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FLASH GENE
Symbol GRB10 contributors: mct/pgu - updated : 13-10-2013
HGNC name growth factor receptor-bound protein 10
HGNC id 4564
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • N-terminal proline-rich region,
  • a Ras-GTPase binding domain,
  • a PH domain,
  • an SH2 domain and a BPS domain in between the PH and SH2 domains
  • C terminal SH2 domain
    • HOMOLOGY
    interspecies homolog to murine Grb10
    Homologene
    FAMILY GRB7/10/14 family
    CATEGORY adaptor , regulatory , signaling , receptor
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,cytosolic
    basic FUNCTION
  • involved in signal transduction in developing embryos
  • regulating cell proliferation and apoptosis
  • signalling adapter protein, expressed predominantly from the maternally-inherited allele and acting to restrict foetal and placental growth
  • can influence reproductive strategy through the allocation of maternal resources such that offspring number is offset against size
  • might act as a connector, bringing NEDD4 close to IGF1R to facilitate the ubiquitination of IGF1R by NEDD4
  • unique imprinted gene, able to influence distinct physiological processes, fetal growth and adult behaviour, owing to actions of the two parental alleles in different tissues
  • intracellular adaptor protein that acts as a negative regulator of insulin and insulin-like growth factor 1 (IGF1) receptors
  • might be a tumor suppressor regulated by MTOR
  • influences fetal growth, adult behavior and tumor formation
  • intracellular adaptor protein which binds directly to several growth factor receptors, including those for insulin and insulin-like growth factor receptor-1 (IGF1), and negatively regulates their actions
  • may act as a negative regulator of myogenesis
    • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling signal transduction
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • RET, IGF1R, GHR, INSR
  • binding insulin and IGF receptors
  • binds to the intracellular portion of LRP6 and negatively regulates Wnt signaling, by interfering with the binding of Axin to LRP6
  • interacts with BCL2L11 and inhibits its proapoptotic activity in a phosphorylation-dependant manner
  • can interact with the C2 domain of the E3 ubiquitin ligase NEDD4 through its Src homology 2 (SH2) domain
  • MTOR-mediated phosphorylation stabilized GRB10, leading to feedback inhibition of the phosphatidylinositol 3-kinase (PI3K)
  • LMX1A is an activator of RGS4 and GRB10 and is responsible for the correct specification of rostral and medial mesodiencephalic dopamine (mdDA) neurons
    • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s) SRS7
    Susceptibility
    Variant & Polymorphism
    Candidate gene candidate for growth disturbance disorders
    Marker
    Therapy target
    ANIMAL & CELL MODELS
  • adult mice deficient in Grb10 have elevated body mass and muscle mass throughout adulthood, up to 12 mo of age, and grb10 plays a previously unrecognized role in regulating the development of fiber number during murine embryonic growth
  • Grb10(-/-) mice exhibit improved whole body glucose homeostasis and an increase in muscle mass associated specifically with an increase in myofiber number