| + |
MAPK3 | down-regulates activity 
phosphorylation
|
BRAF |
0.643 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-259921 |
Ser151 |
VARSNPKsPQKPIVR |
Homo sapiens |
Melanoma Cell |
| pmid |
sentence |
| 21478863 |
We show that overactivation of the MAPK pathway, induced by the oncogenic Ras in melanoma, induces constitutive phosphorylation of BRAF on Ser151 by ERK, which inhibits NRAS-BRAF interaction |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
MAPK1 | down-regulates activity
phosphorylation
|
BRAF |
0.627 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-259920 |
Ser151 |
VARSNPKsPQKPIVR |
Homo sapiens |
Melanoma Cell |
| pmid |
sentence |
| 21478863 |
We show that overactivation of the MAPK pathway, induced by the oncogenic Ras in melanoma, induces constitutive phosphorylation of BRAF on Ser151 by ERK, which inhibits NRAS-BRAF interaction |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-236388 |
Thr753 |
YACASPKtPIQAGGY |
Rattus norvegicus |
PC-12 Cell |
| pmid |
sentence |
| 16508002 |
Erk-induced phosphorylation of b-raf on t753 promoted the disassembly of raf heterodimers, and the mutation of t753 prolonged growth factor-induced heterodimerization. The b-raf t753a mutant enhanced differentiation of pc12 cells, which was previously shown to be dependent on sustained erk signaling. Site is critical for v-src dependent modulation of slk kinase activity. |
|
| Publications: |
2 |
Organism: |
Homo Sapiens, Rattus Norvegicus |
| + |
ERK1/2 | down-regulates activity
phosphorylation
|
BRAF |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-259919 |
Ser151 |
VARSNPKsPQKPIVR |
Homo sapiens |
Melanoma Cell |
| pmid |
sentence |
| 21478863 |
We show that overactivation of the MAPK pathway, induced by the oncogenic Ras in melanoma, induces constitutive phosphorylation of BRAF on Ser151 by ERK, which inhibits NRAS-BRAF interaction |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Acute Myeloid Leukemia, BCR-ABL in AML, FLT3 in AML, KIT in AML, AML_TRIPLETS, Colorectal Carcinoma, EGFR Signaling, ErbB receptors in cancer, FLT3-ITD signaling, Glioblastoma Multiforme, Hepatocellular Tumor, IL6 Signaling, Inhibition of Apoptosis, Luminal Breast Cancer, Malignant Melanoma, NPM1_new, Noonan syndrome, Non-small-cell lung cancer (NSCLC), Pancreatic ductal adenocarcinoma (PDA), PI3K/AKT Signaling, Rett syndrome, Rhabdomyosarcoma, RTKs in cancer, Thyroid cancer, T cell activation, VEGF Signaling |
| + |
BRAF | up-regulates activity 
phosphorylation
|
PAX3 |
0.308 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-278435 |
Ser205 |
APQSDEGsDIDSEPD |
Homo sapiens |
|
| pmid |
sentence |
| 27906130 |
BRAF activates PAX3 to control muscle precursor cell migration during forelimb muscle development.|We found that BRAF clearly induced phosphorylation of PAX3 at Ser205 in both cell types (XREF_FIG). |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Rhabdomyosarcoma |
| + |
BRAF | down-regulates quantity by destabilization
phosphorylation
|
EEF1A1 |
0.263 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-276404 |
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. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-276405 |
Thr88 |
ETSKYYVtIIDAPGH |
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: |
2 |
Organism: |
In Vitro |
| + |
BRAF | down-regulates quantity by destabilization
phosphorylation
|
EEF1A2 |
0.327 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-276406 |
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 |
| + |
BRAF | up-regulates activity
phosphorylation
|
MAP2K1 |
0.788 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-235475 |
Ser218 |
VSGQLIDsMANSFVG |
Mus musculus |
NIH-3T3 Cell |
| pmid |
sentence |
| 8131746 |
Activation of mek family kinases requires phosphorylation of two conserved ser/thr residueserine residues 218 and 222 of human mek1 are the primary sites for phosphorylation by c-raf. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-39054 |
Ser222 |
LIDSMANsFVGTRSY |
in vitro |
|
| pmid |
sentence |
| 8413257 |
Raf-1 phosphorylation of MEK activated it, as judged by its ability to stimulate the phosphorylation of myelin basic protein by glutathione S-transferase-ERK1. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-39058 |
Ser248 |
SVQSDIWsMGLSLVE |
