| + |
CBP/p300 | up-regulates activity 
acetylation
|
SMAD3 |
0.687 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-236126 |
Lys19 |
VKRLLGWkKGEQNGQ |
Homo sapiens |
HeLa Cell, HEK-293T Cell, HaCaT Cell |
| pmid |
sentence |
| 17074756 |
We demonstrate that both smad2 and smad3 are acetylated by the coactivators p300 and cbp in a tgfb-dependent manner. the p300-dependent acetylation of smad3 was attenuated when lys19 was mutated, whereas mutation of lys20 had no effect, suggesting that lys19 is acetylated also in smad3. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-227553 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 9865691 |
The closely related CBP and p300 proteins are also important coactivators for Smad activity. CBP and p300 act as coactivators of several transcription factors by bringing the sequence-specific activators within proximity of the general transcription machinery and by modifying the chromatin structure through histone acetylation.In response to TGF-b, Smad3 associates with CBP/p300 and TGF-b-induced C-terminal phosphorylation of Smad3 promotes this association. This association with CBP/p300 is likely to be essential for transcriptional activity of Smad3. |
|
| Publications: |
2 |
Organism: |
Homo Sapiens |
| Pathways: | TGF-beta Signaling |
| + |
EP300 | up-regulates quantity by stabilization
acetylation
|
SMAD3 |
0.731 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-260431 |
Lys378 |
TIRMSFVkGWGAEYR |
Homo sapiens |
|
| pmid |
sentence |
| 16862174 |
Smad proteins are crucial for the intracellular signaling of transforming growth factor-beta (TGF-beta). Upon their receptor-induced activation, Smad proteins are phosphorylated and translocated to the nucleus to activate the transcription of a select set of target genes. Here, we show that the co-activator p300/CBP bound and acetylated Smad3 as well as Smad2 in vivo, and that the acetylation was stimulated by TGF-beta.A major acetylation site of Smad3 by p300/CBP is Lys-378 in the MH2 domain (Smad3C) known to be critical for the regulation of transcriptional activity. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | COVID-19 Causal Network, Fibrosis, SARS-CoV FIBROSIS |
| + |
MAPK1 |
phosphorylation
|
SMAD3 |
0.74 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-126744 |
Ser204 |
NHSMDAGsPNLSPNP |
Homo sapiens |
|
| pmid |
sentence |
| 15241418 |
We found that ser 203 and ser 207 were phosphorylated by map kinase and that thr 178 was phosphorylated mostly by cdk and to a lesser extent by map kinase |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-161698 |
Ser204 |
NHSMDAGsPNLSPNP |
Homo sapiens |
|
| pmid |
sentence |
| 19914168 |
In contrast, ERK2 phosphorylated all four Smad1 residues almost evenly, while showing a preference for S204 over S208 and S213 in Smad3 |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-126748 |
Ser208 |
DAGSPNLsPNPMSPA |
Homo sapiens |
|
| pmid |
sentence |
| 15241418 |
We found that ser 203 and ser 207 were phosphorylated by map kinase and that thr 178 was phosphorylated mostly by cdk and to a lesser extent by map kinase |
|
| Publications: |
3 |
Organism: |
Homo Sapiens |
| + |
CTDSP2 | up-regulates activity
dephosphorylation
|
SMAD3 |
0.409 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-248293 |
Ser204 |
NHSMDAGsPNLSPNP |
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 17035229 |
Dephosphorylation of Smad2/3 Linkers by SCP2 and SCP3|MAPK-mediated linker phosphorylation appears to have a dual role in Smad2/3 regulation. Mitogens and hyperactive Ras result in extracellular signal-regulated kinase (ERK)-mediated phosphorylation of Smad3 at Ser-204, Ser-208, and Thr-179 and of Smad2 at Ser-245/250/255 and Thr-220. Mutation of these sites increases the ability of Smad3 to activate target genes, suggesting that MAPK phosphorylation of Smad3 is inhibitory (11, 12). However, in contrast, ERK-dependent phosphorylation of Smad2 at Thr-8 enhances its transcriptional activity |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-248294 |
Ser208 |
DAGSPNLsPNPMSPA |
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 17035229 |
Dephosphorylation of Smad2/3 Linkers by SCP2 and SCP3|MAPK-mediated linker phosphorylation appears to have a dual role in Smad2/3 regulation. Mitogens and hyperactive Ras result in extracellular signal-regulated kinase (ERK)-mediated phosphorylation of Smad3 at Ser-204, Ser-208, and Thr-179 and of Smad2 at Ser-245/250/255 and Thr-220. Mutation of these sites increases the ability of Smad3 to activate target genes, suggesting that MAPK phosphorylation of Smad3 is inhibitory (11, 12). However, in contrast, ERK-dependent phosphorylation of Smad2 at Thr-8 enhances its transcriptional activity |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-248295 |
Ser213 |
NLSPNPMsPAHNNLD |
Homo sapiens |
|
| pmid |
sentence |
| 17035229 |
Dephosphorylation of Smad2/3 Linkers by SCP2 and SCP3|MAPK-mediated linker phosphorylation appears to have a dual role in Smad2/3 regulation. Mitogens and hyperactive Ras result in extracellular signal-regulated kinase (ERK)-mediated phosphorylation of Smad3 at Ser-204, Ser-208, and Thr-179 and of Smad2 at Ser-245/250/255 and Thr-220. Mutation of these sites increases the ability of Smad3 to activate target genes, suggesting that MAPK phosphorylation of Smad3 is inhibitory (11, 12). However, in contrast, ERK-dependent phosphorylation of Smad2 at Thr-8 enhances its transcriptional activity |
|
| Publications: |
3 |
Organism: |
Homo Sapiens |
| + |
MAPK14 | up-regulates activity
phosphorylation
|
SMAD3 |
0.547 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-250113 |
Ser204 |
NHSMDAGsPNLSPNP |
Homo sapiens |
MCF-10A Cell |
| pmid |
sentence |
| 15520018 |
Smad3 was phosphorylated at both Ser203 and Ser207 in untreated MCF10CA1h cells and the p38 and ROCK inhibitors each down-regulated phosphorylation at these sites. we demonstrate that phosphorylation at Ser203 and Ser207 residues is required for the full transactivation potential of Smad3, and that these residues are targets of the p38 and Rho/ROCK pathways. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-250112 |
Ser208 |
DAGSPNLsPNPMSPA |
Homo sapiens |
MCF-10A Cell |
| pmid |
sentence |
| 15520018 |
Smad3 was phosphorylated at both Ser203 and Ser207 in untreated MCF10CA1h cells and the p38 and ROCK inhibitors each down-regulated phosphorylation at these sites. we demonstrate that phosphorylation at Ser203 and Ser207 residues is required for the full transactivation potential of Smad3, and that these residues are targets of the p38 and Rho/ROCK pathways. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-236136 |
|
|
Rattus norvegicus |
|
| pmid |
sentence |
| 14512875 |
P38 mapk mediates fibrogenic signal through smad3 phosphorylation in rat myofibroblasts. the phosphorylation promoted hetero-complex formation and nuclear translocation of smad3 and smad4. |
|
| Publications: |
3 |
Organism: |
Homo Sapiens, Rattus Norvegicus |
| Pathways: | TGF-beta Signaling |
| + |
MAPK1 | down-regulates activity 
phosphorylation
|
SMAD3 |
0.74 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-161609 |
Ser204 |
NHSMDAGsPNLSPNP |
Homo sapiens |
|
| pmid |
sentence |
| 19914161 |
Phosphorylation of the linker region of Smads mediated by ERK2, GSK3β, and CDK2/4 negatively regulates Smad activity |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-161613 |
Ser208 |
DAGSPNLsPNPMSPA |
Homo sapiens |
|
| pmid |
sentence |
| 19914161 |
Phosphorylation of the linker region of smads mediated by erk2, gsk3?, And cdk2/4 negatively regulates smad activity by preventing their relocation to the nucleus, by inhibiting their interactions with coactivators, or by accelerating their degradation;in contrast, erk2 phosphorylated all four smad1 residues almost evenly, while showing a preference for s204 over s208 and s213 in smad3 |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-66746 |
Thr179 |
PQSNIPEtPPPGYLS |
Homo sapiens |
|
| pmid |
sentence |
| 10197981 |
Oncogenically activated ras inhibits the tgfbeta-induced nuclear accumulation of smad2 and smad3 and smad-dependent transcription. Ras acting via erk map kinases causes phosphorylation of smad2 and smad3 at specific sites in the region linking the dna-binding domain and the transcriptional activation domain. |
|
| Publications: |
3 |
Organism: |
Homo Sapiens |
| + |
CTDSP1 | up-regulates activity
dephosphorylation
|
SMAD3 |
0.418 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-248791 |
Ser204 |
NHSMDAGsPNLSPNP |
Homo sapiens |
|
| pmid |
sentence |
| 17035229 |
