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Protein

TNF receptor-associated factor 6

Gene

TRAF6

Organism
Sus scrofa (Pig)
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)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri71 – 11040RING-type; degeneratePROSITE-ProRule annotationAdd
BLAST
Zinc fingeri151 – 20353TRAF-type 1PROSITE-ProRule annotationAdd
BLAST
Zinc fingeri204 – 26057TRAF-type 2PROSITE-ProRule annotationAdd
BLAST

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Ligase

Keywords - Biological processi

Immunity, Ubl conjugation pathway

Keywords - Ligandi

Metal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-SSC-166058. MyD88:Mal cascade initiated on plasma membrane.
R-SSC-168638. NOD1/2 Signaling Pathway.
R-SSC-202424. Downstream TCR signaling.
R-SSC-209543. p75NTR recruits signalling complexes.
R-SSC-209560. NF-kB is activated and signals survival.
R-SSC-2871837. FCERI mediated NF-kB activation.
R-SSC-445989. TAK1 activates NFkB by phosphorylation and activation of IKKs complex.
R-SSC-446652. Interleukin-1 signaling.
R-SSC-450302. activated TAK1 mediates p38 MAPK activation.
R-SSC-450321. JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1.
R-SSC-5607764. CLEC7A (Dectin-1) signaling.
R-SSC-937039. IRAK1 recruits IKK complex.
R-SSC-937042. IRAK2 mediated activation of TAK1 complex.
R-SSC-937072. TRAF6 mediated induction of TAK1 complex.
R-SSC-975110. TRAF6 mediated IRF7 activation in TLR7/8 or 9 signaling.
R-SSC-975138. TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation.
R-SSC-975144. IRAK1 recruits IKK complex upon TLR7/8 or 9 stimulation.
R-SSC-975155. MyD88 dependent cascade initiated on endosome.
R-SSC-975163. IRAK2 mediated activation of TAK1 complex upon TLR7/8 or 9 stimulation.
R-SSC-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
OrganismiSus scrofa (Pig)
Taxonomic identifieri9823 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaSuinaSuidaeSus
Proteomesi
  • UP000008227 Componenti: Chromosome 2

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)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 541541TNF receptor-associated factor 6PRO_0000391610Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Cross-linki125 – 125Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO); alternateBy similarity
Cross-linki125 – 125Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin); alternateBy similarity
Cross-linki143 – 143Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)By similarity
Cross-linki472 – 472Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)By similarity

Post-translational modificationi

Sumoylated on Lys-125, Lys-143 and Lys-472 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

PaxDbiA7XUJ6.

Expressioni

Gene expression databases

BgeeiENSSSCG00000013291.

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).By similarity

Protein-protein interaction databases

STRINGi9823.ENSSSCP00000029003.

Structurei

3D structure databases

ProteinModelPortaliA7XUJ6.
SMRiA7XUJ6. Positions 44-129, 366-520.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini369 – 518150MATHPROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni1 – 373373Interaction with TAX1BP1By similarityAdd
BLAST

Coiled coil

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Coiled coili312 – 36756Sequence analysisAdd
BLAST

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)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri71 – 11040RING-type; degeneratePROSITE-ProRule annotationAdd
BLAST
Zinc fingeri151 – 20353TRAF-type 1PROSITE-ProRule annotationAdd
BLAST
Zinc fingeri204 – 26057TRAF-type 2PROSITE-ProRule annotationAdd
BLAST

Keywords - Domaini

Coiled coil, Repeat, Zinc-finger

Phylogenomic databases

eggNOGiENOG410ISDW. Eukaryota.
ENOG410XTXK. LUCA.
GeneTreeiENSGT00550000074359.
HOGENOMiHOG000006625.
HOVERGENiHBG060248.
InParanoidiA7XUJ6.
KOiK03175.
OMAiNFQETIH.
OrthoDBiEOG091G0GHD.
TreeFamiTF321154.

Family and domain databases

Gene3Di2.60.210.10. 1 hit.
3.30.40.10. 1 hit.
InterProiIPR002083. MATH/TRAF_dom.
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.

