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
Human
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
protein homodimerization activity / ATP binding / nerve growth factor binding / transmembrane receptor protein tyrosine kinase activity / nerve growth factor receptor activity / neurotrophin binding
Processes
Ras protein signal transduction / positive regulation of NF-kappaB transcription factor activity / response to hydrostatic pressure / positive regulation of synaptic transmission, glutamatergic / response to axon injury / axon guidance / Sertoli cell development / circadian rhythm / positive regulation of angiogenesis / peptidyl-tyrosine phosphorylation / detection of mechanical stimulus involved in sensory perception of pain / response to activity / transmembrane receptor protein tyrosine kinase signaling pathway / response to ethanol / positive regulation of protein phosphorylation / learning or memory / response to nutrient levels / response to drug / axonogenesis involved in innervation / aging / behavioral response to formalin induced pain / negative regulation of neuron apoptotic process / activation of adenylate cyclase activity / positive regulation of Ras protein signal transduction / positive regulation of GTPase activity / cellular response to nerve growth factor stimulus / response to electrical stimulus / activation of MAPKK activity / sympathetic nervous system development / activation of phospholipase C activity / small GTPase mediated signal transduction / developmental programmed cell death / detection of temperature stimulus involved in sensory perception of pain / negative regulation of cell proliferation / B cell differentiation / phosphatidylinositol-mediated signaling / response to radiation / mechanoreceptor differentiation / neurotrophin TRK receptor signaling pathway / cellular response to nicotine / positive regulation of ERK1 and ERK2 cascade / olfactory nerve development / protein phosphorylation / positive regulation of synapse assembly / protein autophosphorylation / positive regulation of programmed cell death / positive regulation of neuron projection development
Components
neuronal cell body / protein complex / late endosome membrane / early endosome / dendrite / integral component of plasma membrane / early endosome membrane / endosome / plasma membrane / receptor complex / late endosome / cell surface / axon / cytoplasmic vesicle
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
Not Available

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB00619ImatinibapprovedunknownantagonistDetails
DB00321AmitriptylineapprovedunknownagonistDetails
DB08896RegorafenibapprovedyesinhibitorDetails