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Identification
HMDB Protein ID HMDBP01503
Secondary Accession Numbers
  • 6799
Name High affinity nerve growth factor receptor
Synonyms
  1. Neurotrophic tyrosine kinase receptor type 1
  2. TRK1-transforming tyrosine kinase protein
  3. Trk-A
  4. p140-TrkA
Gene Name NTRK1
Protein Type Enzyme
Biological Properties
General Function Involved in protein kinase activity
Specific Function Required for high-affinity binding to nerve growth factor (NGF), neurotrophin-3 and neurotrophin-4/5 but not brain- derived neurotrophic factor (BDNF). Known substrates for the Trk receptors are SHC1, PI 3-kinase, and PLC-gamma-1. Has a crucial role in the development and function of the nociceptive reception system as well as establishment of thermal regulation via sweating. Activates ERK1 by either SHC1- or PLC-gamma-1-dependent signaling pathway
Pathways Not Available
Reactions Not Available
GO Classification
Component
integral to plasma membrane
membrane
cell part
membrane part
intrinsic to membrane
integral to membrane
Function
protein tyrosine kinase activity
transmembrane receptor protein tyrosine kinase activity
neurotrophin receptor activity
binding
catalytic activity
transferase activity
transferase activity, transferring phosphorus-containing groups
kinase activity
nucleoside binding
purine nucleoside binding
adenyl nucleotide binding
adenyl ribonucleotide binding
atp binding
receptor activity
protein binding
molecular transducer activity
signal transducer activity
protein kinase activity
Process
phosphorus metabolic process
phosphate metabolic process
enzyme linked receptor protein signaling pathway
transmembrane receptor protein tyrosine kinase signaling pathway
metabolic process
cellular metabolic process
protein amino acid phosphorylation
signaling
signaling pathway
cell surface receptor linked signaling pathway
phosphorylation
Cellular Location
  1. Cell membrane
  2. Single-pass type I membrane protein
Gene Properties
Chromosome Location Chromosome:1
Locus 1q21-q22
SNPs NTRK1
Gene Sequence
>2391 bp
ATGCTGCGAGGCGGACGGCGCGGGCAGCTTGGCTGGCACAGCTGGGCTGCGGGGCCGGGC
AGCCTGCTGGCTTGGCTGATACTGGCATCTGCGGGCGCCGCACCCTGCCCCGATGCCTGC
TGCCCCCACGGCTCCTCGGGACTGCGATGCACCCGGGATGGGGCCCTGGATAGCCTCCAC
CACCTGCCCGGCGCAGAGAACCTGACTGAGCTCTACATCGAGAACCAGCAGCATCTGCAG
CATCTGGAGCTCCGTGATCTGAGGGGCCTGGGGGAGCTGAGAAACCTCACCATCGTGAAG
AGTGGTCTCCGTTTCGTGGCGCCAGATGCCTTCCATTTCACTCCTCGGCTCAGTCGCCTG
AATCTCTCCTTCAACGCTCTGGAGTCTCTCTCCTGGAAAACTGTGCAGGGCCTCTCCTTA
CAGGAACTGGTCCTGTCGGGGAACCCTCTGCACTGTTCTTGTGCCCTGCGCTGGCTACAG
CGCTGGGAGGAGGAGGGACTGGGCGGAGTGCCTGAACAGAAGCTGCAGTGTCATGGGCAA
GGGCCCCTGGCCCACATGCCCAATGCCAGCTGTGGTGTGCCCACGCTGAAGGTCCAGGTG
CCCAATGCCTCGGTGGATGTGGGGGACGACGTGCTGCTGCGGTGCCAGGTGGAGGGGCGG
GGCCTGGAGCAGGCCGGCTGGATCCTCACAGAGCTGGAGCAGTCAGCCACGGTGATGAAA
TCTGGGGGTCTGCCATCCCTGGGGCTGACCCTGGCCAATGTCACCAGTGACCTCAACAGG
AAGAACGTGACGTGCTGGGCAGAGAACGATGTGGGCCGGGCAGAGGTCTCTGTTCAGGTC
