Molecular Target Synopsis
Overview
Domains and Structures
Drugs and Clinical Candidates
Druggability
Chemistry
Ligand Efficiency Plot
Pathways
Family Cladogram
Interaction Network
Gene Expression
Gene Copy Number Variation
RNAi
Mutations
Germline Genetics

NTRK2 (Q16620) - Overview - Molecular Target Synopsis

Protein


NTRK2, BDNF/NT-3 growth factors receptor
Enzyme Classification 2.7.10.1
UniProt Q16620

Also Known as NTRK2_HUMAN, NTRK2, TRKB

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. 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. 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. Interacts with APPL1 (By similarity). Interacts with MAPK8IP3/JIP3 and KLC1; interaction with KLC1 is mediated by MAPK8IP3/JIP3.

5MO9
STRUCTURE OF HUMAN TRKB RECEPTOR LIGAND BINDING DOMAIN IN COMPLEX WITH THE FAB FRGMENT OF ANTIBODY AB20
RCSB/PDB
Inspect Structure
See all 3D Structures for NTRK2

Isoforms / Transcripts (Protein Coding)


Sub-cellular localization


UniProt: NTRK2 is active in the following subcellular-locations: axon, cell membrane, cell projection, cytoplasm, dendrite, early endosome membrane, endosome membrane, perinuclear region.
GO terms: NTRK2 is active in the following subcellular-locations: axon, axon terminus, cytosol, dendrite, dendritic spine, early endosome, early endosome membrane, Golgi membrane, integral component of plasma membrane, perinuclear region of cytoplasm, plasma membrane, postsynaptic density, receptor complex, terminal bouton.



UniProt
GO terms

Gene Copy Number Variation


In COSMIC - Cell Lines Project NTRK2 has gain in 2 cell-lines, loss in 1 cell-lines and no signal in 1002 cell-lines. (see details)

Gene Expression


In NCI60, the highest expressing cell lines are: SNB_75, MCF7, SK_OV_3

In Array Express (RNA-seq of 675 commonly used human cancer cell lines), the highest expressing cell lines are: KYSE-70, SW 1417, SNU-C1

In Array Express (RNA-seq of long poly adenylated RNA and long non poly adenylated RNA from ENCODE cell lines), the highest expressing cell lines are: SK-N-SH_RA, SK-N-SH, NHLF

(see details)

RNA Interference


NTRK2 was reported in the following RNAI studies:

Cell - Large Scale Profiling of Kinase Dependencies in Cancer Cell Lines, the highest RNAi cell lines are: COV504, HUO3N1. (see details)

3D Structures


For NTRK2 there are:
8 structures (9 chains) solved
3 are solved in complex with at least one small molecule ligand



(see details)
Molecular Target 3D Synopsis

Screening and Chemistry


NTRK2 has been screened with 949 compounds (1576 bioactivities), 136 compounds have bioactivities that show binding affinity of <= 500nM (153 bioactivities). (see details)