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TNFAIP3 Gene

protein-coding   GIFtS: 68
GCID: GC06P138188

Tumor Necrosis Factor, Alpha-Induced Protein 3

Microbiology & Infectious Diseases Congress
  See related diseases
at  

(According to 1HGNC, 2Entrez Gene,
3UniProtKB/Swiss-Prot, 4UniProtKB/TrEMBL, 5OMIM, 6GeneLoc, 7Ensembl, 8DME, 9miRBase, 10fRNAdb, 12H-InvDB, 13NCBI, 14NONCODE, and/or 15RNAdb)
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Aliases
Tumor Necrosis Factor, Alpha-Induced Protein 31 2     A202 5
OTUD7C2 3 5     TNFA1P22
Putative DNA-Binding Protein A202 3     Tumor Necrosis Factor Alpha-Induced Protein 32
Zinc Finger Protein A202 3     Tumor Necrosis Factor Inducible Protein A202
OTU Domain-Containing Protein 7C2 3     EC 3.4.19.123
TNF Alpha-Induced Protein 32 3     EC 6.3.2.-3

External Ids:    HGNC: 118961   Entrez Gene: 71282   Ensembl: ENSG000001185037   OMIM: 1911635   UniProtKB: P215803   

Export aliases for TNFAIP3 gene to outside databases

Previous GC identifers: GC06P137811 GC06P138035 GC06P138123 GC06P138169 GC06P138230 GC06P135750


(According to Entrez Gene, GeneCards, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
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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 (tumor necrosis factor, alpha-induced protein 3) is a protein-coding gene. Diseases associated with TNFAIP3 include nodular lymphocyte predominant hodgkin lymphoma, and marginal zone b-cell lymphoma. GO annotations related to this gene include ubiquitin-protein ligase activity and protease binding. An important paralog of this gene is OTUD7B.

UniProtKB/Swiss-Prot: TNAP3_HUMAN, P21580
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. Deubiquinates
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. Deubiquinates 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


(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 75), Regulatory elements and Epigenetics data according to QIAGEN, and/or SwitchGear Genomics)
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RefSeq DNA sequence:
NC_000006.12  NT_025741.16  NC_018917.2  
Regulatory elements:
   Search for regulatory transcription factor binding sites for TNFAIP3
         Other transcription factors

SwitchGear Promoter luciferase reporter plasmids (see all 2): TNFAIP3 promoter sequence
   Search Chromatin IP Primers for TNFAIP3

Epigenetics:
DNA Methylation CpG Assay Predesigned for Pyrosequencing in human, mouse, rat TNFAIP3


Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 6q23   Ensembl cytogenetic band:  6q23.3   HGNC cytogenetic band: 6q23-q25

TNFAIP3 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
TNFAIP3 gene location

GeneLoc information about chromosome 6         GeneLoc Exon Structure

GeneLoc location for GC06P138188:  view genomic region     (about GC identifiers)

Start:
138,188,351 bp from pter      End:
138,204,449 bp from pter
Size:
16,099 bases      Orientation:
plus strand

(According to 1UniProtKB, HORDE, 2neXtProt, Ensembl, and/or Reactome, Modification sites according to PhosphoSitePlus, Specific Peptides from DME, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, and/or Cloud-Clone Corp.,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Cloud-Clone Corp., Antibodies by EMD Millipore, R&D Systems, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, LSBio, Abcam, and/or Cloud-Clone Corp.)
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UniProtKB/Swiss-Prot: TNAP3_HUMAN, P21580 (See protein sequence)
Recommended Name: Tumor necrosis factor alpha-induced protein 3  
Size: 790 amino acids; 89614 Da
Subunit: 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
Selected PDB 3D structures from and Proteopedia for TNFAIP3 (see all 14):
2EQE (3D)        2EQF (3D)        2EQG (3D)        2VFJ (3D)        3DKB (3D)        3OJ3 (3D)    
Secondary accessions: B2R767 E1P588 Q2HIX9 Q5VXQ7 Q9NSR6