in vitro |
|
| pmid |
sentence |
| 8413257 |
Raf-1 phosphorylation of MEK activated it, as judged by its ability to stimulate the phosphorylation of myelin basic protein by glutathione S-transferase-ERK1. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-39062 |
Ser252 |
DIWSMGLsLVEMAVG |
in vitro |
|
| pmid |
sentence |
| 8413257 |
Raf-1 phosphorylation of MEK activated it, as judged by its ability to stimulate the phosphorylation of myelin basic protein by glutathione S-transferase-ERK1. |
|
| Publications: |
4 |
Organism: |
Mus Musculus, In Vitro |
| + |
BRAF | up-regulates
phosphorylation
|
MAP2K2 |
0.75 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-42664 |
Ser222 |
VSGQLIDsMANSFVG |
Homo sapiens |
|
| pmid |
sentence |
| 8668348 |
We show that, consequently, b-raf interacts with mek-1 and mek-2 with a better affinity than does c-raf-1, thus strengthening the notion that b-raf is a stronger mek activator than c-raf-l. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-42668 |
Ser226 |
LIDSMANsFVGTRSY |
Homo sapiens |
|
| pmid |
sentence |
| 8668348 |
We show that, consequently, b-raf interacts with mek-1 and mek-2 with a better affinity than does c-raf-1, thus strengthening the notion that b-raf is a stronger mek activator than c-raf-l. |
|
| Publications: |
2 |
Organism: |
Homo Sapiens |
| Tissue: |
Brain |
| + |
AKT2 | down-regulates
phosphorylation
|
BRAF |
0.272 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-78681 |
Ser364 |
FGQRDRSsSAPNVHI |
Homo sapiens |
|
| pmid |
sentence |
| 10869359 |
We show that phosphorylation of b-raf by akt occurs at multiple residues within its amino terminal regulatory domain, at both the conserved and unique phosphorylation sites. Akt phosphorylated b-raf on s364 and s428 to inactivate its kinase activity b-raf contains three akt consensus sites, table i. One site, ser364 is conserved with c-raf;however, two sites, ser428 and thr439, are unique to b-raf |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-78685 |
Ser428 |
GPQRERKsSSSSEDR |
Homo sapiens |
|
| pmid |
sentence |
| 10869359 |
We show that phosphorylation of b-raf by akt occurs at multiple residues within its amino terminal regulatory domain, at both the conserved and unique phosphorylation sites. Akt phosphorylated b-raf on s364 and s428 to inactivate its kinase activity b-raf contains three akt consensus sites, table i. One site, ser364 is conserved with c-raf;however, two sites, ser428 and thr439, are unique to b-raf |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-78689 |
Thr440 |
EDRNRMKtLGRRDSS |
Homo sapiens |
|
| pmid |
sentence |
| 10869359 |
We show that phosphorylation of b-raf by akt occurs at multiple residues within its amino terminal regulatory domain, at both the conserved and unique phosphorylation sites. Akt phosphorylated b-raf on s364 and s428 to inactivate its kinase activity b-raf contains three akt consensus sites, table i. One site, ser364 is conserved with c-raf;however, two sites, ser428 and thr439, are unique to b-raf |
|
| Publications: |
3 |
Organism: |
Homo Sapiens |
| + |
AKT | down-regulates
phosphorylation
|
BRAF |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-244152 |
Ser364 |
FGQRDRSsSAPNVHI |
Homo sapiens |
|
| pmid |
sentence |
| 10869359 |
We show that phosphorylation of b-raf by akt occurs at multiple residues within its amino terminal regulatory domain, at both the conserved and unique phosphorylation sites. Akt phosphorylated b-raf on s364 and s428 to inactivate its kinase activity b-raf contains three akt consensus sites, table i. One site, ser364 is conserved with c-raf;however, two sites, ser428 and thr439, are unique to b-raf |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-244160 |
Ser428 |
GPQRERKsSSSSEDR |
Homo sapiens |
|
| pmid |
sentence |
| 10869359 |
We show that phosphorylation of b-raf by akt occurs at multiple residues within its amino terminal regulatory domain, at both the conserved and unique phosphorylation sites. Akt phosphorylated b-raf on s364 and s428 to inactivate its kinase activity b-raf contains three akt consensus sites, table i. One site, ser364 is conserved with c-raf;however, two sites, ser428 and thr439, are unique to b-raf |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-244156 |
Thr440 |
EDRNRMKtLGRRDSS |
