InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: NTRK2

Summary

InnateDB Protein

IDBP-74212.7

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

NTRK2

Protein Name

neurotrophic tyrosine kinase, receptor, type 2

Synonyms

GP145-TrkB; trk-B; TRKB;

Species

Homo sapiens

Ensembl Protein

ENSP00000365387

InnateDB Gene

IDBG-74210 (NTRK2)

Protein Structure

UniProt Annotation

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. {ECO:0000269PubMed:15494731}.

Subcellular Localization

Cell membrane; Single-pass type I membrane protein. Endosome membrane {ECO:0000250}; Single-pass type I membrane protein {ECO:0000250}. Note=Internalized to endosomes upon ligand-binding. {ECO:0000250}.

Disease Associations

Obesity hyperphagia and developmental delay (OHPDD) [MIM:613886]: A disorder characterized by early-onset obesity, hyperphagia, and severe developmental delay in motor function, speech, and language. {ECO:0000269PubMed:15494731}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Tissue Specificity

Isoform TrkB is expressed in the central and peripheral nervous system. In the central nervous system (CNS), expression is observed in the cerebral cortex, hippocampus, thalamus, choroid plexus, granular layer of the cerebellum, brain stem, and spinal cord. In the peripheral nervous system, it is expressed in many cranial ganglia, the ophthalmic nerve, the vestibular system, multiple facial structures, the submaxillary glands, and dorsal root ganglia. Isoform TrkB-T1 is mainly expressed in the brain but also detected in other tissues including pancreas, kidney and heart. Isoform TrkB-T-Shc is predominantly expressed in the brain. {ECO:0000269PubMed:11798182, ECO:0000269PubMed:7936202}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 31 experimentally validated interaction(s) in this database.
They are also associated with 13 interaction(s) predicted by orthology.

Experimentally validated
Total	31 [view]
Protein-Protein	31 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	13 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0004672	protein kinase activity
GO:0004713	protein tyrosine kinase activity
GO:0005515	protein binding
GO:0005524	ATP binding
GO:0016772	transferase activity, transferring phosphorus-containing groups
GO:0042803	protein homodimerization activity
GO:0043121	neurotrophin binding
GO:0048403	brain-derived neurotrophic factor binding
GO:0060175	brain-derived neurotrophic factor-activated receptor activity

Biological Process

GO:0001764	neuron migration
GO:0006468	protein phosphorylation
GO:0007169	transmembrane receptor protein tyrosine kinase signaling pathway
GO:0007190	activation of adenylate cyclase activity
GO:0007612	learning
GO:0008284	positive regulation of cell proliferation
GO:0010628	positive regulation of gene expression
GO:0010976	positive regulation of neuron projection development
GO:0014068	positive regulation of phosphatidylinositol 3-kinase signaling
GO:0018108	peptidyl-tyrosine phosphorylation
GO:0021954	central nervous system neuron development
GO:0021987	cerebral cortex development
GO:0030182	neuron differentiation
GO:0031547	brain-derived neurotrophic factor receptor signaling pathway
GO:0032314	regulation of Rac GTPase activity
GO:0043410	positive regulation of MAPK cascade
GO:0043524	negative regulation of neuron apoptotic process
GO:0046777	protein autophosphorylation
GO:0048011	neurotrophin TRK receptor signaling pathway
GO:0050772	positive regulation of axonogenesis

Cellular Component

GO:0005887	integral component of plasma membrane
GO:0010008	endosome membrane
GO:0043235	receptor complex

Protein Structure and Domains

PDB ID

InterPro

IPR000372 Leucine-rich repeat-containing N-terminal
IPR000483 Cysteine-rich flanking region, C-terminal
IPR000719 Protein kinase domain
IPR001245 Serine-threonine/tyrosine-protein kinase catalytic domain
IPR002290 Serine/threonine/dual specificity protein kinase, catalytic domain
IPR003598 Immunoglobulin subtype 2
IPR003599 Immunoglobulin subtype
IPR007110 Immunoglobulin-like domain
IPR011009 Protein kinase-like domain
IPR013098 Immunoglobulin I-set
IPR020455 Tyrosine-protein kinase, neurotrophic receptor, type 2
IPR020635 Tyrosine-protein kinase, catalytic domain
IPR020777 Tyrosine-protein kinase, neurotrophic receptor

PFAM

PF01462
PF01463
PF00069
PF07714
PF07679

PRINTS

PR00109
PR01941
PR01939

PIRSF

SMART

SM00013
SM00082
SM00220
SM00408
SM00409
SM00219

TIGRFAMs

Post-translational Modifications

Modification

Cross-References

SwissProt