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FLASH GENE
Symbol SRGAP2 contributors: mct - updated : 22-02-2016
HGNC name SLIT-ROBO Rho GTPase-activating protein 2
HGNC id 19751
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • a N-terminal F-BAR (Bin, Amphiphysin, Rvs) domain involved in membrane deformation, and FCH domain; F-BAR displays faster molecular dynamics than F-BAR(SRGAP3) and F-BAR(SRGAP1) at the plasma membrane, which correlates well with its increased potency to induce filopodia
  • a FBH and a HR1 doamains
  • a central Rho-GAP domain which specifically stimulates the GTPase activity of RAC1
  • a C-terminal tail containing a SH3 domain
    • HOMOLOGY
    intraspecies homolog to RHO-GAP hematopoietic protein C1(ARHGAP4)
    paralog to SRGAP2B, SRGAP2C
    Homologene
    FAMILY
  • Rho GTPase family
  • FNBP2 family protein
    • CATEGORY regulatory , signaling
    SUBCELLULAR LOCALIZATION     plasma membrane,junction
        intracellular
    intracellular,cytoplasm,cytosolic
    intracellular,nucleus
    text is associated with synaptic membranes and is detected in the postsynaptic density
    basic FUNCTION
  • axon guidance and neurite outgrowth
  • couplingmembrane deformation to actin cytoskeleton reorganization in various cellular processes
  • controls cortical neuron migration
  • SRGAP, SRGAP2, SRGAP3 are not only involved in the regulation of the Slit-Robo signal transduction, but also in neuronal development and that the translocation of srGAPs is important for their functions
  • negatively regulates neuronal migration and induces neurite outgrowth and branching through the ability of its F-BAR domain to induce filopodia-like membrane protrusions resembling those induced by I-BAR domains
  • regulates neuronal morphogenesis through the ability of its F-BAR domain to regulate membrane deformation and induce filopodia formation
  • implicated in neocortical development
  • is enriched at excitatory synapses
  • promotes spine maturation and limits spine density andco-regulates spine density with the length of spine neck
  • regulates neurite outgrowth and neuronal migration by causing membrane protrusions reminiscent of the activity of I-BAR domain proteins
  • SRGAP2 signaling network as a key regulator of contact inhibition of locomotion (CIL) in fibroblasts
  • specifically controls the duration of RAC1 activity in contact protrusions, but not in contact-free protrusions
    • CELLULAR PROCESS cell communication
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling signal transduction
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • interacting with the intracellular domain of ROBO1
  • physically interacts with protein arginine methyltransferase 5 (PRMT5)
  • after RAC1-dependent activation of FMNL1, SRGAP2 mediates a potent mechanism to limit the duration of RAC1 action and inhibit formin activity during rapid actin dynamics
  • inhibition of SRGAP2 function by SRGAP2B, SRGAP2C has contributed to the evolution of the human neocortex and plays an important role during human brain development
  • function of ancestral SRGAP2 is conserved between mouse and human and is inhibited by SRGAP2C expression
  • interplay between SRGAP1, SRGAP2 and SRGAP3 regulates neuronal differentiation and neurite outgrowth
    • cell & other
    REGULATION
    activated by enhanced by SLIT*
    inhibited by inactivated by CDC42
    ASSOCIATED DISORDERS
    ANIMAL & CELL MODELS