| + |
P300/PCAF | up-regulates activity 
acetylation
|
SMAD2 |
0.625 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-217607 |
Lys19 |
VKRLLGWkKSAGGSG |
Homo sapiens |
|
| pmid |
sentence |
| 17074756 |
Acetylation of the short isoform of Smad2 improves its DNA binding activity in vitro and enhances its association with target promoters in vivo, thereby augmenting its transcriptional activity. Smad2(FL) and Smad2(_E3) were also acetylated by P/CAF in vivo and the acetylation of both proteins was lost following mutation of Lys19 (Fig. 2D), suggesting that Lys19 in Smad2 is also targeted by P/CAF. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
KAT2B | up-regulates
acetylation
|
SMAD2 |
0.566 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-150273 |
Lys19 |
VKRLLGWkKSAGGSG |
Homo sapiens |
|
| pmid |
sentence |
| 17074756 |
We demonstrate that both smad2 and smad3 are acetylated by the coactivators p300 and cbp in a tgfbeta-dependent manner. Smad2 is also acetylated by p/caf. The acetylation of smad2 was significantly higher than that of smad3. Lys(19) in the mh1 domain was identified as the major acetylated residue in both the long and short isoform of smad2.....acetylation of the short isoform of smad2 improves its dna binding activity in vitro and enhances its association with target promoters in vivo, thereby augmenting its transcriptional activity |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
CBP/p300 | up-regulates activity
acetylation
|
SMAD2 |
0.654 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-235899 |
Lys19 |
VKRLLGWkKSAGGSG |
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 tgfbeta-dependent manner. To identify the specific lysine residue acetylated by p300, lys19, and lys20 in smad2(fl) were mutated individually and subjected to p300-mediated acetylation following expression in 293t cells. Mutation of lys19 blocked the p300-mediated acetylation of smad2(fl), whereas mutation of lys20 had no effect (fig. 2b), suggesting that lys19 is the preferred site for p300-mediated acetylation of smad2(fl). |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | TGF-beta Signaling |
| + |
CAMK2A | down-regulates 
phosphorylation
|
SMAD2 |
0.533 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-82966 |
Ser110 |
SFSEQTRsLDGRLQV |
Homo sapiens |
|
| pmid |
sentence |
| 11027280 |
Smad2 is a target substrate for cam kinase ii in vitro at serine-110, -240, and -260. furthermore, cam kinase ii blocked nuclear accumulation of a smad2 and induced smad2-smad4 hetero-oligomerization independently of tgfbeta receptor activation, while preventing tgf-beta-dependent smad2-smad3 interactions. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-82970 |
Ser240 |
SDQQLNQsMDTGSPA |
Homo sapiens |
|
| pmid |
sentence |
| 11027280 |
Smad2 is a target substrate for cam kinase ii in vitro at serine-110, -240, and -260. furthermore, cam kinase ii blocked nuclear accumulation of a smad2 and induced smad2-smad4 hetero-oligomerization independently of tgfbeta receptor activation, while preventing tgfbeta-dependent smad2-smad3 interactions. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-82974 |
Ser260 |
TLSPVNHsLDLQPVT |
Homo sapiens |
|
| pmid |
sentence |
| 11027280 |
Smad2 is a target substrate for cam kinase ii in vitro at serine-110, -240, and -260. furthermore, cam kinase ii blocked nuclear accumulation of a smad2 and induced smad2-smad4 hetero-oligomerization independently of tgfbeta receptor activation, while preventing tgfbeta-dependent smad2-smad3 interactions. |
|
| Publications: |
3 |
Organism: |
Homo Sapiens |
| + |
MAPK3 | up-regulates
phosphorylation
|
SMAD2 |
0.749 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-91730 |
Ser245 |
NQSMDTGsPAELSPT |
Homo sapiens |
|
| pmid |
sentence |
| 12193595 |
These results suggest that oncogenic ras, acting through mek1 and erk kinases, induces the phosphorylation of smad2 and smad3 .we show that phosphorylation of smad2, a mediator of the activin/transforming growth factor-beta signal, by activated extracellular signal-regulated kinase 1 (erk1) increases the amount of smad2 protein and leads to enhanced transcriptional activity |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-66759 |
Ser245 |
NQSMDTGsPAELSPT |
Homo sapiens |
|
| pmid |
sentence |
| 10197981 |
These results suggest that oncogenic ras, acting through mek1 and erk kinases, induces the phosphorylation of smad2 and smad3 .we show that phosphorylation of smad2, a mediator of the activin/transforming growth factor-beta signal, by activated extracellular signal-regulated kinase 1 (erk1) increases the amount of smad2 protein and leads to enhanced transcriptional activity |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-182988 |
Ser245 |
NQSMDTGsPAELSPT |
Homo sapiens |
|
| pmid |
sentence |
| 19115199 |
These results suggest that oncogenic ras, acting through mek1 and erk kinases, induces the phosphorylation of smad2 and smad3 .we show that phosphorylation of smad2, a mediator of the activin/transforming growth factor-beta signal, by activated extracellular signal-regulated kinase 1 (erk1) increases the amount of smad2 protein and leads to enhanced transcriptional activity |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-182992 |
Ser250 |
TGSPAELsPTTLSPV |
Homo sapiens |
|
