Relation Results

Summary

Name BRAF
Full Name Serine/threonine-protein kinase B-raf
Synonyms Proto-oncogene B-Raf, p94, v-Raf murine sarcoma viral oncogene homolog B1 | BRAF1, RAFB1
Primary ID P15056
Links - -
Type protein
Relations 67
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, GPCR_CRC, GPCR_HCC, Hepatocellular Tumor, IL6 Signaling, Inhibition of Apoptosis, Luminal Breast Cancer, LIF in PDAC, Mitochondrial dynamics in T cell exhaustion, 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
Inhibitors regorafenib; 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; 1-methyl-5-[[2-[5-(trifluoromethyl)-1H-imidazol-2-yl]-4-pyridinyl]oxy]-N-[4-(trifluoromethyl)phenyl]-2-benzimidazolamine; sorafenib; CCT239065; 5-[1-(2-hydroxyethyl)-3-pyridin-4-yl-4-pyrazolyl]-2,3-dihydroinden-1-one oxime; PLX-4720; GDC-0879; dabrafenib; sorafenib tosylate; vemurafenib
Function Protein kinase involved in the transduction of mitogenic signals from the cell membrane to the nucleus (Probable). Phosphorylates MAP2K1, and thereby ...
View More

Viewer

Type: Score: Layout: SPV 
0.6260.6420.20.3090.3280.2630.7870.7480.2730.290.20.460.6310.20.2920.80.20.70.7870.80.80.80.8540.6580.80.20.8780.2510.8760.5470.6890.80.20.6270.2950.80.6140.3380.80.80.80.8MAPK1BRAFMAPK3ERK1/2PAX3EEF1A2EEF1A1MAP2K1MAP2K2AKT2AKT3AKTAKT1PRKACAMAPK7regorafenibNFE2L2GlycolysisMEK1/2N-[4-[(4-Ethylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl]-3-[(E)-2-(4-methoxy-1H-pyrrolo[2,3-b]pyridin-5-yl)ethenyl]-4-methylbenzamide1-methyl-5-[[2-[5-(trifluoromethyl)-1H-imidazol-2-yl]-4-pyridinyl]oxy]-N-[4-(trifluoromethyl)phenyl]-2-benzimidazolaminesorafenibNRASCCT239065GbetaHRASTGFB1KRASRIT1RAP1A5-[1-(2-hydroxyethyl)-3-pyridin-4-yl-4-pyrazolyl]-2,3-dihydroinden-1-one oximeSLC5A5KSR1PPP1CAPLX-4720KSR2RNF149GDC-0879dabrafenibsorafenib tosylatevemurafenib

Search Tools

Refine search:

  • by mechanism


  • by effect
  • by organism:


  • by tissue:


