| + |
TRAF6 | up-regulates activity 
ubiquitination
|
IRAK1 |
0.912 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-262298 |
Lys134 |
AEAWSPRkLPSSAST |
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 18347055 |
K63-linked polyubiquitination of proximal signaling proteins is a common mechanism used by diverse innate immune receptors for recruiting IKK and activating NF-_B |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-252252 |
Lys180 |
SPAPSSTkPGPESSV |
Homo sapiens |
|
| pmid |
sentence |
| 18347055 |
K63-linked polyubiquitination of proximal signaling proteins is a common mechanism used by diverse innate immune receptors for recruiting IKK and activating NF-_B |
|
| Publications: |
2 |
Organism: |
Homo Sapiens |
| Pathways: | Innate Immune Response, IL1 Signaling , Toll like receptors |
| + |
TRAF6 | down-regulates activity 
ubiquitination
|
MYC |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-278563 |
Lys148 |
K-->C |
Homo sapiens |
|
| pmid |
sentence |
| 35045331 |
We posited that TRAF6 ubiquitination of MYC at K148 prevents its acetylation, which results in diminished MYC activity ( xref ). |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
TRAF6 | up-regulates activity
ubiquitination
|
TP53 |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-278728 |
Lys24 |
ETFSDLWkLLPENNV |
Homo sapiens |
|
| pmid |
sentence |
| 27818144 |
Here, we show that TRAF6 E3 ligase is a crucial factor to restrict mitochondrial translocation of p53 and spontaneous apoptosis by promoting K63-linked ubiquitination of p53 at K24 in cytosol, and such ubiquitination limits the interaction between p53 and MCL-1/BAK.|We mutated every conserved lysine (K) residue on p53 and found that TRAF6 preferentially ubiquitinates p53 at K24 in the in vivo ubiquitination assay (XREF_FIG, XREF_SUPPLEMENTARY, XREF_SUPPLEMENTARY and XREF_SUPPLEMENTARY). |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | EBV infection, P38 Signaling |
| + |
TRAF6 | up-regulates quantity by stabilization
ubiquitination
|
KLF4 |
0.289 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-277464 |
Lys32 |
SGPAGREkTLRQAGA |
Homo sapiens |
HEK-293T Cell |
| pmid |
sentence |
| 31281496 |
We further found that inhibition of polo-like kinase 1 could downregulate the expression of KLF4 and that PLK1 directly phosphorylated KLF4 at Ser234. Notably, phosphorylation of KLF4 by PLK1 caused the recruitment and binding of the E3 ligase TRAF6, which resulted in KLF4 K32 K63-linked ubiquitination and stabilization. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
TRAF6 | up-regulates activity
ubiquitination
|
MAP3K7 |
0.889 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-236071 |
Lys34 |
NFEEIDYkEIEVEEV |
Homo sapiens |
|
| pmid |
sentence |
| 18758450 |
Intriguingly, TGF-beta-induced TRAF6-mediated Lys 63-linked polyubiquitylation of TAK1 Lys 34 correlates with TAK1 activation. Our data show that TGF-beta specifically activates TAK1 through interaction of TbetaRI with TRAF6, whereas activation of Smad2 is not dependent on TRAF6. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | COVID-19 Causal Network, EBV infection, IL1 Signaling , Inflammosome Activation, NF-KB Canonical, P38 Signaling, SARS-CoV MAPK PERTURBATION, SARS-CoV INFLAMMATORY RESPONSE, TGF-beta Signaling, Toll like receptors |
| + |
RPS6KA3 | up-regulates activity
phosphorylation
|
TRAF6 |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-278302 |
Ser46 |
TASTGNLsSSFMEEI |
Homo sapiens |
|
| pmid |
sentence |
| 29563609 |
These results demonstrate that TRAF6 K63 ubiquitination might be regulated by an RSK2 mediated phosphorylation dependent mechanism and phosphorylation of TRAF6 at Ser46, 47 and 48 enhances its ubiquitin mediated inflammation signaling. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
GSK3B | down-regulates quantity by destabilization
phosphorylation
|
TRAF6 |
0.487 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-277438 |
Thr266 |
ARHLQENtQSHMRML |
Homo sapiens |
HEK-293T Cell |
| pmid |
sentence |
| 30806153 |
TRAF6 was phosphorylated at Thr266 by GSK3B in most clinical CRC, which triggered K48-linked polyubiquitination and degradation of TRAF6 and thereby attenuated its inhibitory activity towards the autophagy-dependent CTNNB1 signaling. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
SRC | up-regulates activity
phosphorylation
|
TRAF6 |
