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.
Uniprot primary ID | P04049 |
PDB ID | 3O8I 3KUD 1RFA 4IEA 1FAR 3IQJ 3KUC 3CU8 3IQV 3IQU 4IHL 1GUA 3NKX 4G0N 4FJ3 4G3X 1FAQ 1C1Y 3OMV |
DrugBank ID | DB00398 DB08896 DB08912 |
BioGrid ID | 111831 |
GuidetoPHARMACOLOGY ID | 2184 |
PharmGKB ID | PA34183 |
KEGG ID | hsa:5894 |
BioCyc | |
Entrez Gene (Gene ID) | 5894 |
DIP | DIP-1048N |
STRING | 9606ENSP00000251849 |
MINT | MINT-86694 |
IntAct | P04049 |
DMDM | 125651 |
BREDNA | 27102 |
Rectome | R-HSA-5675221 R-HSA-5674499 R-HSA-5674135 R-HSA-442742 R-HSA-5621575 R-HSA-430116 R-HSA-2672351 R-HSA-392517 R-HSA-5673000 |
SignaLink | P04049 |
BindingDB | P04049 |
Fingerprint type | F1_CV | AUC_CV | Accuracy_CV | Sensitivity_CV | Specificity_CV | F1_test | AUC_test | Accuracy_test | Sensitivity_test | Specificity_test | Download model |
---|---|---|---|---|---|---|---|---|---|---|---|
FP2 fingerprints | 0.877 | 0.915 | 0.880 | 0.852 | 0.908 | 0.842 | 0.891 | 0.855 | 0.809 | 0.898 | Download |
MACCS fingerprints | 0.836 | 0.920 | 0.837 | 0.827 | 0.847 | 0.850 | 0.930 | 0.859 | 0.850 | 0.867 | Download |
Daylight fingerprints | 0.787 | 0.833 | 0.816 | 0.674 | 0.960 | 0.782 | 0.823 | 0.822 | 0.675 | 0.953 | Download |
ECFP2 fingerprints | 0.878 | 0.949 | 0.876 | 0.893 | 0.858 | 0.871 | 0.938 | 0.871 | 0.921 | 0.827 | Download |
ECFP4 fingerprints | 0.895 | 0.957 | 0.897 | 0.870 | 0.925 | 0.876 | 0.944 | 0.884 | 0.868 | 0.898 | Download |
ECFP6 fingerprints | 0.873 | 0.946 | 0.882 | 0.808 | 0.956 | 0.834 | 0.935 | 0.855 | 0.772 | 0.929 | Download |
Positive dataset | Negative dataset |
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School of Pharmaceutical Sciences, Central South University.
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