| + |
CSNK2A2 | down-regulates activity 
phosphorylation
|
EIF4EBP1 |
0.338 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-249334 |
Ser112 |
KRAGGEEsQFEMDI |
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 9806882 |
The kinase is quite distinct from casein kinase 2, which also phosphorylates Ser-111 of 4E-BP1. The possible importance of these kinases in the phosphorylation of 4E-BP1 in fat cells is discussed. It is suggested that the phosphorylation of Ser-111 might be a priming event that facilitates the subsequent phosphorylation of Thr-36, Thr-45, Ser-64 and Thr69 by a rapamycin-sensitive process that initiates the dissociation of 4E-BP1 from eIF4E and hence the formation of the eIF4F complex. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
CSNK2A1 | down-regulates
phosphorylation
|
EIF4EBP1 |
0.346 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-98280 |
Ser112 |
KRAGGEEsQFEMDI |
Homo sapiens |
|
| pmid |
sentence |
| 12588975 |
Phosphorylation at s112 directly affects binding of 4e-bp1 to eif4e without influencing phosphorylation of other sites. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | COVID-19 Causal Network, SARS-CoV STRESS GRANULES |
| + |
ATM | down-regulates
phosphorylation
|
EIF4EBP1 |
0.528 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-85619 |
Ser112 |
KRAGGEEsQFEMDI |
Homo sapiens |
|
| pmid |
sentence |
| 11146653 |
Here we report that atm... phosphorylates 4e-bp1 at ser 111cells lacking atm kinase activity exhibit a significant decrease in the insulin-induced dissociation of 4e-bp1 from eif-4e. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
RPS6KA5 | down-regulates activity
phosphorylation
|
EIF4EBP1 |
0.658 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-262993 |
Ser65 |
FLMECRNsPVTKTPP |
|
|
| pmid |
sentence |
| 12213813 |
In response to UV-B irradiation, the translation factor 4E-BP1 (eukaryotic initiation factor 4E [eIF4E]-binding protein 1) was phosphorylated at Thr36, Thr45, Ser64 and Thr69. Using either p38 MAPK inhibitors or the MSK inhibitor H89, UV-B-irradiation-induced phosphorylation was blocked [43]. 4E-BP1 binds to eIF4E in resting cells to prevent formation of a functional eIF4F complex, which is essential for cap-dependent initiation of translation. Phosphorylation of 4E-BP1 leads to dissociation from eIF4E |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-262991 |
Thr37 |
PPGDYSTtPGGTLFS |
|
|
| pmid |
sentence |
| 12213813 |
In response to UV-B irradiation, the translation factor 4E-BP1 (eukaryotic initiation factor 4E [eIF4E]-binding protein 1) was phosphorylated at Thr36, Thr45, Ser64 and Thr69. Using either p38 MAPK inhibitors or the MSK inhibitor H89, UV-B-irradiation-induced phosphorylation was blocked [43]. 4E-BP1 binds to eIF4E in resting cells to prevent formation of a functional eIF4F complex, which is essential for cap-dependent initiation of translation. Phosphorylation of 4E-BP1 leads to dissociation from eIF4E |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-249131 |
Thr45 |
PGGTLFStTPGGTRI |
in vitro |
|
| pmid |
sentence |
| 11777913 |
Here, using mass spectrometry, we identify the serum-responsive, rapamycin-sensitive sites as Ser 65 and Thr 70. | Phosphorylation of Thr 37/Thr 46 is followed by Thr 70 phosphorylation, and Ser 65 is phosphorylated last. Finally, we show that phosphorylation of Ser 65 and Thr 70 alone is insufficient to block binding to eIF4E, indicating that a combination of phosphorylation events is necessary to dissociate 4E-BP1 from eIF4E. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-262992 |
Thr46 |
GGTLFSTtPGGTRII |
|
|
| pmid |
sentence |
| 12213813 |
In response to UV-B irradiation, the translation factor 4E-BP1 (eukaryotic initiation factor 4E [eIF4E]-binding protein 1) was phosphorylated at Thr36, Thr45, Ser64 and Thr69. Using either p38 MAPK inhibitors or the MSK inhibitor H89, UV-B-irradiation-induced phosphorylation was blocked [43]. 4E-BP1 binds to eIF4E in resting cells to prevent formation of a functional eIF4F complex, which is essential for cap-dependent initiation of translation. Phosphorylation of 4E-BP1 leads to dissociation from eIF4E |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-262994 |
Thr70 |
RNSPVTKtPPRDLPT |
|
|
| pmid |
sentence |
| 12213813 |