| pmid |
sentence |
| 19115199 |
These results suggest that oncogenic ras, acting through mek1 and erk kinases, induces the phosphorylation of smad2 and smad3 .we show that phosphorylation of smad2, a mediator of the activin/transforming growth factor-beta signal, by activated extracellular signal-regulated kinase 1 (erk1) increases the amount of smad2 protein and leads to enhanced transcriptional activity |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-91734 |
Ser250 |
TGSPAELsPTTLSPV |
Homo sapiens |
|
| pmid |
sentence |
| 12193595 |
These results suggest that oncogenic ras, acting through mek1 and erk kinases, induces the phosphorylation of smad2 and smad3 .we show that phosphorylation of smad2, a mediator of the activin/transforming growth factor-beta signal, by activated extracellular signal-regulated kinase 1 (erk1) increases the amount of smad2 protein and leads to enhanced transcriptional activity |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-66763 |
Ser250 |
TGSPAELsPTTLSPV |
Homo sapiens |
|
| pmid |
sentence |
| 10197981 |
These results suggest that oncogenic ras, acting through mek1 and erk kinases, induces the phosphorylation of smad2 and smad3 .we show that phosphorylation of smad2, a mediator of the activin/transforming growth factor-beta signal, by activated extracellular signal-regulated kinase 1 (erk1) increases the amount of smad2 protein and leads to enhanced transcriptional activity |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-182996 |
Ser255 |
ELSPTTLsPVNHSLD |
Homo sapiens |
|
| pmid |
sentence |
| 19115199 |
These results suggest that oncogenic ras, acting through mek1 and erk kinases, induces the phosphorylation of smad2 and smad3 .we show that phosphorylation of smad2, a mediator of the activin/transforming growth factor-beta signal, by activated extracellular signal-regulated kinase 1 (erk1) increases the amount of smad2 protein and leads to enhanced transcriptional activity |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-66767 |
Ser255 |
ELSPTTLsPVNHSLD |
Homo sapiens |
|
| pmid |
sentence |
| 10197981 |
These results suggest that oncogenic ras, acting through mek1 and erk kinases, induces the phosphorylation of smad2 and smad3 .we show that phosphorylation of smad2, a mediator of the activin/transforming growth factor-beta signal, by activated extracellular signal-regulated kinase 1 (erk1) increases the amount of smad2 protein and leads to enhanced transcriptional activity |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-91738 |
Ser255 |
ELSPTTLsPVNHSLD |
Homo sapiens |
|
| pmid |
sentence |
| 12193595 |
These results suggest that oncogenic ras, acting through mek1 and erk kinases, induces the phosphorylation of smad2 and smad3 .we show that phosphorylation of smad2, a mediator of the activin/transforming growth factor-beta signal, by activated extracellular signal-regulated kinase 1 (erk1) increases the amount of smad2 protein and leads to enhanced transcriptional activity |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-91742 |
Thr220 |
QSNYIPEtPPPGYIS |
Homo sapiens |
|
| pmid |
sentence |
| 12193595 |
These results suggest that oncogenic ras, acting through mek1 and erk kinases, induces the phosphorylation of smad2 and smad3 .we show that phosphorylation of smad2, a mediator of the activin/transforming growth factor-beta signal, by activated extracellular signal-regulated kinase 1 (erk1) increases the amount of smad2 protein and leads to enhanced transcriptional activity |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-183000 |
Thr220 |
QSNYIPEtPPPGYIS |
Homo sapiens |
|
| pmid |
sentence |
| 19115199 |
These results suggest that oncogenic ras, acting through mek1 and erk kinases, induces the phosphorylation of smad2 and smad3 .we show that phosphorylation of smad2, a mediator of the activin/transforming growth factor-beta signal, by activated extracellular signal-regulated kinase 1 (erk1) increases the amount of smad2 protein and leads to enhanced transcriptional activity |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-66771 |
Thr220 |
QSNYIPEtPPPGYIS |
Homo sapiens |
|
| pmid |
sentence |
| 10197981 |
These results suggest that oncogenic ras, acting through mek1 and erk kinases, induces the phosphorylation of smad2 and smad3 .we show that phosphorylation of smad2, a mediator of the activin/transforming growth factor-beta signal, by activated extracellular signal-regulated kinase 1 (erk1) increases the amount of smad2 protein and leads to enhanced transcriptional activity |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-66775 |
Thr8 |
MSSILPFtPPVVKRL |
Homo sapiens |
|
| pmid |
sentence |
| 10197981 |
These results suggest that oncogenic ras, acting through mek1 and erk kinases, induces the phosphorylation of smad2 and smad3 .we show that phosphorylation of smad2, a mediator of the activin/transforming growth factor-beta signal, by activated extracellular signal-regulated kinase 1 (erk1) increases the amount of smad2 protein and leads to enhanced transcriptional activity |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-183004 |
Thr8 |
MSSILPFtPPVVKRL |
Homo sapiens |
|
| pmid |
sentence |
| 19115199 |
