TrkA 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. 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. Isoform TrkA-III: Resistant to NGF, it constitutively activates AKT1 and NF-kappa-B and is unable to activate the Ras-MAPK signaling cascade. Antagonizes the anti-proliferative NGF-NTRK1 signaling that promotes neuronal precursors differentiation. Isoform TrkA-III promotes angiogenesis and has oncogenic activity when overexpressed. Belongs to the protein kinase superfamily. Tyr protein kinase family. Insulin receptor subfamily. Isoform TrkA-I is found in most non-neuronal tissues. Isoform TrkA-II is primarily expressed in neuronal cells. TrkA-III is specifically expressed by pluripotent neural stem and neural crest progenitors. 4 alternatively spliced human isoforms have been reported. Note: This description may include information from UniProtKB.
Protein type: EC; Kinase, protein; Membrane protein, integral; Oncoprotein; Protein kinase, TK; Protein kinase, tyrosine (receptor); TK group; Trk family
Chromosomal Location of rat Ortholog: 2q34
Cellular Component:  axon; cell surface; cytoplasm; dendrite; early endosome; early endosome membrane; Golgi membrane; late endosome; late endosome membrane; neuronal cell body; plasma membrane; protein-containing complex; receptor complex; recycling endosome; recycling endosome membrane
Molecular Function:  ATP binding; GPI-linked ephrin receptor activity; identical protein binding; kinase binding; nerve growth factor binding; nerve growth factor receptor activity; neurotrophin binding; neurotrophin p75 receptor binding; neurotrophin receptor activity; protein binding; protein homodimerization activity; protein tyrosine kinase activity; transmembrane receptor protein serine/threonine kinase activity; transmembrane receptor protein tyrosine kinase activity
Biological Process:  axon guidance; axonogenesis involved in innervation; B cell differentiation; behavioral response to formalin induced pain; cell differentiation; cellular response to amyloid-beta; cellular response to growth factor stimulus; cellular response to nerve growth factor stimulus; cellular response to nicotine; circadian rhythm; detection of mechanical stimulus involved in sensory perception of pain; detection of temperature stimulus involved in sensory perception of pain; ephrin receptor signaling pathway; innervation; learning or memory; mechanoreceptor differentiation; multicellular organism development; negative regulation of cell population proliferation; negative regulation of neuron apoptotic process; nerve growth factor signaling pathway; nervous system development; neuron apoptotic process; neuron development; neuron projection development; neurotrophin signaling pathway; neurotrophin TRK receptor signaling pathway; olfactory nerve development; peptidyl-tyrosine autophosphorylation; peptidyl-tyrosine phosphorylation; positive regulation of angiogenesis; positive regulation of ERK1 and ERK2 cascade; positive regulation of GTPase activity; positive regulation of kinase activity; positive regulation of neuron projection development; positive regulation of NF-kappaB transcription factor activity; positive regulation of phosphatidylinositol 3-kinase signaling; positive regulation of programmed cell death; positive regulation of protein phosphorylation; positive regulation of Ras protein signal transduction; positive regulation of synapse assembly; positive regulation of synaptic transmission, glutamatergic; programmed cell death involved in cell development; protein autophosphorylation; protein phosphorylation; regulation of protein kinase B signaling; response to activity; response to axon injury; response to electrical stimulus; response to ethanol; response to hydrostatic pressure; response to nicotine; response to nutrient levels; response to xenobiotic stimulus; Sertoli cell development; sympathetic nervous system development; transmembrane receptor protein serine/threonine kinase signaling pathway; transmembrane receptor protein tyrosine kinase signaling pathway
Reference #:  P35739 (UniProtKB)
Alt. Names/Synonyms: High affinity nerve growth factor receptor; Neurotrophic tyrosine kinase receptor type 1; neurotrophic tyrosine kinase, receptor, type 1; Ntrk1; p140-TrkA; Slow nerve growth factor receptor; Trk; Trk-A; Trka; trkA proto-oncogene receptor
Gene Symbols: Ntrk1
Molecular weight: 87,868 Da
Basal Isoelectric point: 5.98  Predict pI for various phosphorylation states
CST Pathways:  Tyrosine Kinases & Substrates
Protein-Specific Antibodies, siRNAs or Recombinant Proteins from Cell Signaling Technology® Total Proteins
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Cross-references to other databases:  AlphaFold  |  STRING  |  Reactome  |  BioGPS  |  Pfam  |  ENZYME  |  Phospho.ELM  |  NetworKIN  |  UniProtKB  |  Entrez-Gene  |  Ensembl Gene