AACGTCTCCTTCCCGGCCAGTGTGCAGCTGCACACGGCGGTGGAGATGCACCACTGGTGC
ATCCCCTTCTCTGTGGATGGGCAGCCGGCACCGTCTCTGCGCTGGCTCTTCAATGGCTCC
GTGCTCAATGAGACCAGCTTCATCTTCACTGAGTTCCTGGAGCCGGCAGCCAATGAGACC
GTGCGGCACGGGTGTCTGCGCCTCAACCAGCCCACCCACGTCAACAACGGCAACTACACG
CTGCTGGCTGCCAACCCCTTCGGCCAGGCCTCCGCCTCCATCATGGCTGCCTTCATGGAC
AACCCTTTCGAGTTCAACCCCGAGGACCCCATCCCTGTCTCCTTCTCGCCGGTGGACACT
AACAGCACATCTGGAGACCCGGTGGAGAAGAAGGACGAAACACCTTTTGGGGTCTCGGTG
GCTGTGGGCCTGGCCGTCTTTGCCTGCCTCTTCCTTTCTACGCTGCTCCTTGTGCTCAAC
AAATGTGGACGGAGAAACAAGTTTGGGATCAACCGCCCGGCTGTGCTGGCTCCAGAGGAT
GGGCTGGCCATGTCCCTGCATTTCATGACATTGGGTGGCAGCTCCCTGTCCCCCACCGAG
GGCAAAGGCTCTGGGCTCCAAGGCCACATCATCGAGAACCCACAATACTTCAGTGATGCC
TGTGTTCACCACATCAAGCGCCGGGACATCGTGCTCAAGTGGGAGCTGGGGGAGGGCGCC
TTTGGGAAGGTCTTCCTTGCTGAGTGCCACAACCTCCTGCCTGAGCAGGACAAGATGCTG
GTGGCTGTCAAGGCACTGAAGGAGGCGTCCGAGAGTGCTCGGCAGGACTTCCAACGTGAG
GCTGAGCTGCTCACCATGCTGCAGCACCAGCACATCGTGCGCTTCTTCGGCGTCTGCACC
GAGGGCCGCCCCCTGCTCATGGTCTTCGAGTATATGCGGCACGGGGACCTCAACCGCTTC
CTCCGATCCCATGGACCCGATGCCAAGCTGCTGGCTGGTGGGGAGGATGTGGCTCCAGGC
CCCCTGGGTCTGGGGCAGCTGCTGGCCGTGGCTAGCCAGGTCGCTGCGGGGATGGTGTAC
CTGGCGGGTCTGCATTTTGTGCACCGGGACCTGGCCACACGCAACTGTCTAGTGGGCCAG
GGACTGGTGGTCAAGATTGGTGATTTTGGCATGAGCAGGGATATCTACAGCACCGACTAT
TACCGTGTGGGAGGCCGCACCATGCTGCCCATTCGCTGGATGCCGCCCGAGAGCATCCTG
TACCGTAAGTTCACCACCGAGAGCGACGTGTGGAGCTTCGGCGTGGTGCTCTGGGAGATC
TTCACCTACGGCAAGCAGCCCTGGTACCAGCTCTCCAACACGGAGGCAATCGACTGCATC
ACGCAGGGACGTGAGTTGGAGCGGCCACGTGCCTGCCCACCAGAGGTCTACGCCATCATG
CGGGGCTGCTGGCAGCGGGAGCCCCAGCAACGCCACAGCATCAAGGATGTGCACGCCCGG
CTGCAAGCCCTGGCCCAGGCACCTCCTGTCTACCTGGATGTCCTGGGCTAG
Protein Properties
Number of Residues 796
Molecular Weight 87496.5
Theoretical pI 6.62
Pfam Domain Function
Signals
  • 1-32
Transmembrane Regions
  • 424-439
Protein Sequence
>High affinity nerve growth factor receptor
MLRGGRRGQLGWHSWAAGPGSLLAWLILASAGAAPCPDACCPHGSSGLRCTRDGALDSLH
HLPGAENLTELYIENQQHLQHLELRDLRGLGELRNLTIVKSGLRFVAPDAFHFTPRLSRL
NLSFNALESLSWKTVQGLSLQELVLSGNPLHCSCALRWLQRWEEEGLGGVPEQKLQCHGQ
GPLAHMPNASCGVPTLKVQVPNASVDVGDDVLLRCQVEGRGLEQAGWILTELEQSATVMK
SGGLPSLGLTLANVTSDLNRKNVTCWAENDVGRAEVSVQVNVSFPASVQLHTAVEMHHWC
IPFSVDGQPAPSLRWLFNGSVLNETSFIFTEFLEPAANETVRHGCLRLNQPTHVNNGNYT
LLAANPFGQASASIMAAFMDNPFEFNPEDPIPVSFSPVDTNSTSGDPVEKKDETPFGVSV
AVGLAVFACLFLSTLLLVLNKCGRRNKFGINRPAVLAPEDGLAMSLHFMTLGGSSLSPTE
GKGSGLQGHIIENPQYFSDACVHHIKRRDIVLKWELGEGAFGKVFLAECHNLLPEQDKML
VAVKALKEASESARQDFQREAELLTMLQHQHIVRFFGVCTEGRPLLMVFEYMRHGDLNRF
LRSHGPDAKLLAGGEDVAPGPLGLGQLLAVASQVAAGMVYLAGLHFVHRDLATRNCLVGQ
GLVVKIGDFGMSRDIYSTDYYRVGGRTMLPIRWMPPESILYRKFTTESDVWSFGVVLWEI
FTYGKQPWYQLSNTEAIDCITQGRELERPRACPPEVYAIMRGCWQREPQQRHSIKDVHAR
LQALAQAPPVYLDVLG
GenBank ID Protein 3869113
UniProtKB/Swiss-Prot ID P04629
UniProtKB/Swiss-Prot Entry Name NTRK1_HUMAN
PDB IDs Not Available
GenBank Gene ID AB019488
GeneCard ID NTRK1
GenAtlas ID NTRK1
HGNC ID HGNC:8031
References
General References
