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Protein

TNF receptor-associated factor 6

Gene

Traf6

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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 (By similarity). 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.By similarity7 Publications

Pathwayi

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri70 – 10940RING-typePROSITE-ProRule annotationAdd
BLAST
Zinc fingeri150 – 20253TRAF-type 1PROSITE-ProRule annotationAdd
BLAST
Zinc fingeri203 – 25957TRAF-type 2PROSITE-ProRule annotationAdd
BLAST

GO - Molecular functioni

  1. histone deacetylase binding Source: MGI
  2. ligase activity Source: UniProtKB-KW
  3. mitogen-activated protein kinase kinase kinase binding Source: MGI
  4. protein kinase B binding Source: MGI
  5. protein kinase binding Source: MGI
  6. protein N-terminus binding Source: MGI
  7. signal transducer activity Source: MGI
  8. thioesterase binding Source: MGI
  9. tumor necrosis factor receptor binding Source: MGI
  10. ubiquitin conjugating enzyme binding Source: MGI
  11. ubiquitin protein ligase activity Source: MGI
  12. ubiquitin protein ligase binding Source: MGI
  13. ubiquitin-protein transferase activity Source: UniProtKB
  14. zinc ion binding Source: InterPro

GO - Biological processi

  1. activation of NF-kappaB-inducing kinase activity Source: MGI
  2. activation of protein kinase activity Source: MGI
  3. antigen processing and presentation of exogenous peptide antigen via MHC class II Source: MGI
  4. bone remodeling Source: UniProtKB
  5. bone resorption Source: UniProtKB
  6. cell development Source: MGI
  7. cellular response to lipopolysaccharide Source: MGI
  8. I-kappaB kinase/NF-kappaB signaling Source: UniProtKB
  9. immune response Source: MGI
  10. interleukin-1-mediated signaling pathway Source: UniProtKB
  11. JNK cascade Source: Ensembl
  12. myeloid dendritic cell differentiation Source: MGI
  13. negative regulation of transcription, DNA-templated Source: MGI
  14. negative regulation of transcription from RNA polymerase II promoter Source: MGI
  15. neural tube closure Source: UniProtKB
  16. odontogenesis of dentin-containing tooth Source: MGI
  17. organ morphogenesis Source: MGI
  18. ossification Source: MGI
  19. osteoclast differentiation Source: UniProtKB
  20. positive regulation of I-kappaB kinase/NF-kappaB signaling Source: UniProtKB
  21. positive regulation of interleukin-12 biosynthetic process Source: MGI
  22. positive regulation of interleukin-2 production Source: MGI
  23. positive regulation of interleukin-6 biosynthetic process Source: MGI
  24. positive regulation of JUN kinase activity Source: MGI
  25. positive regulation of lipopolysaccharide-mediated signaling pathway Source: UniProtKB
  26. positive regulation of NF-kappaB transcription factor activity Source: UniProtKB
  27. positive regulation of osteoclast differentiation Source: MGI
  28. positive regulation of sequence-specific DNA binding transcription factor activity Source: MGI
  29. positive regulation of smooth muscle cell proliferation Source: Ensembl
  30. positive regulation of T cell cytokine production Source: MGI
  31. positive regulation of T cell proliferation Source: UniProtKB
  32. positive regulation of transcription from RNA polymerase II promoter Source: MGI
  33. positive regulation of transcription regulatory region DNA binding Source: MGI
  34. protein autoubiquitination Source: UniProtKB
  35. protein complex assembly Source: Ensembl
  36. protein K63-linked ubiquitination Source: UniProtKB
  37. protein polyubiquitination Source: MGI
  38. protein ubiquitination Source: MGI
  39. regulation of apoptotic process Source: InterPro
  40. regulation of immunoglobulin secretion Source: MGI
  41. response to interleukin-1 Source: MGI
  42. signal transduction Source: MGI
  43. T cell receptor signaling pathway Source: MGI
  44. T-helper 1 type immune response Source: MGI
Complete GO annotation...