In response to UV-B irradiation, the translation factor 4E-BP1 (eukaryotic initiation factor 4E [eIF4E]-binding protein 1) was phosphorylated at Thr36, Thr45, Ser64 and Thr69. Using either p38 MAPK inhibitors or the MSK inhibitor H89, UV-B-irradiation-induced phosphorylation was blocked [43]. 4E-BP1 binds to eIF4E in resting cells to prevent formation of a functional eIF4F complex, which is essential for cap-dependent initiation of translation. Phosphorylation of 4E-BP1 leads to dissociation from eIF4E |
|
| Publications: |
5 |
Organism: |
, In Vitro |
| + |
mTORC1 | down-regulates activity
phosphorylation
|
EIF4EBP1 |
0.753 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-236690 |
Ser65 |
FLMECRNsPVTKTPP |
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 12747827 |
Phosphorylated on serine and threonine residues in response to insulin, egf and pdgf. Phosphorylation at thr-37, thr-46, ser-65 and thr-70, corresponding to the hyperphosphorylated form, is regulated by mtorc1 and abolishes binding to eif4e. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-217137 |
Ser65 |
FLMECRNsPVTKTPP |
Homo sapiens |
|
| pmid |
sentence |
| 23486913 |
These results indicate that arg, leu, and gln act coordinately to stimulate proliferation of ptr cells through activation of the mtor-rps6k-rps6-eif4ebp1 signal transduction pathway. Specifically as part of mtorc1, mtor directly phosphorylates the ribosomal protein s6 kinases (s6k1 and s6k2) and the eukaryotic initiation factor 4e (eif4e)-binding proteins (4e-bp1 and 4e-bp2), both of which control specific steps in the initiation of cap-dependent translation |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-217086 |
Thr36 |
LPPGDYStTPGGTLF |
Homo sapiens |
|
| pmid |
sentence |
| 9465032 |
Mtorc1 promotes protein synthesis by phosphorylating the eukaryotic initiation factor 4e (eif4e)- binding protein 1 (4e-bp1) and the p70 ribosomal s6 kinase 1 (s6k1). Raft1 phosphorylation of 4e-bp1 on thr-36 and thr-45 blocks its association with the cap-binding protein, eif-4e,in vitro. in response to insulin and nutrients, mtorc1, consisting of mtor, raptor (regulatory-associated protein of mtor), and mlst8, is activated and phosphorylates eukaryotic initiation factor 4e-binding protein (4ebp) and p70 s6 kinase to promote protein synthesis and cell size. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-217110 |
Thr37 |
PPGDYSTtPGGTLFS |
Homo sapiens |
|
| pmid |
sentence |
| 23486913 |
These results indicate that arg, leu, and gln act coordinately to stimulate proliferation of ptr cells through activation of the mtor-rps6k-rps6-eif4ebp1 signal transduction pathway. Specifically as part of mtorc1, mtor directly phosphorylates the ribosomal protein s6 kinases (s6k1 and s6k2) and the eukaryotic initiation factor 4e (eif4e)-binding proteins (4e-bp1 and 4e-bp2), both of which control specific steps in the initiation of cap-dependent translation |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-236694 |
Thr37 |
PPGDYSTtPGGTLFS |
Homo sapiens |
|
| pmid |
sentence |
| 12747827 |
Phosphorylated on serine and threonine residues in response to insulin, egf and pdgf. Phosphorylation at thr-37, thr-46, ser-65 and thr-70, corresponding to the hyperphosphorylated form, is regulated by mtorc1 and abolishes binding to eif4e. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-217090 |
Thr45 |
PGGTLFStTPGGTRI |
Homo sapiens |
|
| pmid |
sentence |
| 9465032 |
Mtorc1 promotes protein synthesis by phosphorylating the eukaryotic initiation factor 4e (eif4e)- binding protein 1 (4e-bp1) and the p70 ribosomal s6 kinase 1 (s6k1). Raft1 phosphorylation of 4e-bp1 on thr-36 and thr-45 blocks its association with the cap-binding protein, eif-4e,in vitro. in response to insulin and nutrients, mtorc1, consisting of mtor, raptor (regulatory-associated protein of mtor), and mlst8, is activated and phosphorylates eukaryotic initiation factor 4e-binding protein (4ebp) and p70 s6 kinase to promote protein synthesis and cell size. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-217114 |
Thr46 |
GGTLFSTtPGGTRII |
Homo sapiens |
|
| pmid |
sentence |
| 23486913 |
These results indicate that arg, leu, and gln act coordinately to stimulate proliferation of ptr cells through activation of the mtor-rps6k-rps6-eif4ebp1 signal transduction pathway. Specifically as part of mtorc1, mtor directly phosphorylates the ribosomal protein s6 kinases (s6k1 and s6k2) and the eukaryotic initiation factor 4e (eif4e)-binding proteins (4e-bp1 and 4e-bp2), both of which control specific steps in the initiation of cap-dependent translation |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-236698 |