Explore the universe of human proteins at neXtProt for TNFAIP3: NX_P21580

Explore proteomics data for TNFAIP3 at MOPED

Post-translational modifications: 

  • 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 intact1
  • Ubiquitination2 at Lys541, Lys621, Lys643, Lys676, Lys722
  • Modification sites at PhosphoSitePlus

  • See TNFAIP3 Protein Expression from SPIRE MOPED, PaxDB, and MaxQB

    REFSEQ proteins (3 alternative transcripts): 
    NP_001257436.1  NP_001257437.1  NP_006281.1  

    ENSEMBL proteins: 
     ENSP00000393577   ENSP00000401562   ENSP00000237289   ENSP00000409845  
    Reactome Protein details: P21580

    TNFAIP3 Human Recombinant Protein Products:

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    OriGene Protein Over-expression Lysate for TNFAIP3
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    Novus Biologicals TNFAIP3 Proteins
    Novus Biologicals TNFAIP3 Lysate
    Browse Sino Biological Recombinant Proteins
    Browse Sino Biological Cell Lysates
    Browse ProSpec Recombinant Proteins
    Browse Proteins at Cloud-Clone Corp.

    TNFAIP3 Antibody Products:

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    TNFAIP3 Assay Products:

    Browse Kits and Assays available from EMD Millipore
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    Browse Enzo Life Sciences for kits & assays
    Browse ELISAs at Cloud-Clone Corp.
    Browse CLIAs at Cloud-Clone Corp.


    (According to HGNC, IUPHAR, InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
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    HGNC Gene Families:
    OTUD: OTU domain containing

    2 InterPro protein domains:
     IPR003323 OTU
     IPR002653 Znf_A20

    Graphical View of Domain Structure for InterPro Entry P21580

    ProtoNet protein and cluster: P21580

    2 Blocks protein domains:
    IPB002653 Zn-finger
    IPB003323 OTU-like cysteine protease


    UniProtKB/Swiss-Prot: TNAP3_HUMAN, P21580
    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
    Domain: The OTU domain mediates the deubiquitinase activity
    Similarity: Belongs to the peptidase C64 family
    Similarity: Contains 7 A20-type zinc fingers
    Similarity: Contains 1 OTU domain


    TNFAIP3 for domains           About GeneDecksing


    (According to 1UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or 2DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, inGenious Targeting Laboratory, genOway,
    transcription factor targeting from QIAGEN and/or HOMER, miRNA Gene Targets from miRTarBase, shRNA from OriGene, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, SwitchGear Genomics, Gene Editing from DNA2.0, Clones from OriGene, GenScript, Sino Biological, DNA2.0, and Vector BioLabs, Cell Lines from GenScript, ESI BIO, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Molecular Function:

         UniProtKB/Swiss-Prot Summary: TNAP3_HUMAN, P21580
    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. Deubiquinates
    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. Deubiquinates 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
    Catalytic activity: 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)
    Induction: By TNF

         Genatlas biochemistry entry for TNFAIP3:
    tumor necrosis factor,alpha-induced protein 3

         Enzyme Numbers (IUBMB): EC 6.3.2.-1 EC 3.4.19.121

         Gene Ontology (GO): Selected molecular function terms (see all 10):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0002020protease binding IPI18223652
    GO:0003677DNA binding IEA--
    GO:0004221ubiquitin thiolesterase activity IMP15258597
    GO:0004842ubiquitin-protein ligase activity IDA15258597
    GO:0004843ubiquitin-specific protease activity TAS--
         
    TNFAIP3 for ontologies           About GeneDecksing


    Phenotypes:
         3 GenomeRNAi human phenotypes for TNFAIP3:
     Actin fiber cells  Increased S DNA content  Increased cell number in G2M,  

         14 MGI mutant phenotypes (inferred from 7 alleles(MGI details for Tnfaip3):
     cardiovascular system  cellular  digestive/alimentary  endocrine/exocrine gland  growth/size/body 
     hematopoietic system  homeostasis/metabolism  immune system  integument  liver/biliary system 
     mortality/aging  no phenotypic analysis  renal/urinary system  skeleton 

