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TRAF6 Gene

protein-coding   GIFtS: 67
GCID: GC11M036467

TNF Receptor-Associated Factor 6, E3 Ubiquitin Protein Ligase

(Previous name: TNF receptor-associated factor 6)
Microbiology & Infectious Diseases Congress
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(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
TNF Receptor-Associated Factor 6, E3 Ubiquitin Protein Ligase1 2     E3 Ubiquitin-Protein Ligase TRAF62 3
TNF Receptor-Associated Factor 61 2     RING Finger Protein 852 3
Interleukin-1 Signal Transducer2 3     MGC:33102
RNF852 3     EC 6.3.2.-3

External Ids:    HGNC: 120361   Entrez Gene: 71892   Ensembl: ENSG000001751047   OMIM: 6023555   UniProtKB: Q9Y4K33   

Export aliases for TRAF6 gene to outside databases

Previous GC identifers: GC11M038067 GC11M037188 GC11M036549 GC11M036475 GC11M036212


(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 TRAF6 Gene:
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 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. 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. Two
alternatively spliced transcript variants, encoding an identical protein, have been reported. (provided by
RefSeq, Feb 2012)

GeneCards Summary for TRAF6 Gene:
TRAF6 (TNF receptor-associated factor 6, E3 ubiquitin protein ligase) is a protein-coding gene. Diseases associated with TRAF6 include ectodermal dysplasia 10a, hypohidrotic/hair/nail type, autosomal dominant, and hypohidrotic ectodermal dysplasia. GO annotations related to this gene include protein kinase binding and signal transducer activity. An important paralog of this gene is TRAF1.

UniProtKB/Swiss-Prot: TRAF6_HUMAN, Q9Y4K3
Function: E3 ubiquitin ligase that, together with UBE2N and UBE2V1, mediates the synthesis of
'Lys-63'-linked-polyubiquitin chains conjugated to proteins, such as IKBKG, AKT1 and AKT2. Also mediates
ubiquitination of free/unanchored polyubiquitin chain that leads to MAP3K7 activation. Leads to the activation of
NF-kappa-B and JUN. May be essential for the formation of functional osteoclasts. Seems to also play a role in
dendritic cells (DCs) maturation and/or activation. Represses c-Myb-mediated transactivation, in B-lymphocytes.
Adapter protein that seems to play a role in signal transduction initiated via TNF receptor, IL-1 receptor and
IL-17 receptor. Regulates osteoclast differentiation by mediating the activation of adapter protein complex 1
(AP-1) and NF-kappa-B, in response to RANK-L stimulation. Together with MAP3K8, mediates CD40 signals that
activate ERK in B cells and macrophages, and thus may play a role in the regulation of immunoglobulin production

Gene Wiki entry for TRAF6 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_000011.10  NC_018922.2  NT_009237.19  
Regulatory elements:
   Regulatory transcription factor binding sites in the TRAF6 gene promoter:
         USF1   FOXJ2 (long isoform)   USF-1   STAT3   FOXJ2   NF-kappaB   NF-kappaB1   
         Other transcription factors

SwitchGear Promoter luciferase reporter plasmidTRAF6 promoter sequence
   Search Chromatin IP Primers for TRAF6

Epigenetics:
DNA Methylation CpG Assay Predesigned for Pyrosequencing in human, mouse, rat TRAF6


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

Entrez Gene cytogenetic band: 11p12   Ensembl cytogenetic band:  11p12   HGNC cytogenetic band: 11p12

TRAF6 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
TRAF6 gene location

GeneLoc information about chromosome 11         GeneLoc Exon Structure

GeneLoc location for GC11M036467:  view genomic region     (about GC identifiers)

