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FLASH GENE
Symbol IQSEC1 contributors: mct - updated : 26-11-2019
HGNC name IQ motif and Sec7 domain 1
HGNC id 29112
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • a N-terminal IQ-like motif
  • a central serine-rich region and Sec7 domain (sec7d), a Sec7-PH tandem domain
  • a C-terminal pleckstrin homology (PH) domain, (the PH domain and the interdomain linker of IQSEC1 may be targets for selectively regulating the activity of IQSEC1)
    • HOMOLOGY
    interspecies homolog to murine Iqsec1 (95.8pc)
    Homologene
    FAMILY
  • family of guanine nucleotide exchange factors for ADP ribosylation factors
    • CATEGORY regulatory
    SUBCELLULAR LOCALIZATION     plasma membrane,junction
        intracellular
    intracellular,cytoplasm,cytosolic
    intracellular,nucleus,nucleolus
    text
  • IQSEC1 and ARF5 localize to clathrin-coated pits at the plasma membrane
    • basic FUNCTION
  • having a role in activation of ARF6 for its functions in E-cadherin recycling and actin remodeling
  • responsible for the invasive activity of ARF6 in breast cancer cells
  • IQSEC1, IQSEC2 control activity-dependent removal of AMPA receptors from glutamatergic synapses, a process that is required for long-term synaptic depression
  • in the CNS, IQSEC1 is concentrated in postsynaptic densities and plays a critical role in the development and plasticity of glutamatergic synapses
  • mediates SEMA3E-induced ARF6 activation in endothelial cells
  • plays a significant role in pancreatic cancer invasion through regulating the expression of E-cadherin and the process of mesenchymal to epithelial transition (MET)
  • acts at clathrin-coated pits to promote integrin internalization by activating ARF5 and suggest a previously unrecognized role for ARF5 in clathrin-mediated endocytosis of specific cargoes
  • small GTPases that regulate membrane trafficking and actin cytoskeleton
  • IQSEC1, IQSEC2, IQSEC3 have key roles in the function and organization of distinct excitatory and inhibitory synapses in the retina
  • is essential for developmental and pathological angiogenesis by promoting Endothelial cells sprouting through regulation of adhesion by mediating beta1-integrin internalization
  • having a conserved function in myoblast fusion
  • plays a critical role in neuronal development
    • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling signal transduction
  • IQSEC1-ARF6-ASAP1-cortactin pathway is essential for angiogenesis activities, including cell migration and tubular formation
    • a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • interacting with CTNNA1
  • interacting with ARF6
  • responsible for the ARF6 activation to induce invasion and metastasis, by directly binding to ligand-activated epidermal growth factor receptor (EGFR)
  • functions in phagocytosis via its role in ARF6-dependent actin remodeling
  • in addition to ARF6, endogenous IQSEC1 also activates the class II Arfs, ARF4 and ARF5, and surprisingly, ARF5 mediates integrin internalization
  • MAP4K4 can activate ARF6 via IQSEC1 and enhance focal adhesions dissolution
  • IQSEC1 binds to DLG4
  • IQSEC1 is a guanine nucleotide exchange factor for ADP-ribosylation factor 6 (ARF6), a critical GTPase that regulates endosomal trafficking and actin cytoskeleton remodeling
    • cell & other
    REGULATION
    Other is allosterically regulated by PIP(2) binding to the PH domain and activity depends on the interdomain linker
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancerendocrinepancreas
    possibility of it becoming a potential therapeutic target against pancreatic cancer
    ANIMAL & CELL MODELS
  • loss of Iqsec1 in neurons of the mouse cortex leads to defects in the maturation of dendritic spines