Keywords - Molecular functioni

Ligase

Keywords - Biological processi

Immunity, Osteogenesis, Ubl conjugation pathway

Keywords - Ligandi

Metal-binding, Zinc

Enzyme and pathway databases

ReactomeiREACT_271614. TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation.
REACT_273973. MyD88 cascade initiated on plasma membrane.
REACT_275137. TRAF6 mediated NF-kB activation.
REACT_275622. IRAK1 recruits IKK complex.
REACT_278165. IRAK1 recruits IKK complex upon TLR7/8 or 9 stimulation.
REACT_280649. Downstream TCR signaling.
REACT_288310. JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1.
REACT_295008. p75NTR recruits signalling complexes.
REACT_297122. TRAF6 mediated IRF7 activation in TLR7/8 or 9 signaling.
REACT_301153. NOD1/2 Signaling Pathway.
REACT_305279. TAK1 activates NFkB by phosphorylation and activation of IKKs complex.
REACT_308717. IRAK2 mediated activation of TAK1 complex upon TLR7/8 or 9 stimulation.
REACT_309099. MyD88:Mal cascade initiated on plasma membrane.
REACT_311354. TRAF6 mediated IRF7 activation.
REACT_315145. FCERI mediated NF-kB activation.
REACT_315710. Regulated proteolysis of p75NTR.
REACT_324009. activated TAK1 mediates p38 MAPK activation.
REACT_331416. IRAK2 mediated activation of TAK1 complex.
REACT_333825. NF-kB is activated and signals survival.
REACT_336073. TRAF6 mediated induction of TAK1 complex.
REACT_337033. Interleukin-1 signaling.
REACT_342872. NRIF signals cell death from the nucleus.
REACT_348851. MyD88 dependent cascade initiated on endosome.
UniPathwayiUPA00143.

Names & Taxonomyi

Protein namesi
Recommended name:
TNF receptor-associated factor 6 (EC:6.3.2.-)
Alternative name(s):
E3 ubiquitin-protein ligase TRAF6
Gene namesi
Name:Traf6
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589 Componenti: Chromosome 2

Organism-specific databases

MGIiMGI:108072. Traf6.

Subcellular locationi

  1. Cytoplasm By similarity
  2. Cytoplasmcell cortex By similarity
  3. Nucleus By similarity
  4. Lipid droplet 1 Publication

  5. Note: RSAD2/viperin recruits it to the lipid droplet.

GO - Cellular componenti

  1. CD40 receptor complex Source: BHF-UCL
  2. cell cortex Source: UniProtKB-SubCell
  3. cytoplasm Source: MGI
  4. cytoplasmic side of plasma membrane Source: BHF-UCL
  5. cytosol Source: UniProtKB
  6. lipid particle Source: UniProtKB
  7. mitochondrion Source: MGI
  8. nucleolus Source: MGI
  9. nucleus Source: MGI
  10. perinuclear region of cytoplasm Source: MGI
  11. plasma membrane Source: MGI
  12. protein complex Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Lipid droplet, Nucleus

Pathology & Biotechi

Disruption phenotypei

Abrogation of IL-1-induced activation of NF-kappa-B, MAPK8/JNK and MAPK14/p38. Animals appears normal at birth but becomes smaller after one week. Show runting, failure of tooth eruption and die after three weeks. Exhibit severe osteopetrosis, thymic atrophy, lymph node deficiency, splenomegaly, and have alopecia and lack sweat glands.7 Publications

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 530530TNF receptor-associated factor 6PRO_0000056408Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Cross-linki124 – 124Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO); alternateBy similarity
Cross-linki124 – 124Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin); alternateBy similarity
Cross-linki142 – 142Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)By similarity
Cross-linki461 – 461Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)By similarity

Post-translational modificationi

Sumoylated on Lys-124, Lys-142 and Lys-461 with SUMO1.By similarity
Polyubiquitinated; 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 (By similarity).By similarity

Keywords - PTMi

Isopeptide bond, Ubl conjugation

Proteomic databases

MaxQBiP70196.
PaxDbiP70196.
PRIDEiP70196.