Homo sapiens |
|
| pmid |
sentence |
| 10869359 |
We show that phosphorylation of b-raf by akt occurs at multiple residues within its amino terminal regulatory domain, at both the conserved and unique phosphorylation sites. Akt phosphorylated b-raf on s364 and s428 to inactivate its kinase activity b-raf contains three akt consensus sites, table i. One site, ser364 is conserved with c-raf;however, two sites, ser428 and thr439, are unique to b-raf |
|
| Publications: |
3 |
Organism: |
Homo Sapiens |
| Pathways: | Acute Myeloid Leukemia, BCR-ABL in AML, FLT3 in AML, KIT in AML, AML_TRIPLETS, EGFR Signaling, ErbB receptors in cancer, FLT3-ITD signaling, Glioblastoma Multiforme, Hepatocellular Tumor, Inhibition of Apoptosis, Luminal Breast Cancer, Malignant Melanoma, NPM1_new, Non-small-cell lung cancer (NSCLC), Pancreatic ductal adenocarcinoma (PDA), PI3K/AKT Signaling, Rhabdomyosarcoma, RTKs in cancer, Thyroid cancer, T cell activation, VEGF Signaling |
| + |
AKT3 | down-regulates
phosphorylation
|
BRAF |
0.29 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-78693 |
Ser364 |
FGQRDRSsSAPNVHI |
Homo sapiens |
|
| pmid |
sentence |
| 10869359 |
We show that phosphorylation of b-raf by akt occurs at multiple residues within its aminoterminal regulatory domain, at both the conserved and unique phosphorylation sites. Akt phosphorylated b-raf on s364 and s428 to inactivate its kinase activity. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-78697 |
Ser428 |
GPQRERKsSSSSEDR |
Homo sapiens |
|
| pmid |
sentence |
| 10869359 |
We show that phosphorylation of b-raf by akt occurs at multiple residues within its aminoterminal regulatory domain, at both the conserved and unique phosphorylation sites. Akt phosphorylated b-raf on s364 and s428 to inactivate its kinase activity. |
|
| Publications: |
2 |
Organism: |
Homo Sapiens |
| + |
AKT1 | down-regulates activity
phosphorylation
|
BRAF |
0.46 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-251471 |
Ser365 |
GQRDRSSsAPNVHIN |
Homo sapiens |
|
| pmid |
sentence |
| 10869359 |
Akt phosphorylates both S364 and S428. Akt downregulates B-Raf activity in vivo |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-251472 |
Ser429 |
PQRERKSsSSSEDRN |
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 10869359 |
Akt phosphorylates both S364 and S428. Akt downregulates B-Raf activity in vivo |
|
| Publications: |
2 |
Organism: |
Homo Sapiens |
| Pathways: | FLT3-ITD signaling, Glioblastoma Multiforme |
| + |
PRKACA | down-regulates activity
phosphorylation
|
BRAF |
0.634 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-259922 |
Ser429 |
PQRERKSsSSSEDRN |
Rattus norvegicus |
PC-12 Cell |
| pmid |
sentence |
| 11510412 |
The in vitro phosphorylation of a site unique to B-Raf (Ser429) has been proposed to be responsible for the negative regulation of the isoenzyme by Akt. Using phosphopetide mapping and site-directed mutagenesis we showed that Ser429 is phosphorylated upon cAMP elevation in PC12 cells and proposed that PKA is a major kinase phosphorylating the B-Raf-specific site in vivo |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-250339 |
Ser429 |
PQRERKSsSSSEDRN |
in vitro |
|
| pmid |
sentence |
| 11510412 |
Direct phosphorylation of B-Raf by PKA exerts a negative effect on its kinase activity, essentially via phosphorylation of Ser429 |
|
| Publications: |
2 |
Organism: |
Rattus Norvegicus, In Vitro |
| + |
BRAF | down-regulates activity
phosphorylation
|
BRAF |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-277498 |
Ser465 |
TVGQRIGsGSFGTVY |
Homo sapiens |
|
| pmid |
sentence |
| 31929109 |
We previously identified that BRAFWT can autophosphorylate its P-loop (Ser-465/Ser-467) to inactivate itself in the absence of native substrate MEK |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-277499 |
Ser467 |
GQRIGSGsFGTVYKG |
Homo sapiens |
|
| pmid |
sentence |
| 31929109 |
We previously identified that BRAFWT can autophosphorylate its P-loop (Ser-465/Ser-467) to inactivate itself in the absence of native substrate MEK |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-277255 |
Ser614 |
SHQFEQLsGSILWMA |
Homo sapiens |
HEK-293T Cell |
| pmid |
sentence |
| 27345148 |