Thr46 |
GGTLFSTtPGGTRII |
Homo sapiens |
|
| pmid |
sentence |
| 12747827 |
Phosphorylated on serine and threonine residues in response to insulin, egf and pdgf. Phosphorylation at thr-37, thr-46, ser-65 and thr-70, corresponding to the hyperphosphorylated form, is regulated by mtorc1 and abolishes binding to eif4e. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-235964 |
Thr70 |
RNSPVTKtPPRDLPT |
Homo sapiens |
|
| pmid |
sentence |
| 12747827 |
Phosphorylated on serine and threonine residues in response to insulin, egf and pdgf. Phosphorylation at thr-37, thr-46, ser-65 and thr-70, corresponding to the hyperphosphorylated form, is regulated by mtorc1 and abolishes binding to eif4e. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-217141 |
Thr70 |
RNSPVTKtPPRDLPT |
Homo sapiens |
|
| pmid |
sentence |
| 23486913 |
These results indicate that arg, leu, and gln act coordinately to stimulate proliferation of ptr cells through activation of the mtor-rps6k-rps6-eif4ebp1 signal transduction pathway. Specifically as part of mtorc1, mtor directly phosphorylates the ribosomal protein s6 kinases (s6k1 and s6k2) and the eukaryotic initiation factor 4e (eif4e)-binding proteins (4e-bp1 and 4e-bp2), both of which control specific steps in the initiation of cap-dependent translation |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-236702 |
Thr70 |
RNSPVTKtPPRDLPT |
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 10942774 |
Mammalian target of rapamycin-dependent phosphorylation of phas-i in four (s/t)p sites detected by phospho-specific antibodies. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-235748 |
|
|
Cricetulus griseus |
|
| pmid |
sentence |
| 17510057 |
In response to insulin and nutrients, mTORC1, consisting of mTOR, raptor (regulatory-associated protein of mTOR), and mLST8, is activated and phosphorylates eukaryotic initiation factor 4E-binding protein (4EBP) and p70 S6 kinase to promote protein synthesis and cell size. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-236678 |
|
|
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 12747827 |
Our data demonstrate that the TOS motif functions as a docking site for the mTOR/raptor complex, which is required for multisite phosphorylation of 4E-BP1, eIF4E release from 4E-BP1, and cell growth. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-235745 |
|
|
Mus musculus |
MEF Cell |
| pmid |
sentence |
| 20670887 |
Specifically as part of mTORC1, mTOR directly phosphorylates the ribosomal protein S6 kinases (S6K1 and S6K2) and the eukaryotic initiation factor 4E (eIF4E)-binding proteins (4E-BP1 and 4E-BP2)phosphorylation of the 4E-BPs leads to their inhibition and release from eIF4E at the 5_ cap of mRNAs |
|
| Publications: |
14 |
Organism: |
Homo Sapiens, Cricetulus Griseus, Mus Musculus |
| Pathways: | AMPK Signaling, Insulin Signaling, PI3K/AKT Signaling |
| + |
MAPK1 | down-regulates activity
phosphorylation
|
EIF4EBP1 |
0.649 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-249390 |
Ser65 |
FLMECRNsPVTKTPP |
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 11691836 |
The 4E-BPs inhibit translation in a reversible manner. Hypophosphorylated 4E-BPs interact avidly with eIF4E, whereas 4E-BP hyperphosphorylation, elicited by stimulation of cells with hormones, cytokines, or growth factors, results in an abrogation of eIF4E-binding activity.|These results are at variance with reports that have characterized the 4E-BP1/eIF4E interaction utilizing recombinant 4E-BP1 proteins phosphorylated in vitro with ERK, and harboring alanine substitutions at Thr 37, Thr 46, Thr 70, and Ser 83 |phosphorylation of either Thr 46 or Ser 65 was reported to result in a decrease in eIF4E binding |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-249391 |
Ser83 |
PTIPGVTsPSSDEPP |
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 11691836 |
The 4E-BPs inhibit translation in a reversible manner. Hypophosphorylated 4E-BPs interact avidly with eIF4E, whereas 4E-BP hyperphosphorylation, elicited by stimulation of cells with hormones, cytokines, or growth factors, results in an abrogation of eIF4E-binding activity.|These results are at variance with reports that have characterized the 4E-BP1/eIF4E interaction utilizing recombinant 4E-BP1 proteins phosphorylated in vitro with ERK, and harboring alanine substitutions at Thr 37, Thr 46, Thr 70, and Ser 83 |phosphorylation of either Thr 46 or Ser 65 was reported to result in a decrease in eIF4E binding |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-249392 |