PTM databases

PhosphoSiteiP70196.

Expressioni

Tissue specificityi

Highly expressed in brain, lung, liver, skeletal muscle, and kidney; lower expression in heart, spleen, and testis.

Gene expression databases

BgeeiP70196.
CleanExiMM_TRAF6.
GenevestigatoriP70196.

Interactioni

Subunit structurei

Homotrimer (By similarity). Homooligomer (By similarity). 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 (By similarity). Associates with NGFR, TNFRSF17, IRAK2, IRAK3, PELI2, PELI3, RIPK2, MAP3K1, MAP3K5, MAP3K14, CSK, TRAF, TRAF-interacting protein TRIP and TNF receptor associated protein TDP2. Binds UBE2V1. Interacts with MAVS/IPS1. Interacts with TAX1BP1 (By similarity). Interacts with IL17R. Interacts with SQSTM1 bridging NTRK1 and NGFR. Forms a ternary complex with SQSTM1 and PRKCZ. Interacts with IL1RL1. Interacts with AJUBA (By similarity). Interacts with TRAFD1. Interacts with TICAM1 and TICAM2. Interacts with ZFAND5. Interacts with ARRB1 and ARRB2 (By similarity). 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) (By similarity). Interacts (via TRAF domains) with WDR34 (via WD domains). Interacts with RBCK1 (By similarity). Interacts with TRAF3IP2 (By similarity). Interacts with LIMD1 (via LIM domains). Interacts with RSAD2/viperin. Interacts with IFIT3 (via N-terminus) (By similarity). Interacts (via C-terminus) with EIF2AK2/PKR (via the kinase catalytic domain). Interacts with CARD14 (By similarity). Interacts with CD40 and MAP3K8; the interaction is required for ERK activation.By similarity8 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
Cd40P275122EBI-448028,EBI-525742
EcsitQ9QZH64EBI-448028,EBI-527020
Ern1Q9EQY06EBI-448028,EBI-5480799
Hspa1bP178793EBI-448028,EBI-397360
Irak1Q62406-14EBI-448028,EBI-488313
Irak3Q8K4B23EBI-448028,EBI-646179
Map3k3Q610845EBI-448028,EBI-446250
Nr0b2Q622275EBI-448028,EBI-4310440
Ptpn11P352352EBI-448028,EBI-397236
TifaQ793I82EBI-448028,EBI-524817
Tnfrsf11aO353052EBI-448028,EBI-647362
Traf3ip2Q8C0E53EBI-448028,EBI-530713
Traf3ip2Q8N7N64EBI-448028,EBI-646165
Trafd1Q3UDK12EBI-448028,EBI-1396948
UbcP629912EBI-448028,EBI-413074

Protein-protein interaction databases

BioGridi204307. 83 interactions.
DIPiDIP-29812N.
IntActiP70196. 37 interactions.
MINTiMINT-252449.
STRINGi10090.ENSMUSP00000004949.

Structurei

3D structure databases

ProteinModelPortaliP70196.
SMRiP70196. Positions 54-210, 317-516.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini358 – 507150MATHPROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni1 – 362362Interaction with TAX1BP1By similarityAdd
BLAST

Coiled coil

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Coiled coili299 – 35658Sequence AnalysisAdd
BLAST

Domaini

The coiled coil domain mediates homo- and hetero-oligomerization.
The MATH/TRAF domain binds to receptor cytoplasmic domains.