0.579 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-277865 |
Tyr288 |
SVIPDSGyISEVRNF |
Homo sapiens |
HEK-293T Cell |
| pmid |
sentence |
| 37977223 |
To gain further insights into the molecular mechanisms, we employed mass spectrometry to identify the specific tyrosine residues of Traf6 that are phosphorylated by c-Src.By mutating these phosphorylation sites to phenylalanine, we disrupted Traf6-mediated polyubiquitination and subsequently observed the inactivation of AEP. This finding suggests that the phosphorylation of Traf6 by c-Src is crucial for AEP activation. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-277863 |
Tyr326 |
KMETQSMyVSELKRT |
Homo sapiens |
HEK-293T Cell |
| pmid |
sentence |
| 37977223 |
To gain further insights into the molecular mechanisms, we employed mass spectrometry to identify the specific tyrosine residues of Traf6 that are phosphorylated by c-Src.By mutating these phosphorylation sites to phenylalanine, we disrupted Traf6-mediated polyubiquitination and subsequently observed the inactivation of AEP. This finding suggests that the phosphorylation of Traf6 by c-Src is crucial for AEP activation. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-277864 |
Tyr353 |
AQQCNGIyIWKIGNF |
Homo sapiens |
HEK-293T Cell |
| pmid |
sentence |
| 37977223 |
To gain further insights into the molecular mechanisms, we employed mass spectrometry to identify the specific tyrosine residues of Traf6 that are phosphorylated by c-Src.By mutating these phosphorylation sites to phenylalanine, we disrupted Traf6-mediated polyubiquitination and subsequently observed the inactivation of AEP. This finding suggests that the phosphorylation of Traf6 by c-Src is crucial for AEP activation. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-277866 |
Tyr381 |
VIHSPGFyTGKPGYK |
Homo sapiens |
HEK-293T Cell |
| pmid |
sentence |
| 37977223 |
To gain further insights into the molecular mechanisms, we employed mass spectrometry to identify the specific tyrosine residues of Traf6 that are phosphorylated by c-Src.By mutating these phosphorylation sites to phenylalanine, we disrupted Traf6-mediated polyubiquitination and subsequently observed the inactivation of AEP. This finding suggests that the phosphorylation of Traf6 by c-Src is crucial for AEP activation. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-277867 |
Tyr473 |
RNPKGFGyVTFMHLE |
Homo sapiens |
HEK-293T Cell |
| pmid |
sentence |
| 37977223 |
To gain further insights into the molecular mechanisms, we employed mass spectrometry to identify the specific tyrosine residues of Traf6 that are phosphorylated by c-Src.By mutating these phosphorylation sites to phenylalanine, we disrupted Traf6-mediated polyubiquitination and subsequently observed the inactivation of AEP. This finding suggests that the phosphorylation of Traf6 by c-Src is crucial for AEP activation. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-277862 |
Tyr68 |
DPPLESKyECPICLM |
Homo sapiens |
HEK-293T Cell |
| pmid |
sentence |
| 37977223 |
To gain further insights into the molecular mechanisms, we employed mass spectrometry to identify the specific tyrosine residues of Traf6 that are phosphorylated by c-Src.By mutating these phosphorylation sites to phenylalanine, we disrupted Traf6-mediated polyubiquitination and subsequently observed the inactivation of AEP. This finding suggests that the phosphorylation of Traf6 by c-Src is crucial for AEP activation. |
|
| Publications: |
6 |
Organism: |
Homo Sapiens |
| + |
TRAF6 | down-regulates quantity by destabilization
polyubiquitination
|
RUSC1 |
0.324 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-272774 |
|
|
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 19365808 |
We demonstrated that NESCA and NEMO interact by their N-terminal region. Beside to NEMO, we revealed that NESCA directly associates to the E3 ubiquitin ligase TRAF6, which in turn catalyzes NESCA polyubiquitination. Finally, we demonstrated that NESCA overexpression strongly inhibits TRAF6-mediated polyubiquitination of NEMO. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
TRAF6 | down-regulates quantity by destabilization
polyubiquitination
|
MAP1LC3B |
0.3 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-277439 |
|
|
Homo sapiens |
HEK-293T Cell |
| pmid |
sentence |
| 30806153 |
TRAF6 catalyzes K63-linked polyubiquitination of LC3B and promotes the formation of the LC3B-ATG7 and LC3B-CTNNB1 complexes. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
