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Protein

TNF receptor-associated factor 6

Gene

Traf6

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at transcript 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. Mediates 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 similarity).By similarity

Pathwayi: protein ubiquitination

This protein is involved in the pathway protein ubiquitination, which is part of Protein modification.
View all proteins of this organism that are known to be involved in the pathway protein ubiquitination and in Protein modification.

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri70 – 109RING-type; degeneratePROSITE-ProRule annotationAdd BLAST40
Zinc fingeri150 – 202TRAF-type 1PROSITE-ProRule annotationAdd BLAST53
Zinc fingeri203 – 259TRAF-type 2PROSITE-ProRule annotationAdd BLAST57

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Ligase

Keywords - Biological processi

DNA damage, Immunity, Ubl conjugation pathway

Keywords - Ligandi

Metal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-RNO-166058. MyD88:Mal cascade initiated on plasma membrane.
R-RNO-168638. NOD1/2 Signaling Pathway.
R-RNO-193692. Regulated proteolysis of p75NTR.
R-RNO-202424. Downstream TCR signaling.
R-RNO-205043. NRIF signals cell death from the nucleus.
R-RNO-209543. p75NTR recruits signalling complexes.
R-RNO-209560. NF-kB is activated and signals survival.
R-RNO-2871837. FCERI mediated NF-kB activation.
R-RNO-445989. TAK1 activates NFkB by phosphorylation and activation of IKKs complex.
R-RNO-446652. Interleukin-1 signaling.
R-RNO-450302. activated TAK1 mediates p38 MAPK activation.
R-RNO-450321. JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1.
R-RNO-5607764. CLEC7A (Dectin-1) signaling.
R-RNO-5689896. Ovarian tumor domain proteases.
R-RNO-937039. IRAK1 recruits IKK complex.
R-RNO-937042. IRAK2 mediated activation of TAK1 complex.
R-RNO-975110. TRAF6 mediated IRF7 activation in TLR7/8 or 9 signaling.
R-RNO-975138. TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation.
R-RNO-975144. IRAK1 recruits IKK complex upon TLR7/8 or 9 stimulation.
R-RNO-975155. MyD88 dependent cascade initiated on endosome.
R-RNO-975163. IRAK2 mediated activation of TAK1 complex upon TLR7/8 or 9 stimulation.
R-RNO-975871. MyD88 cascade initiated on plasma membrane.
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
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 3

Organism-specific databases

RGDi1306853. Traf6.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Lipid droplet, Nucleus

Pathology & Biotechi

Keywords - Diseasei

Osteopetrosis

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00003916111 – 530TNF receptor-associated factor 6Add BLAST530

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Cross-linki124Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO); alternateBy similarity
Cross-linki124Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin); alternateBy similarity
Cross-linki142Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)By similarity
Cross-linki461Glycyl 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. Deubiquitinated by USP10 in a TANK-dependent manner, leading to the negative regulation of NF-kappaB signaling upon DNA damage.By similarity

Keywords - PTMi

Isopeptide bond, Ubl conjugation

Proteomic databases

PaxDbiB5DF45.
PeptideAtlasiB5DF45.
PRIDEiB5DF45.

PTM databases

PhosphoSitePlusiB5DF45.

Expressioni

Gene expression databases

BgeeiENSRNOG00000004639.
GenevisibleiB5DF45. RN.

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. 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. Interacts with PELI2 and PELI3. Binds UBE2V1. Interacts with MAVS/IPS1. Interacts with TAX1BP1. Interacts with IL1RL1. Interacts with TRAFD1. Interacts with ZNF675. Interacts with AJUBA. Interacts with TICAM2. Interacts with ZFAND5. 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 (via TRAF domains) with WDR34 (via WD domains). Interacts with RBCK1 (By similarity). Interacts with TRAF3IP2 (By similarity). Interacts with LIMD1 (via LIM domains) (By similarity). Interacts with RSAD2/viperin (By similarity). 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. Interacts with TICAM1 and this interaction is enhanced in the presence of WDFY1 (By similarity). Interacts with TANK; this interaction increases in response to DNA damage (By similarity). Interacts with USP10; this interaction increases in response to DNA damage (By similarity). Interacts with ZC3H12A; this interaction increases in response to DNA damage and is stimulated by TANK (By similarity).By similarity

Protein-protein interaction databases

BioGridi259875. 8 interactors.
STRINGi10116.ENSRNOP00000006148.