These results suggest that oncogenic ras, acting through mek1 and erk kinases, induces the phosphorylation of smad2 and smad3 .we show that phosphorylation of smad2, a mediator of the activin/transforming growth factor-beta signal, by activated extracellular signal-regulated kinase 1 (erk1) increases the amount of smad2 protein and leads to enhanced transcriptional activity |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-91746 |
Thr8 |
MSSILPFtPPVVKRL |
Homo sapiens |
|
| pmid |
sentence |
| 12193595 |
These results suggest that oncogenic ras, acting through mek1 and erk kinases, induces the phosphorylation of smad2 and smad3 .we show that phosphorylation of smad2, a mediator of the activin/transforming growth factor-beta signal, by activated extracellular signal-regulated kinase 1 (erk1) increases the amount of smad2 protein and leads to enhanced transcriptional activity |
|
| Publications: |
15 |
Organism: |
Homo Sapiens |
| Tissue: |
Lung, Lung, Breast |
| + |
CTDSPL | down-regulates activity
dephosphorylation
|
SMAD2 |
0.483 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-248310 |
Ser245 |
NQSMDTGsPAELSPT |
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-248311 |
Ser250 |
TGSPAELsPTTLSPV |
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-248312 |
Ser255 |
ELSPTTLsPVNHSLD |
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-248309 |
Thr220 |
QSNYIPEtPPPGYIS |
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: |
4 |
Organism: |
Homo Sapiens |
| + |
MAPK1 | up-regulates
phosphorylation
|
SMAD2 |
0.72 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-91714 |
Ser245 |
NQSMDTGsPAELSPT |
Homo sapiens |
|
| pmid |
sentence |
| 12193595 |
We show that phosphorylation of smad2, a mediator of the activin/transforming growth factor-beta signal, by activated extracellular signal-regulated kinase 1 (erk1) increases the amount of smad2 protein and leads to enhanced transcriptional activity. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-91718 |
Ser250 |
TGSPAELsPTTLSPV |
Homo sapiens |
|
| pmid |
sentence |
| 12193595 |
Phosphorylation of smad2 by erk increases its transcriptional activity /thr220 and ser245, ser250, and ser255 were possible phosphorylation sites. The phosphorylation of peak a peptide by erk1 is consistent with that prediction. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-91722 |
Ser255 |
ELSPTTLsPVNHSLD |
Homo sapiens |
|
| pmid |
sentence |
| 12193595 |
Phosphorylation of smad2 by erk increases its transcriptional activity /thr220 and ser245, ser250, and ser255 were possible phosphorylation sites. The phosphorylation of peak a peptide by erk1 is consistent with that prediction. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-91726 |
Thr220 |
QSNYIPEtPPPGYIS |
Homo sapiens |
|
| pmid |
sentence |
| 12193595 |
Phosphorylation of smad2 by erk increases its transcriptional activity /thr220 and ser245, ser250, and ser255 were possible phosphorylation sites. The phosphorylation of peak a peptide by erk1 is consistent with that prediction. |
|
| Publications: |
4 |
Organism: |
Homo Sapiens |
| Tissue: |
Lung |
| + |
ERK1/2 | up-regulates
phosphorylation
|
SMAD2 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-244719 |
Ser245 |
NQSMDTGsPAELSPT |
Homo sapiens |
|
| pmid |
sentence |
| 10197981 |
These results suggest that oncogenic ras, acting through mek1 and erk kinases, induces the phosphorylation of smad2 and smad3 .we show that phosphorylation of smad2, a mediator of the activin/transforming growth factor-beta signal, by activated extracellular signal-regulated kinase 1 (erk1) increases the amount of smad2 protein and leads to enhanced transcriptional activity |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-244723 |
Ser250 |
TGSPAELsPTTLSPV |
Homo sapiens |
|
| pmid |
sentence |
| 10197981 |
These results suggest that oncogenic ras, acting through mek1 and erk kinases, induces the phosphorylation of smad2 and smad3 .we show that phosphorylation of smad2, a mediator of the activin/transforming growth factor-beta signal, by activated extracellular signal-regulated kinase 1 (erk1) increases the amount of smad2 protein and leads to enhanced transcriptional activity |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-244727 |
Ser255 |
ELSPTTLsPVNHSLD |
Homo sapiens |
|
| pmid |
sentence |
| 10197981 |
These results suggest that oncogenic ras, acting through mek1 and erk kinases, induces the phosphorylation of smad2 and smad3 .we show that phosphorylation of smad2, a mediator of the activin/transforming growth factor-beta signal, by activated extracellular signal-regulated kinase 1 (erk1) increases the amount of smad2 protein and leads to enhanced transcriptional activity |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-255020 |
Ser255 |
ELSPTTLsPVNHSLD |
Homo sapiens |
|
| pmid |
sentence |
| 26194464 |
Taken together, ERK-mediated Smad2 linker phosphorylation is responsible for TH17 differentiation |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-244731 |
Thr220 |
QSNYIPEtPPPGYIS |
Homo sapiens |
|
| pmid |
sentence |
| 12193595 |
Phosphorylation of smad2 by erk increases its transcriptional activity /thr220 and ser245, ser250, and ser255 were possible phosphorylation sites. The phosphorylation of peak a peptide by erk1 is consistent with that prediction. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-244735 |
Thr8 |
MSSILPFtPPVVKRL |
Homo sapiens |
|
| pmid |
