Description: Homo sapiens v-raf-1 murine leukemia viral oncogene homolog 1 (RAF1), mRNA. RefSeq Summary (NM_002880): 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]. Transcript (Including UTRs) Position: hg19 chr3:12,625,100-12,705,700 Size: 80,601 Total Exon Count: 17 Strand: - Coding Region Position: hg19 chr3:12,626,013-12,660,220 Size: 34,208 Coding Exon Count: 16
ID:RAF1_HUMAN DESCRIPTION: RecName: Full=RAF proto-oncogene serine/threonine-protein kinase; EC=2.7.11.1; AltName: Full=Proto-oncogene c-RAF; Short=cRaf; AltName: Full=Raf-1; 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. CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein. COFACTOR: Binds 2 zinc ions per subunit. ENZYME REGULATION: Regulation is a highly complex process involving membrane recruitment, protein-protein interactions, dimerization, and phosphorylation/dephosphorylation events. Ras- GTP recruits RAF1 to the membrane, thereby promoting its activation. The inactive conformation of RAF1 is maintained by autoinhibitory interactions occurring between the N-terminal regulatory and the C-terminal catalytic domains and by the binding of a 14-3-3 protein that contacts two phosphorylation sites, Ser- 259 and Ser-621. Upon mitogenic stimulation, Ras and PPP2R1A cooperate to release autoinhibition and the subsequent phosphorylation of activating sites: Ser-338, Tyr-341, Thr-491, and Ser-494, yields a fully active kinase. Through a negative feedback mechanism involving MAPK1/ERK2, RAF1 is phosphorylated on Ser-29, Ser-43, Ser-289, Ser-296, Ser-301 and Ser-642 by MAPK1/ERK2, which yields an inactive, desensitized kinase. The signaling-competent conformation of RAF1 is finally re-established by the coordinated action of PIN1, a prolyl isomerase that converts pSer and pThr residues from the cis to the trans conformation, which is preferentially recognized and dephosphorylated by PPP2R1A. Activated by homodimerization and heterodimerization (with BRAF). Also regulated through association with other proteins such as KSR2, CNKSR1/CNK1, PEBP1/RKIP, PHB/prohibitin and SPRY4. PEBP1/RKIP acts by dissociating RAF1 from its substrates MAP2K1/MEK1 and MAP2K2/MEK2. PHB/prohibitin facilitates the displacement of 14-3-3 from RAF1 by activated Ras, thereby promoting cell membrane localization and phosphorylation of RAF1 at the activating Ser-338. SPRY4 inhibits Ras-independent, but not Ras-dependent, activation of RAF1. CNKSR1/CNK1 regulates Src-mediated RAF1 activation. SUBUNIT: Monomer. Homodimer. Heterodimerizes with BRAF and this heterodimer possesses a highly increased kinase activity compared to the respective homodimers or monomers. Heterodimerization is mitogen-regulated and enhanced by 14-3-3 proteins. MAPK1/ERK2 activation can induce a negative feedback that promotes the dissociation of the heterodimer. Forms a multiprotein complex with Ras (M-Ras/MRAS), SHOC2 and protein phosphatase 1 (PPP1CA, PPP1CB and PPP1CC). Interacts with Ras proteins; the interaction is antagonized by RIN1. Weakly interacts with RIT1. Interacts (via N- terminus) with RGS14 (via RBD domains); the interaction mediates the formation of a ternary complex with BRAF, a ternary complex inhibited by GNAI1 (By similarity). Interacts with STK3/MST2; the interaction inhibits its pro-apoptotic activity. Interacts (when phosphorylated at Ser-259) with YWHAZ (unphosphorylated at 'Thr- 232'). Interacts with MAP2K1/MEK1 and MAP2K2/MEK2 (By similarity). Interacts with MAP3K5/ASF1 (via N-terminus) and this interaction inhibits the proapoptotic function of MAP3K5/ASK1. Interacts with PAK1 (via kinase domain). The phosphorylated form interacts with PIN1. The Ser-338 and Ser-339 phosphorylated form (by PAK1) interacts with BCL2. Interacts with PEBP1/RKIP and this interaction is enhanced if RAF1 is phosphorylated