Structurei

3D structure databases

ProteinModelPortaliB5DF45.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini358 – 507MATHPROSITE-ProRule annotationAdd BLAST150

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 362Interaction with TAX1BP1By similarityAdd BLAST362
Regioni363 – 530Interaction with TANKBy similarityAdd BLAST168

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili302 – 356Sequence analysisAdd BLAST55

Domaini

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

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)DescriptionActionsGraphical viewLength
Zinc fingeri70 – 109RING-type; degeneratePROSITE-ProRule annotationAdd BLAST40
Zinc fingeri150 – 202TRAF-type 1PROSITE-ProRule annotationAdd BLAST53
Zinc fingeri203 – 259TRAF-type 2PROSITE-ProRule annotationAdd BLAST57

Keywords - Domaini

Coiled coil, Repeat, Zinc-finger

Phylogenomic databases

eggNOGiENOG410ISDW. Eukaryota.
ENOG410XTXK. LUCA.
GeneTreeiENSGT00550000074359.
HOGENOMiHOG000006625.
HOVERGENiHBG060248.
InParanoidiB5DF45.
KOiK03175.
OMAiNFQETIH.
OrthoDBiEOG091G0GHD.
PhylomeDBiB5DF45.
TreeFamiTF321154.

Family and domain databases

Gene3Di2.60.210.10. 1 hit.
3.30.40.10. 1 hit.
3.90.890.10. 1 hit.
InterProiIPR002083. MATH/TRAF_dom.
IPR013323. SIAH-type.
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:SF85. PTHR10131:SF85. 1 hit.
PfamiPF02176. zf-TRAF. 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]

Sequencei

Sequence statusi: Complete.

B5DF45-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSLLNCENSC ASSQSSSDCC AAMANSCSAA MKDDSVSGCV STGNLSSSFM
60 70 80 90 100
EEIQGYDVEF DPPLESKYEC PICLMALREA VQTPCGHRFC KACITKSIRD
110 120 130 140 150
AGHKCPVDNE ILLENQLFPD NFAKREILSL TVKCPNKGCV QKMELRHLED
160 170 180 190 200
HQVHCEFALV ICPQCQRFFQ KCQINKHIIE DCPRRQVSCV NCAVPMPYEE
210 220 230 240 250
KEIHDQSCPL ANIICEYCGT ILIREQMPNH YDLDCPTAPV PCTFSVFGCH
260 270 280 290 300
EKMQRNHLAR HLQENTQLHM RLLAQAVHNV NLSLRPCDAS SPSRGCRPED
310 320 330 340 350
PNYEETVKQL EGRLVRQDHQ IRELTAKMET QSMHVSELKR TIRSLEDKVA
360 370 380 390 400
EMEAQQCNGI YIWKIGNFGM HLKSQEEERP VVIHSPGFYT GRPGYKLCMR
410 420 430 440 450
LHLQLPTAQR CANYISLFVH TMQGEYDSHL PWPFQGTIRL TILDQSEAVI
460 470 480 490 500
RQNHEEVMDA KPELLAFQRP TIPRNPKGFG YVTFMHLEAL RQGTFIKDDT
510 520 530
LLVRCEVSTR FDMGGLRKEG FQPRSTDAGV
Length:530
Mass (Da):60,253
Last modified:October 14, 2008 - v1
Checksum:i5DCC4DEB4CF2DA4F
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
CH473949 Genomic DNA. Translation: EDL79625.1.
BC168921 mRNA. Translation: AAI68921.1.
RefSeqiNP_001101224.1. NM_001107754.2.
UniGeneiRn.220435.
Rn.24348.

