Free for academic non-profit institutions. Other users need a Commercial license

Aliases for TRAF6 Gene

Aliases for TRAF6 Gene

  • TNF Receptor Associated Factor 6 2 3 5
  • TNF Receptor-Associated Factor 6, E3 Ubiquitin Protein Ligase 2 3
  • E3 Ubiquitin-Protein Ligase TRAF6 3 4
  • Interleukin-1 Signal Transducer 3 4
  • RING Finger Protein 85 3 4
  • RNF85 3 4
  • EC 6.3.2.- 4
  • MGC:3310 3

External Ids for TRAF6 Gene

Previous GeneCards Identifiers for TRAF6 Gene

  • GC11M038067
  • GC11M037188
  • GC11M036549
  • GC11M036475
  • GC11M036212

Summaries for TRAF6 Gene

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) is a Protein Coding gene. Diseases associated with TRAF6 include ectodermal dysplasia 10a, hypohidrotic/hair/nail type, autosomal dominant and incontinentia pigmenti. Among its related pathways are Signaling by GPCR and Immune System. GO annotations related to this gene include identical protein binding and ligase activity. An important paralog of this gene is TRAF5.

UniProtKB/Swiss-Prot for TRAF6 Gene

  • E3 ubiquitin ligase that, together with UBE2N and UBE2V1, mediates the synthesis of Lys-63-linked-polyubiquitin chains conjugated to proteins, such as IKBKG, IRAK1, 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

No data available for Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for TRAF6 Gene

Genomics for TRAF6 Gene

Regulatory Elements for TRAF6 Gene

Promoters for TRAF6 Gene
Ensembl Regulatory Elements (ENSRs) TSS Distance (bp) Size (bp) Binding Sites for Transcription Factors within promoters

ENSRs around TRAF6 on UCSC Golden Path with GeneCards custom track

Genomic Location for TRAF6 Gene

Chromosome:
11
Start:
36,483,767 bp from pter
End:
36,510,313 bp from pter
Size:
26,547 bases
Orientation:
Minus strand

Genomic View for TRAF6 Gene

Genes around TRAF6 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
TRAF6 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for TRAF6 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for TRAF6 Gene

Proteins for TRAF6 Gene

  • Protein details for TRAF6 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q9Y4K3-TRAF6_HUMAN
    Recommended name:
    TNF receptor-associated factor 6
    Protein Accession:
    Q9Y4K3
    Secondary Accessions:
    • A6NKI7
    • A8KAB3
    • D3DR16
    • Q8NEH5

    Protein attributes for TRAF6 Gene

    Size:
    522 amino acids
    Molecular mass:
    59573 Da
    Quaternary structure:
    • 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 TICAM2. Interacts with CARD14. Interacts with CD40 and MAP3K8; the interaction is required for ERK activation (By similarity). Interacts with TICAM1 and this interaction is enhanced in the presence of WDFY1 (PubMed:25736436).

    Three dimensional structures from OCA and Proteopedia for TRAF6 Gene

neXtProt entry for TRAF6 Gene

Proteomics data for TRAF6 Gene at MOPED

Post-translational modifications for TRAF6 Gene

  • 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 form.
  • Sumoylated on Lys-124, Lys-142 and Lys-453 with SUMO1.
  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Other Protein References for TRAF6 Gene

ENSEMBL proteins:
REFSEQ proteins:

Antibody Products

  • Cell Signaling Technology (CST) Antibodies for TRAF6 (TRAF6)

No data available for DME Specific Peptides for TRAF6 Gene

Domains & Families for TRAF6 Gene

Suggested Antigen Peptide Sequences for TRAF6 Gene

GenScript: Design optimal peptide antigens:

Graphical View of Domain Structure for InterPro Entry

Q9Y4K3

UniProtKB/Swiss-Prot:

TRAF6_HUMAN :
  • The coiled coil domain mediates homo- and hetero-oligomerization.
  • Belongs to the TNF receptor-associated factor family. A subfamily.
  • Contains 1 RING-type zinc finger.
Domain:
  • The coiled coil domain mediates homo- and hetero-oligomerization.
  • The MATH/TRAF domain binds to receptor cytoplasmic domains.
  • Contains 1 MATH domain.
Family:
  • Belongs to the TNF receptor-associated factor family. A subfamily.
Similarity:
  • Contains 1 RING-type zinc finger.
  • Contains 2 TRAF-type zinc fingers.
genes like me logo Genes that share domains with TRAF6: view

Function for TRAF6 Gene

Molecular function for TRAF6 Gene

GENATLAS Biochemistry:
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
UniProtKB/Swiss-Prot 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, IRAK1, 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.

Enzyme Numbers (IUBMB) for TRAF6 Gene

Gene Ontology (GO) - Molecular Function for TRAF6 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0042826 histone deacetylase binding IPI 18093978
genes like me logo Genes that share ontologies with TRAF6: view
genes like me logo Genes that share phenotypes with TRAF6: view

Human Phenotype Ontology for TRAF6 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for TRAF6 Gene

MGI Knock Outs for TRAF6:

Animal Model Products

miRNA for TRAF6 Gene

miRTarBase miRNAs that target TRAF6

No data available for Transcription Factor Targets and HOMER Transcription for TRAF6 Gene

Localization for TRAF6 Gene

Subcellular locations from UniProtKB/Swiss-Prot for TRAF6 Gene

Cytoplasm. Cytoplasm, cell cortex. Nucleus. Lipid droplet. 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). {ECO:0000250}.