SCP1 Dephosphorylates Smad2/3 in the Linkers|MAPK-mediated linker phosphorylation appears to have a dual role in Smad2/3 regulation. Mitogens and hyperactive Ras result in extracellular signal-regulated kinase (ERK)-mediated phosphorylation of Smad3 at Ser-204, Ser-208, and Thr-179 and of Smad2 at Ser-245/250/255 and Thr-220. Mutation of these sites increases the ability of Smad3 to activate target genes, suggesting that MAPK phosphorylation of Smad3 is inhibitory (11, 12). However, in contrast, ERK-dependent phosphorylation of Smad2 at Thr-8 enhances its transcriptional activity |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-248792 |
Ser208 |
DAGSPNLsPNPMSPA |
Homo sapiens |
|
| pmid |
sentence |
| 17035229 |
SCP1 Dephosphorylates Smad2/3 in the Linkers|MAPK-mediated linker phosphorylation appears to have a dual role in Smad2/3 regulation. Mitogens and hyperactive Ras result in extracellular signal-regulated kinase (ERK)-mediated phosphorylation of Smad3 at Ser-204, Ser-208, and Thr-179 and of Smad2 at Ser-245/250/255 and Thr-220. Mutation of these sites increases the ability of Smad3 to activate target genes, suggesting that MAPK phosphorylation of Smad3 is inhibitory (11, 12). However, in contrast, ERK-dependent phosphorylation of Smad2 at Thr-8 enhances its transcriptional activity |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-248793 |
Ser213 |
NLSPNPMsPAHNNLD |
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 17035229 |
SCP1 Dephosphorylates Smad2/3 in the Linkers|MAPK-mediated linker phosphorylation appears to have a dual role in Smad2/3 regulation. Mitogens and hyperactive Ras result in extracellular signal-regulated kinase (ERK)-mediated phosphorylation of Smad3 at Ser-204, Ser-208, and Thr-179 and of Smad2 at Ser-245/250/255 and Thr-220. Mutation of these sites increases the ability of Smad3 to activate target genes, suggesting that MAPK phosphorylation of Smad3 is inhibitory (11, 12). However, in contrast, ERK-dependent phosphorylation of Smad2 at Thr-8 enhances its transcriptional activity |
|
| Publications: |
3 |
Organism: |
Homo Sapiens |
| + |
CDK2 |
phosphorylation
|
SMAD3 |
0.737 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-250749 |
Ser204 |
NHSMDAGsPNLSPNP |
in vitro |
|
| pmid |
sentence |
| 15241418 |
Thus, we have shown that Smad3 is phosphorylated by CDK4 and CDK2. Mutation of its CDK phosphorylation sites increases its transcriptional activity and antiproliferative function. | Thr 8 and the four sites in the linker (Thr 178, Ser 203, Ser 207 and Ser 212). Each of the five sites was phosphorylated by both CDK4 and CDK2 in vitro, and only Thr 8, Thr 178 and Ser 212 were phosphorylated by CDK4 and CDK2 in vivo phosphorylated by both CDK4 and CDK2 in vitro, and only Thr 8, Thr 178 and Ser 212 were phosphorylated by CDK4 and CDK2 in vivo. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-250750 |
Ser208 |
DAGSPNLsPNPMSPA |
in vitro |
|
| pmid |
sentence |
| 15241418 |
Thus, we have shown that Smad3 is phosphorylated by CDK4 and CDK2. Mutation of its CDK phosphorylation sites increases its transcriptional activity and antiproliferative function. We propose that under physiological conditions, phosphorylation of Smad3 by CDK inhibits its transcriptional activity, contributing to a decreased level of p15 and an increased level of c-Myc, thus facilitating cell cycle progression from G1 to S phase. |
|
| Publications: |
2 |
Organism: |
In Vitro |
| Pathways: | Adipogenesis |
| + |
CTDSPL | up-regulates activity
dephosphorylation
|
SMAD3 |
0.408 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-248306 |
Ser204 |
NHSMDAGsPNLSPNP |
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 17035229 |
Dephosphorylation of Smad2/3 Linkers by SCP2 and SCP3|MAPK-mediated linker phosphorylation appears to have a dual role in Smad2/3 regulation. Mitogens and hyperactive Ras result in extracellular signal-regulated kinase (ERK)-mediated phosphorylation of Smad3 at Ser-204, Ser-208, and Thr-179 and of Smad2 at Ser-245/250/255 and Thr-220. Mutation of these sites increases the ability of Smad3 to activate target genes, suggesting that MAPK phosphorylation of Smad3 is inhibitory (11, 12). However, in contrast, ERK-dependent phosphorylation of Smad2 at Thr-8 enhances its transcriptional activity |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-248307 |
Ser208 |
DAGSPNLsPNPMSPA |
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 17035229 |
Dephosphorylation of Smad2/3 Linkers by SCP2 and SCP3|MAPK-mediated linker phosphorylation appears to have a dual role in Smad2/3 regulation. Mitogens and hyperactive Ras result in extracellular signal-regulated kinase (ERK)-mediated phosphorylation of Smad3 at Ser-204, Ser-208, and Thr-179 and of Smad2 at Ser-245/250/255 and Thr-220. Mutation of these sites increases the ability of Smad3 to activate target genes, suggesting that MAPK phosphorylation of Smad3 is inhibitory (11, 12). However, in contrast, ERK-dependent phosphorylation of Smad2 at Thr-8 enhances its transcriptional activity |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-248308 |
Ser213 |
NLSPNPMsPAHNNLD |
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 17035229 |
Dephosphorylation of Smad2/3 Linkers by SCP2 and SCP3|MAPK-mediated linker phosphorylation appears to have a dual role in Smad2/3 regulation. Mitogens and hyperactive Ras result in extracellular signal-regulated kinase (ERK)-mediated phosphorylation of Smad3 at Ser-204, Ser-208, and Thr-179 and of Smad2 at Ser-245/250/255 and Thr-220. Mutation of these sites increases the ability of Smad3 to activate target genes, suggesting that MAPK phosphorylation of Smad3 is inhibitory (11, 12). However, in contrast, ERK-dependent phosphorylation of Smad2 at Thr-8 enhances its transcriptional activity |
|
| Publications: |
3 |
Organism: |
Homo Sapiens |
| + |
CDK4 |
phosphorylation
|
SMAD3 |
0.752 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-250766 |
Ser204 |
NHSMDAGsPNLSPNP |
in vitro |
|
| pmid |
sentence |
| 15241418 |
Thus, we have shown that Smad3 is phosphorylated by CDK4 and CDK2. Mutation of its CDK phosphorylation sites increases its transcriptional activity and antiproliferative function. | Thr 8 and the four sites in the linker (Thr 178, Ser 203, Ser 207 and Ser 212). Each of the five sites was phosphorylated by both CDK4 and CDK2 in vitro, and only Thr 8, Thr 178 and Ser 212 were phosphorylated by CDK4 and CDK2 in vivo phosphorylated by both CDK4 and CDK2 in vitro, and only Thr 8, Thr 178 and Ser 212 were phosphorylated by CDK4 and CDK2 in vivo. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-250767 |
Ser208 |
DAGSPNLsPNPMSPA |
in vitro |
|
| pmid |
sentence |
| 15241418 |
Thus, we have shown that Smad3 is phosphorylated by CDK4 and CDK2. Mutation of its CDK phosphorylation sites increases its transcriptional activity and antiproliferative function. | Thr 8 and the four sites in the linker (Thr 178, Ser 203, Ser 207 and Ser 212). Each of the five sites was phosphorylated by both CDK4 and CDK2 in vitro, and only Thr 8, Thr 178 and Ser 212 were phosphorylated by CDK4 and CDK2 in vivo phosphorylated by both CDK4 and CDK2 in vitro, and only Thr 8, Thr 178 and Ser 212 were phosphorylated by CDK4 and CDK2 in vivo. |
|
| Publications: |
2 |
Organism: |
In Vitro |
| Pathways: | Pancreatic ductal adenocarcinoma (PDA) |
| + |
CDK8 | down-regulates activity
phosphorylation
|
SMAD3 |
0.554 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-161553 |
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. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-161561 |
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: |
2 |
Organism: |
Homo Sapiens |
| + |
CKM complex | down-regulates activity
phosphorylation
|
SMAD3 |
0.426 |
| 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 |
| + |
CDK9 | down-regulates activity
phosphorylation
|
SMAD3 |
0.613 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-161581 |
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. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-161589 |
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: |
2 |
Organism: |
Homo Sapiens |
| + |
CDK9 | down-regulates
phosphorylation
|
SMAD3 |
0.613 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-161585 |
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-161678 |
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. |
|
| Publications: |
2 |
Organism: |
Homo Sapiens |
| + |
MAPK1 | down-regulates
phosphorylation
|
SMAD3 |
0.74 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-161706 |
Ser213 |
NLSPNPMsPAHNNLD |
Homo sapiens |
|
| pmid |
sentence |
| 19914168 |
Phosphorylation of the linker region of smads mediated by erk2, gsk3?, And cdk2/4 negatively regulates smad activity by preventing their relocation to the nucleus, by inhibiting their interactions with coactivators, or by accelerating their degradation;in contrast, erk2 phosphorylated all four smad1 residues almost evenly, while showing a preference for s204 over s208 and s213 in smad3 |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-66742 |
Ser213 |
