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NTRK2 (Neurotrophic receptor tyrosine kinase 2)

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Summary of NTRK2

The gene codes for a protein, neurotrophic receptor tyrosine kinase 2. Mutations are linked to obesity and mood disorders [R].

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The Function of NTRK2

Receptor tyrosine kinase involved in the development and the maturation of the central and the peripheral nervous systems through regulation of neuron survival, proliferation, migration, differentiation, and synapse formation and plasticity. Receptor for BDNF/brain-derived neurotrophic factor and NTF4/neurotrophin-4. Alternatively can also bind NTF3/neurotrophin-3 which is less efficient in activating the receptor but regulates neuron survival through NTRK2. Upon ligand-binding, undergoes homodimerization, autophosphorylation and activation. Recruits, phosphorylates and/or activates several downstream effectors including SHC1, FRS2, SH2B1, SH2B2 and PLCG1 that regulate distinct overlapping signaling cascades. Through SHC1, FRS2, SH2B1, SH2B2 activates the GRB2-Ras-MAPK cascade that regulates for instance neuronal differentiation including neurite outgrowth. Through the same effectors controls the Ras-PI3 kinase-AKT1 signaling cascade that mainly regulates growth and survival. Through PLCG1 and the downstream protein kinase C-regulated pathways controls synaptic plasticity. Thereby, plays a role in learning and memory by regulating both short term synaptic function and long-term potentiation. PLCG1 also leads to NF-Kappa-B activation and the transcription of genes involved in cell survival. Hence, it is able to suppress anoikis, the apoptosis resulting from loss of cell-matrix interactions. May also play a role in neutrophin-dependent calcium signaling in glial cells and mediate communication between neurons and glia.

Protein names

Recommended name:

BDNF/NT-3 growth factors receptor

Alternative name(s):

GP145-TrkB
Trk-B
Neurotrophic tyrosine kinase receptor type 2
TrkB tyrosine kinase
Tropomyosin-related kinase B

NTRK2 SNPs

    To see your genotype, you should be logged in and have a file with your genotype uploaded.

  1. RS10868236 (NTRK2) ??
  2. RS1212171 (NTRK2) ??
  3. RS2289658 (NTRK2) ??
  4. RS77362122 (NTRK2) ??

Top Gene-Substance Interactions

NTRK2 Interacts with These Diseases

Disease Score

Substances That Increase NTRK2

Substances Interaction Organism Category

Substances That Decrease NTRK2

Substances Interaction Organism Category

Advanced Summary

     From NCBI Gene: Obesity, hyperphagia, and developmental delayFrom UniProt: Obesity, hyperphagia, and developmental delay (OBHD): A disorder characterized by early-onset obesity, hyperphagia, and severe developmental delay in motor function, speech, and language. [MIM:613886]

     From NCBI Gene: This gene encodes a member of the neurotrophic tyrosine receptor kinase (NTRK) family. This kinase is a membrane-bound receptor that, upon neurotrophin binding, phosphorylates itself and members of the MAPK pathway. Signalling through this kinase leads to cell differentiation. Mutations in this gene have been associated with obesity and mood disorders. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2014] From UniProt: Receptor tyrosine kinase involved in the development and the maturation of the central and the peripheral nervous systems through regulation of neuron survival, proliferation, migration, differentiation, and synapse formation and plasticity. Receptor for BDNF/brain-derived neurotrophic factor and NTF4/neurotrophin-4. Alternatively can also bind NTF3/neurotrophin-3 which is less efficient in activating the receptor but regulates neuron survival through NTRK2. Upon ligand-binding, undergoes homodimerization, autophosphorylation and activation. Recruits, phosphorylates and/or activates several downstream effectors including SHC1, FRS2, SH2B1, SH2B2 and PLCG1 that regulate distinct overlapping signaling cascades. Through SHC1, FRS2, SH2B1, SH2B2 activates the GRB2-Ras-MAPK cascade that regulates for instance neuronal differentiation including neurite outgrowth. Through the same effectors controls the Ras-PI3 kinase-AKT1 signaling cascade that mainly regulates growth and survival. Through PLCG1 and the downstream protein kinase C-regulated pathways controls synaptic plasticity. Thereby, plays a role in learning and memory by regulating both short term synaptic function and long-term potentiation. PLCG1 also leads to NF-Kappa-B activation and the transcription of genes involved in cell survival. Hence, it is able to suppress anoikis, the apoptosis resulting from loss of cell-matrix interactions. May also play a role in neutrophin-dependent calcium signaling in glial cells and mediate communication between neurons and glia.

