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FLASH GENE
Symbol SLIT1 contributors: mct - updated : 05-04-2012
HGNC name slit homolog 1 (Drosophila)
HGNC id 11085
Location 10q24.1      Physical location : 98.757.794 - 98.945.683
Synonym name multiple epidermal growth factor-like motif 4
Synonym symbol(s) MEGF4, SLIL1, SLIT3
DNA
TYPE functioning gene
STRUCTURE 187.89 kb     37 Exon(s)
10 Kb 5' upstream gene genomic sequence study
MAPPING cloned Y linked   status provisional
RNA
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
37 - 7949 168.7 1534 brain 2001 11309622
major
- - 5900 - - brain 2001 11309622
EXPRESSION
Type widely
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Endocrinepancreas   predominantly Homo sapiens
Lymphoid/Immunethymus   highly
Nervousbrain   highly
cells
SystemCellPubmedSpeciesStageRna symbol
Endocrineislet cell (alpha,beta...) Homo sapiens
cell lineage
cell lines
fluid/secretion
at STAGE
physiological period fetal
Text fetal brain
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • secretory protein with four leucine rich repeats (LRR)
  • the second leucine-rich repeat domain (D2) mediates binding to Robo receptors, and also contains a functionally important binding site for heparin
  • two calcium binding type
  • four LRRCC domains
  • nine EGF domains
  • Laminin G (LamG) domain, and SLITCCR domain (Katoh 2005)
  • seven EGF-like motifs
  • cysteine-rich (CTC) knot motif
  • basic residues in the C-terminal cap region
  • HOMOLOGY
    interspecies homolog to SLIT Drosophila 1
    homolog to murine Slit 1
    Homologene
    FAMILY laminin G family
    CATEGORY regulatory , secretory
    SUBCELLULAR LOCALIZATION extracellular
        intracellular
    intracellular,cytoplasm
    basic FUNCTION
  • chemorepellent, involved in histogenesis of central nervous system controlling the migrations of neurons and leukocytes of olfactory system
  • play a key role in guiding dorsally projecting cranial motoneurons and in facilitating their neural tube exit
  • SLIT1 and SLIT2, regulate two distinct aspects of intraretinal axon guidance in a region-specific manner
  • acts via ROBO2 in dendrites as a branching/growth factor but not in guidance, while ROBO2 and ROBO3 function in concert in axons to mediate axonal interactions and respond to Slits as guidance factors
  • multifunctional guidance cues, capable of triggering neurite repulsion, extension, or branching, depending on cell type and developmental context
  • SLIT1 signaling, perhaps in the form of a superficial-to-deep gradient, presents laminar positional cues to ingrowing retinal axons
  • role during the angiogenic process that relies on the directional migration not only of endothelial cells but also of pericytes
  • SLIT2 may act in an autocrine manner on beta cells, whereas SLIT1 and SLIT3 may play both autocrine and paracrine roles
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS development
    text
  • neuronal development,axon guidance
  • 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
  • complexing with ROBO2 (role for ROBO2-SLIT1 signaling in mediating neural crest
  • placode interactions during trigeminal gangliogenesis)
  • part of the SLIT/ROBO signaling that is critical during the initial establishment of dopaminergic pathways, with roles in the dorsoventral positioning and precise pathfinding of these ascending longitudinal axons
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • ligand to GPC1(glypican 1)
  • ligand for ROBO proteins increasing SrGAP1-ROBO1 interaction
  • inactivating CDC42
  • IRX4 is potentially a crucial regulator of SLIT1 expression in the retina
  • only NCK2 is required for the SLIT1-induced changes in cortical neuron morphology
  • binds to Dragnet (COL4A5), a type IV Collagen, which forms the basement membrane on the surface of the tectum
  • CASP3, CASP9, and MAPK14 interacted with SLIT1-ROBO2 signaling
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    ANIMAL & CELL MODELS