Selected-GenAtlas references SOURCE GeneCards NCBI Gene Swiss-Prot Ensembl
HGNC UniGene Nucleotide OMIM UCSC
Home Page
FLASH GENE
Symbol NTRK2 contributors: mct/shn - updated : 05-07-2015
HGNC name neurotrophic tyrosine kinase, receptor, type 2
HGNC id 8032
Location 9q21.33      Physical location : 87.283.465 - 87.638.505
Synonym name
  • GP145-TrkB
  • tyrosine kinase receptor B
  • tropomyosin-related kinase B
  • trkB tyrosine kinase
  • BDNF/NT-3 growth factors receptor
  • BDNF-tropomyosine receptor kinase B
  • Synonym symbol(s) TRKB, RP11-263K15.1, GP145-TrkB, trk-B
    EC.number 2.7.10.1
    DNA
    TYPE functioning gene
    STRUCTURE 355.04 kb     24 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence
    text structure
  • regulatory element designated TCaRE3 (TRKB Ca(2+) response element 3) required for CREB-dependen NTRK2 transcription in neurons (functional interaction between CREB1 bound to the CREs and KLF7 bound to TCaRE3 is essential for the proper regulation of NTRK2 in neurons.)
  • MAPPING cloned Y linked Y status confirmed
    Map cen - D9S152 - D9S1877 - NTRK2 - D9S1790 - D9S1865 - qter
    Physical map
    LOC389761 9 similar to RIKEN cDNA 1700013B16 LOC389762 9 hypothetical gene supported by AK126070 LOC389763 9 similar to RIKEN cDNA 1700013B16 LOC286228 9q21.33 similar to DEAD (Asp-Glu-Ala-Asp) box polypeptide 10; DEAD box-10 LOC392356 9 similar to 40S ribosomal protein S2 LOC392357 9 hypothetical gene supported by AK094743 FLJ31614 9q21.33 hypothetical protein FLJ31614 MGC20553 LOC169505 9q21.33 similar to RIKEN cDNA 5133401N09 UBQLN1 9q21.2-q21.3 ubiquilin 1 GKAP42 9q22.1 protein kinase anchoring protein GKAP42 KIF27 9q22.1 kinesin family member 27 C9orf64 9q22.1 chromosome 9 open reading frame 64 HNRPK 9q21.32-q22.33 heterogeneous nuclear ribonucleoprotein K C9orf76 9q22.1 chromosome 9 open reading frame 76 SLC28A3 9q22.2 solute carrier family 28 (sodium-coupled nucleoside transporter), member 3 NTRK2 9q22.1 neurotrophic tyrosine kinase, receptor, type 2 AGTPBP1 9q21.33 ATP/GTP binding protein 1 LOC389764 9 similar to kinesin family member 27 LOC389765 9 similar to kinesin family member 27 LOC138198 9q22.1 similar to prohibitin FLJ21613 9q22.1 corneal wound healing-related protein GOLPH2 9p24.1-q32 golgi phosphoprotein 2 LOC389766 9 similar to RIKEN cDNA 4921517D22 HBLD2 9q22.1 HESB like domain containing 2 ZCCHC6 9q21 zinc finger, CCHC domain containing 6 LOC392358 9 similar to 40S ribosomal protein S6 (Phosphoprotein NP33) GAS1 9q21.3-q22.1 growth arrest-specific 1 LOC157956 9q22.1 cell division cycle 20 pseudogene LOC392359 9 similar to transactivator HSM-1
    RNA
    TRANSCRIPTS type messenger
    text a truncated non catalytic form (fetal brain)
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    17 splicing 8340 61 553 only in the brain 2007 17889702
  • also called TrkB-T-Shc or variant d
  • located in plasma membrane ,negative regulator of NTRK2 in the brain
  • alternative exon 19
    13 - 7111 53.1 477 - 2007 17889702
    also called TrkB-T1 or variant b
    20 - 5560 92 822 - 2007 17889702
    also called variant c
    21 - 5608 93.8 838 - 2007 17889702
    also called variant a
    16 - 8292 59.2 537 - 2007 17889702
    also called variant e
    EXPRESSION
    Type
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Nervousbrainmidbrainnuclei   Homo sapiens
     brainhindbrainpons predominantly Homo sapiens
     brainmidbrainsubstantia nigra lowly Homo sapiens
     brainhindbrainmedulla oblongata predominantly Homo sapiens
    Visualeyeretina    Homo sapiens
    cells
    SystemCellPubmedSpeciesStageRna symbol
    VisualMuller cell Homo sapiens
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a signal peptide,
  • an extracellular domain consisting of 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
  • conjugated
    mono polymer dimer
    HOMOLOGY
    interspecies ortholog to Ntrk2, Mus musculus
    ortholog to Ntrk2, rattus norvegicus
    ortholog to NTRK2, Pan troglodytes
    Homologene
    FAMILY
  • Trk family tyrosine kinases
  • CATEGORY enzyme , receptor
    SUBCELLULAR LOCALIZATION     plasma membrane
    text receptor tyrosine kinase, class VI
    basic FUNCTION
  • functional receptor for brain derived neurotrophic factor (BDNF)
  • hippocampus-mediating learning
  • essential to the development of GABAergic neurons and regulates synapse formation
  • retinal BDNF/NTRK2 signaling has its primary role in the development of inner retinal neuronal circuits, and this action is not a secondary effect due to the loss of visual signaling in the outer retina
  • modulate specific phases of fear learning and amygdalar synaptic plasticity through two main phosphorylation docking sites
  • its activation stimulates the dendritic branching of mitral/tufted cells in developing olfactory bulb
  • plays important roles in facilitating metastasis in various types of malignant tumors
  • additional component that potentially might contribute to the altered neurotrophic support in Huntington disease
  • with BDNF, are essential in promoting normal development of the central nervous system
  • BDNF and NTRK2 play important roles in controlling respiration, movement, balance and feeding in the brainstem and that the NTRK2 is the most age-sensitive component of this system, especially in the hippocampus
