RAF1
GeneName
RAF1
Summary
RAF1, also known as Raf or Raf-1, is a 73 kDa serine/threonine protein kinase that plays a pivotal role in the MAPK/ERK signalling pathway. It is expressed in various tissues and localised in the cytoplasm, plasma membrane, nucleus, and mitochondria. RAF1 acts as an activator of MAP kinase kinase (MEK), which subsequently activates MAP kinases, leading to cellular responses such as proliferation, differentiation, and survival. It is involved in several biological processes, including apoptosis, insulin receptor signalling, and myelination, and interacts with various proteins through its kinase activity and binding capabilities.
Importance
RAF1 is relevant to: - Cancer research, as it is often mutated or overexpressed in various tumours, contributing to uncontrolled cell proliferation and survival. - Metabolic disorders, given its role in insulin signalling and glucose homeostasis. - Neurobiology, due to its involvement in neurotrophin signalling and myelination processes. - Developmental biology, as it plays a role in processes such as thymus and thyroid gland development, and wound healing.
Top Products
For researchers investigating RAF1, we recommend two excellent primary antibodies. The first is the well-cited polyclonal antibody, Anti-Raf1 antibody (ab137435), which has garnered 36 citations and is highly regarded for its performance in Western blotting (WB), immunohistochemistry (IHC), and immunocytochemistry (ICC). This antibody is a trusted choice for those looking to study RAF1 in various contexts. Additionally, we offer the recombinant antibody, Anti-Raf1 antibody [EP4969] - N-terminal (ab181115), which has been validated in knockout models and is suitable for WB, ICC, and flow cytometry (FC). With 10 citations, this recombinant product provides the batch-to-batch consistency that researchers often seek. Together, these antibodies provide robust options for studying RAF1 effectively.
Abcam Product Citation Summary
The data indicates that RAF1 is being studied in the context of radiation exposure and its effects on lung tissue in mice, as well as its role in the Ras/Raf/MEK/ERK signalling pathway in human cell lines. The use of western blotting suggests a focus on protein expression levels in these studies.
Abcam Product Citation Table
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.
Involvement in disease
Noonan syndrome 5
NS5
A form of Noonan syndrome, a disease characterized by short stature, facial dysmorphic features such as hypertelorism, a downward eyeslant and low-set posteriorly rotated ears, and a high incidence of congenital heart defects and hypertrophic cardiomyopathy. Other features can include a short neck with webbing or redundancy of skin, deafness, motor delay, variable intellectual deficits, multiple skeletal defects, cryptorchidism, and bleeding diathesis. Individuals with Noonan syndrome are at risk of juvenile myelomonocytic leukemia, a myeloproliferative disorder characterized by excessive production of myelomonocytic cells.
None
The disease is caused by variants affecting the gene represented in this entry.
LEOPARD syndrome 2
LPRD2
A disorder characterized by lentigines, electrocardiographic conduction abnormalities, ocular hypertelorism, pulmonic stenosis, abnormalities of genitalia, retardation of growth, and sensorineural deafness.
None
The disease is caused by variants affecting the gene represented in this entry.
Cardiomyopathy, dilated, 1NN
CMD1NN
A disorder characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Patients are at risk of premature death.
None
The disease is caused by variants affecting the gene represented in this entry.
Post-translational modifications
Phosphorylation at Thr-269, Ser-338, Tyr-341, Thr-491 and Ser-494 results in its activation. Phosphorylation at Ser-29, Ser-43, Ser-289, Ser-296, Ser-301 and Ser-642 by MAPK1/ERK2 results in its inactivation. Phosphorylation at Ser-259 induces the interaction with YWHAZ and inactivates kinase activity. Dephosphorylation of Ser-259 by the SHOC2-MRAS-PP1c (SMP) complex consisting of SHOC2, GTP-bound M-Ras/MRAS and the catalytic subunit of protein phosphatase 1 (PPP1CA, PPP1CB or PPP1CC); this relieves inactivation and stimulates kinase activity (PubMed:35768504, PubMed:35831509, PubMed:35830882). Phosphorylation at Ser-338 by PAK1 and PAK5 and Ser-339 by PAK1 is required for its mitochondrial localization. Phosphorylation at Ser-621 in response to growth factor treatment stabilizes the protein, possibly by preventing proteasomal degradation. Phosphorylation at Ser-289, Ser-296, Ser-301, Ser-338 and Ser-621 are somehow linked to the methylation potential of cells. Treatment of cells with HGF in the presence of the methylation inhibitor 5'-methylthioadenosine (MTA) results in increased phosphorylation at Ser-338 and Ser-621 and decreased phosphorylation at Ser-296, Ser-301 and Ser-338. Dephosphorylation at Ser-338 by PPP5C results in an activity decrease.
Methylated at Arg-563 in response to EGF treatment. This modification leads to destabilization of the protein, possibly through proteasomal degradation.
Sequence Similarities
Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family. RAF subfamily.
Tissue Specificity
In skeletal muscle, isoform 1 is more abundant than isoform 2.
Cellular localization
- Cytoplasm
- Cell membrane
- Mitochondrion
- Nucleus
- 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.
Alternative names
RAF, RAF1, RAF proto-oncogene serine/threonine-protein kinase, Proto-oncogene c-RAF, Raf-1, cRaf