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 2.7.11.1; Kinase, protein; Oncoprotein; Protein kinase, Ser/Thr (non-receptor); Protein kinase, TKL; RAF family; RAF subfamily; TKL group

Chromosomal Location of human Ortholog: 3p25.2

Cellular Component: cytoplasm; cytosol; Golgi apparatus; mitochondrial outer membrane; mitochondrion; nucleus; plasma membrane; pseudopodium

Molecular Function: ATP binding; enzyme binding; identical protein binding; MAP kinase kinase kinase activity; metal ion binding; protein binding; protein kinase activity; protein serine kinase activity; protein serine/threonine kinase activity; small GTPase binding

Biological Process: activation of adenylate cyclase activity; apoptotic process; 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; MAPK cascade; negative regulation of apoptotic process; negative regulation of cell population proliferation; negative regulation of cysteine-type endopeptidase activity involved in apoptotic process; negative regulation of extrinsic apoptotic signaling pathway via death domain receptors; negative regulation of protein-containing complex assembly; neurotrophin TRK receptor signaling pathway; positive regulation of MAPK cascade; positive regulation of peptidyl-serine phosphorylation; positive regulation of transcription by RNA polymerase II; protein phosphorylation; regulation of apoptotic process; regulation of cell differentiation; regulation of cell motility; regulation of Rho protein signal transduction; response to muscle stretch; signal transduction; somatic stem cell population maintenance; thymus development; thyroid gland development; type B pancreatic cell proliferation; wound healing

Disease: Cardiomyopathy, Dilated, 1nn; Leopard Syndrome 2; Noonan Syndrome 5

Reference #: P04049 (UniProtKB)

Alt. Names/Synonyms: c-Raf; C-Raf proto-oncogene, serine/threonine kinase; CMD1NN; cRaf; NS5; Oncogene RAF1; Proto-oncogene c-RAF; RAF; raf proto-oncogene serine/threonine protein kinase; RAF proto-oncogene serine/threonine-protein kinase; Raf-1; Raf-1 proto-oncogene, serine/threonine kinase; RAF1; v-raf-1 murine leukemia viral oncogene homolog 1; v-raf-1 murine leukemia viral oncogene-like protein 1

Gene Symbols: RAF1

Molecular weight: 73,052 Da

Basal Isoelectric point: 9.33 Predict pI for various phosphorylation states

Protein-Specific Antibodies, siRNAs or Recombinant Proteins from Cell Signaling Technology^®

Select Structure to View Below
RAF1

Get PyMOL Script Get Chimera Script

Substrate Sequence Logo

Open Substrate Page