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FLASH GENE
Symbol TNFAIP3 contributors: mct - updated : 11-09-2010
HGNC name tumor necrosis factor, alpha-induced protein 3
HGNC id 11896
Location 6q23.3      Physical location : 138.188.580 - 138.204.445
Synonym name
  • tumor necrosis factor inducible protein A20
  • putative DNA-binding protein A20
  • zinc finger protein A20
  • Synonym symbol(s) A20, TNFA1P2, MGC138687, MGC138688, OTUD7C, MGC104522
    EC.number 3.-.-.-
    DNA
    TYPE functioning gene
    STRUCTURE 15.87 kb     9 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked   status provisional
    Map cen - D6S472 - D6S1722 - D6S292 - PEX7 - TNFAIP3 - D6S1684 - D6S453 - qter
    Physical map
    DUFD1 6q23.2 DUF729 domain containing 1 BTF 6q23 DUF729 domain containing 1 MAP7 6q23.3 microtubule-associated protein 7 MAP3K5 6q22.33 mitogen-activated protein kinase kinase kinase 5 PEX7 6q21-q22.2 peroxisomal biogenesis factor 7 SLC35D3 6q23.2 solute carrier family 35, member D3 IL20RA 6q23.3 interleukin 20 receptor, alpha IL22RA2 6q24-q25.1 interleukin 22 receptor, alpha 2 IFNGR1 6q23-q24 interferon gamma receptor 1 OLIG3 6q23.3 oligodendrocyte transcription factor 3 LOC391974 6 similar to RIKEN cDNA 5730434I03 gene LOC134897 6q23.3 similar to protein tyrosine phosphatase TNFAIP3 6q23-q25 tumor necrosis factor, alpha-induced protein 3 PERP 6q24 PERP, TP53 apoptosis effector PBOV1 6q23-q24 prostate and breast cancer overexpressed 1 KIAA1244 6q23.3 KIAA1244 HEBP2 6q24 heme binding protein 2 KIAA1357 6q23.3 KIAA1357 protein LOC389430 6 LOC389430 C6orf80 6q23.1-q24.1 chromosome 6 open reading frame 80 CCRL1P 6q23.3 chemokine (C-C motif) receptor-like 1 pseudogene LOC345930 6q23.3 similar to Ect2 protein REPS1 6q23.1-24.1 RALBP1 associated Eps domain containing 1 C6orf115 6q24.1 chromosome 6 open reading frame 115 HECA 6q23-q24 headcase homolog (Drosophila) C6orf198 6q23.3 chromosome 6 open reading frame 198 CITED2 6q23.3 Cbp/p300-interacting transactivator, with Glu/Asp-rich carboxy-terminal domain, 2 LOC340148 6q23.3 hypothetical LOC340148 LOC391975 6 similar to ATP synthase B chain, mitochondrial precursor
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    9 - 4446 89.5 790 - 1996 8663499
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart    
    Digestiveliver    
    Lymphoid/Immunelymph node   highly
    Nervousbrain    
    Reproductivemale systemprostate   
    Respiratoryrespiratory tractlarynx  highly
     respiratory tracttrachea  highly
    Urinarykidney   highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Blood / Hematopoieticbone marrow   
    Lymphoid    
    Muscularstriatumskeletal  
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • zinc finger protein containing multiple Cys2/Cys2 finger motifs
  • one OTU domain
  • mono polymer homomer , dimer
    HOMOLOGY
    interspecies ortholog to murine Tnfaip3
    homolog to C.elegans F21C3.2
    Homologene
    FAMILY
  • peptidase C64 family
  • CATEGORY structural protein
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,lysosome
    intracellular,cytoplasm,cytoskeleton,microtubule,centrosome
    intracellular,nucleus
    text a fraction of endogenous and ectopically expressed TNFAIP3 is localized to an endocytic membrane compartment that is in association with the lysosome
    basic FUNCTION
  • inhibiting NF-kappa B activation as well as TNF-mediated apoptosis
  • critical for limiting inflammation by terminating TNF-induced NF-kappa B responses
  • may be involvement of a lysosome-associated mechanism in TNFAIP3-dependent termination of NFkappaB signaling
  • playing a role in the function of the lymphoid system
  • contribute to the in vivo effects of TNF
  • inhibitor of NF-kB signaling that may play an important role in lymphomagenesis
  • having a function in the regulation of CARD10 and BCL10 activity in lymphoid and non-lymphoid cells
  • ubiquitin modifying enzyme that restricts NF-kappaB signals and protects cells against tumor necrosis factor (TNF)-induced programmed cell death
  • plays a key role in the negative regulation of inflammation and immunity
  • negatively regulates NFkappaB (nuclear factor kappaB) signaling induced by TNF receptor family and Toll-like receptors
  • negatively regulates TRAF3-stimulated IRF7 ubiquitination and activity in Epstein-Barr virus latency, and its deubiquitinase activity is indispensable for this function
  • tightly regulates NFKB signaling by acting as an Ub editor
  • involved in the negative feedback regulation of NFKB signaling in response to specific proinflammatory stimuli in different cell types
  • TNIP1 cooperates with TAX1BP1 and TNFAIP3 to restrict antiviral signaling
  • plays a critical role in the termination of NFKB signaling after activation
  • CELLULAR PROCESS cell life, antiapoptosis
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA binding
    RNA
    small molecule metal binding,
  • Zn2+
  • protein
  • binding to NAF1, TRAF1 and TRAF2
  • binding to TAX1BP1 (functioning as a negative regulator of ubiquitination of key signaling molecules that are also targeted by TNFAIP3)
  • TNIP1 requires its ubiquitin binding domain and cooperates with TAX1BP1 and TNFAIP3 to restrict antiviral signaling
  • RNF11 and TNFAIP3 interact in a microglial cell line, suggesting the presence of TNFAIP3 ubiquitin-editing protein complex in microglial cells
  • cell & other
    REGULATION
    induced by the tumor necrosis factor (TNF) rapidly
    repressed by PML
    Other different mechanisms of regulation, including phosphorylation, proteolytic processing, and association with ubiquitin binding proteins
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral   deletion    
    in ocular adnexal marginal zone B cell lymphoma
    constitutional     --low  
    reduced expression predisposes to autoimmunity
    Susceptibility to systemic lupus erythematosus (SLE) or rheumatoid arthritis
    Variant & Polymorphism other
  • polymorphisms increasing the risk of systemic lupus erythematosus or rheumatoid arthritis
  • association of rs2230926 G allele with SLE
  • Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
    Knockout A20 mice