The phosphorylation of S614 is mitogen inducible and the result of autophosphorylation. These data suggest that phosphorylation at this site is inhibitory, and part of the physiological shut-down mechanism of BRAF signalling. |
|
| Publications: |
3 |
Organism: |
Homo Sapiens |
| Pathways: | Acute Myeloid Leukemia, BCR-ABL in AML, FLT3 in AML, KIT in AML, AML_TRIPLETS, Colorectal Carcinoma, EGFR Signaling, ErbB receptors in cancer, FLT3-ITD signaling, Glioblastoma Multiforme, Hepatocellular Tumor, IL6 Signaling, Inhibition of Apoptosis, Luminal Breast Cancer, Malignant Melanoma, NPM1_new, Noonan syndrome, Non-small-cell lung cancer (NSCLC), Pancreatic ductal adenocarcinoma (PDA), PI3K/AKT Signaling, Rett syndrome, Rhabdomyosarcoma, RTKs in cancer, Thyroid cancer, T cell activation, VEGF Signaling |
| + |
BRAF | up-regulates quantity
phosphorylation
|
MAPK7 |
0.292 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-278352 |
Thr219 |
AEHQYFMtEYVATRW |
Homo sapiens |
|
| pmid |
sentence |
| 29483645 |
Our data indicate that oncogenic BRAF increases ERK5 protein level, phosphorylation at several residues and kinase activity.|Overexpression of oncogenic BRAF induced ERK5 phosphorylation at Thr218 and Tyr220, although to a lower level than that induced by MEK5DD. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-278353 |
Tyr221 |
HQYFMTEyVATRWYR |
Homo sapiens |
|
| pmid |
sentence |
| 29483645 |
Our data indicate that oncogenic BRAF increases ERK5 protein level, phosphorylation at several residues and kinase activity.|Overexpression of oncogenic BRAF induced ERK5 phosphorylation at Thr218 and Tyr220, although to a lower level than that induced by MEK5DD. |
|
| Publications: |
2 |
Organism: |
Homo Sapiens |
| + |
ERK1/2 | down-regulates
phosphorylation
|
BRAF |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-170339 |
Thr401 |
STTGLSAtPPASLPG |
Homo sapiens |
|
| pmid |
sentence |
| 21135229 |
We show that b-raf is a calcineurin substrate;among calcineurin target residues on b-raf is t401, a site of negative feedback phosphorylation by erk1/2. Blocking calcineurin activity in _ cells prevents dephosphorylation of b-raf t401 and decreases b-raf and erk1/2 activities. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Acute Myeloid Leukemia, BCR-ABL in AML, FLT3 in AML, KIT in AML, AML_TRIPLETS, Colorectal Carcinoma, EGFR Signaling, ErbB receptors in cancer, FLT3-ITD signaling, Glioblastoma Multiforme, Hepatocellular Tumor, IL6 Signaling, Inhibition of Apoptosis, Luminal Breast Cancer, Malignant Melanoma, NPM1_new, Noonan syndrome, Non-small-cell lung cancer (NSCLC), Pancreatic ductal adenocarcinoma (PDA), PI3K/AKT Signaling, Rett syndrome, Rhabdomyosarcoma, RTKs in cancer, Thyroid cancer, T cell activation, VEGF Signaling |
| + |
MAPK3 | down-regulates
phosphorylation
|
BRAF |
0.643 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-161819 |
Thr753 |
YACASPKtPIQAGGY |
Homo sapiens |
|
| pmid |
sentence |
| 19933846 |
Erk-induced phosphorylation of b-raf on t753 promoted the disassembly of raf heterodimers, and the mutation of t753 prolonged growth factor-induced heterodimerization. The b-raf t753a mutant enhanced differentiation of pc12 cells, which was previously shown to be dependent on sustained erk signaling. Site is critical for v-src dependent modulation of slk kinase activity. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-144827 |
Thr753 |
YACASPKtPIQAGGY |
Homo sapiens |
|
| pmid |
sentence |
| 16508002 |
Erk-induced phosphorylation of b-raf on t753 promoted the disassembly of raf heterodimers, and the mutation of t753 prolonged growth factor-induced heterodimerization. The b-raf t753a mutant enhanced differentiation of pc12 cells, which was previously shown to be dependent on sustained erk signaling. Site is critical for v-src dependent modulation of slk kinase activity. |
|
| Publications: |
2 |
Organism: |
Homo Sapiens |
| + |
1-methyl-5-[[2-[5-(trifluoromethyl)-1H-imidazol-2-yl]-4-pyridinyl]oxy]-N-[4-(trifluoromethyl)phenyl]-2-benzimidazolamine | down-regulates activity
chemical inhibition
|
BRAF |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-258097 |
|
|
in vitro |
|
| pmid |
sentence |
| 22037378 |
