| + |
RAF1 | down-regulates 
phosphorylation
|
BAD |
0.647 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-155293 |
Ser118 |
GRELRRMsDEFVDSF |
Homo sapiens |
|
| pmid |
sentence |
| 17535812 |
The activation of several major anti-apoptotic signaling pathways correlates with an increase in the phosphorylation of bad on ser-112, ser-136, and ser-155. These phosphorylation events result in bad inactivation through sequestration by 14-3-3 proteins |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-81165 |
Ser75 |
EIRSRHSsYPAGTED |
Homo sapiens |
|
| pmid |
sentence |
| 15849194 |
Raf-1 protects cells from apoptosis, independently of its signals to MEK and ERK, by translocating to the mitochondria where it binds Bcl-2 and displaces BAD|Upon phosphorylation by Pak1, Raf-1 translocates to mitochondria and phosphorylates BAD at Ser-112. |
|
| Publications: |
2 |
Organism: |
Homo Sapiens |
| Pathways: | COVID-19 Causal Network |
| + |
RAF1 | down-regulates quantity by destabilization
phosphorylation
|
EEF1A2 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-276407 |
Ser21 |
GHVDSGKsTTTGHLI |
in vitro |
|
| pmid |
sentence |
| 22378069 |
Mass spectrometry identified in vitro S21 and T88 as phosphorylation sites mediated by B-Raf but not C-Raf on eEF1A1 whereas S21 was phosphorylated on eEF1A2 by both B- and C-Raf. |
|
| Publications: |
1 |
Organism: |
In Vitro |
| + |
RAF1 | up-regulates activity 
phosphorylation
|
MAP2K1 |
0.739 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-235987 |
Ser218 |
VSGQLIDsMANSFVG |
Homo sapiens |
|
| pmid |
sentence |
| 10359597 |
Among other effectors, active ras binds and activates the raf kinase, iniziating a kinase cascade involving serine phosporylation of mek1/2 (mapkk) and tyrosine and threonine phosphorylation of erk1/2 active raf phosphorylates mek phospholpeptide analysis demostrated that serine residues 218 and 222 of human mek1 are the primary sites for phosphorylation by c-raf. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-235991 |
Ser222 |
LIDSMANsFVGTRSY |
Homo sapiens |
|
| pmid |
sentence |
| 10359597 |
Among other effectors, active ras binds and activates the raf kinase, iniziating a kinase cascade involving serine phosporylation of mek1/2 (mapkk) and tyrosine and threonine phosphorylation of erk1/2 ras activation leads to raf and subsequently mek activation. Phospholipide analysis demostrated that serine residues 218 and 222 of human mek1 are the primary sites for phosphorylation by c-raf. |
|
| Publications: |
2 |
Organism: |
Homo Sapiens |
| Tissue: |
Ovary |
| + |
RAF1 | up-regulates
phosphorylation
|
MAP2K2 |
0.722 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-262292 |
Ser222 |
VSGQLIDsMANSFVG |
Homo sapiens |
|
| pmid |
sentence |
| 8157000 |
To understand the mechanism of activation of MAPKK, we have identified Ser217 and Ser221 of MAPKK1 as the sites phosphorylated by p74raf-1. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-36553 |
Ser226 |
LIDSMANsFVGTRSY |
Homo sapiens |
|
| pmid |
sentence |
| 8157000 |
To understand the mechanism of activation of MAPKK, we have identified Ser217 and Ser221 of MAPKK1 as the sites phosphorylated by p74raf-1. |
|
| Publications: |
2 |
Organism: |
Homo Sapiens |
| + |
PRKACA | down-regulates activity
phosphorylation
|
RAF1 |
0.487 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-250040 |
Ser233 |
VSSQHRYsTPHAFTF |
Chlorocebus aethiops |
|
| pmid |
sentence |
| 12801936 |
Protein kinase A blocks Raf-1 activity by stimulating 14-3-3 binding and blocking Raf-1 interaction with Ras. Cyclic AMP (cAMP) blocks Raf-1 activation by stimulating its phosphorylation on serine 43 (Ser43), serine 233 (Ser233), and serine 259 (Ser259). |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-250041 |
Ser259 |
SQRQRSTsTPNVHMV |
Chlorocebus aethiops |
COS Cell |
| pmid |
sentence |
| 12801936 |
Protein kinase A blocks Raf-1 activity by stimulating 14-3-3 binding and blocking Raf-1 interaction with Ras. Cyclic AMP (cAMP) blocks Raf-1 activation by stimulating its phosphorylation on serine 43 (Ser43), serine 233 (Ser233), and serine 259 (Ser259). |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-250039 |
Ser43 |
FGYQRRAsDDGKLTD |
Chlorocebus aethiops |
COS Cell |
| pmid |
sentence |
| 12801936 |
Protein kinase A blocks Raf-1 activity by stimulating 14-3-3 binding and blocking Raf-1 interaction with Ras. Cyclic AMP (cAMP) blocks Raf-1 activation by stimulating its phosphorylation on serine 43 (Ser43), serine 233 (Ser233), and serine 259 (Ser259). |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-86137 |
Ser621 |
PKINRSAsEPSLHRA |
Homo sapiens |
|
| pmid |
sentence |
| 11971957 |
We have mapped all camp-induced phosphorylation sites in raf-1, showing that serines 43, 259, and 621 are phosphorylated by pka in vitro and induced by camp in vivo |
|
| Publications: |
4 |
Organism: |
Chlorocebus Aethiops, Homo Sapiens |
| Pathways: | COVID-19 Causal Network |
| + |
PRKCA |
phosphorylation
|
RAF1 |
0.548 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-37466 |
Ser233 |
VSSQHRYsTPHAFTF |
Homo sapiens |
|
| pmid |
sentence |
| 12551925 |
For example, PKCα phosphorylates Raf-1 at serine 499 (13), but mutation of this residue did not impede activation of Raf-1 by the physiological stimulators Ras and Lck. Similarly, both v-Src and phorbol esters were able to activate Raf-1 even though the PKC phosphorylation sites at serine 497 and serine 499 were mutated to alanine (14). Thus, although some PKC phosphorylation sites on Raf-1 have been identified, these sites do not appear to be required for activation of Raf-1. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-37844 |
Ser497 |
ATVKSRWsGSQQVEQ |
Homo sapiens |
|
| pmid |
sentence |
| 12551925 |
For example, PKCα phosphorylates Raf-1 at serine 499 (13), but mutation of this residue did not impede activation of Raf-1 by the physiological stimulators Ras and Lck. Similarly, both v-Src and phorbol esters were able to activate Raf-1 even though the PKC phosphorylation sites at serine 497 and serine 499 were mutated to alanine (14). Thus, although some PKC phosphorylation sites on Raf-1 have been identified, these sites do not appear to be required for activation of Raf-1. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-97644 |
Ser499 |
VKSRWSGsQQVEQPT |
Homo sapiens |
|
| pmid |
sentence |
| 12551925 |
For example, PKCα phosphorylates Raf-1 at serine 499 (13), but mutation of this residue did not impede activation of Raf-1 by the physiological stimulators Ras and Lck. Similarly, both v-Src and phorbol esters were able to activate Raf-1 even though the PKC phosphorylation sites at serine 497 and serine 499 were mutated to alanine (14). Thus, although some PKC phosphorylation sites on Raf-1 have been identified, these sites do not appear to be required for activation of Raf-1. |
