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Aliases for TNFAIP3 Gene

Aliases for TNFAIP3 Gene

  • TNF Alpha Induced Protein 3 2 3 5
  • Tumor Necrosis Factor, Alpha-Induced Protein 3 2 3
  • Putative DNA-Binding Protein A20 3 4
  • OTU Domain-Containing Protein 7C 3 4
  • TNF Alpha-Induced Protein 3 3 4
  • Zinc Finger Protein A20 3 4
  • OTUD7C 3 4
  • Tumor Necrosis Factor, Alpha Induced Protein 3 3
  • Tumor Necrosis Factor Inducible Protein A20 3
  • EC 3.4.19.12 4
  • EC 6.3.2.- 4
  • TNFA1P2 3
  • AISBL 3
  • A20 3

External Ids for TNFAIP3 Gene

Previous GeneCards Identifiers for TNFAIP3 Gene

  • GC06P137811
  • GC06P138035
  • GC06P138123
  • GC06P138169
  • GC06P138230
  • GC06P135750
  • GC06P138188

Summaries for TNFAIP3 Gene

Entrez Gene Summary for TNFAIP3 Gene

  • 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]

GeneCards Summary for TNFAIP3 Gene

TNFAIP3 (TNF Alpha Induced Protein 3) is a Protein Coding gene. Diseases associated with TNFAIP3 include nodular lymphocyte predominant hodgkin lymphoma and iridocyclitis. Among its related pathways are Epstein-Barr virus infection and Influenza A. GO annotations related to this gene include ligase activity and thiol-dependent ubiquitin-specific protease activity. An important paralog of this gene is ZRANB1.

UniProtKB/Swiss-Prot for TNFAIP3 Gene

  • 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.

Gene Wiki entry for TNFAIP3 Gene

No data available for Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for TNFAIP3 Gene

Genomics for TNFAIP3 Gene

Regulatory Elements for TNFAIP3 Gene

Enhancers for TNFAIP3 Gene
GeneHancer Identifier Score Enhancer Sources TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor Binding Sites within enhancer Other Gene Targets for Enhancer

Enhancers around TNFAIP3 on UCSC Golden Path with GeneCards custom track

Genomic Location for TNFAIP3 Gene

Chromosome:
6
Start:
137,866,317 bp from pter
End:
137,883,314 bp from pter
Size:
16,998 bases
Orientation:
Plus strand

Genomic View for TNFAIP3 Gene

Genes around TNFAIP3 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
TNFAIP3 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for TNFAIP3 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for TNFAIP3 Gene

Proteins for TNFAIP3 Gene

  • Protein details for TNFAIP3 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    P21580-TNAP3_HUMAN
    Recommended name:
    Tumor necrosis factor alpha-induced protein 3
    Protein Accession:
    P21580
    Secondary Accessions:
    • B2R767
    • E1P588
    • Q2HIX9
    • Q5VXQ7
    • Q9NSR6

    Protein attributes for TNFAIP3 Gene

    Size:
    790 amino acids
    Molecular mass:
    89614 Da
    Quaternary structure:
    • Homodimer. Interacts with TNIP1, TAX1BP1 and TRAF2. Interacts with RNF11, ITCH and TAX1BP1 only after TNF stimulation; these interaction are transient and they are lost after 1 hour of stimulation with TNF (By similarity). Interacts with YWHAZ and YWHAH. Interacts with IKBKG; the interaction is induced by TNF stimulation and by polyubiquitin. Interacts with RIPK1. Interacts with UBE2N; the interaction requires TAX1BP1. Interacts with TRAF6; the interaction is inhibited by HTLV-1 protein Tax.

