Recombinant Human RAF proto-oncogene serine/threonine-protein kinase (RAF1)

Uniprot Id

P04049

Target Species

Human

Target Name

RAF1

Target Full Name

RAF proto-oncogene serine/threonine-protein kinase

Target 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.

Target Involvement

Noonan syndrome 5 (NS5); LEOPARD syndrome 2 (LPRD2); Cardiomyopathy, dilated 1NN (CMD1NN)

Target Subcellular Location

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.

Target Protein Families

Protein kinase superfamily, TKL Ser/Thr protein kinase family, RAF subfamily

Target Tissue Specificity

In skeletal muscle, isoform 1 is more abundant than isoform 2.

Target Research Area

Cancer

Target Synonyms

c Raf; C-raf; C-Raf proto-oncogene, serine/threonine kinase; CMD1NN; Craf 1 transforming gene; cRaf; Craf1 transforming gene; EC 2.7.11.1; kinase Raf1; Murine sarcoma 3611 oncogene 1; NS5; Oncogene MIL; Oncogene RAF1; OTTHUMP00000160218; OTTHUMP00000207813; OTTHUMP00000209389; Protein kinase raf 1; Proto-oncogene c-RAF; Raf 1; Raf 1 proto oncogene serine/threonine kinase; RAF; Raf proto oncogene serine/threonine protein kinase; RAF proto-oncogene serine/threonine-protein kinase; RAF-1; RAF1; RAF1_HUMAN; Similar to murine leukemia viral (V-raf-1) oncogene homolog 1; TRANSFORMING REPLICATION-DEFECTIVE MURINE RETROVIRUS 3611-MSV; v raf 1 murine leukemia viral oncogene homolog 1; v-raf murine sarcoma viral oncogene homolog 1; v-raf-1 murine leukemia viral oncogene-like protein 1; vraf1 murine leukemia viral oncogene homolog 1

Target Background

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.