on residues Ser- 338, Ser-339, Tyr-340 and Tyr-341. Interacts with ADCY2, ADCY5, ADCY6, DGKH, RCAN1/DSCR1, ROCK2, PPP1R12A, PKB/AKT1, PPP2CA, PPP2R1B, SPRY2, SPRY4, CNKSR1/CNK1, KSR2 and PHB/prohibitin. In its active form, interacts with PRMT5. INTERACTION: Self; NbExp=3; IntAct=EBI-365996, EBI-365996; P15056:BRAF; NbExp=30; IntAct=EBI-365996, EBI-365980; P49368:CCT3; NbExp=3; IntAct=EBI-365996, EBI-356673; P30304:CDC25A; NbExp=4; IntAct=EBI-365996, EBI-747671; P31327:CPS1; NbExp=4; IntAct=EBI-365996, EBI-536811; P01112:HRAS; NbExp=8; IntAct=EBI-365996, EBI-350145; P08238:HSP90AB1; NbExp=2; IntAct=EBI-365996, EBI-352572; P11021:HSPA5; NbExp=4; IntAct=EBI-365996, EBI-354921; P01116-2:KRAS; NbExp=2; IntAct=EBI-365996, EBI-367427; Q02750:MAP2K1; NbExp=2; IntAct=EBI-365996, EBI-492564; O43482:OIP5; NbExp=4; IntAct=EBI-365996, EBI-536879; Q13177:PAK2; NbExp=2; IntAct=EBI-365996, EBI-1045887; P14618:PKM; NbExp=3; IntAct=EBI-365996, EBI-353408; P62834:RAP1A; NbExp=2; IntAct=EBI-365996, EBI-491414; P06400:RB1; NbExp=3; IntAct=EBI-365996, EBI-491274; P53805-2:RCAN1; NbExp=4; IntAct=EBI-365996, EBI-1541912; Q3ZCQ8:TIMM50; NbExp=3; IntAct=EBI-365996, EBI-355175; P31946:YWHAB; NbExp=10; IntAct=EBI-365996, EBI-359815; Q04917:YWHAH; NbExp=2; IntAct=EBI-365996, EBI-306940; P63104:YWHAZ; NbExp=3; IntAct=EBI-365996, EBI-347088; 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. TISSUE SPECIFICITY: In skeletal muscle, isoform 1 is more abundant than isoform 2. PTM: Phosphorylated upon DNA damage, probably by ATM or ATR. 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 complex containing protein phosphatase 1, SHOC2 and M-Ras/MRAS relieves inactivation, leading to stimulate RAF1 activity. Phosphorylation at Ser-338 by PAK1 and PAK7/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. PTM: Methylated at Arg-563 in response to EGF treatment. This modification leads to destabilization of the protein, possibly through proteasomal degradation. DISEASE: Defects in RAF1 are the cause of Noonan syndrome type 5 (NS5) [MIM:611553]. Noonan syndrome (NS) is a disorder characterized by dysmorphic facial features, short stature, hypertelorism, cardiac anomalies, deafness, motor delay, and a bleeding diathesis. It is a genetically heterogeneous and relatively common syndrome, with an estimated incidence of 1 in 1000-2500 live births. DISEASE: Defects in RAF1 are the cause of LEOPARD syndrome type 2 (LEOPARD2) [MIM:611554]. LEOPARD syndrome is an autosomal dominant disorder allelic with Noonan syndrome. The acronym LEOPARD stands for lentigines, electrocardiographic conduction abnormalities, ocular hypertelorism, pulmonic stenosis, abnormalities of genitalia, retardation of growth, and deafness. SIMILARITY: Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family. RAF subfamily. SIMILARITY: Contains 1 phorbol-ester/DAG-type zinc finger. SIMILARITY: Contains 1 protein kinase domain. SIMILARITY: Contains 1 RBD (Ras-binding) domain. WEB RESOURCE: Name=GeneReviews; URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/RAF1"; WEB RESOURCE: Name=NIEHS-SNPs; URL="http://egp.gs.washington.edu/data/raf1/"; WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/RAF1ID42032ch3p25.html";
To design primers for a non-coding sequence, zoom to a region of interest and select from the drop-down menu: View > In External Tools > Primer3
Genetic Association Studies of Complex Diseases and Disorders
Genetic Association Database (archive): RAF1 CDC HuGE Published Literature: RAF1 Positive Disease Associations: Cardiomegaly
, Cholesterol Related Studies:
Cardiomegaly Afshin Parsa et al. Clinical and translational science 2011, Hypertrophy-associated polymorphisms ascertained in a founder cohort applied to heart failure risk and mortality., Clinical and translational science.
