UniProt ID | P04049 |
---|---|
Protein Name | RAF proto-oncogene serine/threonine-protein kinase (EC 2.7.11.1) (Proto-oncogene c-RAF) (cRaf) (Raf-1) |
Gene Name | RAF1 |
Position | 259 |
SequenceWindow | SQRQRSTSTPNVHMV |
Function Score? | 0.998 |
Disorder score? | 0.713 Disordered |
Protein-Targeted Drug | Semapimod; BGB-3245; GDC-5573; Belvarafenib; MLN2480; LXH254; ICo-007; LErafAON; SPN-803; RG7304; ISIS 10707; ISIS 9058; "5-(4-hydroxy-2,6-dimethylstyryl)nicotinic acid"; ISIS 7853; ISIS 7855; ISIS 7851; ISIS 15770; ISIS 11061; ISIS 7848; ISIS 6717; ISIS 6720; ISIS 6729; ISIS 7849; L-790070; ISIS 7847; 6-[(E)-2-(4-Fluoro-phenyl)-vinyl]-9H-purine; PLX-ORI3; 6-Benzylsulfanyl-9H-purine; GW-5074; ZM-336372; DEBROMOHYMENIALDISINE; Sorafenib; LErafAON; XL281; iCo-007; Cholecystokinin; Regorafenib; Dabrafenib; Encorafenib; Fostamatinib; U0126; SORAFENIB; XL-281; NULL; BELVARAFENIB; RG-7376; SEMAPIMOD; LY-3009120; C-RAF ANTISENSE OLIGONUCLEOTIDE ISIS 5132; TOVORAFENIB; REGORAFENIB; LXH254; ENCORAFENIB; CHIR-265; ICO-007; PACLITAXEL; DOCETAXEL ANHYDROUS; ARQ-736; TRAMETINIB DIMETHYL SULFOXIDE; CISPLATIN; COBIMETINIB; XL281; LGX-806; CARBOPLATIN; GEMCITABINE . . . more
|
Protein Subcellular 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. . . . more
|
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. {ECO:0000269|PubMed:11427728, ECO:0000269|PubMed:11719507, ECO:0000269|PubMed:15385642, ECO:0000269|PubMed:15618521, ECO:0000269|PubMed:15849194, ECO:0000269|PubMed:16892053, ECO:0000269|PubMed:16924233, ECO:0000269|PubMed:9360956}. . . . more
|
Functional domains |
Distribution of Tumor Phosphorylation Levels (corrected without protein) in Pan-Cancer
Distribution of Tumor Phosphorylation Levels (corrected with protein) in Pan-Cancer
Distribution of Normal Phosphorylation Levels (corrected without protein) in Pan-Cancer
Distribution of Normal Phosphorylation Levels (corrected with protein) in Pan-Cancer
Copyright © Jing Li's group, SJTU. All rights reserved.