A7XUJ6-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSLLHCENSC GSSQSESDCC AAMAASSCGA AAKDDGVSGT ASTGNLSSSF
60 70 80 90 100
MEEIQGYDVE FDPPLESKYE CPICLMALRE AVQTPCGHRF CKACIIKSIR
110 120 130 140 150
DAGHKCPVDN EILLENQLFP DNFAKREILS LTVKCPNVGC LHKMELRHLE
160 170 180 190 200
DHQAHCEFAL MNCPQCQRPF QKCQLNIHIL KECPRRQVSC VNCAVSMAFE
210 220 230 240 250
DKEIHDQNCP LANVICEYCN TVLIREQMPN HYDLDCPTAP VPCTFSTFGC
260 270 280 290 300
HEKMQRNHLA RHLQENTQSH MRMMAQALQG LSLAVAPVPQ RDMLPYDSSP
310 320 330 340 350
LSRISSGCCS DQNFQETIQQ LEGRLVRQDH QIRELTAKME TQSMYVSELK
360 370 380 390 400
RTIRSLEDKV AEIEAQQCNG IYIWKIGNFG MHLKSQEEEK PVVIHSPGFY
410 420 430 440 450
TGKPGYKLCM RLHLQLPTAQ RCANYISLFV HTMQGEYDSH LPWPFQGTIR
460 470 480 490 500
LTILDQSEAP IRQNHEEIMD AKPELLAFQR PTIPRNPKGF GYVTFMHLDA
510 520 530 540
LRQRTFIKDD TLLVRCEVST RFDMGSLRRE GFQPRSTDSG T
Length:541
Mass (Da):61,266
Last modified:October 23, 2007 - v1
Checksum:iCCA939106D3476BE
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
EU095967 mRNA. Translation: ABU75303.1.
RefSeqiNP_001098756.1. NM_001105286.1.
XP_005652858.1. XM_005652801.1.
XP_013845523.1. XM_013990069.1.
UniGeneiSsc.96412.

Genome annotation databases

EnsembliENSSSCT00000014516; ENSSSCP00000014123; ENSSSCG00000013291.
ENSSSCT00000033074; ENSSSCP00000029003; ENSSSCG00000013291.
GeneIDi396629.
KEGGissc:396629.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
EU095967 mRNA. Translation: ABU75303.1.
RefSeqiNP_001098756.1. NM_001105286.1.
XP_005652858.1. XM_005652801.1.
XP_013845523.1. XM_013990069.1.
UniGeneiSsc.96412.

3D structure databases

ProteinModelPortaliA7XUJ6.
SMRiA7XUJ6. Positions 44-129, 366-520.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi9823.ENSSSCP00000029003.

Proteomic databases

PaxDbiA7XUJ6.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSSSCT00000014516; ENSSSCP00000014123; ENSSSCG00000013291.
ENSSSCT00000033074; ENSSSCP00000029003; ENSSSCG00000013291.
GeneIDi396629.
KEGGissc:396629.

Organism-specific databases

CTDi7189.

Phylogenomic databases

eggNOGiENOG410ISDW. Eukaryota.
ENOG410XTXK. LUCA.
GeneTreeiENSGT00550000074359.
HOGENOMiHOG000006625.
HOVERGENiHBG060248.
InParanoidiA7XUJ6.
KOiK03175.
OMAiNFQETIH.
OrthoDBiEOG091G0GHD.
TreeFamiTF321154.

Enzyme and pathway databases

UniPathwayiUPA00143.
ReactomeiR-SSC-166058. MyD88:Mal cascade initiated on plasma membrane.
R-SSC-168638. NOD1/2 Signaling Pathway.
R-SSC-202424. Downstream TCR signaling.
R-SSC-209543. p75NTR recruits signalling complexes.
R-SSC-209560. NF-kB is activated and signals survival.
R-SSC-2871837. FCERI mediated NF-kB activation.
R-SSC-445989. TAK1 activates NFkB by phosphorylation and activation of IKKs complex.
R-SSC-446652. Interleukin-1 signaling.
R-SSC-450302. activated TAK1 mediates p38 MAPK activation.
R-SSC-450321. JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1.
R-SSC-5607764. CLEC7A (Dectin-1) signaling.
R-SSC-937039. IRAK1 recruits IKK complex.
R-SSC-937042. IRAK2 mediated activation of TAK1 complex.
R-SSC-937072. TRAF6 mediated induction of TAK1 complex.
R-SSC-975110. TRAF6 mediated IRF7 activation in TLR7/8 or 9 signaling.
R-SSC-975138. TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation.
R-SSC-975144. IRAK1 recruits IKK complex upon TLR7/8 or 9 stimulation.
R-SSC-975155. MyD88 dependent cascade initiated on endosome.
R-SSC-975163. IRAK2 mediated activation of TAK1 complex upon TLR7/8 or 9 stimulation.
R-SSC-975871. MyD88 cascade initiated on plasma membrane.

Gene expression databases

BgeeiENSSSCG00000013291.

Family and domain databases

Gene3Di2.60.210.10. 1 hit.
3.30.40.10. 1 hit.
InterProiIPR002083. MATH/TRAF_dom.
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_PIG
AccessioniPrimary (citable) accession number: A7XUJ6
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 9, 2010
Last sequence update: October 23, 2007
Last modified: September 7, 2016
This is version 79 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.