Q91987 · NTRK2_CHICK

  • Protein
    BDNF/NT-3 growth factors receptor
  • Gene
    NTRK2
  • Status
    UniProtKB reviewed (Swiss-Prot)
  • Amino acids
  • Protein existence
    Evidence at protein level
  • Annotation score
    5/5

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 (PubMed:8287802, PubMed:8670834).
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 (PubMed:8670834).
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 (By similarity).

Catalytic activity

Activity 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. 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).

Features

Showing features for site, binding site, active site.

TypeIDPosition(s)Description
Site512Interaction with SHC1
Binding site540-548ATP (UniProtKB | ChEBI)
Binding site568ATP (UniProtKB | ChEBI)
Active site672Proton acceptor
Site702Interaction with SH2D1A
Site813Interaction with PLCG1

GO annotations

AspectTerm
Cellular Componentaxon
Cellular Componentaxon terminus
Cellular Componentdendrite
Cellular Componentdendritic spine
Cellular Componentendosome membrane
Cellular Componentperinuclear region of cytoplasm
Cellular Componentplasma membrane
Cellular Componentpostsynaptic density
Cellular Componentreceptor complex
Molecular FunctionATP binding
Molecular Functionbrain-derived neurotrophic factor binding
Molecular Functionbrain-derived neurotrophic factor receptor activity
Molecular FunctionGPI-linked ephrin receptor activity
Molecular Functionneurotrophin binding
Molecular Functionprotein homodimerization activity
Molecular Functionvoltage-gated monoatomic ion channel activity
Biological Processbrain-derived neurotrophic factor receptor signaling pathway
Biological Processcellular response to brain-derived neurotrophic factor stimulus
Biological Processcentral nervous system neuron development
Biological Processcerebral cortex development
Biological Processcollateral sprouting
Biological Processlearning
Biological Processnegative regulation of neuron apoptotic process
Biological Processneuron differentiation
Biological Processneuron migration
Biological Processpositive regulation of axonogenesis
Biological Processpositive regulation of cell population proliferation
Biological Processpositive regulation of collateral sprouting
Biological Processpositive regulation of gene expression
Biological Processpositive regulation of MAPK cascade
Biological Processpositive regulation of neuron projection development
Biological Processpositive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction
Biological Processprotein autophosphorylation
Biological Processregulation of dendrite extension
Biological Processregulation of GTPase activity
Biological Processtrans-synaptic signaling by neuropeptide, modulating synaptic transmission

Keywords

Enzyme and pathway databases

Names & Taxonomy

Protein names

  • Recommended name
    BDNF/NT-3 growth factors receptor
  • EC number
  • Alternative names
    • Neurotrophic tyrosine kinase receptor type 2
    • TrkB tyrosine kinase (Trk-B)

Gene names

    • Name
      NTRK2
    • Synonyms
      TRKB

Organism names

  • Taxonomic identifier
  • Taxonomic lineage
    Eukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Archelosauria > Archosauria > Dinosauria > Saurischia > Theropoda > Coelurosauria > Aves > Neognathae > Galloanserae > Galliformes > Phasianidae > Phasianinae > Gallus

Accessions

  • Primary accession
    Q91987
  • Secondary accessions
    • Q91010

Proteomes

Organism-specific databases

Subcellular Location

Cell membrane
; Single-pass type I membrane protein
Endosome membrane
; Single-pass type I membrane protein
Cell projection, axon
Postsynaptic density
Note: Internalized to endosomes upon ligand-binding.

Features

Showing features for topological domain, transmembrane.

TypeIDPosition(s)Description
Topological domain32-426Extracellular
Transmembrane427-450Helical
Topological domain451-818Cytoplasmic

Keywords

PTM/Processing

Features

Showing features for signal, disulfide bond, chain, glycosylation, modified residue.