    Three dimensional structures from OCA and Proteopedia for TNFAIP3 Gene

neXtProt entry for TNFAIP3 Gene

Proteomics data for TNFAIP3 Gene at MOPED

Post-translational modifications for TNFAIP3 Gene

  • Proteolytically cleaved by MALT1 upon TCR stimulation; disrupts NF-kappa-B inhibitory function and results in increased IL-2 production. It is proposed that only a fraction of TNFAIP3 colocalized with TCR and CBM complex is cleaved, leaving the main TNFAIP3 pool intact.
  • Ubiquitination at Lys 541, Lys 621, Lys 643, Lys 676, and Lys 722
  • Modification sites at PhosphoSitePlus

Antibody Products

  • R&D Systems Antibodies for TNFAIP3 (A20/TNFAIP3)
  • Cell Signaling Technology (CST) Antibodies for TNFAIP3 (TNFAIP3)

No data available for DME Specific Peptides for TNFAIP3 Gene

Domains & Families for TNFAIP3 Gene

Gene Families for TNFAIP3 Gene

Protein Domains for TNFAIP3 Gene

Graphical View of Domain Structure for InterPro Entry

P21580

UniProtKB/Swiss-Prot:

TNAP3_HUMAN :
  • The A20-type zinc fingers mediate the ubiquitin ligase activity. The A20-type zinc finger 4 selectively recognizes Lys-63-linked polyubiquitin. The A20-type zinc finger 4-7 are sufficient to bind polyubiquitin.
  • Belongs to the peptidase C64 family.
  • Contains 7 A20-type zinc fingers.
Domain:
  • The A20-type zinc fingers mediate the ubiquitin ligase activity. The A20-type zinc finger 4 selectively recognizes Lys-63-linked polyubiquitin. The A20-type zinc finger 4-7 are sufficient to bind polyubiquitin.
  • The OTU domain mediates the deubiquitinase activity.
  • Contains 1 OTU domain.
Family:
  • Belongs to the peptidase C64 family.
Similarity:
  • Contains 7 A20-type zinc fingers.
genes like me logo Genes that share domains with TNFAIP3: view

Function for TNFAIP3 Gene

Molecular function for TNFAIP3 Gene

GENATLAS Biochemistry:
tumor necrosis factor,alpha-induced protein 3
UniProtKB/Swiss-Prot CatalyticActivity:
Thiol-dependent hydrolysis of ester, thioester, amide, peptide and isopeptide bonds formed by the C-terminal Gly of ubiquitin (a 76-residue protein attached to proteins as an intracellular targeting signal).
UniProtKB/Swiss-Prot Function:
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.
UniProtKB/Swiss-Prot Induction:
By TNF.

Enzyme Numbers (IUBMB) for TNFAIP3 Gene

Gene Ontology (GO) - Molecular Function for TNFAIP3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0019900 kinase binding IEA --
genes like me logo Genes that share ontologies with TNFAIP3: view
genes like me logo Genes that share phenotypes with TNFAIP3: view

Animal Models for TNFAIP3 Gene

MGI Knock Outs for TNFAIP3:

Animal Model Products

CRISPR Products

miRNA for TNFAIP3 Gene

miRTarBase miRNAs that target TNFAIP3

No data available for Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for TNFAIP3 Gene

Localization for TNFAIP3 Gene

Subcellular locations from UniProtKB/Swiss-Prot for TNFAIP3 Gene

Cytoplasm. Nucleus. Lysosome.
A20p50: Cytoplasm.

Subcellular locations from

COMPARTMENTS
Jensen Localization Image for TNFAIP3 Gene COMPARTMENTS Subcellular localization image for TNFAIP3 gene
Compartment Confidence
cytosol 5
extracellular 5
lysosome 5
nucleus 5
vacuole 5
cytoskeleton 2
mitochondrion 1
peroxisome 1
plasma membrane 1

No data available for Gene Ontology (GO) - Cellular Components for TNFAIP3 Gene

Pathways & Interactions for TNFAIP3 Gene

genes like me logo Genes that share pathways with TNFAIP3: view

SIGNOR curated interactions for TNFAIP3 Gene

Inactivates:
Is activated by:

Gene Ontology (GO) - Biological Process for TNFAIP3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001922 B-1 B cell homeostasis ISS --
GO:0002237 response to molecule of bacterial origin IEA,IDA 19912257
GO:0002634 regulation of germinal center formation IEA,ISS --
GO:0002677 negative regulation of chronic inflammatory response IEA --
GO:0006915 apoptotic process IEA --
genes like me logo Genes that share ontologies with TNFAIP3: view

Drugs & Compounds for TNFAIP3 Gene

(5) Drugs for TNFAIP3 Gene - From: PharmGKB and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Methotrexate Approved Pharma Folate antagonist,inhibits DFHR, Cytotoxic agent 1466
Tumor necrosis factor alpha (TNF-alpha) inhibitors Pharma 0

