BDNF/NT-3 growth factors receptor

Details

Name
BDNF/NT-3 growth factors receptor
Synonyms
  • 2.7.10.1
  • GP145-TrkB
  • Neurotrophic tyrosine kinase receptor type 2
  • Trk-B
  • TRKB
  • TrkB tyrosine kinase
  • Tropomyosin-related kinase B
Gene Name
NTRK2
Organism
Humans
Amino acid sequence
>lcl|BSEQ0006936|BDNF/NT-3 growth factors receptor
MSSWIRWHGPAMARLWGFCWLVVGFWRAAFACPTSCKCSASRIWCSDPSPGIVAFPRLEP
NSVDPENITEIFIANQKRLEIINEDDVEAYVGLRNLTIVDSGLKFVAHKAFLKNSNLQHI
NFTRNKLTSLSRKHFRHLDLSELILVGNPFTCSCDIMWIKTLQEAKSSPDTQDLYCLNES
SKNIPLANLQIPNCGLPSANLAAPNLTVEEGKSITLSCSVAGDPVPNMYWDVGNLVSKHM
NETSHTQGSLRITNISSDDSGKQISCVAENLVGEDQDSVNLTVHFAPTITFLESPTSDHH
WCIPFTVKGNPKPALQWFYNGAILNESKYICTKIHVTNHTEYHGCLQLDNPTHMNNGDYT
LIAKNEYGKDEKQISAHFMGWPGIDDGANPNYPDVIYEDYGTAANDIGDTTNRSNEIPST
DVTDKTGREHLSVYAVVVIASVVGFCLLVMLFLLKLARHSKFGMKGPASVISNDDDSASP
LHHISNGSNTPSSSEGGPDAVIIGMTKIPVIENPQYFGITNSQLKPDTFVQHIKRHNIVL
KRELGEGAFGKVFLAECYNLCPEQDKILVAVKTLKDASDNARKDFHREAELLTNLQHEHI
VKFYGVCVEGDPLIMVFEYMKHGDLNKFLRAHGPDAVLMAEGNPPTELTQSQMLHIAQQI
AAGMVYLASQHFVHRDLATRNCLVGENLLVKIGDFGMSRDVYSTDYYRVGGHTMLPIRWM
PPESIMYRKFTTESDVWSLGVVLWEIFTYGKQPWYQLSNNEVIECITQGRVLQRPRTCPQ
EVYELMLGCWQREPHMRKNIKGIHTLLQNLAKASPVYLDILG
Number of residues
822
Molecular Weight
91998.175
Theoretical pI
6.45
GO Classification
Functions
ATP binding / brain-derived neurotrophic factor binding / brain-derived neurotrophic factor-activated receptor activity / neurotrophin binding / protein homodimerization activity
Processes
activation of adenylate cyclase activity / brain-derived neurotrophic factor receptor signaling pathway / central nervous system neuron development / cerebral cortex development / learning / negative regulation of neuron apoptotic process / neuron differentiation / neuron migration / neurotrophin TRK receptor signaling pathway / positive regulation of axonogenesis / positive regulation of cell proliferation / positive regulation of gene expression / positive regulation of MAPK cascade / positive regulation of neuron projection development / positive regulation of phosphatidylinositol 3-kinase signaling / positive regulation of protein phosphorylation / protein autophosphorylation / regulation of GTPase activity / transmembrane receptor protein tyrosine kinase signaling pathway
Components
endosome membrane / integral component of plasma membrane / receptor complex
General Function
Protein homodimerization activity
Specific Function
Receptor tyrosine kinase involved in the development and the maturation of the central and the peripheral nervous systems through regulation of neuron survival, proliferation, migration, differentiation, and synapse formation and plasticity. Receptor for BDNF/brain-derived neurotrophic factor and NTF4/neurotrophin-4. Alternatively can also bind NTF3/neurotrophin-3 which is less efficient in activating the receptor but regulates neuron survival through NTRK2. Upon 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. Through SHC1, FRS2, SH2B1, SH2B2 activates the GRB2-Ras-MAPK cascade that regulates for instance neuronal differentiation including neurite outgrowth. Through the same effectors controls the Ras-PI3 kinase-AKT1 signaling cascade that mainly regulates growth and survival. Through PLCG1 and the downstream protein kinase C-regulated pathways controls synaptic plasticity. Thereby, plays a role in learning and memory by regulating both short term synaptic function and long-term potentiation. PLCG1 also leads to NF-Kappa-B activation and the transcription of genes involved in cell survival. Hence, it is able to suppress anoikis, the apoptosis resulting from loss of cell-matrix interactions. May also play a role in neutrophin-dependent calcium signaling in glial cells and mediate communication between neurons and glia.
