| + |
Cullin 3-RBX1-Skp1 | down-regulates quantity by destabilization 
ubiquitination
|
DEK |
0.305 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-272831 |
Lys137 |
FSGFPFEkGSVQYKK |
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 25278611 |
Here, we analyzed changes in the ubiquitin landscape induced by prostate cancer-associated mutations of SPOP, an E3 ubiquitin ligase substrate-binding protein. SPOP mutants impaired ubiquitylation of a subset of proteins in a dominant-negative fashion. Of these, DEK and TRIM24 emerged as effector substrates consistently up-regulated by SPOP mutants. Up-regulation of DEK, TRIM24 and NCOA3 is a feature of prostate cancer SPOP mutations. This result aligns well with the observation that multiple ubiquitylated DEK lysine residues were detected in the initial proteome analysis (fig. S2E). |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-272830 |
Lys284 |
VKSANVKkADSSTTK |
Homo sapiens |
|
| pmid |
sentence |
| 25278611 |
Here, we analyzed changes in the ubiquitin landscape induced by prostate cancer-associated mutations of SPOP, an E3 ubiquitin ligase substrate-binding protein. SPOP mutants impaired ubiquitylation of a subset of proteins in a dominant-negative fashion. Of these, DEK and TRIM24 emerged as effector substrates consistently up-regulated by SPOP mutants. Up-regulation of DEK, TRIM24 and NCOA3 is a feature of prostate cancer SPOP mutations. This result aligns well with the observation that multiple ubiquitylated DEK lysine residues were detected in the initial proteome analysis (fig. S2E). |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-272832 |
Lys331 |
ELKETIKkLLASANL |
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 25278611 |
Here, we analyzed changes in the ubiquitin landscape induced by prostate cancer-associated mutations of SPOP, an E3 ubiquitin ligase substrate-binding protein. SPOP mutants impaired ubiquitylation of a subset of proteins in a dominant-negative fashion. Of these, DEK and TRIM24 emerged as effector substrates consistently up-regulated by SPOP mutants. Up-regulation of DEK, TRIM24 and NCOA3 is a feature of prostate cancer SPOP mutations. This result aligns well with the observation that multiple ubiquitylated DEK lysine residues were detected in the initial proteome analysis (fig. S2E). |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-272833 |
Lys344 |
NLEEVTMkQICKKVY |
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 25278611 |
Here, we analyzed changes in the ubiquitin landscape induced by prostate cancer-associated mutations of SPOP, an E3 ubiquitin ligase substrate-binding protein. SPOP mutants impaired ubiquitylation of a subset of proteins in a dominant-negative fashion. Of these, DEK and TRIM24 emerged as effector substrates consistently up-regulated by SPOP mutants. Up-regulation of DEK, TRIM24 and NCOA3 is a feature of prostate cancer SPOP mutations. This result aligns well with the observation that multiple ubiquitylated DEK lysine residues were detected in the initial proteome analysis (fig. S2E). |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-272834 |
Lys349 |
TMKQICKkVYENYPT |
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 25278611 |
Here, we analyzed changes in the ubiquitin landscape induced by prostate cancer-associated mutations of SPOP, an E3 ubiquitin ligase substrate-binding protein. SPOP mutants impaired ubiquitylation of a subset of proteins in a dominant-negative fashion. Of these, DEK and TRIM24 emerged as effector substrates consistently up-regulated by SPOP mutants. Up-regulation of DEK, TRIM24 and NCOA3 is a feature of prostate cancer SPOP mutations. This result aligns well with the observation that multiple ubiquitylated DEK lysine residues were detected in the initial proteome analysis (fig. S2E). |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-272835 |
Lys371 |
DFIKTTVkELIS |
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 25278611 |
Here, we analyzed changes in the ubiquitin landscape induced by prostate cancer-associated mutations of SPOP, an E3 ubiquitin ligase substrate-binding protein. SPOP mutants impaired ubiquitylation of a subset of proteins in a dominant-negative fashion. Of these, DEK and TRIM24 emerged as effector substrates consistently up-regulated by SPOP mutants. Up-regulation of DEK, TRIM24 and NCOA3 is a feature of prostate cancer SPOP mutations. This result aligns well with the observation that multiple ubiquitylated DEK lysine residues were detected in the initial proteome analysis (fig. S2E). |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-272828 |
Lys57 |
KSLIVEGkREKKKVE |
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 25278611 |
Here, we analyzed changes in the ubiquitin landscape induced by prostate cancer-associated mutations of SPOP, an E3 ubiquitin ligase substrate-binding protein. SPOP mutants impaired ubiquitylation of a subset of proteins in a dominant-negative fashion. Of these, DEK and TRIM24 emerged as effector substrates consistently up-regulated by SPOP mutants. Up-regulation of DEK, TRIM24 and NCOA3 is a feature of prostate cancer SPOP mutations. This result aligns well with the observation that multiple ubiquitylated DEK lysine residues were detected in the initial proteome analysis (fig. S2E). |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-272829 |
Lys84 |
PFTIAQGkGQKLCEI |
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 25278611 |
Here, we analyzed changes in the ubiquitin landscape induced by prostate cancer-associated mutations of SPOP, an E3 ubiquitin ligase substrate-binding protein. SPOP mutants impaired ubiquitylation of a subset of proteins in a dominant-negative fashion. Of these, DEK and TRIM24 emerged as effector substrates consistently up-regulated by SPOP mutants. Up-regulation of DEK, TRIM24 and NCOA3 is a feature of prostate cancer SPOP mutations. This result aligns well with the observation that multiple ubiquitylated DEK lysine residues were detected in the initial proteome analysis (fig. S2E). |
|
| Publications: |
8 |
Organism: |
Homo Sapiens |
| + |
Cullin 3-RBX1-Skp1 | down-regulates quantity by destabilization
polyubiquitination
|
INF2 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-272800 |
Lys345 |
VERLLSVkGRPRPSP |
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 28448495 |
SPOP acts as an adaptor protein of the CUL3-RBX1 E3 ubiquitin ligase complex that generally recruits substrates for ubiquitination and subsequent degradation. Here, we revealed that SPOP recognizes a Ser/Thr (S/T)-rich motif in the C-terminal region of INF2 and triggers atypical polyubiquitination of INF2. These ubiquitination modifications do not lead to INF2 instability, but rather reduces INF2 localization in ER and mitochondrially associated DRP1 puncta formation, therefore abrogates its ability to facilitate mitochondrial fission. It revealed that INF2 was ubiquitinated at least at 7 lysine residues (Fig 2I). Interestingly, 5 of 7 ubiquitin attachment sites are localized in a short stretch of sequence (amino acids 612–682) within the FH2 domain of INF2 (Fig 2J). |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-272801 |