[PubMed 21348951]
Cholesterol Tanya M Teslovich et al. Nature 2010, Biological, clinical and population relevance of 95 loci for blood lipids., Nature.
[PubMed 20686565]
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on P04049
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Biological Process: GO:0000165 MAPK cascade GO:0000186 activation of MAPKK activity GO:0001666 response to hypoxia GO:0001678 cellular glucose homeostasis GO:0001934 positive regulation of protein phosphorylation GO:0002223 stimulatory C-type lectin receptor signaling pathway GO:0006468 protein phosphorylation GO:0006915 apoptotic process GO:0007165 signal transduction GO:0007190 activation of adenylate cyclase activity GO:0007275 multicellular organism development GO:0007507 heart development GO:0008283 cell proliferation GO:0008285 negative regulation of cell proliferation GO:0009968 negative regulation of signal transduction GO:0016310 phosphorylation GO:0030154 cell differentiation GO:0030168 platelet activation GO:0030878 thyroid gland development GO:0031333 negative regulation of protein complex assembly GO:0033138 positive regulation of peptidyl-serine phosphorylation GO:0034220 ion transmembrane transport GO:0035019 somatic stem cell population maintenance GO:0035023 regulation of Rho protein signal transduction GO:0035556 intracellular signal transduction GO:0035773 insulin secretion involved in cellular response to glucose stimulus GO:0035994 response to muscle stretch GO:0042060 wound healing GO:0042981 regulation of apoptotic process GO:0043066 negative regulation of apoptotic process GO:0043154 negative regulation of cysteine-type endopeptidase activity involved in apoptotic process GO:0045104 intermediate filament cytoskeleton organization GO:0045595 regulation of cell differentiation GO:0045944 positive regulation of transcription from RNA polymerase II promoter GO:0048011 neurotrophin TRK receptor signaling pathway GO:0048538 thymus development GO:0060324 face development GO:0070374 positive regulation of ERK1 and ERK2 cascade GO:0071550 death-inducing signaling complex assembly GO:1902042 negative regulation of extrinsic apoptotic signaling pathway via death domain receptors GO:2000145 regulation of cell motility
LF208723 - JP 2014500723-A/16226: Polycomb-Associated Non-Coding RNAs. GU149302 - Homo sapiens ESRP1/RAF1 fusion protein mRNA, complete cds. LF384172 - JP 2014500723-A/191675: Polycomb-Associated Non-Coding RNAs. LP830505 - Sequence 7 from Patent EP3211090. X06409 - Human mRNA fragment for activated c-raf-1 (exons 8-17). BC018119 - Homo sapiens v-raf-1 murine leukemia viral oncogene homolog 1, mRNA (cDNA clone MGC:9026 IMAGE:3904404), complete cds. AK226028 - Homo sapiens mRNA for v-raf-1 murine leukemia viral oncogene homolog 1 variant, clone: FCC104F09. FM209427 - Homo sapiens mRNA for SRGAP3:RAF1 fusion protein (SRGAP3:RAF1 gene). X03484 - Human mRNA for raf oncogene. JD303238 - Sequence 284262 from Patent EP1572962. JD360372 - Sequence 341396 from Patent EP1572962. JD192480 - Sequence 173504 from Patent EP1572962. JD352419 - Sequence 333443 from Patent EP1572962. JD404940 - Sequence 385964 from Patent EP1572962. JD520305 - Sequence 501329 from Patent EP1572962. JD367008 - Sequence 348032 from Patent EP1572962. JD185517 - Sequence 166541 from Patent EP1572962. JD081214 - Sequence 62238 from Patent EP1572962. JD317796 - Sequence 298820 from Patent EP1572962. JD224649 - Sequence 205673 from Patent EP1572962. JD074495 - Sequence 55519 from Patent EP1572962. JD090000 - Sequence 71024 from Patent EP1572962. JD559831 - Sequence 540855 from Patent EP1572962. LF365213 - JP 2014500723-A/172716: Polycomb-Associated Non-Coding RNAs. JD383454 - Sequence 364478 from Patent EP1572962. JD504211 - Sequence 485235 from Patent EP1572962. JD464454 - Sequence 445478 from Patent EP1572962. AK303920 - Homo sapiens cDNA FLJ50355 complete cds, highly similar to RAF proto-oncogene serine/threonine-protein kinase (EC 2.7.11.1). AK303561 - Homo sapiens cDNA FLJ57286 complete cds, highly similar to RAF proto-oncogene serine/threonine-protein kinase (EC 2.7.11.1). JD203467 - Sequence 184491 from Patent EP1572962. LF365214 - JP 2014500723-A/172717: Polycomb-Associated Non-Coding RNAs. JD269953 - Sequence 250977 from Patent EP1572962. JD515249 - Sequence 496273 from Patent EP1572962. JD323255 - Sequence 304279 from Patent EP1572962. JD439941 - Sequence 420965 from Patent EP1572962. AK312248 - Homo sapiens cDNA, FLJ92543, highly similar to Homo sapiens v-raf-1 murine leukemia viral oncogene homolog 1(RAF1), mRNA. KJ897443 - Synthetic construct Homo sapiens clone ccsbBroadEn_06837 RAF1 gene, encodes complete protein. KJ905305 - Synthetic construct Homo sapiens clone ccsbBroadEn_14825 RAF1 gene, encodes complete protein. AB384961 - Synthetic construct DNA, clone: pF1KB4573, Homo sapiens RAF1 gene for RAF proto-oncogene serine/threonine-protein kinase, complete cds, without stop codon, in Flexi system. KU178297 - Homo sapiens v-raf-1 murine leukemia viral oncogene-like protein 1 isoform 1 (RAF1) mRNA, partial cds. KU178298 - Homo sapiens v-raf-1 murine leukemia viral oncogene-like protein 1 isoform 2 (RAF1) mRNA, partial cds, alternatively spliced. KU178299 - Homo sapiens v-raf-1 murine leukemia viral oncogene-like protein 1 isoform 3 (RAF1) mRNA, partial cds, alternatively spliced. LF365215 - JP 2014500723-A/172718: Polycomb-Associated Non-Coding RNAs. LF365216 - JP 2014500723-A/172719: Polycomb-Associated Non-Coding RNAs. BX648063 - Homo sapiens mRNA; cDNA DKFZp686J20203 (from clone DKFZp686J20203). LF365218 - JP 2014500723-A/172721: Polycomb-Associated Non-Coding RNAs. LF365223 - JP 2014500723-A/172726: Polycomb-Associated Non-Coding RNAs. JD021389 - Sequence 2413 from Patent EP1572962. JD022890 - Sequence 3914 from Patent EP1572962. JD029810 - Sequence 10834 from Patent EP1572962. CU676186 - Synthetic construct Homo sapiens gateway clone IMAGE:100019979 5' read RAF1 mRNA. DJ444897 - Combinatorial Methods and Compositions for Treatment of Melanoma. LF365233 - JP 2014500723-A/172736: Polycomb-Associated Non-Coding RNAs. JD268889 - Sequence 249913 from Patent EP1572962. JD315409 - Sequence 296433 from Patent EP1572962. LF365234 - JP 2014500723-A/172737: Polycomb-Associated Non-Coding RNAs. LF365242 - JP 2014500723-A/172745: Polycomb-Associated Non-Coding RNAs. MA619749 - JP 2018138019-A/191675: Polycomb-Associated Non-Coding RNAs. MA600790 - JP 2018138019-A/172716: Polycomb-Associated Non-Coding RNAs. MA600791 - JP 2018138019-A/172717: Polycomb-Associated Non-Coding RNAs. MA600792 - JP 2018138019-A/172718: Polycomb-Associated Non-Coding RNAs. MA600793 - JP 2018138019-A/172719: Polycomb-Associated Non-Coding RNAs. MA600795 - JP 2018138019-A/172721: Polycomb-Associated Non-Coding RNAs. MA600800 - JP 2018138019-A/172726: Polycomb-Associated Non-Coding RNAs. MA600810 - JP 2018138019-A/172736: Polycomb-Associated Non-Coding RNAs. MA600811 - JP 2018138019-A/172737: Polycomb-Associated Non-Coding RNAs. MA600819 - JP 2018138019-A/172745: Polycomb-Associated Non-Coding RNAs. MA444300 - JP 2018138019-A/16226: Polycomb-Associated Non-Coding RNAs.
Biochemical and Signaling Pathways
KEGG - Kyoto Encyclopedia of Genes and Genomes hsa04010 - MAPK signaling pathway hsa04012 - ErbB signaling pathway hsa04062 - Chemokine signaling pathway hsa04270 - Vascular smooth muscle contraction hsa04370 - VEGF signaling pathway hsa04510 - Focal adhesion hsa04540 - Gap junction hsa04650 - Natural killer cell mediated cytotoxicity hsa04660 - T cell receptor signaling pathway hsa04662 - B cell receptor signaling pathway hsa04664 - Fc epsilon RI signaling pathway hsa04666 - Fc gamma R-mediated phagocytosis hsa04720 - Long-term potentiation hsa04722 - Neurotrophin signaling pathway hsa04730 - Long-term depression hsa04810 - Regulation of actin cytoskeleton hsa04910 - Insulin signaling pathway hsa04912 - GnRH signaling pathway hsa04914 - Progesterone-mediated oocyte maturation hsa04916 - Melanogenesis hsa05200 - Pathways in cancer hsa05210 - Colorectal cancer hsa05211 - Renal cell carcinoma hsa05212 - Pancreatic cancer hsa05213 - Endometrial cancer hsa05214 - Glioma hsa05215 - Prostate cancer hsa05218 - Melanoma hsa05219 - Bladder cancer hsa05220 - Chronic myeloid leukemia hsa05221 - Acute myeloid leukemia hsa05223 - Non-small cell lung cancer
BioCarta from NCI Cancer Genome Anatomy Project h_gpcrPathway - Signaling Pathway from G-Protein Families h_malPathway - Role of MAL in Rho-Mediated Activation of SRF h_egfPathway - EGF Signaling Pathway h_epoPathway - EPO Signaling Pathway h_her2Pathway - Role of ERBB2 in Signal Transduction and Oncology h_il6Pathway - IL 6 signaling pathway h_tcrPathway - T Cell Receptor Signaling Pathway h_bArrestin-srcPathway - Roles of ¿-arrestin-dependent Recruitment of Src Kinases in GPCR Signaling h_bcrPathway - BCR Signaling Pathway h_biopeptidesPathway - Bioactive Peptide Induced Signaling Pathway h_cdk5Pathway - Phosphorylation of MEK1 by cdk5/p35 down regulates the MAP kinase pathway h_fMLPpathway - fMLP induced chemokine gene expression in HMC-1 cells h_ngfPathway - Nerve growth factor pathway (NGF) h_sppaPathway - Aspirin Blocks Signaling Pathway Involved in Platelet Activation h_TPOPathway - TPO Signaling Pathway h_ecmPathway - Erk and PI-3 Kinase Are Necessary for Collagen Binding in Corneal Epithelia h_erkPathway - Erk1/Erk2 Mapk Signaling pathway h_insulinPathway - Insulin Signaling Pathway h_mapkPathway - MAPKinase Signaling Pathway h_metPathway - Signaling of Hepatocyte Growth Factor Receptor h_CCR3Pathway - CCR3 signaling in Eosinophils h_fcer1Pathway - Fc Epsilon Receptor I Signaling in Mast Cells h_igf1rPathway - Multiple antiapoptotic pathways from IGF-1R signaling lead to BAD phosphorylation h_il3Pathway - IL 3 signaling pathway h_keratinocytePathway - Keratinocyte Differentiation h_pdgfPathway - PDGF Signaling Pathway h_pyk2Pathway - Links between Pyk2 and Map Kinases h_rasPathway - Ras Signaling Pathway h_ceramidePathway - Ceramide Signaling Pathway h_il2Pathway - IL 2 signaling pathway h_il2rbPathway - IL-2 Receptor Beta Chain in T cell Activation h_integrinPathway - Integrin Signaling Pathway h_spryPathway - Sprouty regulation of tyrosine kinase signals h_RacCycDPathway - Influence of Ras and Rho proteins on G1 to S Transition h_cxcr4Pathway - CXCR4 Signaling Pathway h_gleevecpathway - Inhibition of Cellular Proliferation by Gleevec h_At1rPathway - Angiotensin II mediated activation of JNK Pathway via Pyk2 dependent signaling h_barr-mapkPathway - Role of ¿-arrestins in the activation and targeting of MAP kinases h_cdMacPathway - Cadmium induces DNA synthesis and proliferation in macrophages h_ghPathway - Growth Hormone Signaling Pathway h_igf1Pathway - IGF-1 Signaling Pathway h_nfatPathway - NFAT and Hypertrophy of the heart (Transcription in the broken heart)
Reactome (by CSHL, EBI, and GO)
Protein P04049 (Reactome details) participates in the following event(s):
R-HSA-392835 Rap1 sequesters Raf1 to inhibit ERK cascade R-HSA-443439 c-Src binds Raf1 R-HSA-443831 14-3-3-zeta binds Raf1 R-HSA-5624494 RAF1 binds p21 RAS:GTP R-HSA-5675194 Activated MAPK phosphorylates RAF1 R-HSA-5672951 Inactive RAFs bind YWHAB R-HSA-5674140 PAQR3 binds inactive RAFs R-HSA-5624492 PAK phosphorylates p21 RAF1 on S338 R-HSA-8936731 Inactive BRAF mutants:mutant RAS:GTP bind RAF1 R-HSA-5672960 YWHAB dimer dissociates from dephosphorylated RAF R-HSA-5672966 RAS:GTP:'activator' RAF homo/heterodimerizes with other RAF monomers R-HSA-5675431 PP2A dephosphorylates RAF1 R-HSA-442737 Activation of MAPK R-HSA-5675417 PEBP1 binds activated RAF1 R-HSA-5675433 PP5 dephosphorylates RAF1 S338 R-HSA-5672961 PP2A dephosphorylates inactive RAFs R-HSA-2682349 RAF1:SGK:TSC22D3:WPP ubiquitinates SCNN channels R-HSA-8936676 Moderate kinase activity BRAF mutants:RAS:GTP homo/heterodimerize R-HSA-6802908 RAS mutants bind inactive RAF R-HSA-5672969 Phosphorylation