High affinity nerve growth factor receptor

Details

Name
High affinity nerve growth factor receptor
Synonyms
  • 2.7.10.1
  • gp140trk
  • MTC
  • Neurotrophic tyrosine kinase receptor type 1
  • p140-TrkA
  • TRK
  • Trk-A
  • TRK1-transforming tyrosine kinase protein
  • TRKA
  • Tropomyosin-related kinase A
  • Tyrosine kinase receptor
  • Tyrosine kinase receptor A
Gene Name
NTRK1
Organism
Humans
Amino acid sequence
>lcl|BSEQ0002069|High affinity nerve growth factor receptor
MLRGGRRGQLGWHSWAAGPGSLLAWLILASAGAAPCPDACCPHGSSGLRCTRDGALDSLH
HLPGAENLTELYIENQQHLQHLELRDLRGLGELRNLTIVKSGLRFVAPDAFHFTPRLSRL
NLSFNALESLSWKTVQGLSLQELVLSGNPLHCSCALRWLQRWEEEGLGGVPEQKLQCHGQ
GPLAHMPNASCGVPTLKVQVPNASVDVGDDVLLRCQVEGRGLEQAGWILTELEQSATVMK
SGGLPSLGLTLANVTSDLNRKNVTCWAENDVGRAEVSVQVNVSFPASVQLHTAVEMHHWC
IPFSVDGQPAPSLRWLFNGSVLNETSFIFTEFLEPAANETVRHGCLRLNQPTHVNNGNYT
LLAANPFGQASASIMAAFMDNPFEFNPEDPIPVSFSPVDTNSTSGDPVEKKDETPFGVSV
AVGLAVFACLFLSTLLLVLNKCGRRNKFGINRPAVLAPEDGLAMSLHFMTLGGSSLSPTE
GKGSGLQGHIIENPQYFSDACVHHIKRRDIVLKWELGEGAFGKVFLAECHNLLPEQDKML
VAVKALKEASESARQDFQREAELLTMLQHQHIVRFFGVCTEGRPLLMVFEYMRHGDLNRF
LRSHGPDAKLLAGGEDVAPGPLGLGQLLAVASQVAAGMVYLAGLHFVHRDLATRNCLVGQ
GLVVKIGDFGMSRDIYSTDYYRVGGRTMLPIRWMPPESILYRKFTTESDVWSFGVVLWEI
FTYGKQPWYQLSNTEAIDCITQGRELERPRACPPEVYAIMRGCWQREPQQRHSIKDVHAR
LQALAQAPPVYLDVLG
Number of residues
796
Molecular Weight
87496.465
Theoretical pI
6.62
GO Classification
Functions
ATP binding / nerve growth factor binding / nerve growth factor receptor activity / neurotrophin binding / protein homodimerization activity / transmembrane receptor protein tyrosine kinase activity
Processes
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 / peptidyl-tyrosine phosphorylation / 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
Components
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
General Function
Transmembrane receptor protein tyrosine kinase activity
Specific 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.
Pfam Domain Function
Transmembrane Regions
424-439
Cellular Location
Cell membrane
Gene sequence
>lcl|BSEQ0010727|High affinity nerve growth factor receptor (NTRK1)
ATGAAGGAGGCCGCCCTCATCTGCCTGGCACCCTCTGTACCCCCGATCTTGACGGTGAAG
TCCTGGGACACCATGCAGTTGCGGGCTGCTAGATCTCGGTGCACAAACTTGTTGGCAGCA
AGCTACATCGAGAACCAGCAGCATCTGCAGCATCTGGAGCTCCGTGATCTGAGGGGCCTG
GGGGAGCTGAGAAACCTCACCATCGTGAAGAGTGGTCTCCGTTTCGTGGCGCCAGATGCC
TTCCATTTCACTCCTCGGCTCAGTCGCCTGAATCTCTCCTTCAACGCTCTGGAGTCTCTC
TCCTGGAAAACTGTGCAGGGCCTCTCCTTACAGGAACTGGTCCTGTCGGGGAACCCTCTG
CACTGTTCTTGTGCCCTGCGCTGGCTACAGCGCTGGGAGGAGGAGGGACTGGGCGGAGTG
CCTGAACAGAAGCTGCAGTGTCATGGGCAAGGGCCCCTGGCCCACATGCCCAATGCCAGC
TGTGGTGTGCCCACGCTGAAGGTCCAGGTGCCCAATGCCTCGGTGGATGTGGGGGACGAC