Sequence similaritiesi

Contains 1 MATH domain.PROSITE-ProRule annotation
Contains 1 RING-type zinc finger.PROSITE-ProRule annotation
Contains 2 TRAF-type zinc fingers.PROSITE-ProRule annotation

Zinc finger

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri70 – 10940RING-typePROSITE-ProRule annotationAdd
BLAST
Zinc fingeri150 – 20253TRAF-type 1PROSITE-ProRule annotationAdd
BLAST
Zinc fingeri203 – 25957TRAF-type 2PROSITE-ProRule annotationAdd
BLAST

Keywords - Domaini

Coiled coil, Repeat, Zinc-finger

Phylogenomic databases

eggNOGiNOG289765.
GeneTreeiENSGT00550000074359.
HOGENOMiHOG000006625.
HOVERGENiHBG060248.
InParanoidiP70196.
KOiK03175.
OMAiNFQETIH.
OrthoDBiEOG7966G5.
PhylomeDBiP70196.
TreeFamiTF321154.

Family and domain databases

Gene3Di3.30.40.10. 1 hit.
InterProiIPR002083. MATH.
IPR012227. TNF_rcpt--assoc_TRAF.
IPR008974. TRAF-like.
IPR027139. TRAF6.
IPR001841. Znf_RING.
IPR013083. Znf_RING/FYVE/PHD.
IPR017907. Znf_RING_CS.
IPR001293. Znf_TRAF.
[Graphical view]
PANTHERiPTHR10131:SF52. PTHR10131:SF52. 1 hit.
PfamiPF00917. MATH. 1 hit.
[Graphical view]
PIRSFiPIRSF015614. TRAF. 1 hit.
SMARTiSM00061. MATH. 1 hit.
SM00184. RING. 1 hit.
[Graphical view]
SUPFAMiSSF49599. SSF49599. 3 hits.
PROSITEiPS50144. MATH. 1 hit.
PS00518. ZF_RING_1. 1 hit.
PS50089. ZF_RING_2. 1 hit.
PS50145. ZF_TRAF. 2 hits.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P70196-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MSLLNCENSC GSSQSSSDCC AAMAASCSAA VKDDSVSGSA STGNLSSSFM
60 70 80 90 100
EEIQGYDVEF DPPLESKYEC PICLMALREA VQTPCGHRFC KACIIKSIRD
110 120 130 140 150
AGHKCPVDNE ILLENQLFPD NFAKREILSL TVKCPNKGCL QKMELRHLED
160 170 180 190 200
HQVHCEFALV NCPQCQRPFQ KCQVNTHIIE DCPRRQVSCV NCAVSMAYEE
210 220 230 240 250
KEIHDQSCPL ANIICEYCGT ILIREQMPNH YDLDCPTAPI PCTFSVFGCH
260 270 280 290 300
EKMQRNHLAR HLQENTQLHM RLLAQAVHNV NLALRPCDAA SPSRGCRPED
310 320 330 340 350
PNYEETIKQL ESRLVRQDHQ IRELTAKMET QSMYVGELKR TIRTLEDKVA
360 370 380 390 400
EMEAQQCNGI YIWKIGNFGM HLKSQEEERP VVIHSPGFYT GRPGYKLCMR
410 420 430 440 450
LHLQLPTAQR CANYISLFVH TMQGEYDSHL PWPFQGTIRL TILDQSEALI
460 470 480 490 500
RQNHEEVMDA KPELLAFQRP TIPRNPKGFG YVTFMHLEAL RQGTFIKDDT
510 520 530
LLVRCEVSTR FDMGGLRKEG FQPRSTDAGV
Length:530
Mass (Da):60,070
Last modified:February 9, 2010 - v2
Checksum:iF8389250425E4E2D
GO
Isoform 2 (identifier: P70196-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     100-174: DAGHKCPVDN...CQRPFQKCQV → YLILRKHGAL...TQPPGKLQSP
     175-530: Missing.

Note: No experimental confirmation available.