TypeIDPosition(s)Description
Signal1-31
Disulfide bond32↔38
ChainPRO_000001673032-818BDNF/NT-3 growth factors receptor
Disulfide bond36↔45
Glycosylation66N-linked (GlcNAc...) asparagine
Glycosylation94N-linked (GlcNAc...) asparagine
Glycosylation120N-linked (GlcNAc...) asparagine
Disulfide bond151↔175
Disulfide bond153↔193
Glycosylation199N-linked (GlcNAc...) asparagine
Glycosylation204N-linked (GlcNAc...) asparagine
Disulfide bond217↔265
Glycosylation226N-linked (GlcNAc...) asparagine
Glycosylation253N-linked (GlcNAc...) asparagine
Glycosylation287N-linked (GlcNAc...) asparagine
Disulfide bond301↔344
Glycosylation324N-linked (GlcNAc...) asparagine
Glycosylation337N-linked (GlcNAc...) asparagine
Glycosylation408N-linked (GlcNAc...) asparagine
Modified residue512Phosphotyrosine; by autocatalysis
Modified residue698Phosphotyrosine; by autocatalysis
Modified residue702Phosphotyrosine; by autocatalysis
Modified residue703Phosphotyrosine; by autocatalysis
Modified residue813Phosphotyrosine; by autocatalysis

Post-translational modification

Ligand-mediated auto-phosphorylation.

Keywords

Proteomic databases

PTM databases

Expression

Tissue specificity

Detected in embryonic brain and orsal root ganglia.

Gene expression databases

Interaction

Subunit

Exists in a dynamic equilibrium between monomeric (low affinity) and dimeric (high affinity) structures. Interacts (phosphorylated upon activation by BDNF) with SHC1; mediates SHC1 phosphorylation and activation. Interacts (phosphorylated upon activation by BDNF) with PLCG1 and/or PLCG2; mediates PLCG1 phosphorylation and activation. Interacts with SH2B1 and SH2B2. Interacts with NGFR; may regulate the ligand specificity of the receptor (By similarity).
Interacts with SORCS2; this interaction is important for normal targeting to post-synaptic densities in response to high-frequency stimulation (By similarity).
Interacts (phosphorylated upon ligand-binding) with SH2D1A; regulates NTRK2. Interacts with SQSTM1 and KIDINS220 (By similarity).
Interacts (phosphorylated upon ligand-binding) with FRS2; activates the MAPK signaling pathway (By similarity).
Interacts with APPL1 (By similarity).
Interacts with MAPK8IP3/JIP3 and KLC1; interaction with KLC1 is mediated by MAPK8IP3/JIP3 (By similarity).

Protein-protein interaction databases

Structure

Family & Domains

Features

Showing features for repeat, domain, region, compositional bias.

TypeIDPosition(s)Description
Repeat71-92LRR 1
Repeat95-116LRR 2
Domain196-281Ig-like C2-type 1
Domain295-364Ig-like C2-type 2
Region384-394Provides specificity for BDNF as ligand versus NTF3 and NTF4
Region400-420Disordered
Compositional bias469-492Polar residues
Region469-494Disordered
Domain534-803Protein kinase

Sequence similarities

Keywords

Phylogenomic databases

Family and domain databases

Sequence & Isoforms

  • Sequence status
    Complete
  • Sequence processing
    The displayed sequence is further processed into a mature form.

This entry describes 12 isoforms produced by Alternative splicing. Additional isoforms seem to exist.

Q91987-1

This isoform has been chosen as the canonical sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

  • Name
    1
  • Synonyms
    Alpha-FL, cTrkB-L
  • See also
    sequence in UniParc or sequence clusters in UniRef
  • Length
    818
  • Mass (Da)
    91,737
  • Last updated
    1996-11-01 v1
  • Checksum
    D1BA39E2092B2152
MVSWRRRPGPGLARLWGLCCLVLGCWRGALGCPASCRCSSWRIWCSEPVPGITSFPVPQRSTEDDNVTEIYIANQRKLESINDNEVGFYVGLKNLTVVDSGLRFVSRQAFVKNINLQYINLSRNKLSSLSKKPFRHLGLSDLILVDNPFKCSCEIMWIKKFQETKFYTEAQDIYCVDDNNKRIALMDMKVPNCDLPSANLSNYNITVVEGKSITLYCDTTGGPPPNVSWVLTNLVSNHESDTSKNPASLTIKNVSSMDSGLWISCVAENIVGEVQTSAELTVFFAPNITFIESPTPDHHWCIPFTVKGNPKPTLQWFYEGAILNESEYICTKIHVINQSEYHGCLQLDNPTHLNNGAYTLLAKNEYGEDEKRVDAHFMSVPGDGSGPIVDPDVYEYETTPNDLGDTTNNSNQITSPDVSNKENEDSITVYVVVGIAALVCTGLVIMLIILKFGRHSKFGMKGPSSVISNDDDSASPLHHISNGSNTPSSSEGGPDAVIIGMTKIPVIENPQYFGITNSQLKPDTFVQHIKRHNIVLKRELGEGAFGKVFLAECYNLCPEQDKILVAVKTLKDASDNARKDFHREAELLTNLQHEHIVKFYGVCVEGDPLIMVFEYMKHGDLNKFLRAHGPDAVLMAEGNRPAELTQSQMLHIAQQIAAGMVYLASQHFVHRDLATRNCLVGENLLVKIGDFGMSRDVYSTDYYRVGGHTMLPIRWMPPESIMYRKFTTESDVWSLGVVLWEIFTYGKQPWYQLSNNEVIECITQGRVLQRPRTCPKEVYDLMLGCWQREPHMRLNIKEIHSLLQNLAKASPVYLDILG