Start:
36,505,317 bp from pter      End:
36,531,863 bp from pter
Size:
26,547 bases      Orientation:
minus 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: TRAF6_HUMAN, Q9Y4K3 (See protein sequence)
Recommended Name: TNF receptor-associated factor 6  
Size: 522 amino acids; 59573 Da
Subunit: Homotrimer. Homooligomer. N-terminal region is dimeric while C-terminal region is trimeric; maybe
providing a mode of oligomerization. Upon IL1B treatment, forms a complex with PELI1, IRAK1, IRAK4 and MYD88;
this complex recruits MAP3K7/TAK1, TAB1 and TAB2 to mediate NF-kappa-B activation. Direct binding of SMAD6 to
PELI1 prevents the complex formation and hence negatively regulates IL1R-TLR signaling and eventually
NF-kappa-B-mediated gene expression. Binds to TNFRSF5/CD40 and TNFRSF11A/RANK. Associates with NGFR, TNFRSF17,
IRAK2, IRAK3, RIPK2, MAP3K1, MAP3K5, MAP3K14, CSK, TRAF, TRAF-interacting protein TRIP and TNF receptor
associated protein TDP2. Interacts with IL17R. Interacts with SQSTM1 bridging NTRK1 and NGFR. Forms a ternary
complex with SQSTM1 and PRKCZ (By similarity). Interacts with PELI2 and PELI3. Binds UBE2V1. Interacts with
TAX1BP1. Interacts with ZNF675. Interacts with ARRB1 and ARRB2. Interacts with MAP3K7 and TAB1/MAP3K7IP1; during
IL-1 signaling. Interacts with UBE2N. Interacts with TGFBR1, HDAC1 and RANGAP1. Interacts with AKT1, AKT2 and
AKT3. Interacts (via TRAF domains) with NUMBL (via C-terminal). Interacts with RBCK1. Interacts with TRAF3IP2.
Interacts with LIMD1 (via LIM domains) (By similarity). Interacts with RSAD2/viperin (By similarity). Interacts
(via C-terminus) with EIF2AK2/PKR (via the kinase catalytic domain) (By similarity). Interacts with ZFAND5.
Interacts with IL1RL1. Interacts with TRAFD1. Interacts with AJUBA. Interacts with MAVS/IPS1. Interacts (via TRAF
domains) with WDR34 (via WD domains). Interacts with IFIT3 (via N-terminus). Interacts with TICAM1 and TICAM2.
Interacts with CARD14. Interacts with CD40 and MAP3K8; the interaction is required for ERK activation (By
similarity)
Selected PDB 3D structures from and Proteopedia for TRAF6 (see all 8):
1LB4 (3D)        1LB5 (3D)        1LB6 (3D)        2ECI (3D)        2JMD (3D)        3HCS (3D)    
Secondary accessions: A6NKI7 A8KAB3 D3DR16 Q8NEH5

Explore the universe of human proteins at neXtProt for TRAF6: NX_Q9Y4K3

Explore proteomics data for TRAF6 at MOPED

Post-translational modifications: 

  • Sumoylated on Lys-124, Lys-142 and Lys-453 with SUMO11
  • Polyubiquitinated on Lys-124; after cell stimulation with IL-1-beta or TGF-beta. This ligand-induced cell
    stimulation leads to dimerization/oligomerization of TRAF6 molecules, followed by auto-ubiquitination which
    involves UBE2N and UBE2V1 and leads to TRAF6 activation. This 'Lys-63' site-specific poly-ubiquitination appears
    to be associated with the activation of signaling molecules. Endogenous autoubiquitination occurs only for the
    cytoplasmic form1
  • Modification sites at neXtProt
  • Modification sites at PhosphoSitePlus

  • See TRAF6 Protein Expression from SPIRE MOPED, PaxDB, and MaxQB

    REFSEQ proteins (2 alternative transcripts): 
    NP_004611.1  NP_665802.1  

    ENSEMBL proteins: 
     ENSP00000433623   ENSP00000337853  
    Reactome Protein details: Q9Y4K3

    TRAF6 Human Recombinant Protein Products:

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    Novus Biologicals TRAF6 Proteins
    Novus Biologicals TRAF6 Lysates
    Browse Sino Biological Recombinant Proteins
    Browse Sino Biological Cell Lysates
    Browse ProSpec Recombinant Proteins
    Cloud-Clone Corp. Proteins for TRAF6

    TRAF6 Antibody Products:

    EMD Millipore Mono- and Polyclonal Antibodies for the study of TRAF6
    R&D Systems Antibodies for TRAF6 (TRAF-6)
    Cell Signaling Technology (CST) Antibodies for TRAF6 
    OriGene Antibodies for TRAF6
    OriGene Custom Antibody Services for TRAF6
    Novus Biologicals TRAF6 Antibodies
    Abcam antibodies for TRAF6
    Cloud-Clone Corp. Antibodies for TRAF6
    ThermoFisher Antibody for TRAF6
    LSBio Antibodies in human, mouse, rat for TRAF6

    TRAF6 Assay Products:

    Browse Kits and Assays available from EMD Millipore
    OriGene Custom Assay Services for TRAF6
    Browse R&D Systems for biochemical assays
    GenScript Custom Assay Services for TRAF6
    Browse Enzo Life Sciences for kits & assays
    Cloud-Clone Corp. ELISAs for TRAF6
    Cloud-Clone Corp. CLIAs for TRAF6


