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FLASH GENE
Symbol GAB1 contributors: mct - updated : 04-01-2014
HGNC name GRB2-associated binding protein 1
HGNC id 4066
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • N terminal PH domain
  • proline rich sequence
  • several SH3 and SH2 domain binding sites
  • HOMOLOGY
    interspecies homolog to murine Gab1
    Homologene
    FAMILY
  • insulin receptor substrate-1 like family of adaptor molecules
  • GAB family
  • CATEGORY adaptor , signaling , receptor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytosolic
    intracellular,nucleus
    basic FUNCTION
  • playing a role in broad range of growth factor and cytokine signaling pathway
  • important mediator of branching tubulogenesis and plays a central role in cellular growth response, transformation and apoptosis
  • non-redundant and essential roles of GAB1 and GAB2 in endothelial cells, suggesting major contributions of these proteins during angiogenesis
  • is essential for postnatal angiogenesis through mediating angiogenic and survival signaling
  • docking protein that transduces signals from a variety of tyrosine kinases, including Met and the epidermal growth factor receptor (EGFR)
  • role of GAB1 and GAB2 in IL22-mediated keratinocyte proliferation, migration, and differentiation
  • plays an important role as part of the mechanism of by which EGFR induces induced activation of the MAPK and AKT pathway
  • is a negative regulator of epithelial cell polarity that functions as a scaffold for modulating PAR protein complexes on the lateral membrane
  • docking/scaffold protein and key mediator of the MET-tyrosine kinase receptor activated by hepatocyte growth factor/scatter factor (HGF/SF)
  • anti-apoptotic role of caspase-cleaved GAB1 in HGF/SF-MET signaling
  • key coordinator that is tyrosine phosphorylated in response to various growth factors, cytokines, and numerous other molecules
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling signal transduction
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • with SH2 containing proteins (PTPN11), required for EGF signal transduction
  • PTPN11 participates in GH-induced RAS/ERK1/2 activation by dephosphorylating GAB1 on its RASA1 binding sites
  • mediate epidermal growth factor-induced epidermal growth and differentiation via interaction with PTPN11
  • binds MARK2 and enhances its kinase activity
  • GAB1 brings MARK2 and PARD3 into a transient complex, stimulating PARD3 phosphorylation by MARK2
  • GAB1 and PARD6A bind the PARD3 PDZ1 domain and thereby compete for PARD3 binding
  • negatively regulated by PTPN1 (PTPN1 regulates the phosphorylation state of retinal GAB1) )
  • PECAM1 specifically mediating GAB1 tyrosine phosphorylation and its downstream AKT1 and eNOS activation
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancerdigestiveoesophagus
    reducing GAB1 function may sensitize head and neck squamous cell carcinoma (HNSCC) to EGFR inhibitors, hence representing a new therapeutic target HNSCC treatment in combination with EGFR targeting agents
    ANIMAL & CELL MODELS