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TANK TRAF family member associated NFKB activator [ Homo sapiens (human) ]

Gene ID: 10010, updated on 6-Jan-2019

Summary

Official Symbol
TANKprovided by HGNC
Official Full Name
TRAF family member associated NFKB activatorprovided by HGNC
Primary source
HGNC:HGNC:11562
See related
Ensembl:ENSG00000136560 MIM:603893
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
ITRAF; TRAF2; I-TRAF
Summary
The TRAF (tumor necrosis factor receptor-associated factor) family of proteins associate with and transduce signals from members of the tumor necrosis factor receptor superfamily. The protein encoded by this gene is found in the cytoplasm and can bind to TRAF1, TRAF2, or TRAF3, thereby inhibiting TRAF function by sequestering the TRAFs in a latent state in the cytoplasm. For example, the protein encoded by this gene can block TRAF2 binding to LMP1, the Epstein-Barr virus transforming protein, and inhibit LMP1-mediated NF-kappa-B activation. Three alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2010]
Expression
Ubiquitous expression in appendix (RPKM 16.5), lymph node (RPKM 16.3) and 25 other tissues See more
Orthologs

Genomic context

See TANK in Genome Data Viewer
Location:
2q24.2
Exon count:
14
Annotation release Status Assembly Chr Location
109 current GRCh38.p12 (GCF_000001405.38) 2 NC_000002.12 (161136955..161236176)
105 previous assembly GRCh37.p13 (GCF_000001405.25) 2 NC_000002.11 (161993438..162092687)

Chromosome 2 - NC_000002.12Genomic Context describing neighboring genes Neighboring gene RNA, 7SL, cytoplasmic 423, pseudogene Neighboring gene DEAD-box helicase 18 pseudogene Neighboring gene uncharacterized LOC105373719 Neighboring gene uncharacterized LOC101929512 Neighboring gene VISTA enhancer hs416 Neighboring gene long intergenic non-protein coding RNA 1806

Genomic regions, transcripts, and products

Expression

  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

Phenotypes

NHGRI GWAS Catalog

Description
Beyond single-marker analyses: mining whole genome scans for insights into treatment responses in severe sepsis.
NHGRI GWA Catalog
Common genetic variants associated with cognitive performance identified using the proxy-phenotype method.
NHGRI GWA Catalog
Genome-wide association for abdominal subcutaneous and visceral adipose reveals a novel locus for visceral fat in women.
NHGRI GWA Catalog
Genome-wide association study of antiphospholipid antibodies.
NHGRI GWA Catalog
Genome-wide association study of peripheral neuropathy with D-drug-containing regimens in AIDS Clinical Trials Group protocol 384.
NHGRI GWA Catalog
GWAS of 126,559 individuals identifies genetic variants associated with educational attainment.
NHGRI GWA Catalog
Novel genetic loci identified for the pathophysiology of childhood obesity in the Hispanic population.
NHGRI GWA Catalog
Novel locus including FGF21 is associated with dietary macronutrient intake.
NHGRI GWA Catalog