Lys612 |
LFSFPAAkPKEPTMV |
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 28448495 |
SPOP acts as an adaptor protein of the CUL3-RBX1 E3 ubiquitin ligase complex that generally recruits substrates for ubiquitination and subsequent degradation. Here, we revealed that SPOP recognizes a Ser/Thr (S/T)-rich motif in the C-terminal region of INF2 and triggers atypical polyubiquitination of INF2. These ubiquitination modifications do not lead to INF2 instability, but rather reduces INF2 localization in ER and mitochondrially associated DRP1 puncta formation, therefore abrogates its ability to facilitate mitochondrial fission. It revealed that INF2 was ubiquitinated at least at 7 lysine residues (Fig 2I). Interestingly, 5 of 7 ubiquitin attachment sites are localized in a short stretch of sequence (amino acids 612–682) within the FH2 domain of INF2 (Fig 2J). |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-272802 |
Lys636 |
EITFLDAkKSLNLNI |
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 28448495 |
SPOP acts as an adaptor protein of the CUL3-RBX1 E3 ubiquitin ligase complex that generally recruits substrates for ubiquitination and subsequent degradation. Here, we revealed that SPOP recognizes a Ser/Thr (S/T)-rich motif in the C-terminal region of INF2 and triggers atypical polyubiquitination of INF2. These ubiquitination modifications do not lead to INF2 instability, but rather reduces INF2 localization in ER and mitochondrially associated DRP1 puncta formation, therefore abrogates its ability to facilitate mitochondrial fission. It revealed that INF2 was ubiquitinated at least at 7 lysine residues (Fig 2I). Interestingly, 5 of 7 ubiquitin attachment sites are localized in a short stretch of sequence (amino acids 612–682) within the FH2 domain of INF2 (Fig 2J). |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-272803 |
Lys666 |
IRAGDTTkFDVEVLK |
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 28448495 |
SPOP acts as an adaptor protein of the CUL3-RBX1 E3 ubiquitin ligase complex that generally recruits substrates for ubiquitination and subsequent degradation. Here, we revealed that SPOP recognizes a Ser/Thr (S/T)-rich motif in the C-terminal region of INF2 and triggers atypical polyubiquitination of INF2. These ubiquitination modifications do not lead to INF2 instability, but rather reduces INF2 localization in ER and mitochondrially associated DRP1 puncta formation, therefore abrogates its ability to facilitate mitochondrial fission. It revealed that INF2 was ubiquitinated at least at 7 lysine residues (Fig 2I). Interestingly, 5 of 7 ubiquitin attachment sites are localized in a short stretch of sequence (amino acids 612–682) within the FH2 domain of INF2 (Fig 2J). |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-272804 |
Lys673 |
KFDVEVLkQLLKLLP |
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 28448495 |
SPOP acts as an adaptor protein of the CUL3-RBX1 E3 ubiquitin ligase complex that generally recruits substrates for ubiquitination and subsequent degradation. Here, we revealed that SPOP recognizes a Ser/Thr (S/T)-rich motif in the C-terminal region of INF2 and triggers atypical polyubiquitination of INF2. These ubiquitination modifications do not lead to INF2 instability, but rather reduces INF2 localization in ER and mitochondrially associated DRP1 puncta formation, therefore abrogates its ability to facilitate mitochondrial fission. It revealed that INF2 was ubiquitinated at least at 7 lysine residues (Fig 2I). Interestingly, 5 of 7 ubiquitin attachment sites are localized in a short stretch of sequence (amino acids 612–682) within the FH2 domain of INF2 (Fig 2J). |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-272805 |
Lys682 |
LLKLLPEkHEIENLR |
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 28448495 |
SPOP acts as an adaptor protein of the CUL3-RBX1 E3 ubiquitin ligase complex that generally recruits substrates for ubiquitination and subsequent degradation. Here, we revealed that SPOP recognizes a Ser/Thr (S/T)-rich motif in the C-terminal region of INF2 and triggers atypical polyubiquitination of INF2. These ubiquitination modifications do not lead to INF2 instability, but rather reduces INF2 localization in ER and mitochondrially associated DRP1 puncta formation, therefore abrogates its ability to facilitate mitochondrial fission. It revealed that INF2 was ubiquitinated at least at 7 lysine residues (Fig 2I). Interestingly, 5 of 7 ubiquitin attachment sites are localized in a short stretch of sequence (amino acids 612–682) within the FH2 domain of INF2 (Fig 2J). |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-272806 |
Lys982 |
ALLADIRkGFQLRKT |
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 28448495 |
SPOP acts as an adaptor protein of the CUL3-RBX1 E3 ubiquitin ligase complex that generally recruits substrates for ubiquitination and subsequent degradation. Here, we revealed that SPOP recognizes a Ser/Thr (S/T)-rich motif in the C-terminal region of INF2 and triggers atypical polyubiquitination of INF2. These ubiquitination modifications do not lead to INF2 instability, but rather reduces INF2 localization in ER and mitochondrially associated DRP1 puncta formation, therefore abrogates its ability to facilitate mitochondrial fission. It revealed that INF2 was ubiquitinated at least at 7 lysine residues (Fig 2I). Interestingly, 5 of 7 ubiquitin attachment sites are localized in a short stretch of sequence (amino acids 612–682) within the FH2 domain of INF2 (Fig 2J). |
|
| Publications: |
7 |
Organism: |
Homo Sapiens |
| + |
Cullin 3-RBX1-Skp1 | down-regulates activity
monoubiquitination
|
PLK1 |
0.417 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-272110 |
Lys492 |
YMSEHLLkAGANITP |
in vitro |
|
| pmid |
sentence |
| 23455478 |
Here, we identify PLK1 as a target of the cullin 3 (CUL3)-based E3 ubiquitin ligase, containing the BTB adaptor KLHL22, which regulates chromosome alignment and PLK1 kinetochore localization but not PLK1 stability. In the absence of KLHL22, PLK1 accumulates on kinetochores, resulting in activation of the spindle assembly checkpoint (SAC). CUL3-KLHL22 ubiquitylates Lys 492, located within the PBD, leading to PLK1 dissociation from kinetochore phosphoreceptors. |
|
| Publications: |
1 |
Organism: |
In Vitro |
| + |
KLHL3 | up-regulates activity 
binding
|
Cullin 3-RBX1-Skp1 |
0.643 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-272106 |
