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TNFAIP3 TNF alpha induced protein 3 [ Homo sapiens (human) ]

Gene ID: 7128, updated on 26-May-2016
Official Symbol
TNFAIP3provided by HGNC
Official Full Name
TNF alpha induced protein 3provided by HGNC
Primary source
HGNC:HGNC:11896
See related
Ensembl:ENSG00000118503 HPRD:01857; MIM:191163; Vega:OTTHUMG00000015664
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
A20; AISBL; OTUD7C; TNFA1P2
Summary
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]
Orthologs
Location:
6q23
Exon count:
12
Annotation release Status Assembly Chr Location
107 current GRCh38.p2 (GCF_000001405.28) 6 NC_000006.12 (137866317..137883314)
105 previous assembly GRCh37.p13 (GCF_000001405.25) 6 NC_000006.11 (138188325..138204451)

Chromosome 6 - NC_000006.12Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC100507406 Neighboring gene uncharacterized LOC100130476 Neighboring gene uncharacterized LOC105378019 Neighboring gene uncharacterized LOC105378020 Neighboring gene ribosomal protein SA pseudogene 42

GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

NHGRI GWAS Catalog

Description
A genome-wide association study identifies new psoriasis susceptibility loci and an interaction between HLA-C and ERAP1.
NHGRI GWA Catalog
A genome-wide association study in Han Chinese identifies a susceptibility locus for primary Sjögren's syndrome at 7q11.23.
NHGRI GWA Catalog
A regulatory variant in CCR6 is associated with rheumatoid arthritis susceptibility.
NHGRI GWA Catalog
A systemic sclerosis and systemic lupus erythematosus pan-meta-GWAS reveals new shared susceptibility loci.
NHGRI GWA Catalog
Association of genome-wide variation with highly sensitive cardiac troponin-T levels in European Americans and Blacks: a meta-analysis from atherosclerosis risk in communities and cardiovascular health studies.
NHGRI GWA Catalog
Genetic variants near TNFAIP3 on 6q23 are associated with systemic lupus erythematosus.
NHGRI GWA Catalog
Genetics of rheumatoid arthritis contributes to biology and drug discovery.
NHGRI GWA Catalog
Genome-wide association study in a Chinese Han population identifies nine new susceptibility loci for systemic lupus erythematosus.
NHGRI GWA Catalog
Genome-wide association study meta-analysis identifies seven new rheumatoid arthritis risk loci.
NHGRI GWA Catalog
Genome-wide scan reveals association of psoriasis with IL-23 and NF-kappaB pathways.
NHGRI GWA Catalog
Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease.
NHGRI GWA Catalog
Meta-analysis followed by replication identifies loci in or near CDKN1B, TET3, CD80, DRAM1, and ARID5B as associated with systemic lupus erythematosus in Asians.
NHGRI GWA Catalog
Multiple common variants for celiac disease influencing immune gene expression.
NHGRI GWA Catalog
Novel rheumatoid arthritis susceptibility locus at 22q12 identified in an extended UK genome-wide association study.
NHGRI GWA Catalog
Two independent alleles at 6q23 associated with risk of rheumatoid arthritis.
NHGRI GWA Catalog

Protein interactions

Protein Gene Interaction Pubs
Tat tat HIV-1 and the viral protein Tat modulate the expression of tumor necrosis factor, alpha-induced protein 3 (TNFAIP3) in immature dendritic cells and monocyte-derived macrophages PubMed

