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FLASH GENE
Symbol NTRK1 contributors: mct/ - updated : 11-10-2015
HGNC name neurotrophic tyrosine kinase, receptor, type 1
HGNC id 8031
Corresponding disease
HSAN4 hereditary sensory and autonomic neuropathy, type IV
Location 1q23.1      Physical location : 156.785.541 - 156.851.642
Synonym name
  • high affinity nerve growth factor receptor
  • formed by fusion with TPM3 or TFG (see symbols) in papillary thyroid carcinoma
  • tropomyosin-related kinase A
  • oncogene TRK
  • Synonym symbol(s) HNGFR, TRKA, TRK, MTC, p140-TrkA, DKFZp781I14186, TRK1, p140-TrkA
    EC.number 2.7.10.1
    DNA
    TYPE functioning gene
    STRUCTURE 66.10 kb     17 Exon(s)
    Genomic sequence alignment details
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status confirmed
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    16 - 2647 - 790 non neuronal tissues 2009 19250380
    also called variant 1 or TRKA-I
    17 - 2663 - 796 neuronal tissues 2009 19250380
    also called variant 2 or TRKA-II
    17 - 2581 - 760 - 2009 19250380
    also called variant 3 or TRKA-III
    EXPRESSION
    Type restricted
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Endocrinethyroid    
    Nervousbrain     Homo sapiens
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Blood / Hematopoieticbone marrow   
    Nervouscentral    Homo sapiens
    Nervousperipherous    Homo sapiens
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Blood/Hematopoieticmonocyte
    Nervousneuron Homo sapiens
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a signal peptide
  • an extracellular domain with three tandem leucine-rich motifs flanked by two cysteine clusters and two Ig-like domains
  • a single transmembrane segment (1TM)
  • an intracellular domain possessing a tyrosine-kinase domain
  • mono polymer homomer , monomer , dimer
    HOMOLOGY
    Homologene
    FAMILY
  • protein kinase superfamily
  • Tyr protein kinase family
  • insulin receptor subfamily
  • CATEGORY enzyme , protooncogene , receptor
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,organelle,mitochondria
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,organelle,Golgi
    intracellular,cytoplasm,organelle,endosome
    intracellular,nucleus
    text
  • nuclear localization of the intracellular domain of NTRK1 is observed constitutively in liver cells such as hepatocytes and activated stellate cells, while in other cell types it could be induced in response to soluble factors
  • NGFR and NTRK1 are localized in the mitochondrial compartment of undifferentiated human podocytes and in all tissues analyzed including central nervous system
  • basic FUNCTION
  • nerve growth factor receptor, high affinity (dimeric form)
  • involved in the survival differentiation and maintenance of many neural and non neural cell types
  • by attracting microtubules to lipid rafts, may mediate other processes such as axon guidance
  • CELLULAR PROCESS cell life, differentiation
    cell life, cell death/apoptosis
    PHYSIOLOGICAL PROCESS nervous system
    text apoptotic or antiapoptotic function; key regulator of cell fate and cell shape in CNS
    PATHWAY
    metabolism
    signaling signal transduction
  • RUSC1 participates in the NGF-NTRK1 signaling pathway
  • a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • binding nerve growth factor (NGFA, NGFB, NGFC), its high affinity
  • binding neurotrophins (NTF3, NTF4)
  • associates with TID1
  • interaction with KALRN by the pleckstrin homology domain
  • NGF is a cognate ligand for the neurotrophic receptor NTRK1, promoting the interaction between CTBP2 and ACIN1 through triggering ACIN1 phosphorylation by AKT1
  • APP is phosphorylated by NTRK1 and regulates NGF/NTRK1signaling
  • NTRK1 and NGFR collaborate with each other at the plasma membrane to bind NGF
  • RASGRF1 binds nerve growth factor (NGF)-activated NTRK1
  • RUSC1 RUN domain can directly interact with NTRK1
  • NGFR and NTRK1 interact to enhance neurotrophic signaling
  • STX8 facilitates NTRK1 transport from the Golgi to the plasma membrane and regulates the surface levels of NTRK1 but not NTRK2 receptors
  • LINGO1 functions as a negative feedback regulator of signaling by cognate receptor tyrosine kinases including NTRK1, NTRK2 and NTRK3
  • cell & other
    REGULATION
    activated by RUNX1/RUNX1T1 fusion protein in CD34+ cells and in hematopoietic stem cells
    repressed by MYCN (acts directly to repress NTRK1 and NGFR gene transcription)
    ASSOCIATED DISORDERS
    corresponding disease(s) HSAN4
    related resource Mutation Database of Inherited Peripheral Neuropathies
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in association with EPHB6, EFNB2, EFNB3 in low grade neuroblastoma
    tumoral   deletion    
    in thyroid tumor
    tumoral fusion      
    chimeric protein of fusion between NTRK1 and one among tropomyosin, TRP or TAG in thyroid tumor
    constitutional        
    total absence of the expression in keratoconus (repression by Sp3 transcription factor)
    tumoral     --over  
    enhances the tumorigenic properties of breast cancer cells
    constitutional     --low  
    levels of both NGF protein in seminal plasma and NTRK1 mRNA in spermatozoa are low in samples from oligoasthenozoospermic men
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancerhemopathy 
    potential target for therapeutic in t(8;21) positive leukemia
    ANIMAL & CELL MODELS