NLSPNPMsPAHNNLD |
Homo sapiens |
|
| pmid |
sentence |
| 10197981 |
Oncogenically activated ras inhibits the tgfbeta-induced nuclear accumulation of smad2 and smad3 and smad-dependent transcription. Ras acting via erk map kinases causes phosphorylation of smad2 and smad3 at specific sites in the region linking the dna-binding domain and the transcriptional activation domain. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-161617 |
Ser213 |
NLSPNPMsPAHNNLD |
Homo sapiens |
|
| pmid |
sentence |
| 19914161 |
Phosphorylation of the linker region of smads mediated by erk2, gsk3?, And cdk2/4 negatively regulates smad activity by preventing their relocation to the nucleus, by inhibiting their interactions with coactivators, or by accelerating their degradation;in contrast, erk2 phosphorylated all four smad1 residues almost evenly, while showing a preference for s204 over s208 and s213 in smad3 |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-66749 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 10197981 |
These results suggest that oncogenic ras, acting through mek1 and erk kinases, induces the phosphorylation of smad2 and smad3 |
|
| Publications: |
4 |
Organism: |
Homo Sapiens |
| Tissue: |
Lung, Breast |
| + |
CDK4 | down-regulates
phosphorylation
|
SMAD3 |
0.752 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-182979 |
Ser213 |
NLSPNPMsPAHNNLD |
Homo sapiens |
|
| pmid |
sentence |
| 19114991 |
In the nucleus cdk2/4-mediated phosphorylation of smad3 occurs mostly at thr8, thr179, and ser213. Cdk-dependent phosphorylation of smad3 inhibits its transcriptional activity |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-182983 |
Thr8 |
MSSILPFtPPIVKRL |
Homo sapiens |
|
| pmid |
sentence |
| 19114991 |
In the nucleus cdk2/4-mediated phosphorylation of smad3 occurs mostly at thr8, thr179, and ser213. Cdk-dependent phosphorylation of smad3 inhibits its transcriptional activity |
|
| Publications: |
2 |
Organism: |
Homo Sapiens |
| Pathways: | Pancreatic ductal adenocarcinoma (PDA) |
| + |
CDK8 | down-regulates
phosphorylation
|
SMAD3 |
0.554 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-161557 |
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-161646 |
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. |
|
| Publications: |
2 |
Organism: |
Homo Sapiens |
| + |
CDK2 | down-regulates activity
phosphorylation
|
SMAD3 |
0.737 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-232134 |
Ser213 |
NLSPNPMsPAHNNLD |
Homo sapiens |
|
| pmid |
sentence |
| 15241418 |
We have mapped CDK4 and CDK2 phosphorylation sites to Thr 8, Thr 178 and Ser 212 in Smad3. Mutation of the CDK phosphorylation sites increases Smad3 transcriptional activity |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-182971 |
Thr179 |
PQSNIPEtPPPGYLS |
Homo sapiens |
|
| pmid |
sentence |
| 19114991 |
In the nucleus cdk2/4-mediated phosphorylation of smad3 occurs mostly at thr8, thr179, and ser213. Cdk-dependent phosphorylation of smad3 inhibits its transcriptional activity |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-126736 |
Thr179 |
PQSNIPEtPPPGYLS |
Homo sapiens |
|
| pmid |
sentence |
| 15241418 |
We have mapped cdk4 and cdk2 phosphorylation sites to thr 8, thr 178 and ser 212 in smad3. taken together, these findings indicate that cdk phosphorylation of smad3 inhibits its transcriptional activity and antiproliferative function |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-217734 |
Thr8 |
MSSILPFtPPIVKRL |
Homo sapiens |
|
| pmid |
sentence |
| 15241418 |
We have mapped CDK4 and CDK2 phosphorylation sites to Thr 8, Thr 178 and Ser 212 in Smad3. Mutation of the CDK phosphorylation sites increases Smad3 transcriptional activity, |
|
| Publications: |
4 |
Organism: |
Homo Sapiens |
| Pathways: | Adipogenesis |
| + |
CKM complex | down-regulates quantity by destabilization
phosphorylation
|
SMAD3 |
0.426 |
| 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 |
| + |
CDK2 | down-regulates
phosphorylation
|
SMAD3 |
0.737 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-182967 |
Ser213 |
NLSPNPMsPAHNNLD |
Homo sapiens |
|
| pmid |
sentence |
| 19114991 |
In the nucleus cdk2/4-mediated phosphorylation of smad3 occurs mostly at thr8, thr179, and ser213. Cdk-dependent phosphorylation of smad3 inhibits its transcriptional activity |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-126732 |
Ser213 |
NLSPNPMsPAHNNLD |
Homo sapiens |
|
| pmid |
sentence |
| 15241418 |
We have mapped cdk4 and cdk2 phosphorylation sites to thr 8, thr 178 and ser 212 in smad3. taken together, these findings indicate that cdk phosphorylation of smad3 inhibits its transcriptional activity and antiproliferative function |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-126740 |
Thr8 |
MSSILPFtPPIVKRL |
Homo sapiens |
|
| pmid |
sentence |
| 15241418 |
We have mapped cdk4 and cdk2 phosphorylation sites to thr 8, thr 178 and ser 212 in smad3. taken together, these findings indicate that cdk phosphorylation of smad3 inhibits its transcriptional activity and antiproliferative function |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-182975 |
Thr8 |
MSSILPFtPPIVKRL |
Homo sapiens |
|
| pmid |
sentence |
| 19114991 |
In the nucleus cdk2/4-mediated phosphorylation of smad3 occurs mostly at thr8, thr179, and ser213. Cdk-dependent phosphorylation of smad3 inhibits its transcriptional activity |
|
| Publications: |
4 |
Organism: |
Homo Sapiens |
| Pathways: | Adipogenesis |
| + |
CDK4 | down-regulates activity
phosphorylation
|
SMAD3 |
0.752 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-232142 |
Ser213 |
NLSPNPMsPAHNNLD |
Homo sapiens |
|
| pmid |
sentence |
| 15241418 |
We have mapped CDK4 and CDK2 phosphorylation sites to Thr 8, Thr 178 and Ser 212 in Smad3. Mutation of the CDK phosphorylation sites increases Smad3 transcriptional activity |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-182822 |
Thr179 |
PQSNIPEtPPPGYLS |
Homo sapiens |
|
| pmid |
sentence |
| 19114991 |
In the nucleus cdk2/4-mediated phosphorylation of smad3 occurs mostly at thr8, thr179, and ser213. Cdk-dependent phosphorylation of smad3 inhibits its transcriptional activity |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-232146 |
Thr179 |
PQSNIPEtPPPGYLS |
Homo sapiens |
|
| pmid |
sentence |
| 15241418 |
We have mapped CDK4 and CDK2 phosphorylation sites to Thr 8, Thr 178 and Ser 212 in Smad3. Mutation of the CDK phosphorylation sites increases Smad3 transcriptional activity |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-232138 |
Thr8 |
MSSILPFtPPIVKRL |
Homo sapiens |
|
| pmid |
sentence |
| 15241418 |
We have mapped CDK4 and CDK2 phosphorylation sites to Thr 8, Thr 178 and Ser 212 in Smad3. Mutation of the CDK phosphorylation sites increases Smad3 transcriptional activity |
|
| Publications: |
4 |
Organism: |
Homo Sapiens |
| Pathways: | Pancreatic ductal adenocarcinoma (PDA) |
| + |
CSNK1G2 | down-regulates
phosphorylation
|
SMAD3 |
0.34 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-181069 |
Ser418 |
LTQMGSPsIRCSSVS |
Homo sapiens |
|
| pmid |
sentence |
| 18794808 |
Cki?2 Directly phosphorylates smad3 at ser418, leading to the increased ubiquitination and proteasomal degradation of activated smad3 following tgf-? Treatment. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
TGFBR1 | up-regulates activity
phosphorylation
|
SMAD3 |
0.808 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-235385 |
Ser423 |
SPSIRCSsVS |
Mus musculus |
Mv1Lu Cell, C2C12 Cell |
| pmid |
sentence |
| 19458083 |
A major event leading to smad3 activation is the tgf-beta-induced, tbetari-mediated phosphorylation at two c-terminal serine residues, ser-423 and ser-425, which triggers dissociation of smad3 from its receptors to form a complex with smad4 and accumulate in the nucleus |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-235380 |
Ser425 |
SIRCSSVs |
Mus musculus |
Mv1Lu Cell, C2C12 Cell |
| pmid |
sentence |
| 19458083 |
A major event leading to Smad3 activation is the TGF-beta-induced, TbetaRI-mediated phosphorylation at two C-terminal serine residues, Ser-423 and Ser-425, which triggers dissociation of Smad3 from its receptors to form a complex with Smad4 and accumulate in the nucleus |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-254361 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 19701891 |
The binding of TGF‐β1 to its receptor complex activates the intracellular kinase domain of TGF‐βRII, which leads to the phosphorylation and activation of Smad2, Smad3 and Smad4 as well as non‐Smad proteins (Smad‐independent pathway) |
|
| Publications: |
3 |
Organism: |
Mus Musculus, Homo Sapiens |
| Pathways: | Adipogenesis, COVID-19 Causal Network, Colorectal Carcinoma, Fibrosis, Cell cycle: G1/S phase transition, Hepatocellular Tumor, Multiple sclerosis, Pancreatic ductal adenocarcinoma (PDA), SARS-CoV FIBROSIS, TGF-beta Signaling, Thyroid Hormone Metabolism, TGFb in cancer |