Pfam Domain Function
Transmembrane Regions
431-454
Cellular Location
Cell membrane
Gene sequence
>lcl|BSEQ0021932|BDNF/NT-3 growth factors receptor (NTRK2)
ATGTCGTCCTGGATAAGGTGGCATGGACCCGCCATGGCGCGGCTCTGGGGCTTCTGCTGG
CTGGTTGTGGGCTTCTGGAGGGCCGCTTTCGCCTGTCCCACGTCCTGCAAATGCAGTGCC
TCTCGGATCTGGTGCAGCGACCCTTCTCCTGGCATCGTGGCATTTCCGAGATTGGAGCCT
AACAGTGTAGATCCTGAGAACATCACCGAAATTTTCATCGCAAACCAGAAAAGGTTAGAA
ATCATCAACGAAGATGATGTTGAAGCTTATGTGGGACTGAGAAATCTGACAATTGTGGAT
TCTGGATTAAAATTTGTGGCTCATAAAGCATTTCTGAAAAACAGCAACCTGCAGCACATC
AATTTTACCCGAAACAAACTGACGAGTTTGTCTAGGAAACATTTCCGTCACCTTGACTTG
TCTGAACTGATCCTGGTGGGCAATCCATTTACATGCTCCTGTGACATTATGTGGATCAAG
ACTCTCCAAGAGGCTAAATCCAGTCCAGACACTCAGGATTTGTACTGCCTGAATGAAAGC
AGCAAGAATATTCCCCTGGCAAACCTGCAGATACCCAATTGTGGTTTGCCATCTGCAAAT
CTGGCCGCACCTAACCTCACTGTGGAGGAAGGAAAGTCTATCACATTATCCTGTAGTGTG
GCAGGTGATCCGGTTCCTAATATGTATTGGGATGTTGGTAACCTGGTTTCCAAACATATG
AATGAAACAAGCCACACACAGGGCTCCTTAAGGATAACTAACATTTCATCCGATGACAGT
GGGAAGCAGATCTCTTGTGTGGCGGAAAATCTTGTAGGAGAAGATCAAGATTCTGTCAAC
CTCACTGTGCATTTTGCACCAACTATCACATTTCTCGAATCTCCAACCTCAGACCACCAC
TGGTGCATTCCATTCACTGTGAAAGGCAACCCCAAACCAGCGCTTCAGTGGTTCTATAAC
GGGGCAATATTGAATGAGTCCAAATACATCTGTACTAAAATACATGTTACCAATCACACG
GAGTACCACGGCTGCCTCCAGCTGGATAATCCCACTCACATGAACAATGGGGACTACACT
CTAATAGCCAAGAATGAGTATGGGAAGGATGAGAAACAGATTTCTGCTCACTTCATGGGC
TGGCCTGGAATTGACGATGGTGCAAACCCAAATTATCCTGATGTAATTTATGAAGATTAT
GGAACTGCAGCGAATGACATCGGGGACACCACGAACAGAAGTAATGAAATCCCTTCCACA
GACGTCACTGATAAAACCGGTCGGGAACATCTCTCGGTCTATGCTGTGGTGGTGATTGCG
TCTGTGGTGGGATTTTGCCTTTTGGTAATGCTGTTTCTGCTTAAGTTGGCAAGACACTCC
AAGTTTGGCATGAAAGGTTTTGTTTTGTTTCATAAGATCCCACTGGATGGGTAG
Chromosome Location
9
Locus
9q22.1
External Identifiers
ResourceLink
UniProtKB IDQ16620
UniProtKB Entry NameNTRK2_HUMAN
GenBank Protein ID530791
GenBank Gene IDU12140
HGNC IDHGNC:8032
General References
  1. Nakagawara A, Liu XG, Ikegaki N, White PS, Yamashiro DJ, Nycum LM, Biegel JA, Brodeur GM: Cloning and chromosomal localization of the human TRK-B tyrosine kinase receptor gene (NTRK2). Genomics. 1995 Jan 20;25(2):538-46. [Article]
  2. 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. [Article]
  3. Allen SJ, Dawbarn D, Eckford SD, Wilcock GK, Ashcroft M, Colebrook SM, Feeney R, MacGowan SH: Cloning of a non-catalytic form of human trkB and distribution of messenger RNA for trkB in human brain. Neuroscience. 1994 Jun;60(3):825-34. [Article]
  4. Stoilov P, Castren E, Stamm S: Analysis of the human TrkB gene genomic organization reveals novel TrkB isoforms, unusual gene length, and splicing mechanism. Biochem Biophys Res Commun. 2002 Jan 25;290(3):1054-65. [Article]