sentence |
| 12193595 |
These results suggest that oncogenic ras, acting through mek1 and erk kinases, induces the phosphorylation of smad2 and smad3 .we show that phosphorylation of smad2, a mediator of the activin/transforming growth factor-beta signal, by activated extracellular signal-regulated kinase 1 (erk1) increases the amount of smad2 protein and leads to enhanced transcriptional activity |
|
| Publications: |
6 |
Organism: |
Homo Sapiens |
| Tissue: |
Lung, Breast, Lung |
| Pathways: | Hepatocellular Tumor, Pancreatic ductal adenocarcinoma (PDA) |
| + |
CTDSP1 | down-regulates activity
dephosphorylation
|
SMAD2 |
0.502 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-248795 |
Ser245 |
NQSMDTGsPAELSPT |
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 |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-248796 |
Ser250 |
TGSPAELsPTTLSPV |
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 |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-248797 |
Ser255 |
ELSPTTLsPVNHSLD |
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 |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-248794 |
Thr220 |
QSNYIPEtPPPGYIS |
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: |
4 |
Organism: |
Homo Sapiens |
| + |
CTDSP2 | down-regulates activity
dephosphorylation
|
SMAD2 |
0.434 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-248297 |
Ser245 |
NQSMDTGsPAELSPT |
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 |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-248298 |
Ser250 |
TGSPAELsPTTLSPV |
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 |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-248299 |
Ser255 |
ELSPTTLsPVNHSLD |
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-248296 |
Thr220 |
QSNYIPEtPPPGYIS |
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: |
4 |
Organism: |
Homo Sapiens |
| + |
PAK4 | down-regulates quantity by destabilization
phosphorylation
|
SMAD2 |
0.348 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-279084 |
Ser465 |
SPSVRCSsMS |
Homo sapiens |
|
| pmid |
sentence |
| 23934187 |
In addition, PAK4 phosphorylates Smad2 on Ser465, leading to the degradation of Smad2 through ubiquitin-proteasome-dependent pathway under hepatocyte growth factor (HGF) stimulation. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
TGFBR1 | up-regulates activity
phosphorylation
|
SMAD2 |
0.827 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-236107 |
Ser465 |
SPSVRCSsMS |
Chlorocebus aethiops |
COS-1 Cell |
| pmid |
sentence |
| 9346908 |
Recently, it was demonstrated that Smad2 interacts transiently with and is a direct substrate of the transforming growth factor-_ (TGF-_) type I receptor, T_RI. Phosphorylation sites on smad2 were localized to a carboxyl-terminal fragment containing three serine residues at positions 464, 465, and 467. In this report, we show that T_RI specifically phosphorylates Smad2 on serines 465 and 467.These results indicate that receptor-dependent phosphorylation of Smad2 on serines 465 and 467 is required in mammalian cells to permit association with Smad4 and to propagate TGF-_ signals. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-235995 |
Ser467 |
SVRCSSMs |
Chlorocebus aethiops |
|
| pmid |
sentence |
| 9346908 |
Recently, it was demonstrated that Smad2 interacts transiently with and is a direct substrate of the transforming growth factor-beta (TGF-beta) type I receptor, TbetaRI. Phosphorylation sites on Smad2 were localized to a carboxyl-terminal fragment containing three serine residues at positions 464, 465, and 467. These results indicate that receptor-dependent phosphorylation of Smad2 on serines 465 and 467 is required in mammalian cells to permit association with Smad4 and to propagate TGF-_ signals. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-249549 |
|
|
Homo sapiens |
Macrophage |
| pmid |
sentence |
| 10973958 |
The pathway restricted (r)Smads (e.g. Smad1, 2, 3, and 5) are serine/threonine kinase activated proteins that interact in an unphosphorylated state with a TGF-b superfamily receptor. Upon ligand binding they are phosphorylated by the receptor and released. |
|
| Publications: |
3 |
Organism: |
Chlorocebus Aethiops, Homo Sapiens |
| Pathways: | Hepatocellular Tumor, Multiple sclerosis, Pancreatic ductal adenocarcinoma (PDA), TGF-beta Signaling, TGFb in cancer |
| + |
CDK2 | down-regulates activity
phosphorylation
|
SMAD2 |
0.499 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-279678 |
Thr8 |
MSSILPFtPPVVKRL |
Homo sapiens |
|
| pmid |
sentence |
| 19201832 |
Moreover, CDK2 is the predominant CDK that phosphorylates Smad2 on T8 in myeloma cells, leading to inhibition of Smad2-Smad4 association that precludes transcriptional regulation by Smad2.|Moreover, CDK2 is the predominant cyclin-dependent kinase that phosphorylates Smad2 on T8 in myeloma cells, leading to inhibition of Smad2-Smad4 association that precludes transcriptional regulation by Smad2. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
MAPK3 | up-regulates activity
phosphorylation
|
SMAD2 |
0.749 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-227514 |
Thr8 |
MSSILPFtPPVVKRL |
Homo sapiens |
|
| pmid |
sentence |
| 12193595 |