| + |
GSK3B | down-regulates quantity by destabilization
phosphorylation
|
SMAD3 |
0.497 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-160318 |
Thr66 |
NVNTKCItIPRSLDG |
Homo sapiens |
|
| pmid |
sentence |
| 18172167 |
Mechanistically, axin facilitates gsk3-beta-mediated phosphorylation of smad3 at thr66, which triggers smad3 ubiquitination and degradation. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Adipogenesis, Cell cycle: G1/S phase transition, Cell cycle: G2/M phase transition |
| + |
ZFYVE9 | up-regulates activity
binding, relocalization
|
SMAD3 |
0.857 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-62874 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 9865696 |
We now identify SARA (for Smad anchor for receptor activation), a FYVE domain protein that interacts directly with Smad2 and Smad3. SARA functions to recruit Smad2 to the TGFbeta receptor by controlling the subcellular localization of Smad2 and by interacting with the TGFbeta receptor complex. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-232126 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 9865696 |
We now identify SARA (for Smad anchor for receptor activation), a FYVE domain protein that interacts directly with Smad2 and Smad3. SARA functions to recruit Smad2 to the TGFbeta receptor by controlling the subcellular localization of Smad2 and by interacting with the TGFbeta receptor complex. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-59145 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 20515759 |
Smad anchor for receptor activation (SARA) is known as Smad cofactor that interacts directly with Smad2/3 and functions to recruit Smad2/3 to the TGF-beta receptor. |
|
| Publications: |
3 |
Organism: |
Homo Sapiens |
| Pathways: | TGF-beta Signaling |
| + |
SMAD3 | up-regulates activity 
|
LEF1 |
0.524 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-229308 |
|
|
Homo sapiens |
Hep-G2 Cell |
| pmid |
sentence |
| 10890911 |
Coexpression of smad2 and smad4, smad3 alone, or smad3 and smad4 resulted in strong enhancement of lef1-dependent transcriptional activity |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Colorectal Carcinoma, Hepatocellular Tumor |
| + |
Gbeta | down-regulates
phosphorylation
|
SMAD3 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-270015 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 10197981 |
These results suggest that oncogenic ras, acting through mek1 and erk kinases, induces the phosphorylation of smad2 and smad3. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Tissue: |
Lung, Breast |
| + |
SMAD3 | up-regulates
|
FOXP3 |
0.533 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-254362 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 19701891 |
TGF-beta1-activated Smad3 plays a major role in the expression of Foxp3, since TGF-beta1-induced-Treg generation from Smad3(-/-) mice is markedly reduced and abolished by inactivating Smad2 |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-254363 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 15367216 |
The TCR, IL-2R, and TbetaR must all be stimulated to induce Foxp3 + Tregs. Failure to engage any one of these receptors prevents the generation of Foxp3 + Tregs |
|
| Publications: |
2 |
Organism: |
Homo Sapiens |
| + |
PIAS3 | up-regulates activity
binding
|
SMAD3 |
0.587 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-217725 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 14691252 |
We have further shown that PIAS3, Smad3, and p300 can form a ternary complex, which is significantly increased by TGF-_ treatment. Taken together, these results suggest that PIAS3 stimulates Smad transcriptional activity through formation of a complex with Smad proteins and p300/CBP. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
SMAD7 | down-regulates activity
binding
|
SMAD3 |
0.603 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-64085 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 9892110 |
Smad6 and smad7, can prevent tgfb signaling by interacting either with the receptor or with smad2 and smad3. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | COVID-19 Causal Network, Fibrosis, SARS-CoV FIBROSIS, TGF-beta Signaling |
| + |
SMAD3 | down-regulates quantity by repression 
transcriptional regulation
|
MYC |
0.678 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-123087 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 14993291 |
Smad3 is required for both tgf-beta-induced repression of c-myc and subsequent growth arrest in keratinocytes |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Colorectal Carcinoma, Cell cycle: G1/S phase transition, Cell cycle: G2/M phase transition, Hepatocellular Tumor |
| + |
SMAD3 | up-regulates quantity by expression
transcriptional regulation
|
CDKN2B |
0.552 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-245441 |
|
|
Homo sapiens |
T-lymphocyte |
| pmid |
sentence |
| 23032366 |
PD-1 inhibits T cell proliferation by upregulating p27 and p15 and suppressing Cdc25A. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Cell cycle: G1/S phase transition, Pancreatic ductal adenocarcinoma (PDA), TGF-beta Signaling, TGFb in cancer |
| + |
TUBB | down-regulates activity
binding
|
SMAD3 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-232113 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 17429065 |
Smad2/3 also binds to _-tubulin, which provides a negative regulatory mechanism controlling tgf-_ activity. the results showed that the mh2 domain of smad2 binds to _-tubulin with almost the same efficiency as the full-length (wild-type) smad2. Similar results were obtained for the smad3 binding to _-tubulin. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
SKI | down-regulates activity
binding
|
SMAD3 |
0.72 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-232123 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 10575014 |
Smad2/3 interacts with c-ski through its c-terminal mh2 domain in a tgf-beta-dependent mannerc-ski is incorporated in the smad dna binding complex, interferes with the interaction of smad3 with a transcriptional co-activator, p300, and in turn recruits hdac. c-ski is thus a transcriptional co-repressor that links smads to hdac in tgf-beta signaling. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-236077 |
|
|
Homo sapiens |
Melanoma Cell |
| pmid |
sentence |
| 12793438 |
The ski and snon protein family associate with and repress the activity of smad2, smad3, and smad4, three members of the tgf-fl signaling pathway |
|
| Publications: |
2 |
Organism: |
Homo Sapiens |
| Pathways: | TGF-beta Signaling |
| + |
SMAD3 | up-regulates
binding
|
NOTCH1 |
0.554 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-119374 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 14638857 |
Nicd and smad3 were shown to interact directly, both in vitro and in cells, in a ligand-dependent manner, and smad3 could be recruited to csl-binding sites on dna in the presence of csl and nicd |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
SMAD3 | form complex 
binding
|
SMAD3/PIAS3 |
0.587 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-255034 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 26194464 |
In summary, the TGF-b/IL-6/TCR-pERK-Smad2L (Ser255) axis is the positive regulator, whereas unphosphorylated Smad3C-PIAS3 complex is the negative regulator of STAT3-induced transcriptional processes for TH17 differentiation |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
SMAD3 | form complex
binding
|
SMAD3/JUN |
0.745 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-59873 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 9732876 |
These results show a ligand-dependent association of smad3 with c-jun |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
SMAD3 | form complex
binding
|
SMAD3/SMAD4 |
0.703 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-229557 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 9843571 |
TGF-beta treatment initiates a kinase cascade that results in the phosphorylation of Smad3, followed by its heteromerization with Smad4 and subsequent translocation into the nucleus. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | COVID-19 Causal Network, Fibrosis, Hepatocellular Tumor, Multiple sclerosis, Pancreatic ductal adenocarcinoma (PDA), SARS-CoV FIBROSIS, TGF-beta Signaling, TGFb in cancer |
| + |
MECOM | down-regulates
binding
|
SMAD3 |
0.499 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-59132 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 9665135 |
Evi-1 interacts with smad3, an intracellular mediator of tgf-beta signalling, thereby suppressing the transcriptional activity of smad3. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
