| + |
CKM complex | down-regulates activity 
phosphorylation
|
H3C1 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-273170 |
Ser11 |
TKQTARKsTGGKAPR |
|
|
| pmid |
sentence |
| 18418385 |
However, within T/G-Mediator, cdk8 phosphorylates serine-10 on histone H3, which in turn stimulates H3K14 acetylation by GCN5L within the complex. Tandem phosphoacetylation of H3 correlates with transcriptional activation, and ChIP assays demonstrate co-occupancy of T/G-Mediator components at several activated genes in vivo. |
|
| Publications: |
1 |
| + |
CKM complex | down-regulates activity
phosphorylation
|
H3-3A |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-273172 |
Ser11 |
TKQTARKsTGGKAPR |
|
|
| pmid |
sentence |
| 18418385 |
However, within T/G-Mediator, cdk8 phosphorylates serine-10 on histone H3, which in turn stimulates H3K14 acetylation by GCN5L within the complex. Tandem phosphoacetylation of H3 correlates with transcriptional activation, and ChIP assays demonstrate co-occupancy of T/G-Mediator components at several activated genes in vivo. |
|
| Publications: |
1 |
| + |
CKM complex | down-regulates activity
phosphorylation
|
H3-4 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-273174 |
Ser11 |
TKQTARKsTGGKAPR |
|
|
| pmid |
sentence |
| 18418385 |
However, within T/G-Mediator, cdk8 phosphorylates serine-10 on histone H3, which in turn stimulates H3K14 acetylation by GCN5L within the complex. Tandem phosphoacetylation of H3 correlates with transcriptional activation, and ChIP assays demonstrate co-occupancy of T/G-Mediator components at several activated genes in vivo. |
|
| Publications: |
1 |
| + |
CKM complex | down-regulates quantity by destabilization
phosphorylation
|
SMAD1 |
0.334 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-273145 |
Ser187 |
NSHPFPHsPNSSYPN |
Homo sapiens |
|
| pmid |
sentence |
| 19914161 |
Phosphorylation of the linker region of smad1, a receptor-activated smad (r-smad), at serine 206 (s206) and s214 induced by bmp and mediated by cdk8/9 is critical for binding of the e3 ubiquitin ligase smurf1. Binding of smurf1 leads to polyubiquitination of smad1 and its degradation by the proteasome;cdk8 and cyclint-cdk9 showed a preference for s206 and s214 but also phosphorylated s186 and s195 in the case of smad1;and t179, s208 and s213 in the case of smad3. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-273140 |
Ser195 |
PNSSYPNsPGSSSST |
Homo sapiens |
|
| pmid |
sentence |
| 19914161 |
Phosphorylation of the linker region of smad1, a receptor-activated smad (r-smad), at serine 206 (s206) and s214 induced by bmp and mediated by cdk8/9 is critical for binding of the e3 ubiquitin ligase smurf1. Binding of smurf1 leads to polyubiquitination of smad1 and its degradation by the proteasome;cdk8 and cyclint-cdk9 showed a preference for s206 and s214 but also phosphorylated s186 and s195 in the case of smad1;and t179, s208 and s213 in the case of smad3. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-273152 |
Ser195 |
PNSSYPNsPGSSSST |
Homo sapiens |
|
| pmid |
sentence |
| 19914168 |
Phosphorylation of the linker region of smad1, a receptor-activated smad (r-smad), at serine 206 (s206) and s214 induced by bmp and mediated by cdk8/9 is critical for binding of the e3 ubiquitin ligase smurf1. Binding of smurf1 leads to polyubiquitination of smad1 and its degradation by the proteasome;cdk8 and cyclint-cdk9 showed a preference for s206 and s214 but also phosphorylated s186 and s195 in the case of smad1;and t179, s208 and s213 in the case of smad3. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-273144 |
Ser206 |
SSSTYPHsPTSSDPG |
Homo sapiens |
|
| pmid |
sentence |
| 19914161 |
Phosphorylation of the linker region of smad1, a receptor-activated smad (r-smad), at serine 206 (s206) and s214 induced by bmp and mediated by cdk8/9 is critical for binding of the e3 ubiquitin ligase smurf1. Binding of smurf1 leads to polyubiquitination of smad1 and its degradation by the proteasome;cdk8 and cyclint-cdk9 showed a preference for s206 and s214 but also phosphorylated s186 and s195 in the case of smad1;and t179, s208 and s213 in the case of smad3. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-273148 |
Ser214 |
PTSSDPGsPFQMPAD |
Homo sapiens |
|
| pmid |
sentence |
| 19914161 |
