| Gene |
RAF1
|
| Protein Name |
RAF1_HUMAN |
| Organism |
Homo sapiens (Human) |
| Alternative name(s) |
RAF proto-oncogene serine/threonine-protein kinase (EC 2.7.11.1) (Proto-oncogene c-RAF) (cRaf) (Raf-1) |
| Protein Family |
Protein kinase superfamily |
| NCBI Gene ID |
5894
|
| UniProt ID |
P04049
|
| Enzyme Class |
2.7.11.1 |
| Molecular Weight |
73052 |
| Protein Length |
648 |
| Protein Domain |
InterPro |
Pfam
|
| 3D Structure |
PDBe |
PDBj |
RCSB PDB |
DrugPort
ModBase |
SwissModel
|
| Gene Expression |
Gene Expression Atlas
|
| Function and Disease |
OMIM |
| Protein-protein Interaction Database |
STRING |
IntAct |
MINT
|
| Kinase Database |
Phospho.ELM
|
PhosphoSite
| NetworKIN
|
| Catalytic Activity (UniProt annotation) |
ATP + a protein = ADP + a phosphoprotein. |
| Localization |
Cytoplasm. Cell membrane. Mitochondrion. Nucleus. Note=Colocalizes with RGS14 and BRAF in both the cytoplasm and membranes. Phosphorylation at Ser-259 impairs its membrane accumulation. Recruited to the cell membrane by the active Ras protein. Phosphorylation at Ser-338 and Ser-339 by PAK1 is required for its mitochondrial localization. Retinoic acid-induced Ser-621 phosphorylated form of RAF1 is predominantly localized at the nucleus. |
| Function (UniProt annotation) |
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. |
| Gene Ontology |
GO:0000165; GO:0000186; GO:0001666; GO:0002223; GO:0004672; GO:0004674; GO:0004709; GO:0005524; GO:0005737; GO:0005739; GO:0005741; GO:0005794; GO:0005829; GO:0005886; GO:0006468; GO:0006915; GO:0007165; GO:0007190; GO:0007507; GO:0008179; GO:0008283; GO:0008285; GO:0010856; GO:0016301; GO:0016607; GO:0019899; GO:0030154; GO:0030168; GO:0030878; GO:0031143; GO:0031333; GO:0031434; GO:0033138; GO:0034220; GO:0035019; GO:0035023; GO:0035773; GO:0035994; GO:0042060; GO:0042802; GO:0042981; GO:0043066; GO:0043154; GO:0045104; GO:0045595; GO:0045944; GO:0046872; GO:0046982; GO:0048011; GO:0048538; GO:0060324; GO:0071550; GO:1902042; GO:2000145 |
