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FLASH GENE
Symbol SLIT2 contributors: mct/ - updated : 24-03-2014
HGNC name slit homolog 2 (Drosophila)
HGNC id 11086
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • four leucine rich repeats (second LRR domain and the two N-terminal Ig domains of Robo mediates Slit-Robo interaction)
  • two calcium binding type EGF-like repeats
  • four LRRCC domains
  • nine EGF domains
  • Laminin G (LamG) domain, and SLITCCR domain
  • seven EGF-like motifs
  • cysteine-rich (CTC) knot motif
    • mono polymer homomer , dimer
    HOMOLOGY
    interspecies homolog to SLIT Drosophila 2
    homolog to murine Slit2
    Homologene
    FAMILY
  • laminin G family
    • CATEGORY regulatory , secretory
    SUBCELLULAR LOCALIZATION extracellular
        plasma membrane
        intracellular
    intracellular,cytoplasm
    text
  • maximal in the late-luteal phase and significantly reduced after luteal rescue
    • basic FUNCTION
  • chemorepellant, involved in early body axis formation and cell patterning of the neural-tube and endocrine system
  • involved in neuronal migration through the elevation of intracellular concentration of calcium
  • function as a novel tumor suppressor gene
  • induces a tumor-suppressive effect by regulating beta-catenin in breast cancer cells
  • SLIT1 and SLIT2, regulate two distinct aspects of intraretinal axon guidance in a region-specific manner
  • role during the angiogenic process that relies on the directional migration not only of endothelial cells but also of pericytes
  • is a powerful negative regulator of platelet function and thrombus formation
  • SLIT2 may act in an autocrine manner on beta cells, whereas SLIT1 and SLIT3 may play both autocrine and paracrine roles
  • may also be a potential tumor suppressor in renal cell carcinoma (RCC), which is down-regulated in RCC partially due to promoter methylation
    • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS development
    text
  • neurogenesis
  • maintenance of dorsal position by preventing axonal growth into the ventral region
  • prevention of axonal extension toward and across the midline
  • channneling of axons toward particular region
    • PATHWAY
    metabolism
    signaling
    SLIT signaling depletes ER Ca2+ and protects beta cells from ER stress
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • ligand to GPC1 (glypican 1)
  • ligand for ROBO proteins, increasing srGAP(s)-ROBO(s) interaction (Slit-Robo interaction is mediated by the second LRR domain of Slit and the two N-terminal Ig domains of Robo)
  • inactivating CDC42
  • negative regulators of CXCL12 and CXCR4
  • can bind to heparan sulfate and contribute to a Slit-Robo signalling mechanism
  • target of polycomb group (PcG) protein EZH2
  • cooperation between SLIT2 and EPHA1 regulates a balance between the pro- and antiangiogenic functions of SLIT2
  • NEUROD1 directly bound to the first and second E-box of the SLIT2 promoter region
  • regulates the dispersal of oligodendrocyte precursor cells through FYN and RHOA signaling
  • FZD3 is essential for normal development of the commissural plate and its loss-of-function causes SLIT2-dependent defects in axon midline crossing in the embryonic vertebrate forebrain
    • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --low  
    by hypermethylation in various cancers, including breast and lung cancer, colorectal carcinoma, and gliomas
    tumoral     --other  
    epigenetic silencing of in hepatocellular carcinoma (decrease of SLIT2 expression was also associated with lymph node metastasis)
    tumoral       loss of function
    in human cancers and may regulate apoptosis and metastasis
    tumoral     --low  
    by epigenetic mechanisms, in a majority of metastatic prostate tumors, showing a negative correlation with EZH2
    tumoral     --low  
    in pancreatric carcinoma exhibited a higher incidence and a higher fraction of tumor-infiltrated lymph nodes
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
  • potential biomarker for aggressive solid tumors
  • may be a potent noninvasive prognostic biomarker of prostate cancer
    • Therapy target
    SystemTypeDisorderPubmed
    cancerdigestiveliver
    useful as a therapeutic target in the treatment of hepatocellular carcinoma
    ANIMAL & CELL MODELS
  • mice lacking Slit2 or Robo3 have a reduced number of GnRH neurons in the forebrain, but a normal complement of their supporting axons, pointing to a direct role for these molecules in GnRH neuron migration