ID NTRK2_RAT Reviewed; 821 AA.
AC Q63604; Q63605; Q63606;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 27-MAR-2024, entry version 208.
DE RecName: Full=BDNF/NT-3 growth factors receptor;
DE EC=2.7.10.1 {ECO:0000269|PubMed:8106527, ECO:0000269|PubMed:8627351};
DE AltName: Full=Neurotrophic tyrosine kinase receptor type 2;
DE AltName: Full=TrkB tyrosine kinase;
DE Short=Trk-B;
DE Flags: Precursor;
GN Name=Ntrk2; Synonyms=Trkb;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND ALTERNATIVE SPLICING.
RC TISSUE=Cerebellum;
RX PubMed=1846020; DOI=10.1128/mcb.11.1.143-153.1991;
RA Middlemas D.S., Lindberg R.A., Hunter T.;
RT "trkB, a neural receptor protein-tyrosine kinase: evidence for a full-
RT length and two truncated receptors.";
RL Mol. Cell. Biol. 11:143-153(1991).
RN [2]
RP FUNCTION IN BDNF AND NTF3 SIGNALING, PHOSPHORYLATION, AND SUBCELLULAR
RP LOCATION.
RX PubMed=1645620; DOI=10.1016/0092-8674(91)90396-g;
RA Soppet D., Escandon E., Maragos J., Middlemas D.S., Reid S.W., Blair J.,
RA Burton L.E., Stanton B.R., Kaplan D.R., Hunter T., Nicolics K.,
RA Parada L.F.;
RT "The neurotrophic factors brain-derived neurotrophic factor and
RT neurotrophin-3 are ligands for the trkB tyrosine kinase receptor.";
RL Cell 65:895-903(1991).
RN [3]
RP CATALYTIC ACTIVITY, AND PHOSPHORYLATION AT TYR-701; TYR-705; TYR-706 AND
RP TYR-816.
RX PubMed=8106527; DOI=10.1016/s0021-9258(17)37708-6;
RA Middlemas D.S., Meisenhelder J., Hunter T.;
RT "Identification of TrkB autophosphorylation sites and evidence that
RT phospholipase C-gamma 1 is a substrate of the TrkB receptor.";
RL J. Biol. Chem. 269:5458-5466(1994).
RN [4]
RP ALTERNATIVE SPLICING, HOMODIMERIZATION, SUBUNIT, AUTOPHOSPHORYLATION, AND
RP CATALYTIC ACTIVITY.
RX PubMed=8627351; DOI=10.1523/jneurosci.16-10-03123.1996;
RA Eide F.F., Vining E.R., Eide B.L., Zang K., Wang X.Y., Reichardt L.F.;
RT "Naturally occurring truncated trkB receptors have dominant inhibitory
RT effects on brain-derived neurotrophic factor signaling.";
RL J. Neurosci. 16:3123-3129(1996).
RN [5]
RP INTERACTION WITH SH2B1 AND SH2B2.
RX PubMed=9856458; DOI=10.1016/s0896-6273(00)80620-0;
RA Qian X., Riccio A., Zhang Y., Ginty D.D.;
RT "Identification and characterization of novel substrates of Trk receptors
RT in developing neurons.";
RL Neuron 21:1017-1029(1998).
RN [6]
RP FUNCTION IN CELL PROLIFERATION, FUNCTION IN PHOSPHORYLATION OF SHC1 AND
RP PLCG1, AUTOPHOSPHORYLATION, INTERACTION WITH SHC1; PLCG1 AND PLCG2, AND
RP MUTAGENESIS OF LYS-571; TYR-701; TYR-705 AND TYR-706.
RX PubMed=9582017; DOI=10.1038/sj.onc.1201688;
RA McCarty J.H., Feinstein S.C.;
RT "Activation loop tyrosines contribute varying roles to TrkB
RT autophosphorylation and signal transduction.";
RL Oncogene 16:1691-1700(1998).
