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FLASH GENE
Symbol KSR1 contributors: mct/pgu - updated : 12-01-2012
HGNC name kinase suppressor of ras 1
HGNC id 6465
Location 17q11.2      Physical location : 25.799.035 - 25.950.717
Synonym name kinase suppressor of ras
Synonym symbol(s) KSR, RSU2
DNA
TYPE functioning gene
STRUCTURE 151.00 kb     22 Exon(s)
MAPPING cloned Y linked N status provisional
RNA
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
22 - 4552 84.5 762 - 1995 8521512
EXPRESSION
Rna function widely in brain, thymuss and muscle
Type widely
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Digestivepharynx    
Nervousnerve   highly
Reproductivefemale systemplacenta  highly
Urinarykidney    
tissue
SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
Connectiveadipose  highly
cell lineage
cell lines
fluid/secretion
at STAGE
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • one phorbol-ester/DAG-type zinc finger
  • one protein kinase domain
  • conjugated PhosphoP
    HOMOLOGY
    interspecies ortholog to murine Ksr1
    Homologene
    FAMILY
  • protein kinase superfamily
  • TKL Ser/Thr protein kinase family
  • CATEGORY enzyme , regulatory
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm
    text
  • translocation from the cytoplasm to the cell surface in response to growth factor treatment
  • recruited to the plasma membrane by Ras activation
  • basic FUNCTION
  • functions as an essential scaffolding protein to coordinate the assembly of Raf-MEK-ERK complexes
  • promoting MEK and RAF phosphorylation and activity through assembly of an activated signaling complex
  • positive modulator of ras-MAP kinase signaling
  • molecular scaffold kinase suppressor of Ras 1 (KSR1) regulating adipogenesis
  • protecting intestinal epithelium from TNF-alpha-induced apoptosis
  • mitogen-activated protein (MAP) kinase scaffold that enhances the activation of the MAP kinase extracellular signal-regulated kinase (ERK)
  • required for efficient NK-mediated cytolysis and polarization of cytolytic granules
  • recruited to the immunological synapse during T-cell activation and membrane recruitment of KSR1 is required for recruitment of active ERK to the synapse
  • plays a central role in determining the sensitivity of T-cell responses and is thus well positioned as a key control point
  • required for maximal ERK activation induced by growth factors and by some cytotoxic agents
  • playing a specific role in the cellular response to DNA interstrand cross-links
  • likely control point used to fine-tune T-cell responses during T-cell activation and differentiation, suggesting KSR1 as a key regulator of T-cell function and plasticity
  • despite a requirement for KSR1 for full ERK activation in thymocytes, full and efficient ERK activation is not essential for the majority of thymocyte selection events
  • functional protein kinase capable of serine autophosphorylation and direct phosphorylation of MAP2K1
  • KSR1 is a bona fide kinase whose activity is required to cooperate with RAF for the activation of MEK
  • may potentially phosphorylate MEK and this phosphorylation facilitates RAF1 phosphorylation of the activation loop
  • molecular scaffold of the RAF1/MEK/extracellular signal-regulated kinase (ERK) cascade that enhances oncogenic RAS signaling
  • KSR1-dependent control of PPARGC1A- and ESRRA-dependent pathways that are necessary and sufficient for signaling by oncogenic HRAS to regulate metabolism and anchorage-independent growth
  • CELLULAR PROCESS protein, post translation
    PHYSIOLOGICAL PROCESS
    text cell-cycle control
    PATHWAY
    metabolism
    signaling signal transduction
    RAS signal transduction
    a component
  • KSR1, BRAF, and MEK form a ternary complex
  • INTERACTION
    DNA
    RNA
    small molecule metal binding, nucleotide,
  • ATP
  • ion Zn2+
  • protein
  • interacting with HSPCA/HSP90, YWHAB/14-3-3, CDC37, MAP2K/MEK, MARK3, PPP2R1A and PPP2CA
  • binding RAF and MAPK/ERK, in a Ras-dependent manner
  • binding to 14.3.3 proteins, prevents ths membrane localization of phosphorylated KSR1
  • interacting with activated MAPK3/MAPK1 at lipid rafts for PLA2G4A activation
  • modulates MAPK system sensitivity but not system output
  • binds each of the three ERK cascade components to facilitate pathway activation
  • MAP2K1 is a substrate of KSR1, and the catalytic activities of both proteins are required for eliciting cell survival responses downstream of TNF
  • regulates endometrial sensitivity to tumor necrosis factor-related apoptosis-inducing ligand by regulating CFLAR levels
  • cell & other
    REGULATION
    activated by EGF (epidermal growth factor)
    Other translocation regulated by CDC25C-associated kinase-1
    phosphorylated by MARK3
    dephosphorylated by PPP2CA
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --over  
    promote high, sustained ERK activation that phosphorylates and inhibits PPARG inhibiting adipogenesis
    tumoral     --over  
    in endometrial carcinoma (
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS