| Summary | |
|---|---|
| Symbol | RAF1 |
| Name | Raf-1 proto-oncogene, serine/threonine kinase |
| Aliases | Raf-1; c-Raf; CRAF; C-Raf proto-oncogene, serine/threonine kinase; v-raf-1 murine leukemia viral oncogene ho ...... |
| Chromosomal Location | 3p25 |
| External Links | HGNC, NCBI, Ensembl, Uniprot, GeneCards |
| Content |
Basic function annotation. > Subcellular Location, Domain and Function > Gene Ontology > KEGG and Reactome Pathway |
| 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. |
| Domain |
PF00130 Phorbol esters/diacylglycerol binding domain (C1 domain) PF07714 Protein tyrosine kinase PF02196 Raf-like Ras-binding domain |
| 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. |
| Biological Process |
GO:0000186 activation of MAPKK activity GO:0001666 response to hypoxia GO:0001678 cellular glucose homeostasis GO:0002218 activation of innate immune response GO:0002220 innate immune response activating cell surface receptor signaling pathway GO:0002223 stimulatory C-type lectin receptor signaling pathway GO:0002429 immune response-activating cell surface receptor signaling pathway GO:0002757 immune response-activating signal transduction GO:0002758 innate immune response-activating signal transduction GO:0002764 immune response-regulating signaling pathway GO:0002768 immune response-regulating cell surface receptor signaling pathway GO:0002790 peptide secretion GO:0006140 regulation of nucleotide metabolic process GO:0006164 purine nucleotide biosynthetic process GO:0006171 cAMP biosynthetic process GO:0007190 activation of adenylate cyclase activity GO:0007265 Ras protein signal transduction GO:0007266 Rho protein signal transduction GO:0007507 heart development GO:0007596 blood coagulation GO:0007599 hemostasis GO:0008625 extrinsic apoptotic signaling pathway via death domain receptors GO:0009150 purine ribonucleotide metabolic process GO:0009152 purine ribonucleotide biosynthetic process GO:0009165 nucleotide biosynthetic process GO:0009187 cyclic nucleotide metabolic process GO:0009190 cyclic nucleotide biosynthetic process GO:0009260 ribonucleotide biosynthetic process GO:0009306 protein secretion GO:0009612 response to mechanical stimulus GO:0009743 response to carbohydrate GO:0009746 response to hexose GO:0009749 response to glucose GO:0009914 hormone transport GO:0010466 negative regulation of peptidase activity GO:0010817 regulation of hormone levels GO:0010951 negative regulation of endopeptidase activity GO:0015833 peptide transport GO:0018105 peptidyl-serine phosphorylation GO:0018209 peptidyl-serine modification GO:0019827 stem cell population maintenance GO:0023061 signal release GO:0030072 peptide hormone secretion GO:0030073 insulin secretion GO:0030168 platelet activation GO:0030799 regulation of cyclic nucleotide metabolic process GO:0030801 positive regulation of cyclic nucleotide metabolic process GO:0030802 regulation of cyclic nucleotide biosynthetic process GO:0030804 positive regulation of cyclic nucleotide biosynthetic process GO:0030808 regulation of nucleotide biosynthetic process GO:0030810 positive regulation of nucleotide biosynthetic process GO:0030814 regulation of cAMP metabolic process GO:0030816 positive regulation of cAMP metabolic process GO:0030817 regulation of cAMP biosynthetic process GO:0030819 positive regulation of cAMP biosynthetic process GO:0030878 thyroid gland development GO:0031279 regulation of cyclase activity GO:0031281 positive regulation of cyclase activity GO:0031333 negative regulation of protein complex assembly GO:0031349 positive regulation of defense response GO:0032147 activation of protein kinase activity GO:0033135 regulation of peptidyl-serine phosphorylation GO:0033138 positive regulation of peptidyl-serine phosphorylation GO:0033500 carbohydrate homeostasis GO:0033674 positive regulation of kinase activity GO:0034284 response to monosaccharide GO:0035019 somatic stem cell population maintenance GO:0035023 regulation of Rho protein signal transduction GO:0035270 endocrine system development GO:0035773 insulin secretion involved in cellular response to glucose stimulus GO:0035994 response to muscle stretch GO:0036293 response to decreased oxygen levels GO:0038179 neurotrophin signaling pathway GO:0042593 glucose homeostasis GO:0042886 amide transport GO:0043154 negative regulation of cysteine-type endopeptidase activity involved in apoptotic process GO:0043254 regulation of protein complex assembly GO:0043281 regulation of cysteine-type endopeptidase activity involved in apoptotic process GO:0043405 regulation of MAP kinase activity GO:0043410 positive regulation of MAPK cascade GO:0045088 regulation of innate immune response GO:0045089 positive regulation of innate immune response GO:0045103 intermediate filament-based process GO:0045104 intermediate filament cytoskeleton organization GO:0045761 regulation of adenylate cyclase activity GO:0045762 positive regulation of adenylate cyclase activity GO:0045860 positive regulation of protein kinase activity GO:0045861 negative regulation of proteolysis GO:0045981 positive regulation of nucleotide metabolic process GO:0046058 cAMP metabolic process GO:0046390 ribose phosphate biosynthetic process GO:0046578 regulation of Ras protein signal transduction GO:0046879 hormone secretion GO:0048011 neurotrophin TRK receptor signaling pathway GO:0048538 thymus development GO:0048732 gland development GO:0050817 coagulation GO:0050878 regulation of body fluid levels GO:0051056 regulation of small GTPase mediated signal transduction GO:0051339 regulation of lyase activity GO:0051346 negative regulation of hydrolase activity GO:0051349 positive regulation of lyase activity GO:0052547 regulation of peptidase activity GO:0052548 regulation of endopeptidase activity GO:0052652 cyclic purine nucleotide metabolic process GO:0060324 face development GO:0070482 response to oxygen levels GO:0071322 cellular response to carbohydrate stimulus GO:0071326 cellular response to monosaccharide stimulus GO:0071331 cellular response to hexose stimulus GO:0071333 cellular response to glucose stimulus GO:0071550 death-inducing signaling complex assembly GO:0071900 regulation of protein serine/threonine kinase activity GO:0072522 purine-containing compound biosynthetic process GO:0097191 extrinsic apoptotic signaling pathway GO:0098727 maintenance of cell number GO:1900371 regulation of purine nucleotide biosynthetic process GO:1900373 positive regulation of purine nucleotide biosynthetic process GO:1900542 regulation of purine nucleotide metabolic process GO:1900544 positive regulation of purine nucleotide metabolic process GO:1901293 nucleoside phosphate biosynthetic process GO:1902041 regulation of extrinsic apoptotic signaling pathway via death domain receptors GO:1902042 negative regulation of extrinsic apoptotic signaling pathway via death domain receptors GO:2000116 regulation of cysteine-type endopeptidase activity GO:2000117 negative regulation of cysteine-type endopeptidase activity GO:2001233 regulation of apoptotic signaling pathway GO:2001234 negative regulation of apoptotic signaling pathway GO:2001236 regulation of extrinsic apoptotic signaling pathway GO:2001237 negative regulation of extrinsic apoptotic signaling pathway |
| Molecular Function |
GO:0004674 protein serine/threonine kinase activity GO:0004702 receptor signaling protein serine/threonine kinase activity GO:0004709 MAP kinase kinase kinase activity GO:0005057 receptor signaling protein activity GO:0031434 mitogen-activated protein kinase kinase binding GO:0046982 protein heterodimerization activity |
| Cellular Component |
