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    ARAF A-Raf proto-oncogene, serine/threonine kinase [ Homo sapiens (human) ]

    Gene ID: 369, updated on 13-Feb-2019

    Summary

    Official Symbol
    ARAFprovided by HGNC
    Official Full Name
    A-Raf proto-oncogene, serine/threonine kinaseprovided by HGNC
    Primary source
    HGNC:HGNC:646
    See related
    Ensembl:ENSG00000078061 MIM:311010
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    PKS2; A-RAF; ARAF1; RAFA1
    Summary
    This proto-oncogene belongs to the RAF subfamily of the Ser/Thr protein kinase family, and maybe involved in cell growth and development. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Jan 2012]
    Expression
    Ubiquitous expression in bone marrow (RPKM 16.5), spleen (RPKM 14.0) and 25 other tissues See more
    Orthologs

    Genomic context

    See ARAF in Genome Data Viewer
    Location:
    Xp11.3
    Exon count:
    18
    Annotation release Status Assembly Chr Location
    109 current GRCh38.p12 (GCF_000001405.38) X NC_000023.11 (47561100..47571921)
    105 previous assembly GRCh37.p13 (GCF_000001405.25) X NC_000023.10 (47420499..47431320)

    Chromosome X - NC_000023.11Genomic Context describing neighboring genes Neighboring gene zinc finger protein 41 Neighboring gene long intergenic non-protein coding RNA 1560 Neighboring gene NUS1 pseudogene 1 Neighboring gene synapsin I Neighboring gene TIMP metallopeptidase inhibitor 1 Neighboring gene microRNA 4769

    Genomic regions, transcripts, and products

    Expression

    • Project title: HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Apr 4 07:08:55 2018

    Bibliography

    GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

    HIV-1 interactions

    Protein interactions

    Protein Gene Interaction Pubs
    Pr55(Gag) gag The amplified luminescent proximity homogeneous assay (AlphaScreen) identifies the interaction of HIV-1 Gag with ARAF PubMed