|
|
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 23453970 |
Here, we found that KLHL3 interacted with Cullin3 and WNK4, induced WNK4 ubiquitination, and reduced the WNK4 protein level. The reduced interaction of KLHL3 and WNK4 by PHAII-causing mutations in either protein reduced the ubiquitination of WNK4, resulting in an increased level of WNK4 protein. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-272101 |
|
|
Homo sapiens |
HeLa Cell |
| pmid |
sentence |
| 23387299 |
CUL3 assembles with BTB proteins to form Cullin-RING E3 ubiquitin ligase complexes. To explore how a CUL3-KLHL3 complex might operate, we immunoprecipitated KLHL3 and found that it associated strongly with WNK isoforms and CUL3. These results suggest that the CUL3-KLHL3 E3 ligase complex regulates blood pressure via its ability to interact with and ubiquitylate WNK isoforms. |
|
| Publications: |
2 |
Organism: |
Homo Sapiens |
| + |
Cullin 3-RBX1-Skp1 | up-regulates activity
monoubiquitination
|
MACROH2A1 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-272660 |
|
|
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 15897469 |
BMI1 and MACROH2A1 interact with and are ubiquitinated by the CULLIN3 and SPOP ligase complex. t present, we cannot discriminate the main role in vivo of the polyubiquitinated or monoubiquitinated MACROH2A1, because both modifications can be detected (Fig. 2 d and e and ref. 34).Importantly, RNAi-mediated knock-down of CULLIN3 or SPOP results in loss of MACROH2A1 from the inactivated X chromosome (Xi), leading to reactivation of the Xi in the presence of inhibitors of DNA methylation and histone deacetylation. No significant changes in protein stability were observed, suggesting that ubiquitination serves regulatory functions other than protein degradation of BMI1 and MACROH2A1 |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
KEAP1 | up-regulates activity
binding
|
Cullin 3-RBX1-Skp1 |
0.712 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-272646 |
|
|
Chlorocebus aethiops |
COS-1 Cell |
| pmid |
sentence |
| 17046835 |
Keap1-dependent ubiquitination of PGAM5 results in proteasome-dependent degradation of PGAM5. Keap1 is a Bric-a-Brac (BTB) 2 -Kelch protein that functions as a substrate adaptor protein for a Cul3-dependent E3 ubiquitin ligase complex. |
|
| Publications: |
1 |
Organism: |
Chlorocebus Aethiops |
| + |
Cullin 3-RBX1-Skp1 | up-regulates activity
ubiquitination
|
BMI1 |
0.354 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-272661 |
|
|
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 15897469 |
BMI1 and MACROH2A1 interact with and are ubiquitinated by the CULLIN3 and SPOP ligase complex. Polyubiquitination of endogenous BMI1 could not be detected, suggesting that only a small amount of the protein undergoes this modification. No significant changes in protein stability were observed, suggesting that ubiquitination serves regulatory functions other than protein degradation of BMI1 and MACROH2A1 |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
Cullin 3-RBX1-Skp1 | down-regulates quantity by destabilization
polyubiquitination
|
PDE5A |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-272314 |
|
|
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 30896450 |
RhoBTB1 augmented the cGMP response to nitric oxide by restraining the activity of phosphodiesterase 5 (PDE5) by acting as a substrate adaptor delivering PDE5 to the Cullin-3 E3 Ring ubiquitin ligase complex for ubiquitination inhibiting PDE5. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
KLHL18 | up-regulates activity
binding
|
Cullin 3-RBX1-Skp1 |
0.424 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-272022 |
|
|
Homo sapiens |
U2-OS Cell |
| pmid |
sentence |
| 23213400 |
We identify Aurora-A as a KLHL18-interacting partner. Overexpression of KLHL18 and CUL3 promotes Aurora-A ubiquitylation in vivo, and the CUL3-KLHL18-ROC1 ligase ubiquitylates Aurora-A in vitro. Our study reveals that the CUL3-KLHL18 ligase is required for timely entry into mitosis, as well as for the activation of Aurora-A at centrosomes. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
SKP1 | form complex 
binding
|
Cullin 3-RBX1-Skp1 |
0.9 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-271620 |
|
|
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 16547521 |
KLHL12 recruits Dsh to Cullin-3 for protein degradation. In vitro ubiquitination of Dsh3 by KLHL12–Cullin-3–Roc1. The E3 ligase complex was obtained by transfection of HEK293T cells . We show that the BTB-containing protein KLHL12 negatively regulates Dsh function by recruiting a pool of Dsh to the Cullin-3 ligase scaffold, thereby promoting its ubiquitination and degradation. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
Cullin 3-RBX1-Skp1 | down-regulates quantity by destabilization
polyubiquitination
|
GRIK2 |
0.289 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-271614 |
|
|
Chlorocebus aethiops |
COS-7 Cell |
| pmid |
sentence |
| 17062563 |
Here, we report that actinfilin is able to bind to GluR6, a kainate-type glutamate receptor subunit, and target GluR6 for degradation. Like many members of its protein family, actinfilin acts as a substrate adaptor, binding Cullin 3 (Cul3) and linking GluR6 to the E3 ubiquitin-ligase complex. Together our data demonstrate that actinfilin acts as a scaffold, linking GluR6 to the Cul3 ubiquitin ligase to provide a novel mechanism for kainate receptor degradation. |
|
| Publications: |
1 |
Organism: |
Chlorocebus Aethiops |
| + |
Cullin 3-RBX1-Skp1 | up-regulates activity
monoubiquitination
|
SEC31B |
0.304 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-272015 |
|
lys641 |
Homo sapiens |
HeLa Cell |
| pmid |
sentence |
| 22358839 |
By analyzing mouse embryonic stem cell (mESC) division, we have identified Cul3Klhl12 as a regulator of COPII coat formation. Cul3Klhl12 monoubiquitinates Sec31 and drives assembly of large COPII-coats. As a result, ubiquitination by Cul3Klhl12 is essential for collagen export, a step that is required for integrin-dependent mESC division. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-272016 |
|
lys1176 |
Homo sapiens |
HeLa Cell |
| pmid |
sentence |
| 22358839 |
By analyzing mouse embryonic stem cell (mESC) division, we have identified Cul3Klhl12 as a regulator of COPII coat formation. Cul3Klhl12 monoubiquitinates Sec31 and drives assembly of large COPII-coats. As a result, ubiquitination by Cul3Klhl12 is essential for collagen export, a step that is required for integrin-dependent mESC division. |
|
| Publications: |
2 |
Organism: |
Homo Sapiens |
| + |
KLHL9 | up-regulates activity
binding
|
Cullin 3-RBX1-Skp1 |
0.584 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-272455 |
|
|
Homo sapiens |
Glioblastoma Cell |
| pmid |
sentence |