    (According to HGNC, IUPHAR, InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
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    HGNC Gene Families:
    RNF: RING-type (C3HC4) zinc fingers

    Selected InterPro protein domains (see all 8):
     IPR008974 TRAF-like
     IPR017907 Znf_RING_CS
     IPR002083 MATH
     IPR001841 Znf_RING
     IPR012227 TNF_rcpt--assoc_TRAF

    Graphical View of Domain Structure for InterPro Entry Q9Y4K3

    ProtoNet protein and cluster: Q9Y4K3

    3 Blocks protein domains:
    IPB001293 Zn-finger
    IPB001841 Zn-finger
    IPB002083 Meprin/TRAF-like MATH


    UniProtKB/Swiss-Prot: TRAF6_HUMAN, Q9Y4K3
    Domain: The coiled coil domain mediates homo- and hetero-oligomerization
    Domain: The MATH/TRAF domain binds to receptor cytoplasmic domains
    Similarity: Belongs to the TNF receptor-associated factor family. A subfamily
    Similarity: Contains 1 MATH domain
    Similarity: Contains 1 RING-type zinc finger
    Similarity: Contains 2 TRAF-type zinc fingers


    TRAF6 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: TRAF6_HUMAN, Q9Y4K3
    Function: E3 ubiquitin ligase that, together with UBE2N and UBE2V1, mediates the synthesis of
    'Lys-63'-linked-polyubiquitin chains conjugated to proteins, such as IKBKG, AKT1 and AKT2. Also mediates
    ubiquitination of free/unanchored polyubiquitin chain that leads to MAP3K7 activation. Leads to the activation of
    NF-kappa-B and JUN. May be essential for the formation of functional osteoclasts. Seems to also play a role in
    dendritic cells (DCs) maturation and/or activation. Represses c-Myb-mediated transactivation, in B-lymphocytes.
    Adapter protein that seems to play a role in signal transduction initiated via TNF receptor, IL-1 receptor and
    IL-17 receptor. Regulates osteoclast differentiation by mediating the activation of adapter protein complex 1
    (AP-1) and NF-kappa-B, in response to RANK-L stimulation. Together with MAP3K8, mediates CD40 signals that
    activate ERK in B cells and macrophages, and thus may play a role in the regulation of immunoglobulin production

         Genatlas biochemistry entry for TRAF6:
    tumor necrosis factor (TNF)-receptor-associated factor 6,cytoplasmic,involved in the activation of NFKB by
    TNFRSFs,associating with IRAK1 after stimulation by IL1B,also associating with TNFRSF11 and SRC and,in turn
    activating the kinase activity of SRC

         Enzyme Number (IUBMB): EC 6.3.2.-1

         Gene Ontology (GO): Selected molecular function terms (see all 12):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0004842ubiquitin-protein ligase activity TAS--
    GO:0004871signal transducer activity ----
    GO:0005515protein binding IPI10094049
    GO:0008270zinc ion binding IEA--
    GO:0019901protein kinase binding IPI19713527
         
    TRAF6 for ontologies           About GeneDecksing


    Phenotypes:
         5 GenomeRNAi human phenotypes for TRAF6:
     Decreased viability after Chla  Downregulation of NF-kappaB pa  Downregulation of NF-kappaB pa  Increased G1 DNA content 
     Increased cell death HMECs cel 

         Selected MGI mutant phenotypes (inferred from 6 alleles(MGI details for Traf6) (see all 17):
     cardiovascular system  cellular  craniofacial  endocrine/exocrine gland  growth/size/body 
     hematopoietic system  homeostasis/metabolism  immune system  integument  limbs/digits/tail 
     liver/biliary system  mortality/aging  pigmentation  renal/urinary system  reproductive system 

    TRAF6 for phenotypes           About GeneDecksing

    Animal Models:
         MGI mouse knock-outs for TRAF6: Traf6tm1Mak Traf6tm1Jino Traf6tm1Ywc

       inGenious Targeting Laboratory: Let us create your new Knockout/Knockin mouse model for TRAF6
       inGenious Targeting Laboratory: Contact us about creating complex and humanized mouse models for TRAF6

       genOway customized KO model: permanent, tissue-specific or time-controlled inactivation for TRAF6
       genOway customized Knockin model: humanization, point mutation, expression monitoring, etc. for TRAF6

    miRNA
    Products:
        
    miRTarBase miRNAs that target TRAF6:
    hsa-mir-146a-5p (MIRT000711), hsa-mir-146b-5p (MIRT005394)