Our data set represents the most detailed comprehensive assessment of the reactivity of known and clinical kinase inhibitors across the kinome published to date. | The data also show that for at least 15 of the 27 kinases that are the primary, intended targets for the compounds tested and that are represented in the assay panel, selective inhibitors, as assessed by both absolute selectivity across the kinome and selectivity relative to the primary target, are among the 72 tested here. |
|
| Publications: |
1 |
Organism: |
In Vitro |
| + |
sorafenib | down-regulates activity
chemical inhibition
|
BRAF |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-258283 |
|
|
in vitro |
|
| pmid |
sentence |
| 22037378 |
Our data set represents the most detailed comprehensive assessment of the reactivity of known and clinical kinase inhibitors across the kinome published to date. | The data also show that for at least 15 of the 27 kinases that are the primary, intended targets for the compounds tested and that are represented in the assay panel, selective inhibitors, as assessed by both absolute selectivity across the kinome and selectivity relative to the primary target, are among the 72 tested here. |
|
| Publications: |
1 |
Organism: |
In Vitro |
| + |
BRAF | up-regulates activity 
|
ERK1/2 |
0.659 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-260082 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 21900390 |
RAF, a cytoplasmic serine-threonine protein kinase, is a member of the RAS-RAF-MEK-ERK cell-signaling pathway [also known as the MAP kinase (MAPK) pathway], and it plays an essential role in mediating cellular differentiation, proliferation, senescence, and survival in response to extracellular cues. Raf phosphorylates and activates MAP-ERK kinase (MEK), which phosphorylates and activates extracellular signal-regulated kinase (ERK). |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Acute Myeloid Leukemia, BCR-ABL in AML, FLT3 in AML, KIT in AML, AML_TRIPLETS, Colorectal Carcinoma, EGFR Signaling, ErbB receptors in cancer, FLT3-ITD signaling, Glioblastoma Multiforme, Hepatocellular Tumor, IL6 Signaling, Inhibition of Apoptosis, Luminal Breast Cancer, Malignant Melanoma, NPM1_new, Noonan syndrome, Non-small-cell lung cancer (NSCLC), Pancreatic ductal adenocarcinoma (PDA), PI3K/AKT Signaling, Rett syndrome, Rhabdomyosarcoma, RTKs in cancer, Thyroid cancer, T cell activation, VEGF Signaling |
| + |
regorafenib | down-regulates activity
chemical inhibition
|
BRAF |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-259176 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 26254357 |
A novel multi-kinase inhibitor, regorafenib (Figure 1), inhibits vascular endothelial growth factor receptor (VEGFR) 1, VEGFR2, and VEGFR3, that play key roles in angiogenesis, and fibroblast growth factor receptor (FGFR) 1, platelet-derived growth factor receptor-β (PDGFR-β), tyrosine kinase with immunoglobulin and epidermal growth factor homology domain 2 (TIE2) and the mutant oncogenic kinase KIT, RET, B-RAF |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
CCT239065 | down-regulates
chemical inhibition
|
BRAF |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-190907 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| Other |
|
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
HRAS | up-regulates
binding
|
BRAF |
0.878 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-235478 |
|
|
Mus musculus |
NIH-3T3 Cell |
| pmid |
sentence |
| 7706312 |
Association of B-Raf with immobilized Ras occurred independently of prior stimulation of cells with serum, suggesting that primarily the production of GTP-Ras by mitogen stimulation is critical for the formation of B-Raf_GTP-Ras complexes. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-160043 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 18098337 |
BRAF kinase is a downstream target of KRAS and activates the MAPK pathway. |
|
| Publications: |
2 |
Organism: |
Mus Musculus, Homo Sapiens |
| Pathways: | EGFR Signaling, ErbB receptors in cancer, Glioblastoma Multiforme, Hepatocellular Tumor, Noonan syndrome, Non-small-cell lung cancer (NSCLC), PI3K/AKT Signaling, Rett syndrome, RTKs in cancer, T cell activation, VEGF Signaling |
| + |
BRAF | up-regulates activity
phosphorylation
|
MEK1/2 |
0.788 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-244827 |
|
|
Mus musculus |
|
| pmid |
sentence |
| 8131746 |