RN [7]
RP INTERACTION WITH NGFR.
RX PubMed=9927421; DOI=10.1093/emboj/18.3.616;
RA Bibel M., Hoppe E., Barde Y.A.;
RT "Biochemical and functional interactions between the neurotrophin receptors
RT trk and p75NTR.";
RL EMBO J. 18:616-622(1999).
RN [8]
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 [9]
RP FUNCTION IN PHOSPHORYLATION OF FRS2, INTERACTION WITH SHC1, AND MUTAGENESIS
RP OF TYR-515.
RX PubMed=10196222; DOI=10.1074/jbc.274.16.11321;
RA Easton J.B., Moody N.M., Zhu X., Middlemas D.S.;
RT "Brain-derived neurotrophic factor induces phosphorylation of fibroblast
RT growth factor receptor substrate 2.";
RL J. Biol. Chem. 274:11321-11327(1999).
RN [10]
RP FUNCTION IN AXONOGENESIS AND NEURON SURVIVAL.
RX PubMed=10985347; DOI=10.1016/s0896-6273(00)00035-0;
RA Atwal J.K., Massie B., Miller F.D., Kaplan D.R.;
RT "The TrkB-Shc site signals neuronal survival and local axon growth via MEK
RT and P13-kinase.";
RL Neuron 27:265-277(2000).
RN [11]
RP INTERACTION WITH SQSTM1.
RX PubMed=12471037; DOI=10.1074/jbc.m208468200;
RA Geetha T., Wooten M.W.;
RT "Association of the atypical protein kinase C-interacting protein p62/ZIP
RT with nerve growth factor receptor TrkA regulates receptor trafficking and
RT Erk5 signaling.";
RL J. Biol. Chem. 278:4730-4739(2003).
RN [12]
RP INTERACTION WITH KIDINS220.
RX PubMed=15167895; DOI=10.1038/sj.emboj.7600253;
RA Arevalo J.C., Yano H., Teng K.K., Chao M.V.;
RT "A unique pathway for sustained neurotrophin signaling through an ankyrin-
RT rich membrane-spanning protein.";
RL EMBO J. 23:2358-2368(2004).
RN [13]
RP ACTIVITY REGULATION, INTERACTION WITH SH2D1A, AND MUTAGENESIS OF TYR-705.
RX PubMed=16223723; DOI=10.1074/jbc.m506554200;
RA Lo K.Y., Chin W.H., Ng Y.P., Cheng A.W., Cheung Z.H., Ip N.Y.;
RT "SLAM-associated protein as a potential negative regulator in Trk
RT signaling.";
RL J. Biol. Chem. 280:41744-41752(2005).
RN [14]
RP INTERACTION WITH MAPK8IP3 AND KLC1, AND SUBCELLULAR LOCATION.
RX PubMed=21775604; DOI=10.1523/jneurosci.0436-11.2011;
RA Huang S.H., Duan S., Sun T., Wang J., Zhao L., Geng Z., Yan J., Sun H.J.,
RA Chen Z.Y.;
RT "JIP3 mediates TrkB axonal anterograde transport and enhances BDNF
RT signaling by directly bridging TrkB with kinesin-1.";
RL J. Neurosci. 31:10602-10614(2011).
RN [15]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-95 AND ASN-241, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
RX PubMed=24090084; DOI=10.1021/pr400783j;
RA Parker B.L., Thaysen-Andersen M., Solis N., Scott N.E., Larsen M.R.,
RA Graham M.E., Packer N.H., Cordwell S.J.;
RT "Site-specific glycan-peptide analysis for determination of N-glycoproteome
RT heterogeneity.";
RL J. Proteome Res. 12:5791-5800(2013).
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. Receptor for
CC BDNF/brain-derived neurotrophic factor and NTF4/neurotrophin-4.
CC Alternatively can also bind NTF3/neurotrophin-3 which is less efficient
CC in activating the receptor but regulates neuron survival through NTRK2.