    Block miRNA regulation of human, mouse, rat TRAF6 using miScript Target Protectors
    Selected qRT-PCR Assays for microRNAs that regulate TRAF6 (see all 56):
    hsa-miR-607 hsa-miR-15a hsa-miR-146a hsa-miR-1245 hsa-miR-374a* hsa-miR-424 hsa-miR-124 hsa-miR-149
    SwitchGear 3'UTR luciferase reporter plasmidTRAF6 3' UTR sequence
    Inhib. RNA
    Products:
        
    OriGene RNAi products in human, mouse, rat for TRAF6
    Predesigned siRNA for gene silencing in human, mouse, rat TRAF6

    Gene Editing
    Products:
    DNA2.0 Custom Protein Engineering Service for TRAF6

    Clone
    Products:
         
    OriGene clones in human, mouse for TRAF6 (see all 11)
    OriGene ORF clones in mouse, rat for TRAF6
    OriGene custom cloning services - gene synthesis, subcloning, mutagenesis, variant library, vector shuttling
    GenScript: all cDNA clones in your preferred vector (see all 2): TRAF6 (NM_004620)
    Browse Sino Biological Human cDNA Clones
    DNA2.0 Custom Codon Optimized Gene Synthesis Service for TRAF6
    Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat TRAF6

    Cell Line
    Products:
         
    GenScript Custom overexpressing Cell Line Services for TRAF6
    Browse ESI BIO Cell Lines and PureStem Progenitors for TRAF6 
    In Situ Assay
    Products:
       

     
    Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for TRAF6


    (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
    TRAF6_HUMAN, Q9Y4K3: Cytoplasm. Cytoplasm, cell cortex. Nucleus. Lipid droplet (By similarity). Note=Found in the
    nuclei of some aggressive B-cell lymphoma cell lines as well as in the nuclei of both resting and activated T-
    and B-lymphocytes. Found in punctate nuclear body protein complexes. Ubiquitination may occur in the cytoplasm
    and sumoylation in the nucleus. RSAD2/viperin recruits it to the lipid droplet (By similarity)
    Subcellular locations from COMPARTMENTS: 

    CompartmentConfidence
    nucleus5
    cytosol4
    endosome4
    plasma membrane3
    extracellular1
    vacuole1

    Gene Ontology (GO): Selected cellular component terms (see all 14):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0005634nucleus IDA18093978
    GO:0005730nucleolus IDA--
    GO:0005737cytoplasm IDA16378096
    GO:0005739mitochondrion IDA--
    GO:0005811lipid particle ISS--

    TRAF6 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 TRAF6 About   (see all 64)                                                                                              See pathways by source

    SuperPathContained pathways About
    1RANK Signaling in Osteoclasts
    BAFF in B-Cell Signaling0.92
    Apoptosis and survival APRIL and BAFF signaling0.39
    APRIL Pathway0.92
    RANK Pathway0.38
    RANK Signaling in Osteoclasts0.45
    RANKL/RANK Signaling Pathway0.31
    2NOD-like Receptor Signaling Pathways
    Toll-Like receptor Signaling Pathways0.58
    Immune response IL 1 signaling pathway0.42
    IL-1 Family Signaling Pathways0.44
    Immune response Role of TLRs 3 and 4 in cell antiviral response TICAM1 specific signaling pathways0.33
    Mucin expression in CF via TLRs, EGFR signaling pathways0.42
    3IL-17 Family Signaling Pathways
    IL-17 Family Signaling Pathways0.51
    Mucin expression in CF via IL 6, IL 17 signaling pathways0.48
    IL17 signaling pathway0.51
    4Interleukin-1 signaling
    Interleukin-1 signaling0.45
    IL-1 Signaling Pathway0.00
    IL1-mediated signaling events0.45
    5Toll Comparative Pathway
    Toll Comparative Pathway0.61
    IL-1 Pathway0.39
    TLR-TRIF Pathway0.61
    iNOS Signaling0.34
    Immune response MIF in innate immunity response0.46

    Pathways by source                                                                                                                                                                 See SuperPaths
    Show all pathways

    4 R&D Systems Pathways for TRAF6
        IL-1 Family Signaling Pathways
    IL-17 Family Signaling Pathways
    Toll-Like receptor Signaling Pathways
    TGF-beta Signaling Pathways