Thr37 |
PPGDYSTtPGGTLFS |
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 11691836 |
The 4E-BPs inhibit translation in a reversible manner. Hypophosphorylated 4E-BPs interact avidly with eIF4E, whereas 4E-BP hyperphosphorylation, elicited by stimulation of cells with hormones, cytokines, or growth factors, results in an abrogation of eIF4E-binding activity.|These results are at variance with reports that have characterized the 4E-BP1/eIF4E interaction utilizing recombinant 4E-BP1 proteins phosphorylated in vitro with ERK, and harboring alanine substitutions at Thr 37, Thr 46, Thr 70, and Ser 83 |phosphorylation of either Thr 46 or Ser 65 was reported to result in a decrease in eIF4E binding |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-249393 |
Thr46 |
GGTLFSTtPGGTRII |
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 11691836 |
The 4E-BPs inhibit translation in a reversible manner. Hypophosphorylated 4E-BPs interact avidly with eIF4E, whereas 4E-BP hyperphosphorylation, elicited by stimulation of cells with hormones, cytokines, or growth factors, results in an abrogation of eIF4E-binding activity.|These results are at variance with reports that have characterized the 4E-BP1/eIF4E interaction utilizing recombinant 4E-BP1 proteins phosphorylated in vitro with ERK, and harboring alanine substitutions at Thr 37, Thr 46, Thr 70, and Ser 83 |phosphorylation of either Thr 46 or Ser 65 was reported to result in a decrease in eIF4E binding |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-249394 |
Thr70 |
RNSPVTKtPPRDLPT |
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 11691836 |
The 4E-BPs inhibit translation in a reversible manner. Hypophosphorylated 4E-BPs interact avidly with eIF4E, whereas 4E-BP hyperphosphorylation, elicited by stimulation of cells with hormones, cytokines, or growth factors, results in an abrogation of eIF4E-binding activity.|These results are at variance with reports that have characterized the 4E-BP1/eIF4E interaction utilizing recombinant 4E-BP1 proteins phosphorylated in vitro with ERK, and harboring alanine substitutions at Thr 37, Thr 46, Thr 70, and Ser 83 |phosphorylation of either Thr 46 or Ser 65 was reported to result in a decrease in eIF4E binding |
|
| Publications: |
5 |
Organism: |
Homo Sapiens |
| + |
MTOR | down-regulates activity
phosphorylation
|
EIF4EBP1 |
0.924 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-101115 |
Ser65 |
FLMECRNsPVTKTPP |
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 12747827 |
Here, we show that a functional TOS motif is required for 4E-BP1 to bind to raptor (a recently identified mTOR-interacting protein), for 4E-BP1 to be efficiently phosphorylated in vitro by themTOR/raptor complex, and for 4E-BP1 to be phosphorylated in vivo at all identified mTOR-regulated sites. mTOR/raptor regulated phosphorylation is necessary for 4E-BPs efficient release from the translational initiation factor eIF4E. We find that the TOS motif is absolutely required for efficient phosphorylation of 4E-BP1 at all the identified mTOR-regulated sites, namely, Thr37/46, Ser65, and Thr70 in vivo. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-219257 |
Ser65 |
FLMECRNsPVTKTPP |
Sus scrofa |
Trophectoderm |
| pmid |
sentence |
| 23486913 |
These results indicate that arg, leu, and gln act coordinately to stimulate proliferation of ptr cells through activation of the mtor-rps6k-rps6-eif4ebp1 signal transduction pathway. Specifically as part of mtorc1, mtor directly phosphorylates the ribosomal protein s6 kinases (s6k1 and s6k2) and the eukaryotic initiation factor 4e (eif4e)-binding proteins (4e-bp1 and 4e-bp2), both of which control specific steps in the initiation of cap-dependent translation |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-226714 |
Ser65 |
FLMECRNsPVTKTPP |
Homo sapiens |
HEK-293T Cell |
| pmid |
sentence |
| 10942774 |
PHAS-I in adipocytes and HEK293 cells is phosphorylated in the following five sites, all of which conform to a (S/T)P motif (9, 10): Thr-36, Thr-45, Ser-64, Thr-69, and Ser-82. Thr-45 and Ser-64 flank the eIF4E-binding motif (7, 8), and phosphorylation of either site blocks eIF4E binding in vitro (10, 11). Insulin stimulates the phosphorylation of Thr-36, Thr-45, Ser-64, and Thr-69 in both fat cells and HEK293 cells, and incubating cells with rapamycin decreases the phosphorylation of these sites.Immunoprecipitated epitope-tagged mammalian target of rapamycin (mTOR) phosphorylated Thr-36/45. mTOR also phosphorylated Thr-69 and Ser-64 but only when purified immune complexes were incubated with the activating antibody, mTAb1. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-250292 |