| 25303533 |
KLHL9 mediates poly-ubiquitylation of C/EBPβ and C/EBPδ isoforms. We confirmed KLHL9 deletions in an independent cohort and showed that this protein is necessary for Cul3-ligase mediated ubiquitylation and proteasomal degradation of established MES-GBM MRs, C/EBPβ and C/EBPδ. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-271660 |
|
|
Homo sapiens |
HeLa Cell |
| pmid |
sentence |
| 17543862 |
Aurora B Interacts with the Cul3 Complex during Mitosis and Is Ubiquitylated in a Cul3-Dependent Manner In Vivo and In Vitro. our results suggest that Cul3/KLHL9/KLHL13 activity is required to remove the chromosomal passenger protein Aurora B from mitotic chromosomes, and that Aurora B is ubiquitylated in vivo and in vitro in a KLHL9/13-dependent manner. We conclude that the Cul3/KLHL9/KLHL13 E3 ligase is an important cell-cycle regulator which, in addition to the anaphase-promoting complex (APC), coordinates mitotic progression and completion of cytokinesis. |
|
| Publications: |
2 |
Organism: |
Homo Sapiens |
| + |
RHOBTB1 | up-regulates activity
binding
|
Cullin 3-RBX1-Skp1 |
0.494 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-272313 |
|
|
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 30896450 |
RhoBTB1 augmented the cGMP response to nitric oxide by restraining the activity of phosphodiesterase 5 (PDE5) by acting as a substrate adaptor delivering PDE5 to the Cullin-3 E3 Ring ubiquitin ligase complex for ubiquitination inhibiting PDE5. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
KCTD10 | up-regulates activity
binding
|
Cullin 3-RBX1-Skp1 |
0.508 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-272924 |
|
|
Homo sapiens |
HTERT-RPE1 Cell |
| pmid |
sentence |
| 30404837 |
Cullin-3-KCTD10-mediated CEP97 degradation promotes primary cilium formation. we identified the cullin-3-RBX1-KCTD10 complex as the E3 ligase that mediates CEP97 degradation and removal from the mother centriole. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
KLHL12 | up-regulates activity
binding
|
Cullin 3-RBX1-Skp1 |
0.525 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-272011 |
|
|
Homo sapiens |
HeLa Cell |
| pmid |
sentence |
| 22358839 |
By analyzing mouse embryonic stem cell (mESC) division, we have identified Cul3Klhl12 as a regulator of COPII coat formation. Cul3Klhl12 monoubiquitinates Sec31 and drives assembly of large COPII-coats. As a result, ubiquitination by Cul3Klhl12 is essential for collagen export, a step that is required for integrin-dependent mESC division. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-272198 |
|
|
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 32433973 |
Lunapark Is Ubiquitylated by the CRL3KLHL12 Ubiquitin Ligase Complex. Taken together, these results demonstrate that Lunapark is ubiquitylated by the CRL3KLHL12 ubiquitin ligase, and the CRL3KLHL12-dependent ubiquitylation of Lunapark does not lead to its proteasomal degradation. Inhibition of Lunapark Ubiquitylation Affects Lysosomal Recruitment of mTORC2 |
|
| Publications: |
2 |
Organism: |
Homo Sapiens |
| + |
KLHL25 | up-regulates activity
binding
|
Cullin 3-RBX1-Skp1 |
0.512 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-272334 |
|
|
Homo sapiens |
NCI-H1299 Cell |
| pmid |
sentence |
| 27664236 |
Here, we found that CUL3 interacts with ACLY through its adaptor protein, KLHL25 (Kelch-like family member 25), to ubiquitinate and degrade ACLY in cells. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-272050 |
|
|
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 22578813 |
We identified the KLHL25-CUL3 complex as the E3 ubiquitin ligase, which targets hypophosphorylated 4E-BP1. Thus, the activity of eIF4E is under homeostatic control via the regulation of the levels of its repressor protein 4E-BP1 through ubiquitination. |
|
| Publications: |
2 |
Organism: |
Homo Sapiens |
| + |
Cullin 3-RBX1-Skp1 | down-regulates quantity by destabilization
polyubiquitination
|
PGAM5 |
0.418 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-272647 |
|
|
Chlorocebus aethiops |
COS-1 Cell |
| pmid |
sentence |
| 17046835 |
Keap1-dependent ubiquitination of PGAM5 results in proteasome-dependent degradation of PGAM5. Keap1 is a Bric-a-Brac (BTB) 2 -Kelch protein that functions as a substrate adaptor protein for a Cul3-dependent E3 ubiquitin ligase complex. |
|
| Publications: |
1 |
Organism: |
Chlorocebus Aethiops |
| + |
Cullin 3-RBX1-Skp1 | down-regulates quantity by destabilization
polyubiquitination
|
CCNE1 |
0.496 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-272133 |
|
|
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 24145166 |
Here we show that RhoBTB3, a Golgi-associated, Rho-related ATPase, regulates the S/G2 transition of the cell cycle by targeting cyclin E for ubiquitylation. Depletion of RhoBTB3 arrested cells in S phase, triggered Golgi fragmentation, and elevated cyclin E levels. On the Golgi, RhoBTB3 bound cyclin E as part of a Cullin3 (CUL3)-dependent RING-E3 ubiquitin ligase complex comprised of RhoBTB3, CUL3, and RBX1. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
FBXL2 | up-regulates
binding
|
Cullin 3-RBX1-Skp1 |
0.49 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-272112 |
|
|
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 23604317 |
FBXL2 binds p85α and p85β. p85β is targeted for ubiquitylation and degradation by SCF FBXL2. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
Cullin 3-RBX1-Skp1 | down-regulates quantity by destabilization
binding
|
ACLY |
0.291 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-272335 |
|
|
Homo sapiens |
NCI-H1299 Cell |
| pmid |
sentence |
| 27664236 |
Here, we found that CUL3 interacts with ACLY through its adaptor protein, KLHL25 (Kelch-like family member 25), to ubiquitinate and degrade ACLY in cells. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
Cullin 3-RBX1-Skp1 | down-regulates quantity by destabilization
polyubiquitination
|
CEBPD |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-272457 |
|
|
Homo sapiens |
Glioblastoma Cell |
| pmid |
sentence |
| 25303533 |
KLHL9 mediates poly-ubiquitylation of C/EBPβ and C/EBPδ isoforms. We confirmed KLHL9 deletions in an independent cohort and showed that this protein is necessary for Cul3-ligase mediated ubiquitylation and proteasomal degradation of established MES-GBM MRs, C/EBPβ and C/EBPδ. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
Cullin 3-RBX1-Skp1 | up-regulates activity
polyubiquitination
|
AURKB |
0.436 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-271661 |
|
|
Homo sapiens |
HeLa Cell |
| pmid |
sentence |
| 17543862 |