CC Upon ligand-binding, undergoes homodimerization, autophosphorylation
CC and activation. 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 {ECO:0000269|PubMed:10196222, ECO:0000269|PubMed:10985347,
CC ECO:0000269|PubMed:1645620, ECO:0000269|PubMed:9582017}.
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:8106527, ECO:0000269|PubMed:8627351};
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 {ECO:0000269|PubMed:16223723}.
CC -!- SUBUNIT: Exists in a dynamic equilibrium between monomeric (low
CC affinity) and dimeric (high affinity) structures (PubMed:8627351).
CC Interacts (phosphorylated upon activation by BDNF) with SHC1; mediates
CC SHC1 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. Interacts with SORCS2; this interaction is important for
CC normal targeting to post-synaptic densities in response to high-
CC frequency stimulation (By similarity). Interacts (phosphorylated upon
CC ligand-binding) with SH2D1A; regulates NTRK2. Interacts with SQSTM1 and
CC KIDINS220. Interacts (phosphorylated upon ligand-binding) with FRS2;
CC activates the MAPK signaling pathway. Interacts with APPL1 (By
CC similarity). Interacts with MAPK8IP3/JIP3 and KLC1; interaction with
CC KLC1 is mediated by MAPK8IP3/JIP3 (PubMed:21775604). 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 (By similarity). {ECO:0000250|UniProtKB:P15209,
CC ECO:0000250|UniProtKB:Q16620, ECO:0000269|PubMed:10092678,
CC ECO:0000269|PubMed:10196222, ECO:0000269|PubMed:12471037,
CC ECO:0000269|PubMed:15167895, ECO:0000269|PubMed:16223723,
CC ECO:0000269|PubMed:21775604, ECO:0000269|PubMed:8627351,
CC ECO:0000269|PubMed:9582017, ECO:0000269|PubMed:9856458,
CC ECO:0000269|PubMed:9927421}.
CC -!- INTERACTION:
CC Q63604; Q03114: Cdk5; NbExp=5; IntAct=EBI-7287667, EBI-2008531;
CC Q63604; Q04631: Fnta; NbExp=4; IntAct=EBI-7287667, EBI-602447;
CC Q63604; P06536: Nr3c1; NbExp=2; IntAct=EBI-7287667, EBI-1187143;
CC Q63604; O43639: NCK2; Xeno; NbExp=2; IntAct=EBI-7287667, EBI-713635;
CC Q63604; Q8K4V6: Pirb; Xeno; NbExp=3; IntAct=EBI-7287667, EBI-8602514;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:1645620};
CC Single-pass type I membrane protein {ECO:0000269|PubMed:1645620}.
CC Endosome membrane {ECO:0000250|UniProtKB:P15209}; Single-pass type I
CC membrane protein {ECO:0000250|UniProtKB:P15209}. Early endosome
CC membrane {ECO:0000250|UniProtKB:P15209}. Cell projection, axon
CC {ECO:0000269|PubMed:21775604}. Cell projection, dendrite
CC {ECO:0000269|PubMed:21775604}. Cytoplasm, perinuclear region
CC {ECO:0000269|PubMed:21775604}. 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=3;
CC Comment=Additional isoforms seem to exist.;
CC Name=GP145-TrkB;
CC IsoId=Q63604-1; Sequence=Displayed;
CC Name=T1; Synonyms=GP95-TrkB;
CC IsoId=Q63604-2; Sequence=VSP_002910, VSP_002911;
CC Name=T2;
CC IsoId=Q63604-3; Sequence=VSP_002912, VSP_002913;
CC -!- TISSUE SPECIFICITY: Widely expressed in the central and peripheral
CC nervous system. The different forms are differentially expressed in
CC various cell types. Isoform T2 is primarily expressed in neurons.
CC -!- PTM: Phosphorylated. Undergoes ligand-mediated autophosphorylation that
CC is required for interaction with SHC1 and PLCG1 and other downstream
CC effectors. Some isoforms are not phosphorylated.