    Go to the HIV-1, Human Interaction Database

    Pathways from BioSystems

    • ARMS-mediated activation, organism-specific biosystem (from REACTOME)
      ARMS-mediated activation, organism-specific biosystemARMS (Ankyrin-Rich Membrane Spanning/Kidins 220) is a 220kD tetraspanning adaptor protein which becomes rapidly tyrosine phosphorylated by active Trk receptors. ARMS is another adaptor protein which ...
    • Acute myeloid leukemia, organism-specific biosystem (from KEGG)
      Acute myeloid leukemia, organism-specific biosystemAcute myeloid leukemia (AML) is a disease that is characterized by uncontrolled proliferation of clonal neoplastic cells and accumulation in the bone marrow of blasts with an impaired differentiation...
    • Acute myeloid leukemia, conserved biosystem (from KEGG)
      Acute myeloid leukemia, conserved biosystemAcute myeloid leukemia (AML) is a disease that is characterized by uncontrolled proliferation of clonal neoplastic cells and accumulation in the bone marrow of blasts with an impaired differentiation...
    • Alcoholism, organism-specific biosystem (from KEGG)
      Alcoholism, organism-specific biosystemAlcoholism, also called dependence on alcohol (ethanol), is a chronic relapsing disorder that is progressive and has serious detrimental health outcomes. As one of the primary mediators of the reward...
    • Alcoholism, conserved biosystem (from KEGG)
      Alcoholism, conserved biosystemAlcoholism, also called dependence on alcohol (ethanol), is a chronic relapsing disorder that is progressive and has serious detrimental health outcomes. As one of the primary mediators of the reward...
    • Axon guidance, organism-specific biosystem (from REACTOME)
      Axon guidance, organism-specific biosystemAxon guidance / axon pathfinding is the process by which neurons send out axons to reach the correct targets. Growing axons have a highly motile structure at the growing tip called the growth cone, w...
    • Bladder cancer, organism-specific biosystem (from KEGG)
      Bladder cancer, organism-specific biosystemThe urothelium covers the luminal surface of almost the entire urinary tract, extending from the renal pelvis, through the ureter and bladder, to the proximal urethra. The majority of urothelial carc...
    • Bladder cancer, conserved biosystem (from KEGG)
      Bladder cancer, conserved biosystemThe urothelium covers the luminal surface of almost the entire urinary tract, extending from the renal pelvis, through the ureter and bladder, to the proximal urethra. The majority of urothelial carc...
    • Breast cancer, organism-specific biosystem (from KEGG)
      Breast cancer, organism-specific biosystemBreast cancer is the leading cause of cancer death among women worldwide. The vast majority of breast cancers are carcinomas that originate from cells lining the milk-forming ducts of the mammary gla...
    • Breast cancer, conserved biosystem (from KEGG)
      Breast cancer, conserved biosystemBreast cancer is the leading cause of cancer death among women worldwide. The vast majority of breast cancers are carcinomas that originate from cells lining the milk-forming ducts of the mammary gla...
    • Chronic myeloid leukemia, organism-specific biosystem (from KEGG)
      Chronic myeloid leukemia, organism-specific biosystemChronic myeloid leukemia (CML) is a clonal myeloproliferative disorder of a pluripotent stem cell. The natural history of CML has a triphasic clinical course comprising of an initial chronic phase (C...
    • Chronic myeloid leukemia, conserved biosystem (from KEGG)
      Chronic myeloid leukemia, conserved biosystemChronic myeloid leukemia (CML) is a clonal myeloproliferative disorder of a pluripotent stem cell. The natural history of CML has a triphasic clinical course comprising of an initial chronic phase (C...
    • Colorectal cancer, organism-specific biosystem (from KEGG)
      Colorectal cancer, organism-specific biosystemColorectal cancer (CRC) is the second largest cause of cancer-related deaths in Western countries. CRC arises from the colorectal epithelium as a result of the accumulation of genetic alterations in ...
    • Colorectal cancer, conserved biosystem (from KEGG)
      Colorectal cancer, conserved biosystemColorectal cancer (CRC) is the second largest cause of cancer-related deaths in Western countries. CRC arises from the colorectal epithelium as a result of the accumulation of genetic alterations in ...
    • Common Pathways Underlying Drug Addiction, organism-specific biosystem (from WikiPathways)
      Common Pathways Underlying Drug Addiction, organism-specific biosystemThe pathway was modeled after Figure 2 in Li, et al. 2008 and is based on the common pathways identified in their study as well as protein interaction data. Specifically, glutamate and dopamine neuro...
    • Cytokine Signaling in Immune system, organism-specific biosystem (from REACTOME)
      Cytokine Signaling in Immune system, organism-specific biosystemCytokines are small proteins that regulate and mediate immunity, inflammation, and hematopoiesis. They are secreted in response to immune stimuli, and usually act briefly, locally, at very low concen...
    • DAP12 interactions, organism-specific biosystem (from REACTOME)
      DAP12 interactions, organism-specific biosystemDNAX activation protein of 12kDa (DAP12) is an immunoreceptor tyrosine-based activation motif (ITAM)-bearing adapter molecule that transduces activating signals in natural killer (NK) and myeloid cel...
    • DAP12 signaling, organism-specific biosystem (from REACTOME)
      DAP12 signaling, organism-specific biosystemIn response to receptor ligation, the tyrosine residues in DAP12's immunoreceptor tyrosine-based activation motif (ITAM) are phosphorylated by Src family kinases. These phosphotyrosines form the dock...
    • Developmental Biology, organism-specific biosystem (from REACTOME)
      Developmental Biology, organism-specific biosystemAs a first step towards capturing the array of processes by which a fertilized egg gives rise to the diverse tissues of the body, examples of three kinds of processes have been annotated. These are a...
    • Disease, organism-specific biosystem (from REACTOME)
      Disease, organism-specific biosystemBiological processes are captured in Reactome by identifying the molecules (DNA, RNA, protein, small molecules) involved in them and describing the details of their interactions. From this molecular ...
    • Diseases of signal transduction, organism-specific biosystem (from REACTOME)
      Diseases of signal transduction, organism-specific biosystemSignaling processes are central to human physiology (e.g., Pires-da Silva & Sommer 2003), and their disruption by either germ-line and somatic mutation can lead to serious disease. Here, the molecula...
    • Downstream signal transduction, organism-specific biosystem (from REACTOME)
      Downstream signal transduction, organism-specific biosystemThe role of autophosphorylation sites on PDGF receptors are to provide docking sites for downstream signal transduction molecules which contain SH2 domains. The SH2 domain is a conserved motif of aro...
    • EGFR tyrosine kinase inhibitor resistance, organism-specific biosystem (from KEGG)