GO:0005741 mitochondrial outer membrane GO:0019867 outer membrane GO:0031143 pseudopodium GO:0031968 organelle outer membrane |
| KEGG |
hsa04010 MAPK signaling pathway hsa04012 ErbB signaling pathway hsa04014 Ras signaling pathway hsa04015 Rap1 signaling pathway hsa04022 cGMP-PKG signaling pathway hsa04024 cAMP signaling pathway hsa04062 Chemokine signaling pathway hsa04068 FoxO signaling pathway hsa04071 Sphingolipid signaling pathway hsa04140 Regulation of autophagy hsa04150 mTOR signaling pathway hsa04151 PI3K-Akt signaling pathway hsa04210 Apoptosis hsa04270 Vascular smooth muscle contraction hsa04360 Axon guidance hsa04370 VEGF signaling pathway hsa04510 Focal adhesion hsa04540 Gap junction hsa04550 Signaling pathways regulating pluripotency of stem cells hsa04630 Jak-STAT signaling pathway 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 hsa04726 Serotonergic synapse hsa04730 Long-term depression hsa04810 Regulation of actin cytoskeleton hsa04910 Insulin signaling pathway hsa04912 GnRH signaling pathway hsa04914 Progesterone-mediated oocyte maturation hsa04915 Estrogen signaling pathway hsa04916 Melanogenesis hsa04917 Prolactin signaling pathway hsa04919 Thyroid hormone signaling pathway hsa04921 Oxytocin signaling pathway |
| Reactome |
R-HSA-170984: ARMS-mediated activation R-HSA-442755: Activation of NMDA receptor upon glutamate binding and postsynaptic events R-HSA-1280218: Adaptive Immune System R-HSA-422475: Axon guidance R-HSA-5621481: C-type lectin receptors (CLRs) R-HSA-5621575: CD209 (DC-SIGN) signaling R-HSA-442742: CREB phosphorylation through the activation of Ras R-HSA-1280215: Cytokine Signaling in Immune system R-HSA-2172127: DAP12 interactions R-HSA-2424491: DAP12 signaling R-HSA-1266738: Developmental Biology R-HSA-1643685: Disease R-HSA-5663202: Diseases of signal transduction R-HSA-186763: Downstream signal transduction R-HSA-2871796: FCERI mediated MAPK activation R-HSA-2454202: Fc epsilon receptor (FCERI) signaling R-HSA-170968: Frs2-mediated activation R-HSA-430116: GP1b-IX-V activation signalling R-HSA-179812: GRB2 events in EGFR signaling R-HSA-881907: Gastrin-CREB signalling pathway via PKC and MAPK R-HSA-109582: Hemostasis R-HSA-2428924: IGF1R signaling cascade R-HSA-112399: IRS-mediated signalling R-HSA-2428928: IRS-related events triggered by IGF1R R-HSA-168256: Immune System R-HSA-168249: Innate Immune System R-HSA-74751: Insulin receptor signalling cascade R-HSA-912526: Interleukin receptor SHC signaling R-HSA-451927: Interleukin-2 signaling R-HSA-512988: Interleukin-3, 5 and GM-CSF signaling R-HSA-983712: Ion channel transport R-HSA-5674135: MAP2K and MAPK activation R-HSA-5683057: MAPK family signaling cascades R-HSA-5684996: MAPK1/MAPK3 signaling R-HSA-375165: NCAM signaling for neurite out-growth R-HSA-187037: NGF signalling via TRKA from the plasma membrane R-HSA-5674499: Negative feedback regulation of MAPK pathway R-HSA-5675221: Negative regulation of MAPK pathway R-HSA-112316: Neuronal System R-HSA-112314: Neurotransmitter Receptor Binding And Downstream Transmission In The Postsynaptic Cell R-HSA-6802957: Oncogenic MAPK signaling R-HSA-6802955: Paradoxical activation of RAF signaling by kinase inactive BRAF R-HSA-76002: Platelet activation, signaling and aggregation R-HSA-438064: Post NMDA receptor activation events R-HSA-169893: Prolonged ERK activation events R-HSA-5673000: RAF activation R-HSA-5673001: RAF/MAP kinase cascade R-HSA-8853659: RET signaling R-HSA-392517: Rap1 signalling R-HSA-180336: SHC1 events in EGFR signaling R-HSA-112412: SOS-mediated signalling R-HSA-162582: Signal Transduction R-HSA-6802952: Signaling by BRAF and RAF fusions R-HSA-177929: Signaling by EGFR R-HSA-372790: Signaling by GPCR R-HSA-74752: Signaling by Insulin receptor R-HSA-449147: Signaling by Interleukins R-HSA-2586552: Signaling by Leptin R-HSA-186797: Signaling by PDGF R-HSA-6802949: Signaling by RAS mutants R-HSA-1433557: Signaling by SCF-KIT R-HSA-2404192: Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R) R-HSA-194138: Signaling by VEGF R-HSA-6802948: Signaling by high-kinase activity BRAF mutants R-HSA-6802946: Signaling by moderate kinase activity BRAF mutants R-HSA-166520: Signalling by NGF R-HSA-187687: Signalling to ERKs R-HSA-167044: Signalling to RAS R-HSA-187706: Signalling to p38 via RIT and RIN R-HSA-2672351: Stimuli-sensing channels R-HSA-382551: Transmembrane transport of small molecules R-HSA-112315: Transmission across Chemical Synapses R-HSA-4420097: VEGFA-VEGFR2 Pathway R-HSA-5218921: VEGFR2 mediated cell proliferation |
| Summary | |
|---|---|
| Symbol | RAF1 |
| Name | Raf-1 proto-oncogene, serine/threonine kinase |
| Aliases | Raf-1; c-Raf; CRAF; C-Raf proto-oncogene, serine/threonine kinase; v-raf-1 murine leukemia viral oncogene ho ...... |
| Chromosomal Location | 3p25 |
| External Links | HGNC, NCBI, Ensembl, Uniprot, GeneCards |
| Content | Literatures that report relations between RAF1 and anti-tumor immunity. The specific mechanism were also collected if the literature reports that a gene specifically promotes or inhibits the infiltration or function of T/NK cells. |
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Literatures describing the relation between RAF1 and anti-tumor immunity in human cancer.
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| Summary | |
|---|---|
| Symbol | RAF1 |
| Name | Raf-1 proto-oncogene, serine/threonine kinase |
| Aliases | Raf-1; c-Raf; CRAF; C-Raf proto-oncogene, serine/threonine kinase; v-raf-1 murine leukemia viral oncogene ho ...... |
| Chromosomal Location | 3p25 |
| External Links | HGNC, NCBI, Ensembl, Uniprot, GeneCards |
| Content | High-throughput screening data (e.g. CRISPR-Cas9, shRNA and RNAi) for T cell-mediated killing. Genetic screen techniques can identify mechanisms of tumor cell resistance (e.g., PTPN2) and sensitivity (e.g., APLNR) to killing by cytotoxic T cells, the central effectors of anti-tumor immunity. After comprehensively searching, eight groups of screening data sets were collected in the current database. In this tab, users can check whether their selected genes cause resistance or increase sensitivity to T cell-mediated killing in various data sets. |
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> High-throughput Screening
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Statistical results of RAF1 in screening data sets for detecting immune reponses.
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| Summary | |
|---|---|
| Symbol | RAF1 |
| Name | Raf-1 proto-oncogene, serine/threonine kinase |
| Aliases | Raf-1; c-Raf; CRAF; C-Raf proto-oncogene, serine/threonine kinase; v-raf-1 murine leukemia viral oncogene ho ...... |
| Chromosomal Location | 3p25 |
| External Links | HGNC, NCBI, Ensembl, Uniprot, GeneCards |
| Content |
Transcriptomic and genomic profiling of pre-treated tumor biopsies from responders and non-responders to immunotherapy. These data were used to identify signatures and mechanisms of response to checkpoint blockade (e.g., anti-PDL1 and anti-PD1). One example is that mutations in the gene PBRM1 benefit clinical survival of patients with clear cell renal cell carcinoma. After comprehensively searching, we collected 5 and 6 of transcriptomic and genomic data sets, respectively. In this tab, users can check whether their selected genes have significant difference of expression or mutation between responders and non-responders in various data sets. > Expression difference between responders and non-responders > Mutation difference between responders and non-responders |
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Points in the above scatter plot represent the expression difference of RAF1 in various data sets.