TRAF6 | up-regulates activity
binding
|
MAP3K14 |
0.621 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-253048 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 10075662 |
RANK activates NF-κB by interacting with TRAF6 via a novel TRAF6 interaction motif and TRAF6 potentially activates NIK, leading to NF-κB activation. TRAF6 has been demonstrated to interact with NIK. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Innate Immune Response |
| + |
TRAF6 | up-regulates
ubiquitination
|
MALT1 |
0.748 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-158554 |
|
|
Homo sapiens |
T-lymphocyte |
| pmid |
sentence |
| 17948050 |
Traf6 associates with malt1 in response to t-cell activation and can function as an e3 ligase for malt1 in vitro and in vivo, mediating lysine 63-linked ubiquitination of malt1. Multiple lysine residues in the c-terminus of malt1 serve as acceptor sites for the assembly of polyubiquitin chains. (articolo-abstract) |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
CYLD | down-regulates
deubiquitination
|
TRAF6 |
0.783 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-117856 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 12917689 |
The nf-kappab activation by cyld is mediated, at least in part, by the deubiquitination and inactivation of tnfr-associated factor 2 (traf2) and, to a lesser extent, traf6. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Tissue: |
Skin |
| Pathways: | NF-KB Canonical |
| + |
TRAF6 | up-regulates
polyubiquitination
|
TICAM1 |
0.824 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-271428 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 20047764 |
Here, we show that the TRAF family proteins directly bind TICAM-1 and demonstrate that TRAF2 and TRAF6 bind different sites of the N-terminal TICAM-1 and accelerate its polyubiquitination. we speculate that polyubiquitination of TICAM-1 by TRAF2 and TRAF6 is required for TICAM-1 to induce IRF-3 and NF-κB activation. This is supported by the observation that polyubiquitination of TICAM-1 was required for TRAF3-binding to TICAM-1 |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | COVID-19 Causal Network, EBV infection, Innate Immune Response, Inflammosome Activation, SARS-CoV INFLAMMATORY RESPONSE, Toll like receptors |
| + |
TRAF6 | up-regulates activity
binding
|
TAB1 |
0.861 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-205455 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 25290089 |
The irak1/traf6 complex can also activate jnk and p38 signalling through assembly of a catalytically active tab2-tab3-tak1 complex. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | P38 Signaling |
| + |
TRAF6 | down-regulates quantity
ubiquitination
|
HK2 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-260003 |
|
|
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 28980855 |
The Lys63-linked ubiquitination of HK2 catalyzed by the E3 ligase TRAF6 was critical for the subsequent recognition of HK2 by the autophagy receptor protein SQSTM1/p62 for the process of selective autophagic degradation. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
IRAK1 | up-regulates activity
binding
|
TRAF6 |
0.912 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-44234 |
|
|
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 8837778 |
Il-1 treatment of 293 cells induces the association of traf6 with irak. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-92994 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 12242293 |
We now find that the phosphorylated IRAK in turn recruits TRAF6 to the receptor complex (complex I), which differs from the previous concept that IRAK interacts with TRAF6 after it leaves the receptor. IRAK then brings TRAF6 to TAK1 |
|
| Publications: |
2 |
Organism: |
Homo Sapiens |
| Pathways: | Innate Immune Response, IL1 Signaling , Toll like receptors |
| + |
TRIM38 | down-regulates quantity by destabilization
polyubiquitination
|
TRAF6 |
0.439 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-272009 |
|
|
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 22323536 |
As an E3 ligase, TRIM38 bound to TRAF6 and promoted K48-linked polyubiquitination, which led to the proteasomal degradation of TRAF6. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
NLRX1 | down-regulates activity
binding
