NTRK2

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]

Neurotrophic Receptor Tyrosine Kinase 2

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 (By similarity).
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 (PubMed:7574684, PubMed:15494731).
Upon ligand-binding, undergoes homodimerization, autophosphorylation and activation (PubMed:15494731).
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.

Brain-derived neurotrophic factor receptor signaling pathwayManual Assertion Based On ExperimentIMP:UniProtKB
Cellular response to amino acid stimulusIEA:Ensembl
Cellular response to brain-derived neurotrophic factor stimulusManual Assertion Based On ExperimentIBA:GO_Central
Cellular response to nerve growth factor stimulusManual Assertion Based On ExperimentIBA:GO_Central
Central nervous system neuron developmentISS:UniProtKB
Cerebral cortex developmentISS:UniProtKB
Circadian rhythmIEA:Ensembl
Feeding behaviorIEA:Ensembl
Glutamate secretionIEA:Ensembl
LearningISS:UniProtKB
Long-term synaptic potentiationIEA:Ensembl
Mechanoreceptor differentiationIEA:Ensembl
Myelination in peripheral nervous systemIEA:Ensembl
Negative regulation of amyloid-beta formationManual Assertion Based On ExperimentIGI:ARUK-UCL
Negative regulation of anoikisIEA:Ensembl
Negative regulation of neuron apoptotic processISS:UniProtKB
Neuron differentiationISS:UniProtKB
Neuron migrationISS:UniProtKB
Neuronal action potential propagationIEA:Ensembl
Oligodendrocyte differentiationIEA:Ensembl
Peripheral nervous system neuron developmentIEA:Ensembl
Positive regulation of axonogenesisISS:UniProtKB
Positive regulation of cell population proliferationISS:UniProtKB
Positive regulation of gene expressionISS:UniProtKB
Positive regulation of kinase activityManual Assertion Based On ExperimentIBA:GO_Central
Positive regulation of MAPK cascadeISS:UniProtKB
Positive regulation of neuron projection developmentISS:UniProtKB
Positive regulation of peptidyl-serine phosphorylationIEA:Ensembl
Positive regulation of phosphatidylinositol 3-kinase signalingISS:UniProtKB
Positive regulation of protein phosphorylationManual Assertion Based On ExperimentTAS:BHF-UCL
Positive regulation of synapse assemblyIEA:Ensembl
Protein autophosphorylationISS:UniProtKB
Regulation of GTPase activityISS:UniProtKB
Regulation of protein kinase B signalingManual Assertion Based On ExperimentIBA:GO_Central
Retinal rod cell developmentIEA:Ensembl
Trans-synaptic signaling by BDNF, modulating synaptic transmissionIEA:Ensembl
Trans-synaptic signaling by neuropeptide, modulating synaptic transmissionManual Assertion Based On ExperimentIBA:GO_Central
Transmembrane receptor protein tyrosine kinase signaling pathwayManual Assertion Based On ExperimentIBA:GO_Central
VasculogenesisIEA:Ensembl

Cell membrane
Endosome membrane
Early endosome membrane
Cell projection, axon
Cell projection, dendrite
Cytoplasm, perinuclear region
Cell junction, synapse, postsynaptic density
Internalized to endosomes upon ligand-binding.

Developmental and epileptic encephalopathy 58 (DEE58):
A form of epileptic encephalopathy, a heterogeneous group of severe early-onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. DEE58 is an autosomal dominant condition characterized by onset of refractory seizures in the first days or months of life.
Obesity, hyperphagia, and developmental delay (OBHD):
A disorder characterized by early-onset obesity, hyperphagia, and severe developmental delay in motor function, speech, and language.

Extracellular: 32-430
Helical: 431-454
Cytoplasmic: 455-822

Phosphorylated. Undergoes ligand-mediated autophosphorylation that is required for interaction with SHC1 and PLCG1 and other downstream effectors. Isoform TrkB-T-Shc is not phosphorylated.
Ubiquitinated. Undergoes polyubiquitination upon activation; regulated by NGFR. Ubiquitination regulates the internalization of the receptor (By similarity).