|
| Publications: |
3 |
Organism: |
Homo Sapiens |
| + |
AKT1 | down-regulates
phosphorylation
|
RAF1 |
0.691 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-147963 |
Ser259 |
SQRQRSTsTPNVHMV |
Homo sapiens |
Breast Cancer Cell, Prostate Gland Cancer Cell |
| pmid |
sentence |
| 16854453 |
Akt and protein kinase a (pka) phosphorylate s259 on raf-1 and inhibit its activity. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-252588 |
Ser259 |
SQRQRSTsTPNVHMV |
Homo sapiens |
Myoblast |
| pmid |
sentence |
| 10576741 |
Akt and protein kinase a (pka) phosphorylate s259 on raf-1 and inhibit its activity. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-252531 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 22798428 |
Akt negatively regulates the raf and gsk-3 kinases and the cell cycle regulatory transcription factor fkhr. |
|
| Publications: |
3 |
Organism: |
Homo Sapiens |
| Tissue: |
Muscle, Myotube |
| Pathways: | Adipogenesis |
| + |
AMPK | down-regulates
phosphorylation
|
RAF1 |
0.297 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-216523 |
Ser259 |
SQRQRSTsTPNVHMV |
Homo sapiens |
|
| pmid |
sentence |
| 11971957 |
Mutation of serine 259 increased the basal raf-1 activity and rendered it largely resistant to inhibition by pka. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
PRKACA | down-regulates
phosphorylation
|
RAF1 |
0.487 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-86141 |
Ser259 |
SQRQRSTsTPNVHMV |
Homo sapiens |
|
| pmid |
sentence |
| 11971957 |
Serines 43, 259, and 621 are phosphorylated by PKA in vitro and induced by cAMP in vivo.cAMP increased Raf-1 serine 259 phosphorylation in a PKA-dependent manner with kinetics that correlated with ERK deactivation. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-86145 |
Ser43 |
FGYQRRAsDDGKLTD |
Homo sapiens |
|
| pmid |
sentence |
| 11971957 |
Serine 43 phosphorylation decreased the binding to ras in serum-starved but not in mitogen-stimulated cells. However, the kinase activity of a rafs43a mutant was fully inhibited by pka. |
|
| Publications: |
2 |
Organism: |
Homo Sapiens |
| Pathways: | COVID-19 Causal Network |
| + |
AKT | down-regulates
phosphorylation
|
RAF1 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-244337 |
Ser259 |
SQRQRSTsTPNVHMV |
Homo sapiens |
Breast Cancer Cell, Prostate Gland Cancer Cell |
| pmid |
sentence |
| 16854453 |
Akt and protein kinase a (pka) phosphorylate s259 on raf-1 and inhibit its activity. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-72669 |
Ser259 |
SQRQRSTsTPNVHMV |
Homo sapiens |
Myoblast |
| pmid |
sentence |
| 10576741 |
The stage-specific inhibitory action of Akt correlated with its stage-specific ability to form a complex with Raf, suggesting the existence of differentially expressed mediators of an inhibitory Akt-Raf complex. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-244333 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 14967450 |
Akt negatively regulates the raf and gsk-3 kinases and the cell cycle regulatory transcription factor fkhr. |
|
| Publications: |
3 |
Organism: |
Homo Sapiens |
| Tissue: |
Muscle, Myotube |
| Pathways: | COVID-19 Causal Network, Insulin Signaling, Integrin Signaling |
| + |
PP2Ca_R1A_Bd | up-regulates activity
dephosphorylation
|
RAF1 |
0.506 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-243538 |
Ser259 |
SQRQRSTsTPNVHMV |
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 16239230 |
... the PP2A holoenzymes ABC and ABC act downstream of Ras and upstream of MEK1 to promote activation of this MAPK signaling cascade. Furthermore both PP2A holoenzymes were found to associate with Raf1 and catalyze dephosphorylation of inhibitory phospho-Ser-259. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
PRKAA1 | down-regulates
phosphorylation
|
RAF1 |
0.34 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-86133 |
Ser259 |
SQRQRSTsTPNVHMV |
Homo sapiens |
|
| pmid |
sentence |
| 11971957 |
Mutation of serine 259 increased the basal raf-1 activity and rendered it largely resistant to inhibition by pka. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-47148 |
Ser621 |
PKINRSAsEPSLHRA |
Homo sapiens |
|
| pmid |
sentence |
| 9091312 |
Ampk also phosphorylated full-length, kinase-defective raf-1 (k375m) to generate two [32p]phosphopeptides, one co-migrating with synthetic tryptic peptide containing phospho-ser621 and the other with phospho-ser259. The catalytic subunit of PKA also phosphorylated Ser621 in vitro, while its overexpression in intact cells resulted in increased phosphorylation of Ser621 and decreased activity of Raf-1. These results suggest that phosphorylation of Ser621 inactivates Raf-1, but do not prove that PKA is responsible for this in vivo. |
|
| Publications: |
2 |
Organism: |
Homo Sapiens |
| + |
PPP1CA | up-regulates activity
dephosphorylation
|
RAF1 |
0.271 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-251649 |
Ser259 |
SQRQRSTsTPNVHMV |
Homo sapiens |
|
| pmid |
sentence |
| 16630891 |
We have identified a complex comprised of Shoc2/Sur-8 and the catalytic subunit of protein phosphatase 1 (PP1c) as a highly specific M-Ras effector. M-Ras targets Shoc2-PP1c to stimulate Raf activity by dephosphorylating the S259 inhibitory site of Raf proteins |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Noonan syndrome |
| + |
PP2CA_R1A_R2A | up-regulates activity
dephosphorylation
|
RAF1 |
0.512 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-243534 |
Ser259 |
SQRQRSTsTPNVHMV |
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 16239230 |
... the PP2A holoenzymes ABC and ABC act downstream of Ras and upstream of MEK1 to promote activation of this MAPK signaling cascade. Furthermore both PP2A holoenzymes were found to associate with Raf1 and catalyze dephosphorylation of inhibitory phospho-Ser-259. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
MAPK3 | down-regulates activity
phosphorylation
|
RAF1 |
0.63 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-143688 |
Ser289 |
RSHSESAsPSALSSS |
Mus musculus |
|
| pmid |
sentence |
| 15664191 |
Here, we identify six residues of Raf-1 (S29, S43, S289, S296, S301, and S642) that become hyperphosphorylated in a manner coincident with Raf-1 inactivation. | Five of the identified sites are proline-directed targets of activated ERK, and phosphorylation of all six sites requires MEK signaling, indicating a negative feedback mechanism. Hyperphosphorylation of these six sites inhibits the Ras/Raf-1 interaction and desensitizes Raf-1 to additional stimuli.|FLAG-Raf-1 phosphorylated by activated ERK2 |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-143692 |
Ser296 |
SPSALSSsPNNLSPT |
Mus musculus |
|
| pmid |
sentence |
| 15664191 |