    Selected Downloadable PowerPoint Slides of GeneGlobe Pathway Central Maps for TRAF6 (see all 21)
        MAPK Signaling
    14-3-3 Induced Apoptosis
    Toll-Like Receptors Pathway
    TRAF Pathway
    TRAIL Pathway

    2 Cell Signaling Technology (CST) Pathways for TRAF6
        Apoptosis and Autophagy
    NF-kappaB Signaling

    Selected GeneGo (Thomson Reuters) Pathways for TRAF6 (see all 17)
        Immune response TLR3 and TLR4 induce TICAM1-specific signaling pathway
    Immune response Bacterial infections in normal airways
    Immune response MIF in innate immunity response
    Immune response IL-12-induced IFN-gamma production
    Immune response TLR signaling pathways

    Selected BioSystems Pathways for TRAF6 (see all 20)
        MAPK signaling pathway
    EBV LMP1 signaling
    Apoptosis Modulation and Signaling
    IL-1 Signaling Pathway
    BDNF signaling pathway

    Selected Reactome Pathways for TRAF6 (see all 24)
        NRIF signals cell death from the nucleus
    IKK complex recruitment mediated by RIP1
    FCERI mediated NF-kB activation
    TRAF6 mediated IRF7 activation in TLR7/8 or 9 signaling
    TRAF6 mediated IRF7 activation


    Selected Kegg Pathways  (Kegg details for TRAF6) (see all 20):
        MAPK signaling pathway
    NF-kappa B signaling pathway
    Ubiquitin mediated proteolysis
    Endocytosis
    Osteoclast differentiation

    UniProtKB/Swiss-Prot: TRAF6_HUMAN, Q9Y4K3
    Pathway: Protein modification; protein ubiquitination


    TRAF6 for pathways           About GeneDecksing

        Pathway & Disease-focused RT2 Profiler PCR Arrays including TRAF6 (see all 13): 

              Antiviral Response in human mouse rat
              Toll-Like Receptor Signaling Pathway in human mouse rat
              Inflammasomes in human mouse rat
              T-cell & B-cell Activation in human mouse rat
              Inflammatory Response & Autoimmunity 384HT in human mouse rat

    Interactions:

        GeneGlobe Interaction Network for TRAF6

    Selected Interacting proteins for TRAF6 (Q9Y4K31, 2, 3) via UniProtKB, MINT, STRING, and/or I2D (see all 521)
    InteractantInteraction Details
    GeneCardExternal ID(s)
    TAX1BP1Q86VP11, 2, 3EBI-359276,EBI-529518 MINT-6505191 MINT-5226512 MINT-6505206 MINT-6505175 MINT-6505156 I2D: score=8 
    UBCP0CG481, 2, 3EBI-359276,EBI-3390054 MINT-5226492 MINT-5226478 MINT-7297740 MINT-49604 MINT-6505225 I2D: score=6 
    MALT1Q9UDY81, 2, 3EBI-359276,EBI-1047372 MINT-6177590 MINT-6177582 MINT-6177625 I2D: score=7 
    SQSTM1Q135011, 2, 3EBI-359276,EBI-307104 MINT-2844341 MINT-2844322 I2D: score=6 
    SPHK1Q9NYA11, 2, 3EBI-359276,EBI-985303 MINT-4050292 MINT-4050310 I2D: score=2 
    About this table

    Gene Ontology (GO): Selected biological process terms (see all 69):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0000122negative regulation of transcription from RNA polymerase II promoter IMP18093978
    GO:0000187activation of MAPK activity TAS--
    GO:0000209protein polyubiquitination IDA15125833
    GO:0001503ossification IEA--
    GO:0001843neural tube closure IEA--

    TRAF6 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)
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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 TRAF6

    Selected Novoseek inferred chemical compound relationships for TRAF6 gene (see all 15)    About this table
    Compound   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    tab-2 93.3 38 16251197 (4), 10882101 (4), 20222921 (4), 11259596 (3) (see all 17)
    tab-1 83.1 5 16382137 (1), 18353240 (1), 12242293 (1), 17633026 (1) (see all 5)
    bcma 46.1 1 10908663 (1)
    poly(i-c) 40.9 2 14982987 (2)
    zinc 31.9 13 19465916 (3), 11751921 (2), 11438463 (1), 9928991 (1) (see all 10)
    peptidoglycan 26.3 4 17182109 (1), 16230348 (1), 11254583 (1)
    nadph 26.2 2 16052631 (1), 16286467 (1)
    phosphatidylinositol 20.2 2 11406619 (1), 14996708 (1)
    tyrosine 10.7 3 18070880 (2), 10635328 (1)
    threonine 9.65 2 8837778 (1), 10635328 (1)