  • regulates the cell surface expression of KCNJ9
  • unlike NTRK1 and NTRK3, does not trigger neuronal death
  • potent suppressor of anoikis
  • potential tag for synapse-specific expression of late-phase long-term potentiation and long-term memory
  • BDNF/TrkB signaling promotes neuronal survival and can help neurons resist toxic insults
  • NTRK2 and PRKCZ, two critical regulators of synaptic plasticity, facilitate DLG4 targeting to synapses
  • expression of NTRK2 and BDNF is associated with poor prognosis in non-small cell lung cancer patients
  • is necessary for ciliary localization of NTRK2 receptor and activation by BDNF
  • neurotrophin signaling via NTRK2 and NTRK3 promotes the growth of brain tumor-initiating cells
  • plays a key role in tumorigenicity and metastasis of breast cancer cells through suppression of RUNX3 or KEAP1
  • CELLULAR PROCESS cell life, differentiation
    cell organization/biogenesis
    PHYSIOLOGICAL PROCESS development , nervous system , neurogenesis
    text
  • key regulator of cell fate and cell shape in CNS
  • establishment of synapses (GABAergic in cerebellum)
  • PATHWAY
    metabolism
    signaling signal transduction
  • mediating BDNF signaling to sensory neurons
  • BDNF/NTRK2 signaling activates PI3-kinase that promotes anterograde transport of NTRK2 in the putative axon, further enhancing local BDNF/NTRK2 signaling
  • a component BDNF/NTRK2 signaling is essential for the development of photoreceptors and for synaptic communication between photoreceptors and second order retinal neurons
    INTERACTION
    DNA
    RNA
    small molecule nucleotide,
  • ATP
  • protein
  • neurotrophin-3, NT-3
  • brain-derived neurotrophic factor, BDNF
  • Src family tyrosine kinase Fyn
  • rAPS and SH2-B
  • neurotrophin receptor p75(NTR)
  • 14 kDa light chain of cytoplasmic dynein
  • neurotrophins NTF3 and NTF4
  • Nck2
  • ShcB and ShcC
  • phospholipase Cgamma, PLCgamma
  • p62
  • ankyrin-rich transmembrane protein, ARMS
  • Dok5
  • neural cell adhesion molecule NCAM1 and KCNJ9
  • RANBP9 may modulate NTRK2-mediated downstream signaling and biological functions
  • PLCG1
  • regulates BDNF-induced Erk activation and axonal filopodia formation
  • LIMK1 (
  • NTRK2 and NCAM1 are downstream targets of NEUROD1 that contribute to the actions of NEUROD1 in neuroendocrine lung
  • HAP1 stabilized the association of NTRK2 with the intracellular sorting protein sortilin, prevented NTRK2 degradation, and promoted its anterograde transport
  • BDNF, via truncated NTRK2, modulates SLC6A9 and SLC6A5 in astrocytes
  • LINGO1 functions as a negative feedback regulator of signaling by cognate receptor tyrosine kinases including NTRK1, NTRK2 and NTRK3
  • NTRK2 plays a key role in regulation of the tumor suppressors RUNX3 and KEAP1
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --other  
    altered in Huntington disease
    tumoral     --over  
    in colon cancer possibly plays roles in inhibiting apoptosis, promoting proliferation and invasion, facilitating tumor progression by lymphangiogenesis-associated metastasis
    tumoral     --over  
    in disfiguring cutaneous appendageal tumours of CYLD
    tumoral fusion      
    NTRK2 is a new gene fusion target in pilocytic astrocytoma (fusion with QKI, FGFR1)
    Susceptibility to autism
    Variant & Polymorphism other alterations in BDNF/NTRK2 signaling contribute to an increased vulnerability to autism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancer  
    NTRK2 blockade may be a new strategy for transitional cell carcinoma therapy
    neurologyepilepsy 
    disruption of NTRK2-mediated PLCG1 signaling inhibits limbic epileptogenesis, and is a novel target for specific and effective therapeutic intervention
    neurology  
    manipulation of BDNF/TrkB signaling might have therapeutic efficacy in motor neuron diseases
    neurology  
    restoration of the physiological level of the TrkB.T1 receptor by gene targeting rescues Ts16 cortical cell and hippocampal neuronal death, corrects resting Ca2+ levels and restores BDNF-induced intracellular signaling in the trisomy 16 mouse model
    cancerbrainglioma/neuroblstoma
    could be a target for combinatorial treatment of malignant glioma
    ANIMAL & CELL MODELS
  • knockout of trkB restricted to the mouse forebrain during postnatal development leads to increasingly impaired learning behavior or inappropriate coping responses when facing complex and/or stressful learning paradigms, impairment LTP at CA1 hippocampal synapses
  • inhibitory interneurons are strongly affected, express reduced amounts of GABAergic markers and develop reduced numbers of GABAergic boutons and synaptic specializations in cerebellum of TrkB mutant mice
  • mouse mutants that expresses the BDNF receptor TrkB at a quarter of the normal amount showed hyperphagia and excessive weight gain on higher-fat diets
  • trkB(CaMKII-CRE) mice with a trkB-receptor disruption in the forebrain showed a stereotyped hyper-locomotion with reduced explorative activity, and impulsive reactions to novel stimuli
  • in vivo conditional deletion of TrkB from mature motor neurons attenuates mutant superoxide dismutase 1 (SOD1) toxicity