Q91987 · NTRK2_CHICK
- ProteinBDNF/NT-3 growth factors receptor
- GeneNTRK2
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids818 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
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).
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
- ATP + L-tyrosyl-[protein] = ADP + H+ + O-phospho-L-tyrosyl-[protein]
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.
GO annotations
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameBDNF/NT-3 growth factors receptor
- EC number
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Archelosauria > Archosauria > Dinosauria > Saurischia > Theropoda > Coelurosauria > Aves > Neognathae > Galloanserae > Galliformes > Phasianidae > Phasianinae > Gallus
Accessions
- Primary accessionQ91987
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Cell membrane ; Single-pass type I membrane protein
Endosome membrane ; Single-pass type I membrane protein
Note: Internalized to endosomes upon ligand-binding.
Features
Showing features for topological domain, transmembrane.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Topological domain | 32-426 | Extracellular | ||||
Sequence: CPASCRCSSWRIWCSEPVPGITSFPVPQRSTEDDNVTEIYIANQRKLESINDNEVGFYVGLKNLTVVDSGLRFVSRQAFVKNINLQYINLSRNKLSSLSKKPFRHLGLSDLILVDNPFKCSCEIMWIKKFQETKFYTEAQDIYCVDDNNKRIALMDMKVPNCDLPSANLSNYNITVVEGKSITLYCDTTGGPPPNVSWVLTNLVSNHESDTSKNPASLTIKNVSSMDSGLWISCVAENIVGEVQTSAELTVFFAPNITFIESPTPDHHWCIPFTVKGNPKPTLQWFYEGAILNESEYICTKIHVINQSEYHGCLQLDNPTHLNNGAYTLLAKNEYGEDEKRVDAHFMSVPGDGSGPIVDPDVYEYETTPNDLGDTTNNSNQITSPDVSNKENEDS | ||||||
Transmembrane | 427-450 | Helical | ||||
Sequence: ITVYVVVGIAALVCTGLVIMLIIL | ||||||
Topological domain | 451-818 | Cytoplasmic | ||||
Sequence: KFGRHSKFGMKGPSSVISNDDDSASPLHHISNGSNTPSSSEGGPDAVIIGMTKIPVIENPQYFGITNSQLKPDTFVQHIKRHNIVLKRELGEGAFGKVFLAECYNLCPEQDKILVAVKTLKDASDNARKDFHREAELLTNLQHEHIVKFYGVCVEGDPLIMVFEYMKHGDLNKFLRAHGPDAVLMAEGNRPAELTQSQMLHIAQQIAAGMVYLASQHFVHRDLATRNCLVGENLLVKIGDFGMSRDVYSTDYYRVGGHTMLPIRWMPPESIMYRKFTTESDVWSLGVVLWEIFTYGKQPWYQLSNNEVIECITQGRVLQRPRTCPKEVYDLMLGCWQREPHMRLNIKEIHSLLQNLAKASPVYLDILG |
Keywords
- Cellular component
PTM/Processing
Features
Showing features for signal, disulfide bond, chain, glycosylation, modified residue.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Signal | 1-31 | |||||
Sequence: MVSWRRRPGPGLARLWGLCCLVLGCWRGALG | ||||||
Disulfide bond | 32↔38 | |||||
Sequence: CPASCRC | ||||||
Chain | PRO_0000016730 | 32-818 | BDNF/NT-3 growth factors receptor | |||
Sequence: CPASCRCSSWRIWCSEPVPGITSFPVPQRSTEDDNVTEIYIANQRKLESINDNEVGFYVGLKNLTVVDSGLRFVSRQAFVKNINLQYINLSRNKLSSLSKKPFRHLGLSDLILVDNPFKCSCEIMWIKKFQETKFYTEAQDIYCVDDNNKRIALMDMKVPNCDLPSANLSNYNITVVEGKSITLYCDTTGGPPPNVSWVLTNLVSNHESDTSKNPASLTIKNVSSMDSGLWISCVAENIVGEVQTSAELTVFFAPNITFIESPTPDHHWCIPFTVKGNPKPTLQWFYEGAILNESEYICTKIHVINQSEYHGCLQLDNPTHLNNGAYTLLAKNEYGEDEKRVDAHFMSVPGDGSGPIVDPDVYEYETTPNDLGDTTNNSNQITSPDVSNKENEDSITVYVVVGIAALVCTGLVIMLIILKFGRHSKFGMKGPSSVISNDDDSASPLHHISNGSNTPSSSEGGPDAVIIGMTKIPVIENPQYFGITNSQLKPDTFVQHIKRHNIVLKRELGEGAFGKVFLAECYNLCPEQDKILVAVKTLKDASDNARKDFHREAELLTNLQHEHIVKFYGVCVEGDPLIMVFEYMKHGDLNKFLRAHGPDAVLMAEGNRPAELTQSQMLHIAQQIAAGMVYLASQHFVHRDLATRNCLVGENLLVKIGDFGMSRDVYSTDYYRVGGHTMLPIRWMPPESIMYRKFTTESDVWSLGVVLWEIFTYGKQPWYQLSNNEVIECITQGRVLQRPRTCPKEVYDLMLGCWQREPHMRLNIKEIHSLLQNLAKASPVYLDILG | ||||||