We show that phosphorylation of Smad2, a mediator of the activin/transforming growth factor-beta signal, by activated extracellular signal-regulated kinase 1 (ERK1) increases the amount of Smad2 protein and leads to enhanced transcriptional activity.[] A site of ERK-dependent phosphorylation on Smad2 was located to Thr8 |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-217613 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 19115199 |
These results suggest that oncogenic ras, acting through mek1 and erk kinases, induces the phosphorylation of smad2 and smad3 .we show that phosphorylation of smad2, a mediator of the activin/transforming growth factor-beta signal, by activated extracellular signal-regulated kinase 1 (erk1) increases the amount of smad2 protein and leads to enhanced transcriptional activity |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-236067 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 10197981 |
These results suggest that oncogenic ras, acting through mek1 and erk kinases, induces the phosphorylation of smad2 and smad3 .we show that phosphorylation of smad2, a mediator of the activin/transforming growth factor-beta signal, by activated extracellular signal-regulated kinase 1 (erk1) increases the amount of smad2 protein and leads to enhanced transcriptional activity |
|
| Publications: |
3 |
Organism: |
Homo Sapiens |
| Tissue: |
Lung, Breast |
| + |
MAPK1 | down-regulates
phosphorylation
|
SMAD2 |
0.72 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-66738 |
|
|
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 |
| + |
MYC | down-regulates 
|
SMAD2 |
0.681 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-114281 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 11804592 |
Oncogenic c-myc promotes cell growth and cancer development partly by inhibiting the growth inhibitory functions of smads |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Hepatocellular Tumor |
| + |
YAP/TAZ | up-regulates activity
binding
|
SMAD2 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-277661 |
|
|
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 |
| + |
SMAD2 | up-regulates activity
binding
|
SMURF2 |
0.776 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-108490 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 11389444 |
We show that in the presence of TGF-beta signalling, Smad2 interacts through its proline-rich PPXY motif with the tryptophan-rich WW domains of Smurf2, a recently identified E3 ubiquitin ligases.Thus, stimulation by TGF-beta can induce the assembly of a Smad2-Smurf2 ubiquitin ligase complex that functions to target substrates for degradation. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
ACVR1B | up-regulates activity
phosphorylation
|
SMAD2 |
0.803 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-251943 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 11389842 |
Nodal Induces Smad Phosphorylation through ALK4 in a Cripto-Dependent Manner |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-235157 |
|
|
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: |
2 |
Organism: |
Homo Sapiens, Mus Musculus |
| Pathways: | Multiple sclerosis |
| + |
NEDD4L | down-regulates activity
ubiquitination
|
SMAD2 |
0.772 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-217622 |
|
|
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 |
| + |
MAPK3 | down-regulates
phosphorylation
|
SMAD2 |
0.749 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-66778 |
|
|
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 |
| + |
GGCX | up-regulates quantity by expression 
transcriptional regulation
|
SMAD2 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-261232 |
|
|
Rattus norvegicus |
|
| pmid |
sentence |
| 31539109 |
GGCX can regulate osteoporosis via promoting the TGFβ/smad signaling pathway, facilitating BMSCs osteogenic differentiation, and inhibiting BMSCs adipogenic differentiation. The transfection of pcDNA-GGCX plasmid significantly promoted BMSC cell proliferation, increased calcified nodule formation, inhibited adipogenic differentiation, enhanced ALP activity, elevated RUNX2, and OPN mRNA expressions, and upregulated TGFβ1, Smad2, and Smad7 expressions (p < 0.05). |
|
| Publications: |
1 |
Organism: |
Rattus Norvegicus |
| + |
SMURF2 | down-regulates activity
ubiquitination
|
SMAD2 |
0.776 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-236133 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 11016919 |
The ability of smurf2 to promote smad2 destruction required the hect catalytic activity of smurf2 and depended on the proteasome-dependent pathway. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Tissue: |
HEK-293 Cell |
| + |
PML | up-regulates activity
binding
|
SMAD2 |
0.538 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-128738 |
|
|
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 |
| + |
SMAD2 | form complex 
binding
|
SMAD2/STAT3/EP300 |
0.56 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-255023 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 26194464 |
Thus, pSmad2L (Ser255) forms complex with p300 and STAT3 to bind to the proximal promoter of the Rorc and Il17a genes. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
KAT2A | up-regulates
binding
|
SMAD2 |
0.336 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-123315 |
|
|
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 |
