| + |
DCX DET1-COP1 | down-regulates quantity by destabilization 
ubiquitination
|
CRTC2 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-271666 |
Lys212 |
LDGEMDPkVPAIEEN |
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 17805301 |
In the presence of relevant cofactors (DDB1, DET1), COP1 promoted the ubiquitination of wild-type but not COP1-interaction defective VP/AA TORC2 (Fig. 3e). COP1 also stimulated the ubiquitination of TORC2(K213R) but had no effect on TORC2(K628R), suggesting an important role for Lys 628 in this regard (Fig. 3e). We performed mass spectrometry studies to characterize residues in TORC2 that undergo COP1-mediated ubiquitination. This analysis revealed one major (Lys 628) and one minor (Lys 213) site on TORC2 |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-271665 |
Lys629 |
DSSPGFSkEIAAALA |
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 17805301 |
In the presence of relevant cofactors (DDB1, DET1), COP1 promoted the ubiquitination of wild-type but not COP1-interaction defective VP/AA TORC2 (Fig. 3e). COP1 also stimulated the ubiquitination of TORC2(K213R) but had no effect on TORC2(K628R), suggesting an important role for Lys 628 in this regard (Fig. 3e). We performed mass spectrometry studies to characterize residues in TORC2 that undergo COP1-mediated ubiquitination. This analysis revealed one major (Lys 628) and one minor (Lys 213) site on TORC2 |
|
| Publications: |
2 |
Organism: |
Homo Sapiens |
| + |
VRK2 | up-regulates activity 
binding
|
DCX DET1-COP1 |
0.331 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-272874 |
|
|
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 24298020 |
Here, we propose that vaccinia-related kinase 2 (VRK2) is a critical enzyme that negatively regulates TRiC. In mammalian cells, overexpression of wild-type VRK2 decreased endogenous TRiC protein levels by promoting TRiC ubiquitination, but a VRK2 kinase-dead mutant did not.The VRK2-mediated reduction of TRiC protein levels was subsequent to the recruitment of COP1 E3 ligase. Among the members of the COP1 E3 ligase complex, VRK2 interacted with RBX1 and increased E3 ligase activity on TRiC in vitro. Taken together, these results demonstrate that VRK2 is crucial to regulate the ubiquitination-proteosomal degradation of TRiC, which controls folding of polyglutamine proteins involved in Huntington's disease.COP1 functions as an E3 ligase by forming a supercomplex that also includes heterodimeric substrate receptor DET1, adaptor DDB1, scaffold Cul4A, and RBX1 to recruit the E2 enzyme |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
COP1 | form complex 
binding
|
DCX DET1-COP1 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-154514 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 17452440 |
Mammalian det1 regulates cul4a activity and forms stable complexes with e2 ubiquitin-conjugating enzymes |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
DET1 | form complex
binding
|
DCX DET1-COP1 |
0.787 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-154508 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 17452440 |
Mammalian det1 regulates cul4a activity and forms stable complexes with e2 ubiquitin-conjugating enzymes |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
RBX1 | form complex
binding
|
DCX DET1-COP1 |
0.864 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-154511 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 17452440 |
Mammalian det1 regulates cul4a activity and forms stable complexes with e2 ubiquitin-conjugating enzymes |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
CUL4A | form complex
binding
|
DCX DET1-COP1 |
0.897 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-154502 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 17452440 |
Mammalian det1 regulates cul4a activity and forms stable complexes with e2 ubiquitin-conjugating enzymes |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
DCX DET1-COP1 | down-regulates quantity by destabilization
polyubiquitination
|
JUN |
0.379 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-271500 |
|
|
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 14739464 |
We report that human DET1 (hDET1) promotes ubiquitination and degradation of the proto-oncogenic transcription factor c-Jun by assembling a multisubunit ubiquitin ligase containing DNA Damage Binding Protein-1 (DDB1), cullin 4A (CUL4A), Regulator of Cullins-1 (ROC1), and constitutively photomorphogenic-1. Ablation of any subunit by RNA interference stabilized c-Jun and increased c-Jun-activated transcription. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
DCX DET1-COP1 | down-regulates quantity by destabilization
polyubiquitination
|
TRiC |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-272873 |
|
|
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 24298020 |
Here, we propose that vaccinia-related kinase 2 (VRK2) is a critical enzyme that negatively regulates TRiC. In mammalian cells, overexpression of wild-type VRK2 decreased endogenous TRiC protein levels by promoting TRiC ubiquitination, but a VRK2 kinase-dead mutant did not.The VRK2-mediated reduction of TRiC protein levels was subsequent to the recruitment of COP1 E3 ligase. Among the members of the COP1 E3 ligase complex, VRK2 interacted with RBX1 and increased E3 ligase activity on TRiC in vitro. Taken together, these results demonstrate that VRK2 is crucial to regulate the ubiquitination-proteosomal degradation of TRiC, which controls folding of polyglutamine proteins involved in Huntington's disease.COP1 functions as an E3 ligase by forming a supercomplex that also includes heterodimeric substrate receptor DET1, adaptor DDB1, scaffold Cul4A, and RBX1 to recruit the E2 enzyme |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
DDB1 | form complex
binding
|
DCX DET1-COP1 |
0.892 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-154505 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 17452440 |
Mammalian det1 regulates cul4a activity and forms stable complexes with e2 ubiquitin-conjugating enzymes |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
3.0
DCX DET1-COP1