Activation of mek family kinases requires phosphorylation of two conserved ser/thr residueserine residues 218 and 222 of human mek1 are the primary sites for phosphorylation by c-raf. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-244831 |
|
|
in vitro |
|
| pmid |
sentence |
| 8413257 |
Raf-1 phosphorylation of MEK activated it, as judged by its ability to stimulate the phosphorylation of myelin basic protein by glutathione S-transferase-ERK1. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-251988 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 21900390 |
BRAFV600E has been shown to initiate thyroid follicular cell transformation. The BRAFV600E mutation disrupts the hydrophobic interaction, enabling the BRAF kinase to fold into a catalytically active formation, resulting in an almost 500-fold increase in kinase activity. Mutant BRAF can dimerize and activate MEK without Ras activation. |
|
| Publications: |
3 |
Organism: |
Mus Musculus, In Vitro, Homo Sapiens |
| Pathways: | Acute Myeloid Leukemia, BCR-ABL in AML, FLT3 in AML, KIT in AML, AML_TRIPLETS, Colorectal Carcinoma, EGFR Signaling, ErbB receptors in cancer, FLT3-ITD signaling, Glioblastoma Multiforme, Hepatocellular Tumor, IL6 Signaling, Inhibition of Apoptosis, Luminal Breast Cancer, Malignant Melanoma, NPM1_new, Noonan syndrome, Non-small-cell lung cancer (NSCLC), Pancreatic ductal adenocarcinoma (PDA), PI3K/AKT Signaling, Rett syndrome, Rhabdomyosarcoma, RTKs in cancer, Thyroid cancer, T cell activation, VEGF Signaling |
| + |
N-[4-[(4-Ethylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl]-3-[(E)-2-(4-methoxy-1H-pyrrolo[2,3-b]pyridin-5-yl)ethenyl]-4-methylbenzamide | down-regulates activity
chemical inhibition
|
BRAF |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-261986 |
|
|
in vitro |
|
| pmid |
sentence |
| 32069833 |
HG6-64-1 is a specific BRAF inhibitor |
|
| Publications: |
1 |
Organism: |
In Vitro |
| + |
KSR2 | up-regulates activity
binding
|
BRAF |
0.616 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-273877 |
|
|
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 |
| + |
RIT1 | up-regulates activity
binding
|
BRAF |
0.548 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-251650 |
|
|
Mus musculus |
NIH-3T3 Cell |
| pmid |
sentence |
| 23791108 |
It is possible that RIT1 interacts with RAF1 and that gain-of-function mutations in RIT1 and RAF1 exert similar effects in heart development. |
|
| Publications: |
1 |
Organism: |
Mus Musculus |
| Pathways: | Noonan syndrome |
| + |
BRAF | up-regulates
phosphorylation
|
MEK1/2 |
0.788 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-244843 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 8668348 |
We show that, consequently, b-raf interacts with mek-1 and mek-2 with a better affinity than does c-raf-1, thus strengthening the notion that b-raf is a stronger mek activator than c-raf-l. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Acute Myeloid Leukemia, BCR-ABL in AML, FLT3 in AML, KIT in AML, AML_TRIPLETS, Colorectal Carcinoma, EGFR Signaling, ErbB receptors in cancer, FLT3-ITD signaling, Glioblastoma Multiforme, Hepatocellular Tumor, IL6 Signaling, Inhibition of Apoptosis, Luminal Breast Cancer, Malignant Melanoma, NPM1_new, Noonan syndrome, Non-small-cell lung cancer (NSCLC), Pancreatic ductal adenocarcinoma (PDA), PI3K/AKT Signaling, Rett syndrome, Rhabdomyosarcoma, RTKs in cancer, Thyroid cancer, T cell activation, VEGF Signaling |
| + |
KSR1 | up-regulates activity
binding
|
BRAF |
0.628 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-273878 |
|
|
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 |
| + |
Gbeta | down-regulates
phosphorylation
|
BRAF |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-270043 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 16508002 |
Erk-induced phosphorylation of b-raf on t753 promoted the disassembly of raf heterodimers, and the mutation of t753 prolonged growth factor-induced heterodimerization. The b-raf t753a mutant enhanced differentiation of pc12 cells, which was previously shown to be dependent on sustained erk signaling. Site is critical for v-src dependent modulation of slk kinase activity. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
BRAF | down-regulates quantity by repression
transcriptional regulation
|