Here, we identify six residues of Raf-1 (S29, S43, S289, S296, S301, and S642) that become hyperphosphorylated in a manner coincident with Raf-1 inactivation. | Five of the identified sites are proline-directed targets of activated ERK, and phosphorylation of all six sites requires MEK signaling, indicating a negative feedback mechanism. Hyperphosphorylation of these six sites inhibits the Ras/Raf-1 interaction and desensitizes Raf-1 to additional stimuli.|FLAG-Raf-1 phosphorylated by activated ERK2 |
|
| Publications: |
2 |
Organism: |
Mus Musculus |
| + |
MAPK1 | down-regulates activity
phosphorylation
|
RAF1 |
0.624 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-249440 |
Ser289 |
RSHSESAsPSALSSS |
Mus musculus |
|
| pmid |
sentence |
| 15664191 |
Here, we identify six residues of Raf-1 (S29, S43, S289, S296, S301, and S642) that become hyperphosphorylated in a manner coincident with Raf-1 inactivation. | Five of the identified sites are proline-directed targets of activated ERK, and phosphorylation of all six sites requires MEK signaling, indicating a negative feedback mechanism. Hyperphosphorylation of these six sites inhibits the Ras/Raf-1 interaction and desensitizes Raf-1 to additional stimuli.|FLAG-Raf-1 phosphorylated by activated ERK2 |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-249441 |
Ser29 |
FDGSSCIsPTIVQQF |
Mus musculus |
NIH-3T3 Cell |
| pmid |
sentence |
| 15664191 |
Here, we identify six residues of Raf-1 (S29, S43, S289, S296, S301, and S642) that become hyperphosphorylated in a manner coincident with Raf-1 inactivation. | Five of the identified sites are proline-directed targets of activated ERK, and phosphorylation of all six sites requires MEK signaling, indicating a negative feedback mechanism. Hyperphosphorylation of these six sites inhibits the Ras/Raf-1 interaction and desensitizes Raf-1 to additional stimuli.|FLAG-Raf-1 phosphorylated by activated ERK2 |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-249442 |
Ser296 |
SPSALSSsPNNLSPT |
Mus musculus |
|
| pmid |
sentence |
| 15664191 |
Here, we identify six residues of Raf-1 (S29, S43, S289, S296, S301, and S642) that become hyperphosphorylated in a manner coincident with Raf-1 inactivation. | Five of the identified sites are proline-directed targets of activated ERK, and phosphorylation of all six sites requires MEK signaling, indicating a negative feedback mechanism. Hyperphosphorylation of these six sites inhibits the Ras/Raf-1 interaction and desensitizes Raf-1 to additional stimuli.|FLAG-Raf-1 phosphorylated by activated ERK2 |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-249443 |
Ser301 |
SSSPNNLsPTGWSQP |
Mus musculus |
NIH-3T3 Cell |
| pmid |
sentence |
| 15664191 |
Here, we identify six residues of Raf-1 (S29, S43, S289, S296, S301, and S642) that become hyperphosphorylated in a manner coincident with Raf-1 inactivation. | Five of the identified sites are proline-directed targets of activated ERK, and phosphorylation of all six sites requires MEK signaling, indicating a negative feedback mechanism. Hyperphosphorylation of these six sites inhibits the Ras/Raf-1 interaction and desensitizes Raf-1 to additional stimuli.|FLAG-Raf-1 phosphorylated by activated ERK2 |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-249439 |
Ser43 |
FGYQRRAsDDGKLTD |
Mus musculus |
NIH-3T3 Cell |
| pmid |
sentence |
| 15664191 |
Here, we identify six residues of Raf-1 (S29, S43, S289, S296, S301, and S642) that become hyperphosphorylated in a manner coincident with Raf-1 inactivation. | Five of the identified sites are proline-directed targets of activated ERK, and phosphorylation of all six sites requires MEK signaling, indicating a negative feedback mechanism. Hyperphosphorylation of these six sites inhibits the Ras/Raf-1 interaction and desensitizes Raf-1 to additional stimuli.|FLAG-Raf-1 phosphorylated by activated ERK2 |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-249444 |
Ser642 |
NACTLTTsPRLPVF |
Mus musculus |
NIH-3T3 Cell |
| pmid |
sentence |
| 15664191 |
Here, we identify six residues of Raf-1 (S29, S43, S289, S296, S301, and S642) that become hyperphosphorylated in a manner coincident with Raf-1 inactivation. | Five of the identified sites are proline-directed targets of activated ERK, and phosphorylation of all six sites requires MEK signaling, indicating a negative feedback mechanism. Hyperphosphorylation of these six sites inhibits the Ras/Raf-1 interaction and desensitizes Raf-1 to additional stimuli.|FLAG-Raf-1 phosphorylated by activated ERK2 |
|
| Publications: |
6 |
Organism: |
Mus Musculus |
| + |
ERK1/2 | down-regulates activity
phosphorylation
|
RAF1 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-244677 |
Ser289 |
RSHSESAsPSALSSS |
Mus musculus |
|
| pmid |
sentence |
| 15664191 |
Here, we identify six residues of Raf-1 (S29, S43, S289, S296, S301, and S642) that become hyperphosphorylated in a manner coincident with Raf-1 inactivation. | Five of the identified sites are proline-directed targets of activated ERK, and phosphorylation of all six sites requires MEK signaling, indicating a negative feedback mechanism. Hyperphosphorylation of these six sites inhibits the Ras/Raf-1 interaction and desensitizes Raf-1 to additional stimuli.|FLAG-Raf-1 phosphorylated by activated ERK2 |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-244681 |
Ser296 |
SPSALSSsPNNLSPT |
Mus musculus |
|
| pmid |
sentence |
| 15664191 |
Here, we identify six residues of Raf-1 (S29, S43, S289, S296, S301, and S642) that become hyperphosphorylated in a manner coincident with Raf-1 inactivation. | Five of the identified sites are proline-directed targets of activated ERK, and phosphorylation of all six sites requires MEK signaling, indicating a negative feedback mechanism. Hyperphosphorylation of these six sites inhibits the Ras/Raf-1 interaction and desensitizes Raf-1 to additional stimuli.|FLAG-Raf-1 phosphorylated by activated ERK2 |
|
| Publications: |
2 |
Organism: |
Mus Musculus |
| Pathways: | Adipogenesis, COVID-19 Causal Network, Insulin Signaling, Integrin Signaling, Noonan syndrome, Oxytocin signaling, SARS-CoV MAPK PERTURBATION |
| + |
ERK1/2 | down-regulates
phosphorylation
|
RAF1 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-244685 |
Ser301 |
SSSPNNLsPTGWSQP |
Homo sapiens |
|
| pmid |
sentence |
| 16407412 |
Using mass spectrometry, we identified raf-1 phosphorylation on three sp motif sites: s289/s296/s301. These sites were phosphorylated by extracellular signal-regulated kinase (erk)-1 in vitro, and their phosphorylation in vivo was dependent on endogenous erk activity. Functionally, erk-1 expression sustains raf-1 activation in a manner dependent on raf-1 phosphorylation on the identified sites, and s289/296/301a substitution markedly decreases the in vivo activity of raf-1 s259a. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-244688 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 9922370 |