|
TRAF6 |
0.482 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-260364 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 21703539 |
Immunoprecipitation experiments showed that NLRX1 interacted with TRAF6 and TRAF3, but not with TRAF2 or TRAF5. These results further suggest that NLRX1 specifically inhibits TLR-induced TRAF6-dependent NF-kB signaling through targeting TRAF6. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
TGFBR1 | up-regulates activity
binding
|
TRAF6 |
0.437 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-241918 |
|
|
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 18922473 |
We report here that TRAF6 is specifically required for the Smad-independent activation of JNK and p38 and its carboxyl TRAF homology domain physically interacts with TGF-² receptors |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-236119 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 18758450 |
Here we report that the ubiquitin ligase (e3) traf6 interacts with a consensus motif present in tbetari. The tbetari-traf6 interaction is required for tgf-beta-induced autoubiquitylation of traf6 and subsequent activation of the tak1-p38/jnk pathway, which leads to apoptosis. |
|
| Publications: |
2 |
Organism: |
Homo Sapiens |
| Tissue: |
HEK-293T Cell |
| Pathways: | COVID-19 Causal Network, P38 Signaling, SARS-CoV MAPK PERTURBATION, TGF-beta Signaling |
| + |
IL1RL1 | up-regulates activity
binding
|
TRAF6 |
0.581 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-277707 |
|
|
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 16286016 |
As shown in Figure 3D, MyD88, IRAK, IRAK4, and TRAF6 are all recruited to ST2 upon IL-33 stimulation. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
NOTCH2 | down-regulates activity
binding
|
TRAF6 |
0.315 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-265562 |
|
|
Homo sapiens |
Nasopharyngeal Carcinoma Cell Line |
| pmid |
sentence |
| 31699119 |
NOTCH2 attenuated the TRAF6-AKT signaling axis via an interaction between the NOTCH2 intracellular domain (N2ICD) and TRAF6, which inhibited epithelial-mesenchymal transition (EMT) and eventually suppressed NPC metastasis. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
TRAF6 | up-regulates activity
ubiquitination
|
TRAF6 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-252099 |
|
|
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 17135271 |
These data establish a signaling cascade in which regulated site-specific Lys-63-linked TRAF6 auto-ubiquitination is the critical upstream mediator of IKK. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-180562 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 18758450 |
Here we report that the ubiquitin ligase (e3) traf6 interacts with a consensus motif present in tbetari. The tbetari-traf6 interaction is required for tgf-beta-induced autoubiquitylation of traf6 and subsequent activation of the tak1-p38/jnk pathway, which leads to apoptosis. |
|
| Publications: |
2 |
Organism: |
Homo Sapiens |
| Pathways: | COVID-19 Causal Network, EBV infection, Innate Immune Response, IL1 Signaling , Inflammosome Activation, NF-KB Canonical, P38 Signaling, SARS-CoV MAPK PERTURBATION, SARS-CoV INFLAMMATORY RESPONSE, TGF-beta Signaling, Toll like receptors |
| + |
AMBRA1 | up-regulates activity
binding
|
TRAF6 |
0.578 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-272963 |
|
|
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 23524951 |
In this condition, AMBRA1, interacting with the E3-ligase TRAF6, supports ULK1 ubiquitylation by LYS-63-linked chains, and its subsequent stabilization, self-association and function. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
TRAF6 | up-regulates quantity by stabilization
polyubiquitination
|
LGMN |
0.311 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-272853 |
|
|
Homo sapiens |
MDA-MB-231 Cell |
| pmid |
sentence |
| 24610907 |
We demonstrate that TRAF6 ubiquitinates the proform of AEP through K63-linked polyubiquitin, reversible by USP17, and forms a complex with HSP90α to subsequently promote pro-AEP intracellular stability as well as secretion. We now present evidence that AEP is a substrate for TRAF6 ubiquitination, resulting in AEP/TRAF6/HSP90α complex formation. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
Ub:E2 | up-regulates activity
ubiquitination
|
