NTRK2_MOUSE
ID NTRK2_MOUSE Reviewed; 821 AA.
AC P15209; Q3TUF9; Q80WU0; Q91XJ9;
DT 01-APR-1990, integrated into UniProtKB/Swiss-Prot.
DT 01-APR-1990, sequence version 1.
DT 03-AUG-2022, entry version 231.
DE RecName: Full=BDNF/NT-3 growth factors receptor;
DE EC=2.7.10.1 {ECO:0000269|PubMed:27457814};
DE AltName: Full=GP145-TrkB/GP95-TrkB;
DE Short=Trk-B;
DE AltName: Full=Neurotrophic tyrosine kinase receptor type 2;
DE AltName: Full=TrkB tyrosine kinase;
DE Flags: Precursor;
GN Name=Ntrk2 {ECO:0000312|MGI:MGI:97384};
GN Synonyms=Trkb {ECO:0000303|PubMed:21849472, ECO:0000303|PubMed:27457814};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM GP145-TRKB).
RC TISSUE=Brain;
RX PubMed=2555172; DOI=10.1002/j.1460-2075.1989.tb08545.x;
RA Klein R., Parada L.F., Coulier F., Barbacid M.;
RT "trkB, a novel tyrosine protein kinase receptor expressed during mouse
RT neural development.";
RL EMBO J. 8:3701-3709(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS GP145-TRKB AND GP95-TRKB).
RC TISSUE=Brain;
RX PubMed=2160854; DOI=10.1016/0092-8674(90)90476-u;
RA Klein R., Conway D., Parada L.F., Barbacid M.;
RT "The trkB tyrosine protein kinase gene codes for a second neurogenic
RT receptor that lacks the catalytic kinase domain.";
RL Cell 61:647-656(1990).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS GP145-TRKB AND GP95-TRKB).
RC STRAIN=C57BL/6J, and NOD; TISSUE=Thymus;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM GP95-TRKB).
RC STRAIN=C57BL/6J; 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 [5]
RP PARTIAL NUCLEOTIDE SEQUENCE (ISOFORMS L1 AND L10).
RC TISSUE=Trigeminal ganglion;
RX PubMed=9148911; DOI=10.1074/jbc.272.20.13019;
RA Ninkina N., Grashchuck M., Buchman V.L., Davies A.M.;
RT "TrkB variants with deletions in the leucine-rich motifs of the
RT extracellular domain.";
RL J. Biol. Chem. 272:13019-13025(1997).
RN [6]
RP FUNCTION IN BDNF AND NTF3 SIGNALING.
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 [7]
RP DISRUPTION PHENOTYPE, AND FUNCTION.
RX PubMed=8402890; DOI=10.1016/s0092-8674(05)80088-1;
RA Klein R., Smeyne R.J., Wurst W., Long L.K., Auerbach B.A., Joyner A.L.,
RA Barbacid M.;
RT "Targeted disruption of the trkB neurotrophin receptor gene results in
RT nervous system lesions and neonatal death.";
RL Cell 75:113-122(1993).
RN [8]
RP FUNCTION IN NTF3-MEDIATED NEURON SURVIVAL.
RX PubMed=9728914; DOI=10.1016/s0896-6273(00)80542-5;
RA Farinas I., Wilkinson G.A., Backus C., Reichardt L.F., Patapoutian A.;
RT "Characterization of neurotrophin and Trk receptor functions in developing
RT sensory ganglia: direct NT-3 activation of TrkB neurons in vivo.";
RL Neuron 21:325-334(1998).
RN [9]
RP FUNCTION IN LONG-TERM POTENTIATION AND LEARNING.
RX PubMed=10571233; DOI=10.1016/s0896-6273(00)80853-3;
RA Minichiello L., Korte M., Wolfer D., Kuehn R., Unsicker K., Cestari V.,
RA Rossi-Arnaud C., Lipp H.P., Bonhoeffer T., Klein R.;
RT "Essential role for TrkB receptors in hippocampus-mediated learning.";
RL Neuron 24:401-414(1999).
RN [10]
RP FUNCTION IN LONG-TERM POTENTIATION AND LEARNING, INTERACTION WITH SHC1 AND
RP PLCG1, AND MUTAGENESIS OF TYR-515 AND TYR-816.
RX PubMed=12367511; DOI=10.1016/s0896-6273(02)00942-x;
RA Minichiello L., Calella A.M., Medina D.L., Bonhoeffer T., Klein R.,
RA Korte M.;
RT "Mechanism of TrkB-mediated hippocampal long-term potentiation.";
RL Neuron 36:121-137(2002).
RN [11]
RP SUBCELLULAR LOCATION, AND ACTIVITY REGULATION.
RX PubMed=14581459; DOI=10.1083/jcb.200305134;
RA Du J., Feng L., Zaitsev E., Je H.S., Liu X.W., Lu B.;
RT "Regulation of TrkB receptor tyrosine kinase and its internalization by
RT neuronal activity and Ca2+ influx.";
RL J. Cell Biol. 163:385-395(2003).
RN [12]
RP FUNCTION IN CALCIUM SIGNALING (ISOFORM GP95-TRKB).
RX PubMed=14603320; DOI=10.1038/nature01983;
RA Rose C.R., Blum R., Pichler B., Lepier A., Kafitz K.W., Konnerth A.;
RT "Truncated TrkB-T1 mediates neurotrophin-evoked calcium signalling in glia
RT cells.";
RL Nature 426:74-78(2003).
RN [13]
RP FUNCTION IN NEURONAL MIGRATION AND DIFFERENTIATION.