Subcellular locations from

COMPARTMENTS
Jensen Localization Image for TRAF6 Gene COMPARTMENTS Subcellular localization image for TRAF6 gene
Compartment Confidence
cytosol 5
endosome 5
mitochondrion 5
nucleus 5
plasma membrane 5
extracellular 1
lysosome 1
vacuole 1

Gene Ontology (GO) - Cellular Components for TRAF6 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005730 nucleolus IDA --
GO:0005739 mitochondrion IDA --
genes like me logo Genes that share ontologies with TRAF6: view

Pathways & Interactions for TRAF6 Gene

SuperPathways for TRAF6 Gene

Superpath Contained pathways
1 MyD88 cascade initiated on plasma membrane
2 p75 NTR receptor-mediated signalling
3 RANK Signaling in Osteoclasts
4 Toll Comparative Pathway
5 Toll-Like receptor Signaling Pathways
genes like me logo Genes that share pathways with TRAF6: view

UniProtKB/Swiss-Prot Q9Y4K3-TRAF6_HUMAN

  • Pathway: Protein modification; protein ubiquitination.

SIGNOR curated interactions for TRAF6 Gene

Activates:
Is activated by:
Is inactivated by:

Gene Ontology (GO) - Biological Process for TRAF6 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000187 activation of MAPK activity TAS --
GO:0000209 protein polyubiquitination IDA 15125833
GO:0001503 ossification IEA --
GO:0001843 neural tube closure IEA --
GO:0002223 stimulatory C-type lectin receptor signaling pathway TAS --
genes like me logo Genes that share ontologies with TRAF6: view

Drugs & Compounds for TRAF6 Gene

(6) Drugs for TRAF6 Gene - From: Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials

(9) Additional Compounds for TRAF6 Gene - From: Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
genes like me logo Genes that share compounds with TRAF6: view

Transcripts for TRAF6 Gene

mRNA/cDNA for TRAF6 Gene

Unigene Clusters for TRAF6 Gene

TNF receptor-associated factor 6, E3 ubiquitin protein ligase:
Representative Sequences:

Alternative Splicing Database (ASD) splice patterns (SP) for TRAF6 Gene

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

Relevant External Links for TRAF6 Gene

GeneLoc Exon Structure for
TRAF6
ECgene alternative splicing isoforms for
TRAF6

Expression for TRAF6 Gene

mRNA expression in normal human tissues for TRAF6 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Protein differential expression in normal tissues from HIPED for TRAF6 Gene

This gene is overexpressed in Peripheral blood mononuclear cells (14.9), Heart (7.5), and Testis (6.2).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, PaxDb, MOPED, and MaxQB for TRAF6 Gene



SOURCE GeneReport for Unigene cluster for TRAF6 Gene Hs.444172

mRNA Expression by UniProt/SwissProt for TRAF6 Gene

Q9Y4K3-TRAF6_HUMAN
Tissue specificity: Expressed in heart, brain, placenta, lung, liver, skeletal muscle, kidney and pancreas.
genes like me logo Genes that share expression patterns with TRAF6: view

Protein tissue co-expression partners for TRAF6 Gene

- Elite partner

Primer Products

In Situ Assay Products

No data available for mRNA differential expression in normal tissues for TRAF6 Gene

Orthologs for TRAF6 Gene

This gene was present in the common ancestor of animals.

Orthologs for TRAF6 Gene

Organism Taxonomy Gene Similarity Type Details
cow
(Bos Taurus)
Mammalia TRAF6 35
  • 89.21 (n)
  • 92.91 (a)
TRAF6 36
  • 89 (a)
OneToOne
dog
(Canis familiaris)
Mammalia TRAF6 35
  • 90.29 (n)
  • 93.1 (a)
TRAF6 36
  • 80 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Traf6 35
  • 87.1 (n)
  • 89.27 (a)
Traf6 16
Traf6 36
  • 88 (a)
OneToOne
chimpanzee
(Pan troglodytes)
Mammalia TRAF6 35
  • 99.74 (n)
  • 99.62 (a)
TRAF6 36
  • 100 (a)
OneToOne
rat
(Rattus norvegicus)
Mammalia Traf6 35
  • 85.57 (n)
  • 87.74 (a)
oppossum
(Monodelphis domestica)
Mammalia TRAF6 36
  • 80 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia TRAF6 36
  • 81 (a)
OneToOne
chicken
(Gallus gallus)
Aves TRAF6 35
  • 72.67 (n)
  • 76.25 (a)
TRAF6 36
  • 73 (a)
OneToOne
lizard
(Anolis carolinensis)
Reptilia TRAF6 36
  • 70 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia Str.8271 35
traf6 35
  • 66.35 (n)
  • 69.35 (a)
African clawed frog
(Xenopus laevis)
Amphibia Xl.14682 35
zebrafish
(Danio rerio)
Actinopterygii traf6 35
  • 60.14 (n)
  • 59.88 (a)
wufi15f02 35
traf6 36
  • 55 (a)
OneToOne
rainbow trout
(Oncorhynchus mykiss)
Actinopterygii Omy.1398 35
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP003004 35
  • 46.32 (n)
  • 32.66 (a)
fruit fly
(Drosophila melanogaster)
Insecta Traf6 35
  • 43.22 (n)
  • 32.91 (a)
Traf-like 36
  • 14 (a)
ManyToMany
worm
(Caenorhabditis elegans)
Secernentea trf-1 36
  • 23 (a)
ManyToMany
sea squirt
(Ciona savignyi)
Ascidiacea -- 36
  • 40 (a)
OneToMany
-- 36
  • 36 (a)
OneToMany
Species with no ortholog for TRAF6:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)