Ser83 |
PTIPGVTsPSSDEPP |
Homo sapiens |
|
| pmid |
sentence |
| 9204908 |
MTOR phosphorylated PHAS-I on serine and threonine residues in vitro, and these modifications inhibited the binding of PHAS-I to eIF-4E. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-167180 |
Thr36 |
LPPGDYStTPGGTLF |
Mus musculus |
MEF Cell |
| pmid |
sentence |
| 20670887 |
Specifically as part of mTORC1, mTOR directly phosphorylates the ribo- somal protein S6 kinases (S6K1 and S6K2) and the eukaryotic initiation factor 4E (eIF4E)-binding proteins (4E-BP1 and 4E-BP2), both of which control specific steps in the initiation of cap-dependent translation |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-154810 |
Thr36 |
LPPGDYStTPGGTLF |
Homo sapiens |
|
| pmid |
sentence |
| 17510057 |
In response to insulin and nutrients, mTORC1, consisting of mTOR, raptor (regulatory-associated protein of mTOR), and mLST8, is activated and phosphorylates eukaryotic initiation factor 4E-binding protein (4EBP) and p70 S6 kinase to promote protein synthesis and cell size. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-55697 |
Thr36 |
LPPGDYStTPGGTLF |
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 9465032 |
Mtorc1 promotes protein synthesis by phosphorylating the eukaryotic initiation factor 4e (eif4e)- binding protein 1 (4e-bp1) and the p70 ribosomal s6 kinase 1 (s6k1). Raft1 phosphorylation of 4e-bp1 on thr-36 and thr-45 blocks its association with the cap-binding protein, eif-4e,in vitro. in response to insulin and nutrients, mtorc1, consisting of mtor, raptor (regulatory-associated protein of mtor), and mlst8, is activated and phosphorylates eukaryotic initiation factor 4e-binding protein (4ebp) and p70 s6 kinase to promote protein synthesis and cell size. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-219262 |
Thr37 |
PPGDYSTtPGGTLFS |
Sus scrofa |
Trophectoderm |
| pmid |
sentence |
| 23486913 |
These results indicate that arg, leu, and gln act coordinately to stimulate proliferation of ptr cells through activation of the mtor-rps6k-rps6-eif4ebp1 signal transduction pathway. Specifically as part of mtorc1, mtor directly phosphorylates the ribosomal protein s6 kinases (s6k1 and s6k2) and the eukaryotic initiation factor 4e (eif4e)-binding proteins (4e-bp1 and 4e-bp2), both of which control specific steps in the initiation of cap-dependent translation |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-101119 |
Thr37 |
PPGDYSTtPGGTLFS |
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 12747827 |
Here, we show that a functional TOS motif is required for 4E-BP1 to bind to raptor (a recently identified mTOR-interacting protein), for 4E-BP1 to be efficiently phosphorylated in vitro by themTOR/raptor complex, and for 4E-BP1 to be phosphorylated in vivo at all identified mTOR-regulated sites. mTOR/raptor regulated phosphorylation is necessary for 4E-BPs efficient release from the translational initiation factor eIF4E. We find that the TOS motif is absolutely required for efficient phosphorylation of 4E-BP1 at all the identified mTOR-regulated sites, namely, Thr37/46, Ser65, and Thr70 in vivo. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-167184 |
Thr45 |
PGGTLFStTPGGTRI |
Mus musculus |
MEF Cell |
| pmid |
sentence |
| 20670887 |
Specifically as part of mTORC1, mTOR directly phosphorylates the ribo- somal protein S6 kinases (S6K1 and S6K2) and the eukaryotic initiation factor 4E (eIF4E)-binding proteins (4E-BP1 and 4E-BP2), both of which control specific steps in the initiation of cap-dependent translation |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-154814 |
Thr45 |
PGGTLFStTPGGTRI |
Homo sapiens |
HEK-293 Cell, Adipocyte |
| pmid |
sentence |
| 17510057 |
In response to insulin and nutrients, mTORC1, consisting of mTOR, raptor (regulatory-associated protein of mTOR), and mLST8, is activated and phosphorylates eukaryotic initiation factor 4E-binding protein (4EBP) and p70 S6 kinase to promote protein synthesis and cell size. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-55701 |
Thr45 |
PGGTLFStTPGGTRI |
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 9465032 |