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  6. Shelton DL, Sutherland J, Gripp J, Camerato T, Armanini MP, Phillips HS, Carroll K, Spencer SD, Levinson AD: Human trks: molecular cloning, tissue distribution, and expression of extracellular domain immunoadhesins. J Neurosci. 1995 Jan;15(1 Pt 2):477-91. [PubMed:7823156 ]
  7. Ultsch MH, Wiesmann C, Simmons LC, Henrich J, Yang M, Reilly D, Bass SH, de Vos AM: Crystal structures of the neurotrophin-binding domain of TrkA, TrkB and TrkC. J Mol Biol. 1999 Jul 2;290(1):149-59. [PubMed:10388563 ]
  8. Martin-Zanca D, Oskam R, Mitra G, Copeland T, Barbacid M: Molecular and biochemical characterization of the human trk proto-oncogene. Mol Cell Biol. 1989 Jan;9(1):24-33. [PubMed:2927393 ]
  9. Indo Y, Mardy S, Tsuruta M, Karim MA, Matsuda I: Structure and organization of the human TRKA gene encoding a high affinity receptor for nerve growth factor. Jpn J Hum Genet. 1997 Jun;42(2):343-51. [PubMed:9290260 ]
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  25. Greco A, Villa R, Tubino B, Romano L, Penso D, Pierotti MA: A novel NTRK1 mutation associated with congenital insensitivity to pain with anhidrosis. Am J Hum Genet. 1999 Apr;64(4):1207-10. [PubMed:10090906 ]
  26. Mardy S, Miura Y, Endo F, Matsuda I, Sztriha L, Frossard P, Moosa A, Ismail EA, Macaya A, Andria G, Toscano E, Gibson W, Graham GE, Indo Y: Congenital insensitivity to pain with anhidrosis: novel mutations in the TRKA (NTRK1) gene encoding a high-affinity receptor for nerve growth factor. Am J Hum Genet. 1999 Jun;64(6):1570-9. [PubMed:10330344 ]
  27. Gimm O, Greco A, Hoang-Vu C, Dralle H, Pierotti MA, Eng C: Mutation analysis reveals novel sequence variants in NTRK1 in sporadic human medullary thyroid carcinoma. J Clin Endocrinol Metab. 1999 Aug;84(8):2784-7. [PubMed:10443680 ]
  28. Yotsumoto S, Setoyama M, Hozumi H, Mizoguchi S, Fukumaru S, Kobayashi K, Saheki T, Kanzaki T: A novel point mutation affecting the tyrosine kinase domain of the TRKA gene in a family with congenital insensitivity to pain with anhidrosis. J Invest Dermatol. 1999 May;112(5):810-4. [PubMed:10233776 ]
  29. Shatzky S, Moses S, Levy J, Pinsk V, Hershkovitz E, Herzog L, Shorer Z, Luder A, Parvari R: Congenital insensitivity to pain with anhidrosis (CIPA) in Israeli-Bedouins: genetic heterogeneity, novel mutations in the TRKA/NGF receptor gene, clinical findings, and results of nerve conduction studies. Am J Med Genet. 2000 Jun 19;92(5):353-60. [PubMed:10861667 ]
  30. Miura Y, Mardy S, Awaya Y, Nihei K, Endo F, Matsuda I, Indo Y: Mutation and polymorphism analysis of the TRKA (NTRK1) gene encoding a high-affinity receptor for nerve growth factor in congenital insensitivity to pain with anhidrosis (CIPA) families. Hum Genet. 2000 Jan;106(1):116-24. [PubMed:10982191 ]
  31. Greco A, Villa R, Fusetti L, Orlandi R, Pierotti MA: The Gly571Arg mutation, associated with the autonomic and sensory disorder congenital insensitivity to pain with anhidrosis, causes the inactivation of the NTRK1/nerve growth factor receptor. J Cell Physiol. 2000 Jan;182(1):127-33. [PubMed:10567924 ]