P300/PCAF | up-regulates
binding
|
SMAD3 |
0.681 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-217233 |
|
|
Homo sapiens |
Breast Cancer Cell |
| pmid |
sentence |
| 15009097 |
Gcn5 functions like pcaf, in that it binds to tgf-beta-specific r-smads, and enhances transcriptional activity induced by tgf-beta. In addition, gcn5, but not pcaf, interacts with r-smads for bone morphogenetic protein (bmp) signalling pathways, and enhances bmp-induced transcriptional activity, suggesting that gcn5 and pcaf have distinct physiological functions in vivo. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
SMAD3 | down-regulates activity
binding
|
CEBPB |
0.587 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-250567 |
|
|
Mus musculus |
|
| pmid |
sentence |
| 12524424 |
Thus, repression of the activity of C/EBPs by Smad3/4 at C/EBP binding sites inhibited transcription from the PPAR2 and leptin promoters |
|
| Publications: |
1 |
Organism: |
Mus Musculus |
| Pathways: | Adipogenesis |
| + |
SMAD3 | down-regulates activity
binding
|
PAX6 |
0.405 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-251875 |
|
|
Homo sapiens |
Lens Epithelial Cell Line |
| pmid |
sentence |
| 17251190 |
The paired domain of Pax6 interacts with the MH1 domain of Smad3. Smad3 prevents Pax6 paired domain from binding DNA |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
SMAD6 | down-regulates activity
binding
|
SMAD3 |
0.486 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-64071 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 9892110 |
Smad6 and smad7, can prevent tgfb signaling by interacting either with the receptor or with smad2 and smad3 |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | TGF-beta Signaling |
| + |
MAPK3 | down-regulates
phosphorylation
|
SMAD3 |
0.614 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-66781 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 10197981 |
These results suggest that oncogenic ras, acting through mek1 and erk kinases, induces the phosphorylation of smad2 and smad3. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Tissue: |
Lung, Breast |
| + |
MYC | down-regulates activity
binding
|
SMAD3 |
0.678 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-114284 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 11804592 |
Through its direct interaction with smads, c-myc binds to the sp1-smad complex on the promoter of the p15(ink4b) gene, thereby inhibiting the tgf-beta-induced transcriptional activity of sp1 and smad/sp1-dependent transcription of the p15(ink4b) gene. These results suggest that oncogenic c-myc promotes cell growth and cancer development partly by inhibiting the growth inhibitory functions of smads. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Colorectal Carcinoma, Cell cycle: G1/S phase transition, Cell cycle: G2/M phase transition, Hepatocellular Tumor |
| + |
KAT2A | up-regulates
binding
|
SMAD3 |
0.513 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-123318 |
|
|
Homo sapiens |
Breast Cancer Cell |
| pmid |
sentence |
| 15009097 |
Gcn5 functions like pcaf, in that it binds to tgf-beta-specific r-smads, and enhances transcriptional activity induced by tgf-beta. In addition, gcn5, but not pcaf, interacts with r-smads for bone morphogenetic protein (bmp) signalling pathways, and enhances bmp-induced transcriptional activity, suggesting that gcn5 and pcaf have distinct physiological functions in vivo. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
AXIN1 | up-regulates
|
SMAD3 |
0.658 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-145848 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 16601693 |
Axin promotes smad3 phosphorylation;phosphorylated smad3 dissociates from the axin complex and then combines with smad4 to activate transcription in the nucleus. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
STUB1 | down-regulates quantity by destabilization
ubiquitination
|
SMAD3 |
0.558 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-278785 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 24613385 |
These results suggest that Smad3 could be easily ubiquitinated and degraded by CHIP when Hsp90 activity was inhibited.To demonstrate the role of Hsp70 and Hsp90 on the regulation of Smad3 by CHIP, we over-expressed Hsp70 and Hsp90 in mammalian cells. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
SMAD3 | down-regulates activity
binding
|
RUNX2 |
0.732 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-235902 |
|
|
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 11331591 |
Tgf-beta inhibited the expression of the cbfa1 and osteocalcin genes, whose expression is controlled by cbfa1 in osteoblast-like cell lines. This inhibition was mediated by smad3, which interacts physically with cbfa1 and represses its transcriptional activity at the cbfa1-binding ose2 promoter sequence. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | TGF-beta Signaling |
| + |
PJA1 | down-regulates activity
ubiquitination
|
SMAD3 |
0.398 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-278832 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 32127355 |
In summary, these results indicated that PJA1 promotes the ubiquitination of phosphorylated SMAD3, resulting in reduced activity of a TGF-\u03b2/SMAD3/\u03b22SP-dependent tumor-suppressing pathway in HCC cells ( xref ). |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
TUBB | down-regulates
binding
|
SMAD3 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-154319 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 17429065 |
Smad2/3 also binds to _-tubulin, which provides a negative regulatory mechanism controlling tgf-_ activity. the results showed that the mh2 domain of smad2 binds to _-tubulin with almost the same efficiency as the full-length (wild-type) smad2. Similar results were obtained for the smad3 binding to _-tubulin. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
SMAD3 | up-regulates
binding
|
NOTCH |
0.722 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-254325 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 14638857 |
Nicd and smad3 were shown to interact directly, both in vitro and in cells, in a ligand-dependent manner, and smad3 could be recruited to csl-binding sites on dna in the presence of csl and nicd |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
RANBP3 | down-regulates activity
relocalization
|
SMAD3 |
0.395 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-232107 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 20704570 |
Importantly, PPM1A facilitates the interaction of dephosphorylated Smad2/3 with RanBP3, a nuclear export factor [75]. As a result, PPM1A-mediated dephosphorylation of Smad2/3 promotes nuclear export of Smad2/3 and shuts off TGF-_-induced anti-proliferative and transcriptional responses |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-232116 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 19289081 |
RanBP3 directly recognizes dephosphorylated Smad2/3, which results from the activity of nuclear Smad phosphatases, and mediates nuclear export of Smad2/3 in a Ran-dependent manner. |
|
| Publications: |
2 |
Organism: |
Homo Sapiens |
| + |
SMAD3 | down-regulates activity
binding
|
PAX8 |
0.37 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-251992 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 14623893 |
DNA Binding Activity of Pax8 to the NIS Promoter Is Reduced by Smad3. TGF-β decreases Pax8 DNA binding to the NIS promoter and also found a physical interaction between Pax8 and Smad3. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Thyroid Hormone Metabolism |
| + |
SMAD3 | up-regulates activity
binding
|
SMAD4 |
0.703 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-235168 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 9843571 |
TGF-² treatment initiates a kinase cascade that results in the phosphorylation of Smad3, followed by its heteromerization with Smad4 and subsequent translocation into the nucleus. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Colorectal Carcinoma, Hepatocellular Tumor, Pancreatic ductal adenocarcinoma (PDA), TGF-beta Signaling, TGFb in cancer |
| + |
JNK | up-regulates activity
phosphorylation
|
SMAD3 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-236113 |
|
|
Homo sapiens |
Mv1Lu Cell |
| pmid |
sentence |
| 10601313 |
JNK-mediated phosphorylation of Smad3 outside the -SSXS motif enhances Smad3 nuclear translocation and potentiates transcriptional activation independent of Smad3 phosphorylation by T_RI. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | COVID-19 Causal Network, TGF-beta Signaling |
| + |
GREB1 | down-regulates activity
binding
|
SMAD3 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-265885 |
|
|
Homo sapiens |
Hep-G2 Cell |
| pmid |
sentence |
| 31462641 |