Mapkerk1/2 is also able to phopshorylate the egf receptor, the ras exchange factor sos, mkkkraf1, and mkkmek1. The phosphorylation of each of these proteins by mapkerk1/2 is believed to reduce their catalytic activity |
|
| Publications: |
2 |
Organism: |
Homo Sapiens |
| Pathways: | Adipogenesis, COVID-19 Causal Network, Insulin Signaling, Integrin Signaling, Noonan syndrome, Oxytocin signaling, SARS-CoV MAPK PERTURBATION |
| + |
MAPK3 | down-regulates
phosphorylation
|
RAF1 |
0.63 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-143696 |
Ser301 |
SSSPNNLsPTGWSQP |
Homo sapiens |
|
| pmid |
sentence |
| 16407412 |
Using mass spectrometry, we identified raf-1 phosphorylation on three sp motif sites: s289/s296/s301. These sites were phosphorylated by extracellular signal-regulated kinase (erk)-1 in vitro, and their phosphorylation in vivo was dependent on endogenous erk activity. Functionally, erk-1 expression sustains raf-1 activation in a manner dependent on raf-1 phosphorylation on the identified sites, and s289/296/301a substitution markedly decreases the in vivo activity of raf-1 s259a. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-64172 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 9922370 |
Mapkerk1/2 is also able to phopshorylate the egf receptor, the ras exchange factor sos, mkkkraf1, and mkkmek1. The phosphorylation of each of these proteins by mapkerk1/2 is believed to reduce their catalytic activity. previous studies have shown that phosphorylation is required for raf-1 activation, and here, we identify six phosphorylation sites that contribute to the downregulation of raf-1 after mitogen stimulation. Five of the identified sites are proline-directed targets of activated erk |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-133345 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 15664191 |
Mapkerk1/2 is also able to phopshorylate the egf receptor, the ras exchange factor sos, mkkkraf1, and mkkmek1. The phosphorylation of each of these proteins by mapkerk1/2 is believed to reduce their catalytic activity. previous studies have shown that phosphorylation is required for raf-1 activation, and here, we identify six phosphorylation sites that contribute to the downregulation of raf-1 after mitogen stimulation. Five of the identified sites are proline-directed targets of activated erk |
|
| Publications: |
3 |
Organism: |
Homo Sapiens |
| + |
PHLPP1 | down-regulates activity
dephosphorylation
|
RAF1 |
0.276 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-237449 |
Ser338 |
RPRGQRDsSYYWEIE |
Mus musculus |
|
| pmid |
sentence |
| 24530606 |
PHLPP1 and PHLPP2 dephosphorylate RAF1 to reduce its signaling, increase the invasive and migratory activities of CRC cells, and activate the epithelial-mesenchymal transition. In Apc(Min) mice, loss of PHLPP1 promotes tumor progression. |
|
| Publications: |
1 |
Organism: |
Mus Musculus |
| + |
PKN1 | up-regulates
phosphorylation
|
RAF1 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-112549 |
Ser338 |
RPRGQRDsSYYWEIE |
Homo sapiens |
|
| pmid |
sentence |
| 11733498 |
Interaction between active pak1 and raf-1 is necessary for phosphorylation and activation of raf-1. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-135679 |
Ser339 |
PRGQRDSsYYWEIEA |
Homo sapiens |
|
| pmid |
sentence |
| 15849194 |
P21-activated kinase 1 (pak1)-dependent phosphorylation of raf-1 regulates its mitochondrial localization, phosphorylation of bad, and bcl-2 association. moreover, the mitochondrial translocation of raf-1 and the interaction between raf-1 and bcl-2 are regulated by raf-1 phosphorylation at ser-338/ser-339. |
|
| Publications: |
2 |
Organism: |
Homo Sapiens |
| + |
PPP5C | down-regulates activity
dephosphorylation
|
RAF1 |
0.451 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-248537 |
Ser338 |
RPRGQRDsSYYWEIE |
in vitro |
|
| pmid |
sentence |
| 16892053 |
Protein phosphatase 5 (PP5) was identified as an inactivator that associates with Raf-1 on growth factor stimulation and selectively dephosphorylates an essential activating site, Ser 338. The PP5-mediated dephosphorylation of Ser 338 inhibited Raf-1 activity and downstream signalling to MEK |
|
| Publications: |
1 |
Organism: |
In Vitro |
| + |
PLK1 | up-regulates activity
phosphorylation
|
RAF1 |
0.294 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-278190 |
Ser338 |
RPRGQRDsSYYWEIE |
Homo sapiens |
|
| pmid |
sentence |
| 27003818 |
An in vitro kinase assay demonstrated that PLK1 directly phosphorylated CRAF at S338 and S339, but not at S621 (XREF_FIG).|These results demonstrate that PLK1 increases the stability of CRAF protein by preventing proteasome degradation. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-278191 |
Ser339 |
PRGQRDSsYYWEIEA |
Homo sapiens |
|
| pmid |
sentence |
| 27003818 |
An in vitro kinase assay demonstrated that PLK1 directly phosphorylated CRAF at S338 and S339, but not at S621 (Figure 8C).|These results demonstrate that PLK1 increases the stability of CRAF protein by preventing proteasome degradation. |
|
| Publications: |
2 |
Organism: |
Homo Sapiens |
| + |
MAP2K1 | up-regulates activity
phosphorylation
|
RAF1 |
0.739 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-279627 |
Ser338 |
RPRGQRDsSYYWEIE |
Homo sapiens |
|
| pmid |
sentence |
| 23360980 |
In addition, though MEK-1 was able to induce C-Raf phosphorylation at the S338 site, which was shown to play a role in C-Raf activation by certain growth factors [ xref ], MEK-1 was able to bind and activate the S338/339A C-Raf mutant, suggesting that the MEK-1-induced C-Raf activation does not require phosphorylation at these sites ( xref , lanes 4, 5, left panel and lanes 6\u20139, right panel).|MEK-1-induced C-Raf activation is Ras independent. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
PAK6 | up-regulates activity
phosphorylation
|
RAF1 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-278971 |
Ser338 |
RPRGQRDsSYYWEIE |
Homo sapiens |
|
| pmid |
sentence |
| 18465753 |
PAK5 phosphorylates Raf-1 on serine 338 and stimulates Raf-1 activity. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
PAK1 | up-regulates
phosphorylation
|
RAF1 |
0.592 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-180808 |
Ser338 |
RPRGQRDsSYYWEIE |
Homo sapiens |
|
| pmid |
sentence |
| 18775988 |
P21-activated protein kinases (paks) are serine/threonine protein kinases that phosphorylate raf-1 at ser-338 and ser-339. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-180812 |
Ser339 |
PRGQRDSsYYWEIEA |
Homo sapiens |
|
| pmid |
sentence |
| 18775988 |
P21-activated protein kinases (paks) are serine/threonine protein kinases that phosphorylate raf-1 at ser-338 and ser-339. |
|
| Publications: |
2 |
Organism: |
Homo Sapiens |
| + |
PAK3 | up-regulates
phosphorylation
|
RAF1 |