of RAF R-HSA-6802941 RAF is paradoxically phosphorylated downstream of kinase-inactive RAF R-HSA-5674132 WDR83:LAMTOR2:LAMTOR3 binds MAPK components R-HSA-5672950 "Activator" RAF:YWHAB dimer binds RAS:GTP R-HSA-5672980 Dissociation of RAS:RAF complex R-HSA-6802942 RAS:GTP:p-RAF complexes paradoxically bind MAP2Ks and MAPKs R-HSA-6803234 Dissociation of paradoxically activated RAS:BRAF complexes R-HSA-5672972 MAP2Ks and MAPKs bind to the activated RAF complex R-HSA-6802916 RAF is phosphorylated downstream of moderate kinase activity BRAF mutants R-HSA-6802924 RAF is phosphorylated downstream of oncogenic RAS R-HSA-6802927 BRAF and RAF fusion mutant dimers are phosphorylated R-HSA-6802918 Activated MAP2Ks phosphorylate MAPKs downstream of inactive BRAF mutants R-HSA-6802943 RAS:GTP:inactive p-RAF complexes phosphorylate MAP2Ks R-HSA-6802914 RAS:GTP:moderate kinase activity p-RAF complexes bind MAP2Ks and MAPKs R-HSA-6803230 Dissociation of moderate activity BRAF complexes R-HSA-5672978 RAF phosphorylates MAP2K dimer R-HSA-5672973 MAP2Ks phosphorylate MAPKs R-HSA-6802925 Mutant RAS:p-RAF complexes bind MAP2Ks and MAPKs R-HSA-6803233 Dissociation of oncogenic RAS:RAF complex R-HSA-6802919 RAS:GTP:moderate kinase activity p-RAF complexes phosphorylate MAP2Ks R-HSA-6802921 Activated MAP2Ks phosphorylate MAPKs downstream of moderate kinase activity BRAF mutants R-HSA-6802926 Mutant RAS:p-RAF complexes phosphorylate MAP2Ks R-HSA-6802922 Activated MAP2Ks phosphorylate MAPKs downstream of oncogenic RAS R-HSA-392517 Rap1 signalling R-HSA-430116 GP1b-IX-V activation signalling R-HSA-5621575 CD209 (DC-SIGN) signaling R-HSA-5674499 Negative feedback regulation of MAPK pathway R-HSA-5673000 RAF activation R-HSA-5675221 Negative regulation of MAPK pathway R-HSA-1280218 Adaptive Immune System R-HSA-76002 Platelet activation, signaling and aggregation R-HSA-5621481 C-type lectin receptors (CLRs) R-HSA-6802955 Paradoxical activation of RAF signaling by kinase inactive BRAF R-HSA-442742 CREB phosphorylation through the activation of Ras R-HSA-5673001 RAF/MAP kinase cascade R-HSA-2672351 Stimuli-sensing channels R-HSA-168256 Immune System R-HSA-109582 Hemostasis R-HSA-168249 Innate Immune System R-HSA-6802946 Signaling by moderate kinase activity BRAF mutants R-HSA-6802949 Signaling by RAS mutants R-HSA-6802957 Oncogenic MAPK signaling R-HSA-438064 Post NMDA receptor activation events R-HSA-5674135 MAP2K and MAPK activation R-HSA-6802952 Signaling by BRAF and RAF fusions R-HSA-5684996 MAPK1/MAPK3 signaling R-HSA-983712 Ion channel transport R-HSA-5663202 Diseases of signal transduction R-HSA-442755 Activation of NMDA receptor and postsynaptic events R-HSA-5683057 MAPK family signaling cascades R-HSA-382551 Transport of small molecules R-HSA-1643685 Disease R-HSA-112314 Neurotransmitter receptors and postsynaptic signal transmission R-HSA-162582 Signal Transduction R-HSA-112315 Transmission across Chemical Synapses R-HSA-112316 Neuronal System
US Server