(5) Additional Compounds for TNFAIP3 Gene - From: Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
genes like me logo Genes that share compounds with TNFAIP3: view

Transcripts for TNFAIP3 Gene

Unigene Clusters for TNFAIP3 Gene

Tumor necrosis factor, alpha-induced protein 3:
Representative Sequences:

Alternative Splicing Database (ASD) splice patterns (SP) for TNFAIP3 Gene

ExUns: 1 ^ 2 ^ 3a · 3b · 3c · 3d · 3e · 3f ^ 4 ^ 5a · 5b ^ 6a · 6b ^ 7a · 7b ^ 8a · 8b · 8c ^ 9a · 9b ^ 10 ^ 11 ^ 12a · 12b ^ 13a · 13b ·
SP1: - - - -
SP2: - - -
SP3: -
SP4: - - - - - - -
SP5: -
SP6: -
SP7: -
SP8: - -
SP9:

ExUns: 13c
SP1:
SP2:
SP3:
SP4:
SP5:
SP6:
SP7:
SP8:
SP9:

Relevant External Links for TNFAIP3 Gene

GeneLoc Exon Structure for
TNFAIP3
ECgene alternative splicing isoforms for
TNFAIP3

Expression for TNFAIP3 Gene

mRNA expression in normal human tissues for TNFAIP3 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for TNFAIP3 Gene

This gene is overexpressed in Whole Blood (x4.3).

Protein differential expression in normal tissues from HIPED for TNFAIP3 Gene

This gene is overexpressed in Testis (17.2), Lymph node (13.8), Placenta (13.0), Peripheral blood mononuclear cells (10.3), and CD8 Tcells (8.9).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, PaxDb, MOPED, and MaxQB for TNFAIP3 Gene



SOURCE GeneReport for Unigene cluster for TNFAIP3 Gene Hs.211600

genes like me logo Genes that share expression patterns with TNFAIP3: view

Protein tissue co-expression partners for TNFAIP3 Gene

- Elite partner

Primer Products

In Situ Assay Products

No data available for mRNA Expression by UniProt/SwissProt for TNFAIP3 Gene

Orthologs for TNFAIP3 Gene

This gene was present in the common ancestor of chordates.

Orthologs for TNFAIP3 Gene

Organism Taxonomy Gene Similarity Type Details
cow
(Bos Taurus)
Mammalia TNFAIP3 35
  • 85.34 (n)
  • 86.67 (a)
TNFAIP3 36
  • 87 (a)
OneToOne
dog
(Canis familiaris)
Mammalia TNFAIP3 35
  • 87.81 (n)
  • 90.25 (a)
TNFAIP3 36
  • 90 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Tnfaip3 35
  • 85.08 (n)
  • 89.81 (a)
Tnfaip3 16
Tnfaip3 36
  • 90 (a)
OneToOne
chimpanzee
(Pan troglodytes)
Mammalia TNFAIP3 35
  • 99.49 (n)
  • 99.75 (a)
TNFAIP3 36
  • 100 (a)
OneToOne
rat
(Rattus norvegicus)
Mammalia Tnfaip3 35
  • 84.66 (n)
  • 89.56 (a)
oppossum
(Monodelphis domestica)
Mammalia TNFAIP3 36
  • 81 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia TNFAIP3 36
  • 74 (a)
OneToOne
chicken
(Gallus gallus)
Aves TNFAIP3 35
  • 69.64 (n)
  • 66.88 (a)
TNFAIP3 36
  • 65 (a)
OneToOne
lizard
(Anolis carolinensis)
Reptilia TNFAIP3 36
  • 63 (a)
OneToOne
zebrafish
(Danio rerio)
Actinopterygii tnfaip3 35
  • 58.08 (n)
  • 52.98 (a)
tnfaip3 36
  • 50 (a)
OneToOne
Species with no ortholog for TNFAIP3:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • fruit fly (Drosophila melanogaster)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea squirt (Ciona intestinalis)
  • sea squirt (Ciona savignyi)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • tropical clawed frog (Silurana tropicalis)
  • wheat (Triticum aestivum)
  • worm (Caenorhabditis elegans)

