NTRK2_HUMAN
ID NTRK2_HUMAN Reviewed; 822 AA.
AC Q16620; B1ANZ4; B4DFV9; Q16675; Q59GJ1; Q8WXJ5; Q8WXJ6; Q8WXJ7;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 232.
DE RecName: Full=BDNF/NT-3 growth factors receptor;
DE EC=2.7.10.1 {ECO:0000269|PubMed:15494731};
DE AltName: Full=GP145-TrkB;
DE Short=Trk-B;
DE AltName: Full=Neurotrophic tyrosine kinase receptor type 2;
DE AltName: Full=TrkB tyrosine kinase;
DE AltName: Full=Tropomyosin-related kinase B;
DE Flags: Precursor;
GN Name=NTRK2; Synonyms=TRKB;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM TRKB).
RC TISSUE=Hippocampus;
RX PubMed=7789988; DOI=10.1016/0888-7543(95)80055-q;
RA Nakagawara A., Liu X.-G., Ikegaki N., White P.S., Yamashiro D.J.,
RA Nycum L.M., Biegel J.A., Brodeur G.M.;
RT "Cloning and chromosomal localization of the human TRK-B tyrosine kinase
RT receptor gene (NTRK2).";
RL Genomics 25:538-546(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS TRKB AND TRKB-T1).
RC TISSUE=Brain;
RX PubMed=7823156; DOI=10.1523/jneurosci.15-01-00477.1995;
RA Shelton D.L., Sutherland J., Gripp J., Camerato T., Armanini M.P.,
RA Phillips H.S., Carroll K., Spencer S.D., Levinson A.D.;
RT "Human trks: molecular cloning, tissue distribution, and expression of
RT extracellular domain immunoadhesins.";
RL J. Neurosci. 15:477-491(1995).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM TRKB-T1), TISSUE SPECIFICITY, AND
RP DEVELOPMENTAL STAGE.
RC TISSUE=Hippocampus;
RX PubMed=7936202; DOI=10.1016/0306-4522(94)90507-x;
RA Allen S.J., Dawbarn D., Eckford S.D., Wilcock G.K., Ashcroft M.,
RA Colebrook S.M., Feeney R., Macgowan S.H.;
RT "Cloning of a non-catalytic form of human trkB and distribution of
RT messenger RNA for trkB in human brain.";
RL Neuroscience 60:825-834(1994).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS TRKB; TRKB-T1; TRKB-T-SHC; 4 AND 5),
RP ALTERNATIVE SPLICING, TISSUE SPECIFICITY, AND SUBCELLULAR LOCATION.
RX PubMed=11798182; DOI=10.1006/bbrc.2001.6301;
RA Stoilov P., Castren E., Stamm S.;
RT "Analysis of the human TrkB gene genomic organization reveals novel TrkB
RT isoforms, unusual gene length, and splicing mechanism.";
RL Biochem. Biophys. Res. Commun. 290:1054-1065(2002).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM TRKB-T1), AND VARIANT ARG-309.
RA Steinbeck J.A., Thomsen S., Wessig J., Leypoldt F., Lewerenz J.,
RA Methner A.;
RT "Full length truncated TrkB sequence identified in a screen for genes
RT regulated by ischemic preconditioning.";
RL Submitted (MAY-2002) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM TRKB-N-T1).
RC TISSUE=Amygdala;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM TRKB-T-TK).
RC TISSUE=Brain;
RA Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S.,
RA Ohara O., Nagase T., Kikuno R.F.;
RT "Homo sapiens protein coding cDNA.";
RL Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164053; DOI=10.1038/nature02465;
RA Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L.,
RA Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R.,
RA Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S.,
RA Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K.,
RA Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C.,
RA Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E.,
RA Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M.,
RA Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J.,
RA Frankish A., Frankland J.A., French L., Fricker D.G., Garner P.,
RA Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S.,
RA Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E.,
RA Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D.,
RA Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E.,
RA Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K.,
RA Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S.,
RA Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J.,
RA Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E.,
RA McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V.,
RA Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S.,
RA Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K.,
RA Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J.,
RA Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M.,
RA West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L.,
RA Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M.,
RA Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J.,
RA Dunham I.;
RT "DNA sequence and analysis of human chromosome 9.";
RL Nature 429:369-374(2004).
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [10]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM TRKB-T1).
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [11]
RP FUNCTION, DISULFIDE BONDS, AND GLYCOSYLATION AT ASN-67; ASN-95; ASN-121;
RP ASN-178; ASN-205; ASN-241; ASN-254; ASN-280; ASN-338 AND ASN-412.
RX PubMed=7574684; DOI=10.1006/abbi.1995.1460;
RA Haniu M., Talvenheimo J., Le J., Katta V., Welcher A., Rohde M.F.;
RT "Extracellular domain of neurotrophin receptor trkB: disulfide structure,
RT N-glycosylation sites, and ligand binding.";
RL Arch. Biochem. Biophys. 322:256-264(1995).
RN [12]
RP INTERACTION WITH FRS2.
RX PubMed=10092678; DOI=10.1074/jbc.274.14.9861;
RA Meakin S.O., MacDonald J.I.S., Gryz E.A., Kubu C.J., Verdi J.M.;
RT "The signaling adapter FRS-2 competes with Shc for binding to the nerve
RT growth factor receptor TrkA. A model for discriminating proliferation and
RT differentiation.";
RL J. Biol. Chem. 274:9861-9870(1999).
RN [13]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-67; ASN-121 AND ASN-254.
RC TISSUE=Plasma;
RX PubMed=16335952; DOI=10.1021/pr0502065;
RA Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E., Moore R.J.,
RA Smith R.D.;
RT "Human plasma N-glycoproteome analysis by immunoaffinity subtraction,
RT hydrazide chemistry, and mass spectrometry.";
RL J. Proteome Res. 4:2070-2080(2005).
RN [14]
RP ALTERNATIVE SPLICING (ISOFORMS TRKB-T-TK AND TRKB-N-T1).
RX PubMed=20193039; DOI=10.1111/j.1471-4159.2010.06662.x;
RA Luberg K., Wong J., Weickert C.S., Timmusk T.;
RT "Human TrkB gene: novel alternative transcripts, protein isoforms and
RT expression pattern in the prefrontal cerebral cortex during postnatal
RT development.";
RL J. Neurochem. 113:952-964(2010).
RN [15] {ECO:0007744|PDB:1WWB}
RP X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS) OF 283-385, AND DISULFIDE BONDS.
RX PubMed=10388563; DOI=10.1006/jmbi.1999.2816;
RA Ultsch M.H., Wiesmann C., Simmons L.C., Henrich J., Yang M., Reilly D.,
RA Bass S.H., de Vos A.M.;
RT "Crystal structures of the neurotrophin-binding domain of TrkA, TrkB and
RT TrkC.";
RL J. Mol. Biol. 290:149-159(1999).
RN [16] {ECO:0007744|PDB:1HCF}
RP X-RAY CRYSTALLOGRAPHY (2.70 ANGSTROMS) OF 284-383 IN COMPLEX WITH NTF4, AND
RP DISULFIDE BONDS.