Pathways from BioSystems

  • Activated TLR4 signalling, organism-specific biosystem (from REACTOME)
    Activated TLR4 signalling, organism-specific biosystemTLR4 is unique among the TLR family in its ability to recruit four adapters to activate two distinct signaling pathways. One pathway is activated by the pair of the adapters Mal or TIRAP (Toll/inter...
  • Activation of IRF3/IRF7 mediated by TBK1/IKK epsilon, organism-specific biosystem (from REACTOME)
    Activation of IRF3/IRF7 mediated by TBK1/IKK epsilon, organism-specific biosystemCell stimulation with viral ds RNA leads to the activation of two IKK-related serine/threonine kinases, TBK1 and IKK-i which directly phosphorylate IRF3 and IRF7 promoting their dimerization and tran...
  • 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
  • MyD88-independent TLR3/TLR4 cascade, organism-specific biosystem (from REACTOME)
    MyD88-independent TLR3/TLR4 cascade, organism-specific biosystemMyD88-independent signaling pathway is shared by TLR3 and TLR4 cascades. TIR-domain-containing adapter-inducing interferon-beta (TRIF or TICAM1) is a key adapter molecule in transducing signals from ...
  • 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...
  • RIG-I-like Receptor Signaling, organism-specific biosystem (from WikiPathways)
    RIG-I-like Receptor Signaling, organism-specific biosystemViral pathogen RNA are recognized by host helicases called RIG-I-like receptors (RLRs) that include DDX58 (RIG-I), DHX58 (LGP2), IFIH1 (MDA5), SNW1, and DDX17. These RLR proteins then go on to initia...
  • RIG-I-like receptor signaling pathway, organism-specific biosystem (from KEGG)
    RIG-I-like receptor signaling pathway, organism-specific biosystemSpecific families of pattern recognition receptors are responsible for detecting viral pathogens and generating innate immune responses. Non-self RNA appearing in a cell as a result of intracellular ...
  • RIG-I-like receptor signaling pathway, conserved biosystem (from KEGG)
    RIG-I-like receptor signaling pathway, conserved biosystemSpecific families of pattern recognition receptors are responsible for detecting viral pathogens and generating innate immune responses. Non-self RNA appearing in a cell as a result of intracellular ...
  • 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...
  • Structural Pathway of Interleukin 1 (IL-1), organism-specific biosystem (from WikiPathways)
    Structural Pathway of Interleukin 1 (IL-1), organism-specific biosystemPathway published in http://www.ploscompbiol.org/article/info%3Adoi%2F10.1371%2Fjournal.pcbi.1003470 IL-1 signaling pathway reconstructed by combining related pathways and information from the litera...
  • TNF alpha Signaling Pathway, organism-specific biosystem (from WikiPathways)
    TNF alpha Signaling Pathway, organism-specific biosystemTumor necrosis factor alpha (TNF?) is a proinflammatory cytokine involved in various biological processes including regulation of cell proliferation, differentiation, apoptosis and immune response. T...
  • TRAF6 mediated IRF7 activation, organism-specific biosystem (from REACTOME)
    TRAF6 mediated IRF7 activation, organism-specific biosystemTRAF6 is crucial for both RIG-I- and MDA5-mediated antiviral responses. The absence of TRAF6 resulted in enhanced viral replication and a significant reduction in the production of type I IFNs and IL...
  • TRIF-mediated TLR3/TLR4 signaling, organism-specific biosystem (from REACTOME)
    TRIF-mediated TLR3/TLR4 signaling, organism-specific biosystemTRIF(TICAM1) was shown to induce IRF3/7 and NF-?B activation and apoptosis through distinct intracellular signaling pathways [Han KJ et al 2004; Kaiser WJ and Offermann MK et al 2005]. TRIF consists...
  • Toll Like Receptor 3 (TLR3) Cascade, organism-specific biosystem (from REACTOME)
    Toll Like Receptor 3 (TLR3) Cascade, organism-specific biosystemToll-like receptor 3 (TLR3) as was shown for mammals is expressed on myeloid dendritic cells, respiratory epithelium, macrophages, and appears to play a central role in mediating the antiviral and in...
  • Toll Like Receptor 4 (TLR4) Cascade, organism-specific biosystem (from REACTOME)
    Toll Like Receptor 4 (TLR4) Cascade, organism-specific biosystemToll-like Receptor 4 is a Microbe Associated Molecular Pattern receptor well known for it's sensitivity to Bacterial Lipopolysaccharides (LPS). LPS is assembled within diverse Gram-negative bacteria,...
  • Toll-Like Receptors Cascades, organism-specific biosystem (from REACTOME)
    Toll-Like Receptors Cascades, organism-specific biosystemIn human, ten members of the Toll-like receptor (TLR) family (TLR1-TLR10) have been identified (TLR11 has been found in mouse, but not in human). All TLRs have a similar Toll/IL-1 receptor (TIR) doma...

Interactions

Products Interactant Other Gene Complex Source Pubs Description

General gene information

Markers

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
deubiquitinase activator activity IMP
Inferred from Mutant Phenotype
more info
PubMed 
metal ion binding IEA
Inferred from Electronic Annotation
more info
 
protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
contributes_to thiol-dependent ubiquitin-specific protease activity IMP
Inferred from Mutant Phenotype
more info
PubMed 
ubiquitin protein ligase binding IPI
Inferred from Physical Interaction
more info
PubMed 
Process Evidence Code Pubs
I-kappaB kinase/NF-kappaB signaling IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
TRIF-dependent toll-like receptor signaling pathway TAS
Traceable Author Statement
more info
 
cellular response to DNA damage stimulus IMP
Inferred from Mutant Phenotype
more info
PubMed 
cellular response to interleukin-1 IMP
Inferred from Mutant Phenotype
more info
PubMed 
cellular response to ionizing radiation IMP
Inferred from Mutant Phenotype
more info
PubMed 
cellular response to tumor necrosis factor IMP
Inferred from Mutant Phenotype
more info
PubMed 
negative regulation of I-kappaB kinase/NF-kappaB signaling IMP
Inferred from Mutant Phenotype
more info
PubMed 
positive regulation of protein deubiquitination IMP
Inferred from Mutant Phenotype
more info
PubMed 
positive regulation of ubiquitin-specific protease activity IMP
Inferred from Mutant Phenotype
more info
PubMed 
proteolysis IEA
Inferred from Electronic Annotation
more info
 
signal transduction TAS
Traceable Author Statement
more info
PubMed 
viral process IEA
Inferred from Electronic Annotation
more info
 
