RAF1 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. Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family. RAF subfamily. In skeletal muscle, isoform 1 is more abundant than isoform 2. 2 alternatively spliced human isoforms have been reported. Note: This description may include information from UniProtKB.
Protein type: EC; Kinase, protein; Oncoprotein; Protein kinase, Ser/Thr (non-receptor); Protein kinase, TKL; RAF family; RAF subfamily; TKL group
Chromosomal Location of mouse Ortholog: 6 E3|6 53.62 cM
Cellular Component:  cytoplasm; cytosol; Golgi apparatus; membrane; mitochondrion; nucleus; plasma membrane; pseudopodium
Molecular Function:  adenylate cyclase activator activity; adenylate cyclase binding; ATP binding; enzyme binding; identical protein binding; kinase activity; MAP kinase kinase kinase activity; metal ion binding; mitogen-activated protein kinase kinase binding; nucleotide binding; protein binding; protein kinase activity; protein serine/threonine kinase activity; protein-containing complex binding; small GTPase binding; transferase activity
Biological Process:  activation of adenylate cyclase activity; cell differentiation; death-inducing signaling complex assembly; extrinsic apoptotic signaling pathway via death domain receptors; face development; insulin receptor signaling pathway; insulin secretion involved in cellular response to glucose stimulus; insulin-like growth factor receptor signaling pathway; intermediate filament cytoskeleton organization; intracellular glucose homeostasis; intracellular signal transduction; MAPK cascade; negative regulation of apoptotic process; negative regulation of cell population proliferation; negative regulation of extrinsic apoptotic signaling pathway via death domain receptors; negative regulation of protein-containing complex assembly; neurotrophin TRK receptor signaling pathway; phosphorylation; positive regulation of MAPK cascade; positive regulation of peptidyl-serine phosphorylation; positive regulation of protein phosphorylation; positive regulation of transcription by RNA polymerase II; protein phosphorylation; response to hypoxia; response to muscle stretch; signal transduction; somatic stem cell population maintenance; thymus development; thyroid gland development; type B pancreatic cell proliferation
Reference #:  Q99N57 (UniProtKB)
Alt. Names/Synonyms: 6430402F14Rik; AA990557; BB129353; c-R; c-Raf; Cra; Craf; Craf1; Craf1 transforming; D830050J10Rik; MGC102375; murine sarcoma 3611 oncogene 1; OTTMUSP00000022608; OTTMUSP00000022609; Proto-oncogene c-RAF; Raf; RAF proto-oncogene serine/threonine-protein kinase; Raf-1; Raf1; sarcoma 3611 oncogene; v-Raf; v-raf-1 leukemia viral oncogene 1; v-raf-leukemia viral oncogene 1
Gene Symbols: Raf1
Molecular weight: 72,917 Da
Basal Isoelectric point: 9.3  Predict pI for various phosphorylation states
CST Pathways:  B Cell Receptor Signaling  |  ErbB/HER Signaling  |  ESC Pluripotency and Differentiation  |  GPCR Signaling to MAPKs  |  Growth And Differentiation Control by MAPKs  |  IL6 Signaling  |  Inhibition of Apoptosis  |  Insulin Receptor Signaling  |  T Cell Receptor Signaling
Protein-Specific Antibodies, siRNAs or Recombinant Proteins from Cell Signaling Technology® Total Proteins
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Cross-references to other databases:  AlphaFold  |  STRING  |  Reactome  |  BioGPS  |  KinBase  |  Pfam  |  ENZYME  |  Phospho.ELM  |  NetworKIN  |  UniProtKB  |  Entrez-Gene  |  Ensembl Gene