  5. Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. Epub 2003 Dec 21. [Article]
  6. Humphray SJ, Oliver K, Hunt AR, Plumb RW, Loveland JE, Howe KL, Andrews TD, Searle S, Hunt SE, Scott CE, Jones MC, Ainscough R, Almeida JP, Ambrose KD, Ashwell RI, Babbage AK, Babbage S, Bagguley CL, Bailey J, Banerjee R, Barker DJ, Barlow KF, Bates K, Beasley H, Beasley O, Bird CP, Bray-Allen S, Brown AJ, Brown JY, Burford D, Burrill W, Burton J, Carder C, Carter NP, Chapman JC, Chen Y, Clarke G, Clark SY, Clee CM, Clegg S, Collier RE, Corby N, Crosier M, Cummings AT, Davies J, Dhami P, Dunn M, Dutta I, Dyer LW, Earthrowl ME, Faulkner L, Fleming CJ, Frankish A, Frankland JA, French L, Fricker DG, Garner P, Garnett J, Ghori J, Gilbert JG, Glison C, Grafham DV, Gribble S, Griffiths C, Griffiths-Jones S, Grocock R, Guy J, Hall RE, Hammond S, Harley JL, Harrison ES, Hart EA, Heath PD, Henderson CD, Hopkins BL, Howard PJ, Howden PJ, Huckle E, Johnson C, Johnson D, Joy AA, Kay M, Keenan S, Kershaw JK, Kimberley AM, King A, Knights A, Laird GK, Langford C, Lawlor S, Leongamornlert DA, Leversha M, Lloyd C, Lloyd DM, Lovell J, Martin S, Mashreghi-Mohammadi M, Matthews L, McLaren S, McLay KE, McMurray A, Milne S, Nickerson T, Nisbett J, Nordsiek G, Pearce AV, Peck AI, Porter KM, Pandian R, Pelan S, Phillimore B, Povey S, Ramsey Y, Rand V, Scharfe M, Sehra HK, Shownkeen R, Sims SK, Skuce CD, Smith M, Steward CA, Swarbreck D, Sycamore N, Tester J, Thorpe A, Tracey A, Tromans A, Thomas DW, Wall M, Wallis JM, West AP, Whitehead SL, Willey DL, Williams SA, Wilming L, Wray PW, Young L, Ashurst JL, Coulson A, Blocker H, Durbin R, Sulston JE, Hubbard T, Jackson MJ, Bentley DR, Beck S, Rogers J, Dunham I: DNA sequence and analysis of human chromosome 9. Nature. 2004 May 27;429(6990):369-74. [Article]
  7. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [Article]
  8. Haniu M, Talvenheimo J, Le J, Katta V, Welcher A, Rohde MF: Extracellular domain of neurotrophin receptor trkB: disulfide structure, N-glycosylation sites, and ligand binding. Arch Biochem Biophys. 1995 Sep 10;322(1):256-64. [Article]
  9. Meakin SO, MacDonald JI, Gryz EA, Kubu CJ, Verdi JM: The signaling adapter FRS-2 competes with Shc for binding to the nerve growth factor receptor TrkA. A model for discriminating proliferation and differentiation. J Biol Chem. 1999 Apr 2;274(14):9861-70. [Article]