Go to the HIV-1, Human Interaction Database

  • CD40/CD40L signaling, organism-specific biosystem (from Pathway Interaction Database)
    CD40/CD40L signaling, organism-specific biosystem
    CD40/CD40L signaling
  • Canonical NF-kappaB pathway, organism-specific biosystem (from Pathway Interaction Database)
    Canonical NF-kappaB pathway, organism-specific biosystem
    Canonical NF-kappaB pathway
  • Death Receptor Signalling, organism-specific biosystem (from REACTOME)
    Death Receptor Signalling, organism-specific biosystemThe death receptors, all cell-surface receptors, begin the process of caspase activation. The common feature of these type 1 transmembrane proteins is the "death-domain" a conserved cytoplasmic motif...
  • Epstein-Barr virus infection, organism-specific biosystem (from KEGG)
    Epstein-Barr virus infection, organism-specific biosystemEpstein-Barr virus (EBV) is a ubiquitous human herpesvirus that is associated with oncogenesis. EBV infection to primary human B lymphocytes leads to induction of EBV-specific HLA-restricted cytotoxi...
  • Epstein-Barr virus infection, conserved biosystem (from KEGG)
    Epstein-Barr virus infection, conserved biosystemEpstein-Barr virus (EBV) is a ubiquitous human herpesvirus that is associated with oncogenesis. EBV infection to primary human B lymphocytes leads to induction of EBV-specific HLA-restricted cytotoxi...
  • Immune System, organism-specific biosystem (from REACTOME)
    Immune System, organism-specific biosystemHumans are exposed to millions of potential pathogens daily, through contact, ingestion, and inhalation. Our ability to avoid infection depends on the adaptive immune system and during the first crit...
  • Innate Immune System, organism-specific biosystem (from REACTOME)
    Innate Immune System, organism-specific biosystemInnate immunity encompases the nonspecific part of immunity tha are part of an individual's natural biologic makeup
  • Measles, organism-specific biosystem (from KEGG)
    Measles, organism-specific biosystemMeasles virus (MV) is highly contagious virus that leads infant death worldwide. Humans are the unique natural reservoir for this virus. It causes severe immunosuppression favouring secondary bacteri...
  • Measles, conserved biosystem (from KEGG)
    Measles, conserved biosystemMeasles virus (MV) is highly contagious virus that leads infant death worldwide. Humans are the unique natural reservoir for this virus. It causes severe immunosuppression favouring secondary bacteri...
  • NF-kappa B signaling pathway, organism-specific biosystem (from KEGG)
    NF-kappa B signaling pathway, organism-specific biosystemNuclear factor-kappa B (NF-kappa B) is the generic name of a family of transcription factors that function as dimers and regulate genes involved in immunity, inflammation and cell survival. There are...
  • NF-kappa B signaling pathway, conserved biosystem (from KEGG)
    NF-kappa B signaling pathway, conserved biosystemNuclear factor-kappa B (NF-kappa B) is the generic name of a family of transcription factors that function as dimers and regulate genes involved in immunity, inflammation and cell survival. There are...
  • NOD-like receptor signaling pathway, organism-specific biosystem (from KEGG)
    NOD-like receptor signaling pathway, organism-specific biosystemSpecific families of pattern recognition receptors are responsible for detecting various pathogens and generating innate immune responses. The intracellular NOD-like receptor (NLR) family contains mo...
  • NOD-like receptor signaling pathway, conserved biosystem (from KEGG)
    NOD-like receptor signaling pathway, conserved biosystemSpecific families of pattern recognition receptors are responsible for detecting various pathogens and generating innate immune responses. The intracellular NOD-like receptor (NLR) family contains mo...
  • NOD1/2 Signaling Pathway, organism-specific biosystem (from REACTOME)
    NOD1/2 Signaling Pathway, organism-specific biosystemNOD1 is ubiquitously expressed, while NOD2 expression is restricted to monocytes, macrophages, dendritic cells, and intestinal Paneth cells (Inohara et al. 2005). NOD1 and NOD2 activation induces tra...
  • Negative regulators of RIG-I/MDA5 signaling, organism-specific biosystem (from REACTOME)
    Negative regulators of RIG-I/MDA5 signaling, organism-specific biosystemAs with other cytokine systems, production of type I IFN is a transient process, and can be hazardous to the host if unregulated, resulting in chronic cellular toxicity or inflammatory and autoimmune...
  • Nucleotide-binding domain, leucine rich repeat containing receptor (NLR) signaling pathways, organism-specific biosystem (from REACTOME)
    Nucleotide-binding domain, leucine rich repeat containing receptor (NLR) signaling pathways, organism-specific biosystemThe innate immune system is the first line of defense against invading microorganisms, a broad specificity response characterized by the recruitment and activation of phagocytes and the release of an...
  • RIG-I/MDA5 mediated induction of IFN-alpha/beta pathways, organism-specific biosystem (from REACTOME)
    RIG-I/MDA5 mediated induction of IFN-alpha/beta pathways, organism-specific biosystemRIG-I-like helicases (RLHs) the retinoic acid inducible gene-I (RIG-I) and melanoma differentiation associated gene 5 (MDA5) are RNA helicases that recognize viral RNA present within the cytoplasm. F...
  • Regulation of TNFR1 signaling, organism-specific biosystem (from REACTOME)
    Regulation of TNFR1 signaling, organism-specific biosystemTumor necrosis factor-alpha (TNFalpha) is an inflammatory cytokine, that activates either cell survival (e.g.,inflammation, proliferation) or cell death upon association with TNF receptor 1 (TNFR1). ...
  • Signal Transduction, organism-specific biosystem (from REACTOME)
    Signal Transduction, organism-specific biosystemSignal transduction is a process in which extracellular signals elicit changes in cell state and activity. Transmembrane receptors sense changes in the cellular environment by binding ligands, such a...
  • TNF receptor signaling pathway, organism-specific biosystem (from Pathway Interaction Database)
    TNF receptor signaling pathway, organism-specific biosystem
    TNF receptor signaling pathway
  • TNF signaling, organism-specific biosystem (from REACTOME)
    TNF signaling, organism-specific biosystemThe inflammatory cytokine tumor necrosis factor alpha (TNF-alpha) is expressed in immune and nonimmune cell types including macrophages, T cells, mast cells, granulocytes, natural killer (NK) cells, ...
  • TNF signaling pathway, organism-specific biosystem (from KEGG)
    TNF signaling pathway, organism-specific biosystemTumor necrosis factor (TNF), as a critical cytokine, can induce a wide range of intracellular signal pathways including apoptosis and cell survival as well as inflammation and immunity. Activated TNF...
  • TNF signaling pathway, conserved biosystem (from KEGG)
    TNF signaling pathway, conserved biosystemTumor necrosis factor (TNF), as a critical cytokine, can induce a wide range of intracellular signal pathways including apoptosis and cell survival as well as inflammation and immunity. Activated TNF...
  • TNF-alpha/NF-kB Signaling Pathway, organism-specific biosystem (from WikiPathways)
    TNF-alpha/NF-kB Signaling Pathway, organism-specific biosystem"The Tumor Necrosis Factor alpha is a proinflammatory cytokine belonging to the TNF superfamily. It signals through 2 separate receptors - TNFRSF1A and TNFRSF1B, both members of the TNF receptor supe...
  • TNFR1-induced NFkappaB signaling pathway, organism-specific biosystem (from REACTOME)
    TNFR1-induced NFkappaB signaling pathway, organism-specific biosystemActivation of tumor necrosis factor receptor 1 (TNFR1) can trigger multiple signal transduction pathways to induce inflammation, cell proliferation, survival or cell death (Ward C et al. 1999; Michea...
  • TNFR1-induced proapoptotic signaling, organism-specific biosystem (from REACTOME)
    TNFR1-induced proapoptotic signaling, organism-specific biosystemActivation of tumor necrosis factor receptor 1 (TNFR1) can trigger multiple signal transduction pathways to induce cell survival or cell death (Ward C et al. 1999; Micheau O and Tschopp J 2003; Wider...
Products Interactant Other Gene Complex Source Pubs Description