RX PubMed=11738045; DOI=10.1016/s0969-2126(01)00681-5;
RA Banfield M.J., Naylor R.L., Robertson A.G., Allen S.J., Dawbarn D.,
RA Brady R.L.;
RT "Specificity in Trk receptor:neurotrophin interactions: the crystal
RT structure of TrkB-d5 in complex with neurotrophin-4/5.";
RL Structure 9:1191-1199(2001).
RN [17]
RP VARIANT OBHD CYS-706, CHARACTERIZATION OF VARIANT OBHD CYS-706, FUNCTION AS
RP A BDNF-ACTIVATED RECEPTOR, CATALYTIC ACTIVITY, PHOSPHORYLATION, AND
RP SUBCELLULAR LOCATION.
RX PubMed=15494731; DOI=10.1038/nn1336;
RA Yeo G.S., Connie Hung C.C., Rochford J., Keogh J., Gray J.,
RA Sivaramakrishnan S., O'Rahilly S., Farooqi I.S.;
RT "A de novo mutation affecting human TrkB associated with severe obesity and
RT developmental delay.";
RL Nat. Neurosci. 7:1187-1189(2004).
RN [18]
RP VARIANT [LARGE SCALE ANALYSIS] PHE-138.
RX PubMed=17344846; DOI=10.1038/nature05610;
RA Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G.,
RA Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S.,
RA Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G.,
RA Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K.,
RA Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D.,
RA Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R.,
RA Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A.,
RA Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F.,
RA Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F.,
RA Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G.,
RA Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R.,
RA Futreal P.A., Stratton M.R.;
RT "Patterns of somatic mutation in human cancer genomes.";
RL Nature 446:153-158(2007).
RN [19]
RP VARIANTS ILE-697; GLY-699 AND CYS-718.
RX PubMed=18293376; DOI=10.1002/humu.20707;
RA Marchetti A., Felicioni L., Pelosi G., Del Grammastro M., Fumagalli C.,
RA Sciarrotta M., Malatesta S., Chella A., Barassi F., Mucilli F.,
RA Camplese P., D'Antuono T., Sacco R., Buttitta F.;
RT "Frequent mutations in the neurotrophic tyrosine receptor kinase gene
RT family in large cell neuroendocrine carcinoma of the lung.";
RL Hum. Mutat. 29:609-616(2008).
RN [20]
RP VARIANT OBHD 444-GLY--GLY-822 DEL.
RX PubMed=27884935; DOI=10.1136/jmedgenet-2016-104215;
RA Miller K.A., Twigg S.R., McGowan S.J., Phipps J.M., Fenwick A.L.,
RA Johnson D., Wall S.A., Noons P., Rees K.E., Tidey E.A., Craft J.,
RA Taylor J., Taylor J.C., Goos J.A., Swagemakers S.M., Mathijssen I.M.,
RA van der Spek P.J., Lord H., Lester T., Abid N., Cilliers D., Hurst J.A.,
RA Morton J.E., Sweeney E., Weber A., Wilson L.C., Wilkie A.O.;
RT "Diagnostic value of exome and whole genome sequencing in
RT craniosynostosis.";
RL J. Med. Genet. 54:260-268(2017).
RN [21]
RP INVOLVEMENT IN DEE58, VARIANT DEE58 CYS-434, AND VARIANT OBHD ILE-704.
RX PubMed=29100083; DOI=10.1016/j.ajhg.2017.09.008;
RG Deciphering Developmental Disorders Study;
RA Hamdan F.F., Myers C.T., Cossette P., Lemay P., Spiegelman D.,
RA Laporte A.D., Nassif C., Diallo O., Monlong J., Cadieux-Dion M.,
RA Dobrzeniecka S., Meloche C., Retterer K., Cho M.T., Rosenfeld J.A., Bi W.,
RA Massicotte C., Miguet M., Brunga L., Regan B.M., Mo K., Tam C.,
RA Schneider A., Hollingsworth G., FitzPatrick D.R., Donaldson A., Canham N.,
RA Blair E., Kerr B., Fry A.E., Thomas R.H., Shelagh J., Hurst J.A.,
RA Brittain H., Blyth M., Lebel R.R., Gerkes E.H., Davis-Keppen L., Stein Q.,
RA Chung W.K., Dorison S.J., Benke P.J., Fassi E., Corsten-Janssen N.,
RA Kamsteeg E.J., Mau-Them F.T., Bruel A.L., Verloes A., Ounap K.,
RA Wojcik M.H., Albert D.V.F., Venkateswaran S., Ware T., Jones D., Liu Y.C.,
RA Mohammad S.S., Bizargity P., Bacino C.A., Leuzzi V., Martinelli S.,
RA Dallapiccola B., Tartaglia M., Blumkin L., Wierenga K.J., Purcarin G.,
RA O'Byrne J.J., Stockler S., Lehman A., Keren B., Nougues M.C., Mignot C.,
RA Auvin S., Nava C., Hiatt S.M., Bebin M., Shao Y., Scaglia F., Lalani S.R.,
RA Frye R.E., Jarjour I.T., Jacques S., Boucher R.M., Riou E., Srour M.,
RA Carmant L., Lortie A., Major P., Diadori P., Dubeau F., D'Anjou G.,
RA Bourque G., Berkovic S.F., Sadleir L.G., Campeau P.M., Kibar Z.,
RA Lafreniere R.G., Girard S.L., Mercimek-Mahmutoglu S., Boelman C.,
RA Rouleau G.A., Scheffer I.E., Mefford H.C., Andrade D.M., Rossignol E.,
RA Minassian B.A., Michaud J.L.;
RT "High rate of recurrent de novo mutations in developmental and epileptic
RT encephalopathies.";
RL Am. J. Hum. Genet. 101:664-685(2017).
CC -!- FUNCTION: Receptor tyrosine kinase involved in the development and the
CC maturation of the central and the peripheral nervous systems through
CC regulation of neuron survival, proliferation, migration,
CC differentiation, and synapse formation and plasticity (By similarity).
CC Receptor for BDNF/brain-derived neurotrophic factor and
CC NTF4/neurotrophin-4. Alternatively can also bind NTF3/neurotrophin-3
CC which is less efficient in activating the receptor but regulates neuron
CC survival through NTRK2 (PubMed:7574684, PubMed:15494731). Upon ligand-
CC binding, undergoes homodimerization, autophosphorylation and activation
CC (PubMed:15494731). Recruits, phosphorylates and/or activates several
CC downstream effectors including SHC1, FRS2, SH2B1, SH2B2 and PLCG1 that
CC regulate distinct overlapping signaling cascades. Through SHC1, FRS2,
CC SH2B1, SH2B2 activates the GRB2-Ras-MAPK cascade that regulates for
CC instance neuronal differentiation including neurite outgrowth. Through
CC the same effectors controls the Ras-PI3 kinase-AKT1 signaling cascade
CC that mainly regulates growth and survival. Through PLCG1 and the
CC downstream protein kinase C-regulated pathways controls synaptic
CC plasticity. Thereby, plays a role in learning and memory by regulating
CC both short term synaptic function and long-term potentiation. PLCG1
CC also leads to NF-Kappa-B activation and the transcription of genes
CC involved in cell survival. Hence, it is able to suppress anoikis, the
CC apoptosis resulting from loss of cell-matrix interactions. May also
CC play a role in neutrophin-dependent calcium signaling in glial cells
CC and mediate communication between neurons and glia.
