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FLASH GENE
Symbol NTN1 contributors: mct - updated : 28-04-2017
HGNC name netrin 1
HGNC id 8029
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • laminin N terminal domain
  • VI, V-2, and V-3 domains primarily required for dorsal migrations
  • VI and V-3 domains are required for ventral migrations
    • conjugated GlycoP
    HOMOLOGY
    interspecies homolog to murine Ntn1 (99.2pc)
    homolog to rattus Ntn1 (99.0pc)
    Homologene
    FAMILY
  • laminin related secreted proteins family
    • CATEGORY signaling growth factor
    SUBCELLULAR LOCALIZATION extracellular
        intracellular
    intracellular,cytoplasm
    text secreted protein, extracellular space or extracellular matrix
    basic FUNCTION
  • axon outgrow-promoting protein, collaborating with SHH to guide commissural axons to the midline
  • playing a major role during nervous system development in mediating chemo-attraction and chemo-repulsion of axons and neurons by interacting with its receptor DCC
  • regulating the migratory pathway of LHRH neurons
  • involved in colorectal tumorigenesis by regulating apoptosis
  • both Slits and NTN1 contribute to floor plate-derived chemorepulsion of cranial motor axons
  • recruiting DOCK1 through DCC, which then activates small GTPases
  • may regulate the development of placental vessels and plays a key role in the pathogenesis of fetal growth restriction
  • potentially required for oligodendroglial migration into the olfactory bulb, but is dispensable for the proliferation of neurosphere forming progenitor cells and for their differentiation
  • functionally important for the development of the nervous system
  • laminin-related secreted protein, that is highly induced after tissue injury, and may serve as a marker of injury
  • bifunctional guidance cue
  • NTN1/DCC/UNC5C chemotropism contributes to axonal confinement within the CNS
  • NTN1-UNC5C/DCC interaction is involved in controlling the interhemispherical projection in a subset of early born, deep layer callosal neurons
    • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS development , nervous system
    text
  • survival factor via receptors DCC, UNC5A, B, C
  • neuronal development
    • PATHWAY
    metabolism
    signaling
    cell-cell signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • specifically binding to DCC and mediating axon guidance independently of adenosine A2B receptor activation but through the MAPK activation
  • binding to ADORAB, UNC5A, UNC5B, UNC5C
  • crucial role for PlTPNA in NTN1-induced neurite outgrowth, revealing a signalling mechanism for DCC/NEO1 and PlTPNA regulation
  • requiring MAPK activation of DCC for axon outgrowth
  • direct transcriptional target of the transcription factor NFKB
  • binds to DCC and DSCAM mediating axon attraction, and UNC5 mediating axon repulsion
  • in contrast to callosal neurites, in which NTN1 required GAP43 in order to stimulate both outgrowth and guidance, in ventrolateral efferents, NTN1 required GAP43 only to stimulate outgrowth, but not guidance
  • MAPK8 plays an important role in NTN1-mediated axon guidance in the developing nervous system
  • combination of DSCAM with DCC or UNC5C plays an important role in NTN1-mediated axon attraction or repulsion
  • NTN1-UNC5C/DCC interaction is involved in controlling the interhemispherical projection in a subset of early born, deep layer callosal neurons
  • negative regulation of NAA10 towards NTN1 and its receptor UNC5B were also detected upon treatment of all-trans retinoid acid, which was often used to induce morphological differentiation
  • disengagement of UNC5C with polymerized TUBB3 plays an essential role in NTN-1/UNC5C-mediated axon repulsion
  • NTN1, a canonical guidance cue, induced the interaction of TUBB3 with the netrin receptor DCC
  • direct coupling of dynamic TUBB3 in microtubules with netrin receptors is required for NTN1-mediated axon guidance, and the interaction of NTN1 repulsive receptor UNC5C with TUBB3 is involved in NTN1 mediated axonal repulsion
    • cell & other
    REGULATION
    inhibited by netrin attraction is repressed by SLIT through a DCC/ROBO complex
    Other mediated by cytoplasmic Ca2+ signals
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --low  
    in brain tumor and neuroblastama
    constitutional     --over  
    in epithelial cells of ulcerative colitis, and Crohn disease, and required for colorectal cancer progression (Paradisi 2009)
    tumoral     --over  
    strongly upregulated in ovarian malignant tumors but not in benign tumors
    tumoral     --over  
    in inflammatory bowel diseases is required for colorectal cancer progression (
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
  • may represent a novel candidate biomarker for ovarian cancer
    • Therapy target
    SystemTypeDisorderPubmed
    cancerdigestivecolon
    inhibition of NTN1 could be an innovative target for drug therapy in inflammation-driven colorectal cancers
    ANIMAL & CELL MODELS