TRAF6 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-270981 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 34199813 |
The ubiquitination process is mediated sequentially by three classes of enzymes consisting of a Ub-activating enzyme E1, a Ub-conjugating enzyme E2, and a Ub ligase E3. Ub is first activated by E1 in an adenosine 5′-triphosphate (ATP)-dependent manner t |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
TRAF6 | up-regulates quantity by stabilization
ubiquitination
|
ULK1 |
0.535 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-273000 |
|
|
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 23524951 |
AMBRA1, interacting with the E3-ligase TRAF6, supports ULK1 ubiquitylation by LYS-63-linked chains, and its subsequent stabilization, self-association and function. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
TRAF6 | up-regulates activity
binding
|
TNFRSF11A |
0.719 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-253045 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 10075662 |
TRAF6 interacts with a novel motif located between residues 340 and 358 of RANK. TRAF6-binding region (340-358), but not the TRAF2 or TRAF5-binding region, is necessary and sufficient for RANK-induced NF-kappaB activation. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
TRAF6 | up-regulates activity
binding
|
TAB2 |
0.931 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-205458 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 25290089 |
The irak1/traf6 complex can also activate jnk and p38 signalling through assembly of a catalytically active tab2-tab3-tak1 complex. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | IL1 Signaling , NF-KB Canonical |
| + |
TRAF6 | up-regulates activity
binding
|
CSNK2A1 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-273656 |
|
|
Homo sapiens |
THP-1 Cell |
| pmid |
sentence |
| 29733298 |
Here, we show that somatic nuclear autoantigenic sperm protein (sNASP) binds to TRAF6 to prevent TRAF6 autoubiquitination in unstimulated macrophages. Following LPS stimulation, a complex consisting of sNASP, TRAF6, IRAK4, and casein kinase 2 (CK2) is formed. CK2 phosphorylates sNASP at serine 158, allowing sNASP to dissociate from TRAF6. Free TRAF6 is then autoubiquitinated, followed by activation of downstream signaling pathways. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | COVID-19 Causal Network |
| + |
Papain-like proteinase | down-regulates activity
deubiquitination
|
TRAF6 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-260248 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 31226023 |
Also, SARS-CoVPLPro catalyzed deubiquitination ofTNF-receptor-associatedfactor3(TRAF3)and TRAF6, thereby suppressing IFN-I and proinflammatory cytokines induced by TLR7 agonist |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | COVID-19 Causal Network, SARS-CoV INFLAMMATORY RESPONSE |
| + |
BPLF1 | down-regulates activity
deubiquitination
|
TRAF6 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-266739 |
|
|
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 23365429 |
EBV-encoded BPLF1 interacts with and deubiquitinates TRAF6 to inhibit NF-κB signaling during lytic infection. Once lytic replication is induced, BPLF1 then deubiquitinates and inactivates TRAF6 to further block NF-κB signaling, promoting efficient viral genome replication. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | EBV infection |
| + |
9b | down-regulates quantity by destabilization 
|
TRAF6 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-260243 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 25135833 |
SARS-coronavirus Open Reading frame-9b Suppresses Innate Immunity by Targeting Mitochondria and the MAVS/TRAF3/TRAF6 Signalosome. Acting on mitochondria, ORF-9b targets the mitochondrial-associated adaptor molecule MAVS signalosome by usurping PCBP2 and the HECT domain E3 ligase AIP4 to trigger the degradation of MAVS, TRAF3, and TRAF 6. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | COVID-19 Causal Network, SARS-CoV INFLAMMATORY RESPONSE |
| + |
TRAF6 | down-regulates activity
ubiquitination
|
ECSIT |
0.785 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-260370 |
|
|
Mus musculus |
|
| pmid |
sentence |
| 21525932 |