Markers

Homology

Clone Names

  • MGC104522, MGC138687, MGC138688

Gene Ontology Provided by GOA

Function Evidence Code Pubs
DNA binding IEA
Inferred from Electronic Annotation
more info
 
K63-linked polyubiquitin binding IBA
Inferred from Biological aspect of Ancestor
more info
 
kinase binding IEA
Inferred from Electronic Annotation
more info
 
ligase activity IEA
Inferred from Electronic Annotation
more info
 
protease binding IPI
Inferred from Physical Interaction
more info
PubMed 
protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
protein self-association IDA
Inferred from Direct Assay
more info
PubMed 
thiol-dependent ubiquitin-specific protease activity IDA
Inferred from Direct Assay
more info
PubMed 
thiol-dependent ubiquitin-specific protease activity TAS
Traceable Author Statement
more info
PubMed 
ubiquitin binding IPI
Inferred from Physical Interaction
more info
PubMed 
ubiquitin-protein transferase activity IDA
Inferred from Direct Assay
more info
PubMed 
zinc ion binding IEA
Inferred from Electronic Annotation
more info
 
Process Evidence Code Pubs
B-1 B cell homeostasis ISS
Inferred from Sequence or Structural Similarity
more info
 
apoptotic process IEA
Inferred from Electronic Annotation
more info
 
cellular response to hydrogen peroxide ISS
Inferred from Sequence or Structural Similarity
more info
 
cellular response to lipopolysaccharide IDA
Inferred from Direct Assay
more info
PubMed 
establishment of protein localization to vacuole IEA
Inferred from Electronic Annotation
more info
 
inflammatory response IEA
Inferred from Electronic Annotation
more info
 
negative regulation of B cell activation ISS
Inferred from Sequence or Structural Similarity
more info
 
