RAF1
UniProt ID: P04049
Entrez ID: 5894
Protein name: RAF proto-oncogene serine/threonine-protein kinase (EC 2.7.11.1) (Proto-oncogene c-RAF) (cRaf) (Raf-1)
External links: UniprotKB HGNC RefSeq COSMIC
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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 onc...
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. {ECO:0000269|PubMed:11427728, ECO:0000269|PubMed:11719507, ECO:0000269|PubMed:15385642, ECO:0000269|PubMed:15618521, ECO:0000269|PubMed:15849194, ECO:0000269|PubMed:16892053, ECO:0000269|PubMed:16924233, ECO:0000269|PubMed:9360956}.
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GO - Biological processes (BP):
activation of adenylate cyclase activity [GO:0007190]; apoptotic process [GO:0006915]; cell differentiation [GO:0030154]; death-inducing signaling complex assembly [GO:0071550]; face development [GO:0060324]; insulin secretion involved in cellular response to glucose stimulus [GO:0035773]; intermedi...
activation of adenylate cyclase activity [GO:0007190]; apoptotic process [GO:0006915]; cell differentiation [GO:0030154]; death-inducing signaling complex assembly [GO:0071550]; face development [GO:0060324]; insulin secretion involved in cellular response to glucose stimulus [GO:0035773]; intermediate filament cytoskeleton organization [GO:0045104]; MAPK cascade [GO:0000165]; negative regulation of apoptotic process [GO:0043066]; negative regulation of cell population proliferation [GO:0008285]; negative regulation of cysteine-type endopeptidase activity involved in apoptotic process [GO:0043154]; negative regulation of extrinsic apoptotic signaling pathway via death domain receptors [GO:1902042]; negative regulation of protein-containing complex assembly [GO:0031333]; neurotrophin TRK receptor signaling pathway [GO:0048011]; positive regulation of MAPK cascade [GO:0043410]; positive regulation of peptidyl-serine phosphorylation [GO:0033138]; positive regulation of transcription by RNA polymerase II [GO:0045944]; protein phosphorylation [GO:0006468]; regulation of apoptotic process [GO:0042981]; regulation of cell differentiation [GO:0045595]; regulation of cell motility [GO:2000145]; regulation of Rho protein signal transduction [GO:0035023]; response to muscle stretch [GO:0035994]; signal transduction [GO:0007165]; somatic stem cell population maintenance [GO:0035019]; thymus development [GO:0048538]; thyroid gland development [GO:0030878]; wound healing [GO:0042060]
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GO - Molecular function (MF):
ATP binding [GO:0005524]; enzyme binding [GO:0019899]; identical protein binding [GO:0042802]; MAP kinase kinase kinase activity [GO:0004709]; metal ion binding [GO:0046872]; protein kinase activity [GO:0004672]; protein serine/threonine/tyrosine kinase activity [GO:0004712]; protein serine/threonin...
ATP binding [GO:0005524]; enzyme binding [GO:0019899]; identical protein binding [GO:0042802]; MAP kinase kinase kinase activity [GO:0004709]; metal ion binding [GO:0046872]; protein kinase activity [GO:0004672]; protein serine/threonine/tyrosine kinase activity [GO:0004712]; protein serine/threonine kinase activity [GO:0004674]; protein serine kinase activity [GO:0106310]
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GO - Cellular component (CC):
cytoplasm [GO:0005737]; cytosol [GO:0005829]; Golgi apparatus [GO:0005794]; mitochondrial outer membrane [GO:0005741]; mitochondrion [GO:0005739]; nucleus [GO:0005634]; plasma membrane [GO:0005886]; pseudopodium [GO:0031143]...
cytoplasm [GO:0005737]; cytosol [GO:0005829]; Golgi apparatus [GO:0005794]; mitochondrial outer membrane [GO:0005741]; mitochondrion [GO:0005739]; nucleus [GO:0005634]; plasma membrane [GO:0005886]; pseudopodium [GO:0031143]
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RAF1
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*NOTE: the Kaplan plots were collected from OncoLnc