Mtorc1 promotes protein synthesis by phosphorylating the eukaryotic initiation factor 4e (eif4e)- binding protein 1 (4e-bp1) and the p70 ribosomal s6 kinase 1 (s6k1). Raft1 phosphorylation of 4e-bp1 on thr-36 and thr-45 blocks its association with the cap-binding protein, eif-4e,in vitro. in response to insulin and nutrients, mtorc1, consisting of mtor, raptor (regulatory-associated protein of mtor), and mlst8, is activated and phosphorylates eukaryotic initiation factor 4e-binding protein (4ebp) and p70 s6 kinase to promote protein synthesis and cell size. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-101123 |
Thr46 |
GGTLFSTtPGGTRII |
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 12747827 |
Here, we show that a functional TOS motif is required for 4E-BP1 to bind to raptor (a recently identified mTOR-interacting protein), for 4E-BP1 to be efficiently phosphorylated in vitro by themTOR/raptor complex, and for 4E-BP1 to be phosphorylated in vivo at all identified mTOR-regulated sites. mTOR/raptor regulated phosphorylation is necessary for 4E-BPs efficient release from the translational initiation factor eIF4E. We find that the TOS motif is absolutely required for efficient phosphorylation of 4E-BP1 at all the identified mTOR-regulated sites, namely, Thr37/46, Ser65, and Thr70 in vivo. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-219266 |
Thr46 |
GGTLFSTtPGGTRII |
Sus scrofa |
Trophectoderm |
| pmid |
sentence |
| 23486913 |
These results indicate that arg, leu, and gln act coordinately to stimulate proliferation of ptr cells through activation of the mtor-rps6k-rps6-eif4ebp1 signal transduction pathway. Specifically as part of mtorc1, mtor directly phosphorylates the ribosomal protein s6 kinases (s6k1 and s6k2) and the eukaryotic initiation factor 4e (eif4e)-binding proteins (4e-bp1 and 4e-bp2), both of which control specific steps in the initiation of cap-dependent translation |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-226710 |
Thr70 |
RNSPVTKtPPRDLPT |
Homo sapiens |
HEK-293T Cell |
| pmid |
sentence |
| 10942774 |
PHAS-I in adipocytes and HEK293 cells is phosphorylated in the following five sites, all of which conform to a (S/T)P motif (9, 10): Thr-36, Thr-45, Ser-64, Thr-69, and Ser-82. Thr-45 and Ser-64 flank the eIF4E-binding motif (7, 8), and phosphorylation of either site blocks eIF4E binding in vitro (10, 11). Insulin stimulates the phosphorylation of Thr-36, Thr-45, Ser-64, and Thr-69 in both fat cells and HEK293 cells, and incubating cells with rapamycin decreases the phosphorylation of these sites.Immunoprecipitated epitope-tagged mammalian target of rapamycin (mTOR) phosphorylated Thr-36/45. mTOR also phosphorylated Thr-69 and Ser-64 but only when purified immune complexes were incubated with the activating antibody, mTAb1. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-219273 |
Thr70 |
RNSPVTKtPPRDLPT |
Sus scrofa |
Trophectoderm |
| pmid |
sentence |
| 23486913 |
These results indicate that arg, leu, and gln act coordinately to stimulate proliferation of ptr cells through activation of the mtor-rps6k-rps6-eif4ebp1 signal transduction pathway. Specifically as part of mtorc1, mtor directly phosphorylates the ribosomal protein s6 kinases (s6k1 and s6k2) and the eukaryotic initiation factor 4e (eif4e)-binding proteins (4e-bp1 and 4e-bp2), both of which control specific steps in the initiation of cap-dependent translation |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-101127 |
Thr70 |
RNSPVTKtPPRDLPT |
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 12747827 |
Here, we show that a functional TOS motif is required for 4E-BP1 to bind to raptor (a recently identified mTOR-interacting protein), for 4E-BP1 to be efficiently phosphorylated in vitro by themTOR/raptor complex, and for 4E-BP1 to be phosphorylated in vivo at all identified mTOR-regulated sites. mTOR/raptor regulated phosphorylation is necessary for 4E-BPs efficient release from the translational initiation factor eIF4E. We find that the TOS motif is absolutely required for efficient phosphorylation of 4E-BP1 at all the identified mTOR-regulated sites, namely, Thr37/46, Ser65, and Thr70 in vivo. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-80797 |
Thr70 |
RNSPVTKtPPRDLPT |
Homo sapiens |
|
| pmid |
sentence |
| 10942774 |
Mammalian target of rapamycin-dependent phosphorylation of phas-i in four (s/t)p sites detected by phospho-specific antibodies. |
|
| Publications: |
18 |