Evolution for TRAF6 Gene

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

Paralogs for TRAF6 Gene

Paralogs for TRAF6 Gene

(1) SIMAP similar genes for TRAF6 Gene using alignment to 1 proteins:

Pseudogenes.org Pseudogenes for TRAF6 Gene

genes like me logo Genes that share paralogs with TRAF6: view

Variants for TRAF6 Gene

Sequence variations from dbSNP and Humsavar for TRAF6 Gene

SNP ID Clin Chr 11 pos Sequence Context AA Info Type
rs191352 -- 36,496,741(-) TTATT(C/T)TGAGA intron-variant
rs331457 -- 36,502,062(-) ACTGA(A/G)CTGCT intron-variant
rs331458 -- 36,500,256(-) cacag(C/T)gtggt intron-variant
rs331459 -- 36,496,376(-) GGTCT(C/T)GAACT intron-variant
rs331460 -- 36,494,627(-) attta(C/T)aCACT intron-variant

Structural Variations from Database of Genomic Variants (DGV) for TRAF6 Gene

Variant ID Type Subtype PubMed ID
esv2422305 CNV Duplication 17116639
nsv467791 CNV Gain 19166990
esv2678965 CNV Deletion 23128226
esv272785 CNV Insertion 20981092
esv1601897 CNV Insertion 17803354
esv1648317 CNV Insertion 17803354

Variation tolerance for TRAF6 Gene

Residual Variation Intolerance Score: 19.8% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 0.63; 13.59% of all genes are more intolerant (likely to be disease-causing)

Relevant External Links for TRAF6 Gene

HapMap Linkage Disequilibrium report
TRAF6
Human Gene Mutation Database (HGMD)
TRAF6

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for TRAF6 Gene

Disorders for TRAF6 Gene

MalaCards: The human disease database

(5) MalaCards diseases for TRAF6 Gene - From: Orphanet, DISEASES, and GeneCards

Disorder Aliases PubMed IDs
ectodermal dysplasia 10a, hypohidrotic/hair/nail type, autosomal dominant
  • ectodermal dysplasia 11b, hypohidrotic/hair/tooth type, autosomal recessive
incontinentia pigmenti
  • bloch-sulzberger syndrome
cd40 deficiency
  • type 3 hyper-igm immunodeficiency
toxoplasmosis
  • disseminated toxoplasmosis
ectodermal dysplasia 10b, hypohidrotic/hair/tooth type, autosomal recessive
  • hypohidrotic ectodermal dysplasia
- elite association - COSMIC cancer census association via MalaCards
Search TRAF6 in MalaCards View complete list of genes associated with diseases

Relevant External Links for TRAF6

Genetic Association Database (GAD)
TRAF6
Human Genome Epidemiology (HuGE) Navigator
TRAF6
Atlas of Genetics and Cytogenetics in Oncology and Haematology:
TRAF6
genes like me logo Genes that share disorders with TRAF6: view

No data available for UniProtKB/Swiss-Prot and Genatlas for TRAF6 Gene

Publications for TRAF6 Gene

  1. TRAF6 is a signal transducer for interleukin-1. (PMID: 8837778) Cao Z. … Goeddel D.V. (Nature 1996) 2 3 4 23 67
  2. Activation of the alpha3 integrin affects TRAF6 function in the IL-1 signaling pathway of CACO-2 epithelial cells. (PMID: 20064081) Rafferty B.J. … McGee D.W. (Immunol. Invest. 2010) 3 23
  3. NUMBL interacts with TRAF6 and promotes the degradation of TRAF6. (PMID: 20079715) Zhou L. … Huo K. (Biochem. Biophys. Res. Commun. 2010) 3 23
  4. Competition between TRAF2 and TRAF6 regulates NF-kappaB activation in human B lymphocytes. (PMID: 20449947) Zhang W. … Lipsky P.E. (Chin. Med. Sci. J. 2010) 3 23
  5. TRAF6 is autoinhibited by an intramolecular interaction which is counteracted by trans-ubiquitination. (PMID: 20512936) Wang K.Z. … Auron P.E. (J. Cell. Biochem. 2010) 3 23

Products for TRAF6 Gene

Sources for TRAF6 Gene

Back to Top

Content