GREB1 is localized to the nucleus where it binds Smad2/3 in a competitive manner with p300 and inhibits TGFβ signaling, thereby promoting HepG2 HB cell proliferation. Binding of GREB1 to Smad2/3 inhibits transcription |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
SMAD3 | down-regulates activity
binding
|
CEBPA |
0.38 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-241924 |
|
|
Mus musculus |
|
| pmid |
sentence |
| 12524424 |
Thus, repression of the activity of C/EBPs by Smad3/4 at C/EBP binding sites inhibited transcription from the PPAR2 and leptin promoters |
|
| Publications: |
1 |
Organism: |
Mus Musculus |
| Pathways: | Adipogenesis |
| + |
SMAD3 | down-regulates quantity by repression
transcriptional regulation
|
CDC25A |
0.557 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-245445 |
|
|
Homo sapiens |
T-lymphocyte |
| pmid |
sentence |
| 22740686 |
PD-1 also inhibited phosphorylation of the transcription factor Smad3, which increased its activity. These events induced additional inhibitory checkpoints in the cell cycle by increasing the abundance of the G(1) phase inhibitor p15(INK4) and repressing the Cdk-activating phosphatase Cdc25A |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Cell cycle: G1/S phase transition, Cell cycle: G2/M phase transition |
| + |
WWTR1 | up-regulates activity
binding
|
SMAD3 |
0.543 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-232098 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 21084559 |
Taz has been shown to interact with smad2 and smad3 through its coiled-coil region, and to be important in maintaining the nuclear localization of smad2 and smad3 as well as the expression of their target genes in response to tgf-b signaling and, thus, in the maintenance of human esc self-renewal. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Thyroid Hormone Metabolism |
| + |
SMAD3 | up-regulates activity
binding
|
SMAD3 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-217227 |
|
|
Chlorocebus aethiops |
|
| pmid |
sentence |
| 9670020 |
Smad2 and Smad3 form homo-oligomers upon phosphorylation by the constitutively active TGF-beta type I receptor, and this oligomerization does not require Smad4 |
|
| Publications: |
1 |
Organism: |
Chlorocebus Aethiops |
| Pathways: | Adipogenesis, COVID-19 Causal Network, Colorectal Carcinoma, Fibrosis, Cell cycle: G1/S phase transition, Cell cycle: G2/M phase transition, Hepatocellular Tumor, Multiple sclerosis, Pancreatic ductal adenocarcinoma (PDA), SAPK/JNK Signaling, SARS-CoV FIBROSIS, TGF-beta Signaling, Thyroid Hormone Metabolism, TGFb in cancer |
| + |
RANBP3 | down-regulates
relocalization
|
SMAD3 |
0.395 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-184608 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 19289081 |
Ranbp3 directly recognizes dephosphorylated smad2/3, which results from the activity of nuclear smad phosphatases, and mediates nuclear export of smad2/3 in a ran-dependent manner |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
NUP214 | up-regulates
binding
|
SMAD3 |
0.538 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-117644 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 12917407 |
We demonstrate that smad3 and smad4 are capable of interaction with the nucleoporin can/nup214, and this interaction is required for nuclear import. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
PPP2CA | down-regulates
dephosphorylation
|
SMAD3 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-161919 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 19951945 |
Accordingly, smad3-associated pp2a activity was found under hypoxic conditions. Hypoxia attenuated the nuclear accumulation of tgf-beta-induced smad3 but did not affect smad2. Moreover, the influence of tgf-beta on a set of smad3-activated genes was attenuated by hypoxia, and this was reversed by chemical pp2a inhibition. Our data demonstrate the existence of a smad3-specific phosphatase and identify a novel role for pp2a. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-167480 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 20704570 |
Accordingly, smad3-associated pp2a activity was found under hypoxic conditions. Hypoxia attenuated the nuclear accumulation of tgf-beta-induced smad3 but did not affect smad2. Moreover, the influence of tgf-beta on a set of smad3-activated genes was attenuated by hypoxia, and this was reversed by chemical pp2a inhibition. Our data demonstrate the existence of a smad3-specific phosphatase and identify a novel role for pp2a. |
|
| Publications: |
2 |
Organism: |
Homo Sapiens |
| Pathways: | COVID-19 Causal Network |
| + |
JUN | down-regulates activity
binding
|
SMAD3 |
0.745 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-256284 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 10871633 |
These results indicate that interaction between Smad3 and c-Jun may repress Smad3 transcriptional activity. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | SAPK/JNK Signaling, TGF-beta Signaling |
| + |
SMAD3 | down-regulates activity
binding
|
NKX2-1 |
0.293 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-254169 |
|
|
Homo sapiens |
Lung Epithelial Cell |
| pmid |
sentence |
| 18003659 |
TGF-beta represses transcription of pulmonary surfactant protein-B gene in lung epithelial cells. Repression is mediated by SMAD3 through interactions with NKX2.1 and FOXA1, two key transcription factors that are positive regulators of SpB transcription. In this study, we found that SMAD3 interacts through its MAD domains, MH1 and MH2 with NKX2.1 and FOXA1 proteins. The sites of interaction on NKX2.1 are located within the NH2 and COOH domains, known to be involved in transactivation function. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Thyroid Hormone Metabolism |
| + |
EID2 | down-regulates
binding
|
SMAD3 |
0.402 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-119171 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 14612439 |
In this study, we examined the effect of eid-2 on smad-mediated tgf- signaling. Here, we show that eid-2 inhibits tgf- /smad transcriptional responses. Eid-2 interacts constitutively with smad proteins, and most strongly with smad3. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
PIAS4 | down-regulates
binding
|
SMAD3 |
0.639 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-104538 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 12904571 |
Piasy binds most strongly with smad3 and also associates with other receptor-regulated smads and smad4. smad3, smad4, and piasy can form a ternary complex. Piasy does not inhibit smad complex binding to dna, but it represses smad transcriptional activity. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
BTRC | down-regulates
ubiquitination
|
SMAD3 |
0.394 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-108237 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 11359933 |
An e3 ubiquitin ligase complex roc1-scffbw1a consisting of roc1, skp1, cullin1, and fbw1a (also termed trcp1) induces ubiquitination of smad3. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
ACVR2B | up-regulates activity
phosphorylation
|
SMAD3 |
0.682 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-254985 |
|
|
Mus musculus |
|
| pmid |
sentence |
| 21966641 |
It has been suggested that binding of myostatin to the ActRIIB results in the phosphorylation of two serine residues of Smad2 or Smad3 at COOH domains |
|
| Publications: |
1 |
Organism: |
Mus Musculus |
| Pathways: | Multiple sclerosis |
| + |
TRIM33 | up-regulates activity
binding
|
SMAD3 |
0.574 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-236060 |
|
|
Homo sapiens |
Hematopoietic Cell, Mesenchymal Cell, Epithelial Cell |
| pmid |
sentence |
| 16751102 |
The ubiquitious nuclear protein transcriptional intermediary factor 1gamma (tif1gamma) selectively binds receptor-phosphorylated smad2/3 in competition with smad4. Rapid and robust binding of tif1gamma to smad2/3 occurs in hematopoietic, mesenchymal, and epithelial cell types in response to tgfbeta. Tif1gamma mediates the differentiation response while smad4 mediates the antiproliferative response with smad2/3 participating in both responses. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
WWTR1 | up-regulates
binding
|
SMAD3 |
0.543 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-169841 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 21084559 |
Taz has been shown to interact with smad2 and smad3 through its coiled-coil region, and to be important in maintaining the nuclear localization of smad2 and smad3 as well as the expression of their target genes in response to tgf-b signaling and, thus, in the maintenance of human esc self-renewal. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Thyroid Hormone Metabolism |
| + |
MTMR4 | down-regulates
dephosphorylation
|
SMAD3 |