      EGFR tyrosine kinase inhibitor resistance, organism-specific biosystemEGFR is a tyrosine kinase that participates in the regulation of cellular homeostasis. EGFR also serves as a stimulus for cancer growth. EGFR gene mutations and protein overexpression, both of which ...
    • EGFR tyrosine kinase inhibitor resistance, conserved biosystem (from KEGG)
      EGFR tyrosine kinase inhibitor resistance, conserved biosystemEGFR is a tyrosine kinase that participates in the regulation of cellular homeostasis. EGFR also serves as a stimulus for cancer growth. EGFR gene mutations and protein overexpression, both of which ...
    • Endocrine resistance, organism-specific biosystem (from KEGG)
      Endocrine resistance, organism-specific biosystemEndocrine therapy is a key treatment strategy to control or eradicate hormone-responsive breast cancer. The most commonly used endocrine therapy agents are selective estrogen receptor modulators (SER...
    • Endocrine resistance, conserved biosystem (from KEGG)
      Endocrine resistance, conserved biosystemEndocrine therapy is a key treatment strategy to control or eradicate hormone-responsive breast cancer. The most commonly used endocrine therapy agents are selective estrogen receptor modulators (SER...
    • Endometrial cancer, organism-specific biosystem (from KEGG)
      Endometrial cancer, organism-specific biosystemEndometrial cancer (EC) is the most common gynaecological malignancy and the fourth most common malignancy in women in the developed world after breast, colorectal and lung cancer. Two types of endom...
    • Endometrial cancer, conserved biosystem (from KEGG)
      Endometrial cancer, conserved biosystemEndometrial cancer (EC) is the most common gynaecological malignancy and the fourth most common malignancy in women in the developed world after breast, colorectal and lung cancer. Two types of endom...
    • ErbB Signaling Pathway, organism-specific biosystem (from WikiPathways)
      ErbB Signaling Pathway, organism-specific biosystemThe ErbB protein family or epidermal growth factor receptor (EGFR) family is a family of four structurally related receptor tyrosine kinases. Insufficient ErbB signaling in humans is associated with ...
    • ErbB signaling pathway, organism-specific biosystem (from KEGG)
      ErbB signaling pathway, organism-specific biosystemThe ErbB family of receptor tyrosine kinases (RTKs) couples binding of extracellular growth factor ligands to intracellular signaling pathways regulating diverse biologic responses, including prolife...
    • ErbB signaling pathway, conserved biosystem (from KEGG)
      ErbB signaling pathway, conserved biosystemThe ErbB family of receptor tyrosine kinases (RTKs) couples binding of extracellular growth factor ligands to intracellular signaling pathways regulating diverse biologic responses, including prolife...
    • FCERI mediated MAPK activation, organism-specific biosystem (from REACTOME)
      FCERI mediated MAPK activation, organism-specific biosystemFormation of the LAT signaling complex leads to activation of MAPK and production of cytokines. The sequence of events that leads from LAT to cytokine production has not been as clearly defined as th...
    • Fc epsilon receptor (FCERI) signaling, organism-specific biosystem (from REACTOME)
      Fc epsilon receptor (FCERI) signaling, organism-specific biosystemMast cells (MC) are distributed in tissues throughout the human body and have long been recognized as key cells of type I hypersensitivity reactions. They also play important roles in inflammatory an...
    • Focal Adhesion, organism-specific biosystem (from WikiPathways)
      Focal Adhesion, organism-specific biosystemCell-matrix adhesions play essential roles in important biological processes including cell motility, cell proliferation, cell differentiation, regulation of gene expression and cell survival. At the...
    • FoxO signaling pathway, organism-specific biosystem (from KEGG)
      FoxO signaling pathway, organism-specific biosystemThe forkhead box O (FOXO) family of transcription factors regulates the expression of genes in cellular physiological events including apoptosis, cell-cycle control, glucose metabolism, oxidative str...
    • Frs2-mediated activation, organism-specific biosystem (from REACTOME)
      Frs2-mediated activation, organism-specific biosystemThe adaptor protein Frs2 (Fibroblast growth factor receptor substrate 2) can mediate the prolonged activation of the MAPK (ERK) cascade.
    • GRB2 events in EGFR signaling, organism-specific biosystem (from REACTOME)
      GRB2 events in EGFR signaling, organism-specific biosystemAutophosphorylated EGFR tyrosine residues are docking sites for many downstream effectors in EGFR signaling. The adaptor protein GRB2 binds to phosphotyrosine residues in the C-tail of EGFR through i...
    • Gastrin-CREB signalling pathway via PKC and MAPK, organism-specific biosystem (from REACTOME)
      Gastrin-CREB signalling pathway via PKC and MAPK, organism-specific biosystemGastrin is a hormone whose main function is to stimulate secretion of hydrochloric acid by the gastric mucosa, which results in gastrin formation inhibition. This hormone also acts as a mitogenic fac...
    • Glioma, organism-specific biosystem (from KEGG)
      Glioma, organism-specific biosystemGliomas are the most common of the primary brain tumors and account for more than 40% of all central nervous system neoplasms. Gliomas include tumours that are composed predominantly of astrocytes (a...
    • Glioma, conserved biosystem (from KEGG)
      Glioma, conserved biosystemGliomas are the most common of the primary brain tumors and account for more than 40% of all central nervous system neoplasms. Gliomas include tumours that are composed predominantly of astrocytes (a...
    • Hepatitis C, organism-specific biosystem (from KEGG)
      Hepatitis C, organism-specific biosystemHepatitis C virus (HCV) is a major cause of chronic liver disease. The HCV employ several strategies to perturb host cell immunity. After invasion, HCV RNA genome functions directly as an mRNA in the...
    • Hepatitis C, conserved biosystem (from KEGG)
      Hepatitis C, conserved biosystemHepatitis C virus (HCV) is a major cause of chronic liver disease. The HCV employ several strategies to perturb host cell immunity. After invasion, HCV RNA genome functions directly as an mRNA in the...
    • IGF1R signaling cascade, organism-specific biosystem (from REACTOME)
      IGF1R signaling cascade, organism-specific biosystemAfter autophosphorylation the type 1 insulin-like growth factor receptor (IGF1R) binds and phosphorylates scaffold proteins, IRS1/2/4 and SHC1, which in turn bind effectors possessing enzymatic activ...
    • IRS-mediated signalling, organism-specific biosystem (from REACTOME)
      IRS-mediated signalling, organism-specific biosystemRelease of phospho-IRS from the insulin receptor triggers a cascade of signalling events via PI3K, SOS, RAF and the MAP kinases.
    • IRS-related events triggered by IGF1R, organism-specific biosystem (from REACTOME)
      IRS-related events triggered by IGF1R, organism-specific biosystemThe phosphorylated type 1 insulin-like growth factor receptor phosphorylates IR1, IRS2, IRS4 and possibly other IRS/DOK family members (reviewed in Pavelic et al. 2007, Chitnis et al. 2008, Maki et a...
    • Immune System, organism-specific biosystem (from REACTOME)