Organism: |
Homo Sapiens, Sus Scrofa, Mus Musculus |
| Pathways: | MTOR Signaling |
| + |
MAPK14 | down-regulates activity
phosphorylation
|
EIF4EBP1 |
0.444 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-250097 |
Ser65 |
FLMECRNsPVTKTPP |
Homo sapiens |
JB6 Cl41 Cell |
| pmid |
sentence |
| 11777913 |
4E-BP1 Is Phosphorylated in Vitro by Active p38 Kinase. In the present study we demonstrated that UVB induced 4E-BP1 phosphorylation at multiple sites, Thr-36, Thr-45, Ser-64, and Thr-69, leading to dissociation of 4E-BP1 from eIF-4E. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-250098 |
Thr37 |
PPGDYSTtPGGTLFS |
Homo sapiens |
JB6 Cl41 Cell |
| pmid |
sentence |
| 11777913 |
4E-BP1 Is Phosphorylated in Vitro by Active p38 Kinase. In the present study we demonstrated that UVB induced 4E-BP1 phosphorylation at multiple sites, Thr-36, Thr-45, Ser-64, and Thr-69, leading to dissociation of 4E-BP1 from eIF-4E. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-250099 |
Thr46 |
GGTLFSTtPGGTRII |
Homo sapiens |
JB6 Cl41 Cell |
| pmid |
sentence |
| 11777913 |
4E-BP1 Is Phosphorylated in Vitro by Active p38 Kinase. In the present study we demonstrated that UVB induced 4E-BP1 phosphorylation at multiple sites, Thr-36, Thr-45, Ser-64, and Thr-69, leading to dissociation of 4E-BP1 from eIF-4E. |
|
| Publications: |
3 |
Organism: |
Homo Sapiens |
| + |
GSK3B | down-regulates activity
phosphorylation
|
EIF4EBP1 |
0.373 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-236026 |
Thr37 |
PPGDYSTtPGGTLFS |
Homo sapiens |
|
| pmid |
sentence |
| 18701453 |
We found that gsk-3Beta phosphorylates and inactivates 4e-bp1, thereby increasing eif4e-dependent protein synthesis. upon stimulation, 4e-bp1 is phosphorylated on several threonine and serine residues, including thr-37/46 (36). This results in dissolution of the complex, freeing eif4e to bind with mrna cap to promote translation initiation. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-236660 |
Thr46 |
GGTLFSTtPGGTRII |
Homo sapiens |
|
| pmid |
sentence |
| 18701453 |
We found that gsk-3Beta phosphorylates and inactivates 4e-bp1, thereby increasing eif4e-dependent protein synthesis. upon stimulation, 4e-bp1 is phosphorylated on several threonine and serine residues, including thr-37/46 (36). This results in dissolution of the complex, freeing eif4e to bind with mrna cap to promote translation initiation. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-201699 |
Thr46 |
GGTLFSTtPGGTRII |
Homo sapiens |
|
| pmid |
sentence |
| 23584478 |
Glycogen synthase kinase-3_ positively regulates protein synthesis and cell proliferation through the regulation of translation initiation factor 4E-binding protein 1We found that GSK-3_ phosphorylates and inactivates 4E-BP1, thereby increasing eIF4E-dependent protein synthesis. |
|
| Publications: |
3 |
Organism: |
Homo Sapiens |
| Tissue: |
Kidney |
| Pathways: | Insulin Signaling, MTOR Signaling, PI3K/AKT Signaling |
| + |
CSNK1E | down-regulates
phosphorylation
|
EIF4EBP1 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-203240 |
Thr41 |
YSTTPGGtLFSTTPG |
Homo sapiens |
Breast Cancer Cell |
| pmid |
sentence |
| 24247720 |
Mechanistic investigations showed that ck1_ interacted with and phosphorylated 4e-bp1 at two novel sites t41 and t50, which were essential for 4e-bp1 inactivation along with increased mrna translation and cell proliferation. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-203276 |
Thr50 |
FSTTPGGtRIIYDRK |
Homo sapiens |
Breast Cancer Cell |
| pmid |
sentence |
| 24247720 |
Mechanistic investigations showed that ck1_ interacted with and phosphorylated 4e-bp1 at two novel sites t41 and t50, which were essential for 4e-bp1 inactivation along with increased mrna translation and cell proliferation. |
|
| Publications: |
2 |
Organism: |
Homo Sapiens |
| + |
MAPK1 | down-regulates
phosphorylation
|
EIF4EBP1 |
0.649 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-113563 |
Thr45 |
PGGTLFStTPGGTRI |
Homo sapiens |
|
| pmid |
sentence |
| 11777913 |
Phosphorylation of 4e-bp1 is mediated by the p38/msk1 pathway in response to uvb irradiation. In the present study we demonstrated that uvb induced 4e-bp1 phosphorylation at multiple sites, thr-36, thr-45, ser-64, and thr-69, leading to dissociation of 4e-bp1 from eif-4e. Uvb-induced phosphorylation of 4e-bp1 was blocked by p38 kinase inhibitors, pd169316 and sb202190, and msk1 inhibitor, h89, but not by mitogen-activated protein kinase kinase inhibitors, pd98059 or u0126. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