0.503 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-163034 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 20061380 |
Here we demonstrate that myotubularin-related protein 4 |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
KPNB1 | up-regulates
relocalization
|
SMAD3 |
0.51 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-78191 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 10846168 |
Here we show that the isolated smad 3 mh1 domain displays significant specific binding to importin beta. we propose that activation of all of the pathway-specific smad proteins (smads 1, 2, 3, 5, 8, and 9) exposes the conserved nls motif, which then binds directly to importin beta and triggers nuclear translocation. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
SCF-betaTRCP | down-regulates quantity by destabilization
polyubiquitination
|
SMAD3 |
0.437 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-272944 |
|
|
Chlorocebus aethiops |
COS-7 Cell |
| pmid |
sentence |
| 11359933 |
Smad3 interacts with a RING finger protein, ROC1, through its C-terminal MH2 domain in a ligand-dependent manner. An E3 ubiquitin ligase complex ROC1-SCF(Fbw1a) consisting of ROC1, Skp1, Cullin1, and Fbw1a (also termed betaTrCP1) induces ubiquitination of Smad3. |
|
| Publications: |
1 |
Organism: |
Chlorocebus Aethiops |
| + |
YAP/TAZ | up-regulates activity
binding
|
SMAD3 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-277662 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 25287865 |
YAP and TAZ were repeatedly isolated as binding proteins for Smads, key transducer of the TGF- and BMP signaling pathways (2, 207, 208). Cytoplasmic YAP/TAZ participate in Smad2/3 cytoplasmic retention, even overruling the ef- fects of high levels of TGF- ligands |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
PPM1A | down-regulates activity
dephosphorylation
|
SMAD3 |
0.613 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-232110 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 16751101 |
Ppm1a dephosphorylates and promotes nuclear export of tgfbeta-activated smad2/3; these results suggest that phospho-smad2 is a direct substrate of mg2+-dependent ppm1a. in conclusion, ppm1a is a bona fide phosphatase that directly dephosphorylates the critical sxs motif of r-smads. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
SMAD3 | down-regulates activity
binding
|
FOXA1 |
0.335 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-254168 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 18003659 |
TGF-beta represses transcription of pulmonary surfactant protein-B gene in lung epithelial cells. Repression is mediated by SMAD3 through interactions with NKX2.1 and FOXA1, two key transcription factors that are positive regulators of SpB transcription. In this study, we found that SMAD3 interacts through its MAD domains, MH1 and MH2 with NKX2.1 and FOXA1 proteins. The sites of interaction on NKX2.1 are located within the NH2 and COOH domains, known to be involved in transactivation function. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
PML | up-regulates activity
binding
|
SMAD3 |
0.535 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-232090 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 15356634 |
Cytoplasmic pml physically interacts with smad2/3 and sara (smad anchor for receptor activation) and is required for association of smad2/3 with sara and for the accumulation of sara and tgf-beta receptor in the early endosome. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
WWTR1 | up-regulates quantity by expression
transcriptional regulation
|
SMAD3 |
0.543 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-255607 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 22470139 |
Efficient knockdown of WWTR1, demonstrated by quantitative real-time PCR, led to upregulation of ASNS and downregulation of SMAD3, LTBR, BAX and BAK1 in WWTR1 knockdown cells, suggesting that these genes may be involved in the repression of cell proliferation. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Thyroid Hormone Metabolism |
| + |
AKT | down-regulates
binding
|
SMAD3 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-252345 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 15048128 |
Pkb inhibits smad3 by preventing its phosphorylation, binding to smad4 and nuclear translocation. [...] Regulation of smad3 by pkb occurs through a kinase-activity-independent mechanism, resulting in a decrease in smad3-mediated transcription and protection of cells against tgf-beta-induced apoptosis. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | COVID-19 Causal Network, Cell cycle: G1/S phase transition, Cell cycle: G2/M phase transition, Hepatocellular Tumor, Pancreatic ductal adenocarcinoma (PDA), Thyroid Hormone Metabolism |
| + |
SMAD3 | up-regulates
|
Fibrosis |
0.7 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-260432 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 30017632 |
Transforming growth factor-β1 (TGF-β1) is considered as a crucial mediator in tissue fibrosis and causes tissue scarring largely by activating its downstream small mother against decapentaplegic (Smad) signaling. Different TGF-β signalings play different roles in fibrogenesis. TGF-β1 directly activates Smad signaling which triggers pro-fibrotic gene overexpression. Excessive studies have demonstrated that dysregulation of TGF-β1/Smad pathway was an important pathogenic mechanism in tissue fibrosis. Smad2 and Smad3 are the two major downstream regulator that promote TGF-β1-mediated tissue fibrosis, while Smad7 serves as a negative feedback regulator of TGF-β1/Smad pathway thereby protects against TGF-β1-mediated fibrosis. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | COVID-19 Causal Network, Fibrosis, SARS-CoV FIBROSIS, TGF-beta Signaling |
| + |
N | up-regulates activity
binding
|
SMAD3 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-260434 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 18055455 |
In this study, we demonstrate that SARS-associated coronavirus (SARS-CoV) nucleocapsid (N) protein potentiates transforming growth factor-beta (TGF-beta)-induced expression of plasminogen activator inhibitor-1 but attenuates Smad3/Smad4-mediated apoptosis of human peripheral lung epithelial HPL1 cells. The promoting effect of N protein on the transcriptional responses of TGF-beta is Smad3-specific. N protein associates with Smad3 and promotes Smad3-p300 complex formation while it interferes with the complex formation between Smad3 and Smad4. These findings provide evidence of a novel mechanism whereby N protein modulates TGF-beta signaling to block apoptosis of SARS-CoV-infected host cells and meanwhile promote tissue fibrosis. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | COVID-19 Causal Network, SARS-CoV FIBROSIS |
| + |
PIAS3 | up-regulates
binding
|
SMAD3 |
0.587 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-120359 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 14691252 |
Taken together, our studies indicate that on tgf-beta treatment, pias3 can form a complex with smads and p300/cbp and activate smad transcriptional activity. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
SMAD3 | down-regulates activity
binding
|
MYOD1 |
0.724 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-252071 |
|
|
Mus musculus |
C2C12 Cell |
| pmid |
sentence |
| 11711431 |
We show that the TGF-beta intracellular effector Smad3, but not Smad2, mediates the inhibition of myogenic differentiation in MyoD-expressing C3H10T1/2 cells and C2C12 myoblasts by repressing the activity of the MyoD family of transcriptional factors. |
|
| Publications: |
1 |
Organism: |
Mus Musculus |
| + |
PPM1A | down-regulates
dephosphorylation
|
SMAD3 |
0.613 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-146922 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 16751101 |
Ppm1a dephosphorylates and promotes nuclear export of tgfbeta-activated smad2/3. in conclusion, ppm1a is a bona fide phosphatase that directly dephosphorylates the critical sxs motif of r-smads. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
SMAD3 | down-regulates quantity by repression
transcriptional regulation
|
MYC |
0.678 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-251494 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 11689553 |
Down-regulation of c-Myc is a critical event for growth inhibition induced by transforming growth factor-β (TGF-β) and is frequently impaired in cancer cells. We determined a Smad-responsive element in the c-mycpromoter. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Colorectal Carcinoma, Cell cycle: G1/S phase transition, Cell cycle: G2/M phase transition, Hepatocellular Tumor |
| + |
NEDD4L | down-regulates activity
ubiquitination
|
SMAD3 |
