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FLASH GENE
Symbol RAF1 contributors: mct - updated : 24-12-2012
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
    Physical map
    SLC6A1 3p25-p24 solute carrier family 6 (neurotransmitter transporter, GABA), member 1 LOC391509 3 similar to Drosophila melanogaster CG8797 gene product-related LOC391510 3 similar to FLJ31709 protein HRH1 3p25 histamine receptor H1 APG7L 3p25.3-3p24.1 APG7 autophagy 7-like (S. cerevisiae) KIAA0121 3p25.2 KIAA0121 gene product LOC132001 3p25.2 hypothetical protein BC015088 DKFZp434E0519 3p25.2 hypothetical protein DKFZp434E0519 HCP12 3p25.2 cytochrome c, somatic pseudogene SYN2 3p25 synapsin II TIMP4 3p25 tissue inhibitor of metalloproteinase 4 LOC391511 3 similar to Glutathione S-transferase Mu 1 (GSTM1-1) (HB subunit 4) (GTH4) (GSTM1a-1a) (GSTM1b-1b) (GST class-mu 1) PPARG 3p25 peroxisome proliferative activated receptor, gamma MGC2776 3p25.2 hypothetical protein MGC2776 MKRN2 3p25 makorin, ring finger protein, 2 RAF1 3p25 v-raf-1 murine leukemia viral oncogene homolog 1 FLJ11036 3p25.2 hypothetical protein FLJ11036 LOC344866 3p25.2 similar to Keratin, type I cytoskeletal 18 (Cytokeratin 18) (K18) (CK 18) TIP120B 3p25.2-p24.2 similar to Keratin, type I cytoskeletal 18 (Cytokeratin 18) (K18) (CK 18) RPL32 3p25-p24 ribosomal protein L32 LOC391512 3 similar to WD repeat domain 10 isoform 3 LOC391513 3 similar to ENSANGP00000014786 LOC391514 3 similar to MAP/microtubule affinity-regulating kinase 1 LOC389096 3 similar to nucleoporin 210; nuclear pore membrane glycoprotein 210; gp210 KIAA0763 3p25.1 similar to nucleoporin 210; nuclear pore membrane glycoprotein 210; gp210 NUP210 3p25.2-p25.1 nucleoporin 210 HDAC11 3p25.1 histone deacetylase 11 FBLN2 3p25-p24 fibulin 2 WNT7A 3p25 wingless-type MMTV integration site family, member 7A FLJ35107 3p25.1 hypothetical protein FLJ35107 LOC391515 3 similar to putative pheromone receptor gV1R1 FLJ31709 MGC3222 3p25.1 hypothetical protein MGC3222 XPC 3p25.1 xeroderma pigmentosum, complementation group C LSM3 3p25.1 LSM3 homolog, U6 small nuclear RNA associated (S. cerevisiae)
    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
  • 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