      Immune System, organism-specific biosystemHumans are exposed to millions of potential pathogens daily, through contact, ingestion, and inhalation. Our ability to avoid infection depends on the adaptive immune system and during the first crit...
    • Innate Immune System, organism-specific biosystem (from REACTOME)
      Innate Immune System, organism-specific biosystemInnate immunity encompases the nonspecific part of immunity tha are part of an individual's natural biologic makeup
    • Insulin receptor signalling cascade, organism-specific biosystem (from REACTOME)
      Insulin receptor signalling cascade, organism-specific biosystemAutophosphorylation of the insulin receptor triggers a series of signalling events, mediated by SHC or IRS, and resulting in activation of the Ras/RAF and MAP kinase cascades. A second effect of the ...
    • Insulin signaling pathway, organism-specific biosystem (from KEGG)
      Insulin signaling pathway, organism-specific biosystemInsulin binding to its receptor results in the tyrosine phosphorylation of insulin receptor substrates (IRS) by the insulin receptor tyrosine kinase (INSR). This allows association of IRSs with the r...
    • Insulin signaling pathway, conserved biosystem (from KEGG)
      Insulin signaling pathway, conserved biosystemInsulin binding to its receptor results in the tyrosine phosphorylation of insulin receptor substrates (IRS) by the insulin receptor tyrosine kinase (INSR). This allows association of IRSs with the r...
    • Integrated Breast Cancer Pathway, organism-specific biosystem (from WikiPathways)
      Integrated Breast Cancer Pathway, organism-specific biosystemThis pathway incorporates the most important proteins for Breast Cancer. The Rp score from the Connectivity-Maps (C-Maps) webserver was used to determine the rank of the most important proteins in Br...
    • Integrin-mediated Cell Adhesion, organism-specific biosystem (from WikiPathways)
      Integrin-mediated Cell Adhesion, organism-specific biosystemIntegrins are receptors that mediate attachment between a cell and the tissues surrounding it, which may be other cells or the extracellular matrix (ECM). They also play a role in cell signaling and ...
    • Interleukin receptor SHC signaling, organism-specific biosystem (from REACTOME)
      Interleukin receptor SHC signaling, organism-specific biosystemPhosphorylation of Shc at three tyrosine residues, 239, 240 (Gotoh et al. 1996) and 317 (Salcini et al. 1994) involves unidentified tyrosine kinases presumed to be part of the activated receptor comp...
    • Interleukin-2 signaling, organism-specific biosystem (from REACTOME)
      Interleukin-2 signaling, organism-specific biosystemInterleukin-2 (IL-2) is a cytokine that is produced by T cells in response to antigen stimulation. Originally, IL-2 was discovered because of its potent growth factor activity on activated T cells in...
    • Interleukin-3, 5 and GM-CSF signaling, organism-specific biosystem (from REACTOME)
      Interleukin-3, 5 and GM-CSF signaling, organism-specific biosystemThe Interleukin-3 (IL-3), IL-5 and Granulocyte-macrophage colony stimulating factor (GM-CSF) receptors form a family of heterodimeric receptors that have specific alpha chains but share a common beta...
    • Long-term depression, organism-specific biosystem (from KEGG)
      Long-term depression, organism-specific biosystemCerebellar long-term depression (LTD), thought to be a molecular and cellular basis for cerebellar learning, is a process involving a decrease in the synaptic strength between parallel fiber (PF) and...
    • Long-term depression, conserved biosystem (from KEGG)
      Long-term depression, conserved biosystemCerebellar long-term depression (LTD), thought to be a molecular and cellular basis for cerebellar learning, is a process involving a decrease in the synaptic strength between parallel fiber (PF) and...
    • Long-term potentiation, organism-specific biosystem (from KEGG)
      Long-term potentiation, organism-specific biosystemHippocampal long-term potentiation (LTP), a long-lasting increase in synaptic efficacy, is the molecular basis for learning and memory. Tetanic stimulation of afferents in the CA1 region of the hippo...
    • Long-term potentiation, conserved biosystem (from KEGG)
      Long-term potentiation, conserved biosystemHippocampal long-term potentiation (LTP), a long-lasting increase in synaptic efficacy, is the molecular basis for learning and memory. Tetanic stimulation of afferents in the CA1 region of the hippo...
    • MAP2K and MAPK activation, organism-specific biosystem (from REACTOME)
      MAP2K and MAPK activation, organism-specific biosystemActivated RAF proteins are restricted substrate kinases whose primary downstream targets are the two MAP2K proteins, MAPK2K1 and MAP2K2 (also known as MEK1 and MEK2) (reviewed in Roskoski, 2010, Rosk...
    • MAPK (ERK1/2) signaling, organism-specific biosystem (from KEGG)
      MAPK (ERK1/2) signaling, organism-specific biosystemFunctional set; Cellular processes; Cell signaling
    • MAPK (ERK1/2) signaling, conserved biosystem (from KEGG)
      MAPK (ERK1/2) signaling, conserved biosystemFunctional set; Cellular processes; Cell signaling
    • MAPK Cascade, organism-specific biosystem (from WikiPathways)
      MAPK Cascade, organism-specific biosystem
      MAPK Cascade
    • MAPK family signaling cascades, organism-specific biosystem (from REACTOME)
      MAPK family signaling cascades, organism-specific biosystemThe mitogen activated protein kinases (MAPKs) are a family of conserved protein serine threonine kinases that respond to varied extracellular stimuli to activate intracellular processes including gen...
    • MAPK1/MAPK3 signaling, organism-specific biosystem (from REACTOME)
      MAPK1/MAPK3 signaling, organism-specific biosystemThe extracellular signal regulated kinases (ERKs) 1 and 2, also known as MAPK3 and MAPK1, are phosphorylated by the MAP2Ks 1 and 2 in response to a wide range of extracellular stimuli to promote diff...
    • Melanoma, organism-specific biosystem (from KEGG)
      Melanoma, organism-specific biosystemMelanoma is a form of skin cancer that has a poor prognosis and which is on the rise in Western populations. Melanoma arises from the malignant transformation of pigment-producing cells, melanocytes...
    • Melanoma, conserved biosystem (from KEGG)
      Melanoma, conserved biosystemMelanoma is a form of skin cancer that has a poor prognosis and which is on the rise in Western populations. Melanoma arises from the malignant transformation of pigment-producing cells, melanocytes...
    • NCAM signaling for neurite out-growth, organism-specific biosystem (from REACTOME)
      NCAM signaling for neurite out-growth, organism-specific biosystemThe neural cell adhesion molecule, NCAM, is a member of the immunoglobulin (Ig) superfamily and is involved in a variety of cellular processes of importance for the formation and maintenance of the n...
    • NGF signalling via TRKA from the plasma membrane, organism-specific biosystem (from REACTOME)
      NGF signalling via TRKA from the plasma membrane, organism-specific biosystemTrk receptors signal from the plasma membrane and from intracellular membranes, particularly from early endosomes. Signalling from the plasma membrane is fast but transient; signalling from endosomes...
