activity|
|negative regulation of endothelial cell apoptotic process|
|negative regulation of B cell activation|
|protein K63-linked deubiquitination|
|protein K48-linked deubiquitination|
|negative regulation of interleukin-1 production|
|cytoplasmic pattern recognition receptor signaling pathway|
|regulation of defense response to virus by host|
|negative regulation of extrinsic apoptotic signaling pathway via death domain receptors|
|negative regulation of toll-like receptor signaling pathway|
|regulation of bone resorption|
|negative regulation of epithelial cell apoptotic process|
|negative regulation of interleukin-6 production|
|negative regulation of I-kappaB kinase/NF-kappaB signaling|
|negative regulation of type I interferon production|
|negative regulation of smooth muscle cell proliferation|
|regulation of interleukin-1 beta secretion|
|establishment of protein localization to vacuole|
|regulation of bone remodeling|
|regulation of endothelial cell apoptotic process|
|protein K48-linked ubiquitination|
|lymphocyte homeostasis|
|regulation of interleukin-2 production|
|regulation of interleukin-1 secretion|
|thiol-dependent ubiquitinyl hydrolase activity|
|protein self-association|
|regulation of extrinsic apoptotic signaling pathway via death domain receptors|
|negative regulation of innate immune response|
|regulation of tumor necrosis factor-mediated signaling pathway|
|negative regulation of tumor necrosis factor production|
|negative regulation of tumor necrosis factor superfamily cytokine production|
|protein localization to vacuole|
|negative regulation of cytokine secretion|
|regulation of toll-like receptor signaling pathway|
|leukocyte homeostasis|
|cellular response to hydrogen peroxide|
|negative regulation of protein ubiquitination|
|regulation of defense response to virus|
|regulation of tissue remodeling|
|negative regulation of leukocyte proliferation|
|regulation of epithelial cell apoptotic process|
|ubiquitin binding|
|positive regulation of animal organ morphogenesis|
|regulation of interleukin-1 beta production|
|negative regulation of NF-kappaB transcription factor activity|
|negative regulation of protein modification by small protein conjugation or removal|
|negative regulation of response to biotic stimulus|
|kinase binding|
|regulation of interleukin-1 production|
|regulation of cyclin-dependent protein serine/threonine kinase activity|
|negative regulation of extrinsic apoptotic signaling pathway|
|protease binding|
|regulation of cyclin-dependent protein kinase activity|
|thiol-dependent ubiquitin-specific protease activity|
|cellular response to antibiotic|
|response to hydrogen peroxide|
|regulation of type I interferon production|
|pattern recognition receptor signaling pathway|
|cellular response to reactive oxygen species|
|negative regulation of protein secretion|
|negative regulation of protein serine/threonine kinase activity|
|regulation of smooth muscle cell proliferation|
|negative regulation of inflammatory response|
|regulation of wound healing|
|negative regulation of peptide secretion|
|regulation of interleukin-6 production|
|positive regulation of cellular protein catabolic process|
|regulation of adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains|
|negative regulation of lymphocyte activation|
|regulation of tumor necrosis factor production|
|negative regulation of immune response|
|regulation of tumor necrosis factor superfamily cytokine production|
|regulation of extrinsic apoptotic signaling pathway|
|regulation of adaptive immune response|
|negative regulation of DNA-binding transcription factor activity|
|regulation of cytokine-mediated signaling pathway|
|intracellular receptor signaling pathway|
|regulation of response to wounding|
|negative regulation of leukocyte activation|
|regulation of response to cytokine stimulus|
|positive regulation of Wnt signaling pathway|
|negative regulation of protein transport|
|cellular response to lipopolysaccharide|
|negative regulation of establishment of protein localization|
|positive regulation of epithelial cell proliferation|
|cellular response to molecule of bacterial origin|
|response to reactive oxygen species|
|negative regulation of cell activation|
|homeostasis of number of cells|
|regulation of protein ubiquitination|
|negative regulation of secretion by cell|
|regulation of cytokine secretion|
|negative regulation of defense response|
|regulation of B cell activation|
|cellular response to toxic substance|
|negative regulation of multi-organism process|
|cellular response to biotic stimulus|
|positive regulation of protein catabolic process|
|regulation of leukocyte proliferation|
|negative regulation of protein kinase activity|
|negative regulation of apoptotic signaling pathway|
|regulation of protein modification by small protein conjugation or removal|
|negative regulation of secretion|
|innate immune response-activating signal transduction|
|regulation of I-kappaB kinase/NF-kappaB signaling|
|cellular response to oxidative stress|
|negative regulation of kinase activity|
|ubiquitin-protein transferase activity|
|regulation of cellular protein catabolic process|
|lysosome|
|regulation of animal organ morphogenesis|
|activation of innate immune response|
|negative regulation of cytokine production|
|negative regulation of transferase activity|
|protein deubiquitination|
|regulation of angiogenesis|
|protein modification by small protein removal|
|protein polyubiquitination|
|response to antibiotic|
|response to lipopolysaccharide|
|regulation of vasculature development|
|response to molecule of bacterial origin|
|regulation of epithelial cell proliferation|
