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FLASH GENE
Symbol SEMA3F contributors: mct - updated : 30-10-2018
HGNC name sema domain, immunoglobulin domain (Ig), short basic domain, secreted, (semaphorin) 3F
HGNC id 10728
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • N terminal signal peptide, the SEMA domain containing about 14 cysteine residues with a RGD domain
  • an Ig-like C2-type (immunoglobulin-like) domain
  • a transmembrane domain (TM)
  • a C terminal short basic domain
    • HOMOLOGY
    interspecies homolog to murine Sema3f (96.4pc)
    homolog to rattus Sema3f (95.8pc)
    Homologene
    FAMILY
  • semaphorin III family
    • CATEGORY motor/contractile
    SUBCELLULAR LOCALIZATION extracellular
    basic FUNCTION
  • repellent of the nerve growth cone guidance
  • may play a role in cell motility and cell adhesion
  • potent metastasis inhibitor that targets both tumor and stromal cells
  • may help to establish the dopaminergic projection from the midbrain to the striatum during embryonic development (Hernández-Montiel 2008)
  • had a repulsive effect on dopaminergic axons (Hernández-Montiel 2008)
  • having a striking effect on tumor cell and EC morphology, causing cytoskeleton collapse, loss of stress fibers, loss of adhesion, and depolymerization of F-actin, rapidly within minutes
  • axon guidance molecule, involved in TP53-regulated antiangiogenesis
  • functions as an antiangiogenic factor that repels endothelial cells and compromises their proliferation/survival (Varshavsky 2008)
  • can inhibit the binding of VEGF to neuropilin (Parker 2010)
  • potent anti-angiogenic effects of Semaphorin 3F on both retinal and choroidal vessels
  • functional role for Semaphorin 3F in the outer retina where it acts as a vasorepulsive cue to maintain physiologic avascularity
  • SEMA3F and NRP2 are further regulators of human thymocyte migration in physiological and pathological conditions
  • provides neuronal guidance cues via its ability to bind neuropilin 2 (NRP2) and Plexin A family molecules
  • role in guiding axonal migration during neuronal development
  • SEMA3A, -3C, and -3F, likely with coreceptors NRP1, NRP2, and plexin-A1 and/or -A3, promote migration and possibly other activities of human DCs during innate and adaptive immune responses
    • CELLULAR PROCESS cell organization/biogenesis
    cell communication
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • complex with NRP2 (neuropilin-2) and plexin A1
  • NRCAM is a novel postnatal regulator of dendritic spine density in cortical pyramidal neurons, and an integral component of the SEMA3F receptor complex
    • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • FMR1 (RNA target of FMR1)
  • neuropilin-2 (NRP2) agonist (functional receptor for SEMA3F)
  • interacting with SEMA3A (combinations of SEMA3A and SEMA3F may be able to inhibit tumor angiogenesis more effectively than single semaphorins)
  • interacting with TP53 (TP53-binding sequence in intron 1 of SEMA3F interacts with TP53 and has a TP53-responsive transcriptional activity, negatively regulating tumor vessel formation and cell growth)
  • interacting with ID2 (SEMA3F, a potent inhibitor of metastasis, was repressed by ID2)
  • hypoxia induces tumor and endothelial cell migration in a SEMA3F- and VEGFA-dependent manner via transcriptional repression of their common receptor NRP2
  • SEMA3F can induce CHN2 activation and CHN2 is required for SEMA3F-dependent inhibition of Rac-GTP levels and does not significantly affect levels of activated CDC42
  • SEMA3F can down-regulate TP53 expression in primary hippocampal neurons, thereby contributing to growth cone collapse
  • PLXNA3 is involved in SEMA3F-mediated oligodendrocyte precursor cell migration
  • SEMA3F regulates MTOR signaling in diverse human cell types, suggesting that it has broad therapeutic implications.
  • SEMA3F functions as an unconventional SEMA3 that promotes extraembryonic angiogenesis by inhibiting the MYC-regulated synthesis of THBS1 in visceral yolk sac epithelial cells
  • NRCAM mediate spine pruning as a subunit of the receptor complex for the repellent ligand SEMA3F
  • NRCAM stabilizes binding between NRP2 and PLXNA3 necessary for SEMA3F-induced spine pruning
    • cell & other
    REGULATION
    activated by histone deacetylase inhibition
    repressed by promoter methylation
    Other proteolytically processed by FURIN (Parker 2010)
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --low  
    in metastatic tumor
    tumoral     --low  
    in lung cancer
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
  • semaphorin 3F amniotic level at 16-18 weeks of gestation was reduced in women who subsequently developed preeclampsia compared to women with a normal pregnancy
    • Therapy target
    SystemTypeDisorderPubmed
    neurosensorialvisualdegenerative
    use of SEMA3F in protecting the outer retina against subretinal neovascularization.
    ANIMAL & CELL MODELS