Here we demonstrate that engagement of a subset of Toll-like receptors (TLR1, TLR2 and TLR4) results in the recruitment of mitochondria to macrophage phagosomes and augments mROS production. This response involves translocation of a TLR signalling adaptor, tumour necrosis factor receptor-associated factor 6 (TRAF6), to mitochondria, where it engages the protein ECSIT (evolutionarily conserved signalling intermediate in Toll pathways), which is implicated in mitochondrial respiratory chain assembly. Interaction with TRAF6 leads to ECSIT ubiquitination and enrichment at the mitochondrial periphery, resulting in increased mitochondrial and cellular ROS generation |
|
| Publications: |
1 |
Organism: |
Mus Musculus |
| + |
RIPK1 | up-regulates activity
binding
|
TRAF6 |
0.65 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-216325 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 20404851 |
Collectively, TRIF forms a multiprotein signaling complex along with TRAF6, TRADD, Pellino-1 and RIP1 for the activation of TAK1, which in turn activates the NF-_B and MAPK pathways. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | COVID-19 Causal Network, Innate Immune Response, Inflammosome Activation, NF-KB Canonical, SARS-CoV INFLAMMATORY RESPONSE |
| + |
TRAF6 | up-regulates activity
binding
|
TAB3 |
0.705 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-205461 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 25290089 |
The irak1/traf6 complex can also activate jnk and p38 signalling through assembly of a catalytically active tab2-tab3-tak1 complex. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | NF-KB Canonical |
| + |
RUNX3 | up-regulates quantity by expression 
transcriptional regulation
|
TRAF6 |
0.252 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-255098 |
|
|
Homo sapiens |
MKN-1 Cell |
| pmid |
sentence |
| 17956589 |
Comprehensive analysis using a cDNA microarray showed that RUNX3 upregulated 17 apoptosis-related genes (including FADD, TRAF6, caspase-2, ING1, ING4, Calpain 10, and DNase1) and downregulated 135 apoptosis-related genes (including FLIP, PEA15, TXN2, HSPD1, IKK, and TIAL1) in MKN-1 cells. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
INPP5D | down-regulates activity
binding
|
TRAF6 |
0.336 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-261429 |
|
|
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 24817116 |
Of note, SHIP1 was associated with TRAF6 in co-transfected HEK293T cells (Fig. 6A). Moreover, SHIP1 overexpression suppressed TRAF6 autoubiquitination in a dose-dependent manner |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
NASP | down-regulates activity
binding
|
TRAF6 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-273655 |
|
|
Homo sapiens |
THP-1 Cell |
| pmid |
sentence |
| 29733298 |
SNASP inhibits TLR4-induced NF-κB activation through TRAF6.Reciprocal immunoprecipitation and Western blot analyses confirmed that endogenous sNASP binds to TRAF6 in human monocyte cell line THP-1 (Figure 1B).Here, we show that somatic nuclear autoantigenic sperm protein (sNASP) binds to TRAF6 to prevent TRAF6 autoubiquitination in unstimulated macrophages. Following LPS stimulation, a complex consisting of sNASP, TRAF6, IRAK4, and casein kinase 2 (CK2) is formed. CK2 phosphorylates sNASP at serine 158, allowing sNASP to dissociate from TRAF6. Free TRAF6 is then autoubiquitinated, followed by activation of downstream signaling pathways. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
TRIM23 | up-regulates activity
ubiquitination
|
TRAF6 |
0.318 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-266655 |
|
|
Homo sapiens |
Hairy Cell Leukemia Cell |
| pmid |
sentence |
| 19176615 |
We show here that the upregulation of NF-kappaB by UL144 is dependent upon cellular tripartite motif 23 (TRIM23) protein. We propose a mechanism by which UL144 activates NF-kappaB through a direct interaction with the cellular protein TRIM23 in a complex containing TRAF6. we propose that TRIM23 mediates TRAF6 autoubiquitination in the presence of UL144, resulting in the virally controlled activation of NF-κB stimulation at early times of HCMV infection. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
TRAF6 | down-regulates quantity
ubiquitination
|
Hexokinase |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-270271 |
|
|
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 28980855 |
The Lys63-linked ubiquitination of HK2 catalyzed by the E3 ligase TRAF6 was critical for the subsequent recognition of HK2 by the autophagy receptor protein SQSTM1/p62 for the process of selective autophagic degradation. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
