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

    Gene ID: 10010, updated on 10-Dec-2024

    Summary

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    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; AllianceGenome:HGNC:11562
    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
    mouse all
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    Genomic context

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    See TANK in Genome Data Viewer
    Location:
    2q24.2
    Exon count:
    12
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 2 NC_000002.12 (161136963..161236230)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 2 NC_060926.1 (161595211..161694538)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 2 NC_000002.11 (161993474..162092741)

    Chromosome 2 - NC_000002.12Genomic Context describing neighboring genes Neighboring gene RNA, 7SL, cytoplasmic 423, pseudogene Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_54344 Neighboring gene DEAD-box helicase 18 pseudogene Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_54373 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_54429 Neighboring gene Sharpr-MPRA regulatory region 6450 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 16702 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 12050 Neighboring gene TANK antisense RNA 1 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 16703 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 12051 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 12052 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 12053 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 16704 Neighboring gene H3K27ac hESC enhancer GRCh37_chr2:162016649-162017412 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_54722 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 16705 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 16706 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 16707 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_54734 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_54744 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_54751 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_54752 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 16708 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 12054 Neighboring gene VISTA enhancer hs416 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 12056 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 16710 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 16709 Neighboring gene PSMD14 divergent transcript Neighboring gene H3K27ac hESC enhancer GRCh37_chr2:162101046-162101546 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 12057 Neighboring gene long intergenic non-protein coding RNA 1806 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr2:162134920-162135556 Neighboring gene OCT4-H3K27ac hESC enhancer GRCh37_chr2:162135557-162136192 Neighboring gene Sharpr-MPRA regulatory region 15701 Neighboring gene Sharpr-MPRA regulatory region 9806 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 16712 Neighboring gene proteasome 26S subunit, non-ATPase 14 Neighboring gene MXRA7 pseudogene 1

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • 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

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    Related articles in PubMed

    1. TANK shapes an immunosuppressive microenvironment and predicts prognosis and therapeutic response in glioma. Li S, et al. Front Immunol, 2023. PMID 37215097, Free PMC Article
    2. Tumor necrosis factor receptor associated factor 2 is a mediator of NF-kappa B activation by latent infection membrane protein 1, the Epstein-Barr virus transforming protein. Kaye KM, et al. Proc Natl Acad Sci U S A, 1996 Oct 1. PMID 8855313, Free PMC Article
    3. Association of a TANK gene polymorphism with outcomes of hepatitis B virus infection in a Chinese Han population. Song QL, et al. Viral Immunol, 2012 Feb. PMID 22225470
    4. TRAF family member-associated NF-KB activator (TANK) gene polymorphism in chronic periodontitis and peri-implantitis patients. Kadkhodazadeh M, et al. J Long Term Eff Med Implants, 2012. PMID 23428248
    5. Association of a promoter haplotype (-1542G/-525C) in the tumor necrosis factor receptor associated factor-interacting protein gene with low bone mineral density in Japanese women. Ishida R, et al. Bone, 2003 Aug. PMID 14499357