Disulfide bond | 36↔45 | |||||
Sequence: CRCSSWRIWC | ||||||
Glycosylation | 66 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 94 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 120 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Disulfide bond | 151↔175 | |||||
Sequence: CSCEIMWIKKFQETKFYTEAQDIYC | ||||||
Disulfide bond | 153↔193 | |||||
Sequence: CEIMWIKKFQETKFYTEAQDIYCVDDNNKRIALMDMKVPNC | ||||||
Glycosylation | 199 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 204 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Disulfide bond | 217↔265 | |||||
Sequence: CDTTGGPPPNVSWVLTNLVSNHESDTSKNPASLTIKNVSSMDSGLWISC | ||||||
Glycosylation | 226 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 253 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 287 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Disulfide bond | 301↔344 | |||||
Sequence: CIPFTVKGNPKPTLQWFYEGAILNESEYICTKIHVINQSEYHGC | ||||||
Glycosylation | 324 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 337 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 408 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Modified residue | 512 | Phosphotyrosine; by autocatalysis | ||||
Sequence: Y | ||||||
Modified residue | 698 | Phosphotyrosine; by autocatalysis | ||||
Sequence: Y | ||||||
Modified residue | 702 | Phosphotyrosine; by autocatalysis | ||||
Sequence: Y | ||||||
Modified residue | 703 | Phosphotyrosine; by autocatalysis | ||||
Sequence: Y | ||||||
Modified residue | 813 | Phosphotyrosine; by autocatalysis | ||||
Sequence: Y |
Post-translational modification
Ligand-mediated auto-phosphorylation.
Keywords
- PTM
Proteomic databases
PTM databases
Expression
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).
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.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Repeat | 71-92 | LRR 1 | ||||
Sequence: YIANQRKLESINDNEVGFYVGL | ||||||
Repeat | 95-116 | LRR 2 | ||||
Sequence: LTVVDSGLRFVSRQAFVKNINL | ||||||
Domain | 196-281 | Ig-like C2-type 1 | ||||
Sequence: PSANLSNYNITVVEGKSITLYCDTTGGPPPNVSWVLTNLVSNHESDTSKNPASLTIKNVSSMDSGLWISCVAENIVGEVQTSAELT | ||||||
Domain | 295-364 | Ig-like C2-type 2 | ||||
Sequence: TPDHHWCIPFTVKGNPKPTLQWFYEGAILNESEYICTKIHVINQSEYHGCLQLDNPTHLNNGAYTLLAKN | ||||||
Region | 384-394 | Provides specificity for BDNF as ligand versus NTF3 and NTF4 | ||||
Sequence: GSGPIVDPDVY | ||||||
Region | 400-420 | Disordered | ||||
Sequence: PNDLGDTTNNSNQITSPDVSN | ||||||
Compositional bias | 469-492 | Polar residues | ||||
Sequence: NDDDSASPLHHISNGSNTPSSSEG | ||||||
Region | 469-494 | Disordered | ||||
Sequence: NDDDSASPLHHISNGSNTPSSSEGGP | ||||||
Domain | 534-803 | Protein kinase | ||||
Sequence: IVLKRELGEGAFGKVFLAECYNLCPEQDKILVAVKTLKDASDNARKDFHREAELLTNLQHEHIVKFYGVCVEGDPLIMVFEYMKHGDLNKFLRAHGPDAVLMAEGNRPAELTQSQMLHIAQQIAAGMVYLASQHFVHRDLATRNCLVGENLLVKIGDFGMSRDVYSTDYYRVGGHTMLPIRWMPPESIMYRKFTTESDVWSLGVVLWEIFTYGKQPWYQLSNNEVIECITQGRVLQRPRTCPKEVYDLMLGCWQREPHMRLNIKEIHSLL |
Sequence similarities
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence & Isoforms
- Sequence statusComplete
- Sequence processingThe 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.
