| + |
LIMK2 | down-regulates activity 
phosphorylation
|
SPOP |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-278339 |
Ser171 |
VQDSVNIsGQNTMNM |
Homo sapiens |
|
| pmid |
sentence |
| 33311589 |
LIMK2 phosphorylates SPOP at S59, S171 and S226.|Together, these results depict that LIMK2-mediated SPOP degradation is a key mechanism that regulates AR stability. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-278338 |
Ser226 |
AARSPVFsAMFEHEM |
Homo sapiens |
|
| pmid |
sentence |
| 33311589 |
LIMK2 phosphorylates SPOP at S59, S171 and S226.|Together, these results depict that LIMK2-mediated SPOP degradation is a key mechanism that regulates AR stability. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-278337 |
Ser59 |
IKSSTFSsGANDKLK |
Homo sapiens |
|
| pmid |
sentence |
| 33311589 |
LIMK2 phosphorylates SPOP at S59, S171 and S226.|Together, these results depict that LIMK2-mediated SPOP degradation is a key mechanism that regulates AR stability. |
|
| Publications: |
3 |
Organism: |
Homo Sapiens |
| + |
SPOP | down-regulates activity
binding
|
INF2 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-272798 |
|
|
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 |
| + |
SPOP | down-regulates quantity
ubiquitination
|
BRMS1 |
0.404 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-268857 |
|
|
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 22085717 |
Intriguingly, BRMS1 turns out to be a potent substrate that is ubiquitinated by the Cul3-SPOP complex. Knockdown of SPOP increases the level of BRMS1 protein and represses the expression of BRMS1 repressive target genes such as OPN and uPA in breast cancer cells. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
SPOP | down-regulates quantity
ubiquitination
|
CD274 |
0.328 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-274978 |
|
|
Homo sapiens |
LNCaP-C4-2 Cell |
| pmid |
sentence |
| 29160310 |
Loss-of-function mutations in SPOP compromise ubiquitination-mediated PD-L1 degradation, leading to increased PD-L1 levels and reduced numbers of tumor-infiltrating lymphocytes (TILs) in mouse tumors and in primary human prostate cancer specimens. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
SPOP | up-regulates activity 
binding
|
CUL3 |
0.921 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-268927 |
|
|
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 34599168 |
Here we show that the CULLIN3 E3 ubiquitin ligase adaptor protein SPOP binds Geminin at endogenous level and regulates DNA replication. SPOP promotes K27-linked non-degradative poly-ubiquitination of Geminin at lysine residues 100 and 127. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
SPOP | down-regulates quantity by destabilization
binding
|
TRIM24 |
0.34 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-272825 |
|
|
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. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
1-phosphatidyl-1D-myo-inositol 5-phosphate(3-) | up-regulates activity
binding
|
SPOP |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-268863 |
|
|
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 18218622 |
Taken together, these data define a novel mechanism whereby the phosphoinositide PI5P leads to stimulation of Cul3-SPOP ubiquitin ligase activity and also implicate PIPKIIbeta as a key regulator of this signaling pathway through its association with the Cul3-SPOP complex. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
SPOP | down-regulates quantity by destabilization
binding
|
GLYR1 |
0.276 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-272824 |
|
|
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. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
SPOP | down-regulates activity
ubiquitination
|
GMNN |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-268926 |
|
|
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 34599168 |
SPOP promotes K27-linked non-degradative poly-ubiquitination of Geminin at lysine residues 100 and 127. This poly-ubiquitination of Geminin prevents DNA replication over-firing by indirectly blocking the association of Cdt1 with the MCM protein complex, an interaction required for DNA unwinding and replication. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
SPOP | up-regulates activity
binding
|
BMI1 |
0.401 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-272658 |
|
|
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 |
| + |
SPOP | down-regulates quantity by destabilization
binding
|
DEK |
0.441 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-272826 |
|
|
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: |
1 |
Organism: |
Homo Sapiens |
| + |
SPOP | down-regulates quantity
ubiquitination
|
DAXX |
0.487 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-268858 |
|
|
Homo sapiens |
HEK-293T Cell |
| pmid |
sentence |
| 16524876 |
These results suggest that SPOP/Cul3-ubiquitin ligase plays an essential role in the control of Daxx level and, thus, in the regulation of Daxx-mediated cellular processes, including transcriptional regulation and apoptosis. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
SPOP | down-regulates quantity by destabilization
binding
|
NCOA3 |
0.482 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-251529 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 24239470 |
Mutations in SPOP represent the most common point mutations in primary prostate cancer,with recurrent mutations in SPOP in 6% to 15% of multiple independent cohorts. Wild-type SPOP will bind and promote the degradation of SRC-3,whereas prostate cancer–derived SPOP mutants lose this ability,leading to increased androgen signaling in certain model systems. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-272827 |
|
|
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. |
|
| Publications: |
2 |
Organism: |
Homo Sapiens |
| Pathways: | Prostate Cancer |
| + |
SPOP | down-regulates quantity
ubiquitination
|
HDAC6 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-268862 |
|
|
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 28599312 |
Cullin3 SPOP ubiquitin E3 ligase promotes the poly-ubiquitination and degradation of HDAC6 |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
SPOP | down-regulates quantity
ubiquitination
|
PDX1 |
0.326 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-268859 |
|
|
Mus musculus |
Pancreatic Beta Cell |
| pmid |
sentence |
| 20811152 |
Pdx1 C terminus-interacting factor-1 (Pcif1, also known as SPOP) is a nuclear protein that inhibits Pdx1 transactivation. Here, we show that Pcif1 targets Pdx1 for ubiquitination and proteasomal degradation. |
|
| Publications: |
1 |
Organism: |
Mus Musculus |
| + |
SPOP | up-regulates
binding
|
Cullin 3-RBX1-Skp1 |
0.661 |
| 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 |
| + |
SPOP | down-regulates quantity
ubiquitination
|
GLI2 |
0.708 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-268860 |
|
|
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 20463034 |
RNAi knockdown of Spop (a substrate-binding adaptor for the cullin3-based ubiquitin E3 ligase) in Sufu mutant mouse embryonic fibroblasts (MEFs) can restore the levels of Gli2 and Gli3 full-length proteins |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
SPOP | up-regulates activity
binding
|
MACROH2A1 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-272657 |
|
|
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. BMI1 and MACROH2A1 interact with and are ubiquitinated by the CULLIN3 and SPOP ligase complex. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
SPOP | down-regulates quantity
ubiquitination
|
GLI3 |
0.702 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-268861 |
|
|
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 20463034 |
RNAi knockdown of Spop (a substrate-binding adaptor for the cullin3-based ubiquitin E3 ligase) in Sufu mutant mouse embryonic fibroblasts (MEFs) can restore the levels of Gli2 and Gli3 full-length proteins |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
SPOP | up-regulates activity
binding
|
Cullin 3-RBX1-Skp1 |
0.661 |
| 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 |
| + |
SPOP | down-regulates quantity by destabilization
ubiquitination
|
EGLN2 |
0.348 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-261996 |
|
|
Homo sapiens |
Prostate Cancer Cell Line |
| pmid |
sentence |
| 28089830 |
Tumor suppressor SPOP ubiquitinates and degrades EglN2 to compromise growth of prostate cancer cells |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
3.0
SPOP
- 
- 