|regulation of inflammatory response|
|positive regulation of innate immune response|
|regulation of Wnt signaling pathway|
|positive regulation of response to biotic stimulus|
|negative regulation of response to external stimulus|
|positive regulation of cellular catabolic process|
|regulation of protein catabolic process|
|response to oxidative stress|
|regulation of apoptotic signaling pathway|
|cellular response to drug|
|negative regulation of protein phosphorylation|
|regulation of DNA-binding transcription factor activity|
|positive regulation of catabolic process|
|establishment of protein localization to organelle|
|negative regulation of immune system process|
|negative regulation of phosphorylation|
|regulation of innate immune response|
|regulation of protein secretion|
|regulation of immune effector process|
|response to peptide|
|positive regulation of defense response|
|negative regulation of transport|
|regulation of peptide secretion|
|inflammatory response|
|response to toxic substance|
|negative regulation of intracellular signal transduction|
|positive regulation of multi-organism process|
|regulation of lymphocyte activation|
|regulation of protein serine/threonine kinase activity|
|protein complex oligomerization|
|cellular response to lipid|
|regulation of response to biotic stimulus|
|ubiquitin-dependent protein catabolic process|
|modification-dependent protein catabolic process|
|response to inorganic substance|
|modification-dependent macromolecule catabolic process|
|negative regulation of phosphate metabolic process|
|negative regulation of phosphorus metabolic process|
|immune response-activating signal transduction|
|negative regulation of cell cycle|
|proteolysis involved in cellular protein catabolic process|
|negative regulation of protein modification process|
|immune response-regulating signaling pathway|
|regulation of leukocyte activation|
|positive regulation of response to external stimulus|
|cellular protein catabolic process|
|activation of immune response|
|regulation of cell activation|
|immune system development|
|negative regulation of cell population proliferation|
|protein catabolic process|
|intracellular membrane-bounded organelle|
|protein ubiquitination|
|response to bacterium|
|regulation of cytokine production|
|regulation of protein transport|
|protein localization to organelle|
|regulation of peptide transport|
|regulation of establishment of protein localization|
|regulation of secretion by cell|
|regulation of defense response|
|protein modification by small protein conjugation|
|regulation of multi-organism process|
|negative regulation of catalytic activity|
|regulation of protein kinase activity|
|regulation of secretion|
|regulation of cellular catabolic process|
|zinc ion binding|
|response to lipid|
|positive regulation of immune response|
|regulation of kinase activity|
|negative regulation of apoptotic process|
|cellular macromolecule catabolic process|
|negative regulation of programmed cell death|
|positive regulation of cell population proliferation|
|apoptotic process|
|cell migration|
|regulation of transferase activity|
|protein modification by small protein conjugation or removal|
|regulation of catabolic process|
|negative regulation of cell death|
|response to organonitrogen compound|
|response to drug|
|regulation of protein localization|
|negative regulation of cellular protein metabolic process|
|macromolecule catabolic process|
|programmed cell death|
|cellular response to oxygen-containing compound|
|organonitrogen compound catabolic process|
|regulation of anatomical structure morphogenesis|
|identical protein binding|
|localization of cell|
|cell motility|
|response to nitrogen compound|
|cell death|
|regulation of response to external stimulus|
|negative regulation of protein metabolic process|
|cytoskeleton organization|
|negative regulation of molecular function|
|regulation of immune response|
|positive regulation of immune system process|
|regulation of cell cycle|
|negative regulation of multicellular organismal process|
|negative regulation of signal transduction|
|proteolysis|
|response to other organism|
|response to external biotic stimulus|
|locomotion|
|response to biotic stimulus|
|defense response|
|negative regulation of cell communication|
|negative regulation of signaling|
|positive regulation of developmental process|
|regulation of protein phosphorylation|
|DNA binding|
|regulation of response to stress|
|regulation of apoptotic process|
|movement of cell or subcellular component|
|response to oxygen-containing compound|
|protein-containing complex assembly|
|regulation of programmed cell death|
|cellular protein localization|
|regulation of phosphorylation|
|cellular macromolecule localization|
|positive regulation of cellular protein metabolic process|
|establishment of protein localization|
|regulation of cell population proliferation|
|negative regulation of response to stimulus|
|homeostatic process|
|positive regulation of signal transduction|
|regulation of immune system process|
|regulation of cell death|
|intracellular signal transduction|
|cellular response to stress|
|positive regulation of protein metabolic process|
|positive regulation of multicellular organismal process|
|organic substance catabolic process|
|regulation of phosphate metabolic process|
|regulation of phosphorus metabolic process|
|cellular catabolic process|
|positive regulation of cell communication|
|positive regulation of signaling|
|regulation of intracellular signal transduction|
|regulation of protein modification process|
|protein-containing complex subunit organization|
|regulation of transport|
</modal>
\\