CC {ECO:0000250|UniProtKB:P15209, ECO:0000269|PubMed:15494731,
CC ECO:0000269|PubMed:7574684}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-tyrosyl-[protein] = ADP + H(+) + O-phospho-L-tyrosyl-
CC [protein]; Xref=Rhea:RHEA:10596, Rhea:RHEA-COMP:10136, Rhea:RHEA-
CC COMP:10137, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:46858,
CC ChEBI:CHEBI:82620, ChEBI:CHEBI:456216; EC=2.7.10.1;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU10028,
CC ECO:0000269|PubMed:15494731};
CC -!- ACTIVITY REGULATION: The neuronal activity and the influx of calcium
CC positively regulate the kinase activity and the internalization of the
CC receptor which are both important for active signaling. Regulated by
CC NGFR that may control the internalization of the receptor. NGFR may
CC also stimulate the activation by BDNF compared to NTF3 and NTF4. SH2D1A
CC inhibits the autophosphorylation of the receptor, and alters the
CC recruitment and activation of downstream effectors and signaling
CC cascades. The formation of active receptors dimers able to fully
CC transduce the ligand-mediated signal, may be negatively regulated by
CC the formation of inactive heterodimers with the non-catalytic isoforms
CC (By similarity). {ECO:0000250|UniProtKB:P15209,
CC ECO:0000250|UniProtKB:Q63604}.
CC -!- SUBUNIT: Exists in a dynamic equilibrium between monomeric (low
CC affinity) and dimeric (high affinity) structures. Interacts
CC (phosphorylated upon activation by BDNF) with SHC1; mediates SHC1
CC phosphorylation and activation. Interacts (phosphorylated upon
CC activation by BDNF) with PLCG1 and/or PLCG2; mediates PLCG1
CC phosphorylation and activation. Interacts with SH2B1 and SH2B2.
CC Interacts with NGFR; may regulate the ligand specificity of the
CC receptor (By similarity). Interacts with SORCS2; this interaction is
CC important for normal targeting to post-synaptic densities in response
CC to high-frequency stimulation (By similarity). Interacts
CC (phosphorylated upon ligand-binding) with SH2D1A; regulates NTRK2.
CC Interacts with SQSTM1 and KIDINS220 (By similarity). Interacts
CC (phosphorylated upon ligand-binding) with FRS2; activates the MAPK
CC signaling pathway (PubMed:10092678). Interacts with APPL1 (By
CC similarity). Interacts with MAPK8IP3/JIP3 and KLC1; interaction with
CC KLC1 is mediated by MAPK8IP3/JIP3 (By similarity). Interacts with
CC SORL1; this interaction facilitates NTRK2 trafficking between synaptic
CC plasma membranes, postsynaptic densities and cell soma, hence
CC positively regulates BDNF signaling (By similarity).
CC {ECO:0000250|UniProtKB:P04629, ECO:0000250|UniProtKB:P15209,
CC ECO:0000250|UniProtKB:Q63604, ECO:0000269|PubMed:10092678,
CC ECO:0000269|PubMed:11738045}.
CC -!- INTERACTION:
CC Q16620; Q03114: Cdk5; Xeno; NbExp=3; IntAct=EBI-3904881, EBI-2008531;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:15494731};
CC Single-pass type I membrane protein {ECO:0000305}. Endosome membrane
CC {ECO:0000250|UniProtKB:P15209}; Single-pass type I membrane protein
CC {ECO:0000250|UniProtKB:P15209}. Early endosome membrane
CC {ECO:0000250|UniProtKB:P15209}. Cell projection, axon
CC {ECO:0000250|UniProtKB:Q63604}. Cell projection, dendrite
CC {ECO:0000250|UniProtKB:Q63604}. Cytoplasm, perinuclear region
CC {ECO:0000250|UniProtKB:Q63604}. Postsynaptic density
CC {ECO:0000250|UniProtKB:P15209}. Note=Internalized to endosomes upon
CC ligand-binding. {ECO:0000250|UniProtKB:P15209}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=7;
CC Comment=Additional isoforms seem to exist.;
CC Name=TrkB; Synonyms=gp145-TrkB;
CC IsoId=Q16620-1; Sequence=Displayed;
CC Name=TrkB-T1;
CC IsoId=Q16620-2; Sequence=VSP_002901, VSP_002902;
CC Name=TrkB-T-Shc;
CC IsoId=Q16620-3; Sequence=VSP_002903, VSP_002904;
CC Name=4;
CC IsoId=Q16620-4; Sequence=VSP_041942;
CC Name=5;
CC IsoId=Q16620-5; Sequence=VSP_041942, VSP_002903, VSP_002904;
CC Name=TrkB-T-TK;
CC IsoId=Q16620-6; Sequence=VSP_042178, VSP_042179;
CC Name=TrkB-N-T1;
CC IsoId=Q16620-7; Sequence=VSP_042177, VSP_002901, VSP_002902;
CC -!- TISSUE SPECIFICITY: Isoform TrkB is expressed in the central and
CC peripheral nervous system. In the central nervous system (CNS),
CC expression is observed in the cerebral cortex, hippocampus, thalamus,
CC choroid plexus, granular layer of the cerebellum, brain stem, and
CC spinal cord. In the peripheral nervous system, it is expressed in many
CC cranial ganglia, the ophthalmic nerve, the vestibular system, multiple
CC facial structures, the submaxillary glands, and dorsal root ganglia.
CC Isoform TrkB-T1 is mainly expressed in the brain but also detected in
CC other tissues including pancreas, kidney and heart. Isoform TrkB-T-Shc
CC is predominantly expressed in the brain. {ECO:0000269|PubMed:11798182,
CC ECO:0000269|PubMed:7936202}.
CC -!- DEVELOPMENTAL STAGE: Widely expressed in fetal brain.
CC {ECO:0000269|PubMed:7936202}.
CC -!- PTM: Phosphorylated. Undergoes ligand-mediated autophosphorylation that
CC is required for interaction with SHC1 and PLCG1 and other downstream
CC effectors. Isoform TrkB-T-Shc is not phosphorylated.
CC {ECO:0000269|PubMed:15494731}.
CC -!- PTM: Ubiquitinated. Undergoes polyubiquitination upon activation;
CC regulated by NGFR. Ubiquitination regulates the internalization of the
CC receptor (By similarity). {ECO:0000250}.
