Names & Taxonomy

Uniprot ID:
Q16620
Entry Name:
NTRK2_HUMAN
Status:
reviewed
Protein Names:
BDNF/NT-3 growth factors receptor (EC 2.7.10.1) (GP145-TrkB) (Trk-B) (Neurotrophic tyrosine kinase receptor type 2) (TrkB tyrosine kinase) (Tropomyosin-related kinase B)
Gene Names:
NTRK2 TRKB
Gene Names Primary:
NTRK2
Organism:
Homo sapiens (Human)

Structure

Length:
822
Sequence:
MSSWIRWHGPAMARLWGFCWLVVGFWRAAFACPTSCKCSASRIWCSDPSPGIVAFPRLEPNSVDPENITEIFIANQKRLEIINEDDVEAYVGLRNLTIVDSGLKFVAHKAFLKNSNLQHINFTRNKLTSLSRKHFRHLDLSELILVGNPFTCSCDIMWIKTLQEAKSSPDTQDLYCLNESSKNIPLANLQIPNCGLPSANLAAPNLTVEEGKSITLSCSVAGDPVPNMYWDVGNLVSKHMNETSHTQGSLRITNISSDDSGKQISCVAENLVGEDQDSVNLTVHFAPTITFLESPTSDHHWCIPFTVKGNPKPALQWFYNGAILNESKYICTKIHVTNHTEYHGCLQLDNPTHMNNGDYTLIAKNEYGKDEKQISAHFMGWPGIDDGANPNYPDVIYEDYGTAANDIGDTTNRSNEIPSTDVTDKTGREHLSVYAVVVIASVVGFCLLVMLFLLKLARHSKFGMKGPASVISNDDDSASPLHHISNGSNTPSSSEGGPDAVIIGMTKIPVIENPQYFGITNSQLKPDTFVQHIKRHNIVLKRELGEGAFGKVFLAECYNLCPEQDKILVAVKTLKDASDNARKDFHREAELLTNLQHEHIVKFYGVCVEGDPLIMVFEYMKHGDLNKFLRAHGPDAVLMAEGNPPTELTQSQMLHIAQQIAAGMVYLASQHFVHRDLATRNCLVGENLLVKIGDFGMSRDVYSTDYYRVGGHTMLPIRWMPPESIMYRKFTTESDVWSLGVVLWEIFTYGKQPWYQLSNNEVIECITQGRVLQRPRTCPQEVYELMLGCWQREPHMRKNIKGIHTLLQNLAKASPVYLDILG
Proteomes:
UP000005640

Subcellular location

Subcellular Location:
Cell membrane; Single-pass type I membrane protein. Endosome membrane

Function

Function:
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.
Catalytic Activity:
ATP + a -L-tyrosine = ADP + a -L-tyrosine phosphate.
Enzyme Regulation:
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 (By similarity).
Active Site:
ACT_SITE 676 676 Proton acceptor.
Cross Reference Drug Bank:
DB00321
Gene Ontology Go:
cell surface
cytosol
dendritic spine
endosome membrane
growth cone
integral component of plasma membrane
neuronal postsynaptic density
perikaryon
postsynaptic membrane
presynaptic active zone
receptor complex
rough endoplasmic reticulum
terminal bouton
ATP binding
brain-derived neurotrophic factor binding
brain-derived neurotrophic factor-activated receptor activity
neurotrophin binding
protein homodimerization activity
activation of adenylate cyclase activity
aging
brain-derived neurotrophic factor receptor signaling pathway
calcium-mediated signaling using intracellular calcium source
cellular response to amino acid stimulus
cellular response to brain-derived neurotrophic factor stimulus
cellular response to tumor necrosis factor
central nervous system neuron development
cerebral cortex development
circadian rhythm
feeding behavior
glutamate secretion
inflammatory response
learning
long-term memory
long-term synaptic potentiation
mechanoreceptor differentiation
negative regulation of anoikis
negative regulation of neuron apoptotic process
neuromuscular junction development
neuron differentiation
neuron migration
neurotrophin TRK receptor signaling pathway
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
positive regulation of synaptic transmission, glutamatergic
protein autophosphorylation
regulation of dendrite development
regulation of GTPase activity
regulation of neurotransmitter secretion
regulation of protein kinase B signaling
response to auditory stimulus
response to light stimulus
retina development in camera-type eye
retinal rod cell development
transmembrane receptor protein tyrosine kinase signaling pathway
vasculogenesis
Gene Ontology Biological Process:
activation of adenylate cyclase activity
aging
brain-derived neurotrophic factor receptor signaling pathway
calcium-mediated signaling using intracellular calcium source
cellular response to amino acid stimulus
cellular response to brain-derived neurotrophic factor stimulus
cellular response to tumor necrosis factor
central nervous system neuron development
cerebral cortex development
circadian rhythm
feeding behavior
glutamate secretion
inflammatory response
learning
long-term memory
long-term synaptic potentiation
mechanoreceptor differentiation
negative regulation of anoikis
negative regulation of neuron apoptotic process
neuromuscular junction development
neuron differentiation
neuron migration
neurotrophin TRK receptor signaling pathway
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
positive regulation of synaptic transmission, glutamatergic
protein autophosphorylation
regulation of dendrite development
regulation of GTPase activity
regulation of neurotransmitter secretion
regulation of protein kinase B signaling
response to auditory stimulus
response to light stimulus
retina development in camera-type eye
retinal rod cell development
transmembrane receptor protein tyrosine kinase signaling pathway
vasculogenesis
Gene Ontology Molecular Function:
ATP binding
brain-derived neurotrophic factor-activated receptor activity
brain-derived neurotrophic factor binding
neurotrophin binding
protein homodimerization activity
Gene Ontology Cellular Component:
cell surface
cytosol
dendritic spine
endosome membrane
growth cone
integral component of plasma membrane
neuronal postsynaptic density
perikaryon
postsynaptic membrane
presynaptic active zone
receptor complex
rough endoplasmic reticulum
terminal bouton
Keywords:
3D-structure
ATP-binding
Alternative splicing
Cell membrane
Complete proteome
Developmental protein
Differentiation
Disease mutation
Disulfide bond
Endosome
Glycoprotein
Immunoglobulin domain
Kinase
Leucine-rich repeat
Membrane
Neurogenesis
Nucleotide-binding
Obesity
Phosphoprotein
Polymorphism
Receptor
Reference proteome
Repeat
Signal
Transferase
Transmembrane
Transmembrane helix
Tyrosine-protein kinase
Ubl conjugation

Publication

PubMed ID:
7789988 7823156 7936202 11798182 14702039 15164053 15489334 7574684 10092678 16335952 20193039 10388563 11738045 15494731 17344846 18293376