CC {ECO:0000269|PubMed:1645620, ECO:0000269|PubMed:8106527,
CC ECO:0000269|PubMed:8627351}.
CC -!- PTM: Ubiquitinated. Undergoes polyubiquitination upon activation;
CC regulated by NGFR. Ubiquitination regulates the internalization of the
CC receptor (By similarity). {ECO:0000250}.
CC -!- MISCELLANEOUS: [Isoform T1]: Non-catalytic isoform. {ECO:0000305}.
CC -!- MISCELLANEOUS: [Isoform T2]: 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 ---------------------------------------------------------------------------
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; M55291; AAA42279.1; -; mRNA.
DR EMBL; M55292; AAA42280.1; -; mRNA.
DR EMBL; M55293; AAA42281.1; -; mRNA.
DR PIR; A39667; A39667.
DR PIR; B39667; B39667.
DR PIR; C39667; C39667.
DR RefSeq; NP_001156640.1; NM_001163168.2. [Q63604-2]
DR RefSeq; NP_036863.1; NM_012731.2. [Q63604-1]
DR AlphaFoldDB; Q63604; -.
DR SMR; Q63604; -.
DR BioGRID; 247131; 16.
DR CORUM; Q63604; -.
DR DIP; DIP-5717N; -.
DR IntAct; Q63604; 19.
DR MINT; Q63604; -.
DR STRING; 10116.ENSRNOP00000073595; -.
DR ChEMBL; CHEMBL1795111; -.
DR GlyCosmos; Q63604; 12 sites, 8 glycans.
DR GlyGen; Q63604; 12 sites, 8 N-linked glycans (2 sites).
DR iPTMnet; Q63604; -.
DR PhosphoSitePlus; Q63604; -.
DR PaxDb; 10116-ENSRNOP00000045635; -.
DR Ensembl; ENSRNOT00000042145.3; ENSRNOP00000045635.1; ENSRNOG00000018839.8. [Q63604-1]
DR Ensembl; ENSRNOT00000090914.2; ENSRNOP00000070128.1; ENSRNOG00000018839.8. [Q63604-2]
DR Ensembl; ENSRNOT00060034905; ENSRNOP00060028660; ENSRNOG00060020051. [Q63604-1]
DR Ensembl; ENSRNOT00065043944; ENSRNOP00065036031; ENSRNOG00065025416. [Q63604-1]
DR GeneID; 25054; -.
DR KEGG; rno:25054; -.
DR UCSC; RGD:3213; rat. [Q63604-1]
DR AGR; RGD:3213; -.
DR CTD; 4915; -.
DR RGD; 3213; Ntrk2.
DR eggNOG; KOG1026; Eukaryota.
DR GeneTree; ENSGT00940000155181; -.
DR HOGENOM; CLU_000288_74_1_1; -.
DR InParanoid; Q63604; -.
DR OrthoDB; 1614410at2759; -.
DR PhylomeDB; Q63604; -.
DR TreeFam; TF106465; -.
DR BRENDA; 2.7.10.1; 5301.
DR Reactome; R-RNO-9026527; Activated NTRK2 signals through PLCG1.
DR Reactome; R-RNO-9028731; Activated NTRK2 signals through FRS2 and FRS3.
DR Reactome; R-RNO-9032759; NTRK2 activates RAC1.
DR PRO; PR:Q63604; -.
DR Proteomes; UP000002494; Chromosome 17.
DR Bgee; ENSRNOG00000018839; Expressed in frontal cortex and 15 other cell types or tissues.
DR ExpressionAtlas; Q63604; baseline and differential.
DR Genevisible; Q63604; RN.
DR GO; GO:0030424; C:axon; IDA:UniProtKB.
DR GO; GO:0043679; C:axon terminus; IDA:RGD.
DR GO; GO:0009986; C:cell surface; IDA:RGD.