Conditions with Increased Gene Activity

Condition Change (log2fold) Comparison Species Experimental variables Experiment name

Conditions with Decreased Gene Activity

Condition Change (log2fold) Comparison Species Experimental variables Experiment name

Technical

The following transcription factors affect gene expression:

  • NF-kappaB
  • CREB
  • AP-1
  • c-Jun
  • deltaCREB
  • NF-kappaB1
  • C/EBPbeta
  • C/EBPalpha
  • Sox9

Tissue specificity:

Isoform TrkB is expressed in the central and peripheral nervous system. In the central nervous system (CNS), expression is observed in the cerebral cortex, hippocampus, thalamus, choroid plexus, granular layer of the cerebellum, brain stem, and spinal cord. In the peripheral nervous system, it is expressed in many cranial ganglia, the ophthalmic nerve, the vestibular system, multiple facial structures, the submaxillary glands, and dorsal root ganglia. Isoform TrkB-T1 is mainly expressed in the brain but also detected in other tissues including pancreas, kidney and heart. Isoform TrkB-T-Shc is predominantly expressed in the brain.

Gene Pathways:

  • MAPK signaling pathway
  • Signal Transduction
  • Neurotrophin signaling pathway

Developmental stage:

Widely expressed in fetal brain.

Enzyme Regulation:

The neuronal activity and the influx of calcium positively regulate the kinase activity and the internalization of the receptor which are both important for active signaling. Regulated by NGFR that may control the internalization of the receptor. NGFR may also stimulate the activation by BDNF compared to NTF3 and NTF4. SH2D1A inhibits the autophosphorylation of the receptor, and alters the recruitment and activation of downstream effectors and signaling cascades. The formation of active receptors dimers able to fully transduce the ligand-mediated signal, may be negatively regulated by the formation of inactive heterodimers with the non-catalytic isoforms.

Molecular Function:

  • Atp Binding
  • Brain-Derived Neurotrophic Factor-Activated Receptor Activity
  • Brain-Derived Neurotrophic Factor Binding
  • Neurotrophin Binding
  • Protein Homodimerization Activity

Biological Processes:

  • Brain-Derived Neurotrophic Factor Receptor Signaling Pathway
  • Cellular Response To Amino Acid Stimulus
  • Central Nervous System Neuron Development
  • Cerebral Cortex Development
  • Circadian Rhythm
  • Feeding Behavior
  • Glutamate Secretion
  • Learning
  • Long-Term Synaptic Potentiation
  • Mechanoreceptor Differentiation
  • Negative Regulation Of Anoikis
  • Negative Regulation Of Neuron Apoptotic Process
  • Neuromuscular Junction Development
  • Neuron Differentiation
  • Neuron Migration
  • Oligodendrocyte Differentiation
  • Peripheral Nervous System Neuron Development
  • Positive Regulation Of Axonogenesis
  • Positive Regulation Of Cell Proliferation
  • Positive Regulation Of Gene Expression
  • Positive Regulation Of Mapk Cascade
  • Positive Regulation Of Neuron Projection Development
  • Positive Regulation Of Peptidyl-Serine Phosphorylation
  • Positive Regulation Of Phosphatidylinositol 3-Kinase Signaling
  • Positive Regulation Of Protein Phosphorylation
  • Positive Regulation Of Synapse Assembly
  • Protein Autophosphorylation
  • Regulation Of Gtpase Activity
  • Regulation Of Protein Kinase B Signaling
  • Retina Development In Camera-Type Eye
  • Retinal Rod Cell Development
  • Vasculogenesis
  • Aging
  • Calcium-Mediated Signaling Using Intracellular Calcium Source
  • Cellular Response To Brain-Derived Neurotrophic Factor Stimulus
  • Cellular Response To Tumor Necrosis Factor
  • Inflammatory Response
  • Long-Term Memory
  • Positive Regulation Of Synaptic Transmission, Glutamatergic
  • Regulation Of Dendrite Development
  • Regulation Of Neurotransmitter Secretion
  • Response To Auditory Stimulus
  • Response To Light Stimulus

Drug Bank:

  • Amitriptyline
*synonyms

Synonyms/Aliases/Alternative Names of the Gene:

hypothetical protein| ntrk2| tyrosine kinase receptor| AS27_03051| AS28_10973| BDNF/NT-3 growth factors receptor| BDNF-tropomyosine receptor kinase B| CB1_000657006| D623_10034362| EGK_07828| GP145-TrkB| GP145-TrkB/GP95-TrkB| H920_15562| I79_019796| M959_10806| MDA_GLEAN10012059| N300_09241| N301_05636| N302_09767| N303_06745| N305_03683| N306_13540| N307_06355| N308_14219| N309_08440| N326_09128| N336_12595| neural receptor protein-tyrosine kinase (trkB)| neurotrophic tyrosine kinase receptor type 2| neurotrophic tyrosine kinase, receptor, type 2| neurotrophic tyrosine kinase, receptor, type 2 isoform b precursor isoform 3-like protein| neurotrophic tyrosine receptor kinase type 2| ntrk2-a| ntrk2-b| PAL_GLEAN10008323| PANDA_003010| RATTRKB1| Tkrb| TREES_T100006104| trkB| trk-B| TRKB1| trkB tyrosine kinase| tropomyosin-related kinase B| tyrosine kinase receptor B| UY3_12396| xtrkb| Y1Q_015939| Z169_10028

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