A7XUJ6 (TRAF6_PIG) Reviewed, UniProtKB/Swiss-Prot
Last modified May 1, 2013. Version 50. History...
Names and origin
|Protein names||Recommended name:|
TNF receptor-associated factor 6
E3 ubiquitin-protein ligase TRAF6
|Organism||Sus scrofa (Pig) [Reference proteome]|
|Taxonomic identifier||9823 [NCBI]|
|Taxonomic lineage||Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Laurasiatheria › Cetartiodactyla › Suina › Suidae › Sus|
|Sequence length||541 AA.|
|Protein existence||Evidence at transcript level|
General annotation (Comments)
E3 ubiquitin ligase that, together with UBE2N and UBE2V1, mediates the synthesis of 'Lys-63'-linked-polyubiquitin chains conjugated to proteins, such as IKBKG, 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 By similarity.
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 TICAM1 and 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.
The coiled coil domain mediates homo- and hetero-oligomerization By similarity.
The MATH/TRAF domain binds to receptor cytoplasmic domains By similarity.
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.
Contains 1 MATH domain.
Contains 1 RING-type zinc finger.
Contains 2 TRAF-type zinc fingers.
Sequence annotation (Features)
|Feature key||Position(s)||Length||Description||Graphical view||Feature identifier|
|Chain||1 – 541||541||TNF receptor-associated factor 6||PRO_0000391610|
|Domain||369 – 518||150||MATH|
|Zinc finger||71 – 110||40||RING-type; degenerate|
|Zinc finger||151 – 203||53||TRAF-type 1|
|Zinc finger||204 – 260||57||TRAF-type 2|
|Region||1 – 373||373||Interaction with TAX1BP1 By similarity|
|Coiled coil||312 – 367||56||Potential|
Amino acid modifications
|Cross-link||125||Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO); alternate By similarity|
|Cross-link||125||Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin); alternate By similarity|
|Cross-link||143||Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) By similarity|
|Cross-link||472||Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) By similarity|
|EU095967 mRNA. Translation: ABU75303.1.|
|RefSeq||NP_001098756.1. NM_001105286.1. |
3D structure databases
|SMR||A7XUJ6. Positions 44-129, 366-520. |
Protein-protein interaction databases
Protocols and materials databases
Genome annotation databases
|Ensembl||ENSSSCT00000014516; ENSSSCP00000014123; ENSSSCG00000013291. |
ENSSSCT00000033074; ENSSSCP00000029003; ENSSSCG00000013291.
Enzyme and pathway databases
Family and domain databases
|Gene3D||220.127.116.11. 1 hit. |
|InterPro||IPR002083. MATH. |
|PANTHER||PTHR10131:SF48. PTHR10131:SF48. 1 hit. |
|Pfam||PF00917. MATH. 1 hit. |
|PIRSF||PIRSF015614. TRAF. 1 hit. |
|SMART||SM00061. MATH. 1 hit. |
SM00184. RING. 1 hit.
|SUPFAM||SSF49599. Traf_like. 3 hits. |
|PROSITE||PS50144. MATH. 1 hit. |
PS00518. ZF_RING_1. 1 hit.
PS50089. ZF_RING_2. 1 hit.
PS50145. ZF_TRAF. 2 hits.
|Accession||Primary (citable) accession number: A7XUJ6|
|Entry status||Reviewed (UniProtKB/Swiss-Prot)|
|Annotation program||Chordata Protein Annotation Program|