Evolution for TNFAIP3 Gene

ENSEMBL:
Gene Tree for TNFAIP3 (if available)
TreeFam:
Gene Tree for TNFAIP3 (if available)

Paralogs for TNFAIP3 Gene

Paralogs for TNFAIP3 Gene

genes like me logo Genes that share paralogs with TNFAIP3: view

Variants for TNFAIP3 Gene

Sequence variations from dbSNP and Humsavar for TNFAIP3 Gene

SNP ID Clin Chr 06 pos Sequence Context AA Info Type
rs5029941 - 137,874,923(+) GAAGG(C/T)GCTGT reference, missense, utr-variant-5-prime
rs2230926 - 137,874,929(+) GCTGT(C/G/T)CAGCA reference, missense, utr-variant-5-prime
rs5029957 - 137,881,242(-) CCCCC(C/G/T)CCTGT reference, missense, utr-variant-3-prime
rs1065077 -- 137,874,987(+) GAGTC(C/T)CTCAA reference, synonymous-codon, utr-variant-5-prime
rs5029932 -- 137,870,506(+) CAAAG(C/T)ATCTT intron-variant, upstream-variant-2KB

Structural Variations from Database of Genomic Variants (DGV) for TNFAIP3 Gene

Variant ID Type Subtype PubMed ID
nsv470863 CNV Loss 18288195
nsv830818 CNV Gain 17160897
nsv830819 CNV Loss 17160897
nsv5493 CNV Insertion 18451855
nsv523826 CNV Loss 19592680

Variation tolerance for TNFAIP3 Gene

Residual Variation Intolerance Score: 25.7% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 6.54; 77.84% of all genes are more intolerant (likely to be disease-causing)

Relevant External Links for TNFAIP3 Gene

HapMap Linkage Disequilibrium report
TNFAIP3
Human Gene Mutation Database (HGMD)
TNFAIP3

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for TNFAIP3 Gene

Disorders for TNFAIP3 Gene

MalaCards: The human disease database

(7) MalaCards diseases for TNFAIP3 Gene - From: DISEASES and GeneCards

Disorder Aliases PubMed IDs
nodular lymphocyte predominant hodgkin lymphoma
  • nlphl
iridocyclitis
  • primary iridocyclitis
blind loop syndrome
  • bacterial overgrowth syndrome
marginal zone b-cell lymphoma
  • marginal zone lymphoma
fuchs' heterochromic uveitis
  • fuch's heterochromic iridocyclitis
- elite association - COSMIC cancer census association via MalaCards

Relevant External Links for TNFAIP3

Genetic Association Database (GAD)
TNFAIP3
Human Genome Epidemiology (HuGE) Navigator
TNFAIP3
Atlas of Genetics and Cytogenetics in Oncology and Haematology:
TNFAIP3
genes like me logo Genes that share disorders with TNFAIP3: view

No data available for UniProtKB/Swiss-Prot and Genatlas for TNFAIP3 Gene

Publications for TNFAIP3 Gene

  1. The A20 cDNA induced by tumor necrosis factor alpha encodes a novel type of zinc finger protein. (PMID: 2118515) Opipari A.W. Jr. … Dixit V.M. (J. Biol. Chem. 1990) 2 3 4 23 67
  2. Mutations in the genes coding for the NF-I_B regulating factors II_BI+ and A20 are uncommon in nodular lymphocyte-predominant Hodgkin's lymphoma. (PMID: 19648161) Schumacher M.A. … KA1ppers R. (Haematologica 2010) 3 23
  3. Ca2+ influx via TRPC channels induces NF-kappaB-dependent A20 expression to prevent thrombin-induced apoptosis in endothelial cells. (PMID: 20032510) Thippegowda P.B. … Tiruppathi C. (Am. J. Physiol., Cell Physiol. 2010) 3 23
  4. Targeting A20 decreases glioma stem cell survival and tumor growth. (PMID: 20186265) Hjelmeland A.B. … Rich J.N. (PLoS Biol. 2010) 3 23
  5. Association of the 6q23 region with the rate of joint destruction in rheumatoid arthritis. (PMID: 19366996) Scherer H.U. … Toes R.E. (Ann. Rheum. Dis. 2010) 3 23

Products for TNFAIP3 Gene

Sources for TNFAIP3 Gene

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