Aurora B Interacts with the Cul3 Complex during Mitosis and Is Ubiquitylated in a Cul3-Dependent Manner In Vivo and In Vitro. our results suggest that Cul3/KLHL9/KLHL13 activity is required to remove the chromosomal passenger protein Aurora B from mitotic chromosomes, and that Aurora B is ubiquitylated in vivo and in vitro in a KLHL9/13-dependent manner. We conclude that the Cul3/KLHL9/KLHL13 E3 ligase is an important cell-cycle regulator which, in addition to the anaphase-promoting complex (APC), coordinates mitotic progression and completion of cytokinesis. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-271662 |
|
|
Homo sapiens |
HeLa Cell |
| pmid |
sentence |
| 17543862 |
Aurora B Interacts with the Cul3 Complex during Mitosis and Is Ubiquitylated in a Cul3-Dependent Manner In Vivo and In Vitro. our results suggest that Cul3/KLHL9/KLHL13 activity is required to remove the chromosomal passenger protein Aurora B from mitotic chromosomes, and that Aurora B is ubiquitylated in vivo and in vitro in a KLHL9/13-dependent manner. We conclude that the Cul3/KLHL9/KLHL13 E3 ligase is an important cell-cycle regulator which, in addition to the anaphase-promoting complex (APC), coordinates mitotic progression and completion of cytokinesis. |
|
| Publications: |
2 |
Organism: |
Homo Sapiens |
| + |
KCTD17 | up-regulates activity
binding
|
Cullin 3-RBX1-Skp1 |
0.443 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-272464 |
|
|
Homo sapiens |
Retinal Pigment Epithelium Cell |
| pmid |
sentence |
| 25270598 |
We have identified KCTD17 as a substrate-adaptor for Cul3-RING E3 ligases (CRL3s) that polyubiquitylates trichoplein. Depletion of KCTD17 specifically arrests ciliogenesis at the initial step of axoneme extension through aberrant trichoplein-Aurora-A activity. Thus, CRL3-KCTD17 targets trichoplein to proteolysis to initiate the axoneme extension during ciliogenesis. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
Cullin 3-RBX1-Skp1 | down-regulates quantity by destabilization
polyubiquitination
|
TUT1 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-272321 |
|
|
Homo sapiens |
SW-620 Cell |
| pmid |
sentence |
| 29032201 |
Kelch-like protein 7 (KLHL7) is a component of Cul3-based Cullin-RING ubiquitin ligase. In this study, we report that KLHL7 increases terminal uridylyl transferase 1 (TUT1) ubiquitination involved in nucleolar integrity. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
SPOP | up-regulates activity
binding
|
Cullin 3-RBX1-Skp1 |
0.653 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-272659 |
|
|
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 15897469 |
Here, we describe an E3 ubiquitin ligase consisting of SPOP and CULLIN3 that is able to ubiquitinate the PcG protein BMI1 and the variant histone MACROH2A1. To investigate whether BMI1 can form a complex with SPOP and CULLIN3 in vivo, we reconstituted the complex in 293HEK cells. We find that BMI1 readily immunoprecipitates both hemagglutinin (HA)-SPOP and CULLIN3, and, conversely, CULLIN3 immunoprecipitates BMI1 (Fig. 2a). Complex formation depends on the presence of SPOP, in accordance with BMI1 binding to the MATH domain of SPOP (Fig. 1b) and previously published data showing SPOP–CULLIN interaction by means of the BTB/POZ domain of SPOP (30). |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
Cullin 3-RBX1-Skp1 | down-regulates quantity by destabilization
polyubiquitination
|
WNK4 |
0.398 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-272107 |
|
|
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 23453970 |
Here, we found that KLHL3 interacted with Cullin3 and WNK4, induced WNK4 ubiquitination, and reduced the WNK4 protein level. The reduced interaction of KLHL3 and WNK4 by PHAII-causing mutations in either protein reduced the ubiquitination of WNK4, resulting in an increased level of WNK4 protein. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-272123 |
|
|
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 23838290 |
We found that KLHL2, as well as KLHL3, was co-immunoprecipitated with all four WNK isoforms. The direct interaction of KLHL2 with WNKs was confirmed on fluorescence correlation spectroscopy. Co-expression of KLHL2 and Cullin3 decreased the abundance of WNK1, WNK3 and WNK4 within HEK293T cells, and a significant increase of WNK4 ubiquitination by KLHL2 and Cullin3 was observed both in HEK293T cells and in an in vitro ubiquitination assay. These results suggest that KLHL2-Cullin3 also functions as an E3-ligase for WNK isoforms within the body. |
|
| Publications: |
2 |
Organism: |
Homo Sapiens |
| + |
Cullin 3-RBX1-Skp1 | down-regulates quantity by destabilization
polyubiquitination
|
WNK2 |
0.301 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-272125 |
|
|
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 23838290 |
We found that KLHL2, as well as KLHL3, was co-immunoprecipitated with all four WNK isoforms. The direct interaction of KLHL2 with WNKs was confirmed on fluorescence correlation spectroscopy. Co-expression of KLHL2 and Cullin3 decreased the abundance of WNK1, WNK3 and WNK4 within HEK293T cells, and a significant increase of WNK4 ubiquitination by KLHL2 and Cullin3 was observed both in HEK293T cells and in an in vitro ubiquitination assay. These results suggest that KLHL2-Cullin3 also functions as an E3-ligase for WNK isoforms within the body. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
KLHL15 | up-regulates activity
binding
|
Cullin 3-RBX1-Skp1 |
0.471 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-272411 |
|
|
Homo sapiens |
U2-OS Cell |
| pmid |
sentence |
| 27561354 |
Here, we identify the Cullin3 E3 ligase substrate adaptor Kelch-like protein 15 (KLHL15) as a new interaction partner of CtIP and show that KLHL15 promotes CtIP protein turnover via the ubiquitin-proteasome pathway. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-272018 |
|
|
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 23135275 |
Here, we report that KLHL15-Cul3 specifically targets B'β to promote turnover of the PP2A subunit by ubiquitylation and proteasomal degradation. We mapped KLHL15 residues critical for homodimerization as well as interaction with Cul3 and B'β. |
|
| Publications: |
2 |
Organism: |
Homo Sapiens |
| + |
CUL3 | form complex
binding
|
Cullin 3-RBX1-Skp1 |
0.875 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-271560 |
|
|
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 16547521 |
KLHL12 recruits Dsh to Cullin-3 for protein degradation. In vitro ubiquitination of Dsh3 by KLHL12–Cullin-3–Roc1. The E3 ligase complex was obtained by transfection of HEK293T cells . We show that the BTB-containing protein KLHL12 negatively regulates Dsh function by recruiting a pool of Dsh to the Cullin-3 ligase scaffold, thereby promoting its ubiquitination and degradation. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
KLHL2 | up-regulates activity
binding
|
Cullin 3-RBX1-Skp1 |