DR GO; GO:0005829; C:cytosol; ISO:RGD.
DR GO; GO:0030425; C:dendrite; IDA:UniProtKB.
DR GO; GO:0043197; C:dendritic spine; IDA:SynGO.
DR GO; GO:0005769; C:early endosome; ISS:UniProtKB.
DR GO; GO:0031901; C:early endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005768; C:endosome; ISO:RGD.
DR GO; GO:0060076; C:excitatory synapse; IDA:RGD.
DR GO; GO:0098978; C:glutamatergic synapse; IDA:SynGO.
DR GO; GO:0000139; C:Golgi membrane; TAS:Reactome.
DR GO; GO:0030426; C:growth cone; IDA:RGD.
DR GO; GO:0043025; C:neuronal cell body; IDA:RGD.
DR GO; GO:0043204; C:perikaryon; IDA:RGD.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0098794; C:postsynapse; IDA:SynGO.
DR GO; GO:0014069; C:postsynaptic density; ISO:RGD.
DR GO; GO:0045211; C:postsynaptic membrane; IDA:SynGO.
DR GO; GO:0048786; C:presynaptic active zone; IDA:RGD.
DR GO; GO:0043235; C:receptor complex; ISO:RGD.
DR GO; GO:0045202; C:synapse; ISO:RGD.
DR GO; GO:0043195; C:terminal bouton; ISO:RGD.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0048403; F:brain-derived neurotrophic factor binding; IDA:UniProtKB.
DR GO; GO:0060175; F:brain-derived neurotrophic factor receptor activity; IDA:UniProtKB.
DR GO; GO:0043121; F:neurotrophin binding; IDA:UniProtKB.
DR GO; GO:0005030; F:neurotrophin receptor activity; IDA:RGD.
DR GO; GO:0002020; F:protease binding; ISO:RGD.
DR GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB.
DR GO; GO:0004713; F:protein tyrosine kinase activity; TAS:Reactome.
DR GO; GO:0030971; F:receptor tyrosine kinase binding; IPI:RGD.
DR GO; GO:0004675; F:transmembrane receptor protein serine/threonine kinase activity; TAS:Reactome.
DR GO; GO:0004714; F:transmembrane receptor protein tyrosine kinase activity; IMP:RGD.
DR GO; GO:0031547; P:brain-derived neurotrophic factor receptor signaling pathway; IDA:UniProtKB.
DR GO; GO:0035584; P:calcium-mediated signaling using intracellular calcium source; ISO:RGD.
DR GO; GO:0071230; P:cellular response to amino acid stimulus; ISO:RGD.
DR GO; GO:1990416; P:cellular response to brain-derived neurotrophic factor stimulus; IEP:RGD.
DR GO; GO:1990090; P:cellular response to nerve growth factor stimulus; IEP:RGD.
DR GO; GO:0071356; P:cellular response to tumor necrosis factor; IEP:RGD.
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; ISO:RGD.
DR GO; GO:0007631; P:feeding behavior; ISO:RGD.
DR GO; GO:0014047; P:glutamate secretion; ISO:RGD.
DR GO; GO:0007612; P:learning; ISS:UniProtKB.
DR GO; GO:0007616; P:long-term memory; IDA:RGD.
DR GO; GO:0060291; P:long-term synaptic potentiation; ISO:RGD.
DR GO; GO:0042490; P:mechanoreceptor differentiation; ISO:RGD.
DR GO; GO:0022011; P:myelination in peripheral nervous system; ISO:RGD.
DR GO; GO:1902430; P:negative regulation of amyloid-beta formation; ISO:RGD.
DR GO; GO:2000811; P:negative regulation of anoikis; ISO:RGD.
DR GO; GO:0043524; P:negative regulation of neuron apoptotic process; IMP: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; ISO:RGD.
DR GO; GO:0048709; P:oligodendrocyte differentiation; ISO:RGD.
DR GO; GO:0048935; P:peripheral nervous system neuron development; ISO:RGD.