Component Evidence Code Pubs
cytosol IDA
Inferred from Direct Assay
more info
 
cytosol TAS
Traceable Author Statement
more info
 
protein-containing complex IDA
Inferred from Direct Assay
more info
PubMed 

General protein information

Preferred Names
TRAF family member-associated NF-kappa-B activator
Names
TRAF-interacting protein

NCBI Reference Sequences (RefSeq)

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.

mRNA and Protein(s)

  1. NM_001199135.2NP_001186064.1  TRAF family member-associated NF-kappa-B activator isoform a

    See identical proteins and their annotated locations for NP_001186064.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) has an alternate 5' UTR exon compared to variant 1. Variants 1 and 2 encode the same isoform (a).
    Source sequence(s)
    AC009299, AC009313
    Consensus CDS
    CCDS2215.1
    UniProtKB/Swiss-Prot
    Q92844
    UniProtKB/TrEMBL
    B2R7S3, Q6NW12
    Related
    ENSP00000376505.2, ENST00000392749.6
    Conserved Domains (1) summary
    pfam12845
    Location:135186
    TBD; TBD domain
  2. NM_004180.2NP_004171.2  TRAF family member-associated NF-kappa-B activator isoform a

    See identical proteins and their annotated locations for NP_004171.2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) is the longer transcript and encodes the longer isoform (a).
    Source sequence(s)
    U59863
    Consensus CDS
    CCDS2215.1
    UniProtKB/Swiss-Prot
    Q92844
    Related
    ENSP00000259075.2, ENST00000259075.6
    Conserved Domains (1) summary
    pfam12845
    Location:135186
    TBD; TBD domain
  3. NM_133484.1NP_597841.1  TRAF family member-associated NF-kappa-B activator isoform b

    See identical proteins and their annotated locations for NP_597841.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) lacks multiple exons from the 3' end and contains an alternate 3' segment compared to variant 1. The resulting isoform (b) has a shorter and distinct C-terminus, as compared to isoform (a).
    Source sequence(s)
    BC003388, U59863
    Consensus CDS
    CCDS46436.1
    UniProtKB/Swiss-Prot
    Q92844
    Related
    ENSP00000385983.1, ENST00000403609.1

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 109

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

Reference GRCh38.p12 Primary Assembly

Genomic

  1. NC_000002.12 Reference GRCh38.p12 Primary Assembly

    Range
    161136955..161236176
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_024452337.1XP_024308105.1  TRAF family member-associated NF-kappa-B activator isoform X7

    Conserved Domains (1) summary
    pfam12845
    Location:133
    TBD; TBD domain
  2. XM_017003094.1XP_016858583.1  TRAF family member-associated NF-kappa-B activator isoform X3

  3. XM_017003095.1XP_016858584.1  TRAF family member-associated NF-kappa-B activator isoform X5

  4. XM_017003097.1XP_016858586.1  TRAF family member-associated NF-kappa-B activator isoform X6

    UniProtKB/Swiss-Prot
    Q92844
    Conserved Domains (1) summary
    pfam12845
    Location:135186
    TBD; TBD domain
  5. XM_017003093.1XP_016858582.1  TRAF family member-associated NF-kappa-B activator isoform X2

    Conserved Domains (1) summary
    pfam12845
    Location:193244
    TBD; TBD domain
  6. XM_024452335.1XP_024308103.1  TRAF family member-associated NF-kappa-B activator isoform X4

    Conserved Domains (1) summary
    pfam12845
    Location:164215
    TBD; TBD domain
  7. XM_017003096.1XP_016858585.1  TRAF family member-associated NF-kappa-B activator isoform X6

    UniProtKB/Swiss-Prot
    Q92844
    Related
    ENSP00000385487.1, ENST00000405852.5
    Conserved Domains (1) summary
    pfam12845
    Location:135186
    TBD; TBD domain
  8. XM_024452333.1XP_024308101.1  TRAF family member-associated NF-kappa-B activator isoform X2

    Conserved Domains (1) summary
    pfam12845
    Location:193244
    TBD; TBD domain
  9. XM_005246207.3XP_005246264.2  TRAF family member-associated NF-kappa-B activator isoform X1

    See identical proteins and their annotated locations for XP_005246264.2

    Conserved Domains (1) summary
    pfam12845
    Location:161212
    TBD; TBD domain
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