Show »
Length:174
Mass (Da):18,961
Checksum:iF66189179AA9F9D3
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti251 – 2511E → Q in BAA12705 (PubMed:8910514).Curated
Sequence conflicti251 – 2511E → Q in BAC30850 (PubMed:16141072).Curated
Sequence conflicti367 – 3671N → K in BAA12705 (PubMed:8910514).Curated
Sequence conflicti367 – 3671N → K in BAC30850 (PubMed:16141072).Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei100 – 17475DAGHK…QKCQV → YLILRKHGALQQPNVKSMLE TGHPKNRQTENTGQEHSRMD RNLRQLGSHPSLYYGMNRGL LPCLPTQPPGKLQSP in isoform 2. 1 PublicationVSP_007404Add
BLAST
Alternative sequencei175 – 530356Missing in isoform 2. 1 PublicationVSP_007405Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D84655 mRNA. Translation: BAA12705.1.
AK041172 mRNA. Translation: BAC30850.1.
AK155434 mRNA. Translation: BAE33263.1.
AL929571 Genomic DNA. Translation: CAM20505.1.
CH466519 Genomic DNA. Translation: EDL27656.1.
CH466519 Genomic DNA. Translation: EDL27657.1.
BC060705 mRNA. Translation: AAH60705.1.
CCDSiCCDS16464.1. [P70196-1]
RefSeqiNP_001290202.1. NM_001303273.1. [P70196-1]
NP_033450.2. NM_009424.3. [P70196-1]
UniGeneiMm.292729.

Genome annotation databases

EnsembliENSMUST00000004949; ENSMUSP00000004949; ENSMUSG00000027164. [P70196-1]
GeneIDi22034.
KEGGimmu:22034.
UCSCiuc008lhl.1. mouse. [P70196-2]
uc008lhm.1. mouse. [P70196-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D84655 mRNA. Translation: BAA12705.1.
AK041172 mRNA. Translation: BAC30850.1.
AK155434 mRNA. Translation: BAE33263.1.
AL929571 Genomic DNA. Translation: CAM20505.1.
CH466519 Genomic DNA. Translation: EDL27656.1.
CH466519 Genomic DNA. Translation: EDL27657.1.
BC060705 mRNA. Translation: AAH60705.1.
CCDSiCCDS16464.1. [P70196-1]
RefSeqiNP_001290202.1. NM_001303273.1. [P70196-1]
NP_033450.2. NM_009424.3. [P70196-1]
UniGeneiMm.292729.

3D structure databases

ProteinModelPortaliP70196.
SMRiP70196. Positions 54-210, 317-516.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi204307. 83 interactions.
DIPiDIP-29812N.
IntActiP70196. 37 interactions.
MINTiMINT-252449.
STRINGi10090.ENSMUSP00000004949.

PTM databases

PhosphoSiteiP70196.

Proteomic databases

MaxQBiP70196.
PaxDbiP70196.
PRIDEiP70196.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000004949; ENSMUSP00000004949; ENSMUSG00000027164. [P70196-1]
GeneIDi22034.
KEGGimmu:22034.
UCSCiuc008lhl.1. mouse. [P70196-2]
uc008lhm.1. mouse. [P70196-1]

Organism-specific databases

CTDi7189.
MGIiMGI:108072. Traf6.

Phylogenomic databases

eggNOGiNOG289765.
GeneTreeiENSGT00550000074359.
HOGENOMiHOG000006625.
HOVERGENiHBG060248.
InParanoidiP70196.
KOiK03175.
OMAiNFQETIH.
OrthoDBiEOG7966G5.
PhylomeDBiP70196.
TreeFamiTF321154.