negative regulation of CD40 signaling pathway IMP
Inferred from Mutant Phenotype
more info
PubMed 
negative regulation of I-kappaB kinase/NF-kappaB signaling IDA
Inferred from Direct Assay
more info
PubMed 
negative regulation of NF-kappaB transcription factor activity IDA
Inferred from Direct Assay
more info
PubMed 
negative regulation of bone resorption NAS
Non-traceable Author Statement
more info
PubMed 
negative regulation of chronic inflammatory response IEA
Inferred from Electronic Annotation
more info
 
negative regulation of cyclin-dependent protein serine/threonine kinase activity IEA
Inferred from Electronic Annotation
more info
 
negative regulation of endothelial cell apoptotic process IDA
Inferred from Direct Assay
more info
PubMed 
negative regulation of extrinsic apoptotic signaling pathway via death domain receptors IDA
Inferred from Direct Assay
more info
PubMed 
negative regulation of inflammatory response ISS
Inferred from Sequence or Structural Similarity
more info
 
negative regulation of innate immune response ISS
Inferred from Sequence or Structural Similarity
more info
 
negative regulation of interleukin-1 beta production IEA
Inferred from Electronic Annotation
more info
 
negative regulation of interleukin-2 production IMP
Inferred from Mutant Phenotype
more info
PubMed 
negative regulation of interleukin-6 production ISS
Inferred from Sequence or Structural Similarity
more info
 
negative regulation of nucleotide-binding oligomerization domain containing 1 signaling pathway IEA
Inferred from Electronic Annotation
more info
 
negative regulation of nucleotide-binding oligomerization domain containing 2 signaling pathway IEA
Inferred from Electronic Annotation
more info
 
negative regulation of osteoclast proliferation NAS
Non-traceable Author Statement
more info
PubMed 
negative regulation of protein ubiquitination IDA
Inferred from Direct Assay
more info
PubMed 
negative regulation of smooth muscle cell proliferation IDA
Inferred from Direct Assay
more info
PubMed 
negative regulation of toll-like receptor 2 signaling pathway NAS
Non-traceable Author Statement
more info
PubMed 
negative regulation of toll-like receptor 3 signaling pathway IDA
Inferred from Direct Assay
more info
PubMed 
negative regulation of toll-like receptor 4 signaling pathway NAS
Non-traceable Author Statement
more info
PubMed 
negative regulation of toll-like receptor 5 signaling pathway IEA
Inferred from Electronic Annotation
more info
 
negative regulation of tumor necrosis factor production ISS
Inferred from Sequence or Structural Similarity
more info
 
negative regulation of type I interferon production TAS
Traceable Author Statement
more info
 
nucleotide-binding oligomerization domain containing signaling pathway TAS
Traceable Author Statement
more info
 
positive regulation of cellular protein catabolic process IEA
Inferred from Electronic Annotation
more info
 
positive regulation of hepatocyte proliferation IEA
Inferred from Electronic Annotation
more info
 
positive regulation of protein catabolic process IDA
Inferred from Direct Assay
more info
PubMed 
protein K11-linked deubiquitination IDA
Inferred from Direct Assay
more info
PubMed 
protein K48-linked deubiquitination IDA
Inferred from Direct Assay
more info
PubMed 
protein K48-linked ubiquitination IDA
Inferred from Direct Assay
more info
PubMed 
protein K63-linked deubiquitination IDA
Inferred from Direct Assay
more info
PubMed 
protein deubiquitination TAS
Traceable Author Statement
more info
PubMed 
protein deubiquitination involved in ubiquitin-dependent protein catabolic process IBA
Inferred from Biological aspect of Ancestor
more info
 
protein oligomerization NAS
Non-traceable Author Statement
more info
PubMed 
regulation of defense response to virus by host NAS
Non-traceable Author Statement
more info
PubMed 
regulation of germinal center formation ISS
Inferred from Sequence or Structural Similarity
more info
 
regulation of inflammatory response IBA
Inferred from Biological aspect of Ancestor
more info
 
regulation of tumor necrosis factor-mediated signaling pathway TAS
Traceable Author Statement
more info
 
regulation of vascular wound healing NAS
Non-traceable Author Statement
more info
PubMed 
response to molecule of bacterial origin IDA
Inferred from Direct Assay
more info
PubMed 
response to muramyl dipeptide IEA
Inferred from Electronic Annotation
more info
 
tolerance induction to lipopolysaccharide IMP
Inferred from Mutant Phenotype
more info
PubMed 
Component Evidence Code Pubs
cytoplasm IBA
Inferred from Biological aspect of Ancestor
more info
 
cytosol TAS
Traceable Author Statement
more info
 
extracellular exosome IDA
Inferred from Direct Assay
more info
PubMed 
lysosome IEA
Inferred from Electronic Annotation
more info
 
nucleus IDA
Inferred from Direct Assay
more info
PubMed 
Preferred Names
tumor necrosis factor alpha-induced protein 3
Names
OTU domain-containing protein 7C
TNF alpha-induced protein 3
putative DNA-binding protein A20
tumor necrosis factor inducible protein A20
tumor necrosis factor, alpha induced protein 3
tumor necrosis factor, alpha-induced protein 3
zinc finger protein A20
NP_001257436.1
NP_001257437.1
NP_006281.1

RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

  1. NG_032761.1 RefSeqGene

    Range
    4745..20871
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_001270507.1NP_001257436.1  tumor necrosis factor alpha-induced protein 3

    See identical proteins and their annotated locations for NP_001257436.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) differs in the 5' UTR compared to variant 1. All three variants encode the same protein.
    Source sequence(s)
    CB528739, DB143089, HY085289, M59465
    Consensus CDS
    CCDS5187.1
    UniProtKB/Swiss-Prot
    P21580
    Conserved Domains (3) summary
    smart00259
    Location:759784
    ZnF_A20; A20-like zinc fingers
    pfam01754
    Location:384407
    zf-A20; A20-like zinc finger
    pfam02338
    Location:98257
    OTU; OTU-like cysteine protease
  2. NM_001270508.1NP_001257437.1  tumor necrosis factor alpha-induced protein 3

    See identical proteins and their annotated locations for NP_001257437.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) represents the longest transcript. All three variants encode the same protein.
    Source sequence(s)
    CB528739, HY009939, M59465
    Consensus CDS
    CCDS5187.1
    UniProtKB/Swiss-Prot
    P21580
    Related
    ENSP00000481570, ENST00000612899
    Conserved Domains (3) summary
    smart00259
    Location:759784
    ZnF_A20; A20-like zinc fingers
    pfam01754
    Location:384407
    zf-A20; A20-like zinc finger
    pfam02338
    Location:98257
    OTU; OTU-like cysteine protease
  3. NM_006290.3NP_006281.1  tumor necrosis factor alpha-induced protein 3

    See identical proteins and their annotated locations for NP_006281.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) differs in the 5' UTR compared to variant 1. All three variants encode the same protein.
    Source sequence(s)
    CB528739, HY085289, M59465
    Consensus CDS
    CCDS5187.1
    UniProtKB/Swiss-Prot
    P21580
    Related
    ENSP00000237289, OTTHUMP00000017289, ENST00000237289, OTTHUMT00000042414
    Conserved Domains (3) summary
    smart00259
    Location:759784
    ZnF_A20; A20-like zinc fingers
    pfam01754
    Location:384407
    zf-A20; A20-like zinc finger
    pfam02338
    Location:98257
    OTU; OTU-like cysteine protease

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 107 details...

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p2 Primary Assembly

Genomic

  1. NC_000006.12 Reference GRCh38.p2 Primary Assembly

    Range
    137866317..137883314
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_011536095.1XP_011534397.1  

    See identical proteins and their annotated locations for XP_011534397.1

    UniProtKB/Swiss-Prot
    P21580
    Conserved Domains (3) summary
    smart00259
    Location:759784
    ZnF_A20; A20-like zinc fingers
    pfam01754
    Location:384407
    zf-A20; A20-like zinc finger
    pfam02338
    Location:98257
    OTU; OTU-like cysteine protease
  2. XM_011536096.1XP_011534398.1  

    Conserved Domains (3) summary
    smart00259
    Location:475500
    ZnF_A20; A20-like zinc fingers
    pfam01754
    Location:384407
    zf-A20; A20-like zinc finger
    pfam02338
    Location:98257
    OTU; OTU-like cysteine protease
  3. XM_005267119.1XP_005267176.1  

    See identical proteins and their annotated locations for XP_005267176.1

    UniProtKB/Swiss-Prot
    P21580
    Related
    ENSP00000481454, ENST00000620204
    Conserved Domains (3) summary
    smart00259
    Location:759784
    ZnF_A20; A20-like zinc fingers
    pfam01754
    Location:384407
    zf-A20; A20-like zinc finger
    pfam02338
    Location:98257
    OTU; OTU-like cysteine protease
  4. XM_006715555.1XP_006715618.1  

    Conserved Domains (2) summary
    smart00259
    Location:546571
    ZnF_A20; A20-like zinc fingers
    pfam01754
    Location:171194
    zf-A20; A20-like zinc finger

Alternate CHM1_1.1

Genomic

  1. NC_018917.2 Alternate CHM1_1.1

    Range
    138450716..138466833
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)