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FLASH GENE
Symbol SRGAP3 contributors: mct/npt - updated : 23-02-2016
HGNC name SLIT-ROBO Rho GTPase activating protein 3
HGNC id 19744
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • a N terminal FCH, and F-BAR(3) inducing filopodia in both cell types, though less potently than F-BAR(SRGAP2) , and F-BAR localizes SRGAP3 to the leading edge of cellular protrusions
  • a central RHO-GAP
  • a FBH and a SH3 domains, important for focal adhesion targeting
  • a single PXXP motif in the C-terminal region of SRGAP3 mediates binding to multiple SH3 domains
    • HOMOLOGY
    intraspecies homolog to RHO-GAP hematopoietic protein C1(ARHGAP4)
    Homologene
    FAMILY
  • Rho GTPases family
  • FNBP2 family
  • Slit-Robo GAP (srGAP) family
    • CATEGORY regulatory , signaling
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytosolic
    intracellular,nucleus
    text
  • undergoes regulated shuttling between the cytoplasm and the nucleus during neuronal development
  • RAPH1 localizes with SRGAP3 at the leading edge
    • basic FUNCTION
  • involved in axon guidance and neurite outgrowth and in mental development
  • 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
  • implicated in repulsive axon guidance and neuronal migration through Slit-Robo-mediated signal transduction
  • inhibitory role of SRGAP3 on actin dynamics, specifically on lamellipodia formation
  • controls actin and microtubule dynamics through negative regulation of RAC1
  • has tumor suppressor-like activity in mammary epithelial cells, likely through its activity as a negative regulator of RAC1
  • SRGAP3-mediated cytoskeletal reorganisation has an important influence on a variety of neurodevelopmental processes, which may be required for normal cognitive function
  • important modulator of actin cytoskeletal dynamics and has an important influence on a variety of neurodevelopmental processe
  • implicated in different critical aspects of neuronal development
  • via its interactions SRGAP3 could link receptor signalling events to the endocytic machinery
    • CELLULAR PROCESS cell communication
    PHYSIOLOGICAL PROCESS development
    PATHWAY
    metabolism
    signaling signal transduction
    a component
  • component of the WAVE1 complex
    • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • interacting with the intracellular domain of ROBO1
  • binding partner of WASF1/WAVE1 that funtions as a signal termination factor for Rac
  • SRGAP3 influences RAPH1-evoked lamellipodial dynamics
  • interplay between SRGAP1, SRGAP2 and SRGAP3 regulates neuronal differentiation and neurite outgrowth
  • nuclear-localized SRGAP3 interacts with the SWI/SNF remodeling factor sMARCA4
    • cell & other
    REGULATION
    activated by enhanced by SLIT*
    Other inactivated by CDC42
    ASSOCIATED DISORDERS
    corresponding disease(s) MRAJ , DEL3PD
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral fusion      
    in-frame oncogenic fusion between SRGAP3 and RAF1 in Pilocytic astrocytomas (Jones 2009)
    Susceptibility
    Variant & Polymorphism
    Candidate gene for MR in 3p deletion
    Marker
    Therapy target
    ANIMAL & CELL MODELS