U.S. flag

An official website of the United States government

Format

Send to:

Choose Destination
    • Showing Current items.

    TRAF6 TNF receptor associated factor 6 [ Homo sapiens (human) ]

    Gene ID: 7189, updated on 26-Feb-2024

    Summary

    Official Symbol
    TRAF6provided by HGNC
    Official Full Name
    TNF receptor associated factor 6provided by HGNC
    Primary source
    HGNC:HGNC:12036
    See related
    Ensembl:ENSG00000175104 MIM:602355; AllianceGenome:HGNC:12036
    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
    RNF85; MGC:3310
    Summary
    The protein encoded by this gene is a member of the TNF receptor associated factor (TRAF) protein family. TRAF proteins are associated with, and mediate signal transduction from, members of the TNF receptor superfamily. This protein has an amino terminal RING domain which is followed by four zinc-finger motifs, a central coiled-coil region and a highly conserved carboxyl terminal domain, known as the TRAF-C domain and mediates signaling from members of the TNF receptor superfamily as well as the Toll/IL-1 family. Signals from receptors such as CD40, TNFSF11/RANCE and IL-1 have been shown to be mediated by this protein. This protein also interacts with various protein kinases including IRAK1/IRAK, SRC and PKCzeta, which provides a link between distinct signaling pathways. This protein functions as a signal transducer in the NF-kappaB pathway that activates IkappaB kinase (IKK) in response to proinflammatory cytokines. The interaction of this protein with UBE2N/UBC13, and UBE2V1/UEV1A, which are ubiquitin conjugating enzymes catalyzing the formation of polyubiquitin chains, has been found to be required for IKK activation by this protein. This protein also interacts with the transforming growth factor (TGF) beta receptor complex and is required for Smad-independent activation of the JNK and p38 kinases. The protein encoded by this gene is a key molecule in antiviral innate and antigen-specific immune responses. [provided by RefSeq, Nov 2021]
    Annotation information
    Note: This gene has been reviewed for its involvement in coronavirus biology, and is involved in immune response or antiviral activity.
    Expression
    Ubiquitous expression in bone marrow (RPKM 5.9), thyroid (RPKM 3.6) and 25 other tissues See more
    Orthologs
    NEW
    Try the new Gene table
    Try the new Transcript table

    Genomic context

    See TRAF6 in Genome Data Viewer
    Location:
    11p12
    Exon count:
    8
    Annotation release Status Assembly Chr Location
    RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 11 NC_000011.10 (36483769..36510272, complement)
    RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 11 NC_060935.1 (36626229..36653443, complement)
    105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 11 NC_000011.9 (36505319..36531822, complement)

    Chromosome 11 - NC_000011.10Genomic Context describing neighboring genes Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr11:36310336-36311038 Neighboring gene COMM domain containing 9 Neighboring gene proline rich 5 like Neighboring gene Sharpr-MPRA regulatory region 5372 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr11:36398745-36399316 Neighboring gene Sharpr-MPRA regulatory region 14138 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 4632 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr11:36476801-36477325 Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr11:36522348-36523547 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 4633 Neighboring gene recombination activating 1 Neighboring gene NANOG hESC enhancer GRCh37_chr11:36603130-36603633 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 4634 Neighboring gene intraflagellar transport associated protein Neighboring gene recombination activating 2

    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 Functions

    What's a GeneRIF?

    HIV-1 interactions

    Protein interactions

    Protein Gene Interaction Pubs
    Nef nef The interaction of HIV-1 Nef with TRAF2, TRAF5, and TRAF6 proteins activates NF-kappaB, leading to the degradation of IkappaB-alpha and the increased phosphorylation of IKK-alpha and IKK-beta in monocyte-derived macrophages PubMed
    nef HIV-1 Nef interacts with TRAF2, TRAF5, and TRAF6 proteins via its C-terminal region (residues 55-206) in monocyte-derived macrophages PubMed
    nef TRAF2 and TRAF6 proteins are required for the HIV-1 Nef-induced tyrosine phosphorylation of STAT1 and STAT2 proteins PubMed
    nef The acidic cluster AQEEEE (residues 64-69) of HIV-1 Nef binds to the residues R392, M450, R466, K469, F471, and Y473 of TRAF6 PubMed
    Vpr vpr The ability of HIV-1 Vpr to activate NF-kappaB or activator protein 1-dependent luciferase expression requires TAK1, TRAF6, or TAB3 in cells PubMed
    vpr HIV-1 Vpr-induced phosphorylation of TAK1 requires TRAF6 and Vpr increases the polyubiquitination of TAK1 in cells PubMed