| + |
PPM1A | down-regulates activity
dephosphorylation
|
SMAD2 |
0.664 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-217628 |
|
|
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. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-277034 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 25026293 |
All of these results lead to the conclusion that PPM1A inhibits the TGF-\u03b2-induced the activity of Smad2, Smad3 and transcriotional responses, whereas depletion of PPM1A enhances the activation of TGF-\u03b2/Smads signaling in bladder cancer cells.|Protein phosphatase PPM1A has been reported to dephosphorylate TGF-\u03b2-activated Smad2/3, thus inhibiting the TGF-\u03b2 signaling pathway. |
|
| Publications: |
2 |
Organism: |
Homo Sapiens |
| + |
ZFYVE9 | up-regulates activity
relocalization
|
SMAD2 |
0.904 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-165786 |
|
|
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: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | TGF-beta Signaling |
| + |
SMAD2 | form complex
binding
|
SMAD2/SMURF2 |
0.776 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-108487 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 11389444 |
We show that in the presence of tgf-beta, smad2 interacts through its proline-rich ppxy motif with the tryptophan-rich ww domains of smurf2, a recently identified e3 ubiquitin ligases. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
UCHL5 | up-regulates
deubiquitination
|
SMAD2 |
0.382 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-138876 |
|
|
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 |
| + |
ITCH | up-regulates
ubiquitination
|
SMAD2 |
0.455 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-128647 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 15350225 |
Itch promotes ubiquitination of smad2 and augments smad2 phosphorylation that requires an intact ligase activity of itch. Moreover, itch facilitates complex formation between tgf-beta receptor and smad2 and enhances tgf-beta-induced transcription. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
SMAD2 | up-regulates activity
|
LEF1 |
0.456 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-78988 |
|
|
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: | Hepatocellular Tumor |
| + |
HGS | up-regulates
|
SMAD2 |
0.365 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-84616 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 11094085 |
Hgs and sara, are prerequisites for receptor-mediated activation of smad2 |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
MAPK11 | down-regulates
phosphorylation
|
SMAD2 |
0.359 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-167848 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 20820849 |
Smads can also be phosphorylated in the linker region most prominently by the action of mitogen-activated protein (map) kinaseslinker region phosphorylation can prevent nuclear translocation of smads and inhibit tgf-_ signalling, potentially leading to oncogenesis. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
SMAD2 | up-regulates activity
binding
|
SMAD4 |
0.704 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-235183 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 11274206 |
the receptor-regulated Smad, such as Smad2, forms a heterocomplex with the co-mediator Smad, Smad4 |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Hepatocellular Tumor, Pancreatic ductal adenocarcinoma (PDA), TGF-beta Signaling, TGFb in cancer |
| + |
GREB1 | down-regulates activity
binding
|
SMAD2 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-265884 |
|
|
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 |
| + |
FBN1 | up-regulates activity
|
SMAD2 |
0.376 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-251889 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 17242066 |
Fibrillin-1 sequence encoded by exons 44-49 releases endogenous TGFbeta1, thereby stimulating TGFbeta receptor-mediated Smad2 signaling. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
SKI | down-regulates activity
binding
|
SMAD2 |
0.731 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-236155 |
|
|
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 |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-217658 |
|
|
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. |
|
| Publications: |
2 |
Organism: |
Homo Sapiens |
| Pathways: | TGF-beta Signaling |
| + |
ACVR2A | up-regulates activity
phosphorylation
|
SMAD2 |
0.71 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-279786 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 34003511 |
In ACVR2A/B dKO parental cells, only ACVR2A , but not ACVR2A , could rescue both pSMAD2 and pSMAD1/5 (Fig\u00a04B).|In marked contrast, in ACVR2A/B dKO HOM1 cells, ACVR2A restored SMAD1/5 phosphorylation, but not SMAD2 phosphorylation (Fig\u00a04C). |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Multiple sclerosis |
| + |
PML | up-regulates
binding
|
SMAD2 |
0.538 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-128735 |
|
|
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 |
| + |
SMAD2 | form complex
binding
|
SMAD2/SMAD4 |
0.704 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-235188 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 11274206 |