    TNFAIP3 for phenotypes           About GeneDecksing

    Animal Models:
         MGI mouse knock-outs for TNFAIP3: Tnfaip3tm1.2Gvl Tnfaip3tm1Ama

       inGenious Targeting Laboratory: Let us create your new Knockout/Knockin mouse model for TNFAIP3
       inGenious Targeting Laboratory: Contact us about creating complex and humanized mouse models for TNFAIP3

       genOway customized KO model: permanent, tissue-specific or time-controlled inactivation for TNFAIP3
       genOway customized Knockin model: humanization, point mutation, expression monitoring, etc. for TNFAIP3

    miRNA
    Products:
        
    miRTarBase miRNAs that target TNFAIP3:
    hsa-mir-125a-5p (MIRT006471), hsa-mir-26b-5p (MIRT029863), hsa-mir-24-3p (MIRT030581), hsa-mir-125b-5p (MIRT006472), hsa-mir-29a-3p (MIRT006380), hsa-mir-21-5p (MIRT005955)

    Block miRNA regulation of human, mouse, rat TNFAIP3 using miScript Target Protectors
    Selected qRT-PCR Assays for microRNAs that regulate TNFAIP3 (see all 63):
    hsa-miR-142-5p hsa-miR-4291 hsa-miR-607 hsa-let-7d hsa-miR-106a hsa-miR-200a hsa-miR-605 hsa-miR-485-3p
    SwitchGear 3'UTR luciferase reporter plasmidTNFAIP3 3' UTR sequence
    Inhib. RNA
    Products:
        
    OriGene RNAi products in human, mouse, rat for TNFAIP3
    Predesigned siRNA for gene silencing in human, mouse, rat TNFAIP3

    Gene Editing
    Products:
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    Clone
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    GenScript: all cDNA clones in your preferred vector: TNFAIP3 (NM_006290)
    Sino Biological Human cDNA Clone for TNFAIP3
    DNA2.0 Custom Codon Optimized Gene Synthesis Service for TNFAIP3
    Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat TNFAIP3

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    Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for TNFAIP3


    (According to UniProtKB, COMPARTMENTS Subcellular localization database, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Subcellular locations from UniProtKB/Swiss-Prot
    TNAP3_HUMAN, P21580: Cytoplasm. Nucleus. Lysosome
    TNAP3_HUMAN, P21580: A20p50: Cytoplasm
    Subcellular locations from COMPARTMENTS: 

    CompartmentConfidence
    lysosome5
    nucleus5
    vacuole5
    cytoskeleton4
    cytosol4
    extracellular1
    mitochondrion1
    peroxisome1

    Gene Ontology (GO): Selected cellular component terms (see all 6):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0005634nucleus IDA11463333
    GO:0005737cytoplasm IDA--
    GO:0005764lysosome IEA--
    GO:0005813centrosome IDA--
    GO:0005829cytosol TAS--

    TNFAIP3 for ontologies           About GeneDecksing


    (SuperPaths according to PathCards, Pathways according to R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Sino Biological, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to QIAGEN, and/or STRING, Interactions according to 1UniProtKB, 2MINT, 3I2D, and/or 4STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene).
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    SuperPaths for TNFAIP3 About   (see all 18)  
    See pathways by source

    SuperPathContained pathways About
    1Nucleotide-binding domain, leucine rich repeat containing receptor (NLR) signaling pathways
    Nucleotide-binding domain, leucine rich repeat containing receptor (NLR) signaling pathways0.68
    NOD-like receptor signaling pathway0.37
    NOD1/2 Signaling Pathway0.68
    24-1BB Pathway
    CD40 Signaling0.54
    TNFR2 Pathway0.37
    3RIG-I/MDA5 mediated induction of IFN-alpha/beta pathways
    RIG-I/MDA5 mediated induction of IFN-alpha/beta pathways0.47
    Negative regulators of RIG-I/MDA5 signaling0.42
    4NF-KappaB Family Pathway
    NF-KappaB (p50-p65) Pathway0.72
    5TWEAK Pathway
    TNFR1 Pathway0.56