DR GO; GO:0050772; P:positive regulation of axonogenesis; IMP:UniProtKB.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; IDA:UniProtKB.
DR GO; GO:0010628; P:positive regulation of gene expression; ISS:UniProtKB.
DR GO; GO:2000324; P:positive regulation of glucocorticoid receptor signaling pathway; IGI:MGI.
DR GO; GO:0043410; P:positive regulation of MAPK cascade; IMP: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; ISO:RGD.
DR GO; GO:0051897; P:positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction; IMP:UniProtKB.
DR GO; GO:0051965; P:positive regulation of synapse assembly; ISO:RGD.
DR GO; GO:0051968; P:positive regulation of synaptic transmission, glutamatergic; IMP:RGD.
DR GO; GO:0046777; P:protein autophosphorylation; IDA:UniProtKB.
DR GO; GO:0050773; P:regulation of dendrite development; IMP:RGD.
DR GO; GO:0043087; P:regulation of GTPase activity; ISS:UniProtKB.
DR GO; GO:0043408; P:regulation of MAPK cascade; IDA:UniProtKB.
DR GO; GO:0019222; P:regulation of metabolic process; ISO:RGD.
DR GO; GO:0046928; P:regulation of neurotransmitter secretion; IDA:RGD.
DR GO; GO:0051896; P:regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction; ISO:RGD.
DR GO; GO:0010996; P:response to auditory stimulus; IEP:RGD.
DR GO; GO:0009416; P:response to light stimulus; IEP:RGD.
DR GO; GO:0060041; P:retina development in camera-type eye; ISO:RGD.
DR GO; GO:0046548; P:retinal rod cell development; ISO:RGD.
DR GO; GO:0099183; P:trans-synaptic signaling by BDNF, modulating synaptic transmission; ISO:RGD.
DR GO; GO:0099551; P:trans-synaptic signaling by neuropeptide, modulating synaptic transmission; ISO:RGD.
DR GO; GO:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; IBA:GO_Central.
DR GO; GO:0001570; P:vasculogenesis; ISO:RGD.
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 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; 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.
PE 1: Evidence at protein level;
KW Alternative splicing; ATP-binding; Cell membrane; Cell projection;
KW Cytoplasm; Developmental protein; Differentiation; Disulfide bond;
KW Endosome; Glycoprotein; Immunoglobulin domain; Kinase; Leucine-rich repeat;
KW Membrane; Neurogenesis; Nucleotide-binding; Phosphoprotein; Receptor;
KW Reference proteome; Repeat; Signal; Synapse; Transferase; Transmembrane;
KW Transmembrane helix; Tyrosine-protein kinase; Ubl conjugation.
FT SIGNAL 1..31
FT /evidence="ECO:0000250"
FT CHAIN 32..821
FT /note="BDNF/NT-3 growth factors receptor"
FT /id="PRO_0000016729"
FT TOPO_DOM 32..429
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 430..453
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 454..821
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 537..806
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 454..465
FT /note="Interaction with MAPK8IP3/JIP3"
FT /evidence="ECO:0000269|PubMed:21775604"
FT REGION 474..497
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 474..495
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 675
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10028"
FT BINDING 543..551
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 571
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT SITE 515
FT /note="Interaction with SHC1"
FT SITE 705
FT /note="Interaction with SH2D1A"
FT SITE 816
FT /note="Interaction with PLCG1"
FT /evidence="ECO:0000250"
FT MOD_RES 515
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:P15209"
FT MOD_RES 701
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:8106527"
FT MOD_RES 705
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:8106527"
FT MOD_RES 706
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:8106527"
FT MOD_RES 816
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:8106527"
FT CARBOHYD 67
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 95
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0007744|PubMed:24090084"
FT CARBOHYD 121
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 178
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 205
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 241
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0007744|PubMed:24090084"
FT CARBOHYD 254
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 280
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
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:0000255"
FT CARBOHYD 350
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 411
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 32..38
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 36..45
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 152..176
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 154..194
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 218..266
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 302..345
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT VAR_SEQ 466..476
FT /note="PASVISNDDDS -> FVLFHKIPLDG (in isoform T1)"
FT /evidence="ECO:0000305"
FT /id="VSP_002910"
FT VAR_SEQ 466..474
FT /note="PASVISNDD -> KQKCAYFAS (in isoform T2)"
FT /evidence="ECO:0000305"
FT /id="VSP_002912"
FT VAR_SEQ 475..821
FT /note="Missing (in isoform T2)"
FT /evidence="ECO:0000305"
FT /id="VSP_002913"
FT VAR_SEQ 477..821
FT /note="Missing (in isoform T1)"
FT /evidence="ECO:0000305"
FT /id="VSP_002911"
FT MUTAGEN 515
FT /note="Y->F: Loss of interaction with SHC1."