- Name1
- SynonymsAlpha-FL, cTrkB-L
- Length818
- Mass (Da)91,737
- Last updated1996-11-01 v1
- ChecksumD1BA39E2092B2152
Q91987-2
- Name2
- SynonymsBeta-FL
- NoteIt is unsure whether Leu-144 or Met-188 is the initiator of isoform 2.
- Differences from canonical
- 1-187: Missing
Q91987-3
- Name3
- SynonymsED
- Differences from canonical
- 384-394: Missing
Q91987-4
- Name4
- SynonymsJD
- Differences from canonical
- 462-465: Missing
Q91987-5
- Name5
- SynonymsJ1
- Differences from canonical
- 462-462: G → VHGEVKGVGLVDQIWLSLQDCDNEG
Q91987-6
- Name6
- SynonymsAlpha-T1
Q91987-7
- Name7
- SynonymsJ1+T1
Q91987-8
- Name8
- SynonymsJ2+T1
Q91987-9
- Name9
- SynonymsED J2+T1, cTrkB-S
- NoteSpecifically activated by BDNF but not NTF3 and NTF4.
Q91987-10
- Name10
- SynonymsJ1+J2+T1
Q91987-11
- Name11
- SynonymsT3
Q91987-12
- Name12
- SynonymsED J1+J2+T1
Features
Showing features for alternative sequence, compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Alternative sequence | VSP_002914 | 1-187 | in isoform 2 | |||
Sequence: Missing | ||||||
Alternative sequence | VSP_002915 | 384-394 | in isoform 3, isoform 9 and isoform 12 | |||
Sequence: Missing | ||||||
Alternative sequence | VSP_002922 | 462 | in isoform 10 and isoform 12 | |||
Sequence: G → VHGEVKGVGLVDQIWLSLQDCDNEEQVMVTVNSDVHNNSTASDNNRLG | ||||||
Alternative sequence | VSP_002920 | 462 | in isoform 5 and isoform 7 | |||
Sequence: G → VHGEVKGVGLVDQIWLSLQDCDNEG | ||||||
Alternative sequence | VSP_002921 | 462 | in isoform 8 and isoform 9 | |||
Sequence: G → EQVMVTVNSDVHNNSTASDNNRLG | ||||||
Alternative sequence | VSP_002923 | 462-465 | in isoform 4 | |||
Sequence: Missing | ||||||
Alternative sequence | VSP_002916 | 462-467 | in isoform 11 | |||
Sequence: GPSSVI → ERGRRK | ||||||
Alternative sequence | VSP_002918 | 463-473 | in isoform 6, isoform 7, isoform 8, isoform 9, isoform 10 and isoform 12 | |||
Sequence: PSSVISNDDDS → FVLFHKIPLDG | ||||||
Alternative sequence | VSP_002917 | 468-818 | in isoform 11 | |||
Sequence: Missing | ||||||
Compositional bias | 469-492 | Polar residues | ||||
Sequence: NDDDSASPLHHISNGSNTPSSSEG | ||||||
Alternative sequence | VSP_002919 | 474-818 | in isoform 6, isoform 7, isoform 8, isoform 9, isoform 10 and isoform 12 | |||
Sequence: Missing |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
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 |