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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
RNA
TRANSCRIPTS type messenger
text subject to alternative splicing of the 5prime exons, many of which are non-coding (PMID: 19487367)
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
16 - 4713 68 594 biallelic, paternally expressed only in the brain 2010 19487367
a potential SH3 binding sequence, PH and SH2 domains
15 - 4575 60 548 skeletal muscle, pancreas 2010 19487367
a truncated PH domain
16 - 4793 50 536 skeletal muscle, pancreas, biallelic, paternally expressed only in the brain 2010 19487367
17 - 5040 - 605 biallelic, paternally expressed only in the brain 2010 19487367
  • a third alternative N terminal, a PH domain
  • GRB10 epsilon or KIAA0207
  • - - 1849 - 594 paternally expressed only in the brain 2010 19487367
    - - 2629 - 694 testicular 2010 19487367
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveesophagus   highly
    Endocrinepancreas   highly
     thyroid   highly
    Nervousbrain    
    Reproductivemale systemtestis   
    Urinarykidney    
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Blood / Hematopoieticbone marrow   
    Muscularstriatumskeletal  
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period embryo, fetal
    IMPRINTING maternally
    text
  • in fetal brain
  • maternal allele-specific expression is conserved only in the placental villous trophoblasts, an essential part of the placenta involved in nutrient transfer
  • predominantly expressed from the maternal allele during embryogenesis
  • 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