0.609 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-272122 |
|
|
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 23838290 |
We found that KLHL2, as well as KLHL3, was co-immunoprecipitated with all four WNK isoforms. The direct interaction of KLHL2 with WNKs was confirmed on fluorescence correlation spectroscopy. Co-expression of KLHL2 and Cullin3 decreased the abundance of WNK1, WNK3 and WNK4 within HEK293T cells, and a significant increase of WNK4 ubiquitination by KLHL2 and Cullin3 was observed both in HEK293T cells and in an in vitro ubiquitination assay. These results suggest that KLHL2-Cullin3 also functions as an E3-ligase for WNK isoforms within the body. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
KLHL8 | up-regulates activity
binding
|
Cullin 3-RBX1-Skp1 |
0.412 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-271783 |
|
|
Mus musculus |
NIH-3T3 Cell |
| pmid |
sentence |
| 19158078 |
We found that rapsyn was polyubiquitinated by KLHL8-containing E3 ligase, but not by KEAP1-containing E3 ligase, clearly indicating that rapsyn is a direct substrate of KLHL8-containing E3 ligase in mammals. We next examined the effect of KLHL-8 depletion on the ubiquitination of rapsyn by performing RNAi experiments in mammalian cells. We found that knockdown of KLHL8 in 3T3 cells reduced the level of rapsyn ubiquitination (Fig. 5C), again indicating that the maintenance mechanism for rapsyn stability is conserved in mammals.The in vitro ubiquitination of mammalian rapsyn by CUL3-containing E3 ligase and the effect of KLHL8 knockdown on the ubiquitination of rapsyn. |
|
| Publications: |
1 |
Organism: |
Mus Musculus |
| + |
KLHL13 | up-regulates activity
binding
|
Cullin 3-RBX1-Skp1 |
0.558 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-271659 |
|
|
Homo sapiens |
HeLa Cell |
| pmid |
sentence |
| 17543862 |
Aurora B Interacts with the Cul3 Complex during Mitosis and Is Ubiquitylated in a Cul3-Dependent Manner In Vivo and In Vitro. our results suggest that Cul3/KLHL9/KLHL13 activity is required to remove the chromosomal passenger protein Aurora B from mitotic chromosomes, and that Aurora B is ubiquitylated in vivo and in vitro in a KLHL9/13-dependent manner. We conclude that the Cul3/KLHL9/KLHL13 E3 ligase is an important cell-cycle regulator which, in addition to the anaphase-promoting complex (APC), coordinates mitotic progression and completion of cytokinesis. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
RHOBTB3 | up-regulates activity
binding
|
Cullin 3-RBX1-Skp1 |
0.39 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-272132 |
|
|
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 24145166 |
Here we show that RhoBTB3, a Golgi-associated, Rho-related ATPase, regulates the S/G2 transition of the cell cycle by targeting cyclin E for ubiquitylation. Depletion of RhoBTB3 arrested cells in S phase, triggered Golgi fragmentation, and elevated cyclin E levels. On the Golgi, RhoBTB3 bound cyclin E as part of a Cullin3 (CUL3)-dependent RING-E3 ubiquitin ligase complex comprised of RhoBTB3, CUL3, and RBX1. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
RBX1 | form complex
binding
|
Cullin 3-RBX1-Skp1 |
0.929 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-271561 |
|
|
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 16547521 |
KLHL12 recruits Dsh to Cullin-3 for protein degradation. In vitro ubiquitination of Dsh3 by KLHL12–Cullin-3–Roc1. The E3 ligase complex was obtained by transfection of HEK293T cells . We show that the BTB-containing protein KLHL12 negatively regulates Dsh function by recruiting a pool of Dsh to the Cullin-3 ligase scaffold, thereby promoting its ubiquitination and degradation. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
Cullin 3-RBX1-Skp1 | down-regulates quantity by destabilization
polyubiquitination
|
RBBP8 |
0.285 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-272412 |
|
|
Homo sapiens |
U2-OS Cell |
| pmid |
sentence |
| 27561354 |
Here, we identify the Cullin3 E3 ligase substrate adaptor Kelch-like protein 15 (KLHL15) as a new interaction partner of CtIP and show that KLHL15 promotes CtIP protein turnover via the ubiquitin-proteasome pathway. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
Cullin 3-RBX1-Skp1 | up-regulates activity
ubiquitination
|
EB1/MLL |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-272409 |
|
|
Homo sapiens |
HeLa Cell |
| pmid |
sentence |
| 27641145 |
Indeed, KLHL21 localizes to FA structures preferentially at the leading edge, and in complex with Cul3, ubiquitylates EB1 within its microtubule-interacting CH-domain. Cells lacking CRL3(KLHL21) activity or expressing a non-ubiquitylatable EB1 mutant protein are unable to migrate and exhibit strong defects in FA dynamics, lamellipodia formation and cortical plasticity. Our study thus reveals an important mechanism to regulate cortical dynamics during cell migration that involves ubiquitylation of EB1 at focal adhesions. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
Cullin 3-RBX1-Skp1 | down-regulates quantity by destabilization
polyubiquitination
|
BECN1 |
0.336 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-272419 |
|
|
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 26687681 |
Cul3-KLHL20 Ubiquitin Ligase Governs the Turnover of ULK1 and VPS34 Complexes to Control Autophagy Termination. KLHL20 promotes ubiquitination of phagophore-residing VPS34 and Beclin-1 |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
Cullin 3-RBX1-Skp1 | up-regulates activity
monoubiquitination
|
SEC31A |
0.386 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-272013 |
|
lys1217 |
Homo sapiens |
HeLa Cell |
| pmid |
sentence |
| 22358839 |
By analyzing mouse embryonic stem cell (mESC) division, we have identified Cul3Klhl12 as a regulator of COPII coat formation. Cul3Klhl12 monoubiquitinates Sec31 and drives assembly of large COPII-coats. As a result, ubiquitination by Cul3Klhl12 is essential for collagen export, a step that is required for integrin-dependent mESC division. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-272012 |
|
lys647 |
Homo sapiens |
HeLa Cell |
| pmid |
sentence |
| 22358839 |
By analyzing mouse embryonic stem cell (mESC) division, we have identified Cul3Klhl12 as a regulator of COPII coat formation. Cul3Klhl12 monoubiquitinates Sec31 and drives assembly of large COPII-coats. As a result, ubiquitination by Cul3Klhl12 is essential for collagen export, a step that is required for integrin-dependent mESC division. |
|
| Publications: |
2 |
Organism: |
Homo Sapiens |
| + |
Cullin 3-RBX1-Skp1 | down-regulates quantity by destabilization
ubiquitination, polyubiquitination
|
WNK1 |
0.328 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-272100 |
|
|
Homo sapiens |
HeLa Cell |
| pmid |
sentence |
| 23387299 |