CC -!- DISEASE: Developmental and epileptic encephalopathy 58 (DEE58)
CC [MIM:617830]: A form of epileptic encephalopathy, a heterogeneous group
CC of severe early-onset epilepsies characterized by refractory seizures,
CC neurodevelopmental impairment, and poor prognosis. Development is
CC normal prior to seizure onset, after which cognitive and motor delays
CC become apparent. DEE58 is an autosomal dominant condition characterized
CC by onset of refractory seizures in the first days or months of life.
CC {ECO:0000269|PubMed:29100083}. Note=The disease may be caused by
CC variants affecting the gene represented in this entry.
CC -!- DISEASE: Obesity, hyperphagia, and developmental delay (OBHD)
CC [MIM:613886]: A disorder characterized by early-onset obesity,
CC hyperphagia, and severe developmental delay in motor function, speech,
CC and language. {ECO:0000269|PubMed:15494731,
CC ECO:0000269|PubMed:27884935, ECO:0000269|PubMed:29100083}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- MISCELLANEOUS: Trk also stands for tropomyosin-related kinase since the
CC first Trk was isolated as an oncogenic protein which was the result of
CC a fusion between the tropomyosin gene TPM3 and NTRK1.
CC -!- MISCELLANEOUS: [Isoform TrkB-T1]: Non-catalytic isoform. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein
CC kinase family. Insulin receptor subfamily. {ECO:0000255|PROSITE-
CC ProRule:PRU00159}.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/NTRK2ID41589ch9q21.html";
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DR EMBL; U12140; AAC51371.1; -; mRNA.
DR EMBL; S76473; AAB33109.1; -; mRNA.
DR EMBL; S76474; AAB33110.1; -; mRNA.
DR EMBL; X75958; CAA53571.1; -; mRNA.
DR EMBL; AF410899; AAL67965.1; -; mRNA.
DR EMBL; AF410900; AAL67966.1; -; mRNA.
DR EMBL; AF410901; AAL67967.1; -; mRNA.
DR EMBL; AF508964; AAM77876.1; -; mRNA.
DR EMBL; AB209118; BAD92355.1; -; mRNA.
DR EMBL; AK294285; BAG57570.1; -; mRNA.
DR EMBL; AL390777; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL445532; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL596132; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471089; EAW62688.1; -; Genomic_DNA.
DR EMBL; BC031835; AAH31835.1; -; mRNA.
DR CCDS; CCDS35050.1; -. [Q16620-1]
DR CCDS; CCDS35051.1; -. [Q16620-5]
DR CCDS; CCDS35052.1; -. [Q16620-3]
DR CCDS; CCDS35053.1; -. [Q16620-2]
DR CCDS; CCDS6671.1; -. [Q16620-4]
DR PIR; A56853; A56853.
DR PIR; I73631; I73631.
DR RefSeq; NP_001007098.1; NM_001007097.2. [Q16620-2]
DR RefSeq; NP_001018074.1; NM_001018064.2. [Q16620-1]
DR RefSeq; NP_001018075.1; NM_001018065.2. [Q16620-5]
DR RefSeq; NP_001018076.1; NM_001018066.2. [Q16620-3]
DR RefSeq; NP_006171.2; NM_006180.4. [Q16620-4]
DR RefSeq; XP_005252058.1; XM_005252001.2. [Q16620-4]
DR RefSeq; XP_005252060.1; XM_005252003.2. [Q16620-4]
DR RefSeq; XP_005252061.1; XM_005252004.2. [Q16620-4]
DR RefSeq; XP_005252063.1; XM_005252006.3. [Q16620-5]
DR RefSeq; XP_005252064.1; XM_005252007.3.
DR RefSeq; XP_011517020.1; XM_011518718.2. [Q16620-1]
DR RefSeq; XP_011517022.1; XM_011518720.2. [Q16620-3]
DR RefSeq; XP_016870240.1; XM_017014751.1. [Q16620-4]
DR RefSeq; XP_016870241.1; XM_017014752.1. [Q16620-1]
DR RefSeq; XP_016870242.1; XM_017014753.1. [Q16620-1]
DR RefSeq; XP_016870243.1; XM_017014754.1.
DR RefSeq; XP_016870244.1; XM_017014755.1. [Q16620-5]
DR RefSeq; XP_016870245.1; XM_017014756.1.
DR RefSeq; XP_016870246.1; XM_017014757.1.
DR RefSeq; XP_016870247.1; XM_017014758.1.
DR RefSeq; XP_016870248.1; XM_017014759.1.
DR RefSeq; XP_016870249.1; XM_017014760.1. [Q16620-2]
DR RefSeq; XP_016870250.1; XM_017014761.1.
DR PDB; 1HCF; X-ray; 2.70 A; X/Y=286-383.
DR PDB; 1WWB; X-ray; 2.10 A; X=283-385.
DR PDB; 2MFQ; NMR; -; B=497-519.
DR PDB; 4ASZ; X-ray; 1.70 A; A=527-822.
DR PDB; 4AT3; X-ray; 1.77 A; A=527-822.
DR PDB; 4AT4; X-ray; 2.36 A; A=527-822.
DR PDB; 4AT5; X-ray; 1.71 A; A=527-822.
DR PDB; 5MO9; X-ray; 2.59 A; X=278-426.
DR PDBsum; 1HCF; -.
DR PDBsum; 1WWB; -.
DR PDBsum; 2MFQ; -.
DR PDBsum; 4ASZ; -.
DR PDBsum; 4AT3; -.
DR PDBsum; 4AT4; -.
DR PDBsum; 4AT5; -.
DR PDBsum; 5MO9; -.
DR AlphaFoldDB; Q16620; -.
DR SMR; Q16620; -.
DR BioGRID; 110970; 37.
DR DIP; DIP-5720N; -.
DR IntAct; Q16620; 12.
DR STRING; 9606.ENSP00000277120; -.
DR BindingDB; Q16620; -.
DR ChEMBL; CHEMBL4898; -.
DR DrugBank; DB00321; Amitriptyline.
DR DrugBank; DB11986; Entrectinib.
DR DrugBank; DB11823; Esketamine.
DR DrugBank; DB12010; Fostamatinib.
DR DrugBank; DB14723; Larotrectinib.
DR DrugCentral; Q16620; -.
DR GuidetoPHARMACOLOGY; 1818; -.
DR TCDB; 8.A.23.1.38; the basigin (basigin) family.
DR GlyConnect; 1029; 12 N-Linked glycans (7 sites).
DR GlyGen; Q16620; 13 sites, 13 N-linked glycans (7 sites), 1 O-linked glycan (1 site).
DR iPTMnet; Q16620; -.
DR PhosphoSitePlus; Q16620; -.
DR BioMuta; NTRK2; -.
DR DMDM; 2497560; -.
DR EPD; Q16620; -.
DR jPOST; Q16620; -.
DR MassIVE; Q16620; -.
DR PaxDb; Q16620; -.
DR PeptideAtlas; Q16620; -.