Genome annotation databases

EnsembliENSRNOT00000006148; ENSRNOP00000006148; ENSRNOG00000004639.
GeneIDi311245.
KEGGirno:311245.
UCSCiRGD:1306853. rat.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
CH473949 Genomic DNA. Translation: EDL79625.1.
BC168921 mRNA. Translation: AAI68921.1.
RefSeqiNP_001101224.1. NM_001107754.2.
UniGeneiRn.220435.
Rn.24348.

3D structure databases

ProteinModelPortaliB5DF45.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi259875. 8 interactors.
STRINGi10116.ENSRNOP00000006148.

PTM databases

PhosphoSitePlusiB5DF45.

Proteomic databases

PaxDbiB5DF45.
PeptideAtlasiB5DF45.
PRIDEiB5DF45.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSRNOT00000006148; ENSRNOP00000006148; ENSRNOG00000004639.
GeneIDi311245.
KEGGirno:311245.
UCSCiRGD:1306853. rat.

Organism-specific databases

CTDi7189.
RGDi1306853. Traf6.

Phylogenomic databases

eggNOGiENOG410ISDW. Eukaryota.
ENOG410XTXK. LUCA.
GeneTreeiENSGT00550000074359.
HOGENOMiHOG000006625.
HOVERGENiHBG060248.
InParanoidiB5DF45.
KOiK03175.
OMAiNFQETIH.
OrthoDBiEOG091G0GHD.
PhylomeDBiB5DF45.
TreeFamiTF321154.

Enzyme and pathway databases

UniPathwayiUPA00143.
ReactomeiR-RNO-166058. MyD88:Mal cascade initiated on plasma membrane.
R-RNO-168638. NOD1/2 Signaling Pathway.
R-RNO-193692. Regulated proteolysis of p75NTR.
R-RNO-202424. Downstream TCR signaling.
R-RNO-205043. NRIF signals cell death from the nucleus.
R-RNO-209543. p75NTR recruits signalling complexes.
R-RNO-209560. NF-kB is activated and signals survival.
R-RNO-2871837. FCERI mediated NF-kB activation.
R-RNO-445989. TAK1 activates NFkB by phosphorylation and activation of IKKs complex.
R-RNO-446652. Interleukin-1 signaling.
R-RNO-450302. activated TAK1 mediates p38 MAPK activation.
R-RNO-450321. JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1.
R-RNO-5607764. CLEC7A (Dectin-1) signaling.
R-RNO-5689896. Ovarian tumor domain proteases.
R-RNO-937039. IRAK1 recruits IKK complex.
R-RNO-937042. IRAK2 mediated activation of TAK1 complex.
R-RNO-975110. TRAF6 mediated IRF7 activation in TLR7/8 or 9 signaling.
R-RNO-975138. TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation.
R-RNO-975144. IRAK1 recruits IKK complex upon TLR7/8 or 9 stimulation.
R-RNO-975155. MyD88 dependent cascade initiated on endosome.
R-RNO-975163. IRAK2 mediated activation of TAK1 complex upon TLR7/8 or 9 stimulation.
R-RNO-975871. MyD88 cascade initiated on plasma membrane.

Miscellaneous databases

PROiB5DF45.

Gene expression databases

BgeeiENSRNOG00000004639.
GenevisibleiB5DF45. RN.

Family and domain databases

Gene3Di2.60.210.10. 1 hit.
3.30.40.10. 1 hit.
3.90.890.10. 1 hit.
InterProiIPR002083. MATH/TRAF_dom.
IPR013323. SIAH-type.
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:SF85. PTHR10131:SF85. 1 hit.
PfamiPF02176. zf-TRAF. 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...

Entry informationi

Entry nameiTRAF6_RAT
AccessioniPrimary (citable) accession number: B5DF45
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 9, 2010
Last sequence update: October 14, 2008
Last modified: November 30, 2016
This is version 80 of the entry and version 1 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. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  2. SIMILARITY comments
    Index of protein domains and families

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 one 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.