the receptor-regulated Smad, such as Smad2, forms a heterocomplex with the co-mediator Smad, Smad4 |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Hepatocellular Tumor, Multiple sclerosis, Pancreatic ductal adenocarcinoma (PDA), TGF-beta Signaling, TGFb in cancer |
| + |
SKIL | down-regulates activity
binding
|
SMAD2 |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-227479 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 10531062 |
Thus, SnoN can interact with Smad4 and Smad2 and inhibit their abilities to activate transcription. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-236099 |
|
|
Homo sapiens |
|
| 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 |
| + |
SMURF2 | down-regulates quantity by destabilization
polyubiquitination
|
SMAD2 |
0.776 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-272935 |
|
|
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 11016919 |
The ability of Smurf2 to promote Smad2 destruction required the HECT catalytic activity of Smurf2 and depended on the proteasome-dependent pathway. Consistent with these results, Smurf2 potently reduced the transcriptional activity of Smad2. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
BMP2 | up-regulates
|
SMAD2 |
0.488 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-175273 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 21793042 |
Upon bmp binding to the bmpr-ii, bmpr-i is recruited to form an activated quaternary complex, which then phosphorylates and activates intracellular smad proteins. Receptor smads bind to a co-smad and translocate to the nucleus to serve as transcription factors. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
SMAD2 | up-regulates
binding
|
MEF2A |
0.39 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-235846 |
|
|
Mus musculus |
C2C12 Cell |
| pmid |
sentence |
| 11160896 |
Our studies indicate that smad2 and 4 (smad2/4) complexes cooperate with mef2 regulatory proteins in a gal4-based one-hybrid reporter gene assay. |
|
| Publications: |
1 |
Organism: |
Mus Musculus |
| Tissue: |
Myotube |
| + |
P300/PCAF | up-regulates
binding
|
SMAD2 |
0.625 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-217230 |
|
|
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 |
| + |
MTMR4 | down-regulates
dephosphorylation
|
SMAD2 |
0.516 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-163031 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 20061380 |
Here we demonstrate that myotubularin-related protein 4 (mtmr4), a fyve domain-containing dual-specificity protein phosphatase (dsp), attenuates tgfbeta signaling by reducing the phosphorylation level of r-smads in early endosomes. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
RANBP3 | down-regulates activity
relocalization
|
SMAD2 |
0.441 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-217625 |
|
|
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-217634 |
|
|
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 |
| + |
TUBB | down-regulates
binding
|
SMAD2 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-154316 |
|
|
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 |
| + |
MAP3K1 | up-regulates activity
phosphorylation
|
SMAD2 |
0.467 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-279064 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 10647776 |
As yet, the apparent discrepancy between these and above data is not clear, but obviously the type of cell under study and the cellular context may play an important role.In endothelial cells, Smad2 activity is stimulated by MEKK1, a component of the Stress Activated Protein Kinase and c-Jun N terminal kinase (SAPK and JNK) pathway.|Phosphorylation of Smad2 by MEKK1 increased its association with Smad4, its nuclear accumulation and its transcription induction activity . |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | EBV infection |
| + |
Gbeta | up-regulates
phosphorylation
|
SMAD2 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-270065 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 10197981 |
These results suggest that oncogenic ras, acting through mek1 and erk kinases, induces the phosphorylation of smad2 and smad3 .we show that phosphorylation of smad2, a mediator of the activin/transforming growth factor-beta signal, by activated extracellular signal-regulated kinase 1 (erk1) increases the amount of smad2 protein and leads to enhanced transcriptional activity |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Tissue: |
Lung, Breast |
| + |
RNF111 | down-regulates activity
ubiquitination
|
SMAD2 |
0.679 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-235394 |
|
|
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 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 |
| + |
PPM1A | down-regulates
dephosphorylation
|
SMAD2 |
0.664 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-146919 |
|
|
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 |
| + |
TUBB | down-regulates activity
binding
|
SMAD2 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-217631 |
|
|
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 |
| + |
UCHL5 | up-regulates activity
deubiquitination
|
SMAD2 |
0.382 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-217610 |
|
|