DR PRIDE; Q16620; -.
DR ProteomicsDB; 60955; -. [Q16620-1]
DR ProteomicsDB; 60956; -. [Q16620-2]
DR ProteomicsDB; 60957; -. [Q16620-3]
DR ProteomicsDB; 60958; -. [Q16620-4]
DR ProteomicsDB; 60959; -. [Q16620-5]
DR ProteomicsDB; 60960; -. [Q16620-6]
DR ProteomicsDB; 60961; -. [Q16620-7]
DR ABCD; Q16620; 146 sequenced antibodies.
DR Antibodypedia; 2081; 1327 antibodies from 48 providers.
DR DNASU; 4915; -.
DR Ensembl; ENST00000277120.8; ENSP00000277120.3; ENSG00000148053.18. [Q16620-4]
DR Ensembl; ENST00000304053.11; ENSP00000306167.7; ENSG00000148053.18. [Q16620-3]
DR Ensembl; ENST00000359847.4; ENSP00000352906.3; ENSG00000148053.18. [Q16620-2]
DR Ensembl; ENST00000376208.6; ENSP00000365381.1; ENSG00000148053.18. [Q16620-3]
DR Ensembl; ENST00000376213.6; ENSP00000365386.1; ENSG00000148053.18. [Q16620-1]
DR Ensembl; ENST00000395882.6; ENSP00000379221.1; ENSG00000148053.18. [Q16620-2]
DR Ensembl; ENST00000685720.1; ENSP00000509031.1; ENSG00000148053.18. [Q16620-5]
DR Ensembl; ENST00000686259.1; ENSP00000509743.1; ENSG00000148053.18. [Q16620-1]
DR Ensembl; ENST00000686322.1; ENSP00000510032.1; ENSG00000148053.18. [Q16620-7]
DR Ensembl; ENST00000686324.1; ENSP00000510134.1; ENSG00000148053.18. [Q16620-4]
DR Ensembl; ENST00000686443.1; ENSP00000509093.1; ENSG00000148053.18. [Q16620-3]
DR Ensembl; ENST00000686496.1; ENSP00000510060.1; ENSG00000148053.18. [Q16620-1]
DR Ensembl; ENST00000687148.1; ENSP00000510717.1; ENSG00000148053.18. [Q16620-2]
DR Ensembl; ENST00000687596.1; ENSP00000509999.1; ENSG00000148053.18. [Q16620-2]
DR Ensembl; ENST00000687636.1; ENSP00000508829.1; ENSG00000148053.18. [Q16620-5]
DR Ensembl; ENST00000688013.1; ENSP00000508443.1; ENSG00000148053.18. [Q16620-2]
DR Ensembl; ENST00000689685.1; ENSP00000509169.1; ENSG00000148053.18. [Q16620-2]
DR Ensembl; ENST00000689815.1; ENSP00000510451.1; ENSG00000148053.18. [Q16620-2]
DR Ensembl; ENST00000690281.1; ENSP00000510757.1; ENSG00000148053.18. [Q16620-2]
DR Ensembl; ENST00000691415.1; ENSP00000509058.1; ENSG00000148053.18. [Q16620-2]
DR Ensembl; ENST00000691788.1; ENSP00000509401.1; ENSG00000148053.18. [Q16620-1]
DR Ensembl; ENST00000692181.1; ENSP00000510619.1; ENSG00000148053.18. [Q16620-1]
DR Ensembl; ENST00000692389.1; ENSP00000508497.1; ENSG00000148053.18. [Q16620-2]
DR Ensembl; ENST00000692506.1; ENSP00000508622.1; ENSG00000148053.18. [Q16620-2]
DR Ensembl; ENST00000692762.1; ENSP00000510071.1; ENSG00000148053.18. [Q16620-2]
DR Ensembl; ENST00000693109.1; ENSP00000509456.1; ENSG00000148053.18. [Q16620-2]
DR Ensembl; ENST00000693539.1; ENSP00000510640.1; ENSG00000148053.18. [Q16620-5]
DR GeneID; 4915; -.
DR KEGG; hsa:4915; -.
DR MANE-Select; ENST00000277120.8; ENSP00000277120.3; NM_006180.6; NP_006171.2. [Q16620-4]
DR UCSC; uc004anz.1; human. [Q16620-1]
DR CTD; 4915; -.
DR DisGeNET; 4915; -.
DR GeneCards; NTRK2; -.
DR HGNC; HGNC:8032; NTRK2.
DR HPA; ENSG00000148053; Tissue enhanced (brain, thyroid gland).
DR MalaCards; NTRK2; -.
DR MIM; 600456; gene.
DR MIM; 613886; phenotype.
DR MIM; 617830; phenotype.
DR neXtProt; NX_Q16620; -.
DR OpenTargets; ENSG00000148053; -.
DR Orphanet; 3451; Infantile spasms syndrome.
DR Orphanet; 442835; Non-specific early-onset epileptic encephalopathy.
DR Orphanet; 251615; Pilomyxoid astrocytoma.
DR PharmGKB; PA31818; -.
DR VEuPathDB; HostDB:ENSG00000148053; -.
DR eggNOG; KOG1026; Eukaryota.
DR GeneTree; ENSGT00940000155181; -.
DR HOGENOM; CLU_000288_74_1_1; -.
DR InParanoid; Q16620; -.
DR OMA; TCSCEIM; -.
DR PhylomeDB; Q16620; -.
DR TreeFam; TF106465; -.
DR BRENDA; 2.7.10.1; 2681.
DR PathwayCommons; Q16620; -.
DR Reactome; R-HSA-187024; NGF-independant TRKA activation.
DR Reactome; R-HSA-9024909; BDNF activates NTRK2 (TRKB) signaling.
DR Reactome; R-HSA-9025046; NTF3 activates NTRK2 (TRKB) signaling.
DR Reactome; R-HSA-9026357; NTF4 activates NTRK2 (TRKB) signaling.
DR Reactome; R-HSA-9026519; Activated NTRK2 signals through RAS.
DR Reactome; R-HSA-9026527; Activated NTRK2 signals through PLCG1.
DR Reactome; R-HSA-9028335; Activated NTRK2 signals through PI3K.
DR Reactome; R-HSA-9028731; Activated NTRK2 signals through FRS2 and FRS3.
DR Reactome; R-HSA-9032500; Activated NTRK2 signals through FYN.
DR Reactome; R-HSA-9032759; NTRK2 activates RAC1.
DR Reactome; R-HSA-9032845; Activated NTRK2 signals through CDK5.
DR SignaLink; Q16620; -.
DR SIGNOR; Q16620; -.
DR BioGRID-ORCS; 4915; 10 hits in 1102 CRISPR screens.
DR ChiTaRS; NTRK2; human.
DR EvolutionaryTrace; Q16620; -.
DR GeneWiki; TrkB_receptor; -.
DR GenomeRNAi; 4915; -.
DR Pharos; Q16620; Tclin.
DR PRO; PR:Q16620; -.