  • by cell-line

▶Modifications Tables

Relations
Regulator
Mechanism
target
score ℹ
+ MAPK1down-regulates activity img/direct_inhibition.png phosphorylation BRAF 0.626
Identifier Residue Sequence Organism Cell Line
SIGNOR-259920 Ser151 VARSNPKsPQKPIVR Homo sapiens Melanoma Cell
pmid sentence
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
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
+ MAPK3down-regulates activity img/direct_inhibition.png phosphorylation BRAF 0.642
Identifier Residue Sequence Organism Cell Line
SIGNOR-259921 Ser151 VARSNPKsPQKPIVR Homo sapiens Melanoma Cell
pmid sentence
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
+ ERK1/2down-regulates activity img/direct_inhibition.png phosphorylation BRAF 0.2
Identifier Residue Sequence Organism Cell Line
SIGNOR-259919 Ser151 VARSNPKsPQKPIVR Homo sapiens Melanoma Cell
pmid sentence
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
+ BRAFup-regulates activity img/direct-activation.png phosphorylation PAX3 0.309
Identifier Residue Sequence Organism Cell Line
SIGNOR-278435 Ser205 APQSDEGsDIDSEPD Homo sapiens
pmid sentence
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
+ BRAFdown-regulates quantity by destabilization img/direct_inhibition.png phosphorylation EEF1A2 0.328
Identifier Residue Sequence Organism Cell Line
SIGNOR-276406 Ser21 GHVDSGKsTTTGHLI in vitro
pmid sentence
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
+ BRAFdown-regulates quantity by destabilization img/direct_inhibition.png phosphorylation EEF1A1 0.263
Identifier Residue Sequence Organism Cell Line
SIGNOR-276404 Ser21 GHVDSGKsTTTGHLI in vitro
pmid sentence
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
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
+ BRAFup-regulates activity img/direct-activation.png phosphorylation MAP2K1 0.787
Identifier Residue Sequence Organism Cell Line
SIGNOR-235475 Ser218 VSGQLIDsMANSFVG Mus musculus NIH-3T3 Cell
pmid sentence
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
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
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
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
+ BRAFup-regulates img/direct-activation.png phosphorylation MAP2K2 0.748
Identifier Residue Sequence Organism Cell Line
SIGNOR-42664 Ser222 VSGQLIDsMANSFVG Homo sapiens
pmid sentence
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
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
+ AKT2down-regulates img/direct_inhibition.png phosphorylation BRAF 0.273
Identifier Residue Sequence Organism Cell Line
SIGNOR-78681 Ser364 FGQRDRSsSAPNVHI Homo sapiens
pmid sentence
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
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
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
+ AKT3down-regulates img/direct_inhibition.png phosphorylation BRAF 0.29
Identifier Residue Sequence Organism Cell Line
SIGNOR-78693 Ser364 FGQRDRSsSAPNVHI Homo sapiens
pmid sentence
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
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
+ AKTdown-regulates img/direct_inhibition.png phosphorylation BRAF 0.2
Identifier Residue Sequence Organism Cell Line
SIGNOR-244152 Ser364 FGQRDRSsSAPNVHI Homo sapiens
pmid sentence
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
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
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
+ AKT1down-regulates activity img/direct_inhibition.png phosphorylation BRAF 0.46
Identifier Residue Sequence Organism Cell Line
SIGNOR-251471 Ser365 GQRDRSSsAPNVHIN Homo sapiens
pmid sentence
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
Akt phosphorylates both S364 and S428. Akt downregulates B-Raf activity in vivo
Publications: 2 Organism: Homo Sapiens
Pathways:FLT3-ITD signaling, Glioblastoma Multiforme
+ PRKACAdown-regulates activity img/direct_inhibition.png phosphorylation BRAF 0.631
Identifier Residue Sequence Organism Cell Line
SIGNOR-259922 Ser429 PQRERKSsSSSEDRN Rattus norvegicus PC-12 Cell
pmid sentence
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
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
+ BRAFdown-regulates activity img/direct_inhibition.png phosphorylation BRAF 0.2
Identifier Residue Sequence Organism Cell Line
SIGNOR-277498 Ser465 TVGQRIGsGSFGTVY Homo sapiens
pmid sentence
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
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
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
+ BRAFup-regulates quantity img/direct-activation.png phosphorylation MAPK7 0.292
Identifier Residue Sequence Organism Cell Line
SIGNOR-278352 Thr219 AEHQYFMtEYVATRW Homo sapiens
pmid sentence
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
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
+ ERK1/2down-regulates img/direct_inhibition.png phosphorylation BRAF 0.2
Identifier Residue Sequence Organism Cell Line
SIGNOR-170339 Thr401 STTGLSAtPPASLPG Homo sapiens
pmid sentence
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
+ MAPK3down-regulates img/direct_inhibition.png phosphorylation BRAF 0.642
Identifier Residue Sequence Organism Cell Line
SIGNOR-161819 Thr753 YACASPKtPIQAGGY Homo sapiens
pmid sentence
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
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
+ regorafenibdown-regulates activity img/direct_inhibition.png chemical inhibition BRAF 0.8
Identifier Residue Sequence Organism Cell Line
SIGNOR-259176 Homo sapiens
pmid sentence
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
+ BRAFup-regulates quantity by expression img/indirect-activation.png transcriptional regulation NFE2L2 0.2
Identifier Residue Sequence Organism Cell Line
SIGNOR-267362 Homo sapiens
pmid sentence
Oncogenic proteins that regulate proliferation, such as KRAS, BRAF, and MYC increase the transcription of NRF2
Publications: 1 Organism: Homo Sapiens
Pathways:Hepatocellular Tumor
+ BRAFup-regulates img/indirect-activation.png Glycolysis 0.7
Identifier Residue Sequence Organism Cell Line
SIGNOR-259373 Homo sapiens Colonic Cancer Cell Line
pmid sentence
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
+ BRAFup-regulates activity img/direct-activation.png phosphorylation MEK1/2 0.787
Identifier Residue Sequence Organism Cell Line