    Pathways by source                                                                                                                                                                 See SuperPaths
    Show all pathways

    Selected Downloadable PowerPoint Slides of GeneGlobe Pathway Central Maps for TNFAIP3 (see all 6)
        14-3-3 Induced Apoptosis
    NF-KappaB (p50-p65) Pathway
    14-3-3 and Regulation of BAD Activity
    CD40 Signaling
    TNFR2 Pathway

    2 Cell Signaling Technology (CST) Pathways for TNFAIP3
        Apoptosis and Autophagy
    NF-kappaB Signaling

    4 BioSystems Pathways for TNFAIP3
        TNF-alpha/NF-kB Signaling Pathway
    Canonical NF-kappaB pathway
    CD40/CD40L signaling
    TNF receptor signaling pathway

    1 Sino Biological Pathway for TNFAIP3
        NF-kB (NFkB) Pathway

    2 Reactome Pathways for TNFAIP3
        Negative regulators of RIG-I/MDA5 signaling
    NOD1/2 Signaling Pathway


    5 Kegg Pathways  (Kegg details for TNFAIP3):
        NF-kappa B signaling pathway
    NOD-like receptor signaling pathway
    TNF signaling pathway
    Measles
    Epstein-Barr virus infection


    TNFAIP3 for pathways           About GeneDecksing

        Pathway & Disease-focused RT2 Profiler PCR Arrays including TNFAIP3 (see all 6): 
              Atherosclerosis in human mouse rat
              Toll-Like Receptor Signaling Pathway in human mouse rat
              TNF Ligands & Receptors in human mouse rat
              NFKB Signaling Pathway in human mouse rat
              Apoptosis 384HT in human mouse rat

    Interactions:

        GeneGlobe Interaction Network for TNFAIP3

    STRING Interaction Network Preview (showing 5 interactants - click image to see 25)

    Selected Interacting proteins for TNFAIP3 (P215801, 2, 3 ENSP000002372894) via UniProtKB, MINT, STRING, and/or I2D (see all 78)
    InteractantInteraction Details
    GeneCardExternal ID(s)
    RNF11Q9Y3C51, 2, 3, ENSP000002427194EBI-527670,EBI-396669 MINT-7040677 MINT-60883 I2D: score=4 STRING: ENSP00000242719
    ENSG00000204490P013752, 3MINT-8410390 I2D: score=1 
    ENSG00000206439P013752, 3MINT-8410390 I2D: score=1 
    ENSG00000223952P013752, 3MINT-8410390 I2D: score=1 
    ENSG00000228849P013752, 3MINT-8410390 I2D: score=1 
    About this table

    Gene Ontology (GO): Selected biological process terms (see all 50):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0001922B-1 B cell homeostasis ISS--
    GO:0002237response to molecule of bacterial origin IDA19912257
    GO:0002634regulation of germinal center formation ISS--
    GO:0002677negative regulation of chronic inflammatory response IEA--
    GO:0006508proteolysis ----

    TNFAIP3 for ontologies           About GeneDecksing



    (Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience, ApexBio, HMDB, BitterDB, and/or Novoseek, Ligands according to IUPHAR, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB)
    About This Section

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    Browse Small Molecules at EMD Millipore
       Browse drugs & compounds from Enzo Life Sciences
      Browse compounds at ApexBio 

    Browse Tocris compounds for TNFAIP3 (TNAP3)

    8 Novoseek inferred chemical compound relationships for TNFAIP3 gene    About this table
    Compound   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    zinc 69.2 55 18366681 (3), 10652565 (2), 11389905 (2), 12813034 (2) (see all 36)
    cycloheximide 43.3 3 11359904 (1), 9763560 (1), 9516122 (1)
    manganese superoxide 30.4 1 11880364 (1)
    oxygen 0 1 10652565 (1)
    nitric oxide 0 3 10523611 (2)
    progesterone 0 3 15297189 (1), 17297453 (1)
    superoxide 0 2 9054379 (1), 8065303 (1)
    h2o2 0 3 8663499 (1), 8557994 (1)