    TRAF6 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 TRAF6 gene (2 alternative transcripts): 
    NM_004620.3  NM_145803.2  

    Unigene Cluster for TRAF6:

    TNF receptor-associated factor 6, E3 ubiquitin protein ligase
    Hs.444172  [show with all ESTs]
    Unigene Representative Sequence: NM_145803
    3 Ensembl transcripts including schematic representations, and UCSC links where relevant:
    ENST00000526995(uc001mwq.2 uc001mws.2) ENST00000348124 ENST00000529150

    Congresses - knowledge worth sharing:
    European Congress of Clinical Microbiology and Infectious Diseases (ECCMID) 10 - 13 May 2014

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    hsa-miR-607 hsa-miR-15a hsa-miR-146a hsa-miR-1245 hsa-miR-374a* hsa-miR-424 hsa-miR-124 hsa-miR-149
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    Additional mRNA sequence: 

    AK128396.1 AK292978.1 BC031052.1 U78798.1 

    3 DOTS entries:

    DT.100676763  DT.95268361  DT.211093 

    Selected AceView cDNA sequences (see all 124):

    BE672410 BX110845 AA683502 AL544165 NM_145803 BF765244 AA972639 BM930694 
    AA361471 CR590964 CR612801 BG024717 AA906241 BU743323 BM855452 NM_004620 
    BM150289 BU739857 AA917774 BX950992 AW339590 BE222017 AW467912 AA456692 

    GeneLoc Exon Structure

    3 Alternative Splicing Database (ASD) splice patterns (SP) for TRAF6    About this scheme

    ExUns: 1a · 1b ^ 2 ^ 3 ^ 4 ^ 5 ^ 6 ^ 7 ^ 8a · 8b
    SP1:                                                            
    SP2:              -                                             
    SP3:              -     -                                       


    ECgene alternative splicing isoforms for TRAF6

    (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)
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    TRAF6 expression in normal human tissues (normalized intensities)      TRAF6 embryonic expression: see
    See probesets specificity/sensitivity at GeneAnnot
    About this imageBioGPS <intensity>2/3
    CGAP TAG: CCAGACTGAC
    TRAF6 Expression
    About this image


    TRAF6 expression in embryonic tissues and stem cells    About this table
    Data from LifeMap, the Embryonic Development and Stem Cells Database
     selected tissues (see all 3) fully expand
     
     Tooth (Integumentary System)    fully expand to see all 6 entries
             Dental Placode Cells Dental Placode
     
     Epithelial Cells
             Dental Placode Cells Dental Placode
     
     Pancreas (Endocrine System)
    TRAF6 Protein expression data from MOPED1, PaxDb2 and MaxQB3    About this image

    TRAF6 Protein Expression

    SOURCE GeneReport for Unigene cluster: Hs.444172

    UniProtKB/Swiss-Prot: TRAF6_HUMAN, Q9Y4K3
    Tissue specificity: Expressed in heart, brain, placenta, lung, liver, skeletal muscle, kidney and pancreas

        Pathway & Disease-focused RT2 Profiler PCR Arrays including TRAF6 (see all 13): 
              Antiviral Response in human mouse rat
              Toll-Like Receptor Signaling Pathway in human mouse rat
              Inflammasomes in human mouse rat
              T-cell & B-cell Activation in human mouse rat
              Inflammatory Response & Autoimmunity 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 animals.

    Orthologs for TRAF6 gene from Selected species (see all 17)    About this table
    Organism Taxonomic
    classification
    Gene Description Human
    Similarity
    Orthology
    Type
    Details
    mouse
    (Mus musculus)
    Mammalia Traf61 , 5 TNF receptor-associated factor 61, 5 87.1(n)1
    89.27(a)1
      2 (53.90 cM)5
    220341  NM_009424.21  NP_033450.21 
     1016784295 
    chicken
    (Gallus gallus)
    Aves TRAF61 TNF receptor-associated factor 6, E3 ubiquitin protein more 72.67(n)
    76.25(a)
      423163  XM_004941547.1  XP_004941604.1 
    lizard
    (Anolis carolinensis)
    Reptilia TRAF66
    Uncharacterized protein
    70(a)
    1 ↔ 1
    1(53549466-53583943)
    African clawed frog
    (Xenopus laevis)
    Amphibia Xl.146822 Xenopus laevis transcribed sequence with moderate similarity more 73.58(n)    CF342115.1 
    zebrafish
    (Danio rerio)
    Actinopterygii wufi15f022 wufi15f02 76.73(n)   327524  BC055214.1 
    fruit fly
    (Drosophila melanogaster)
    Insecta Traf61 TNF-receptor-associated factor 6 43.22(n)
    32.91(a)
      31746  NM_078525.3  NP_511080.2 
    worm
    (Caenorhabditis elegans)
    Secernentea trf-16
    Protein TRF-1 (trf-1) mRNA, complete cds
    23(a)
    many ↔ many
    III(13430462-13433438) WBGene00006612