Phosphorylation of the linker region of smad1, a receptor-activated smad (r-smad), at serine 206 (s206) and s214 induced by bmp and mediated by cdk8/9 is critical for binding of the e3 ubiquitin ligase smurf1. Binding of smurf1 leads to polyubiquitination of smad1 and its degradation by the proteasome;cdk8 and cyclint-cdk9 showed a preference for s206 and s214 but also phosphorylated s186 and s195 in the case of smad1;and t179, s208 and s213 in the case of smad3. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-273143 |
Ser214 |
PTSSDPGsPFQMPAD |
Homo sapiens |
|
| pmid |
sentence |
| 19914168 |
Phosphorylation of the linker region of smad1, a receptor-activated smad (r-smad), at serine 206 (s206) and s214 induced by bmp and mediated by cdk8/9 is critical for binding of the e3 ubiquitin ligase smurf1. Binding of smurf1 leads to polyubiquitination of smad1 and its degradation by the proteasome;cdk8 and cyclint-cdk9 showed a preference for s206 and s214 but also phosphorylated s186 and s195 in the case of smad1;and t179, s208 and s213 in the case of smad3. |
|
| Publications: |
6 |
Organism: |
Homo Sapiens |
| + |
CKM complex | down-regulates activity
phosphorylation
|
SMAD3 |
0.447 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-273151 |
Ser208 |
DAGSPNLsPNPMSPA |
Homo sapiens |
|
| pmid |
sentence |
| 19914161 |
Similarly, tgf-?-Induced and cdk8/9-mediated phosphorylation of smad3 at threonine 179 (t179) is important for binding of the nedd4l e3 ubiquitin ligase, which accelerates smad3 turnover;cdk8 and cyclint-cdk9 showed a preference for s206 and s214 but also phosphorylated s186 and s195 in the case of smad1;and t179, s208 and s213 in the case of smad3. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
CKM complex | down-regulates quantity by destabilization
phosphorylation
|
SMAD3 |
0.447 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-273146 |
Ser213 |
NLSPNPMsPAHNNLD |
Homo sapiens |
|
| pmid |
sentence |
| 19914168 |
Similarly, tgf-?-Induced and cdk8/9-mediated phosphorylation of smad3 at threonine 179 (t179) is important for binding of the nedd4l e3 ubiquitin ligase, which accelerates smad3 turnover;cdk8 and cyclint-cdk9 showed a preference for s206 and s214 but also phosphorylated s186 and s195 in the case of smad1;and t179, s208 and s213 in the case of smad3. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-273147 |
Ser213 |
NLSPNPMsPAHNNLD |
Homo sapiens |
|
| pmid |
sentence |
| 19914161 |
Similarly, tgf-?-Induced and cdk8/9-mediated phosphorylation of smad3 at threonine 179 (t179) is important for binding of the nedd4l e3 ubiquitin ligase, which accelerates smad3 turnover;cdk8 and cyclint-cdk9 showed a preference for s206 and s214 but also phosphorylated s186 and s195 in the case of smad1;and t179, s208 and s213 in the case of smad3. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-273142 |
Thr179 |
PQSNIPEtPPPGYLS |
Homo sapiens |
|
| pmid |
sentence |
| 19914161 |
Similarly, tgf-?-Induced and cdk8/9-mediated phosphorylation of smad3 at threonine 179 (t179) is important for binding of the nedd4l e3 ubiquitin ligase, which accelerates smad3 turnover;cdk8 and cyclint-cdk9 showed a preference for s206 and s214 but also phosphorylated s186 and s195 in the case of smad1;and t179, s208 and s213 in the case of smad3. |
|
| Publications: |
3 |
Organism: |
Homo Sapiens |
| + |
CKM complex | down-regulates activity
phosphorylation
|
CCNH |
0.435 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-273141 |
Ser304 |
YEDDDYVsKKSKHEE |
Homo sapiens |
|
| pmid |
sentence |
| 10993082 |
Cdk8 phosphorylates mammalian cyclin h in the vicinity of its functionally unique amino-terminal and carboxy-terminal alpha-helical domains. This phosphorylation represses both the ability of tfiih to activate transcription and its ctd kinase activity |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-273139 |
Ser5 |
sSQKRHWT |
Homo sapiens |
|
| pmid |
sentence |
| 10993082 |
Here we show that cdk8/cyclin c can regulate transcription by targeting the cdk7/cyclin h subunits of the general transcription initiation factor iih (tfiih). cdk8 phosphorylates mammalian cyclin h in the vicinity of its functionally unique amino-terminal and carboxy-terminal alpha-helical domains. This phosphorylation represses both the ability of tfiih to activate transcription and its ctd kinase activity. In addition, mimicking cdk8 phosphorylation of cyclin h in vivo has a dominant-negative effect on cell growth. |