    TNFAIP3 for compounds           About GeneDecksing



    (Secondary structures according to fRNAdb,
    GenBank/EMBL/DDBJ Accessions according to
    Unigene (Build 236 Homo sapiens; Apr 25 2013) or GenBank,
    RefSeq according to Entrez Gene,
    DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
    Conferences by KenesGroup, exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
    siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN, SwitchGear Genomics,
    Tagged/untagged cDNA clones from OriGene, GenScript, DNA2.0, Vector BioLabs, Primers from OriGene, and/or QIAGEN )
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    REFSEQ mRNAs for TNFAIP3 gene (3 alternative transcripts): 
    NM_001270507.1  NM_001270508.1  NM_006290.3  

    Unigene Cluster for TNFAIP3:

    Tumor necrosis factor, alpha-induced protein 3
    Hs.211600  [show with all ESTs]
    Unigene Representative Sequence: NM_001270508
    5 Ensembl transcripts including schematic representations, and UCSC links where relevant:
    ENST00000421450 ENST00000420009 ENST00000237289(uc003qhr.3 uc003qhs.3 uc021zfv.1)
    ENST00000433680 ENST00000485192
    Congresses - knowledge worth sharing:
    European Congress of Clinical Microbiology and Infectious Diseases (ECCMID) 10 - 13 May 2014

    miRNA
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    Block miRNA regulation of human, mouse, rat TNFAIP3 using miScript Target Protectors
    Selected qRT-PCR Assays for microRNAs that regulate TNFAIP3 (see all 63):
    hsa-miR-142-5p hsa-miR-4291 hsa-miR-607 hsa-let-7d hsa-miR-106a hsa-miR-200a hsa-miR-605 hsa-miR-485-3p
    SwitchGear 3'UTR luciferase reporter plasmidTNFAIP3 3' UTR sequence
    Inhib. RNA
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    Predesigned siRNA for gene silencing in human, mouse, rat TNFAIP3
    Clone
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    Additional mRNA sequence: 

    AK312862.1 AL157444.1 AY820830.1 BC041790.1 BC113871.1 BC114480.1 FJ434402.1 FJ434405.1 
    FJ434406.1 FJ434407.1 FJ434408.1 FJ434409.1 FJ434410.1 FJ434411.1 FJ434412.1 FJ434413.1 
    FJ434414.1 FJ434415.1 FJ434417.1 FJ434418.1 FJ434419.1 M59465.1 

    12 DOTS entries:

    DT.444982  DT.99936679  DT.75109697  DT.97821671  DT.100662344  DT.121318267  DT.91957700  DT.99944754 
    DT.102831495  DT.121318224  DT.75187699  DT.91721214 

    Selected AceView cDNA sequences (see all 196):

    M59465 CD678965 BU675179 AI656032 W02692 AI913095 AL157444 BU689466 
    AI554862 T11383 AI086721 AU134501 CB528739 AA113383 AW118863 BQ002744 
    AW206495 AI802180 T29516 AL046675 AA864665 NM_006290 BP336895 AA281660 

    GeneLoc Exon Structure

    Selected Alternative Splicing Database (ASD) splice patterns (SP) for TNFAIP3 (see all 9)    About this scheme

    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:                                                                                            -                                                               

    ExUns: 13c
    SP1:      
    SP2:      
    SP3:      
    SP4:      
    SP5:      


    ECgene alternative splicing isoforms for TNFAIP3

    (RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, Protein expression images according to data from SPIRE 1MOPED, 2PaxDb, and 3MaxQB, plus additional links to SOURCE, and/or BioGPS, and/or UniProtKB,
    PCR Arrays from QIAGEN, Primers from OriGene, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
    About This Section

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    TNFAIP3 expression in normal human tissues (normalized intensities)
    See probesets specificity/sensitivity at GeneAnnot
    About this imageBioGPS <intensity>2/3
    CGAP TAG: AGTATGAGGA
    TNFAIP3 Expression
    About this image


