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FLASH GENE
Symbol NTN1 contributors: mct - updated : 28-04-2017
HGNC name netrin 1
HGNC id 8029
Location 17p13.1      Physical location : 8.924.858 - 9.147.316
Synonym name netrin 1, mouse, homolog of
Synonym symbol(s) NTN1L, UNC-6
DNA
TYPE functioning gene
STRUCTURE 222.46 kb     7 Exon(s)
10 Kb 5' upstream gene genomic sequence study
MAPPING cloned Y linked N status provisional
RNA
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
7 - 5954 67 604 - 2004 14750959
EXPRESSION
Type widely
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Cardiovascularheart   highly
Digestiveintestinesmall intestine  highly
 intestinelarge intestinecolon highly
 liver   highly
 mouthtongue  highly
Reproductivefemale systembreastmammary gland highly
 male systemprostate  highly
Urinarykidney   highly
tissue
SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
Blood / hematopoieticbone marrow   
Epithelialabsorptive excretorydigestive epithelium (mucosa)  
cells
SystemCellPubmedSpeciesStageRna symbol
Digestiveenterocyte
cell lineage
cell lines
fluid/secretion
at STAGE
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