UBE2V1 | up-regulates activity
binding
|
TRAF6 |
0.69 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-83603 |
|
|
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 11057907 |
We find that traf6, a ring domain protein, functions together with ubc13/uev1a to catalyze the synthesis of unique polyubiquitin chains linked through lysine-63 (k63) of ubiquitin |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | IL1 Signaling , NF-KB Canonical |
| + |
MYD88 | up-regulates activity
binding
|
TRAF6 |
0.92 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-260160 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 28404732 |
In innate immunity, nearly all Toll-like receptors (TLRs), as well as the receptors of the interleukin 1 (IL-1) family of cytokines, initiate signaling by recruiting the adaptor protein MyD88. This is followed by the interaction of IL-1-receptor (IL-R)-associated kinase 4 (IRAK4) with MyD88 and then the interaction of other IRAK family members with IRAK4, to form an oligomeric complex, termed the Myddosome (8, 9). IRAK1 and IRAK2 can then interact with TRAF6 (10, 11) and induce TRAF6 dimerization (12), which triggers the activation of its E3 ligase activity |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | COVID-19 Causal Network, EBV infection, Innate Immune Response, IL1 Signaling , Inflammosome Activation, SARS-CoV INFLAMMATORY RESPONSE, Toll like receptors |
| + |
TDP2 | up-regulates activity
binding
|
TRAF6 |
0.384 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-277189 |
|
|
Homo sapiens |
HEK-293T Cell |
| pmid |
sentence |
| 21980489 |
TTRAP associates with TRAF6.The TAK1-TTRAP-TRAF6 complex is stabilized by ubiquitylation and recruited to TβRI. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
TRAF6 | up-regulates
|
Osteoclast_differentiation |
0.7 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-253046 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 17572386 |
TRAF6 ubiquitin ligase is essential for RANKL signaling and osteoclast differentiation. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
TRAF6 | up-regulates activity
|
MAP3K8 |
0.426 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-252254 |
|
|
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 16371247 |
The activation of Cot-MKK1-ERK1/ERK2 signalling pathway by IL-1 is dependent on the activity of the transducer protein TRAF6. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Toll like receptors |
| + |
TNFAIP3 | down-regulates activity
deubiquitination
|
TRAF6 |
0.693 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-160223 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 18164316 |
A20 is a deubiquitinating enzyme (dub) for lys63-linked polyubiquitinated signaling mediators such as traf6 |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | IL1 Signaling , NF-KB Canonical |
| + |
TRAF6 | down-regulates quantity by destabilization
ubiquitination
|
IL1R1 |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-278576 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 19232518 |
We found that of all TRAFs and E3 ligases examined, TRAF6 preferentially ubiquitinated IL-1R1. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | IL1 Signaling |
| + |
TRAF6 | up-regulates quantity by stabilization
ubiquitination
|
PSEN1 |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-278601 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 23707529 |
We have also observed that ubiquitination of PS1 by TRAF6 increases the stability of PS1 holoprotein, and TRAF6-deficiency coincides with reduced endogenous PS1 and PS2 levels. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
TRAF6 | down-regulates activity
ubiquitination
|
STAT3 |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-278618 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 23185365 |
TRAF6 Interacts with STAT3 and Mediates the Ubiquitination of STAT3.|TRAF6 Represses the Transcriptional Activity of STAT3. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | EBV infection |
| + |
STUB1 | down-regulates quantity by destabilization
ubiquitination
|
TRAF6 |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-278670 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 24578159 |
