InnateDB: Systems Biology of the Innate Immune Response

Mus musculus Protein: Ntrk2

Summary

InnateDB Protein

IDBP-158488.6

Last Modified

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

Gene Symbol

Ntrk2

Protein Name

neurotrophic tyrosine kinase, receptor, type 2

Synonyms

GP145-TrkB/GP95-TrkB; Tkrb; trk-B; trkB;

Species

Mus musculus

Ensembl Protein

ENSMUSP00000078757

InnateDB Gene

IDBG-158484 (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. Isoform GP95-TRKB may also play a role in neutrophin-dependent calcium signaling in glial cells and mediate communication between neurons and glia. {ECO:0000269PubMed:10571233, ECO:0000269PubMed:12367511, ECO:0000269PubMed:15329723, ECO:0000269PubMed:15372074, ECO:0000269PubMed:1645620, ECO:0000269PubMed:16801538, ECO:0000269PubMed:21414899, ECO:0000269PubMed:8402890, ECO:0000269PubMed:9728914}.

Subcellular Localization

Cell membrane {ECO:0000269PubMed:14581459}; Single-pass type I membrane protein {ECO:0000269PubMed:14581459}. Endosome membrane {ECO:0000269PubMed:14581459}; Single-pass type I membrane protein {ECO:0000269PubMed:14581459}. Note=Internalized to endosomes upon ligand-binding.

Disease Associations

Tissue Specificity

Widely expressed in the central and peripheral nervous system. The different forms are differentially expressed in various cell types. Isoform GP95-TRKB is specifically expressed in glial cells.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 21 experimentally validated interaction(s) in this database.
They are also associated with 22 interaction(s) predicted by orthology.

Experimentally validated
Total	21 [view]
Protein-Protein	21 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	22 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0004672	protein kinase activity
GO:0004713	protein tyrosine kinase activity
GO:0004714	transmembrane receptor protein tyrosine kinase activity
GO:0005030	neurotrophin receptor 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:0046875	ephrin receptor binding
GO:0048403	brain-derived neurotrophic factor binding
GO:0060175	brain-derived neurotrophic factor-activated receptor activity

Biological Process

GO:0001570	vasculogenesis
GO:0001764	neuron migration
GO:0006468	protein phosphorylation
GO:0006954	inflammatory response
GO:0007528	neuromuscular junction development
GO:0007568	aging
GO:0007612	learning
GO:0007616	long-term memory
GO:0007623	circadian rhythm
GO:0007631	feeding behavior
GO:0008284	positive regulation of cell proliferation
GO:0009416	response to light stimulus
GO:0010628	positive regulation of gene expression
GO:0010976	positive regulation of neuron projection development
GO:0010996	response to auditory stimulus
GO:0014047	glutamate secretion
GO:0014068	positive regulation of phosphatidylinositol 3-kinase signaling
GO:0018108	peptidyl-tyrosine phosphorylation
GO:0019222	regulation of metabolic process
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:0035584	calcium-mediated signaling using intracellular calcium source
GO:0038179	neurotrophin signaling pathway
GO:0042490	mechanoreceptor differentiation
GO:0043408	regulation of MAPK cascade
GO:0043410	positive regulation of MAPK cascade
GO:0043524	negative regulation of neuron apoptotic process
GO:0046548	retinal rod cell development
GO:0046777	protein autophosphorylation
GO:0046928	regulation of neurotransmitter secretion
GO:0048709	oligodendrocyte differentiation
GO:0048935	peripheral nervous system neuron development
GO:0050772	positive regulation of axonogenesis
GO:0050773	regulation of dendrite development
GO:0051896	regulation of protein kinase B signaling
GO:0051968	positive regulation of synaptic transmission, glutamatergic
GO:0060291	long-term synaptic potentiation
GO:0071356	cellular response to tumor necrosis factor
GO:1990090	cellular response to nerve growth factor stimulus
GO:2000811	negative regulation of anoikis

Cellular Component

GO:0005737	cytoplasm
GO:0005768	endosome
GO:0005791	rough endoplasmic reticulum
GO:0005829	cytosol
GO:0005886	plasma membrane
GO:0005887	integral component of plasma membrane
GO:0009986	cell surface
GO:0010008	endosome membrane
GO:0014069	postsynaptic density
GO:0030424	axon
GO:0030425	dendrite
GO:0030426	growth cone
GO:0043025	neuronal cell body
GO:0043195	terminal bouton
GO:0043197	dendritic spine
GO:0043204	perikaryon
GO:0043235	receptor complex
GO:0043679	axon terminus
GO:0045211	postsynaptic membrane
GO:0048786	presynaptic active zone
GO:0060076	excitatory synapse
GO:0097481	neuronal postsynaptic density

Protein Structure and Domains

PDB ID

MGI:97384

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