RAF proto-oncogene serine/threonine-protein kinase
Serine/threonine-protein kinase that acts as a regulatory link between the membrane-associated Ras GTPases and the MAPK/ERK cascade, and this critical regulatory link functions as a switch determining cell fate decisions including proliferation, differentiation, apoptosis, survival and oncogenic transformation. RAF1 activation initiates a mitogen-activated protein kinase (MAPK) cascade that comprises a sequential phosphorylation of the dual-specific MAPK kinases (MAP2K1/MEK1 and MAP2K2/MEK2) and the extracellular signal-regulated kinases (MAPK3/ERK1 and MAPK1/ERK2). The phosphorylated form of RAF1 (on residues Ser-338 and Ser-339, by PAK1) phosphorylates BAD/Bcl2- antagonist of cell death at 'Ser-75'. Phosphorylates adenylyl cyclases: ADCY2, ADCY5 and ADCY6, resulting in their activation. Phosphorylates PPP1R12A resulting in inhibition of the phosphatase activity. Phosphorylates TNNT2/cardiac muscle troponin T. Can promote NF-kB activation and inhibit signal transducers involved in motility (ROCK2), apoptosis (MAP3K5/ASK1 and STK3/MST2), proliferation and angiogenesis (RB1). Can protect cells from apoptosis also by translocating to the mitochondria where it binds BCL2 and displaces BAD/Bcl2-antagonist of cell death. Regulates Rho signaling and migration, and is required for normal wound healing. Plays a role in the oncogenic transformation of epithelial cells via repression of the TJ protein, occludin (OCLN) by inducing the up-regulation of a transcriptional repressor SNAI2/SLUG, which induces down-regulation of OCLN. Restricts caspase activation in response to selected stimuli, notably Fas stimulation, pathogen-mediated macrophage apoptosis, and erythroid differentiation.
Database | Links |
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UniProt | P04049 |
PDB | 1C1Y, 1FAQ, 1FAR, 1GUA, 1RFA, 3CU8, 3IQJ, 3IQU, 3IQV, 3KUC, 3KUD, 3NKX, 3O8I, 3OMV, 4FJ3, 4G0N, 4G3X, 4IEA, 4IHL |
BioGrid | 111831 |
BindingDB | P04049 |
DrugBank | DB00398 |
Guide to PHARMACOLOGY | 2184 |
PharmGKB | PA34183 |
KEGG | hsa:5894 |
BioCyc | Not available |
Entrez Gene (GeneID) | 5894 |
Metric | Mean Value | Standard Deviation |
---|---|---|
AUC | 0.9509 | 0.0026 |
Accuracy | 0.8857 | 0.0044 |
Sensitivity | 0.8435 | 0.0094 |
Specificity | 0.9255 | 0.0065 |
BEDROC | 0.9956 | 0.0015 |
MCC Threshold | 0.414 | N/A |
MCC | 0.7736 | N/A |
F-score Threshold | 0.414 | N/A |
F-score | 0.8825 | N/A |