    • Natural killer cell mediated cytotoxicity, organism-specific biosystem (from KEGG)
      Natural killer cell mediated cytotoxicity, organism-specific biosystemNatural killer (NK) cells are lymphocytes of the innate immune system that are involved in early defenses against both allogeneic (nonself) cells and autologous cells undergoing various forms of stre...
    • Natural killer cell mediated cytotoxicity, conserved biosystem (from KEGG)
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    • Negative regulation of MAPK pathway, organism-specific biosystem (from REACTOME)
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    • Non-small cell lung cancer, organism-specific biosystem (from KEGG)
      Non-small cell lung cancer, organism-specific biosystemLung cancer is a leading cause of cancer death among men and women in industrialized countries. Non-small-cell lung cancer (NSCLC) accounts for approximately 85% of lung cancer and represents a heter...
    • Non-small cell lung cancer, conserved biosystem (from KEGG)
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    • Oncogenic MAPK signaling, organism-specific biosystem (from REACTOME)
      Oncogenic MAPK signaling, organism-specific biosystemThe importance of the RAS/RAF/MAPK cascade in regulating cellular proliferation, differentiation and survival is highlighted by the fact that components of the pathway are mutated with high frequency...
    • Pancreatic cancer, organism-specific biosystem (from KEGG)
      Pancreatic cancer, organism-specific biosystemInfiltrating ductal adenocarcinoma is the most common malignancy of the pancreas. When most investigators use the term 'pancreatic cancer' they are referring to pancreatic ductal adenocarcinoma (PDA)...
    • Pancreatic cancer, conserved biosystem (from KEGG)
      Pancreatic cancer, conserved biosystemInfiltrating ductal adenocarcinoma is the most common malignancy of the pancreas. When most investigators use the term 'pancreatic cancer' they are referring to pancreatic ductal adenocarcinoma (PDA)...
    • Paradoxical activation of RAF signaling by kinase inactive BRAF, organism-specific biosystem (from REACTOME)
      Paradoxical activation of RAF signaling by kinase inactive BRAF, organism-specific biosystemWhile BRAF-specific inhibitors inhibit MAPK/ERK activation in the presence of the BRAF V600E mutant, paradoxical activation of ERK signaling has been observed after treatment of cells with inhibitor ...
    • Pathways in cancer, organism-specific biosystem (from KEGG)
      Pathways in cancer, organism-specific biosystem
      Pathways in cancer
    • Progesterone-mediated oocyte maturation, organism-specific biosystem (from KEGG)
      Progesterone-mediated oocyte maturation, organism-specific biosystemXenopus oocytes are naturally arrested at G2 of meiosis I. Exposure to either insulin/IGF-1 or the steroid hormone progesterone breaks this arrest and induces resumption of the two meiotic division c...
    • Progesterone-mediated oocyte maturation, conserved biosystem (from KEGG)
      Progesterone-mediated oocyte maturation, conserved biosystemXenopus oocytes are naturally arrested at G2 of meiosis I. Exposure to either insulin/IGF-1 or the steroid hormone progesterone breaks this arrest and induces resumption of the two meiotic division c...
    • Prolonged ERK activation events, organism-specific biosystem (from REACTOME)
      Prolonged ERK activation events, organism-specific biosystemAfter NGF binding, activated Trk receptors provide multiple docking sites for adaptor proteins and enzymes. Two docking proteins, the Ankyrin-Rich Membrane Spanning protein (ARMS/Kidins220) and Fibro...
    • Prostate cancer, organism-specific biosystem (from KEGG)
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    • Prostate cancer, conserved biosystem (from KEGG)
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    • Proteoglycans in cancer, organism-specific biosystem (from KEGG)
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    • Proteoglycans in cancer, conserved biosystem (from KEGG)
      Proteoglycans in cancer, conserved biosystemMany proteoglycans (PGs) in the tumor microenvironment have been shown to be key macromolecules that contribute to biology of various types of cancer including proliferation, adhesion, angiogenesis a...
    • RAF activation, organism-specific biosystem (from REACTOME)
      RAF activation, organism-specific biosystemMammals have three RAF isoforms, A, B and C, that are activated downstream of RAS and stimulate the MAPK pathway. Although CRAF (also known as RAF-1) was the first identified and remains perhaps the ...
    • RAF/MAP kinase cascade, organism-specific biosystem (from REACTOME)
      RAF/MAP kinase cascade, organism-specific biosystemThe RAS-RAF-MEK-ERK pathway regulates processes such as proliferation, differentiation, survival, senescence and cell motility in response to growth factors, hormones and cytokines, among others. Bin...
    • RET signaling, organism-specific biosystem (from REACTOME)
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    • Regulation of actin cytoskeleton, organism-specific biosystem (from KEGG)
      Regulation of actin cytoskeleton, organism-specific biosystem
      Regulation of actin cytoskeleton
    • Regulation of actin cytoskeleton, conserved biosystem (from KEGG)
      Regulation of actin cytoskeleton, conserved biosystem
      Regulation of actin cytoskeleton
    • Renal cell carcinoma, organism-specific biosystem (from KEGG)
      Renal cell carcinoma, organism-specific biosystemRenal cell cancer (RCC) accounts for ~3% of human malignancies and its incidence appears to be rising. Although most cases of RCC seem to occur sporadically, an inherited predisposition to renal canc...
    • Renal cell carcinoma, conserved biosystem (from KEGG)
      Renal cell carcinoma, conserved biosystemRenal cell cancer (RCC) accounts for ~3% of human malignancies and its incidence appears to be rising. Although most cases of RCC seem to occur sporadically, an inherited predisposition to renal canc...
    • SHC1 events in EGFR signaling, organism-specific biosystem (from REACTOME)
      SHC1 events in EGFR signaling, organism-specific biosystemGRB2 can bind EGFR directly or through another SH2-containing protein, SHC1. This association leads to RAS activation.
    • SOS-mediated signalling, organism-specific biosystem (from REACTOME)
      SOS-mediated signalling, organism-specific biosystemSOS is recruited to the plasma membrane and mediates activation of Ras.
    • Serotonergic synapse, organism-specific biosystem (from KEGG)
      Serotonergic synapse, organism-specific biosystemSerotonin (5-Hydroxytryptamine, 5-HT) is a monoamine neurotransmitter that plays important roles in physiological functions such as learning and memory, emotion, sleep, pain, motor function and endoc...
    • Signal Transduction, organism-specific biosystem (from REACTOME)
      Signal Transduction, organism-specific biosystemSignal transduction is a process in which extracellular signals elicit changes in cell state and activity. Transmembrane receptors sense changes in the cellular environment by binding ligands, such a...
    • Signaling Pathways in Glioblastoma, organism-specific biosystem (from WikiPathways)