FT /evidence="ECO:0000269|PubMed:10196222"
FT MUTAGEN 571
FT /note="K->A: Loss of kinase activity."
FT /evidence="ECO:0000269|PubMed:9582017"
FT MUTAGEN 701
FT /note="Y->F: Loss of autophosphorylation and altered
FT interaction with SHC1 and PLCG1; when associated with F-705
FT and F-706."
FT /evidence="ECO:0000269|PubMed:9582017"
FT MUTAGEN 705
FT /note="Y->F: Loss of autophosphorylation; when associated
FT with F-701 and F-706."
FT /evidence="ECO:0000269|PubMed:16223723,
FT ECO:0000269|PubMed:9582017"
FT MUTAGEN 706
FT /note="Y->F: Loss of autophosphorylation; when associated
FT with F-701 and F-705."
FT /evidence="ECO:0000269|PubMed:9582017"
SQ SEQUENCE 821 AA; 92186 MW; 0DDACDA212CDAA0E CRC64;
MSPWPRWHGP AMARLWGLCL LVLGFWRASL ACPMSCKCST TRIWCTEPSP GIVAFPRLEP
NSIDPENITE ILIANQKRLE IINEDDVEAY VGLKNLTIVD SGLKFVAYKA FLKNGNLRHI
NFTRNKLTSL SRRHFRHLDL SDLILTGNPF TCSCDIMWLK TLQETKSSPD TQDLYCLNES
SKNTPLANLQ IPNCGLPSAR LAAPNLTVEE GKSVTISCSV GGDPLPTLYW DVGNLVSKHM
NETSHTQGSL RITNISSDDS GKQISCVAEN LVGEDQDSVN LTVHFAPTIT FLESPTSDHH
WCIPFTVRGN PKPALQWFYN GAILNESKYI CTKIHVTNHT EYHGCLQLDN PTHMNNGDYT
LMAKNEYGKD ERQISAHFMG RPGVDYETNP NYPEVLYEDW TTPTDIGDTT NKSNEIPSTD
VADQTNREHL SVYAVVVIAS VVGFCLLVML LLLKLARHSK FGMKGPASVI SNDDDSASPL
HHISNGSNTP SSSEGGPDAV IIGMTKIPVI ENPQYFGITN SQLKPDTFVQ HIKRHNIVLK
RELGEGAFGK VFLAECYNLC PEQDKILVAV KTLKDASDNA RKDFHREAEL LTNLQHEHIV
KFYGVCVEGD PLIMVFEYMK HGDLNKFLRA HGPDAVLMAE GNPPTELTQS QMLHIAQQIA
AGMVYLASQH FVHRDLATRN CLVGENLLVK IGDFGMSRDV YSTDYYRVGG HTMLPIRWMP
PESIMYRKFT TESDVWSLGV VLWEIFTYGK QPWYQLSNNE VIECITQGRV LQRPRTCPQE
VYELMLGCWQ REPHTRKNIK NIHTLLQNLA KASPVYLDIL G
//