|
| Publications: |
2 |
Organism: |
Homo Sapiens |
| + |
CKM complex | down-regulates activity
phosphorylation
|
E2F1 |
0.356 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-273149 |
Ser375 |
PVDEDRLsPLVAADS |
Homo sapiens |
|
| pmid |
sentence |
| 18794899 |
E2F1 activity is also repressed by cyclin-dependent kinase-8 (CDK8), a colorectal oncoprotein. Elevated levels of CDK8 protect beta-catenin/TCF-dependent transcription from inhibition by E2F1. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-273138 |
Ser375 |
PVDEDRLsPLVAADS |
Homo sapiens |
|
| pmid |
sentence |
| 22945643 |
Cdk8 regulates e2f1 transcriptional activity through s375 phosphorylation. |
|
| Publications: |
2 |
Organism: |
Homo Sapiens |
| + |
CKM complex | up-regulates activity 
phosphorylation
|
STAT1 |
0.292 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-273182 |
Ser727 |
TDNLLPMsPEEFDEV |
|
|
| pmid |
sentence |
| 29239838 |
We previously demonstrated that Mediator kinase inhibitor cortistatin A (CA) reduced proliferation of JAK2-mutant AML in vitro and in vivo and also suppressed CDK8-dependent phosphorylation of STAT1 at serine 727. Here we report that phosphorylation of STAT1 S727 promotes the proliferation of AML cells with JAK-STAT pathway activation. |
|
| Publications: |
1 |
| + |
MED13L | form complex 
binding
|
CKM complex |
0.779 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-266702 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 23563140 |
The CDK8 kinase module (CKM) is a conserved, dissociable Mediator subcomplex whose component subunits were genetically linked to the RNA polymerase II (RNAPII) C-terminal domain (CTD) and individually recognized as transcriptional repressors before Mediator was identified as a pre-eminent complex in eukaryotic transcription regulation. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
CKM complex | down-regulates quantity by destabilization
phosphorylation
|
NOTCH1 |
0.391 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-273160 |
|
|
in vitro |
|
| pmid |
sentence |
| 25344755 |
Mapping of cyclin C-dependent phosphosites on ICN1, using mass spectrometry revealed that several of them are located within the PEST-domain of Notch1, which controls ICN1 degradation38,39 (Fig. 5g and Supplementary Table 1). Three of them (T2512, S2514 and S2517) are localized within the consensus motif, “Cdc4 phosphodegron”, which is shared by most substrates of Fbw7 (Cdc4) ubiquitin ligase38. Two of these residues (S2514 and S2517) were previously shown by Fryer et al.20 to be phosphorylated by cyclin C-CDK8 in vitro, and all three were shown to play a role in controlling ICN1 stability via Fbw740. We verified that cyclin C-CDK8, C-CDK19 and C-CDK3 phosphorylate ICN1 on these three residues |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-273158 |
|
|
in vitro |
|
| pmid |
sentence |
| 25344755 |
Mapping of cyclin C-dependent phosphosites on ICN1, using mass spectrometry revealed that several of them are located within the PEST-domain of Notch1, which controls ICN1 degradation38,39 (Fig. 5g and Supplementary Table 1). Three of them (T2512, S2514 and S2517) are localized within the consensus motif, “Cdc4 phosphodegron”, which is shared by most substrates of Fbw7 (Cdc4) ubiquitin ligase38. Two of these residues (S2514 and S2517) were previously shown by Fryer et al.20 to be phosphorylated by cyclin C-CDK8 in vitro, and all three were shown to play a role in controlling ICN1 stability via Fbw740. We verified that cyclin C-CDK8, C-CDK19 and C-CDK3 phosphorylate ICN1 on these three residues |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-273150 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 15546612 |
Purified recombinant cycc:cdk8 phosphorylates the notch icd within the tad and pest domains, and expression of cycc:cdk8 strongly enhances notch icd hyperphosphorylation and pest-dependent degradation by the fbw7/sel10 ubiquitin ligase in vivo. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-273159 |
|
|
in vitro |
|
| pmid |
sentence |
| 25344755 |