 === CRISPR Data ===
<button type='primary' size='small' modal='Compound_Hit'>Compound Hit</button>
<button type='primary' size='small' modal='Most_Correlated_Genes'>Most Correlated Genes in Chemogenomics</button>
<button type='primary' size='small' modal='Essential_Avana'>Tissues where Essential in the Avana Dataset (DepMap 20Q1)</button>

<modal id='Compound_Hit' size='lg' title='Compound Hit'>
^Screen^Score^
|[[:results:exp533|TNF-alpha 44ng/ml R08 exp533]]|-4.04|
|[[:results:exp175|3-Bromopyruvate 7μM R04 exp175]]|-3.12|
|[[:results:exp180|Dynasore 10μM R04 exp180]]|-2.8|
|[[:results:exp38|Wortmannin 5μM R00 exp38]]|-2.34|
|[[:results:exp359|FK-506 30μM R07 exp359]]|-2.27|
|[[:results:exp84|UM0125461 0.74μM R02 exp84]]|-2.11|
|[[:results:exp446|4-Nitroquinoline-1-oxide 0.5μM R08 exp446]]|-1.98|
|[[:results:exp240|Pyridostatin 4μM R05 exp240]]|-1.97|
|[[:results:exp89|Vemurafenib 6.6μM R02 exp89]]|-1.92|
|[[:results:exp436|Dynasore 7μM R08 exp436]]|-1.84|
|[[:results:exp343|Centrinone 0.5μM R07 exp343]]|-1.81|
|[[:results:exp210|LB-100 2μM R05 exp210]]|-1.73|
|[[:results:exp199|Etoposide 0.3μM R05 exp199]]|1.93|
</modal>

<modal id='Most_Correlated_Genes' size='lg' title='Most Correlated Genes in Chemogenomics'>
^Gene^Correlation^
|[[:human genes:h:hars|HARS]]|0.48|
</modal>

<modal id='Essential_Avana' size='lg' title='Tissues where Essential in the Avana Dataset (DepMap 20Q1)'>
Global Fraction of Cell Lines Where Essential: 0/739
^Tissue^Fraction Of Cell Lines Where Essential^
|1290807.0|0/1|
|909776.0|0/1|
|bile duct|0/28|
|blood|0/28|
|bone|0/26|
|breast|0/33|
|central nervous system|0/56|
|cervix|0/4|
|colorectal|0/17|
|esophagus|0/13|
|fibroblast|0/1|
|gastric|0/16|
|kidney|0/21|
|liver|0/20|
|lung|0/75|
|lymphocyte|0/16|
|ovary|0/26|
|pancreas|0/24|
|peripheral nervous system|0/16|
|plasma cell|0/15|
|prostate|0/1|
|skin|0/24|
|soft tissue|0/9|
|thyroid|0/2|
|upper aerodigestive|0/22|
|urinary tract|0/29|
|uterus|0/5|
</modal>

== Essentiality in NALM6  ==
    * **<color #00a2e8>Essentiality Rank</color>**: 7332
    * **<color #00a2e8>Expression level (log2 read counts)</color>**: 7.02 
<button type='primary' size='small' modal='Dist_expr'>Expression Distribution</button>
<modal id='Dist_expr' size='lg' title='TNFAIP3 Expression in NALM6 Cells: 7.02'>
{{:chemogenomics:nalm6 dist.png?nolink |}}
</modal>