DR Proteomes; UP000005640; Chromosome 9.
DR RNAct; Q16620; protein.
DR Bgee; ENSG00000148053; Expressed in cranial nerve II and 194 other tissues.
DR ExpressionAtlas; Q16620; baseline and differential.
DR Genevisible; Q16620; HS.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0030424; C:axon; ISS:UniProtKB.
DR GO; GO:0043679; C:axon terminus; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; IEA:Ensembl.
DR GO; GO:0030425; C:dendrite; ISS:UniProtKB.
DR GO; GO:0043197; C:dendritic spine; IBA:GO_Central.
DR GO; GO:0005769; C:early endosome; ISS:UniProtKB.
DR GO; GO:0031901; C:early endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005887; C:integral component of plasma membrane; IDA:UniProtKB.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:HPA.
DR GO; GO:0014069; C:postsynaptic density; ISS:ARUK-UCL.
DR GO; GO:0043235; C:receptor complex; IDA:MGI.
DR GO; GO:0043195; C:terminal bouton; IEA:Ensembl.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0048403; F:brain-derived neurotrophic factor binding; ISS:UniProtKB.
DR GO; GO:0060175; F:brain-derived neurotrophic factor receptor activity; IMP:UniProtKB.
DR GO; GO:0043121; F:neurotrophin binding; IDA:UniProtKB.
DR GO; GO:0005030; F:neurotrophin receptor activity; IBA:GO_Central.
DR GO; GO:0002020; F:protease binding; IPI:ARUK-UCL.
DR GO; GO:0042803; F:protein homodimerization activity; ISS:UniProtKB.
DR GO; GO:0004714; F:transmembrane receptor protein tyrosine kinase activity; IBA:GO_Central.
DR GO; GO:0031547; P:brain-derived neurotrophic factor receptor signaling pathway; IMP:UniProtKB.
DR GO; GO:0071230; P:cellular response to amino acid stimulus; IEA:Ensembl.
DR GO; GO:1990416; P:cellular response to brain-derived neurotrophic factor stimulus; IBA:GO_Central.
DR GO; GO:1990090; P:cellular response to nerve growth factor stimulus; IBA:GO_Central.
DR GO; GO:0021954; P:central nervous system neuron development; ISS:UniProtKB.
DR GO; GO:0021987; P:cerebral cortex development; ISS:UniProtKB.
DR GO; GO:0007623; P:circadian rhythm; IEA:Ensembl.
DR GO; GO:0007631; P:feeding behavior; IEA:Ensembl.
DR GO; GO:0014047; P:glutamate secretion; IEA:Ensembl.
DR GO; GO:0007612; P:learning; ISS:UniProtKB.
DR GO; GO:0060291; P:long-term synaptic potentiation; IEA:Ensembl.
DR GO; GO:0042490; P:mechanoreceptor differentiation; IEA:Ensembl.
DR GO; GO:0022011; P:myelination in peripheral nervous system; IEA:Ensembl.
DR GO; GO:1902430; P:negative regulation of amyloid-beta formation; IGI:ARUK-UCL.
DR GO; GO:2000811; P:negative regulation of anoikis; IEA:Ensembl.
DR GO; GO:0043524; P:negative regulation of neuron apoptotic process; ISS:UniProtKB.
DR GO; GO:0030182; P:neuron differentiation; ISS:UniProtKB.
DR GO; GO:0001764; P:neuron migration; ISS:UniProtKB.
DR GO; GO:0019227; P:neuronal action potential propagation; IEA:Ensembl.
DR GO; GO:0048709; P:oligodendrocyte differentiation; IEA:Ensembl.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; IEA:Ensembl.
DR GO; GO:0048935; P:peripheral nervous system neuron development; IEA:Ensembl.
DR GO; GO:0050772; P:positive regulation of axonogenesis; ISS:UniProtKB.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; ISS:UniProtKB.
DR GO; GO:0010628; P:positive regulation of gene expression; ISS:UniProtKB.
DR GO; GO:0033674; P:positive regulation of kinase activity; IBA:GO_Central.
DR GO; GO:0043410; P:positive regulation of MAPK cascade; ISS:UniProtKB.
DR GO; GO:0010976; P:positive regulation of neuron projection development; ISS:UniProtKB.
DR GO; GO:0033138; P:positive regulation of peptidyl-serine phosphorylation; IEA:Ensembl.
DR GO; GO:0014068; P:positive regulation of phosphatidylinositol 3-kinase signaling; ISS:UniProtKB.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; TAS:BHF-UCL.
DR GO; GO:0051965; P:positive regulation of synapse assembly; IEA:Ensembl.
DR GO; GO:0046777; P:protein autophosphorylation; ISS:UniProtKB.
DR GO; GO:0043087; P:regulation of GTPase activity; ISS:UniProtKB.
DR GO; GO:0051896; P:regulation of protein kinase B signaling; IBA:GO_Central.
DR GO; GO:0046548; P:retinal rod cell development; IEA:Ensembl.
DR GO; GO:0099183; P:trans-synaptic signaling by BDNF, modulating synaptic transmission; IEA:Ensembl.
DR GO; GO:0099551; P:trans-synaptic signaling by neuropeptide, modulating synaptic transmission; IBA:GO_Central.
DR GO; GO:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; IBA:GO_Central.
DR GO; GO:0001570; P:vasculogenesis; IEA:Ensembl.
DR Gene3D; 2.60.40.10; -; 2.
DR Gene3D; 3.80.10.10; -; 1.
DR IDEAL; IID00672; -.
DR InterPro; IPR000483; Cys-rich_flank_reg_C.
DR InterPro; IPR007110; Ig-like_dom.
DR InterPro; IPR036179; Ig-like_dom_sf.
DR InterPro; IPR013783; Ig-like_fold.
DR InterPro; IPR013098; Ig_I-set.
DR InterPro; IPR003599; Ig_sub.
DR InterPro; IPR003598; Ig_sub2.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR001611; Leu-rich_rpt.
DR InterPro; IPR032675; LRR_dom_sf.
DR InterPro; IPR000372; LRRNT.
DR InterPro; IPR020777; NTRK.
DR InterPro; IPR020455; NTRK2.
DR InterPro; IPR031635; NTRK_LRRCT.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR001245; Ser-Thr/Tyr_kinase_cat_dom.
DR InterPro; IPR008266; Tyr_kinase_AS.
DR InterPro; IPR020635; Tyr_kinase_cat_dom.
DR InterPro; IPR002011; Tyr_kinase_rcpt_2_CS.
DR Pfam; PF07679; I-set; 2.
DR Pfam; PF13855; LRR_8; 1.
DR Pfam; PF16920; LRRCT_2; 1.
DR Pfam; PF01462; LRRNT; 1.
DR Pfam; PF07714; PK_Tyr_Ser-Thr; 1.
DR PRINTS; PR01939; NTKRECEPTOR.
DR PRINTS; PR01941; NTKRECEPTOR2.