    TNFAIP3 expression in embryonic tissues and stem cells    About this table
    Data from LifeMap, the Embryonic Development and Stem Cells Database
     selected tissues (see all 6) fully expand
     
     Adipose (Muscoskeletal System)    fully expand to see all 2 entries
             Body Subcutaneous White Adipose
     
     Epithelial Cells
             Duct Cells Pancreatic Ducts
     
     Pancreas (Endocrine System)
             Duct Cells Pancreatic Ducts
     
     Bone (Muscoskeletal System)
             Bone Marrow
     
     Ovary (Reproductive System)
    TNFAIP3 Protein expression data from MOPED1, PaxDb2 and MaxQB3    About this image

    TNFAIP3 Protein Expression

    SOURCE GeneReport for Unigene cluster: Hs.211600
        Pathway & Disease-focused RT2 Profiler PCR Arrays including TNFAIP3 (see all 6): 
              Atherosclerosis in human mouse rat
              Toll-Like Receptor Signaling Pathway in human mouse rat
              TNF Ligands & Receptors in human mouse rat
              NFKB Signaling Pathway in human mouse rat
              Apoptosis 384HT in human mouse rat

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    (Orthologs according to 1,2HomoloGene (2older version, for species not in 1newer version), 3euGenes, 4SGD , 5MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or 6Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
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    This gene was present in the common ancestor of chordates.

    Orthologs for TNFAIP3 gene from Selected species (see all 10)    About this table
    Organism Taxonomic
    classification
    Gene Description Human
    Similarity
    Orthology
    Type
    Details
    mouse
    (Mus musculus)
    Mammalia Tnfaip31 , 5 tumor necrosis factor, alpha-induced protein 31, 5 85.08(n)1
    89.81(a)1
      10 (8.08 cM)5
    219291  NM_001166402.11  NP_001159874.11 
     190009105 
    chicken
    (Gallus gallus)
    Aves TNFAIP31 tumor necrosis factor, alpha-induced protein 3 69.64(n)
    66.88(a)
      421684  XM_003640919.2  XP_003640967.2 
    lizard
    (Anolis carolinensis)
    Reptilia TNFAIP36
    tumor necrosis factor, alpha-induced protein 3
    63(a)
    1 ↔ 1
    GL343200.1(1575549-1605067)
    zebrafish
    (Danio rerio)
    Actinopterygii tnfaip31 tumor necrosis factor, alpha-induced protein 3 58.08(n)
    52.98(a)
      564497  XM_687830.4  XP_692922.3 


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

    (Paralogs according to 1HomoloGene,
    2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
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    Paralogs for TNFAIP3 gene
    OTUD7B2  ZRANB12  OTUD7A2  
    1 SIMAP similar gene for TNFAIP3 using alignment to 20 protein entries:     TNAP3_HUMAN (see all proteins):
    OTUD7B

    TNFAIP3 for paralogs           About GeneDecksing



    (SNPs/Variants according to the 1NCBI SNP Database, 2Ensembl, 3PupaSUITE, 4UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD), the Human Cytochrome P450 Allele Nomenclature Database, and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers, Cancer Mutation PCR Arrays and Assays, and Copy Number PCR Arrays from QIAGEN)
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    Selected SNPs for TNFAIP3 (see all 425)    About this table    
    Genomic DataTranscription Related DataAllele Frequencies
    SNP IDValidClinical
    significance
    Chr 6 posSequence#AA
    Chg
    TypeMore#Allele
    freq
    PopTotal
    sample
    More
    ----------
    rs1385924271,2
    --138186871(+) GACAGA/CAAGAC 3 -- us2k10--------
    rs791220461,2
    C--138186912(+) GGAGGA/GTTGAA 3 -- us2k10--------
    rs596930831,2
    C,F--138186976(+) CCAGCA/GGGAGA 3 -- us2k18Minor allele frequency- G:0.30WA NA CSA EA 367
    rs1415916601,2
    --138187012(+) CAGGGA/TCTTTC 3 -- us2k10--------
    rs735662271,2
    C--138187071(+) TCCTGA/GAGGTG 3 -- us2k12Minor allele frequency- G:0.04WA 120
    rs744853271,2
    C--138187138(+) GTTTTG/TAGAGG 3 -- us2k10--------
    rs1913536631,2
    --138187167(+) AAAGAC/GTACCT 3 -- us2k10--------
    rs50299221,2
    C--138187180(+) CTCACA/GGGATC 3 -- us2k13Minor allele frequency- G:0.01NS NA 84
    rs1171641571,2
    C,F--138187392(+) GCCCTG/TGACTC 3 -- us2k11Minor allele frequency- T:0.03EA 120
    rs50299231,2
    C,F,H--138187624(+) ACCCCC/TATCTC 3 -- us2k17Minor allele frequency- T:0.03NS WA 996