0.544 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-62043 |
Ser338 |
RPRGQRDsSYYWEIE |
Homo sapiens |
|
| pmid |
sentence |
| 9823899 |
The protein kinase pak3 positively regulates raf-1 activity through phosphorylation of serine 338. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
PRKCA | down-regulates
phosphorylation
|
RAF1 |
0.548 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-34761 |
Ser43 |
FGYQRRAsDDGKLTD |
Homo sapiens |
|
| pmid |
sentence |
| 7935389 |
Pka can inhibit raf-1 function directly via phosphorylation of the raf-1 kinase domain |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
PRKCB | up-regulates
phosphorylation
|
RAF1 |
0.436 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-37474 |
Ser497 |
ATVKSRWsGSQQVEQ |
Homo sapiens |
|
| pmid |
sentence |
| 8288587 |
Pkc can effectively phosphorylate raf-1, this is a direct effect of activated pkc and not the result of raf-1 autophosphorylation. the sites of pkc-mediated raf-1 phosphorylation are deduced to be ser497 and ser619. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-37478 |
Ser619 |
SLPKINRsASEPSLH |
Homo sapiens |
|
| pmid |
sentence |
| 8288587 |
Pkc can effectively phosphorylate raf-1, this is a direct effect of activated pkc and not the result of raf-1 autophosphorylation. the sites of pkc-mediated raf-1 phosphorylation are deduced to be ser497 and ser619. |
|
| Publications: |
2 |
Organism: |
Homo Sapiens |
| + |
PRKCG | up-regulates
phosphorylation
|
RAF1 |
0.393 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-37541 |
Ser497 |
ATVKSRWsGSQQVEQ |
Homo sapiens |
|
| pmid |
sentence |
| 8288587 |
Pkc can effectively phosphorylate raf-1, this is a direct effect of activated pkc and not the result of raf-1 autophosphorylation. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-37545 |
Ser619 |
SLPKINRsASEPSLH |
Homo sapiens |
|
| pmid |
sentence |
| 8288587 |
Pkc can effectively phosphorylate raf-1, this is a direct effect of activated pkc and not the result of raf-1 autophosphorylation. |
|
| Publications: |
2 |
Organism: |
Homo Sapiens |
| + |
PRKCA | up-regulates
phosphorylation
|
RAF1 |
0.548 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-37470 |
Ser497 |
ATVKSRWsGSQQVEQ |
Homo sapiens |
|
| pmid |
sentence |
| 8288587 |
Pkc can effectively phosphorylate raf-1, this is a direct effect of activated pkc and not the result of raf-1 autophosphorylation. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-97648 |
Ser619 |
SLPKINRsASEPSLH |
Homo sapiens |
|
| pmid |
sentence |
| 12551925 |
Pkc can effectively phosphorylate raf-1, this is a direct effect of activated pkc and not the result of raf-1 autophosphorylation. |
|
| Publications: |
2 |
Organism: |
Homo Sapiens |
| + |
AMPK | up-regulates
phosphorylation
|
RAF1 |
0.297 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-216616 |
Ser621 |
PKINRSAsEPSLHRA |
Homo sapiens |
|
| pmid |
sentence |
| 9091312 |
Ampk also phosphorylated full-length, kinase-defective raf-1 (k375m) to generate two [32p]phosphopeptides, one co-migrating with synthetic tryptic peptide containing phospho-ser621 and the other with phospho-ser259 |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
RAF1 | up-regulates activity
phosphorylation
|
RAF1 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-235770 |
Ser621 |
PKINRSAsEPSLHRA |
Chlorocebus aethiops |
|
| pmid |
sentence |
| 19595761 |
We show that phosphorylation of s621 turns over rapidly and is enriched in the activated pool of endogenous raf-1. The phosphorylation on this site can be mediated by raf-1 itself but also by other kinase(s) |
|
| Publications: |
1 |
Organism: |
Chlorocebus Aethiops |
| Pathways: | Adipogenesis, COVID-19 Causal Network, Insulin Signaling, Integrin Signaling, Noonan syndrome, Oxytocin signaling, SARS-CoV MAPK PERTURBATION |
| + |
RAF1 |
phosphorylation
|
RAF1 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-248917 |
Thr268 |
PNVHMVStTLPVDSR |
in vitro |
|
| pmid |
sentence |
| 8349614 |
Furthermore, we find that Thr268 is the predominant Raf-1 residue phosphorylated in in vitro autokinase assays. |
|
| Publications: |
1 |
Organism: |
In Vitro |
| Pathways: | Adipogenesis, COVID-19 Causal Network, Insulin Signaling, Integrin Signaling, Noonan syndrome, Oxytocin signaling, SARS-CoV MAPK PERTURBATION |
| + |
KSR1 | up-regulates
phosphorylation
|
RAF1 |
0.644 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-85386 |
Thr269 |
NVHMVSTtLPVDSRM |
Homo sapiens |
|
| pmid |
sentence |
| 11134016 |
Here we show that phosphorylation of c-raf-1 on thr(269) by ksr is necessary for optimal activation in response to egf stimulation. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
RAF1 | down-regulates quantity by destabilization
phosphorylation
|
KLF10 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-276502 |
Thr93 |
TIPAFCLtPPYSPSD |
Homo sapiens |
A-549 Cell |
| pmid |
sentence |
| 23994618 |
RAF1 phosphorylates the Thr93 site of KLF10 in vivo. Since the phosphorylation of Thr93 enables KLF10 and PIN1 to bind, it seems likely that RAF-1 will have an effect on KLF10 stability that is similar to that of PIN1.PIN1 facilitates KLF10 protein degradation. ( |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
SRC | up-regulates
phosphorylation
|
RAF1 |
0.596 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-97635 |
Tyr340 |
RGQRDSSyYWEIEAS |
Homo sapiens |
|
| pmid |
sentence |
| 12551923 |
We also show that phosphorylation of raf-1 on serine 338 by pak1 and tyrosines 340 and 341 by src relieves autoinhibition and that this occurs through a specific decrease in the binding of the raf-1 regulatory domain to its catalytic domain. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-32081 |
Tyr340 |
RGQRDSSyYWEIEAS |
Homo sapiens |
|
| pmid |
sentence |
| 7692235 |
We also show that phosphorylation of raf-1 on serine 338 by pak1 and tyrosines 340 and 341 by src relieves autoinhibition and that this occurs through a specific decrease in the binding of the raf-1 regulatory domain to its catalytic domain. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-82150 |
Tyr340 |
RGQRDSSyYWEIEAS |
Homo sapiens |
|
| pmid |
sentence |
| 10998357 |
We also show that phosphorylation of raf-1 on serine 338 by pak1 and tyrosines 340 and 341 by src relieves autoinhibition and that this occurs through a specific decrease in the binding of the raf-1 regulatory domain to its catalytic domain. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-97639 |
Tyr341 |
GQRDSSYyWEIEASE |
Homo sapiens |
|
| pmid |
sentence |
| 12551923 |
We also show that phosphorylation of raf-1 on serine 338 by pak1 and tyrosines 340 and 341 by src relieves autoinhibition and that this occurs through a specific decrease in the binding of the raf-1 regulatory domain to its catalytic domain. |
|
| Publications: |
4 |
Organism: |
Homo Sapiens |