GTGCTGCTGCGGTGCCAGGTGGAGGGGCGGGGCCTGGAGCAGGCCGGCTGGATCCTCACA
GAGCTGGAGCAGTCAGCCACGGTGATGAAATCTGGGGGTCTGCCATCCCTGGGGCTGACC
CTGGCCAATGTCACCAGTGACCTCAACAGGAAGAACGTGACGTGCTGGGCAGAGAACGAT
GTGGGCCGGGCAGAGGTCTCTGTTCAGGTCAACGTCTCCTTCCCGGCCAGTGTGCAGCTG
CACACGGCGGTGGAGATGCACCACTGGTGCATCCCCTTCTCTGTGGATGGGCAGCCGGCA
CCGTCTCTGCGCTGGCTCTTCAATGGCTCCGTGCTCAATGAGACCAGCTTCATCTTCACT
GAGTTCCTGGAGCCGGCAGCCAATGAGACCGTGCGGCACGGGTGTCTGCGCCTCAACCAG
CCCACCCACGTCAACAACGGCAACTACACGCTGCTGGCTGCCAACCCCTTCGGCCAGGCC
TCCGCCTCCATCATGGCTGCCTTCATGGACAACCCTTTCGAGTTCAACCCCGAGGACCCC
ATCCCTGACACTAACAGCACATCTGGAGACCCGGTGGAGAAGAAGGACGAAACACCTTTT
GGGGTCTCGGTGGCTGTGGGCCTGGCCGTCTTTGCCTGCCTCTTCCTTTCTACGCTGCTC
CTTGTGCTCAACAAATGTGGACGGAGAAACAAGTTTGGGATCAACCGCCCGGCTGTGCTG
GCTCCAGAGGATGGGCTGGCCATGTCCCTGCATTTCATGACATTGGGTGGCAGCTCCCTG
TCCCCCACCGAGGGCAAAGGCTCTGGGCTCCAAGGCCACATCATCGAGAACCCACAATAC
TTCAGTGATGCCTGTGTTCACCACATCAAGCGCCGGGACATCGTGCTCAAGTGGGAGCTG
GGGGAGGGCGCCTTTGGGAAGGTCTTCCTTGCTGAGTGCCACAACCTCCTGCCTGAGCAG
GACAAGATGCTGGTGGCTGTCAAGGCACTGAAGGAGGCGTCCGAGAGTGCTCGGCAGGAC
TTCCAGCGTGAGGCTGAGCTGCTCACCATGCTGCAGCACCAGCACATCGTGCGCTTCTTC
GGCGTCTGCACCGAGGGCCGCCCCCTGCTCATGGTCTTTGAGTATATGCGGCACGGGGAC
CTCAACCGCTTCCTCCGATCCCATGGACCTGATGCCAAGCTGCTGGCTGGTGGGGAGGAT
GTGGCTCCAGGCCCCCTGGGTCTGGGGCAGCTGCTGGCCGTGGCTAGCCAGGTCGCTGCG
GGGATGGTGTACCTGGCGGGTCTGCATTTTGTGCACCGGGACCTGGCCACACGCAACTGT
CTAGTGGGCCAGGGACTGGTGGTCAAGATTGGTGATTTTGGCATGAGCAGGGATATCTAC
AGCACCGACTATTACCGTGTGGGAGGCCGCACCATGCTGCCCATTCGCTGGATGCCGCCC
GAGAGCATCCTGTACCGTAAGTTCACCACCGAGAGCGACGTGTGGAGCTTCGGCGTGGTG
CTCTGGGAGATCTTCACCTACGGCAAGCAGCCCTGGTACCAGCTCTCCAACACGGAGGCA
ATCGACTGCATCACGCAGGGACGTGAGTTGGAGCGGCCACGTGCCTGCCCACCAGAGGTC
TACGCCATCATGCGGGGCTGCTGGCAGCGGGAGCCCCAGCAACGCCACAGCATCAAGGAT
GTGCACGCCCGGCTGCAAGCCCTGGCCCAGGCACCTCCTGTCTACCTGGATGTCCTGGGC
TAG
Chromosome Location
1
Locus
1q21-q22
External Identifiers
ResourceLink
UniProtKB IDP04629
UniProtKB Entry NameNTRK1_HUMAN
GenBank Protein ID339918
GenBank Gene IDM23102
GenAtlas IDNTRK1
HGNC IDHGNC:8031
General References
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Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB00619ImatinibapprovedunknownantagonistDetails
DB00321AmitriptylineapprovedunknownagonistactivatorDetails
DB08896RegorafenibapprovedyesinhibitorDetails
DB12010Fostamatinibapproved, investigationalunknowninhibitorDetails
DB13926Cenegerminapproved, investigationalyesstimulatorDetails
DB14723Larotrectinibapproved, investigationalyesinhibitorDetails
DB11986Entrectinibapproved, investigationalyesinhibitorDetails
DB15822Pralsetinibapproved, investigationalunknowninhibitorDetails
DB16826Repotrectinibapproved, investigationalyesinhibitorDetails