      Signaling Pathways in Glioblastoma, organism-specific biosystemThe most frequently altered genes in glioblastoma. This pathway originally accompanied the 2008 Nature publication on the comprehensive genomic characterization of human glioblastoma genes and core p...
    • Signaling by BRAF and RAF fusions, organism-specific biosystem (from REACTOME)
      Signaling by BRAF and RAF fusions, organism-specific biosystemIn addition to the more prevalent point mutations, BRAF and RAF1 are also subject to activation as a result of translocation events that yield truncated or fusion products (Jones et al, 2008; Cin et ...
    • Signaling by EGFR, organism-specific biosystem (from REACTOME)
      Signaling by EGFR, organism-specific biosystemThe epidermal growth factor receptor (EGFR) is one member of the ERBB family of transmembrane glycoprotein tyrosine receptor kinases (RTK). Binding of EGFR to its ligands induces conformational chang...
    • Signaling by GPCR, organism-specific biosystem (from REACTOME)
      Signaling by GPCR, organism-specific biosystemG protein-coupled receptors (GPCRs; 7TM receptors; seven transmembrane domain receptors; heptahelical receptors; G protein-linked receptors [GPLR]) are the largest family of transmembrane receptors i...
    • Signaling by Insulin receptor, organism-specific biosystem (from REACTOME)
      Signaling by Insulin receptor, organism-specific biosystemInsulin binding to its receptor results in receptor autophosphorylation on tyrosine residues and the tyrosine phosphorylation of insulin receptor substrates (e.g. IRS and Shc) by the insulin receptor...
    • Signaling by Interleukins, organism-specific biosystem (from REACTOME)
      Signaling by Interleukins, organism-specific biosystemInterleukins are low molecular weight proteins that bind to cell surface receptors and act in an autocrine and/or paracrine fashion. They were first identified as factors produced by leukocytes but a...
    • Signaling by Leptin, organism-specific biosystem (from REACTOME)
      Signaling by Leptin, organism-specific biosystemLeptin (LEP, OB, OBS), a circulating adipokine, and its receptor LEPR (DB, OBR) control food intake and energy balance and are implicated in obesity-related diseases (recently reviewed in Amitani et ...
    • Signaling by PDGF, organism-specific biosystem (from REACTOME)
      Signaling by PDGF, organism-specific biosystemPlatelet-derived Growth Factor (PDGF) is a potent stimulator of growth and motility of connective tissue cells such as fibroblasts and smooth muscle cells as well as other cells such as capillary end...
    • Signaling by RAS mutants, organism-specific biosystem (from REACTOME)
      Signaling by RAS mutants, organism-specific biosystemMembers of the RAS gene family were the first oncogenes to be identified, and mutations in RAS are present in ~20-30% of human cancers (reviewed in Prior et al, 2012). Mutations in the KRAS gene are ...
    • Signaling by SCF-KIT, organism-specific biosystem (from REACTOME)
      Signaling by SCF-KIT, organism-specific biosystemStem cell factor (SCF) is a growth factor with membrane bound and soluble forms. It is expressed by fibroblasts and endothelial cells throughout the body, promoting proliferation, migration, survival...
    • Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R), organism-specific biosystem (from REACTOME)
      Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R), organism-specific biosystemBinding of IGF1 (IGF-I) or IGF2 (IGF-II) to the extracellular alpha peptides of the type 1 insulin-like growth factor receptor (IGF1R) triggers the activation of two major signaling pathways: the SOS...
    • Signaling by VEGF, organism-specific biosystem (from REACTOME)
      Signaling by VEGF, organism-specific biosystemIn normal development vascular endothelial growth factors (VEGFs) are crucial regulators of vascular development during embryogenesis (vasculogenesis) and blood-vessel formation in the adult (angioge...
    • Signaling by high-kinase activity BRAF mutants, organism-specific biosystem (from REACTOME)
      Signaling by high-kinase activity BRAF mutants, organism-specific biosystemBRAF is mutated in about 8% of human cancers, with high prevalence in hairy cell leukemia, melanoma, papillary thyroid and ovarian carcinomas, colorectal cancer and a variety of other tumors (Davies ...
    • Signaling by moderate kinase activity BRAF mutants, organism-specific biosystem (from REACTOME)
      Signaling by moderate kinase activity BRAF mutants, organism-specific biosystemIn addition to the highly prevalent and activating V600E BRAF mutations, numerous moderately activating and less common mutations have also been identified in human cancers (Forbes et al, 2015). Unl...
    • Signalling by NGF, organism-specific biosystem (from REACTOME)
      Signalling by NGF, organism-specific biosystemNeurotrophins (NGF, BDNF, NT-3, NT-4/5) play pivotal roles in survival, differentiation, and plasticity of neurons in the peripheral and central nervous system. They are produced, and secreted in mi...
    • Signalling to ERKs, organism-specific biosystem (from REACTOME)
      Signalling to ERKs, organism-specific biosystemNeurotrophins utilize multiple pathways to activate ERKs (ERK1 and ERK2), a subgroup of the large MAP kinase (MAPK) family, from the plasma membrane. The major signalling pathways to ERKs are via RAS...
    • Signalling to RAS, organism-specific biosystem (from REACTOME)
      Signalling to RAS, organism-specific biosystemSignalling through Shc adaptor proteins appears to be identical for both NGF and EGF. It leads to a fast, but transient, MAPK/ERK activation, which is insufficient to explain the prolonged activation...
    • Signalling to p38 via RIT and RIN, organism-specific biosystem (from REACTOME)
      Signalling to p38 via RIT and RIN, organism-specific biosystemRIT and RIN are two small guanine nucleotide binding proteins that share more than 50% sequence identity with RAS, including highly conserved core effector domains. Unlike RAS, the C termini of RIT a...
    • VEGFA-VEGFR2 Pathway, organism-specific biosystem (from REACTOME)
      VEGFA-VEGFR2 Pathway, organism-specific biosystemAngiogenesis is the formation of new blood vessels from preexisting vasculature. One of the most important proangiogenic factors is vascular endothelial growth factor (VEGF). VEGF exerts its biologic...
    • VEGFR2 mediated cell proliferation, organism-specific biosystem (from REACTOME)
      VEGFR2 mediated cell proliferation, organism-specific biosystemVEGFR2 stimulates ERK not via GRB2-SOS-RAS, but via pY1175-dependent phosphorylation of PLC gamma and subsequent activation of PKCs. PKC plays an important mediatory role in the proliferative Ras/Raf...
    • Vascular smooth muscle contraction, organism-specific biosystem (from KEGG)
      Vascular smooth muscle contraction, organism-specific biosystemThe vascular smooth muscle cell (VSMC) is a highly specialized cell whose principal function is contraction. On contraction, VSMCs shorten, thereby decreasing the diameter of a blood vessel to regula...
    • Vascular smooth muscle contraction, conserved biosystem (from KEGG)
      Vascular smooth muscle contraction, conserved biosystemThe vascular smooth muscle cell (VSMC) is a highly specialized cell whose principal function is contraction. On contraction, VSMCs shorten, thereby decreasing the diameter of a blood vessel to regula...

