TrkA iso2 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 Human Ortholog: 1q23.1
Cellular Component:  cell surface; dendrite; early endosome; early endosome membrane; endosome membrane; Golgi membrane; integral component of plasma membrane; late endosome; late endosome membrane; neuronal cell body; plasma membrane; protein-containing complex; receptor complex; recycling endosome membrane
Molecular Function:  ATP binding; GPI-linked ephrin receptor activity; kinase binding; nerve growth factor binding; nerve growth factor receptor activity; neurotrophin p75 receptor binding; protein binding; protein homodimerization activity; protein tyrosine kinase activity; transmembrane receptor protein tyrosine kinase activity
Biological Process:  activation of MAPKK activity; aging; axon guidance; axonogenesis involved in innervation; B cell differentiation; behavioral response to formalin induced pain; 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; learning or memory; mechanoreceptor differentiation; negative regulation of apoptotic process; negative regulation of cell proliferation; negative regulation of neuron apoptotic process; nerve growth factor signaling pathway; neurotrophin TRK receptor signaling pathway; olfactory nerve development; peptidyl-tyrosine autophosphorylation; peptidyl-tyrosine phosphorylation; phosphatidylinositol-mediated signaling; positive regulation of ERK1 and ERK2 cascade; positive regulation of GTPase activity; positive regulation of neuron projection development; positive regulation of NF-kappaB transcription factor activity; 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; response to axon injury; response to electrical stimulus; response to hydrostatic pressure; response to nutrient levels; response to radiation; Sertoli cell development; sympathetic nervous system development
Disease: Insensitivity To Pain, Congenital, With Anhidrosis
Reference #:  P04629-2 (UniProtKB)
Alt. Names/Synonyms: DKFZp781I14186; gp140trk; High affinity nerve growth factor receptor; MTC; neurotrophic receptor tyrosine kinase 1; Neurotrophic tyrosine kinase receptor type 1; neurotrophic tyrosine kinase, receptor, type 1; NTRK1; Oncogene TRK; p140-TrkA; TRK; Trk-A; TRK1; TRK1-transforming tyrosine kinase protein; TRKA; TrkA iso2; Tropomyosin-related kinase A; Tyrosine kinase receptor; tyrosine kinase receptor A
Gene Symbols: NTRK1
Molecular weight: 86,880 Da
Basal Isoelectric point: 6.17  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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TrkA iso2

Protein Structure Not Found.

Cross-references to other databases:  cBioPortal  |  Wikipedia  |  Pfam  |  UniProtKB  |  Entrez-Gene  |  GenPept  |  Ensembl Gene  |  Ensembl Protein