CUL3 assembles with BTB proteins to form Cullin-RING E3 ubiquitin ligase complexes. To explore how a CUL3-KLHL3 complex might operate, we immunoprecipitated KLHL3 and found that it associated strongly with WNK isoforms and CUL3. These results suggest that the CUL3-KLHL3 E3 ligase complex regulates blood pressure via its ability to interact with and ubiquitylate WNK isoforms. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-272124 |
|
|
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 23838290 |
We found that KLHL2, as well as KLHL3, was co-immunoprecipitated with all four WNK isoforms. The direct interaction of KLHL2 with WNKs was confirmed on fluorescence correlation spectroscopy. Co-expression of KLHL2 and Cullin3 decreased the abundance of WNK1, WNK3 and WNK4 within HEK293T cells, and a significant increase of WNK4 ubiquitination by KLHL2 and Cullin3 was observed both in HEK293T cells and in an in vitro ubiquitination assay. These results suggest that KLHL2-Cullin3 also functions as an E3-ligase for WNK isoforms within the body. |
|
| Publications: |
2 |
Organism: |
Homo Sapiens |
| + |
Cullin 3-RBX1-Skp1 | down-regulates quantity by destabilization
polyubiquitination
|
DVL1 |
0.405 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-271562 |
|
|
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 16547521 |
KLHL12 recruits Dsh to Cullin-3 for protein degradation. In vitro ubiquitination of Dsh3 by KLHL12–Cullin-3–Roc1. The E3 ligase complex was obtained by transfection of HEK293T cells . We show that the BTB-containing protein KLHL12 negatively regulates Dsh function by recruiting a pool of Dsh to the Cullin-3 ligase scaffold, thereby promoting its ubiquitination and degradation. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
Cullin 3-RBX1-Skp1 | down-regulates quantity by destabilization
polyubiquitination
|
EIF4EBP1 |
0.274 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-272051 |
|
|
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 22578813 |
We identified the KLHL25-CUL3 complex as the E3 ubiquitin ligase, which targets hypophosphorylated 4E-BP1. Thus, the activity of eIF4E is under homeostatic control via the regulation of the levels of its repressor protein 4E-BP1 through ubiquitination. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
Cullin 3-RBX1-Skp1 | down-regulates quantity by destabilization
polyubiquitination
|
WNK3 |
0.343 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-272126 |
|
|
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 23838290 |
We found that KLHL2, as well as KLHL3, was co-immunoprecipitated with all four WNK isoforms. The direct interaction of KLHL2 with WNKs was confirmed on fluorescence correlation spectroscopy. Co-expression of KLHL2 and Cullin3 decreased the abundance of WNK1, WNK3 and WNK4 within HEK293T cells, and a significant increase of WNK4 ubiquitination by KLHL2 and Cullin3 was observed both in HEK293T cells and in an in vitro ubiquitination assay. These results suggest that KLHL2-Cullin3 also functions as an E3-ligase for WNK isoforms within the body. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
Cullin 3-RBX1-Skp1 | down-regulates quantity by destabilization
polyubiquitination
|
ULK1 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-272417 |
|
|
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 26687681 |
Cul3-KLHL20 Ubiquitin Ligase Governs the Turnover of ULK1 and VPS34 Complexes to Control Autophagy Termination. KLHL20 promotes ubiquitination of phagophore-residing VPS34 and Beclin-1 |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
KLHL17 | up-regulates activity
binding
|
Cullin 3-RBX1-Skp1 |
0.332 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-271613 |
|
|
Chlorocebus aethiops |
COS-7 Cell |
| pmid |
sentence |
| 17062563 |
Here, we report that actinfilin is able to bind to GluR6, a kainate-type glutamate receptor subunit, and target GluR6 for degradation. Like many members of its protein family, actinfilin acts as a substrate adaptor, binding Cullin 3 (Cul3) and linking GluR6 to the E3 ubiquitin-ligase complex. Together our data demonstrate that actinfilin acts as a scaffold, linking GluR6 to the Cul3 ubiquitin ligase to provide a novel mechanism for kainate receptor degradation. |
|
| Publications: |
1 |
Organism: |
Chlorocebus Aethiops |
| + |
SPOP | up-regulates
binding
|
Cullin 3-RBX1-Skp1 |
0.653 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-272799 |
|
|
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 28448495 |
SPOP acts as an adaptor protein of the CUL3-RBX1 E3 ubiquitin ligase complex that generally recruits substrates for ubiquitination and subsequent degradation. Here, we revealed that SPOP recognizes a Ser/Thr (S/T)-rich motif in the C-terminal region of INF2 and triggers atypical polyubiquitination of INF2. These ubiquitination modifications do not lead to INF2 instability, but rather reduces INF2 localization in ER and mitochondrially associated DRP1 puncta formation, therefore abrogates its ability to facilitate mitochondrial fission. It revealed that INF2 was ubiquitinated at least at 7 lysine residues (Fig 2I). Interestingly, 5 of 7 ubiquitin attachment sites are localized in a short stretch of sequence (amino acids 612–682) within the FH2 domain of INF2 (Fig 2J). |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
KLHL22 | up-regulates activity
binding
|
Cullin 3-RBX1-Skp1 |
0.518 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-272109 |
|
|
in vitro |
|
| pmid |
sentence |
| 23455478 |
Here, we identify PLK1 as a target of the cullin 3 (CUL3)-based E3 ubiquitin ligase, containing the BTB adaptor KLHL22, which regulates chromosome alignment and PLK1 kinetochore localization but not PLK1 stability. In the absence of KLHL22, PLK1 accumulates on kinetochores, resulting in activation of the spindle assembly checkpoint (SAC). CUL3-KLHL22 ubiquitylates Lys 492, located within the PBD, leading to PLK1 dissociation from kinetochore phosphoreceptors. |
|
| Publications: |
1 |
Organism: |
In Vitro |
| + |
Cullin 3-RBX1-Skp1 | up-regulates activity
polyubiquitination
|
LNPK |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-272199 |
|
|
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 32433973 |
Lunapark Is Ubiquitylated by the CRL3KLHL12 Ubiquitin Ligase Complex. Taken together, these results demonstrate that Lunapark is ubiquitylated by the CRL3KLHL12 ubiquitin ligase, and the CRL3KLHL12-dependent ubiquitylation of Lunapark does not lead to its proteasomal degradation. Inhibition of Lunapark Ubiquitylation Affects Lysosomal Recruitment of mTORC3 |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
KLHL20 | up-regulates activity
binding
|
Cullin 3-RBX1-Skp1 |
0.537 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-272416 |
|
|
