InnateDB: Systems Biology of the Innate Immune Response

Mus musculus Protein: Ntrk1

Summary

InnateDB Protein

IDBP-158648.6

Last Modified

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

Gene Symbol

Ntrk1

Protein Name

neurotrophic tyrosine kinase, receptor, type 1

Synonyms

C80751; Tkr; trk; TrkA;

Species

Mus musculus

Ensembl Protein

ENSMUSP00000029712

InnateDB Gene

IDBG-158646 (Ntrk1)

Protein Structure

UniProt Annotation

Function

Receptor tyrosine kinase involved in the development and the maturation of the central and peripheral nervous systems through regulation of proliferation, differentiation and survival of sympathetic and nervous neurons. High affinity receptor for NGF which is its primary ligand, it can also bind and be activated by NTF3/neurotrophin-3. However, NTF3 only supports axonal extension through NTRK1 but has no effect on neuron survival. Upon dimeric NGF 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 driving cell survival and differentiation. Through SHC1 and FRS2 activates a GRB2-Ras-MAPK cascade that regulates cell differentiation and survival. Through PLCG1 controls NF-Kappa-B activation and the transcription of genes involved in cell survival. Through SHC1 and SH2B1 controls a Ras- PI3 kinase-AKT1 signaling cascade that is also regulating survival. In absence of ligand and activation, may promote cell death, making the survival of neurons dependent on trophic factors. {ECO:0000269PubMed:21816277, ECO:0000269PubMed:8145823, ECO:0000269PubMed:8815902}.

Subcellular Localization

Cell membrane {ECO:0000250}; Single-pass type I membrane protein {ECO:0000250}. Early endosome membrane {ECO:0000269PubMed:21816277}; Single-pass type I membrane protein {ECO:0000269PubMed:21816277}. Late endosome membrane {ECO:0000250}; Single-pass type I membrane protein {ECO:0000250}. Note=Localized at cell membrane and early endosomes before nerve growth factor (NGF) stimulation. Recruited to late endosomes after NGF stimulation. Colocalized with RAPGEF2 at late endosomes (By similarity). Internalized to endosomes upon binding of NGF or NTF3 and further transported to the cell body via a retrograde axonal transport. {ECO:0000250}.

Disease Associations

Tissue Specificity

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 12 experimentally validated interaction(s) in this database.
They are also associated with 41 interaction(s) predicted by orthology.

Experimentally validated
Total	12 [view]
Protein-Protein	12 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	41 [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:0005166	neurotrophin p75 receptor binding
GO:0005515	protein binding
GO:0005524	ATP binding
GO:0010465	nerve growth factor receptor activity
GO:0016772	transferase activity, transferring phosphorus-containing groups
GO:0042803	protein homodimerization activity
GO:0046875	ephrin receptor binding
GO:0048406	nerve growth factor binding

Biological Process

GO:0006468	protein phosphorylation
GO:0007399	nervous system development
GO:0007411	axon guidance
GO:0007568	aging
GO:0007611	learning or memory
GO:0007623	circadian rhythm
GO:0008285	negative regulation of cell proliferation
GO:0009314	response to radiation
GO:0010623	developmental programmed cell death
GO:0010976	positive regulation of neuron projection development
GO:0014823	response to activity
GO:0018108	peptidyl-tyrosine phosphorylation
GO:0019233	sensory perception of pain
GO:0021553	olfactory nerve development
GO:0030183	B cell differentiation
GO:0031667	response to nutrient levels
GO:0032320	positive regulation of Ras GTPase activity
GO:0035094	response to nicotine
GO:0038180	nerve growth factor signaling pathway
GO:0042490	mechanoreceptor differentiation
GO:0042493	response to drug
GO:0043068	positive regulation of programmed cell death
GO:0043524	negative regulation of neuron apoptotic process
GO:0045471	response to ethanol
GO:0045766	positive regulation of angiogenesis
GO:0046579	positive regulation of Ras protein signal transduction
GO:0046777	protein autophosphorylation
GO:0048011	neurotrophin TRK receptor signaling pathway
GO:0048485	sympathetic nervous system development
GO:0048678	response to axon injury
GO:0050965	detection of temperature stimulus involved in sensory perception of pain
GO:0050966	detection of mechanical stimulus involved in sensory perception of pain
GO:0051092	positive regulation of NF-kappaB transcription factor activity
GO:0051599	response to hydrostatic pressure
GO:0051602	response to electrical stimulus
GO:0051968	positive regulation of synaptic transmission, glutamatergic
GO:0060009	Sertoli cell development
GO:0060385	axonogenesis involved in innervation
GO:0070374	positive regulation of ERK1 and ERK2 cascade
GO:0071316	cellular response to nicotine
GO:0071363	cellular response to growth factor stimulus
GO:1901215	negative regulation of neuron death
GO:1990090	cellular response to nerve growth factor stimulus

Cellular Component

GO:0005737	cytoplasm
GO:0005769	early endosome
GO:0005770	late endosome
GO:0005886	plasma membrane
GO:0005887	integral component of plasma membrane
GO:0009986	cell surface
GO:0030424	axon
GO:0030425	dendrite
GO:0031410	cytoplasmic vesicle
GO:0031901	early endosome membrane
GO:0031902	late endosome membrane
GO:0043025	neuronal cell body
GO:0043234	protein complex
GO:0043235	receptor complex

Protein Structure and Domains

PDB ID

MGI:97383

InterPro

IPR000719 Protein kinase domain
IPR001245 Serine-threonine/tyrosine-protein kinase catalytic domain
IPR002290 Serine/threonine- /dual specificity protein kinase, catalytic domain
IPR007110 Immunoglobulin-like domain
IPR011009 Protein kinase-like domain
IPR020461 Tyrosine-protein kinase, neurotrophic receptor, type 1
IPR020635 Tyrosine-protein kinase, catalytic domain
IPR020777 Tyrosine-protein kinase, neurotrophic receptor

PFAM

PF00069
PF07714

PRINTS

PR00109
PR01940
PR01939

PIRSF

SMART

SM00220
SM00219

TIGRFAMs

Post-translational Modifications

Modification

Cross-References

SwissProt