    Interactions

    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

    Markers

    Homology

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    ATP binding IEA
    Inferred from Electronic Annotation
    more info
     
    metal ion binding IEA
    Inferred from Electronic Annotation
    more info
     
    protein binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    protein kinase activity TAS
    Traceable Author Statement
    more info
    PubMed 
    protein serine/threonine kinase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    PubMed 
    protein serine/threonine kinase activity IDA
    Inferred from Direct Assay
    more info
    PubMed 
    Process Evidence Code Pubs
    MAPK cascade IBA
    Inferred from Biological aspect of Ancestor
    more info
    PubMed 
    MAPK cascade TAS
    Traceable Author Statement
    more info
     
    cellular protein modification process TAS
    Traceable Author Statement
    more info
    PubMed 
    negative regulation of apoptotic process IDA
    Inferred from Direct Assay
    more info
    PubMed 
    positive regulation of peptidyl-serine phosphorylation IDA
    Inferred from Direct Assay
    more info
    PubMed 
    regulation of TOR signaling IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    regulation of proteasomal ubiquitin-dependent protein catabolic process IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    Component Evidence Code Pubs
    cellular_component ND
    No biological Data available
    more info
     
    cytosol IBA
    Inferred from Biological aspect of Ancestor
    more info
    PubMed 
    cytosol TAS
    Traceable Author Statement
    more info
     
    mitochondrion IBA
    Inferred from Biological aspect of Ancestor
    more info
    PubMed 

    General protein information

    Preferred Names
    serine/threonine-protein kinase A-Raf
    Names
    A-Raf proto-oncogene serine/threonine-protein kinase
    Oncogene ARAF1
    Ras-binding protein DA-Raf
    proto-oncogene A-Raf-1
    proto-oncogene Pks
    v-raf murine sarcoma 3611 viral oncogene homolog 1
    v-raf murine sarcoma 3611 viral oncogene-like protein
    NP_001243125.1
    NP_001243126.1
    NP_001645.1
    XP_006724592.1
    XP_011542208.1
    XP_011542210.1
    XP_011542211.1

    NCBI Reference Sequences (RefSeq)

    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    Genomic

    1. NG_016339.2 RefSeqGene

      Range
      4984..15805
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001256196.1NP_001243125.1  serine/threonine-protein kinase A-Raf isoform 2