Mapping of cyclin C-dependent phosphosites on ICN1, using mass spectrometry revealed that several of them are located within the PEST-domain of Notch1, which controls ICN1 degradation38,39 (Fig. 5g and Supplementary Table 1). Three of them (T2512, S2514 and S2517) are localized within the consensus motif, “Cdc4 phosphodegron”, which is shared by most substrates of Fbw7 (Cdc4) ubiquitin ligase38. Two of these residues (S2514 and S2517) were previously shown by Fryer et al.20 to be phosphorylated by cyclin C-CDK8 in vitro, and all three were shown to play a role in controlling ICN1 stability via Fbw740. We verified that cyclin C-CDK8, C-CDK19 and C-CDK3 phosphorylate ICN1 on these three residues |
|
| Publications: |
4 |
Organism: |
In Vitro, Homo Sapiens |
| + |
CKM complex | down-regulates quantity by destabilization
phosphorylation
|
NOTCH |
0.391 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-273153 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 15546612 |
Purified recombinant cycc:cdk8 phosphorylates the notch icd within the tad and pest domains, and expression of cycc:cdk8 strongly enhances notch icd hyperphosphorylation and pest-dependent degradation by the fbw7/sel10 ubiquitin ligase in vivo. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
CCNC | form complex
binding
|
CKM complex |
0.925 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-266685 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 23563140 |
The CDK8 kinase module (CKM) is a conserved, dissociable Mediator subcomplex whose component subunits were genetically linked to the RNA polymerase II (RNAPII) C-terminal domain (CTD) and individually recognized as transcriptional repressors before Mediator was identified as a pre-eminent complex in eukaryotic transcription regulation. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
CDK8 | form complex
binding
|
CKM complex |
0.905 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-266686 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 23563140 |
The CDK8 kinase module (CKM) is a conserved, dissociable Mediator subcomplex whose component subunits were genetically linked to the RNA polymerase II (RNAPII) C-terminal domain (CTD) and individually recognized as transcriptional repressors before Mediator was identified as a pre-eminent complex in eukaryotic transcription regulation. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
MED12 | form complex
binding
|
CKM complex |
0.925 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-266683 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 23563140 |
The CDK8 kinase module (CKM) is a conserved, dissociable Mediator subcomplex whose component subunits were genetically linked to the RNA polymerase II (RNAPII) C-terminal domain (CTD) and individually recognized as transcriptional repressors before Mediator was identified as a pre-eminent complex in eukaryotic transcription regulation. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
CKM complex | down-regulates activity
binding
|
Core mediator complex |
0.771 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-266687 |
|
|
in vitro |
|
| pmid |
sentence |
| 23563140 |
We found that interaction of the CKM with Mediator's middle module interferes with CTD-dependent RNAPII binding to a previously unknown middle-module CTD-binding site and with the holoenzyme formation process. Taken together, our results reveal the basis for CKM repression, clarify the origin of the connection between CKM subunits and the CTD and suggest that a combination of competitive interactions and conformational changes that facilitate holoenzyme formation underlie the mechanism of transcription regulation by Mediator. |
|
| Publications: |
1 |
Organism: |
In Vitro |
| + |
MED13 | form complex
binding
|
CKM complex |
0.81 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-266684 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 23563140 |
The CDK8 kinase module (CKM) is a conserved, dissociable Mediator subcomplex whose component subunits were genetically linked to the RNA polymerase II (RNAPII) C-terminal domain (CTD) and individually recognized as transcriptional repressors before Mediator was identified as a pre-eminent complex in eukaryotic transcription regulation. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
4.0
CKM complex
CPX-3232