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 26687681 |
Cul3-KLHL20 Ubiquitin Ligase Governs the Turnover of ULK1 and VPS34 Complexes to Control Autophagy Termination. KLHL20 promotes ubiquitination of phagophore-residing VPS34 and Beclin-1 |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
SKP1 | up-regulates activity
binding
|
Cullin 3-RBX1-Skp1 |
0.9 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-271619 |
|
|
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 16547521 |
KLHL12 recruits Dsh to Cullin-3 for protein degradation. In vitro ubiquitination of Dsh3 by KLHL12–Cullin-3–Roc1. The E3 ligase complex was obtained by transfection of HEK293T cells . We show that the BTB-containing protein KLHL12 negatively regulates Dsh function by recruiting a pool of Dsh to the Cullin-3 ligase scaffold, thereby promoting its ubiquitination and degradation. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
Cullin 3-RBX1-Skp1 | up-regulates activity
monoubiquitination
|
AURKA |
0.419 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-272023 |
|
|
Homo sapiens |
U2-OS Cell |
| pmid |
sentence |
| 23213400 |
We identify Aurora-A as a KLHL18-interacting partner. Overexpression of KLHL18 and CUL3 promotes Aurora-A ubiquitylation in vivo, and the CUL3-KLHL18-ROC1 ligase ubiquitylates Aurora-A in vitro. Our study reveals that the CUL3-KLHL18 ligase is required for timely entry into mitosis, as well as for the activation of Aurora-A at centrosomes. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
Cullin 3-RBX1-Skp1 | down-regulates quantity by destabilization
polyubiquitination
|
PIK3C3 |
0.284 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-272418 |
|
|
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 26687681 |
Cul3-KLHL20 Ubiquitin Ligase Governs the Turnover of ULK1 and VPS34 Complexes to Control Autophagy Termination. KLHL20 promotes ubiquitination of phagophore-residing VPS34 and Beclin-1 |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
Cullin 3-RBX1-Skp1 | down-regulates quantity by destabilization
polyubiquitination
|
CEP97 |
0.272 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-272925 |
|
|
Homo sapiens |
HTERT-RPE1 Cell |
| pmid |
sentence |
| 30404837 |
Cullin-3-KCTD10-mediated CEP97 degradation promotes primary cilium formation. we identified the cullin-3-RBX1-KCTD10 complex as the E3 ligase that mediates CEP97 degradation and removal from the mother centriole. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
Cullin 3-RBX1-Skp1 | down-regulates quantity by destabilization
ubiquitination
|
RAPSN |
0.265 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-271782 |
|
|
Mus musculus |
NIH-3T3 Cell |
| pmid |
sentence |
| 19158078 |
We found that rapsyn was polyubiquitinated by KLHL8-containing E3 ligase, but not by KEAP1-containing E3 ligase, clearly indicating that rapsyn is a direct substrate of KLHL8-containing E3 ligase in mammals. We next examined the effect of KLHL-8 depletion on the ubiquitination of rapsyn by performing RNAi experiments in mammalian cells. We found that knockdown of KLHL8 in 3T3 cells reduced the level of rapsyn ubiquitination (Fig. 5C), again indicating that the maintenance mechanism for rapsyn stability is conserved in mammals.The in vitro ubiquitination of mammalian rapsyn by CUL3-containing E3 ligase and the effect of KLHL8 knockdown on the ubiquitination of rapsyn. |
|
| Publications: |
1 |
Organism: |
Mus Musculus |
| + |
Cullin 3-RBX1-Skp1 | down-regulates quantity by destabilization
polyubiquitination
|
TCHP |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-272465 |
|
|
Homo sapiens |
Retinal Pigment Epithelium Cell |
| pmid |
sentence |
| 25270598 |
We have identified KCTD17 as a substrate-adaptor for Cul3-RING E3 ligases (CRL3s) that polyubiquitylates trichoplein. Depletion of KCTD17 specifically arrests ciliogenesis at the initial step of axoneme extension through aberrant trichoplein-Aurora-A activity. Thus, CRL3-KCTD17 targets trichoplein to proteolysis to initiate the axoneme extension during ciliogenesis. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
Cullin 3-RBX1-Skp1 | down-regulates quantity by destabilization
polyubiquitination
|
CEBPB |
0.271 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-272456 |
|
|
Homo sapiens |
Glioblastoma Cell |
| pmid |
sentence |
| 25303533 |
KLHL9 mediates poly-ubiquitylation of C/EBPβ and C/EBPδ isoforms. We confirmed KLHL9 deletions in an independent cohort and showed that this protein is necessary for Cul3-ligase mediated ubiquitylation and proteasomal degradation of established MES-GBM MRs, C/EBPβ and C/EBPδ. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
Cullin 3-RBX1-Skp1 | down-regulates quantity by destabilization
polyubiquitination
|
PIK3R2 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-272113 |
|
|
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 23604317 |
FBXL2 binds p85α and p85β. p85β is targeted for ubiquitylation and degradation by SCF FBXL2. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
KLHL21 | up-regulates activity
binding
|
Cullin 3-RBX1-Skp1 |
0.552 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-272408 |
|
|
Homo sapiens |
HeLa Cell |
| pmid |
sentence |
| 27641145 |
Indeed, KLHL21 localizes to FA structures preferentially at the leading edge, and in complex with Cul3, ubiquitylates EB1 within its microtubule-interacting CH-domain. Cells lacking CRL3(KLHL21) activity or expressing a non-ubiquitylatable EB1 mutant protein are unable to migrate and exhibit strong defects in FA dynamics, lamellipodia formation and cortical plasticity. Our study thus reveals an important mechanism to regulate cortical dynamics during cell migration that involves ubiquitylation of EB1 at focal adhesions. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
KLHL7 | up-regulates activity
binding
|
Cullin 3-RBX1-Skp1 |
0.408 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-272320 |
|
|
Homo sapiens |
SW-620 Cell |
| pmid |
sentence |
| 29032201 |
Kelch-like protein 7 (KLHL7) is a component of Cul3-based Cullin-RING ubiquitin ligase. In this study, we report that KLHL7 increases terminal uridylyl transferase 1 (TUT1) ubiquitination involved in nucleolar integrity. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
Cullin 3-RBX1-Skp1 | down-regulates quantity by destabilization
polyubiquitination
|
PPP2R5B |
0.371 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-272019 |
|
|
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 23135275 |
Here, we report that KLHL15-Cul3 specifically targets B'β to promote turnover of the PP2A subunit by ubiquitylation and proteasomal degradation. We mapped KLHL15 residues critical for homodimerization as well as interaction with Cul3 and B'β. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
3.0
Cullin 3-RBX1-Skp1