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Aliases for TRAF6 Gene

Aliases for TRAF6 Gene

  • TNF Receptor-Associated Factor 6, E3 Ubiquitin Protein Ligase 2 3
  • E3 Ubiquitin-Protein Ligase TRAF6 3 4
  • TNF Receptor-Associated Factor 6 2 3
  • 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, E3 Ubiquitin Protein Ligase) is a Protein Coding gene. Diseases associated with TRAF6 include ectodermal dysplasia 10a, hypohidrotic/hair/nail type, autosomal dominant. Among its related pathways are PI-3K cascade and Signaling by FGFR. GO annotations related to this gene include protein kinase binding and signal transducer 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

Epigenetics Products

  • DNA Methylation CpG Assay Predesigned for Pyrosequencing in human,mouse,rat

Genomic Location for TRAF6 Gene

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

UCSC Golden Path with GeneCards custom track
Cytogenetic band:
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 TICAM1 and TICAM2. Interacts with CARD14. Interacts with CD40 and MAP3K8; the interaction is required for ERK activation (By similarity).

    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:
Reactome Protein details:
REFSEQ proteins:

Antibody Products

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

No data available for DME Specific Peptides for TRAF6 Gene

Domains for TRAF6 Gene

Gene Families for TRAF6 Gene

HGNC:
  • RNF :RING-type (C3HC4) zinc fingers

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 :
  • Q9Y4K3
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:0004842 ubiquitin-protein transferase activity TAS --
GO:0004871 signal transducer activity --
GO:0005164 tumor necrosis factor receptor binding IPI 11728344
GO:0005515 protein binding IPI 10094049
GO:0008270 zinc ion binding IEA --
genes like me logo Genes that share ontologies with TRAF6: view
genes like me logo Genes that share phenotypes with TRAF6: view

Animal Models for TRAF6 Gene

MGI Knock Outs for TRAF6:

Animal Model Products

CRISPR Products

miRNA for TRAF6 Gene

miRTarBase miRNAs that target TRAF6

miRNA Products

In Situ Assay Products

Flow Cytometry Products

No data available for Transcription Factor Targeting 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
nucleus 5
cytosol 4
endosome 4
plasma membrane 3
extracellular 1
vacuole 1

Gene Ontology (GO) - Cellular Components for TRAF6 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005634 nucleus IDA 18093978
GO:0005730 nucleolus IDA --
GO:0005737 cytoplasm IDA 16378096
GO:0005739 mitochondrion IDA --
GO:0005811 lipid particle ISS --
genes like me logo Genes that share ontologies with TRAF6: view

Pathways for TRAF6 Gene

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

PCR Array Products

UniProtKB/Swiss-Prot Q9Y4K3-TRAF6_HUMAN

  • Pathway: Protein modification; protein ubiquitination

Gene Ontology (GO) - Biological Process for TRAF6 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000122 negative regulation of transcription from RNA polymerase II promoter IMP 18093978
GO:0000187 activation of MAPK activity TAS --
GO:0000209 protein polyubiquitination IDA 15125833
GO:0001503 ossification IEA --
GO:0001843 neural tube closure IEA --
genes like me logo Genes that share ontologies with TRAF6: view

Compounds for TRAF6 Gene

(15) Novoseek inferred chemical compound relationships for TRAF6 Gene

Compound -log(P) Hits PubMed IDs
tab-2 93.3 36
tab-1 83.1 5
bcma 46.1 1
poly(i-c) 40.9 2
zinc 31.9 13
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:

CRISPR Products

miRNA Products

Primer Products

Flow Cytometry Products

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

Integrated Proteomics: protein expression 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 expressions with TRAF6: view

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
chimpanzee
(Pan troglodytes)
Mammalia TRAF6 35
  • 99.74 (n)
  • 99.62 (a)
TRAF6 36
  • 100 (a)
OneToOne
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
oppossum
(Monodelphis domestica)
Mammalia TRAF6 36
  • 80 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia TRAF6 36
  • 81 (a)
OneToOne
rat
(Rattus norvegicus)
Mammalia Traf6 35
  • 85.57 (n)
  • 87.74 (a)
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
African clawed frog
(Xenopus laevis)
Amphibia Xl.14682 35
tropical clawed frog
(Silurana tropicalis)
Amphibia Str.8271 35
traf6 35
  • 66.35 (n)
  • 69.35 (a)
rainbow trout
(Oncorhynchus mykiss)
Actinopterygii Omy.1398 35
zebrafish
(Danio rerio)
Actinopterygii traf6 35
  • 60.14 (n)
  • 59.88 (a)
traf6 36
  • 55 (a)
OneToOne
wufi15f02 35
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP003004 35
  • 46.32 (n)
  • 32.66 (a)
fruit fly
(Drosophila melanogaster)
Insecta Traf-like 36
  • 14 (a)
ManyToMany
Traf6 35
  • 43.22 (n)
  • 32.91 (a)
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

Selected 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 MAF
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

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

MalaCards: The human disease database. (1) Diseases for TRAF6 Gene including...

Search for TRAF6 Gene in MalaCards »

(1) University of Copenhagen DISEASES for TRAF6 Gene

(13) Novoseek inferred disease relationships for TRAF6 Gene

Disease -log(P) Hits PubMed IDs
necrosis 71.7 69
tumors 56.5 65
inflammation 38.9 6
ectodermal dysplasia 25.6 1
bone diseases 14.6 1

Relevant External Links for TRAF6

Genetic Association Database (GAD)
TRAF6
Human Genome Epidemiology (HuGE) Navigator
TRAF6
genes like me logo Genes that share disorders with TRAF6: view

No data available for UniProtKB/Swiss-Prot 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
  2. Tumor necrosis factor receptor-associated factor 6 (TRAF6) stimulates extracellular signal-regulated kinase (ERK) activity in CD40 signaling along a ras-independent pathway. (PMID: 9432981) Kashiwada M. … Takemori T. (J. Exp. Med. 1998) 3 4 23
  3. Association of the p75 neurotrophin receptor with TRAF6. (PMID: 9915784) Khursigara G. … Chao M.V. (J. Biol. Chem. 1999) 3 4 23
  4. Signaling by proinflammatory cytokines: oligomerization of TRAF2 and TRAF6 is sufficient for JNK and IKK activation and target gene induction via an amino-terminal effector domain. (PMID: 10346818) Baud V. … Karin M. (Genes Dev. 1999) 3 4 23
  5. TRANCE, a TNF family member, activates Akt/PKB through a signaling complex involving TRAF6 and c-Src. (PMID: 10635328) Wong B.R. … Choi Y. (Mol. Cell 1999) 3 4 23

Products for TRAF6 Gene

  • Addgene plasmids for TRAF6

Sources for TRAF6 Gene

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