Protein: BDNF/NT-3 growth factors receptor (EC 2.7.10.1) (Neurotrophic tyrosine kinase receptor type 2) (TrkB tyrosine kinase) (Trk-B) (Q91987)
Organism: Gallus gallus (Chicken)
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 (By similarity).
Subcellular location: Cell membrane {ECO:0000269|PubMed:8287802, ECO:0000269|PubMed:8670834}; Single-pass type I membrane protein {ECO:0000305}. Endosome membrane {ECO:0000250}; Single-pass type I membrane protein {ECO:0000250}. Cell projection, axon {ECO:0000250|UniProtKB:Q63604}. Cell projection, dendrite {ECO:0000250|UniProtKB:Q63604}. Cytoplasm, perinuclear region {ECO:0000250|UniProtKB:Q63604}. Postsynaptic density {ECO:0000250|UniProtKB:P15209}. Note=Internalized to endosomes upon ligand-binding. {ECO:0000250|UniProtKB:P15209}.
Sequence: MVSWRRRPGPGLARLWGLCCLVLGCWRGALGCPASCRCSSWRIWCSEPVPGITSFPVPQRSTEDDNVTEIYIANQRKLESINDNEVGFYVGLKNLTVVDSGLRFVSRQAFVKNINLQYINLSRNKLSSLSKKPFRHLGLSDLILVDNPFKCSCEIMWIKKFQETKFYTEAQDIYCVDDNNKRIALMDMKVPNCDLPSANLSNYNITVVEGKSITLYCDTTGGPPPNVSWVLTNLVSNHESDTSKNPASLTIKNVSSMDSGLWISCVAENIVGEVQTSAELTVFFAPNITFIESPTPDHHWCIPFTVKGNPKPTLQWFYEGAILNESEYICTKIHVINQSEYHGCLQLDNPTHLNNGAYTLLAKNEYGEDEKRVDAHFMSVPGDGSGPIVDPDVYEYETTPNDLGDTTNNSNQITSPDVSNKENEDSITVYVVVGIAALVCTGLVIMLIILKFGRHSKFGMKGPSSVISNDDDSASPLHHISNGSNTPSSSEGGPDAVIIGMTKIPVIENPQYFGITNSQLKPDTFVQHIKRHNIVLKRELGEGAFGKVFLAECYNLCPEQDKILVAVKTLKDASDNARKDFHREAELLTNLQHEHIVKFYGVCVEGDPLIMVFEYMKHGDLNKFLRAHGPDAVLMAEGNRPAELTQSQMLHIAQQIAAGMVYLASQHFVHRDLATRNCLVGENLLVKIGDFGMSRDVYSTDYYRVGGHTMLPIRWMPPESIMYRKFTTESDVWSLGVVLWEIFTYGKQPWYQLSNNEVIECITQGRVLQRPRTCPKEVYDLMLGCWQREPHMRLNIKEIHSLLQNLAKASPVYLDILG
InterPro domains: - IPR020635: Tyrosine-protein kinase, catalytic domain (domain) [534-803]
- IPR032675: Leucine-rich repeat domain superfamily (homologous_superfamily) [32-184]
- IPR036179: Immunoglobulin-like domain superfamily (homologous_superfamily) [203-376]
- IPR013783: Immunoglobulin-like fold (homologous_superfamily) [186-382]
- IPR000372: Leucine-rich repeat N-terminal domain (domain) [31-64]
- IPR007110: Immunoglobulin-like domain (domain) [196-281]
- IPR020777: Growth factor receptor NTRK (family) [85-360]
- IPR001245: Serine-threonine/tyrosine-protein kinase, catalytic domain (domain) [535-802]
- IPR000719: Protein kinase domain (domain) [534-803]
- IPR002011: Tyrosine-protein kinase, receptor class II, conserved site (conserved_site) [696-704]
- IPR011009: Protein kinase-like domain superfamily (homologous_superfamily) [513-802]
- IPR013098: Immunoglobulin I-set (domain) [203-373]
- IPR020455: BDNF/NT-3 growth factors receptor NTRK2 (family) [16-342]
- IPR001611: Leucine-rich repeat (repeat) [91-148]
- IPR003599: Immunoglobulin domain subtype (domain) [202-283]
- IPR017441: Protein kinase, ATP binding site (binding_site) [540-568]
- IPR008266: Tyrosine-protein kinase, active site (active_site) [668-680]
- IPR031635: Growth factor receptor NTRK, leucine rich repeat C-terminal (domain) [150-194]
- IPR003598: Immunoglobulin subtype 2 (domain) [208-272]
- IPR000483: Cysteine-rich flanking region, C-terminal (domain) [147-194]
Interaction partners: - Neurotrophin-3
- Neurotrophic factor BDNF precursor form
- Ephrin-A5
- Fibroblast growth factor receptor substrate 2
- SHC-transforming protein 1
- Ephrin-A2
- Ephrin RBD domain-containing protein
- Glial cell derived neurotrophic factor.
- Fibroblast growth factor 2
- Sortilin.
Gene Ontology annotations:
Molecular Function (MF): GO:0003674 (molecular function), GO:0005488 (binding), GO:0005515 (protein binding), GO:0019838 (growth factor binding)
Biological Process (BP): GO:0008150 (biological process), GO:0050896 (response to stimulus), GO:0042221 (response to chemical), GO:0010033 (response to organic substance), GO:1901700 (response to oxygen-containing compound), GO:0032355 (response to estradiol), GO:0033993 (response to lipid), GO:0014070 (response to organic cyclic compound)
Cellular Component (CC): GO:0005575 (cellular component), GO:0110165 (cellular anatomical entity), GO:0071944 (cell periphery), GO:0016020 (membrane), GO:0005886 (plasma membrane)