SLC5A5 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-251989 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 19861538 |
The BRAFV600E oncogene induces transforming growth factor beta secretion leading to sodium iodide symporter repression and increased malignancy in thyroid cancer. BRAF induces TGFβ secretion leading to NIS repression in a MEK-ERK–independent manner but cooperating with the MEK-ERK pathway to induce strong tumor invasion, two major traits acquired during PTC progression. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Thyroid cancer |
| + |
PPP1CA | up-regulates activity
dephosphorylation
|
BRAF |
0.295 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-277160 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 29335436 |
To address whether PP1\u03b1 activates B-Raf through these inhibitory sites, we made use of B-Raf protein mutants in which an individual inhibitory site, as well as all four sites (4A), were mutated to alanine.|We confirmed that GST-B-Raf was phosphorylated by ERK2 in vitro xref , mainly on S151 and T753 (Fig.\u00a0 xref ), and found that PP1\u03b1 dephosphorylated B-Raf on both ERK phosphorylation sites (Fig.\u00a0 xref ). |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Noonan syndrome |
| + |
BRAF | up-regulates quantity
relocalization
|
TGFB1 |
0.251 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-251987 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 19861538 |
The BRAFV600E oncogene induces transforming growth factor beta secretion leading to sodium iodide symporter repression and increased malignancy in thyroid cancer. BRAF induces TGFβ secretion leading to NIS repression in a MEK-ERK–independent manner but cooperating with the MEK-ERK pathway to induce strong tumor invasion, two major traits acquired during PTC progression. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Colorectal Carcinoma, Thyroid cancer |
| + |
RNF149 | down-regulates quantity by destabilization
polyubiquitination
|
BRAF |
0.338 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-272043 |
|
|
Homo sapiens |
HCT-116 Cell |
| pmid |
sentence |
| 22628551 |
We showed that RNF149 bound directly to the C-terminal kinase-containing domain of wild-type BRAF and induced ubiquitination, followed by proteasome-dependent degradation, of the latter protein. Functionally, RNF149 attenuated the increase in cell growth induced by wild-type BRAF. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
KRAS | up-regulates activity
binding
|
BRAF |
0.876 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-156906 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 21779497 |
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. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Acute Myeloid Leukemia, BCR-ABL in AML, FLT3 in AML, Colorectal Carcinoma, FLT3-ITD signaling, Glioblastoma Multiforme, Luminal Breast Cancer, Noonan syndrome, Non-small-cell lung cancer (NSCLC), Pancreatic ductal adenocarcinoma (PDA), Rhabdomyosarcoma, Thyroid cancer |
| + |
NRAS | up-regulates activity
binding
|
BRAF |
0.854 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-175219 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 21779497 |
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. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Acute Myeloid Leukemia, KIT in AML, AML_TRIPLETS, IL6 Signaling, Inhibition of Apoptosis, Malignant Melanoma, NPM1_new, Noonan syndrome |
| + |
HRAS | up-regulates activity
binding
|
BRAF |
0.878 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-147327 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 21779497 |
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. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | EGFR Signaling, ErbB receptors in cancer, Glioblastoma Multiforme, Hepatocellular Tumor, Noonan syndrome, Non-small-cell lung cancer (NSCLC), PI3K/AKT Signaling, Rett syndrome, RTKs in cancer, T cell activation, VEGF Signaling |
| + |
dabrafenib | down-regulates activity
chemical inhibition
|
BRAF |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-259215 |
|
|
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 |
| + |
sorafenib tosylate | down-regulates activity
chemical inhibition
|
BRAF |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-259220 |
|
|