| Pathways: | Integrin Signaling |
| + |
JAK2 | up-regulates activity
phosphorylation
|
RAF1 |
0.607 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-251361 |
Tyr340 |
RGQRDSSyYWEIEAS |
Mus musculus |
CTLL-2 Cell |
| pmid |
sentence |
| 8876196 |
JAK2 phosphorylated Raf-1. e sites at 340/341 are indeed phosphorylated by JAK2 and that this phosphorylation represents a major component of the activation process. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-251362 |
Tyr341 |
GQRDSSYyWEIEASE |
Mus musculus |
CTLL-2 Cell |
| pmid |
sentence |
| 8876196 |
JAK2 phosphorylated Raf-1. e sites at 340/341 are indeed phosphorylated by JAK2 and that this phosphorylation represents a major component of the activation process. |
|
| Publications: |
2 |
Organism: |
Mus Musculus |
| + |
SPRY4 | down-regulates activity
binding
|
RAF1 |
0.437 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-253033 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 12717443 |
Here we show that mammalian Sprouty4 suppresses vascular epithelial growth factor (VEGF)-induced, Ras-independent activation of Raf1 but does not affect epidermal growth factor (EGF)-induced, Ras-dependent activation of Raf1. Sprouty4 binds to Raf1 through its carboxy-terminal cysteine-rich domain, and this binding is necessary for the inhibitory activity of Sprouty4. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
PDPK1 | up-regulates activity
phosphorylation
|
RAF1 |
0.313 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-280063 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 29575487 |
PDK1, but not PKCs, phosphorylate and activate Raf1 in MAPK pathway when platelets are stimulated with 2MeSADP. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Adipogenesis, Insulin Signaling |
| + |
HRAS | up-regulates
binding
|
RAF1 |
0.933 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-236656 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 21779497 |
The first RAS effector pathway to be identified was the RAF-MEK-ERK pathway. This pathway is an essential, shared element of mitogenic signaling involving tyrosine kinase receptors, leading to a wide range of cellular responses, including growth, differentiation, inflammation, and apoptosis.23 The RAF family of proteins (Raf-1, A-Raf, and B-Raf) is serine/threonine kinases that bind to the effector region of RAS-GTP, thus inducing translocation of the protein to the plasma membrane. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-235786 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 9020159 |
We have examined whether the other two members of the Raf family, A-Raf and B-Raf, are regulated in a similar way to Raf-1. A-Raf behaves like Raf-1, being weakly activated by oncogenic Ras more strongly activated by oncogenic Src, and these signals synergize to give maximal activation. B-Raf by contrast is strongly activated by oncogenic Ras alone and is not activated by oncogenic Src. |
|
| Publications: |
2 |
Organism: |
Homo Sapiens |
| Pathways: | Insulin Signaling, Integrin Signaling, Noonan syndrome, Oxytocin signaling |
| + |
HECTD3 | down-regulates quantity by destabilization
polyubiquitination
|
RAF1 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-272328 |
|
|
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 28636940 |
By western blot, we observed robust degradation of endogenous native CRAF in untransformed HEK293 cells treated with control siRNA 24 hr after the addition of AUY922, but this was substantially reduced in cells in which HECTD3 was knocked down, confirming that endogenous CRAF is a bona fide degradation target of HECTD3 |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
WDR83 | up-regulates
binding
|
RAF1 |
0.514 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-124476 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 15118098 |
Morg1 specifically associates with several components of the erk pathway, including mp1, raf-1, mek, and erk, and stabilizes their assembly into an oligomeric complex. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
sorafenib | down-regulates
chemical inhibition
|
RAF1 |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-174039 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 21654832 |
Inhibition of map kinases mek, jnk, p38, and multikinases (braf, craf, vegfp by sorafenib) in wm-115 and m14 human melanoma cell lines led to either significant reduction or complete inhibition of the plk-1 protein expression. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
PEBP1 | down-regulates
binding
|
RAF1 |
0.762 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-70838 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 10490027 |
Suppression of raf-1 kinase activity and map kinase by rkip. Rkip binds to raf-1, mek and erk, but not to ras. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
ZM 336372 | down-regulates
chemical inhibition
|
RAF1 |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-207911 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| Other |
|
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
sorafenib tosylate | down-regulates activity
chemical inhibition
|
RAF1 |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-259228 |
|
|
in vitro |
|
| pmid |
sentence |
| 16757355 |
This effort culminated in the identification of the clinical candidate BAY 43-9006 (Sorafenib, Nexavar), which has recently been approved by the FDA for advanced renal cell carcinoma in phase III clinical trials. Sorafenib inhibited the kinase activity of both C-RAF and B-RAF (wild type and V600E mutant). |
|
| Publications: |
1 |
Organism: |
In Vitro |
| + |
4-methyl-3-[[1-methyl-6-(3-pyridinyl)-4-pyrazolo[3,4-d]pyrimidinyl]amino]-N-[3-(trifluoromethyl)phenyl]benzamide | down-regulates
chemical inhibition
|
RAF1 |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-194922 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| Other |
|
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
PPP2R5D | up-regulates activity
binding
|
RAF1 |
0.438 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-243420 |
|
|
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 16239230 |
... the PP2A holoenzymes ABC and ABC act downstream of Ras and upstream of MEK1 to promote activation of this MAPK signaling cascade. Furthermore both PP2A holoenzymes were found to associate with Raf1 and catalyze dephosphorylation of inhibitory phospho-Ser-259. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
1-methyl-5-[[2-[5-(trifluoromethyl)-1H-imidazol-2-yl]-4-pyridinyl]oxy]-N-[4-(trifluoromethyl)phenyl]-2-benzimidazolamine | down-regulates
chemical inhibition
|
RAF1 |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-206385 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| Other |
|
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