CHIP promotes TRAF6 ubiquitination and degradation.|These results suggest that CHIP negatively regulates the stability of TRAF6. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
TRAF6 | up-regulates activity
ubiquitination
|
LAT |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-278675 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 23514740 |
Interestingly, this study has demonstrated that the membrane-proximal region of linker for activation of T cells preceding tyrosine-132 mediates its association with TRAF6, which promotes the ubiquitination of linker for activation of T cells and, in turn, the phosphorylation of tyrosine residues on linker for activation of T cells.|Moreover, LAT was ubiquitinated at Lysine 88 by TRAF6 via K63 linked chain. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
PELI3 | down-regulates quantity
ubiquitination
|
TRAF6 |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-278707 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 25526310 |
Finally, we used coexpression studies to directly demonstrate that Pellino3 inhibits the ability of wild-type TRAF6 to stabilize HIF-1alpha but not the stabilizing effects of the K124A TRAF6 mutant that is resistant to ubiquitination.|In the present study, Pellino3 ubiquitinates TRAF6 with lysine 63-linked polyubiquitin chains to block the interaction of TRAF6 with HIF-1\u03b1. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
TRAF6 | up-regulates activity
ubiquitination
|
TDP2 |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-278717 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 21980489 |
TTRAP is ubiquitylated by TRAF6 and promotes TRAF6 dependent ubiquitylation of TAK1.|In addition, we noted that the presence of TRAF6 strengthened the interaction between TTRAP and the TGF-\u03b2 receptor complex (see also later). |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
TRAF6 | down-regulates quantity
ubiquitination
|
CRTC2 |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-278725 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 27990298 |
Consistently, TRAF6 reduced G6pase gene expression or reporter activity induced by wild-type CRTC1 and CRTC2 but not TRAF6-interaction-defective CRTC1 and CRTC2 (XREF_FIG and XREF_SUPPLEMENTARY).|Indeed, TRAF6, the E3 ubiquitin ligase activated by IL-1beta associates with and ubiquitinates CRTC2. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
TRAF6 | up-regulates activity
ubiquitination
|
MCL1 |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-278726 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 25340740 |
TRAF6 likely directly ubiquitinates MCL-1 since purified TRAF6 promoted the ubiquitination of recombinant GST-MCL-1 and co-expression of Tax with TRAF6 further enhanced MCL-1 ubiquitination .|Therefore, TRAF6 mediated MCL-1 stabilization appears to be a common mechanism of cell survival usurped by both viral and non viral cancers. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | COVID-19 Causal Network |
| + |
TRAF6 | up-regulates activity
ubiquitination
|
PIK3CA |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-278727 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 29729098 |
In contrast to NEDD4L, overexpression of TRAF6 increases the stability of PIK3CA protein and promotes PI3K activation.|TRAF6 ubiquitinates PIK3CA in vivo. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
TRAF6 | up-regulates activity
ubiquitination
|
IRF7 |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-278788 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 29202128 |
We have shown that TRAF6 E3 ligase promotes IRF7 K63-linked ubiquitination that is required for EBV LMP1 activation of IRF7 [ xref ]; however, A20, a member with both E3 ligase and deubiquitinase activities in the OTU family, inhibits LMP1-stimulated IRF7 activity by acting as a deubiquitinase [ xref ]. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | EBV infection, Innate Immune Response |
| + |
TRAF6 | up-regulates activity
ubiquitination
|
MTOR |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-278789 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 23911927 |
Together, these results demonstrate that mTOR polyubiquitination by TRAF6 modulates its activation in response to amino acids and point to a role for K63 ubiquitin modification as a sensor of nutrient status. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
3.0
TRAF6
- 
- 