    Go to the HIV-1, Human Interaction Database

    Pathways from PubChem

    Interactions

    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

    Markers

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables histone deacetylase binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    enables identical protein binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    enables protein kinase B binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    enables tumor necrosis factor receptor binding IEA
    Inferred from Electronic Annotation
    more info
     
    enables ubiquitin conjugating enzyme binding IDA
    Inferred from Direct Assay
    more info
    PubMed 
    enables ubiquitin protein ligase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    enables ubiquitin protein ligase activity IDA
    Inferred from Direct Assay
    more info
    PubMed 
    enables ubiquitin-protein transferase activity EXP
    Inferred from Experiment
    more info
    PubMed 
    enables ubiquitin-protein transferase activity TAS
    Traceable Author Statement
    more info
     
    enables ubiquitin-ubiquitin ligase activity IDA
    Inferred from Direct Assay
    more info
    PubMed 
    enables zinc ion binding IEA
    Inferred from Electronic Annotation
    more info
     
    Process Evidence Code Pubs
    involved_in DNA damage response IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in Fc-epsilon receptor signaling pathway TAS
    Traceable Author Statement
    more info
     
    involved_in MyD88-dependent toll-like receptor signaling pathway TAS
    Traceable Author Statement
    more info
     
    involved_in T cell receptor signaling pathway IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in T cell receptor signaling pathway IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in T cell receptor signaling pathway TAS
    Traceable Author Statement
    more info
     
    involved_in T-helper 1 type immune response IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in TRIF-dependent toll-like receptor signaling pathway TAS
    Traceable Author Statement
    more info
     
    involved_in activation of NF-kappaB-inducing kinase activity IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in activation of protein kinase activity IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in antigen processing and presentation of exogenous peptide antigen via MHC class II IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in antiviral innate immune response IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in autophagosome assembly IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in bone resorption IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in canonical NF-kappaB signal transduction IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in canonical NF-kappaB signal transduction IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in canonical NF-kappaB signal transduction TAS
    Traceable Author Statement
    more info
     
    involved_in cellular response to cytokine stimulus IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    acts_upstream_of_or_within cellular response to lipopolysaccharide IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in cytoplasmic pattern recognition receptor signaling pathway IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in cytoplasmic pattern recognition receptor signaling pathway TAS
    Traceable Author Statement
    more info
     
    involved_in in utero embryonic development IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in innate immune response IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    involved_in interleukin-1-mediated signaling pathway TAS
    Traceable Author Statement
    more info
     
    involved_in interleukin-17-mediated signaling pathway IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in interleukin-17A-mediated signaling pathway IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in interleukin-33-mediated signaling pathway IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in lipopolysaccharide-mediated signaling pathway IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    involved_in myeloid dendritic cell differentiation IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in negative regulation of DNA-templated transcription IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in negative regulation of transcription by RNA polymerase II IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in neural tube closure IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in non-canonical NF-kappaB signal transduction IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in odontogenesis of dentin-containing tooth IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in ossification IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in osteoclast differentiation IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in positive regulation of DNA-binding transcription factor activity IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in positive regulation of JUN kinase activity IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in positive regulation of JUN kinase activity NAS
    Non-traceable Author Statement
    more info
    PubMed 
    involved_in positive regulation of NF-kappaB transcription factor activity IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    involved_in positive regulation of NF-kappaB transcription factor activity IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in positive regulation of NF-kappaB transcription factor activity IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in positive regulation of T cell cytokine production IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in positive regulation of T cell proliferation IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in positive regulation of canonical NF-kappaB signal transduction IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in positive regulation of interleukin-12 production IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in positive regulation of interleukin-2 production IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in positive regulation of interleukin-6 production IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in positive regulation of leukocyte adhesion to vascular endothelial cell IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in positive regulation of lipopolysaccharide-mediated signaling pathway IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in positive regulation of osteoclast differentiation IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in positive regulation of protein ubiquitination NAS
    Non-traceable Author Statement
    more info
    PubMed 
    involved_in positive regulation of transcription by RNA polymerase II IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in positive regulation of transcription by RNA polymerase II NAS
    Non-traceable Author Statement
    more info
    PubMed 
    involved_in positive regulation of transcription regulatory region DNA binding IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in positive regulation of type I interferon production IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in protein K63-linked ubiquitination IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    involved_in protein K63-linked ubiquitination IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in protein K63-linked ubiquitination IGI
    Inferred from Genetic Interaction
    more info
    PubMed 
    acts_upstream_of_or_within protein autoubiquitination IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in protein autoubiquitination IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in protein autoubiquitination TAS
    Traceable Author Statement
    more info
    PubMed 
    involved_in protein polyubiquitination IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in regulation of apoptotic process IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in regulation of canonical NF-kappaB signal transduction IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    involved_in regulation of immunoglobulin production IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in response to interleukin-1 IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in stimulatory C-type lectin receptor signaling pathway TAS
    Traceable Author Statement
    more info
     
    involved_in toll-like receptor 3 signaling pathway TAS
    Traceable Author Statement
    more info
     
    involved_in toll-like receptor 4 signaling pathway IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in tumor necrosis factor-mediated signaling pathway IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    Component Evidence Code Pubs
    part_of CD40 receptor complex ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    located_in cell cortex IEA
    Inferred from Electronic Annotation
    more info
     