CyclinK/CDK13 | up-regulates activity 
phosphorylation
|
EIF4EBP1 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-273114 |
Thr46 |
GGTLFSTtPGGTRII |
Homo sapiens |
HCT-116 Cell |
| pmid |
sentence |
| 36882522 |
CDK13 directly phosphorylates 4E-BP1 at Thr46 and eIF4B at Ser422; genetically or pharmacologically inhibiting CDK13 disrupts mRNA translation. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
CDK13 | up-regulates activity
phosphorylation
|
EIF4EBP1 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-273113 |
Thr46 |
GGTLFSTtPGGTRII |
Homo sapiens |
HCT-116 Cell |
| pmid |
sentence |
| 36882522 |
CDK13 directly phosphorylates 4E-BP1 at Thr46 and eIF4B at Ser422; genetically or pharmacologically inhibiting CDK13 disrupts mRNA translation. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
CDK1 | down-regulates activity
phosphorylation
|
EIF4EBP1 |
0.407 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-110416 |
Thr70 |
RNSPVTKtPPRDLPT |
Homo sapiens |
|
| pmid |
sentence |
| 11553333 |
Phosphorylation of 4e-bp1 is critical in causing its dissociation from eif-4e, leaving 4e available to form translationally active eif-4f complexes, switching on mrna translation. We show that the cyclin-dependent kinase, cdc2, phosphorylates 4e-bp1 at thr-70 and that phosphorylation of this site is permissive for ser-65 phosphorylation. Crucially, the increased phosphorylation of 4e-bp1 during mitosis results in its complete dissociation from eif-4e. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
BRDT | up-regulates quantity
binding
|
EIF4EBP1 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-262049 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 33125143 |
It was revealed that eIF4EBP1 interacted with BRDT, a novel interacting protein. In addition, the present study further demonstrated that BRDT inhibitors PLX51107 and INCB054329 blocked the progression of RCC cells, along with suppressing eIF4EBP1 and c‑myc expression. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
MAPK14 | down-regulates 
|
EIF4EBP1 |
0.444 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-113566 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 11777913 |
Phosphorylation of 4e-bp1 is mediated by the p38/msk1 pathway in response to uvb irradiation. In the present study we demonstrated that uvb induced 4e-bp1 phosphorylation at multiple sites, thr-36, thr-45, ser-64, and thr-69, leading to dissociation of 4e-bp1 from eif-4e. Uvb-induced phosphorylation of 4e-bp1 was blocked by p38 kinase inhibitors, pd169316 and sb202190, and msk1 inhibitor, h89, but not by mitogen-activated protein kinase kinase inhibitors, pd98059 or u0126. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
Cullin 3-RBX1-Skp1 | down-regulates quantity by destabilization
polyubiquitination
|
EIF4EBP1 |
0.274 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-272051 |
|
|
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 22578813 |
We identified the KLHL25-CUL3 complex as the E3 ubiquitin ligase, which targets hypophosphorylated 4E-BP1. Thus, the activity of eIF4E is under homeostatic control via the regulation of the levels of its repressor protein 4E-BP1 through ubiquitination. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
EIF4EBP1 | down-regulates activity
binding
|
EIF4E |
0.938 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-167176 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 23584478 |
The rate-limiting factor for translation is eukaryotic translation initiation factor 4E (eIF4E), which is negatively regulated by eIF4E-binding protein 1 (4E-BP1). |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | COVID-19 Causal Network, Insulin Signaling, MTOR Signaling, PI3K/AKT Signaling, SARS-CoV STRESS GRANULES |
| + |
KLHL25 | down-regulates quantity by destabilization
binding
|
EIF4EBP1 |
0.417 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-272049 |
|
|
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 22578813 |
We identified the KLHL25-CUL3 complex as the E3 ubiquitin ligase, which targets hypophosphorylated 4E-BP1. Thus, the activity of eIF4E is under homeostatic control via the regulation of the levels of its repressor protein 4E-BP1 through ubiquitination. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
3.0
EIF4EBP1
- 
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