Q91987-2

  • Name
    2
  • Synonyms
    Beta-FL
  • Note
    It is unsure whether Leu-144 or Met-188 is the initiator of isoform 2.
  • See also
    sequence in UniParc or sequence clusters in UniRef
  • Differences from canonical

Q91987-3

  • Name
    3
  • Synonyms
    ED
  • See also
    sequence in UniParc or sequence clusters in UniRef
  • Differences from canonical

Q91987-4

  • Name
    4
  • Synonyms
    JD
  • See also
    sequence in UniParc or sequence clusters in UniRef
  • Differences from canonical

Q91987-5

  • Name
    5
  • Synonyms
    J1
  • See also
    sequence in UniParc or sequence clusters in UniRef
  • Differences from canonical
    • 462-462: G → VHGEVKGVGLVDQIWLSLQDCDNEG

Q91987-6

  • Name
    6
  • Synonyms
    Alpha-T1
  • See also
    sequence in UniParc or sequence clusters in UniRef
  • Differences from canonical

Q91987-7

  • Name
    7
  • Synonyms
    J1+T1
  • See also
    sequence in UniParc or sequence clusters in UniRef
  • Differences from canonical

Q91987-8

  • Name
    8
  • Synonyms
    J2+T1
  • See also
    sequence in UniParc or sequence clusters in UniRef
  • Differences from canonical

Q91987-9

  • Name
    9
  • Synonyms
    ED J2+T1, cTrkB-S
  • Note
    Specifically activated by BDNF but not NTF3 and NTF4.
  • See also
    sequence in UniParc or sequence clusters in UniRef
  • Differences from canonical

Q91987-10

  • Name
    10
  • Synonyms
    J1+J2+T1
  • See also
    sequence in UniParc or sequence clusters in UniRef
  • Differences from canonical
    • 462-462: G → VHGEVKGVGLVDQIWLSLQDCDNEEQVMVTVNSDVHNNSTASDNNRLG
    • 463-473: PSSVISNDDDS → FVLFHKIPLDG
    • 474-818: Missing

Q91987-11

  • Name
    11
  • Synonyms
    T3
  • See also
    sequence in UniParc or sequence clusters in UniRef
  • Differences from canonical

Q91987-12

  • Name
    12
  • Synonyms
    ED J1+J2+T1
  • See also
    sequence in UniParc or sequence clusters in UniRef
  • Differences from canonical

Features

Showing features for alternative sequence, compositional bias.

TypeIDPosition(s)Description
Alternative sequenceVSP_0029141-187in isoform 2
Alternative sequenceVSP_002915384-394in isoform 3, isoform 9 and isoform 12
Alternative sequenceVSP_002922462in isoform 10 and isoform 12
Alternative sequenceVSP_002920462in isoform 5 and isoform 7
Alternative sequenceVSP_002921462in isoform 8 and isoform 9
Alternative sequenceVSP_002923462-465in isoform 4
Alternative sequenceVSP_002916462-467in isoform 11
Alternative sequenceVSP_002918463-473in isoform 6, isoform 7, isoform 8, isoform 9, isoform 10 and isoform 12
Alternative sequenceVSP_002917468-818in isoform 11
Compositional bias469-492Polar residues
Alternative sequenceVSP_002919474-818in isoform 6, isoform 7, isoform 8, isoform 9, isoform 10 and isoform 12

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
X77251
EMBL· GenBank· DDBJ
CAA54468.1
EMBL· GenBank· DDBJ
mRNA
X77252
EMBL· GenBank· DDBJ
CAA54469.1
EMBL· GenBank· DDBJ
mRNA
X74109
EMBL· GenBank· DDBJ
CAA52210.1
EMBL· GenBank· DDBJ
mRNA

Genome annotation databases

Similar Proteins

Disclaimer

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