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Points in the above scatter plot represent the mutation difference of RAF1 in various data sets.
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| Summary | |
|---|---|
| Symbol | RAF1 |
| Name | Raf-1 proto-oncogene, serine/threonine kinase |
| Aliases | Raf-1; c-Raf; CRAF; C-Raf proto-oncogene, serine/threonine kinase; v-raf-1 murine leukemia viral oncogene ho ...... |
| Chromosomal Location | 3p25 |
| External Links | HGNC, NCBI, Ensembl, Uniprot, GeneCards |
| Content |
Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of RAF1. The immune-related signatures of 28 TIL types from Charoentong's study, which can be viewed in the download page. For each cancer type, the relative abundance of TILs were inferred by using gene set variation analysis (GSVA) based on gene expression profile. In this tab, users can examine which kinds of TILs might be regulated by the current gene. |
| Summary | |
|---|---|
| Symbol | RAF1 |
| Name | Raf-1 proto-oncogene, serine/threonine kinase |
| Aliases | Raf-1; c-Raf; CRAF; C-Raf proto-oncogene, serine/threonine kinase; v-raf-1 murine leukemia viral oncogene ho ...... |
| Chromosomal Location | 3p25 |
| External Links | HGNC, NCBI, Ensembl, Uniprot, GeneCards |
| Content |
Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of RAF1. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by RAF1. > Immunoinhibitor > Immunostimulator > MHC molecule |
| Summary | |
|---|---|
| Symbol | RAF1 |
| Name | Raf-1 proto-oncogene, serine/threonine kinase |
| Aliases | Raf-1; c-Raf; CRAF; C-Raf proto-oncogene, serine/threonine kinase; v-raf-1 murine leukemia viral oncogene ho ...... |
| Chromosomal Location | 3p25 |
| External Links | HGNC, NCBI, Ensembl, Uniprot, GeneCards |
| Content |
Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of RAF1. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene. > Chemokine > Receptor |
| Summary | |
|---|---|
| Symbol | RAF1 |
| Name | Raf-1 proto-oncogene, serine/threonine kinase |
| Aliases | Raf-1; c-Raf; CRAF; C-Raf proto-oncogene, serine/threonine kinase; v-raf-1 murine leukemia viral oncogene ho ...... |
| Chromosomal Location | 3p25 |
| External Links | HGNC, NCBI, Ensembl, Uniprot, GeneCards |
| Content |
Distribution of RAF1 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype |
| Summary | |
|---|---|
| Symbol | RAF1 |
| Name | Raf-1 proto-oncogene, serine/threonine kinase |
| Aliases | Raf-1; c-Raf; CRAF; C-Raf proto-oncogene, serine/threonine kinase; v-raf-1 murine leukemia viral oncogene ho ...... |
| Chromosomal Location | 3p25 |
| External Links | HGNC, NCBI, Ensembl, Uniprot, GeneCards |
| Content |
Associations between RAF1 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade |
| Summary | |
|---|---|
| Symbol | RAF1 |
| Name | Raf-1 proto-oncogene, serine/threonine kinase |
| Aliases | Raf-1; c-Raf; CRAF; C-Raf proto-oncogene, serine/threonine kinase; v-raf-1 murine leukemia viral oncogene ho ...... |
| Chromosomal Location | 3p25 |
| External Links | HGNC, NCBI, Ensembl, Uniprot, GeneCards |
| Content | Drugs targeting RAF1 collected from DrugBank database. |
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Details on drugs targeting RAF1.
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