    HapMap Linkage Disequilibrium report for TNFAIP3 (138188351 - 138204449 bp)

    Structural Variations
         Database of Genomic Variants (DGV) 5 variations for TNFAIP3:    About this table    
    Variant IDTypeSubtypePubMed ID
    nsv5493CNV Insertion18451855
    nsv523826CNV Loss19592680
    nsv470863CNV Loss18288195
    nsv830819CNV Loss17160897
    nsv830818CNV Gain17160897

    Human Gene Mutation Database (HGMD): TNFAIP3
    Selected Site Specific Mutation Identification with PCR Assays for TNFAIP3 (see all 6):
    Cosmic IdAA Change
    36249p.N102S
    35978p.R271*
    35943p.D134fs*5
    35911p.E452*
    35955p.D279fs*5
    SeqTarget long-range PCR primers for resequencing TNFAIP3
    DNA2.0 Custom Variant and Variant Library Synthesis for TNFAIP3

    (in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Conferences by KenesGroup, Novoseek, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
    About This Section

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    OMIM gene information: 191163    OMIM disorders: --

    Selected diseases for TNFAIP3 (see all 57):    
    About MalaCards
    nodular lymphocyte predominant hodgkin lymphoma    marginal zone b-cell lymphoma    b-cell lymphomas    malt lymphoma
    patent ductus arteriosus    mediastinitis    adenoid cystic carcinoma    wegener's granulomatosis
    fibrosarcoma    arteriosclerosis    adenoiditis    diffuse large b-cell lymphoma
    acne    systemic lupus erythematosus    cystitis    burns
    lupus nephritis    wiskott-aldrich syndrome    measles    nephritis

    3 diseases from the University of Copenhagen DISEASES database for TNFAIP3:
    Rheumatoid arthritis     Systemic lupus erythematosus     Psoriasis

    TNFAIP3 for disorders           About GeneDecksing

    9 Novoseek inferred disease relationships for TNFAIP3 gene    About this table

    Disease   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    necrosis 64.8 50 15527421 (4), 10652565 (2), 1381359 (2), 2118515 (2) (see all 34)
    leukemia t-cell 50.3 4 8444879 (2), 18246070 (1), 10385526 (1)
    tumors 46.5 62 20186265 (3), 17297453 (2), 1381359 (2), 16365179 (2) (see all 31)
    inflammation 42 7 11319609 (1), 14748687 (1), 17982095 (1), 18813897 (1) (see all 6)
    breast carcinoma 27.9 3 1618749 (1), 8557994 (1)
    fibrosarcoma 18.2 1 8557994 (1)
    virus infection 0 5 16765340 (3)
    breast cancer 0 3 17297453 (2)
    cancer 0 1 15862966 (1)

    Genetic Association Database (GAD): TNFAIP3
    Human Genome Epidemiology (HuGE) Navigator: TNFAIP3 (65 documents)

    Export disorders for TNFAIP3 gene to outside databases

    (in PubMed. Associations of this gene to articles via 1Entrez Gene, 2UniProtKB/Swiss-Prot, 3HGNC, 4GAD, 5PharmGKB, 6HMDB, 7DrugBank, 8UniProtKB/TrEMBL, 9 Novoseek, and/or 10fRNAdb)
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    PubMed articles for TNFAIP3 gene, integrated from 10 sources (see all 295):
    (articles sorted by number of sources associating them with TNFAIP3)
        Utopia: connect your pdf to the dynamic
    world of online information