SIGNOR-244827 Mus musculus
pmid sentence
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
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
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-methylbenzamidedown-regulates activity img/direct_inhibition.png chemical inhibition BRAF 0.8
Identifier Residue Sequence Organism Cell Line
SIGNOR-261986 in vitro
pmid sentence
HG6-64-1 is a specific BRAF inhibitor
Publications: 1 Organism: In Vitro
+ 1-methyl-5-[[2-[5-(trifluoromethyl)-1H-imidazol-2-yl]-4-pyridinyl]oxy]-N-[4-(trifluoromethyl)phenyl]-2-benzimidazolaminedown-regulates activity img/direct_inhibition.png chemical inhibition BRAF 0.8
Identifier Residue Sequence Organism Cell Line
SIGNOR-258097 in vitro
pmid sentence
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
+ sorafenibdown-regulates activity img/direct_inhibition.png chemical inhibition BRAF 0.8
Identifier Residue Sequence Organism Cell Line
SIGNOR-258283 in vitro
pmid sentence
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
+ NRASup-regulates activity img/direct-activation.png binding BRAF 0.854
Identifier Residue Sequence Organism Cell Line
SIGNOR-175219 Homo sapiens
pmid sentence
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
+ BRAFup-regulates activity img/indirect-activation.png ERK1/2 0.658
Identifier Residue Sequence Organism Cell Line
SIGNOR-260082 Homo sapiens
pmid sentence
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
+ CCT239065down-regulates img/direct_inhibition.png chemical inhibition BRAF 0.8
Identifier Residue Sequence Organism Cell Line
SIGNOR-190907 Homo sapiens
pmid sentence
Publications: 1 Organism: Homo Sapiens
+ Gbetadown-regulates img/direct_inhibition.png phosphorylation BRAF 0.2
Identifier Residue Sequence Organism Cell Line
SIGNOR-270043 Homo sapiens
pmid sentence
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
+ HRASup-regulates img/direct-activation.png binding BRAF 0.878
Identifier Residue Sequence Organism Cell Line
SIGNOR-235478 Mus musculus NIH-3T3 Cell
pmid sentence
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
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
+ BRAFup-regulates quantity img/indirect-activation.png relocalization TGFB1 0.251
Identifier Residue Sequence Organism Cell Line
SIGNOR-251987 Homo sapiens
pmid sentence
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
+ BRAFup-regulates img/direct-activation.png phosphorylation MEK1/2 0.787
Identifier Residue Sequence Organism Cell Line
SIGNOR-244843 Homo sapiens
pmid sentence
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
+ KRASup-regulates activity img/direct-activation.png binding BRAF 0.876
Identifier Residue Sequence Organism Cell Line
SIGNOR-156906 Homo sapiens
pmid sentence
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
+ RIT1up-regulates activity img/direct-activation.png binding BRAF 0.547
Identifier Residue Sequence Organism Cell Line
SIGNOR-251650 Mus musculus NIH-3T3 Cell
pmid sentence
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
+ RAP1Aup-regulates activity img/direct-activation.png binding BRAF 0.689
Identifier Residue Sequence Organism Cell Line
SIGNOR-276608 Homo sapiens HEK-293T Cell
pmid sentence
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
+ 5-[1-(2-hydroxyethyl)-3-pyridin-4-yl-4-pyrazolyl]-2,3-dihydroinden-1-one oximedown-regulates activity img/direct_inhibition.png chemical inhibition BRAF 0.8
Identifier Residue Sequence Organism Cell Line
SIGNOR-258112 in vitro
pmid sentence
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
+ BRAFdown-regulates quantity by repression img/direct_inhibition.png transcriptional regulation SLC5A5 0.2
Identifier Residue Sequence Organism Cell Line
SIGNOR-251989 Homo sapiens
pmid sentence
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
+ KSR1up-regulates activity img/direct-activation.png binding BRAF 0.627
Identifier Residue Sequence Organism Cell Line
SIGNOR-273878 Homo sapiens HEK-293 Cell
pmid sentence
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
+ PPP1CAup-regulates activity img/direct-activation.png dephosphorylation BRAF 0.295
Identifier Residue Sequence Organism Cell Line
SIGNOR-277160 Homo sapiens
pmid sentence
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
+ PLX-4720down-regulates activity img/direct_inhibition.png chemical inhibition BRAF 0.8
Identifier Residue Sequence Organism Cell Line
SIGNOR-258267 in vitro
pmid sentence
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
+ KSR2up-regulates activity img/direct-activation.png binding BRAF 0.614
Identifier Residue Sequence Organism Cell Line
SIGNOR-273877 Homo sapiens HEK-293 Cell
pmid sentence
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
+ HRASup-regulates activity img/direct-activation.png binding BRAF 0.878
Identifier Residue Sequence Organism Cell Line
SIGNOR-147327 Homo sapiens
pmid sentence
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
+ RNF149down-regulates quantity by destabilization img/direct_inhibition.png polyubiquitination BRAF 0.338
Identifier Residue Sequence Organism Cell Line
SIGNOR-272043 Homo sapiens HCT-116 Cell
pmid sentence
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
+ GDC-0879down-regulates img/direct_inhibition.png chemical inhibition BRAF 0.8
Identifier Residue Sequence Organism Cell Line
SIGNOR-192592 Homo sapiens
pmid sentence
Publications: 1 Organism: Homo Sapiens
+ dabrafenibdown-regulates activity img/direct_inhibition.png chemical inhibition BRAF 0.8
Identifier Residue Sequence Organism Cell Line
SIGNOR-259215 in vitro
pmid sentence
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 tosylatedown-regulates activity img/direct_inhibition.png chemical inhibition BRAF 0.8
Identifier Residue Sequence Organism Cell Line
SIGNOR-259220 in vitro
pmid sentence
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
+ vemurafenibdown-regulates activity img/direct_inhibition.png chemical inhibition BRAF 0.8
Identifier Residue Sequence Organism Cell Line
SIGNOR-259281 Homo sapiens
pmid sentence
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
+ sorafenibdown-regulates img/direct_inhibition.png chemical inhibition BRAF 0.8
Identifier Residue Sequence Organism Cell Line
SIGNOR-174036 Homo sapiens Melanoma Cell
pmid sentence
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
a simple tooltip