Enzyme and pathway databases

UniPathwayiUPA00143.
ReactomeiREACT_271614. TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation.
REACT_273973. MyD88 cascade initiated on plasma membrane.
REACT_275137. TRAF6 mediated NF-kB activation.
REACT_275622. IRAK1 recruits IKK complex.
REACT_278165. IRAK1 recruits IKK complex upon TLR7/8 or 9 stimulation.
REACT_280649. Downstream TCR signaling.
REACT_288310. JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1.
REACT_295008. p75NTR recruits signalling complexes.
REACT_297122. TRAF6 mediated IRF7 activation in TLR7/8 or 9 signaling.
REACT_301153. NOD1/2 Signaling Pathway.
REACT_305279. TAK1 activates NFkB by phosphorylation and activation of IKKs complex.
REACT_308717. IRAK2 mediated activation of TAK1 complex upon TLR7/8 or 9 stimulation.
REACT_309099. MyD88:Mal cascade initiated on plasma membrane.
REACT_311354. TRAF6 mediated IRF7 activation.
REACT_315145. FCERI mediated NF-kB activation.
REACT_315710. Regulated proteolysis of p75NTR.
REACT_324009. activated TAK1 mediates p38 MAPK activation.
REACT_331416. IRAK2 mediated activation of TAK1 complex.
REACT_333825. NF-kB is activated and signals survival.
REACT_336073. TRAF6 mediated induction of TAK1 complex.
REACT_337033. Interleukin-1 signaling.
REACT_342872. NRIF signals cell death from the nucleus.
REACT_348851. MyD88 dependent cascade initiated on endosome.

Miscellaneous databases

NextBioi301798.
PROiP70196.
SOURCEiSearch...

Gene expression databases

BgeeiP70196.
CleanExiMM_TRAF6.
GenevestigatoriP70196.