RAF1 | down-regulates
binding
|
STK3/4 |
0.358 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-269942 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 15618521 |
Raf-1 prevents dimerization and phosphorylation of the activation loop of mst2 independently of its protein kinase activity.Raf-1 counteracts apoptosis by suppressing the activation of mammalian sterile 20-like kinase (mst2) |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
PPP2CA | up-regulates
dephosphorylation
|
RAF1 |
0.58 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-141170 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 16239230 |
Both pp2a holoenzymes were found to associate with raf1 and catalyze dephosphorylation of inhibitory phospho-ser-259. Together these findings indicate that pp2a abalphac and abdeltac holoenzymes function as positive regulators of raf1-mek1/2-erk1/2 signaling by targeting raf1. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Tissue: |
Kidney |
| Pathways: | COVID-19 Causal Network |
| + |
MAPK1 | down-regulates
phosphorylation
|
RAF1 |
0.624 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-64169 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 9922370 |
Mapkerk1/2 is also able to phopshorylate the egf receptor, the ras exchange factor sos, mkkkraf1, and mkkmek1. The phosphorylation of each of these proteins by mapkerk1/2 is believed to reduce their catalytic activity |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
CNKSR1 | up-regulates
binding
|
RAF1 |
0.706 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-135674 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 15845549 |
Here we demonstrate that the connector enhancer of ksr1, cnk1, mediates src-dependent tyrosine phosphorylation and activation of raf-1. Cnk1 binds preactivated raf-1 and activated src and forms a trimeric complex. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
dabrafenib | down-regulates activity
chemical inhibition
|
RAF1 |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-259218 |
|
|
in vitro |
|
| pmid |
sentence |
| 24720932 |
Dabrafenib is known to inhibit V600E, V600K and V600D BRAF enzymes with in vitro IC50 values of 0.65, 0.5 and 1.84 nM, respectively. Dabrafenib can inhibit wild-type BRAF and CRAF kinases with IC50 values of 3.2 and 5.0 nM. Other kinases (SIK1, NEK111 and LIMK1) can be inhibited by dabrafenib when administered in high concentrations |
|
| Publications: |
1 |
Organism: |
In Vitro |
| + |
2-chloro-5-(2-phenyl-5-pyridin-4-yl-1H-imidazol-4-yl)phenol | down-regulates
chemical inhibition
|
RAF1 |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-100358 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 12970777 |
The raf inhibitor l-779,450. This raf inhibitor was less effective on b-raf- or mek1-responsive cells, demonstrating the specificity of this drug. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
RAF1 | up-regulates activity
phosphorylation
|
XIAP |
0.504 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-279105 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 16964381 |
Interaction and stabilization of X-linked inhibitor of apoptosis by Raf-1 protein kinase.|We also demonstrate that Raf-1 phosphorylates XIAP in vitro and in vivo. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
KRAS | up-regulates
binding
|
RAF1 |
0.843 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-141641 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 16293107 |
Among other effectors, active ras binds and activates the raf kinase, iniziating a kinase cascade involving serine phosporylation of mek1/2 (mapkk) and tyrosine and threonine phosphorylation of erk1/2. the raf family of proteins (raf-1, a-raf, and b-raf) is serine/threonine kinases that bind to the effector region of ras-gtp, thus inducing translocation of the protein to the plasma membrane. Once there, raf proteins are activated and phosphorylated by different protein kinases.. Association of ras with the mapk kinase kinase, raf, initiates the raf mek erk map kinase cascade. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-78911 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 10882715 |
Among other effectors, active ras binds and activates the raf kinase, iniziating a kinase cascade involving serine phosporylation of mek1/2 (mapkk) and tyrosine and threonine phosphorylation of erk1/2. the raf family of proteins (raf-1, a-raf, and b-raf) is serine/threonine kinases that bind to the effector region of ras-gtp, thus inducing translocation of the protein to the plasma membrane. Once there, raf proteins are activated and phosphorylated by different protein kinases.. Association of ras with the mapk kinase kinase, raf, initiates the raf mek erk map kinase cascade. |
|
| Publications: |
2 |
Organism: |
Homo Sapiens |
| Pathways: | Adipogenesis, COVID-19 Causal Network, Noonan syndrome, SARS-CoV MAPK PERTURBATION |
| + |
KSR1 | up-regulates activity
binding
|
RAF1 |
0.644 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-273880 |
|
|
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 29433126 |
In mammals, RAF family kinases include three catalytically competent enzymes (ARAF, BRAF and CRAF) and two pseudokinases (KSR1 and KSR2) that have been described as scaffolds owing to their apparent ability to bridge RAF isoforms and their substrate, mitogen-activated protein kinase kinase (MEK).Kinase suppressor of Ras (KSR) pseudokinases were also shown to dimerize with kinase-competent RAFs to stimulate catalysis allosterically. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
NRAS | up-regulates
relocalization
|
RAF1 |
0.867 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-175231 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 21779497 |
The raf family of proteins (raf-1, a-raf, and b-raf) bind to the effector region of ras-gtp, thus inducing translocation of the protein to the plasma membrane. Once there, raf proteins are activated and phosphorylated by different protein kinases. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Noonan syndrome |
| + |
RAF1 | down-regulates
binding
|
MAP3K5 |
0.395 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-109023 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 11427728 |
Raf-1 interacts with the proapoptotic, stress-activated protein kinase ask1 (apoptosis signal-regulating kinase 1) in vitro and in vivo. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
regorafenib | down-regulates
chemical inhibition
|
RAF1 |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-206418 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| Other |
|
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
CDC25A | down-regulates
dephosphorylation
|
RAF1 |
0.396 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-32548 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 7744247 |