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 |
| + |
ERK1/2 | down-regulates
phosphorylation
|
SMAD2 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-244576 |
|
|
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: | Hepatocellular Tumor, Pancreatic ductal adenocarcinoma (PDA) |
| + |
RNF111 | down-regulates quantity by destabilization
ubiquitination
|
SMAD2 |
0.679 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-236873 |
|
|
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 |
| + |
SMAD2 | up-regulates activity
binding
|
SMAD2 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-232149 |
|
|
Homo sapiens |
|
| 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: |
Homo Sapiens |
| Pathways: | EBV infection, Hepatocellular Tumor, Multiple sclerosis, Pancreatic ductal adenocarcinoma (PDA), TGF-beta Signaling, TGFb in cancer |
| + |
SMAD2 | up-regulates
binding
|
CREB1 |
0.334 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-59462 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 9689110 |
We demonstrate that human smad2 and smad4, two essential smad proteins involved in mediating tgf-beta transcriptional responses in endothelial and other cell types, can functionally interact with the transcriptional coactivator creb binding protein (cbp). This interaction is specific in that it requires ligand (tgf-beta) activation and is mediated by the transcriptional activation domains of the smad proteins. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
FOXH1 | up-regulates activity
binding
|
SMAD2 |
0.778 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-108333 |
|
|
Homo sapiens |
COS-1 Cell |
| pmid |
sentence |
| 9858566 |
FAST-2 also interacts directly with Smad2, a cytoplasmic protein which is translocated to the nucleus in response to TGF-beta, and forms a multimeric complex with Smad2 and Smad4 on the activin response element, a high-affinity binding site for FAST-1. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
EBNA1 | down-regulates quantity
destabilization
|
SMAD2 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-267615 |
|
|
Homo sapiens |
Nasopharyngeal Carcinoma Cell |
| pmid |
sentence |
| 17486072 |
The studies described above show that SMAD2 protein levels are reduced by EBNA1 with consequent attenuation of SMAD2 activation in response to TGFβ1. This analysis confirmed the stability of the EBNA1 protein and revealed that the SMAD2 protein is more rapidly degraded in Ad/AH cells expressing EBNA1 as compared to the control cells. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | EBV infection |
| + |
NEDD4L | down-regulates
ubiquitination
|
SMAD2 |
0.772 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-161710 |
|
|
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 |
| + |
SMURF | down-regulates activity
ubiquitination
|
SMAD2 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-253263 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 11016919 |
The ability of smurf2 to promote smad2 destruction required the hect catalytic activity of smurf2 and depended on the proteasome-dependent pathway. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Tissue: |
HEK-293 Cell |
| Pathways: | TGF-beta Signaling |
| + |
WWTR1 | up-regulates
binding
|
SMAD2 |
0.586 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-169835 |
|
|
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 |
| + |
WNK1 | up-regulates quantity
phosphorylation
|
SMAD2 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-280164 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 28236964 |
In addition, WNK1 and WNK4 can phosphorylate Smad2, and silencing of WNK1 reduces Smad2 protein levels in HeLa cells, suggesting that WNKs have complex effects on TGFbeta signaling, which itself can promote cancer or act in a tumor suppressing manner. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
ACVR2B | up-regulates activity
phosphorylation
|
SMAD2 |
0.775 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-254984 |
|
|
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 |
| + |
WWTR1 | up-regulates activity
binding
|
SMAD2 |
0.586 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-169838 |
|
|
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 |
| + |
ARAF | down-regulates quantity by destabilization
phosphorylation
|
SMAD2 |
0.379 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-279391 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 23591895 |
Araf promotes Smad2 linker phosphorylation through S253.|In this study, we demonstrate that Araf can directly bind to and phosphorylate the linker of Smad2, leading to degradation of activated Smad2. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
TRIM33 | up-regulates activity
binding
|
SMAD2 |
0.631 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-236064 |
|
|
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 |
| + |
PIM1 | up-regulates activity
phosphorylation
|
SMAD2 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-279090 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 29472550 |
We further showed that PIM1 could interact with and phosphorylate Smad2 or Smad3 in the nucleus to induce transcription factor (ZEB1, ZEB2, Snail1, Snail2 and Twist) expression and EMT. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
4.0
SMAD2
- 
- 