DR PRINTS; PR00109; TYRKINASE.
DR SMART; SM00409; IG; 1.
DR SMART; SM00408; IGc2; 1.
DR SMART; SM00082; LRRCT; 1.
DR SMART; SM00013; LRRNT; 1.
DR SMART; SM00219; TyrKc; 1.
DR SUPFAM; SSF48726; SSF48726; 2.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS50835; IG_LIKE; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00109; PROTEIN_KINASE_TYR; 1.
DR PROSITE; PS00239; RECEPTOR_TYR_KIN_II; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; ATP-binding; Cell membrane;
KW Cell projection; Cytoplasm; Developmental protein; Differentiation;
KW Disease variant; Disulfide bond; Endosome; Epilepsy; Glycoprotein;
KW Immunoglobulin domain; Kinase; Leucine-rich repeat; Membrane; Neurogenesis;
KW Nucleotide-binding; Obesity; Phosphoprotein; Receptor; Reference proteome;
KW Repeat; Signal; Synapse; Transferase; Transmembrane; Transmembrane helix;
KW Tyrosine-protein kinase; Ubl conjugation.
FT SIGNAL 1..31
FT CHAIN 32..822
FT /note="BDNF/NT-3 growth factors receptor"
FT /id="PRO_0000016727"
FT TOPO_DOM 32..430
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 431..454
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 455..822
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 32..61
FT /note="LRRNT"
FT REPEAT 92..113
FT /note="LRR 1"
FT REPEAT 116..137
FT /note="LRR 2"
FT DOMAIN 148..196
FT /note="LRRCT"
FT DOMAIN 197..282
FT /note="Ig-like C2-type 1"
FT DOMAIN 295..365
FT /note="Ig-like C2-type 2"
FT DOMAIN 538..807
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 455..466
FT /note="Interaction with MAPK8IP3/JIP3"
FT /evidence="ECO:0000250|UniProtKB:Q63604"
FT REGION 475..498
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 475..496
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 676
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10028"
FT BINDING 544..552
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 572
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT SITE 516
FT /note="Interaction with SHC1"
FT /evidence="ECO:0000250"
FT SITE 706
FT /note="Interaction with SH2D1A"
FT /evidence="ECO:0000250"
FT SITE 817
FT /note="Interaction with PLCG1"
FT /evidence="ECO:0000250"
FT MOD_RES 516
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:P15209"
FT MOD_RES 702
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:Q63604"
FT MOD_RES 706
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:Q63604"
FT MOD_RES 707
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:Q63604"
FT MOD_RES 817
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:Q63604"
FT CARBOHYD 67
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:16335952,
FT ECO:0000269|PubMed:7574684"
FT CARBOHYD 95
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:7574684"
FT CARBOHYD 121
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:16335952,
FT ECO:0000269|PubMed:7574684"
FT CARBOHYD 178
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:7574684"
FT CARBOHYD 205
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:7574684"
FT CARBOHYD 241
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:7574684"
FT CARBOHYD 254
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:16335952,
FT ECO:0000269|PubMed:7574684"
FT CARBOHYD 280
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:7574684"
FT CARBOHYD 325
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 338
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:7574684"
FT CARBOHYD 412
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:7574684"
FT DISULFID 32..38
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114,
FT ECO:0000269|PubMed:7574684"
FT DISULFID 36..45
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114,
FT ECO:0000269|PubMed:7574684"
FT DISULFID 152..176
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114,
FT ECO:0000269|PubMed:7574684"
FT DISULFID 154..194
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114,
FT ECO:0000269|PubMed:7574684"
FT DISULFID 218..266
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114,
FT ECO:0000269|PubMed:7574684"
FT DISULFID 302..345
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114,
FT ECO:0000269|PubMed:10388563, ECO:0000269|PubMed:11738045,
FT ECO:0000269|PubMed:7574684, ECO:0007744|PDB:1HCF,
FT ECO:0007744|PDB:1WWB, ECO:0007744|PDB:5MO9"
FT VAR_SEQ 1..156
FT /note="Missing (in isoform TrkB-N-T1)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_042177"
FT VAR_SEQ 465
FT /note="K -> KDFSWFGFGKVKSRQGV (in isoform 4 and isoform 5)"
FT /evidence="ECO:0000303|PubMed:11798182"
FT /id="VSP_041942"
FT VAR_SEQ 467..477
FT /note="PASVISNDDDS -> FVLFHKIPLDG (in isoform TrkB-T1 and
FT isoform TrkB-N-T1)"
FT /evidence="ECO:0000303|PubMed:11798182,
FT ECO:0000303|PubMed:14702039, ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:7823156, ECO:0000303|PubMed:7936202,
FT ECO:0000303|Ref.5"
FT /id="VSP_002901"
FT VAR_SEQ 478..822
FT /note="Missing (in isoform TrkB-T1 and isoform TrkB-N-T1)"
FT /evidence="ECO:0000303|PubMed:11798182,
FT ECO:0000303|PubMed:14702039, ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:7823156, ECO:0000303|PubMed:7936202,
FT ECO:0000303|Ref.5"
FT /id="VSP_002902"
FT VAR_SEQ 529..537
FT /note="FVQHIKRHN -> WPRGSPKTA (in isoform TrkB-T-Shc and
FT isoform 5)"
