Target name

P04049: RAF proto-oncogene serine/threonine-protein kinase


  Protein function

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

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
DIP ID DIP-1048N
STRING ID 9606.ENSP00000251849
IntAct ID P04049
DMDM 125651
BRENDA 2.7.10.2
Reactome 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
BioCyc
Entrez Gene (Gene ID) 5894
BindingDB P04049

  Model Performance Metrics

Fingerprint type Sensitivity SEN_std Specificity SPE_std Accuracy ACC_std F1-score F1-score_std AUC AUC_std MCC MCC_std Download model
FP2 fingerprints 0.845 0.005 0.931 0.005 0.888 0.004 0.885 0.005 0.951 0.003 0.783 0.008 Download
Estate fingerprints 0.821 0.006 0.855 0.004 0.838 0.004 0.835 0.005 0.910 0.000 0.674 0.007 Download
MACCS fingerprints 0.820 0.000 0.856 0.006 0.838 0.004 0.834 0.005 0.921 0.003 0.674 0.005 Download
Daylight fingerprints 0.732 0.009 0.950 0.007 0.841 0.006 0.825 0.008 0.918 0.004 0.702 0.011 Download
ECFP2 fingerprints 0.881 0.003 0.907 0.005 0.894 0.005 0.894 0.005 0.960 0.000 0.791 0.007 Download
ECFP4 fingerprints 0.867 0.005 0.959 0.005 0.913 0.005 0.908 0.004 0.970 0.000 0.829 0.009 Download
ECFP6 fingerprints 0.832 0.008 0.974 0.003 0.903 0.005 0.896 0.005 0.964 0.005 0.817 0.009 Download

  Download datasets

Positive dataset Negative dataset


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 E-mail: biomed@csu.edu.cn