      See identical proteins and their annotated locations for NP_001243125.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) has an alternate splice site in the coding region, which does not affect the reading frame, compared to variant 1. The resulting isoform (2) is 3 aa longer than isoform 1.
      Source sequence(s)
      BC002466, BC007514, DC362427
      Consensus CDS
      CCDS75970.1
      UniProtKB/Swiss-Prot
      P10398
      UniProtKB/TrEMBL
      Q96II5
      Related
      ENSP00000290277.7, ENST00000290277.10
      Conserved Domains (3) summary
      cd01816
      Location:2091
      Raf_RBD; Ubiquitin domain of Raf serine/threonine kinases
      cd14150
      Location:312576
      STKc_A-Raf; Catalytic domain of the Serine/Threonine Kinase, A-Raf (Rapidly Accelerated Fibrosarcoma) kinase
      pfam00130
      Location:99146
      C1_1; Phorbol esters/diacylglycerol binding domain (C1 domain)
    2. NM_001256197.1NP_001243126.1  serine/threonine-protein kinase A-Raf isoform 3

      See identical proteins and their annotated locations for NP_001243126.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) lacks several exons and its transcription extends past a splice site that is used in variant 1, resulting in an immediate translation termination and a novel 3' UTR compared to variant 1. The resulting isoform (3) has a shorter C-terminus, compared to isoform 1.
      Source sequence(s)
      AB158254, CA424869, DC362427
      Consensus CDS
      CCDS59164.1
      UniProtKB/Swiss-Prot
      P10398
      Related
      ENSP00000366238.1, ENST00000377039.2
      Conserved Domains (2) summary
      cd01816
      Location:2091
      Raf_RBD; Ubiquitin domain of Raf serine/threonine kinases
      pfam00130
      Location:99146
      C1_1; Phorbol esters/diacylglycerol binding domain (C1 domain)
    3. NM_001654.5NP_001645.1  serine/threonine-protein kinase A-Raf isoform 1

      See identical proteins and their annotated locations for NP_001645.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) encodes the predominant isoform (1).
      Source sequence(s)
      BC002466, DC362427
      Consensus CDS
      CCDS35232.1
      UniProtKB/Swiss-Prot
      P10398
      UniProtKB/TrEMBL
      A0A024R178
      Related
      ENSP00000366244.4, ENST00000377045.8
      Conserved Domains (3) summary
      cd01816
      Location:2091
      Raf_RBD; Ubiquitin domain of Raf serine/threonine kinases
      cd14150
      Location:309573
      STKc_A-Raf; Catalytic domain of the Serine/Threonine Kinase, A-Raf (Rapidly Accelerated Fibrosarcoma) kinase
      pfam00130
      Location:99146
      C1_1; Phorbol esters/diacylglycerol binding domain (C1 domain)

    RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 109

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p12 Primary Assembly

    Genomic

    1. NC_000023.11 Reference GRCh38.p12 Primary Assembly

      Range
      47561100..47571921
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_006724529.3XP_006724592.1  serine/threonine-protein kinase A-Raf isoform X1

      See identical proteins and their annotated locations for XP_006724592.1

      Conserved Domains (4) summary
      cd01816
      Location:2091
      Raf_RBD; Ubiquitin domain of Raf serine/threonine kinases
      cd14150
      Location:314578
      STKc_A-Raf; Catalytic domain of the Serine/Threonine Kinase, A-Raf (Rapidly Accelerated Fibrosarcoma) kinase
      pfam00069
      Location:316570
      Pkinase; Protein kinase domain
      pfam00130
      Location:99146
      C1_1; Phorbol esters/diacylglycerol binding domain (C1 domain)
    2. XM_011543906.3XP_011542208.1  serine/threonine-protein kinase A-Raf isoform X1

      See identical proteins and their annotated locations for XP_011542208.1

      Conserved Domains (4) summary
      cd01816
      Location:2091
      Raf_RBD; Ubiquitin domain of Raf serine/threonine kinases
      cd14150
      Location:314578
      STKc_A-Raf; Catalytic domain of the Serine/Threonine Kinase, A-Raf (Rapidly Accelerated Fibrosarcoma) kinase
      pfam00069
      Location:316570
      Pkinase; Protein kinase domain
      pfam00130
      Location:99146
      C1_1; Phorbol esters/diacylglycerol binding domain (C1 domain)
    3. XM_011543908.3XP_011542210.1  serine/threonine-protein kinase A-Raf isoform X2

      See identical proteins and their annotated locations for XP_011542210.1

      UniProtKB/Swiss-Prot
      P10398
      UniProtKB/TrEMBL
      A0A024R178
      Conserved Domains (3) summary
      cd01816
      Location:2091
      Raf_RBD; Ubiquitin domain of Raf serine/threonine kinases
      cd14150
      Location:309573
      STKc_A-Raf; Catalytic domain of the Serine/Threonine Kinase, A-Raf (Rapidly Accelerated Fibrosarcoma) kinase
      pfam00130
      Location:99146
      C1_1; Phorbol esters/diacylglycerol binding domain (C1 domain)
    4. XM_011543909.3XP_011542211.1  serine/threonine-protein kinase A-Raf isoform X3

      Conserved Domains (2) summary
      cd14150
      Location:90354
      STKc_A-Raf; Catalytic domain of the Serine/Threonine Kinase, A-Raf (Rapidly Accelerated Fibrosarcoma) kinase
      pfam00069
      Location:92346
      Pkinase; Protein kinase domain
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