    ENSEMBL Gene Tree for TRAF6 (if available)
    TreeFam Gene Tree for TRAF6 (if available)

    (Paralogs according to 1HomoloGene,
    2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
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    Paralogs for TRAF6 gene
    TRAF12  TRAF42  TRAF52  TRAF22  TRAF32  
    1 SIMAP similar gene for TRAF6 using alignment to 1 protein entry:     TRAF6_HUMAN:
    TRAF2

    TRAF6 for paralogs           About GeneDecksing


    1 Pseudogenes.org Pseudogene for TRAF6
    PGOHUM00000238497


    (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 TRAF6 (see all 658)    About this table    
    Genomic DataTranscription Related DataAllele Frequencies
    SNP IDValidClinical
    significance
    Chr 11 posSequence#AA
    Chg
    TypeMore#Allele
    freq
    PopTotal
    sample
    More
    ----------
    rs3314671,2
    C,H--36504820(+) AAATGA/GAACCT 2 -- ds500113Minor allele frequency- G:0.01NA WA CSA EA 376
    rs71089131,2
    C,F--36504828(+) CCTCAC/ATTACC 2 -- ds50011Minor allele frequency- A:0.03WA 118
    rs71091691,2
    C,F,A,H--36504867(+) TTCAAG/ATGAAA 2 -- ds500123Minor allele frequency- A:0.19NS EA NA WA CSA 2351
    rs1490953501,2
    --36504888(+) GAAACG/TGTTCT 2 -- ds50010--------
    rs1825622141,2
    --36504955(+) CTAAGG/TAGTTA 2 -- ds50010--------
    rs71282831,2
    C,F,A,H--36505048(+) TGAGGG/TCAGGA 2 -- ds50015Minor allele frequency- T:0.40NA WA 10
    rs358715041,2
    C--36505087(+) AAACC-/CTGTCTC 2 -- ds50010--------
    rs1862201421,2
    --36505129(+) TTAGTC/TGGGTG 2 -- ds50010--------
    rs1396209771,2
    --36505158(+) GTTTC-/AGCTAC 2 -- ds50010--------
    rs1911225251,2
    --36505197(+) GAACCC/TGGGAG 2 -- ds50010--------

    HapMap Linkage Disequilibrium report for TRAF6 (36505317 - 36531863 bp)

    Structural Variations
         Database of Genomic Variants (DGV) 6 variations for TRAF6:    About this table    
    Variant IDTypeSubtypePubMed ID
    esv2678965CNV Deletion23128226
    esv2422305CNV Duplication17116639
    esv1601897CNV Insertion17803354
    esv1648317CNV Insertion17803354
    esv272785CNV Insertion20981092
    nsv467791CNV Gain19166990

    Human Gene Mutation Database (HGMD): TRAF6
    Site Specific Mutation Identification with PCR Assays
    SeqTarget long-range PCR primers for resequencing TRAF6
    DNA2.0 Custom Variant and Variant Library Synthesis for TRAF6

    (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.)
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    OMIM gene information: 602355    OMIM disorders: --

    Selected diseases for TRAF6 (see all 66):    About MalaCards
    ectodermal dysplasia 10a, hypohidrotic/hair/nail type, autosomal dominant    hypohidrotic ectodermal dysplasia    n syndrome    ectodermal dysplasia
    malt lymphoma    trypanosomiasis    dengue hemorrhagic fever    toxoplasmosis
    chagas disease    laryngeal carcinoma    osteoporosis    hemorrhagic fever
    kawasaki disease    measles    human t-cell leukemia virus type 1    pertussis
    synovitis    narcolepsy    leishmaniasis    psoriatic arthritis

    1 disease from the University of Copenhagen DISEASES database for TRAF6:
    Hypohidrotic ectodermal dysplasia

    TRAF6 for disorders           About GeneDecksing


    Congresses - knowledge worth sharing:
    The International Symposium on Pneumococci and Pneumococcal Diseases (ISPPD) 9 - 13 March 2014
    Alzheimer's & Parkinson's Diseases Congress (ADPD) 18 - 22 March 2015

