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 27-MAR-2024, entry version 241. 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 INTERACTION WITH SLITRK2. RX PubMed=35840571; DOI=10.1038/s41467-022-31566-z; RA El Chehadeh S., Han K.A., Kim D., Jang G., Bakhtiari S., Lim D., Kim H.Y., RA Kim J., Kim H., Wynn J., Chung W.K., Vitiello G., Cutcutache I., Page M., RA Gecz J., Harper K., Han A.R., Kim H.M., Wessels M., Bayat A., Jaen A.F., RA Selicorni A., Maitz S., de Brouwer A.P.M., Silfhout A.V., Armstrong M., RA Symonds J., Kuery S., Isidor B., Cogne B., Nizon M., Feger C., Muller J., RA Torti E., Grange D.K., Willems M., Kruer M.C., Ko J., Piton A., Um J.W.; RT "SLITRK2 variants associated with neurodevelopmental disorders impair RT excitatory synaptic function and cognition in mice."; RL Nat. Commun. 13:4112-4112(2022). RN [18] 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 [19] 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 [20] 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 [21] 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 [22] RP VARIANT DEE58 CYS-434, VARIANT OBHD ILE-704, AND INVOLVEMENT IN DEE58. 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). Interacts with CC SLITRK2 (PubMed:35840571). {ECO:0000250|UniProtKB:P04629, CC ECO:0000250|UniProtKB:P15209, ECO:0000250|UniProtKB:Q63604, CC ECO:0000269|PubMed:10092678, ECO:0000269|PubMed:11738045, CC ECO:0000269|PubMed:35840571}. CC -!- INTERACTION: CC Q16620; Q16288: NTRK3; NbExp=3; IntAct=EBI-3904881, EBI-3936704; 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="https://atlasgeneticsoncology.org/gene/41589/NTRK2"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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 CCDS; CCDS94429.1; -. [Q16620-7] 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. 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. 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; 130. DR DIP; DIP-5720N; -. DR IntAct; Q16620; 105. 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 GlyCosmos; Q16620; 13 sites, 14 glycans. 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; 9606-ENSP00000277120; -. DR PeptideAtlas; 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; 1684 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 AGR; HGNC:8032; -. 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; HIAMQIA; -. DR OrthoDB; 1614410at2759; -. 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 1188 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 196 other cell types or tissues. DR ExpressionAtlas; Q16620; baseline and differential. 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: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:0002020; F:protease binding; IPI:ARUK-UCL. DR GO; GO:0042803; F:protein homodimerization activity; ISS:UniProtKB. 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: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: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: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:0051897; P:positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction; 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 phosphatidylinositol 3-kinase/protein kinase B signal transduction; 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 CDD; cd05855; IgI_TrkB_d5; 1. DR CDD; cd05093; PTKc_TrkB; 1. DR Gene3D; 2.60.40.10; Immunoglobulins; 2. DR Gene3D; 3.80.10.10; Ribonuclease Inhibitor; 1. DR Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 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 PANTHER; PTHR24416:SF136; BDNF_NT-3 GROWTH FACTORS RECEPTOR; 1. DR PANTHER; PTHR24416; TYROSINE-PROTEIN KINASE RECEPTOR; 1. 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; Immunoglobulin; 2. DR SUPFAM; SSF52058; L domain-like; 1. DR SUPFAM; SSF56112; Protein kinase-like (PK-like); 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. DR Genevisible; Q16620; HS. 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; uncertain 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; uncertain 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 //