Aliases for RAF1 Gene
External Ids for RAF1 Gene
This gene is the cellular homolog of viral raf gene (v-raf). The encoded protein is a MAP kinase kinase kinase (MAP3K), which functions downstream of the Ras family of membrane associated GTPases to which it binds directly. Once activated, the cellular RAF1 protein can phosphorylate to activate the dual specificity protein kinases MEK1 and MEK2, which in turn phosphorylate to activate the serine/threonine specific protein kinases, ERK1 and ERK2. Activated ERKs are pleiotropic effectors of cell physiology and play an important role in the control of gene expression involved in the cell division cycle, apoptosis, cell differentiation and cell migration. Mutations in this gene are associated with Noonan syndrome 5 and LEOPARD syndrome 2. [provided by RefSeq, Jul 2008]
GeneCards Summary for RAF1 Gene
RAF1 (Raf-1 Proto-Oncogene, Serine/Threonine Kinase) is a Protein Coding gene. Diseases associated with RAF1 include noonan syndrome 5 and leopard syndrome 2. Among its related pathways are PI3K-Akt signaling pathway and PI-3K cascade. GO annotations related to this gene include identical protein binding and protein serine/threonine kinase activity. An important paralog of this gene is MAP3K9.
UniProtKB/Swiss-Prot for RAF1 Gene
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.
Raf kinases, a family of three serine/threonine kinases, are part of the ras-MAPK signaling cascade and phosphorylate MEK. Upon growth factor stimulation, Raf-1 (or c-Raf) is activated by GTP-bound Ras and recruited to the cell membrane. This activation process is tightly regulated by a number of factors including phosphatases (e.g. PP1, PP2A, PP5), kinases (e.g. Src, ERK, Akt, PKC) and proteins that bind directly to Raf-1 (e.g. RKIP, 14-3-3zeta, KSR, Hsp90). Raf-1 is also thought to be able to dimerize with wild type B-Raf in a Ras-dependent process. B-raf is commonly mutated and thereby activated in many human cancers, the most frequent mutation being the V600E mutation of the kinase domain. Whilst wt b-Raf and Raf-1 are strongly activated by growth factor signals via Ras and Src, a-Raf is only modestly activated and has low basal activity. All three isoforms of Raf are considered to be oncogenic.