    See all (110) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. TANK shapes an immunosuppressive microenvironment and predicts prognosis and therapeutic response in glioma.
      Title: TANK shapes an immunosuppressive microenvironment and predicts prognosis and therapeutic response in glioma.
    2. UBAC1/KPC2 Regulates TLR3 Signaling in Human Keratinocytes through Functional Interaction with the CARD14/CARMA2sh-TANK Complex.
      Title: UBAC1/KPC2 Regulates TLR3 Signaling in Human Keratinocytes through Functional Interaction with the CARD14/CARMA2sh-TANK Complex.
    3. CARD14/CARMA2sh and TANK differentially regulate poly(I:C)-induced inflammatory reaction in keratinocytes.
      Title: CARD14/CARMA2sh and TANK differentially regulate poly(I:C)-induced inflammatory reaction in keratinocytes.
    4. SNP rs197273 in TANK is associated both with gene expression and regional methylation. Neuroimaging studies among up to 1896 adolescents reveal that TANK is involved in the control of brain activity in areas of aversive interoceptive processing, including the insular cortex. TANK is associated with enhanced aversive emotional processing that better protects from the establishment of alcohol drinking behavior.
      Title: The Cortical Neuroimmune Regulator TANK Affects Emotional Processing and Enhances Alcohol Drinking: A Translational Study.
    5. Therefore, Seneca Valley virus suppressed antiviral interferon production to escape host antiviral innate immune responses by cleaving host adaptor molecules MAVS, TRIF, and TANK by its 3C protease.
      Title: Seneca Valley Virus Suppresses Host Type I Interferon Production by Targeting Adaptor Proteins MAVS, TRIF, and TANK for Cleavage.
    6. Data suggest that Encephalomyocarditis virus 3C protease cleaves TANK and disrupts the TANK-TBK1-IKKepsilon-IRF3 complex, resulting in reduction in IRF3 phosphorylation and type I interferon production. (TANK = TRAF family member associated NFKB activator; TBK1 = TANK binding kinase 1; IKKepsilon = inhibitor of nuclear factor kappa B kinase subunit epsilon; IRF3 = interferon regulatory factor 3)
      Title: Encephalomyocarditis virus 3C protease attenuates type I interferon production through disrupting the TANK-TBK1-IKKε-IRF3 complex.
    7. Molecular basis for TANK recognition by TRAF1 revealed by the crystal structure of TRAF1/TANK complex has been reported.
      Title: Molecular basis for TANK recognition by TRAF1 revealed by the crystal structure of TRAF1/TANK complex.
    8. these results suggest that TANK is a novel target of some viral proteases, indicating that some positive RNA viruses have evolved to utilize their major proteases to regulate NF-kappaB activation.
      Title: Encephalomyocarditis Virus 3C Protease Relieves TRAF Family Member-associated NF-κB Activator (TANK) Inhibitory Effect on TRAF6-mediated NF-κB Signaling through Cleavage of TANK.
    9. TANK serves as an important negative regulator of NF-kappaB signaling cascades induced by genotoxic stress and IL-1R/Toll-like receptor stimulation in a manner dependent on MCPIP1/USP10-mediated TRAF6 deubiquitination.
      Title: TRAF Family Member-associated NF-κB Activator (TANK) Inhibits Genotoxic Nuclear Factor κB Activation by Facilitating Deubiquitinase USP10-dependent Deubiquitination of TRAF6 Ligase.
    10. Two SNPs in TANK (rs17705608 and rs7309) were significantly associated with breast cancer risk in our study sample.
      Title: Genetic variation in TLR or NFkappaB pathways and the risk of breast cancer: a case-control study.
    Submit: New GeneRIF Correction See all GeneRIFs (26)

    Phenotypes

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    Find tests for this gene in the NIH Genetic Testing Registry (GTR)

    Review eQTL and phenotype association data in this region using PheGenI

    EBI GWAS Catalog

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

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    contributes_to cysteine-type deubiquitinase activity IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    enables deubiquitinase activator activity IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    enables metal ion binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables molecular adaptor activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables molecular function inhibitor activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables ubiquitin protein ligase binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in DNA damage response IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in cellular response to interleukin-1 IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in cellular response to ionizing radiation IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in cellular response to tumor necrosis factor IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in defense response to virus NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    involved_in negative regulation of canonical NF-kappaB signal transduction IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in negative regulation of tumor necrosis factor-mediated signaling pathway IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in positive regulation of protein deubiquitination IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in positive regulation of type I interferon production IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in positive regulation of ubiquitin-specific protease activity IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in signal transduction TAS
    Traceable Author Statement
    more info
    		 PubMed 
    involved_in type I interferon-mediated signaling pathway NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    Component Evidence Code Pubs
    is_active_in cytoplasm IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in cytosol IDA
    Inferred from Direct Assay
    more info
    		  
    located_in cytosol TAS
    Traceable Author Statement
    more info
    		  
    part_of protein-containing complex IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    part_of serine/threonine protein kinase complex NAS
    Non-traceable Author Statement
    more info
    		 PubMed 

    General protein information

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

    NCBI Reference Sequences (RefSeq)

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    NEW Try the new Transcript table

    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_001199135.3 → NP_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
      D3DPB5, Q7Z4J6, Q92844, Q92885
      UniProtKB/TrEMBL
      B2R7S3, Q6NW12
      Related
      ENSP00000376505.2, ENST00000392749.7
      Conserved Domains (1) summary
      pfam12845
      Location:135 → 186
      TBD; TBD domain

    2. NM_004180.3 → NP_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)
      AC009299, AC009313
      Consensus CDS
      CCDS2215.1
      UniProtKB/Swiss-Prot
      D3DPB5, Q7Z4J6, Q92844, Q92885
      UniProtKB/TrEMBL
      B2R7S3, Q6NW12
      Related
      ENSP00000259075.2, ENST00000259075.6
      Conserved Domains (1) summary
      pfam12845
      Location:135 → 186
      TBD; TBD domain