FT /evidence="ECO:0000303|PubMed:11798182"
FT /id="VSP_002903"
FT VAR_SEQ 538..822
FT /note="Missing (in isoform TrkB-T-Shc and isoform 5)"
FT /evidence="ECO:0000303|PubMed:11798182"
FT /id="VSP_002904"
FT VAR_SEQ 710..735
FT /note="GGHTMLPIRWMPPESIMYRKFTTESD -> SSCADQRPQGPLSLRDPCCICL
FT LRLS (in isoform TrkB-T-TK)"
FT /evidence="ECO:0000303|Ref.7"
FT /id="VSP_042178"
FT VAR_SEQ 736..822
FT /note="Missing (in isoform TrkB-T-TK)"
FT /evidence="ECO:0000303|Ref.7"
FT /id="VSP_042179"
FT VARIANT 138
FT /note="L -> F (in a lung adenocarcinoma sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041470"
FT VARIANT 309
FT /note="G -> R"
FT /evidence="ECO:0000269|Ref.5"
FT /id="VAR_016320"
FT VARIANT 338
FT /note="N -> Y (in dbSNP:rs1047856)"
FT /id="VAR_011973"
FT VARIANT 434
FT /note="Y -> C (in DEE58; unknown pathological significance;
FT dbSNP:rs886041091)"
FT /evidence="ECO:0000269|PubMed:29100083"
FT /id="VAR_080659"
FT VARIANT 444..822
FT /note="Missing (in OBHD)"
FT /evidence="ECO:0000269|PubMed:27884935"
FT /id="VAR_080660"
FT VARIANT 545
FT /note="G -> V (in dbSNP:rs1075108)"
FT /id="VAR_049715"
FT VARIANT 697
FT /note="M -> I (in a lung carcinoma sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:18293376"
FT /id="VAR_046518"
FT VARIANT 699
FT /note="R -> G (in a lung carcinoma sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:18293376"
FT /id="VAR_046519"
FT VARIANT 704
FT /note="T -> I (in OBHD; unknown pathological significance;
FT dbSNP:rs1554774973)"
FT /evidence="ECO:0000269|PubMed:29100083"
FT /id="VAR_080661"
FT VARIANT 706
FT /note="Y -> C (in OBHD; expressed normally on the cell
FT surface; results in markedly impaired ligand-induced
FT phosphorylation as well as impaired downstream MAPK1
FT phosphorylation; dbSNP:rs121434633)"
FT /evidence="ECO:0000269|PubMed:15494731"
FT /id="VAR_065890"
FT VARIANT 718
FT /note="R -> C (in a lung carcinoma sample; somatic
FT mutation; dbSNP:rs1324578301)"
FT /evidence="ECO:0000269|PubMed:18293376"
FT /id="VAR_046520"
FT STRAND 285..292
FT /evidence="ECO:0007829|PDB:5MO9"
FT STRAND 300..308
FT /evidence="ECO:0007829|PDB:1WWB"
FT STRAND 314..319
FT /evidence="ECO:0007829|PDB:1WWB"
FT STRAND 322..324
FT /evidence="ECO:0007829|PDB:1WWB"
FT STRAND 328..337
FT /evidence="ECO:0007829|PDB:1WWB"
FT STRAND 339..350
FT /evidence="ECO:0007829|PDB:1WWB"
FT HELIX 353..355
FT /evidence="ECO:0007829|PDB:1WWB"
FT STRAND 357..364
FT /evidence="ECO:0007829|PDB:1WWB"
FT STRAND 369..376
FT /evidence="ECO:0007829|PDB:1WWB"
FT STRAND 380..382
FT /evidence="ECO:0007829|PDB:5MO9"
FT STRAND 500..503
FT /evidence="ECO:0007829|PDB:2MFQ"
FT STRAND 506..512
FT /evidence="ECO:0007829|PDB:2MFQ"
FT TURN 515..517
FT /evidence="ECO:0007829|PDB:2MFQ"
FT HELIX 535..537
FT /evidence="ECO:0007829|PDB:4ASZ"
FT STRAND 538..545
FT /evidence="ECO:0007829|PDB:4ASZ"
FT STRAND 552..557
FT /evidence="ECO:0007829|PDB:4ASZ"
FT STRAND 567..574
FT /evidence="ECO:0007829|PDB:4ASZ"
FT HELIX 579..592
FT /evidence="ECO:0007829|PDB:4ASZ"
FT STRAND 603..607
FT /evidence="ECO:0007829|PDB:4ASZ"
FT STRAND 609..618
FT /evidence="ECO:0007829|PDB:4ASZ"
FT HELIX 625..631
FT /evidence="ECO:0007829|PDB:4ASZ"
FT HELIX 634..638
FT /evidence="ECO:0007829|PDB:4ASZ"
FT STRAND 641..643
FT /evidence="ECO:0007829|PDB:4AT5"
FT HELIX 650..669
FT /evidence="ECO:0007829|PDB:4ASZ"
FT HELIX 679..681
FT /evidence="ECO:0007829|PDB:4ASZ"
FT STRAND 682..684
FT /evidence="ECO:0007829|PDB:4ASZ"
FT HELIX 686..688
FT /evidence="ECO:0007829|PDB:4ASZ"
FT STRAND 690..692
FT /evidence="ECO:0007829|PDB:4ASZ"
FT HELIX 698..701
FT /evidence="ECO:0007829|PDB:4ASZ"
FT HELIX 703..705
FT /evidence="ECO:0007829|PDB:4ASZ"
FT STRAND 707..709
FT /evidence="ECO:0007829|PDB:4ASZ"
FT TURN 710..712
FT /evidence="ECO:0007829|PDB:4ASZ"
FT STRAND 713..715
FT /evidence="ECO:0007829|PDB:4ASZ"
FT HELIX 717..719
FT /evidence="ECO:0007829|PDB:4ASZ"
FT HELIX 722..727
FT /evidence="ECO:0007829|PDB:4ASZ"
FT HELIX 732..747
FT /evidence="ECO:0007829|PDB:4ASZ"
FT TURN 748..750
FT /evidence="ECO:0007829|PDB:4ASZ"
FT TURN 753..756
FT /evidence="ECO:0007829|PDB:4ASZ"
FT HELIX 759..768
FT /evidence="ECO:0007829|PDB:4ASZ"
FT HELIX 780..789
FT /evidence="ECO:0007829|PDB:4ASZ"
FT HELIX 794..796
FT /evidence="ECO:0007829|PDB:4ASZ"
FT HELIX 800..813
FT /evidence="ECO:0007829|PDB:4ASZ"
SQ SEQUENCE 822 AA; 91999 MW; 2FEB9159948F0D13 CRC64;
MSSWIRWHGP AMARLWGFCW LVVGFWRAAF ACPTSCKCSA SRIWCSDPSP GIVAFPRLEP
NSVDPENITE IFIANQKRLE IINEDDVEAY VGLRNLTIVD SGLKFVAHKA FLKNSNLQHI
NFTRNKLTSL SRKHFRHLDL SELILVGNPF TCSCDIMWIK TLQEAKSSPD TQDLYCLNES
SKNIPLANLQ IPNCGLPSAN LAAPNLTVEE GKSITLSCSV AGDPVPNMYW DVGNLVSKHM
NETSHTQGSL RITNISSDDS GKQISCVAEN LVGEDQDSVN LTVHFAPTIT FLESPTSDHH
WCIPFTVKGN PKPALQWFYN GAILNESKYI CTKIHVTNHT EYHGCLQLDN PTHMNNGDYT
LIAKNEYGKD EKQISAHFMG WPGIDDGANP NYPDVIYEDY GTAANDIGDT TNRSNEIPST
DVTDKTGREH LSVYAVVVIA SVVGFCLLVM LFLLKLARHS KFGMKGPASV ISNDDDSASP
LHHISNGSNT PSSSEGGPDA VIIGMTKIPV IENPQYFGIT NSQLKPDTFV QHIKRHNIVL
KRELGEGAFG KVFLAECYNL CPEQDKILVA VKTLKDASDN ARKDFHREAE LLTNLQHEHI
VKFYGVCVEG DPLIMVFEYM KHGDLNKFLR AHGPDAVLMA EGNPPTELTQ SQMLHIAQQI
AAGMVYLASQ HFVHRDLATR NCLVGENLLV KIGDFGMSRD VYSTDYYRVG GHTMLPIRWM
PPESIMYRKF TTESDVWSLG VVLWEIFTYG KQPWYQLSNN EVIECITQGR VLQRPRTCPQ
EVYELMLGCW QREPHMRKNI KGIHTLLQNL AKASPVYLDI LG