  10. Liu T, Qian WJ, Gritsenko MA, Camp DG 2nd, Monroe ME, Moore RJ, Smith RD: Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry. J Proteome Res. 2005 Nov-Dec;4(6):2070-80. [Article]
  11. Luberg K, Wong J, Weickert CS, Timmusk T: Human TrkB gene: novel alternative transcripts, protein isoforms and expression pattern in the prefrontal cerebral cortex during postnatal development. J Neurochem. 2010 May;113(4):952-64. doi: 10.1111/j.1471-4159.2010.06662.x. Epub 2010 Feb 27. [Article]
  12. 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. [Article]
  13. Banfield MJ, Naylor RL, Robertson AG, Allen SJ, Dawbarn D, Brady RL: Specificity in Trk receptor:neurotrophin interactions: the crystal structure of TrkB-d5 in complex with neurotrophin-4/5. Structure. 2001 Dec;9(12):1191-9. [Article]
  14. Yeo GS, Connie Hung CC, Rochford J, Keogh J, Gray J, Sivaramakrishnan S, O'Rahilly S, Farooqi IS: A de novo mutation affecting human TrkB associated with severe obesity and developmental delay. Nat Neurosci. 2004 Nov;7(11):1187-9. Epub 2004 Oct 24. [Article]
  15. Greenman C, Stephens P, Smith R, Dalgliesh GL, Hunter C, Bignell G, Davies H, Teague J, Butler A, Stevens C, Edkins S, O'Meara S, Vastrik I, Schmidt EE, Avis T, Barthorpe S, Bhamra G, Buck G, Choudhury B, Clements J, Cole J, Dicks E, Forbes S, Gray K, Halliday K, Harrison R, Hills K, Hinton J, Jenkinson A, Jones D, Menzies A, Mironenko T, Perry J, Raine K, Richardson D, Shepherd R, Small A, Tofts C, Varian J, Webb T, West S, Widaa S, Yates A, Cahill DP, Louis DN, Goldstraw P, Nicholson AG, Brasseur F, Looijenga L, Weber BL, Chiew YE, DeFazio A, Greaves MF, Green AR, Campbell P, Birney E, Easton DF, Chenevix-Trench G, Tan MH, Khoo SK, Teh BT, Yuen ST, Leung SY, Wooster R, Futreal PA, Stratton MR: Patterns of somatic mutation in human cancer genomes. Nature. 2007 Mar 8;446(7132):153-8. [Article]
  16. Marchetti A, Felicioni L, Pelosi G, Del Grammastro M, Fumagalli C, Sciarrotta M, Malatesta S, Chella A, Barassi F, Mucilli F, Camplese P, D'Antuono T, Sacco R, Buttitta F: Frequent mutations in the neurotrophic tyrosine receptor kinase gene family in large cell neuroendocrine carcinoma of the lung. Hum Mutat. 2008 May;29(5):609-16. doi: 10.1002/humu.20707. [Article]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB00321AmitriptylineapprovedunknownagonistDetails
DB12010Fostamatinibapproved, investigationalunknowninhibitorDetails
DB14723Larotrectinibapproved, investigationalyesinhibitorDetails
DB11823Esketamineapproved, investigationalunknownDetails
DB11986Entrectinibapproved, investigationalunknowninhibitorDetails