Family and domain databases

Gene3Di3.30.40.10. 1 hit.
InterProiIPR002083. MATH.
IPR012227. TNF_rcpt--assoc_TRAF.
IPR008974. TRAF-like.
IPR027139. TRAF6.
IPR001841. Znf_RING.
IPR013083. Znf_RING/FYVE/PHD.
IPR017907. Znf_RING_CS.
IPR001293. Znf_TRAF.
[Graphical view]
PANTHERiPTHR10131:SF52. PTHR10131:SF52. 1 hit.
PfamiPF00917. MATH. 1 hit.
[Graphical view]
PIRSFiPIRSF015614. TRAF. 1 hit.
SMARTiSM00061. MATH. 1 hit.
SM00184. RING. 1 hit.
[Graphical view]
SUPFAMiSSF49599. SSF49599. 3 hits.
PROSITEiPS50144. MATH. 1 hit.
PS00518. ZF_RING_1. 1 hit.
PS50089. ZF_RING_2. 1 hit.
PS50145. ZF_TRAF. 2 hits.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Identification of TRAF6, a novel tumor necrosis factor receptor-associated factor protein that mediates signaling from an amino-terminal domain of the CD40 cytoplasmic region."
    Ishida T., Mizushima S., Azuma S., Kobayashi N., Tojo T., Suzuki K., Aizawa S., Watanabe T., Mosialos G., Kieff E., Yamamoto T., Inoue J.
    J. Biol. Chem. 271:28745-28748(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
    Strain: C57BL/Kaplan.
    Tissue: T-cell lymphoma.
  2. "The transcriptional landscape of the mammalian genome."
    Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.
    , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
    Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
    Strain: C57BL/6J.
    Tissue: Aorta and Vein.
  3. Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.
    Submitted (JAN-2009) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  4. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Strain: C57BL/6.
    Tissue: Brain.
  5. "Severe osteopetrosis, defective interleukin-1 signalling and lymph node organogenesis in TRAF6-deficient mice."
    Naito A., Azuma S., Tanaka S., Miyazaki T., Takaki S., Takatsu K., Nakao K., Nakamura K., Katsuki M., Yamamoto T., Inoue J.
    Genes Cells 4:353-362(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: DISRUPTION PHENOTYPE, FUNCTION.
  6. Cited for: DISRUPTION PHENOTYPE, FUNCTION.
  7. "The atypical PKC-interacting protein p62 channels NF-kappaB activation by the IL-1-TRAF6 pathway."
    Sanz L., Diaz-Meco M.T., Nakano H., Moscat J.
    EMBO J. 19:1576-1586(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH SQSTM1 AND PRKCZ.
  8. "Requirement of tumor necrosis factor receptor-associated factor (TRAF)6 in interleukin 17 signal transduction."
    Schwandner R., Yamaguchi K., Cao Z.
    J. Exp. Med. 191:1233-1240(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH IL17R.
  9. "The atypical protein kinase C-interacting protein p62 is a scaffold for NF-kappaB activation by nerve growth factor."
    Wooten M.W., Seibenhener M.L., Mamidipudi V., Diaz-Meco M.T., Barker P.A., Moscat J.
    J. Biol. Chem. 276:7709-7712(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH SQSTM1; PRKCZ AND NGFR.
  10. Cited for: DISRUPTION PHENOTYPE.
  11. "Tpl2 transduces CD40 and TNF signals that activate ERK and regulates IgE induction by CD40."
    Eliopoulos A.G., Wang C.C., Dumitru C.D., Tsichlis P.N.
    EMBO J. 22:3855-3864(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH CD40 AND MAP3K8.
  12. Cited for: DISRUPTION PHENOTYPE, FUNCTION.
  13. "TNFR-associated factor (TRAF) 6 is essential for MyD88-dependent pathway but not toll/IL-1 receptor domain-containing adaptor-inducing IFN-beta (TRIF)-dependent pathway in TLR signaling."
    Gohda J., Matsumura T., Inoue J.
    J. Immunol. 173:2913-2917(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: DISRUPTION PHENOTYPE, FUNCTION.
  14. "The p62 scaffold regulates nerve growth factor-induced NF-kappaB activation by influencing TRAF6 polyubiquitination."
    Wooten M.W., Geetha T., Seibenhener M.L., Babu J.R., Diaz-Meco M.T., Moscat J.
    J. Biol. Chem. 280:35625-35629(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: UBIQUITINATION.
  15. "Dependence of self-tolerance on TRAF6-directed development of thymic stroma."
    Akiyama T., Maeda S., Yamane S., Ogino K., Kasai M., Kajiura F., Matsumoto M., Inoue J.
    Science 308:248-251(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: DISRUPTION PHENOTYPE.
  16. "Smad6 negatively regulates interleukin 1-receptor-Toll-like receptor signaling through direct interaction with the adaptor Pellino-1."
    Choi K.C., Lee Y.S., Lim S., Choi H.K., Lee C.H., Lee E.K., Hong S., Kim I.H., Kim S.J., Park S.H.
    Nat. Immunol. 7:1057-1065(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: IDENTIFICATION IN COMPLEX WITH IRAK1; IRAK4; MYD88 AND PELI1.
  17. "Characteristics and biological functions of TRAF6."
    Inoue J., Gohda J., Akiyama T.
    Adv. Exp. Med. Biol. 597:72-79(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: DISRUPTION PHENOTYPE, FUNCTION.
  18. "The LIM protein, Limd1, regulates AP-1 activation through an interaction with Traf6 to influence osteoclast development."
    Feng Y., Zhao H., Luderer H.F., Epple H., Faccio R., Ross F.P., Teitelbaum S.L., Longmore G.D.
    J. Biol. Chem. 282:39-48(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH LIMD1.
  19. "FLN29 deficiency reveals its negative regulatory role in the Toll-like receptor (TLR) and retinoic acid-inducible gene I (RIG-I)-like helicase signaling pathway."
    Sanada T., Takaesu G., Mashima R., Yoshida R., Kobayashi T., Yoshimura A.
    J. Biol. Chem. 283:33858-33864(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH TRAFD1.
  20. "Antiviral protein Viperin promotes Toll-like receptor 7- and Toll-like receptor 9-mediated type I interferon production in plasmacytoid dendritic cells."
    Saitoh T., Satoh T., Yamamoto N., Uematsu S., Takeuchi O., Kawai T., Akira S.
    Immunity 34:352-363(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH RSAD2, SUBCELLULAR LOCATION.

Entry informationi

Entry nameiTRAF6_MOUSE
AccessioniPrimary (citable) accession number: P70196
Secondary accession number(s): Q6P9M0, Q8BLV2
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 9, 2003
Last sequence update: February 9, 2010
Last modified: April 29, 2015
This is version 156 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  3. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.