    Selected Novoseek inferred disease relationships for TRAF6 gene (see all 13)    About this table

    Disease   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    necrosis 71.7 88 12566447 (2), 9625770 (2), 14550571 (2), 18759964 (2) (see all 63)
    tumors 56.5 86 12566447 (2), 9625770 (2), 14550571 (2), 18759964 (2) (see all 60)
    inflammation 38.9 10 16143987 (2), 17925880 (1), 18093978 (1), 18772140 (1) (see all 5)
    ectodermal dysplasia 25.6 1 16527194 (1)
    bone diseases 14.6 1 18778854 (1)
    rheumatoid arthritis 6.12 2 18759964 (1)
    virus infection 3.1 3 19479062 (1), 20097753 (1)
    bone loss 1.75 2 12716453 (1), 15320903 (1)
    pathological processes 0 1 16697380 (1)
    osteoporosis 0 1 14579250 (1)

    Genetic Association Database (GAD): TRAF6
    Human Genome Epidemiology (HuGE) Navigator: TRAF6 (28 documents)

    Export disorders for TRAF6 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 TRAF6 gene, integrated from 10 sources (see all 597):
    (articles sorted by number of sources associating them with TRAF6)
        Utopia: connect your pdf to the dynamic
    world of online information

    1. TRAF6 is a signal transducer for interleukin-1. (PubMed id 8837778)1, 2, 3, 9 Cao Z.... Goeddel D.V. (Nature 1996)
    2. NUMBL interacts with TRAF6 and promotes the degradation of TRAF6. (PubMed id 20079715)1, 2, 9 Zhou L.... Huo K. (Biochem. Biophys. Res. Commun. 2010)
    3. E2 interaction and dimerization in the crystal structure of TRAF6. (PubMed id 19465916)1, 2, 9 Yin Q.... Wu H. (Nat. Struct. Mol. Biol. 2009)
    4. Distinct molecular mechanism for initiating TRAF6 signalling. (PubMed id 12140561)1, 2, 9 Ye H.... Wu H. (Nature 2002)
    5. Structure, interactions, and dynamics of the RING domain from human TRAF6. (PubMed id 17327397)1, 2, 9 Mercier P....Spyracopoulos L. (Protein Sci. 2007)
    6. Tumor necrosis factor receptor-associated factor 6 (TRAF6) stimulates extracellular signal-regulated kinase (ERK) activity in CD40 signaling along a ras-independent pathway. (PubMed id 9432981)1, 2, 9 Kashiwada M.... Takemori T. (J. Exp. Med. 1998)
    7. Nuclear tumor necrosis factor receptor-associated factor 6 in lymphoid cells negatively regulates c-Myb-mediated transactivation through small ubiquitin-related modifier-1 modification. (PubMed id 18093978)1, 2, 9 Pham L.V.... Ford R.J. (J. Biol. Chem. 2008)
    8. Association of the p75 neurotrophin receptor with TRAF6. (PubMed id 9915784)1, 2, 9 Khursigara G.... Chao M.V. (J. Biol. Chem. 1999)
    9. The type I TGF-beta receptor engages TRAF6 to activate TAK1 in a receptor kinase-independent manner. (PubMed id 18758450)1, 2, 9 Sorrentino A.... Landstrom M. (Nat. Cell Biol. 2008)
    10. Toll-like receptor 3-mediated activation of NF-kappaB and IRF3 diverges at Toll-IL-1 receptor domain-containing adapter inducing IFN- beta. (PubMed id 14982987)1, 2, 9 Jiang Z.... Li X. (Proc. Natl. Acad. Sci. U.S.A. 2004)

    (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: 7189 HGNC: 12036 AceView: TRAF6 Ensembl:ENSG00000175104 euGenes: HUgn7189
    ECgene: TRAF6 Kegg: 7189 H-InvDB: TRAF6

    (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 TRAF6 Pharmacogenomics, SNPs, Pathways
    ATLAS Chromosomes in Cancer entry for TRAF6 Genetics and Cytogenetics in Oncology and Haematology
    SeattleSNPshttp://pga.gs.washington.edu/data/traf6/

    (Patent information from GeneIP,
    Licensable technologies from WIS Yeda, Salk, Tufts,
    IP news from LifeMap Sciences, Inc.)
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    Patent Information for TRAF6 gene:
    Search GeneIP for patents involving TRAF6

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



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