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Names & Taxonomy

Uniprot ID:: P04629
Entry Name:: NTRK1_HUMAN
Status:: reviewed
Protein Names:: High affinity nerve growth factor receptor (EC 2.7.10.1) (Neurotrophic tyrosine kinase receptor type 1) (TRK1-transforming tyrosine kinase protein) (Tropomyosin-related kinase A) (Tyrosine kinase receptor) (Tyrosine kinase receptor A) (Trk-A) (gp140trk) (p140-TrkA)
Gene Names:: NTRK1 MTC TRK TRKA
Gene Names Primary:: NTRK1
Organism:: Homo sapiens (Human)

Structure

Length:: 796
Sequence:: MLRGGRRGQLGWHSWAAGPGSLLAWLILASAGAAPCPDACCPHGSSGLRCTRDGALDSLHHLPGAENLTELYIENQQHLQHLELRDLRGLGELRNLTIVKSGLRFVAPDAFHFTPRLSRLNLSFNALESLSWKTVQGLSLQELVLSGNPLHCSCALRWLQRWEEEGLGGVPEQKLQCHGQGPLAHMPNASCGVPTLKVQVPNASVDVGDDVLLRCQVEGRGLEQAGWILTELEQSATVMKSGGLPSLGLTLANVTSDLNRKNVTCWAENDVGRAEVSVQVNVSFPASVQLHTAVEMHHWCIPFSVDGQPAPSLRWLFNGSVLNETSFIFTEFLEPAANETVRHGCLRLNQPTHVNNGNYTLLAANPFGQASASIMAAFMDNPFEFNPEDPIPVSFSPVDTNSTSGDPVEKKDETPFGVSVAVGLAVFACLFLSTLLLVLNKCGRRNKFGINRPAVLAPEDGLAMSLHFMTLGGSSLSPTEGKGSGLQGHIIENPQYFSDACVHHIKRRDIVLKWELGEGAFGKVFLAECHNLLPEQDKMLVAVKALKEASESARQDFQREAELLTMLQHQHIVRFFGVCTEGRPLLMVFEYMRHGDLNRFLRSHGPDAKLLAGGEDVAPGPLGLGQLLAVASQVAAGMVYLAGLHFVHRDLATRNCLVGQGLVVKIGDFGMSRDIYSTDYYRVGGRTMLPIRWMPPESILYRKFTTESDVWSFGVVLWEIFTYGKQPWYQLSNTEAIDCITQGRELERPRACPPEVYAIMRGCWQREPQQRHSIKDVHARLQALAQAPPVYLDVLG
Proteomes:: UP000005640

Subcellular location

Subcellular Location:: Cell membrane

Function

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.; Isoform TrkA-III is resistant to NGF, 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.
Catalytic Activity:: ATP + a -L-tyrosine = ADP + a -L-tyrosine phosphate.
Enzyme Regulation:: ENZYME REGULATION: The pro-survival signaling effect of NTRK1 in neurons requires its endocytosis into signaling early endosomes and its retrograde axonal transport. This is regulated by different proteins including CFL1, RAC1 and SORT1. NTF3 is unable to induce this signaling probably due to the lability of the NTF3-NTRK1 complex in endosomes. SH2D1A inhibits the autophosphorylation of the receptor, and alters the recruitment and activation of downstream effectors and signaling cascades (By similarity). Regulated by NGFR (By similarity).
Active Site:: ACT_SITE 650 650 Proton acceptor.
Cross Reference Drug Bank:: DB00321 DB00619 DB08896
Gene Ontology Go:: axon
cell surface
cytoplasmic vesicle
dendrite
early endosome
early endosome membrane
endosome
integral component of plasma membrane
late endosome
late endosome membrane
neuronal cell body
plasma membrane
protein complex
receptor complex
ATP binding
GPI-linked ephrin receptor activity
nerve growth factor binding
nerve growth factor receptor activity
neurotrophin binding
protein homodimerization activity
transmembrane receptor protein tyrosine kinase activity
activation of adenylate cyclase activity
activation of MAPKK activity
activation of phospholipase C 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
developmental programmed cell death
learning or memory
mechanoreceptor differentiation
negative regulation of cell proliferation
negative regulation of neuron apoptotic process
neurotrophin TRK receptor signaling pathway
olfactory nerve development
phosphatidylinositol-mediated signaling
positive regulation of angiogenesis
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
protein autophosphorylation
protein phosphorylation
Ras protein signal transduction
response to activity
response to axon injury
response to drug
response to electrical stimulus
response to ethanol
response to hydrostatic pressure
response to nutrient levels
response to radiation
Sertoli cell development
small GTPase mediated signal transduction
sympathetic nervous system development
transmembrane receptor protein tyrosine kinase signaling pathway
Gene Ontology Biological Process:: activation of adenylate cyclase activity
activation of MAPKK activity
activation of phospholipase C 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
developmental programmed cell death
learning or memory
mechanoreceptor differentiation
negative regulation of cell proliferation
negative regulation of neuron apoptotic process
neurotrophin TRK receptor signaling pathway
olfactory nerve development
phosphatidylinositol-mediated signaling
positive regulation of angiogenesis
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
protein autophosphorylation
protein phosphorylation
Ras protein signal transduction
response to activity
response to axon injury
response to drug
response to electrical stimulus
response to ethanol
response to hydrostatic pressure
response to nutrient levels
response to radiation
Sertoli cell development
small GTPase mediated signal transduction
sympathetic nervous system development
transmembrane receptor protein tyrosine kinase signaling pathway
Gene Ontology Molecular Function:: ATP binding
GPI-linked ephrin receptor activity
nerve growth factor binding
nerve growth factor receptor activity
neurotrophin binding
protein homodimerization activity
transmembrane receptor protein tyrosine kinase activity
Gene Ontology Cellular Component:: axon
cell surface
cytoplasmic vesicle
dendrite
early endosome
early endosome membrane
endosome
integral component of plasma membrane
late endosome
late endosome membrane
neuronal cell body
plasma membrane
protein complex
receptor complex
Keywords:: 3D-structure
ATP-binding
Alternative splicing
Cell membrane
Chromosomal rearrangement
Complete proteome
Developmental protein
Differentiation
Disease mutation
Disulfide bond
Endosome
Glycoprotein
Immunoglobulin domain
Kinase
Leucine-rich repeat
Membrane
Neurogenesis
Nucleotide-binding
Phosphoprotein
Polymorphism
Proto-oncogene
Receptor
Reference proteome
Repeat
Signal
Transferase
Transmembrane
Transmembrane helix
Tyrosine-protein kinase
Ubl conjugation
Interacts With:: P22681; P01138; Q8K4V6; P18031; Q99523

Names & Taxonomy

Structure

Subcellular location

Function

Publication