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 |
| + |
RAP1A | up-regulates activity
binding
|
BRAF |
0.691 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-276608 |
|
|
Homo sapiens |
HEK-293T Cell |
| pmid |
sentence |
| 24290981 |
Our data are consistent with a pathway involving the cAMP-mediated activation of Rapgef2, which then stimulates Rap1, leading to increases in B-Raf, MEK, and ERK activity.Increased intracellular concentrations of cAMP enhanced the Rapgef2-dependent activation of Rap1, which in turn associated with B-Raf to enable the activation of ERK and subsequent neuronal- and endocrine-specific cellular outcomes, such as induction of neuroendocrine-specific genes and extension of neuritic processes (neuritogenesis). |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
vemurafenib | down-regulates activity
chemical inhibition
|
BRAF |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-259281 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 23094782 |
Metastatic melanoma is an aggressive disease resistant to chemotherapy. Recent clinical trials have reported improved survival for two novel agents; ipilimumab, a humanized, IgG1 monoclonal antibody that blocks cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and vemurafenib , a BRAF (v-raf murine sarcoma viral oncogene homolog B1) inhibitor targeting an activating mutation in the serine-threonine-protein kinase BRAF gene. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
5-[1-(2-hydroxyethyl)-3-pyridin-4-yl-4-pyrazolyl]-2,3-dihydroinden-1-one oxime | down-regulates activity
chemical inhibition
|
BRAF |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-258112 |
|
|
in vitro |
|
| pmid |
sentence |
| 22037378 |
Our data set represents the most detailed comprehensive assessment of the reactivity of known and clinical kinase inhibitors across the kinome published to date. | The data also show that for at least 15 of the 27 kinases that are the primary, intended targets for the compounds tested and that are represented in the assay panel, selective inhibitors, as assessed by both absolute selectivity across the kinome and selectivity relative to the primary target, are among the 72 tested here. |
|
| Publications: |
1 |
Organism: |
In Vitro |
| + |
GDC-0879 | down-regulates
chemical inhibition
|
BRAF |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-192592 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| Other |
|
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
BRAF | up-regulates quantity by expression
transcriptional regulation
|
NFE2L2 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-267362 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 29731393 |
Oncogenic proteins that regulate proliferation, such as KRAS, BRAF, and MYC increase the transcription of NRF2 |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Hepatocellular Tumor |
| + |
BRAF | up-regulates
|
Glycolysis |
0.7 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-259373 |
|
|
Homo sapiens |
Colonic Cancer Cell Line |
| pmid |
sentence |
| 27340238 |
These alterations corresponded to mutant KRAS and BRAF-dependent increases in glucose uptake and lactate production. Metabolic reprogramming and glucose conversion to lactate in RKO cells were proportional to levels of BRAF V600E protein. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
PLX-4720 | down-regulates activity
chemical inhibition
|
BRAF |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-258267 |
|
|
in vitro |
|
| pmid |
sentence |
| 22037378 |
Our data set represents the most detailed comprehensive assessment of the reactivity of known and clinical kinase inhibitors across the kinome published to date. | The data also show that for at least 15 of the 27 kinases that are the primary, intended targets for the compounds tested and that are represented in the assay panel, selective inhibitors, as assessed by both absolute selectivity across the kinome and selectivity relative to the primary target, are among the 72 tested here. |
|
| Publications: |
1 |
Organism: |
In Vitro |
| + |
sorafenib | down-regulates
chemical inhibition
|
BRAF |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-174036 |
|
|
Homo sapiens |
Melanoma Cell |
| 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 |
BRAF
3.0