    is_active_in cytoplasm IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    is_active_in cytoplasm IC
    Inferred by Curator
    more info
    PubMed 
    is_active_in cytoplasm IDA
    Inferred from Direct Assay
    more info
    PubMed 
    located_in cytoplasm IDA
    Inferred from Direct Assay
    more info
    PubMed 
    located_in cytoplasmic side of plasma membrane ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    located_in cytosol TAS
    Traceable Author Statement
    more info
     
    located_in endosome membrane TAS
    Traceable Author Statement
    more info
     
    is_active_in extrinsic component of cytoplasmic side of plasma membrane IC
    Inferred by Curator
    more info
    PubMed 
    is_active_in extrinsic component of cytoplasmic side of plasma membrane IDA
    Inferred from Direct Assay
    more info
    PubMed 
    located_in lipid droplet ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    located_in nucleus IDA
    Inferred from Direct Assay
    more info
    PubMed 
    located_in perinuclear region of cytoplasm IDA
    Inferred from Direct Assay
    more info
    PubMed 
    located_in plasma membrane IDA
    Inferred from Direct Assay
    more info
    PubMed 
    located_in plasma membrane TAS
    Traceable Author Statement
    more info
     
    part_of plasma membrane signaling receptor complex IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    part_of protein-containing complex IDA
    Inferred from Direct Assay
    more info
    PubMed 

    General protein information

    Preferred Names
    TNF receptor-associated factor 6
    Names
    E3 ubiquitin-protein ligase TRAF6
    RING finger protein 85
    RING-type E3 ubiquitin transferase TRAF6
    TNF receptor-associated factor 6, E3 ubiquitin protein ligase
    interleukin-1 signal transducer
    NP_004611.1
    NP_665802.1

    NCBI Reference Sequences (RefSeq)

    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_004620.4NP_004611.1  TNF receptor-associated factor 6

      See identical proteins and their annotated locations for NP_004611.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) lacks a segment in the 5' UTR, compared to variant 1. Variants 1 and 2 encode the same protein.
      Source sequence(s)
      AC009656, AK292978, BQ187062
      Consensus CDS
      CCDS7901.1
      UniProtKB/Swiss-Prot
      A6NKI7, A8KAB3, D3DR16, Q8NEH5, Q9Y4K3
      Related
      ENSP00000433623.1, ENST00000526995.6
      Conserved Domains (3) summary
      cd00162
      Location:69107
      RING; RING-finger (Really Interesting New Gene) domain, a specialized type of Zn-finger of 40 to 60 residues that binds two atoms of zinc; defined by the 'cross-brace' motif C-X2-C-X(9-39)-C-X(1-3)- H-X(2-3)-(N/C/H)-X2-C-X(4-48)C-X2-C; probably involved in ...
      cd03776
      Location:351500
      MATH_TRAF6; Tumor Necrosis Factor Receptor (TNFR)-Associated Factor (TRAF) family, TRAF6 subfamily, TRAF domain, C-terminal MATH subdomain; composed of proteins with similarity to human TRAF6, including the Drosophila protein DTRAF2. TRAF molecules serve as adapter ...
      pfam02176
      Location:204261
      zf-TRAF; TRAF-type zinc finger
    2. NM_145803.3NP_665802.1  TNF receptor-associated factor 6

      See identical proteins and their annotated locations for NP_665802.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the longer transcript. Variants 1 and 2 encode the same protein.
      Source sequence(s)
      AC009656, AC061999, BC031052, BQ187062
      Consensus CDS
      CCDS7901.1
      UniProtKB/Swiss-Prot
      A6NKI7, A8KAB3, D3DR16, Q8NEH5, Q9Y4K3
      Related
      ENSP00000337853.5, ENST00000348124.5
      Conserved Domains (3) summary
      cd00162
      Location:69107
      RING; RING-finger (Really Interesting New Gene) domain, a specialized type of Zn-finger of 40 to 60 residues that binds two atoms of zinc; defined by the 'cross-brace' motif C-X2-C-X(9-39)-C-X(1-3)- H-X(2-3)-(N/C/H)-X2-C-X(4-48)C-X2-C; probably involved in ...
      cd03776
      Location:351500
      MATH_TRAF6; Tumor Necrosis Factor Receptor (TNFR)-Associated Factor (TRAF) family, TRAF6 subfamily, TRAF domain, C-terminal MATH subdomain; composed of proteins with similarity to human TRAF6, including the Drosophila protein DTRAF2. TRAF molecules serve as adapter ...
      pfam02176
      Location:204261
      zf-TRAF; TRAF-type zinc finger

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

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

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000011.10 Reference GRCh38.p14 Primary Assembly

      Range
      36483769..36510272 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060935.1 Alternate T2T-CHM13v2.0

      Range
      36626229..36653443 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)