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This gene is the cellular homolog of viral raf gene (v-raf). The encoded protein is a MAP kinase kinase kinase (MAP3K), which functions downstream of the Ras family of membrane associated GTPases to which it binds directly. Once activated, the cellular RAF1 protein can phosphorylate to activate the dual specificity protein kinases MEK1 and MEK2, which in turn phosphorylate to activate the serine/threonine specific protein kinases, ERK1 and ERK2. Activated ERKs are pleiotropic effectors of cell physiology and play an important role in the control of gene expression involved in the cell division cycle, apoptosis, cell differentiation and cell migration. Mutations in this gene are associated with Noonan syndrome 5 and LEOPARD syndrome 2. [provided by RefSeq, Jul 2008]
RAF1 (Raf-1 Proto-Oncogene, Serine/Threonine Kinase) is a Protein Coding gene. Diseases associated with RAF1 include Noonan Syndrome 5 and Leopard Syndrome 2. Among its related pathways are Association Between Physico-Chemical Features and Toxicity Associated Pathways and Common Cytokine Receptor Gamma-Chain Family Signaling Pathways. Gene Ontology (GO) annotations related to this gene include identical protein binding and protein kinase activity. An important paralog of this gene is ARAF.
Raf kinases, a family of three serine/threonine kinases, are part of the Ras-MAPK signaling cascade and phosphorylate MEK. Upon growth factor stimulation, Raf-1 (c-Raf) is activated by GTP-bound Ras and recruited to the cell membrane. This activation process is tightly regulated.
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0000166 | nucleotide binding | IEA | -- |
GO:0004672 | protein kinase activity | IEA,TAS | 8063729 |
GO:0004674 | protein serine/threonine kinase activity | IEA,IDA | 19667065 |
GO:0004709 | MAP kinase kinase kinase activity | IEA | -- |
GO:0005515 | protein binding | IPI | 7644510 |
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0005623 | cell | IEA | -- |
GO:0005634 | nucleus | IEA | -- |
GO:0005737 | cytoplasm | IDA,ISS | -- |
GO:0005739 | mitochondrion | IBA | 21873635 |
GO:0005741 | mitochondrial outer membrane | TAS | 8929532 |
SuperPathway | Contained pathways | ||
---|---|---|---|
1 | RET signaling |
.92
|
.92
|
2 | IL-2 Pathway |
ErbB Family Pathway
.59
ErbB4 Pathway
.59
Prolactin Signaling
.54
Thrombopoietin Pathway
.51
ErbB2-ErbB3 Heterodimers
.49
IL-2 Pathway
.48
|
LPS Stimulated MAPK Signaling
.47
UVC-Induced MAPK Signaling
.44
TREM1 Pathway
.43
PI3K Signaling in B-Lymphocyte
.35
IL-4 Pathway
.34
|
3 | Regulation of lipid metabolism Insulin signaling-generic cascades |
Regulation of lipid metabolism Insulin signaling-generic cascades
.59
Translation Insulin regulation of translation
.59
Transcription Receptor-mediated HIF regulation
.51
Translation Regulation of EIF2 activity
.47
Translation Regulation of EIF4F activity
.44
|
Development CNTF receptor signaling
.43
Cell adhesion PLAU signaling
.35
Development Growth hormone signaling via PI3K/AKT and MAPK cascades
.34
|
4 | Common Cytokine Receptor Gamma-Chain Family Signaling Pathways |
Immune response IL-9 signaling pathway
.42
Development Thrombopoietin-regulated cell processes
.38
|
|
5 | Endometrial cancer |
Signal transduction PTEN pathway
.44
.32
|
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0000165 | MAPK cascade | TAS | -- |
GO:0000186 | activation of MAPKK activity | IDA | 10644344 |
GO:0001666 | response to hypoxia | IEA | -- |
GO:0001678 | cellular glucose homeostasis | IEA | -- |
GO:0001934 | positive regulation of protein phosphorylation | IEA | -- |
Name | Status | Disease Links | Group | Role | Mechanism of Action | Clinical Trials |
---|---|---|---|---|---|---|
Sorafenib | Approved, Investigational | Pharma | Target, inhibitor, inhibitors | Raf kinases and tyrosine kinases inhibitor, RAF, VEGFR2, and PDGFR-beta inhibitors, Kinase Inhibitors, Vascular endothelial growth factor (VEGF) and VEGF receptor (VEGFR) inhibitors | 779 | |
regorafenib | Approved | Pharma | Target, inhibitor | Inhibitor of VEGFR/PDGFR/FGFR/mutant kit/RET/Raf-1, Kinase Inhibitors, Vascular endothelial growth factor (VEGF) and VEGF receptor (VEGFR) inhibitors | 0 | |
Cisplatin | Approved | Pharma | Inhibits DNA synthesis,chemotherapy drug, Potent pro-apoptotic anticancer agent; activates caspase-3, Platinum | 3412 | ||
Docetaxel | Approved, Investigational | Pharma | Microtubulin disassembly inhibitor, Tubulin and VEGF inhibitor, Taxanes | 2330 | ||
Paclitaxel | Approved, Vet_approved | Pharma | Tubulin and Bcl2 inhibitor, Taxanes | 3701 |
Name | Synonyms | Role | CAS Number | PubChem IDs | PubMed IDs | |
---|---|---|---|---|---|---|
ZM 336372 |
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208260-29-1 |
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ADP |
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Agonist, Full agonist, Partial agonist, Gating inhibitor, Antagonist | 58-64-0 |
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Diglycerides Group A |
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Diglycerides Group B |
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Diglycerides Group C |
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Compound | Action | Cas Number |
---|---|---|
AZ 628 | Raf kinases,potent and ATP-competitive | 878739-06-1 |
B-Raf IN 1 | 950736-05-7 | |
B-Raf inhibitor 1 | 1093100-40-3 | |
CEP-32496 | BRAF(V600E)inhibitor,highly potent | 1188910-76-0 |
CEP-32496 hydrochloride | B-Raf/C-Raf inhibitor,highly potent | 1227678-26-3 |
GDC-0879 | B-Raf inhibitor,potent and selective | 905281-76-7 |
GW5074 | C-Raf inhibitor,potent and selective | 220904-83-6 |
L-779,450 | 303727-31-3 | |
LGX818 | RAF inhibitor,potent and selective | 1269440-17-6 |
LY3009120 | pan-RAF and RAF dimer inhibitor | 1454682-72-4 |
ML 786 dihydrochloride | Raf kinase inhibitor | 1237536-18-3 |
MLN 2480 | Pan-Raf kinase inhibitor,investigational | 1096708-71-2 |
OSI-930 | Inhibitor of Kit, KDR, Flt, CSF-1R, c-Raf and Lck | 728033-96-3 |
RAF265 | Multiple intracellular kinases inhibitor | 927880-90-8 |
Regorafenib | Inhibitor of VEGFR/PDGFR/FGFR/mutant kit/RET/Raf-1 | 755037-03-7 |
Regorafenib monohydrate | Tyrosine kinase inhibitor | 1019206-88-2 |
Sorafenib | Raf kinases and tyrosine kinases inhibitor | 284461-73-0 |
Sorafenib Tosylate | Raf kinases and tyrosine kinases inhibitor | 475207-59-1 |
TAK-632 | Pan-RAF inhibitor,potent and selective | 1228591-30-7 |
Tautomycetin | 119757-73-2 | |
ZM336372 | C-Raf inhibitor, potent and selective | 208260-29-1 |