    1. The A20 cDNA induced by tumor necrosis factor alpha encodes a novel type of zinc finger protein. (PubMed id 2118515)1, 2, 3, 9 Opipari A.W. Jr.... Dixit V.M. (J. Biol. Chem. 1990)
    2. A20 negatively regulates T cell receptor signaling to NF-kappaB by cleaving Malt1 ubiquitin chains. (PubMed id 19494296)1, 2, 9 Duwel M.... Krappmann D. (J. Immunol. 2009)
    3. The zinc finger protein A20 interacts with a novel anti-apoptotic protein which is cleaved by specific caspases. (PubMed id 10435631)1, 2, 9 de Valck D.... Beyaert R. (Oncogene 1999)
    4. The tumor necrosis factor-inducible zinc finger protein A20 interacts with TRAF1/TRAF2 and inhibits NF-kappaB activation. (PubMed id 8692885)1, 2, 9 Song H.Y.... Goeddel D.V. (Proc. Natl. Acad. Sci. U.S.A. 1996)
    5. Zinc-finger protein A20, a regulator of inflammation and cell survival, has de-ubiquitinating activity. (PubMed id 14748687)1, 2, 9 Evans P.C.... Smith T.S. (Biochem. J. 2004)
    6. Tag polymorphisms at the A20 (TNFAIP3) locus are associated with lower gene expression and increased risk of coronary artery disease in type 2 diabetes. (PubMed id 17259397)1, 4, 9 Boonyasrisawat W....Doria A. (Diabetes 2007)
    7. Multiple polymorphisms in the TNFAIP3 region are independently associated with systemic lupus erythematosus. (PubMed id 19165919)1, 4, 9 Musone S.L....Criswell L.A. (Nat. Genet. 2008)
    8. Polymorphisms in the tumour necrosis factor alpha-induced protein 3 (TNFAIP3) gene are associated with chronic rhinosinusitis. (PubMed id 19344623)1, 4, 9 Cormier C....Desrosiers M. (amp 2009)
    9. Structure of the A20 OTU domain and mechanistic insights into deubiquitination. (PubMed id 17961127)1, 2, 9 Komander D. and Barford D. (Biochem. J. 2008)
    10. Association of the 6q23 region with the rate of joint destruction in rheumatoid arthritis. (PubMed id 19366996)1, 4, 9 Scherer H.U....Toes R.E. (Ann. Rheum. Dis. 2010)

    (in PubMed, OMIM, and NCBI Bookshelf)
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     ANDOR
    Aliases
    Disorders
    Free Text  

      Query String
    PubMed
    OMIM
    NCBI Bookshelf
      (Note: In FireFox, select the above section and copy using Ctrl-C)

    (According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
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    Entrez Gene: 7128 HGNC: 11896 AceView: TNFAIP3 Ensembl:ENSG00000118503 euGenes: HUgn7128
    ECgene: TNFAIP3 Kegg: 7128 H-InvDB: TNFAIP3

    (According to HUGE)
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      --

    (According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, UniProtKB/TrEMBL, and/or others, e.g. Wikipedia and GeneReviews, via UniProtKB/Swiss-Prot)
    About This Section

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    NameDescription
    PharmGKB entry for TNFAIP3 Pharmacogenomics, SNPs, Pathways
    ATLAS Chromosomes in Cancer entry for TNFAIP3 Genetics and Cytogenetics in Oncology and Haematology
    SeattleSNPshttp://pga.gs.washington.edu/data/tnfaip3/

    (Patent information from GeneIP,
    Licensable technologies from WIS Yeda, Salk, Tufts,
    IP news from LifeMap Sciences, Inc.)
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    Patent Information for TNFAIP3 gene:
    Search GeneIP for patents involving TNFAIP3

    GeneCards and IP:
    Japan Patent Office Licenses GeneCards     European Patent Office Licenses GeneCards     Improving the IP Search



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