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FLASH GENE
Symbol RAF1 contributors: mct - updated : 24-12-2015
HGNC name v-raf-1 murine leukemia viral oncogene homolog 1
HGNC id 9829
Corresponding disease
LEOPS2 Leopard syndrome 2
NS5 Noonan syndrome 5
Location 3p25.2      Physical location : 12.625.101 - 12.705.700
Synonym name
  • RAF proto-oncogene serine/threonine protein kinase
  • oncogene RAF1
  • Synonym symbol(s) MIL, KRAF, C-RAF, Raf-1, CRAF, NS5
    EC.number 2.7.11.1
    DNA
    TYPE functioning gene
    SPECIAL FEATURE head to head
    STRUCTURE 80.60 kb     17 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked Y status confirmed
    Map pter - D3S1442 , D3S1443 , D13S1444 , D3S17 - D3S18 - VHL VHL - D3S1317 - [D3S601 - D3S1038 ],ATP2B2 - D3S587 - D3S720 - D3S1250 - D3S732 - RAF1 - D3S651 - D3S656 - D3S1110 - D3S1255 - THRB THRB - cen
    Text see PTPRG
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    17 - 3291 72.9 648 - 1992 1639773
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    blood / hematopoieticthymus   highly
    Cardiovascularheart   highly
    Respiratorylung   highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Lymphoid    
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • serine/threonine kinase, RAF-like RAS binding domain (RBD)
  • one zinc dependant phorbol-ester and DAG binding domain
  • three CR, conserved region (CR1, AA 61-192, CR2 AA 251-266 and CR3 AA 333-625)
  • a CRD, cysteine-rich domain
  • a minimal 24 AAs long PEBP1 binding domain in the N-region
  • HOMOLOGY
    interspecies homolog to murine leukemia viral oncogene 1 v-raf-1
    Homologene
    FAMILY
  • protein kinase superfamily
  • TKL Ser/Thr protein kinase family
  • RAF subfamily
  • CATEGORY enzyme , protooncogene
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,organelle,mitochondria,outer
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,cytosolic
    intracellular,nucleus
    text
  • translocate to mitochondria and thereby protect cells from stress-mediated apoptosis
  • basic FUNCTION
  • regulator of cellular proliferation, differentiation, and apoptosis
  • effector kinase of Ras, crucial integrator in the mitogenic cytoplasmic kinase MAPK pathway
  • participating to the RAS-RAF-MEK-ERK- pathway in promoting tumorigenesis
  • downstream effector of RAS signaling in the MAPK pathway
  • may induce cell proliferation through hypermethylation of tumor suppressor gene CDKN2A
  • STK3 serves as a hub to integrate biological outputs of the RAF1 and AKT pathways
  • its activity is essential to establish the balance between cell proliferation and death in neuroepithelial otic precursors, and for otic neuron differentiation and axonal growth at the acoustic-vestibular ganglion
  • plays a unique role in mediating KRAS signaling and makes it a suitable target for therapeutic intervention
  • elevated RAF1 mitochondrial translocation induced the increased anti-apoptotic effect and subsequently promoted HBx-mediated hepatocarcinogenesis
  • major downstream target of several growth factors that promote proliferation and survival of many cell types, including the pancreatic beta cells
  • RAF1 signaling is essential for the regulation of basal insulin transcription and the supply of releasable insulin
  • CELLULAR PROCESS cell life, differentiation
    cell life, proliferation/growth
    cell life, cell death/apoptosis
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling signal transduction
  • amplification of RAF1/MEK/MAPK oncogenic signaling during tumor growth promotes the genesis of metastatic lesions from primary tumors by activating the mesenchymal epithelial transition
  • a component
  • components of the two MAPK cascades, MAP3K5-MAP2K4-MAPK10 and RAF1-MAPK1-MAP2K1 interacting with arrestins
  • in the heart, melusin forms a supramolecular complex with the proto-oncogene RAF1, MAPKK1/2 and MAPK1/MAPK3
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • phosphorylating MEKs (MAP2Ks)
  • NFKB through MEKK1 activation
  • interacting with TC21 for activation and translocation to plasma membrane
  • interacting with CNKSR1 (mediates Src-dependent tyrosine phosphorylation and activation of RAF1)
  • interaction with PEBP1 (binds to RAF1 interfering with binding of the MEK substrate and potentially also RAF1 activation)
  • physically associated with the IL2RB (p75) in T-cell blasts (following tyrosine phosphorylation, enzymatically active RAF1 dissociates from the IL2 receptor and translocates into the cytosol)
  • potent regulator of RAF1 activity and may control RAF1 dependent signaling at mitochondria
  • interacting with BIRC4
  • binding of 14-3-3 proteins to the N terminus of RAF1 attenuates the Ras-RAF-MAPK pathway by sequestering RAF1 in the cytoplasm
  • association of BRAF with RAF1 induces the activation of RAF1
  • ARRB2-RAF1 interaction is enhanced by receptor binding
  • RAF1 and ADRBK1 are direct interaction partners of PEBP1 (PEBP1 dimer formation controls its target switch from RAF1 to ADRBK1)
  • DIRAS3 interacts with RAF1 to specifically suppress the activating phosphorylations on MEK and ERK, thus restricting migration of non-cancer cells
  • MAP2K1 activates RAF1 through a Ras-independent mechanism
  • PDE8A is a physiological regulator of RAF1 signaling in some cells
  • PDE8A exerts part of its control of T cell function through RAF1 kinase signaling pathway
  • cell & other
    REGULATION
    Other ubiquitinated after its binding to XIAP
    regulated by HSPA5 (may stabilize RAF1 to maintain mitochondrial permeability and thus protect cells from ER stress-induced apoptosis
    ASSOCIATED DISORDERS
    corresponding disease(s) LEOPS2 , NS5
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral fusion      
    in-frame oncogenic fusion between SRGAP3 and RAF1 in Pilocytic astrocytomas
    constitutional     --other  
    dysfunction (expression) of the FGFR1, SOS1 and RAF1 genes is involved in the development of unilateral or bilateral cryptorchidism
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cardiovascularvalvulopathy 
    modulating the RAF1Ser(259)/14-3-3 protein-protein interaction with a stabilizing small molecule may yield a novel potential approach for treatment of diseases resulting from an overactive Ras-RAF-MAPK pathway, as Noonan or Leopard syndrome
    cancer  
    excellent molecular target for anticancer therapy
    ANIMAL & CELL MODELS