    3. NM_133484.2 → NP_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)
      AC009299, AC009313
      Consensus CDS
      CCDS46436.1
      UniProtKB/TrEMBL
      E7EWR8
      Related
      ENSP00000385983.1, ENST00000403609.1

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

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

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000002.12 Reference GRCh38.p14 Primary Assembly

      Range
      161136963..161236230
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_047441820.1 → XP_047297776.1  TRAF family member-associated NF-kappa-B activator isoform X6

      UniProtKB/TrEMBL
      B2R7S3, Q6NW12

    2. XM_047441804.1 → XP_047297760.1  TRAF family member-associated NF-kappa-B activator isoform X1

    3. XM_005246207.4 → XP_005246264.3  TRAF family member-associated NF-kappa-B activator isoform X2

    4. XM_047441814.1 → XP_047297770.1  TRAF family member-associated NF-kappa-B activator isoform X5

      UniProtKB/TrEMBL
      B2R7S3, Q6NW12

    5. XM_047441806.1 → XP_047297762.1  TRAF family member-associated NF-kappa-B activator isoform X3

      UniProtKB/TrEMBL
      B2R7S3, Q6NW12

    6. XM_047441812.1 → XP_047297768.1  TRAF family member-associated NF-kappa-B activator isoform X5

      UniProtKB/TrEMBL
      B2R7S3, Q6NW12

    7. XM_047441805.1 → XP_047297761.1  TRAF family member-associated NF-kappa-B activator isoform X3

      UniProtKB/TrEMBL
      B2R7S3, Q6NW12

    8. XM_047441809.1 → XP_047297765.1  TRAF family member-associated NF-kappa-B activator isoform X4

      UniProtKB/TrEMBL
      B2R7S3, Q6NW12

    9. XM_024452335.2 → XP_024308103.1  TRAF family member-associated NF-kappa-B activator isoform X6

      UniProtKB/TrEMBL
      B2R7S3, Q6NW12
      Conserved Domains (1) summary
      pfam12845
      Location:164 → 215
      TBD; TBD domain

    10. XM_047441821.1 → XP_047297777.1  TRAF family member-associated NF-kappa-B activator isoform X7

      UniProtKB/Swiss-Prot
      D3DPB5, Q7Z4J6, Q92844, Q92885
      UniProtKB/TrEMBL
      B2R7S3, Q6NW12

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060926.1 Alternate T2T-CHM13v2.0

      Range
      161595211..161694538
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054340043.1 → XP_054196018.1  TRAF family member-associated NF-kappa-B activator isoform X6

      UniProtKB/TrEMBL
      B2R7S3, Q6NW12

    2. XM_054340035.1 → XP_054196010.1  TRAF family member-associated NF-kappa-B activator isoform X2

    3. XM_054340041.1 → XP_054196016.1  TRAF family member-associated NF-kappa-B activator isoform X5

      UniProtKB/TrEMBL
      B2R7S3, Q6NW12

    4. XM_054340037.1 → XP_054196012.1  TRAF family member-associated NF-kappa-B activator isoform X3

      UniProtKB/TrEMBL
      B2R7S3, Q6NW12

    5. XM_054340038.1 → XP_054196013.1  TRAF family member-associated NF-kappa-B activator isoform X8

      UniProtKB/TrEMBL
      B2R7S3, Q6NW12

    6. XM_054340040.1 → XP_054196015.1  TRAF family member-associated NF-kappa-B activator isoform X5

      UniProtKB/TrEMBL
      B2R7S3, Q6NW12

    7. XM_054340036.1 → XP_054196011.1  TRAF family member-associated NF-kappa-B activator isoform X3

      UniProtKB/TrEMBL
      B2R7S3, Q6NW12

    8. XM_054340039.1 → XP_054196014.1  TRAF family member-associated NF-kappa-B activator isoform X4

      UniProtKB/TrEMBL
      B2R7S3, Q6NW12

    9. XM_054340042.1 → XP_054196017.1  TRAF family member-associated NF-kappa-B activator isoform X6

      UniProtKB/TrEMBL
      B2R7S3, Q6NW12

    10. XM_054340044.1 → XP_054196019.1  TRAF family member-associated NF-kappa-B activator isoform X7

      UniProtKB/Swiss-Prot
      D3DPB5, Q7Z4J6, Q92844, Q92885
      UniProtKB/TrEMBL
      B2R7S3, Q6NW12

    11. XM_054340045.1 → XP_054196020.1  TRAF family member-associated NF-kappa-B activator isoform X9

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q92844.2 GenPept UniProtKB/Swiss-Prot:Q92844

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