Protein / target
BDNF/NT-3 growth factors receptor
Protein at a glance
Biological role
Brain-derived neurotrophic factor receptor activity
Primary system
Nervous system
Strongest disease association
obesity, hyperphagia, and developmental delay
Therapeutic maturity
Clinically validated target
Druggability
Small molecule
Clinical development
6 approved · 7 in clinical development
Derived from structured UniProt, Open Targets and literature data on this page.
Protein profile
Canonical identity and biological annotation from UniProt.
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 (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:15494731, PubMed:7574684). 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
Subcellular location
Domains and Gene Ontology detail (47)Hide
Domains & features
Gene Ontology
- Caxon
- Caxon terminus
- Ccytosol
- Cdendrite
- Cdendritic spine
- Cearly endosome
- Cearly endosome membrane
- Cperinuclear region of cytoplasm
- Cplasma membrane
- Cpostsynaptic density
- Creceptor complex
- Cterminal bouton
Biological roles
What this protein does, drawn together from its UniProt function, Gene Ontology terms and Reactome pathways.
View supporting evidenceHide supporting evidence
Synaptic signalling
- ·Receptor tyrosine kinase involved in the development and the maturation of the central a…
- ·Postsynaptic density
- ·postsynaptic density
- ·trans-synaptic signaling by BDNF, modulating synaptic transmission
Kinase signalling
- ·Receptor tyrosine kinase involved in the development and the maturation of the central a…
- ·positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction
- ·protein autophosphorylation
Transcriptional regulation
- ·Receptor tyrosine kinase involved in the development and the maturation of the central a…
- ·positive regulation of gene expression
Proteolysis
- ·protease binding
Apoptosis & cell death
- ·negative regulation of neuron apoptotic process
View underlying pathways (14)Hide underlying pathways
Concepts derived from UniProt GO Reactome — each badge above shows which sources supported that role.
Interaction neighbourhood
Proteins with the strongest functional or physical association. Node size and line weight reflect STRING confidence; hover or select a partner to inspect one association.
Functional and physical associations from STRING v12.0. Only associations with this protein are drawn — partner-to-partner links are not part of this evidence.
Drugs targeting this protein
Whether each drug engages this protein directly or through a complex, and how many other targets are recorded for it. Direct binders with few recorded targets are listed first.
Neurotrophic tyrosine kinase receptor type 2 inhibitor
Appears in clinical studies involving non-small cell lung carcinoma, non-small cell lung carcinoma, non-small cell lung carcinoma, cancer
Neurotrophic tyrosine kinase receptor inhibitor
Appears in clinical studies involving neoplasm, cancer, plasma cell myeloma, lymphoma
ChEMBL mechanism, action type and target identity. Open Targets clinical status and indications.
Translational evidence
Why this target matters therapeutically — disease associations, drugs in development, tractability and safety, from Open Targets.
Strongest genetic associations
Human genetic evidence — the most direct causal link between this target and a disease.
Highest-confidence therapeutic associations
Diseases where a drug acting on this target has already reached clinical development.
Highest overall evidence
Remaining associations by Open Targets' aggregated evidence score.
Show all associationsHide all associations
Open Targets ranks 2,159 associations for this target and we store the top 10 by aggregated score. The long tail is largely literature co-mention and RNA-expression evidence, not evidence that this target drives those diseases.
Known drugs · 13 total
acute myeloid leukemia by FAB classification · myeloid leukemia · acute lymphoblastic leukemia
metastasis · cancer · neoplasm
neoplasm · cancer · plasma cell myeloma
keratitis · eye disorder · Sensory neuropathy
non-small cell lung carcinoma · non-small cell lung carcinoma · neoplasm
non-small cell lung carcinoma · non-small cell lung carcinoma · non-small cell lung carcinoma
non-small cell lung carcinoma · non-small cell lung carcinoma · neoplasm
Tractability
Safety liabilities
Clinical trials
Trials of drugs that target this protein — reached indirectly through those drugs, so a trial listed here studies the drug, not the protein.
Show remaining trials (16)Hide
ClinicalTrials.gov via the drug-target graph.
Forefront confidence
Our own weighting of the evidence behind each disease association. Human genetics and clinical evidence count for most; literature co-mention counts for little, because two entities sharing an abstract is not evidence that one drives the other.
The evidence agreement range shows how closely the independent evidence families agree — it is not a statistical confidence interval, and nothing here is fitted to outcome data. Derived from Open Targets evidence types under Forefront weighting; the underlying per-type scores are shown above so the calculation can be checked.
What's happening now
Recent activity around this target, drawn from one canonical event stream. Every item is reached through 2 drugs that target this protein, so each event is news about that drug rather than about the protein directly.
- Regulatory approval
Approval: Augtyro (EMA)
- New publicationRepotrectinib in <i>ROS1</i> Fusion-Positive Non-Small-Cell Lung Cancer.
- New publicationEfficacy of Larotrectinib in TRK Fusion-Positive Cancers in Adults and Children.
Objective event titles are shown unmodified; the event kind and significance line are derived from structured fields. Forefront AttentionEvent stream aggregating Europe PMC Regulatory filings ClinicalTrials.gov.