Cdc25a can act on substrates other than cdks, since it dephosphorylates the homeodomain transcription factor cut and interacts with and dephosphorylates the proto-oncogene raf-1, resulting in a significant decrease in raf-1 kinase activity |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
RAF1 | down-regulates
binding
|
STK4 |
0.272 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-191843 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 22898666 |
Raf1 binding to mst2 sarah domain interdicts mst2 homodimerization and autoactivation, and recruits protein phosphates 2a thereby promoting mst2 inactivation. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
PPP2R2A | up-regulates activity
binding
|
RAF1 |
0.455 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-243417 |
|
|
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 16239230 |
... the PP2A holoenzymes ABC and ABC act downstream of Ras and upstream of MEK1 to promote activation of this MAPK signaling cascade. Furthermore both PP2A holoenzymes were found to associate with Raf1 and catalyze dephosphorylation of inhibitory phospho-Ser-259. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
RAF1 | down-regulates activity
phosphorylation
|
RB1 |
0.568 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-279481 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 9819434 |
Further, Raf-1 was able to phosphorylate Rb in vitro quite efficiently.|Raf-1 can inactivate Rb function and can reverse Rb mediated repression of E2F1 transcription and cell proliferation efficiently. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
RAF1 | up-regulates activity
phosphorylation
|
MEK1/2 |
0.739 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-244945 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 11018021 |
The best characterized Raf substrates are MEK1 and MEK2. The activation of MEK1/2 by Raf is required to mediate many of the cellular responses to Raf activation, suggesting that MEK1/2 are the dominant Raf effector proteins. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Tissue: |
Ovary |
| Pathways: | Adipogenesis, COVID-19 Causal Network, Insulin Signaling, Integrin Signaling, Noonan syndrome, Oxytocin signaling, SARS-CoV MAPK PERTURBATION |
| + |
CNKSR2 | up-regulates
binding
|
RAF1 |
0.764 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-119039 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 14597674 |
We show cnk2 interacts with raf. cnk2 interacts with the gef domain of rlf and with both the regulatory and catalytic domains of raf. The raf interaction was also mapped to the carboxyl-terminal half of cnk2. Overexpression of cnk2 results in inhibition of the mapk signaling pathway. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
3-(2-cyanopropan-2-yl)-N-[4-methyl-3-[(3-methyl-4-oxo-6-quinazolinyl)amino]phenyl]benzamide | down-regulates
chemical inhibition
|
RAF1 |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-190146 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| Other |
|
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
KSR2 | up-regulates activity
binding
|
RAF1 |
0.594 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-273879 |
|
|
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 29433126 |
In mammals, RAF family kinases include three catalytically competent enzymes (ARAF, BRAF and CRAF) and two pseudokinases (KSR1 and KSR2) that have been described as scaffolds owing to their apparent ability to bridge RAF isoforms and their substrate, mitogen-activated protein kinase kinase (MEK).Kinase suppressor of Ras (KSR) pseudokinases were also shown to dimerize with kinase-competent RAFs to stimulate catalysis allosterically. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
RAF1 | down-regulates
binding
|
STK3 |
0.358 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-132824 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 15618521 |
Raf-1 prevents dimerization and phosphorylation of the activation loop of mst2 independently of its protein kinase activity.Raf-1 counteracts apoptosis by suppressing the activation of mammalian sterile 20-like kinase (mst2) |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
RAF1 | up-regulates
phosphorylation
|
MEK1/2 |
0.739 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-244952 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 11018021 |
The best characterized Raf substrates are MEK1 and MEK2. The activation of MEK1/2 by Raf is required to mediate many of the cellular responses to Raf activation, suggesting that MEK1/2 are the dominant Raf effector proteins. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Adipogenesis, COVID-19 Causal Network, Insulin Signaling, Integrin Signaling, Noonan syndrome, Oxytocin signaling, SARS-CoV MAPK PERTURBATION |
| + |
RAF1 | down-regulates activity
phosphorylation
|
PPP1R12A |
0.276 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-278979 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 22225925 |
In hESC, Raf-1 directly phosphorylates and inactivates MYPT1, and this process requires kinase active Raf-1 protein. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
AKT2 | down-regulates activity
phosphorylation
|
RAF1 |
0.445 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-235678 |
|
|
Homo sapiens |
Breast Cancer Cell |
| pmid |
sentence |
| 10576742 |
Akt (protein kinase b), a member of a different signaling pathway that also regulates these responses, interacted with raf and phosphorylated this protein at a highly conserved serine residue in its regulatory domain in vivo. This phosphorylation of raf by akt inhibited activation of the raf-mek-erk signaling pathway and shifted the cellular response in a human breast cancer cell line from cell cycle arrest to proliferation. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
Gbeta | down-regulates
phosphorylation
|
RAF1 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-270010 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 16407412 |
Using mass spectrometry, we identified raf-1 phosphorylation on three sp motif sites: s289/s296/s301. These sites were phosphorylated by extracellular signal-regulated kinase (erk)-1 in vitro, and their phosphorylation in vivo was dependent on endogenous erk activity. Functionally, erk-1 expression sustains raf-1 activation in a manner dependent on raf-1 phosphorylation on the identified sites, and s289/296/301a substitution markedly decreases the in vivo activity of raf-1 s259a. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
Raf265 derivative | down-regulates
chemical inhibition
|
RAF1 |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-206394 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| Other |
|
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
4.0
RAF1
- 
- 