0.799 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-232104 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 19917253 |
Through its ww domain, nedd4l specifically recognizes a tgf-beta-induced phosphothr-protyr motif in the linker region, resulting in smad2/3 polyubiquitination and degradation |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
KAT2B | up-regulates
binding
|
SMAD3 |
0.668 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-83607 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 11058129 |
P/caf was found to interact directly with smad3 in vitro. Moreover, smad2 and smad3 interacted with p/caf upon tgf-beta type i receptor activation in cultured mammalian cells. these results demonstrate the co-activator function of p/caf for smad2 and smad3. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
SMAD7 | down-regulates quantity
transcriptional regulation
|
SMAD3 |
0.603 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-260437 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 30017632 |
The downstream molecules including mad2, smad3, smad4 and smad7 are involved in TGF-β1-induced EMT,while Smad7 blocks the smad3 expression |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | COVID-19 Causal Network, Fibrosis, SARS-CoV FIBROSIS, TGF-beta Signaling |
| + |
FBXW11 | up-regulates
ubiquitination
|
SMAD3 |
0.263 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-108240 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 11359933 |
Here, we show that smad3 activated by tgf-beta is degraded by the ubiquitin-proteasome pathway. Smad3 interacts with a ring finger protein, roc1, through its c-terminal mh2 domain in a ligand-dependent manner. An e3 ubiquitin ligase complex roc1-scf(fbw1a) consisting of roc1, skp1, cullin1, and fbw1a (also termed betatrcp1) induces ubiquitination of smad3. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
TGFb | up-regulates
|
SMAD3 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-97123 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 12524424 |
Because tgf-beta inhibits adipogenesis by signaling through smad3, we examined physical and functional interactions of smad3 and smad4 with c/ebpbeta, c/ebpdelta, and ppargamma2. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | COVID-19 Causal Network, Fibrosis, Hepatocellular Tumor, Multiple sclerosis, Pancreatic ductal adenocarcinoma (PDA), SARS-CoV FIBROSIS, TGFb in cancer |
| + |
AKT1 | down-regulates
binding
|
SMAD3 |
0.635 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-123606 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 15048128 |
Pkb inhibits smad3 by preventing its phosphorylation, binding to smad4 and nuclear translocation. [...] Regulation of smad3 by pkb occurs through a kinase-activity-independent mechanism, resulting in a decrease in smad3-mediated transcription and protection of cells against tgf-beta-induced apoptosis. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Adipogenesis |
| + |
RNF111 | down-regulates
ubiquitination
|
SMAD3 |
0.645 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-236876 |
|
|
Mus musculus |
C2C12 Cell, Myoblast |
| pmid |
sentence |
| 17341133 |
Arkadia represses the expression of myoblast differentiation markers through degradation of ski and the ski-bound smad complex in c2c12 myoblastsarkadia bound smad2/3 via ski to induce the ubiquitination of smad2/3. These results suggest that arkadia targets ski-bound, inactive phospho-smad2/3 to regulate positively myostatin/tgf-beta signaling. |
|
| Publications: |
1 |
Organism: |
Mus Musculus |
| + |
CSMD1 | up-regulates activity
binding
|
SMAD3 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-265151 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 22538441 |
CSMD1 co-immunoprecipitated with SMAD3, confirming our results that CSMD1 interacts with Smad3 in A375 cells. CSMD1 interacts with Smad3 and induces phosphorylation (p-Smad3). Phosphorylated Smad3 promotes Smad2 phosphorylation and Smad2/3/4 complex formation. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
TRIM33 | up-regulates
binding
|
SMAD3 |
0.574 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-146986 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 16751102 |
The ubiquitious nuclear protein transcriptional intermediary factor 1gamma (tif1gamma) selectively binds receptor-phosphorylated smad2/3 in competition with smad4. Rapid and robust binding of tif1gamma to smad2/3 occurs in hematopoietic, mesenchymal, and epithelial cell types in response to tgfbeta. In human hematopoietic stem/progenitor cells, where tgfbeta inhibits proliferation and stimulates erythroid differentiation, tif1gamma mediates the differentiation response while smad4 mediates the antiproliferative response with smad2/3 participating in both responses. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
PML | up-regulates
binding
|
SMAD3 |
0.535 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-128741 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 15356634 |
Cytoplasmic pml physically interacts with smad2/3 and sara (smad anchor for receptor activation) and is required for association of smad2/3 with sara and for the accumulation of sara and tgf-beta receptor in the early endosome. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
BCAR1 | down-regulates
binding
|
SMAD3 |
0.28 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-161265 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 18321991 |
In this study, we show that, after tyrosine phosphorylation of p130cas mediated by integrin signaling, the phosphorylated p130cas is able to interact with phosphorylated smad3 and in turn prevent transcriptional activation by smad3 |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
ERK1/2 | down-regulates
phosphorylation
|
SMAD3 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-270142 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 10197981 |
These results suggest that oncogenic ras, acting through mek1 and erk kinases, induces the phosphorylation of smad2 and smad3. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Tissue: |
Lung, Breast |
| Pathways: | Adipogenesis, COVID-19 Causal Network, Colorectal Carcinoma, Hepatocellular Tumor, Pancreatic ductal adenocarcinoma (PDA) |
| + |
NEDD4L | down-regulates
ubiquitination
|
SMAD3 |
0.799 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-161713 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 19917253 |
Through its ww domain, nedd4l specifically recognizes a tgf-beta-induced phosphothr-protyr motif in the linker region, resulting in smad2/3 polyubiquitination and degradation |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
SMAD3 | down-regulates quantity by repression
transcriptional regulation
|
BCL2 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-256294 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 16766264 |
This protection is conferred by Smad3’s ability to promote apoptosis by repressing Bcl-2 transcription in vivo through a GC-rich element in the Bcl-2 promoter. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | COVID-19 Causal Network, Colorectal Carcinoma |
| + |
UCHL5 | up-regulates activity
deubiquitination
|
SMAD3 |
0.402 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-232101 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 16027725 |
Here, we report a novel interaction between smads and ubiquitin c-terminal hydrolase uch37, a deubiquitinating enzyme that could potentially reverse smurf-mediated ubiquitination. In gst pull down experiments, uch37 bound weakly to smad2 and smad3, and bound very strongly to smad7 in a region that is distinct from the -py- motif in smad7 that interacts with smurf ubiquitin ligases |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
RNF111 | down-regulates activity
ubiquitination
|
SMAD3 |
0.645 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-235388 |
|
|
Mus musculus |
|
| pmid |
sentence |
| 17341133 |
Arkadia represses the expression of myoblast differentiation markers through degradation of ski and the ski-bound smad complex in c2c12 myoblasts. Arkadia bound smad2/3 via ski to induce the ubiquitination of smad2/3. These results suggest that arkadia targets ski-bound, inactive phospho-smad2/3 to regulate positively myostatin/tgf-beta signaling. |
|
| Publications: |
1 |
Organism: |
Mus Musculus |
| + |
ACVR1B | up-regulates activity
phosphorylation
|
SMAD3 |
0.735 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-235160 |
|
|
Mus musculus |
|
| pmid |
sentence |
| 14517293 |
ActRIIB, and then partners with a type I receptor, either activin receptor-like kinase 4 (ALK4 or ActRIB) or ALK5 (T²RI), to induce phosphorylation of Smad2/Smad3 and activate a TGF-²-like signaling pathway |
|
| Publications: |
1 |
Organism: |
Mus Musculus |
| Pathways: | Multiple sclerosis |
3.0
SMAD3
- 
- 