RX PubMed=15372074; DOI=10.1038/sj.emboj.7600399;
RA Medina D.L., Sciarretta C., Calella A.M., Von Bohlen Und Halbach O.,
RA Unsicker K., Minichiello L.;
RT "TrkB regulates neocortex formation through the Shc/PLCgamma-mediated
RT control of neuronal migration.";
RL EMBO J. 23:3803-3814(2004).
RN [14]
RP FUNCTION AS A SUPPRESSOR OF ANOIKIS.
RX PubMed=15329723; DOI=10.1038/nature02765;
RA Douma S., Van Laar T., Zevenhoven J., Meuwissen R., Van Garderen E.,
RA Peeper D.S.;
RT "Suppression of anoikis and induction of metastasis by the neurotrophic
RT receptor TrkB.";
RL Nature 430:1034-1039(2004).
RN [15]
RP UBIQUITINATION, AND ACTIVITY REGULATION.
RX PubMed=16113645; DOI=10.1038/sj.embor.7400503;
RA Makkerh J.P., Ceni C., Auld D.S., Vaillancourt F., Dorval G., Barker P.A.;
RT "p75 neurotrophin receptor reduces ligand-induced Trk receptor
RT ubiquitination and delays Trk receptor internalization and degradation.";
RL EMBO Rep. 6:936-941(2005).
RN [16]
RP ACTIVITY REGULATION, AND INTERACTION WITH SH2D1A.
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 [17]
RP FUNCTION IN PHOSPHORYLATION OF TIAM1, FUNCTION IN CELL DIFFERENTIATION, AND
RP INTERACTION WITH TIAM1.
RX PubMed=16801538; DOI=10.1073/pnas.0603914103;
RA Miyamoto Y., Yamauchi J., Tanoue A., Wu C., Mobley W.C.;
RT "TrkB binds and tyrosine-phosphorylates Tiam1, leading to activation of
RT Rac1 and induction of changes in cellular morphology.";
RL Proc. Natl. Acad. Sci. U.S.A. 103:10444-10449(2006).
RN [18]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-515, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
RX PubMed=18034455; DOI=10.1021/pr0701254;
RA Ballif B.A., Carey G.R., Sunyaev S.R., Gygi S.P.;
RT "Large-scale identification and evolution indexing of tyrosine
RT phosphorylation sites from murine brain.";
RL J. Proteome Res. 7:311-318(2008).
RN [19]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [20]
RP INTERACTION WITH APPL1, AND SUBCELLULAR LOCATION.
RX PubMed=21849472; DOI=10.1091/mbc.e11-04-0308;
RA Fu X., Yang Y., Xu C., Niu Y., Chen T., Zhou Q., Liu J.J.;
RT "Retrolinkin cooperates with endophilin A1 to mediate BDNF-TrkB early
RT endocytic trafficking and signaling from early endosomes.";
RL Mol. Biol. Cell 22:3684-3698(2011).
RN [21]
RP FUNCTION IN SYNAPSE FORMATION.
RX PubMed=21414899; DOI=10.1523/jneurosci.4991-10.2011;
RA Chen A.I., Nguyen C.N., Copenhagen D.R., Badurek S., Minichiello L.,
RA Ranscht B., Reichardt L.F.;
RT "TrkB (tropomyosin-related kinase B) controls the assembly and maintenance
RT of GABAergic synapses in the cerebellar cortex.";
RL J. Neurosci. 31:2769-2780(2011).
RN [22]
RP INDUCTION.
RX PubMed=23785138; DOI=10.1523/jneurosci.2757-12.2013;
RA Baeza-Raja B., Eckel-Mahan K., Zhang L., Vagena E., Tsigelny I.F.,
RA Sassone-Corsi P., Ptacek L.J., Akassoglou K.;
RT "p75 neurotrophin receptor is a clock gene that regulates oscillatory
RT components of circadian and metabolic networks.";
RL J. Neurosci. 33:10221-10234(2013).
RN [23]
RP INTERACTION WITH SORL1, AND TISSUE SPECIFICITY.
RX PubMed=23977241; DOI=10.1371/journal.pone.0072164;
RA Rohe M., Hartl D., Fjorback A.N., Klose J., Willnow T.E.;
RT "SORLA-mediated trafficking of TrkB enhances the response of neurons to
RT BDNF.";
RL PLoS ONE 8:E72164-E72164(2013).
RN [24]
RP FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, INTERACTION WITH
RP SORCS2, AND TISSUE SPECIFICITY.
RX PubMed=27457814; DOI=10.1038/mp.2016.108;
RA Glerup S., Bolcho U., Moelgaard S., Boeggild S., Vaegter C.B., Smith A.H.,
RA Nieto-Gonzalez J.L., Ovesen P.L., Pedersen L.F., Fjorback A.N., Kjolby M.,
RA Login H., Holm M.M., Andersen O.M., Nyengaard J.R., Willnow T.E.,
RA Jensen K., Nykjaer A.;
RT "SorCS2 is required for BDNF-dependent plasticity in the hippocampus.";
RL Mol. Psychiatry 21:1740-1751(2016).
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. Isoform
CC GP95-TRKB may also play a role in neutrophin-dependent calcium
CC signaling in glial cells and mediate communication between neurons and
CC glia. {ECO:0000269|PubMed:10571233, ECO:0000269|PubMed:12367511,
CC ECO:0000269|PubMed:15329723, ECO:0000269|PubMed:15372074,
CC ECO:0000269|PubMed:1645620, ECO:0000269|PubMed:16801538,
CC ECO:0000269|PubMed:21414899, ECO:0000269|PubMed:27457814,
CC ECO:0000269|PubMed:8402890, ECO:0000269|PubMed:9728914}.
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:27457814};
CC -!- ACTIVITY REGULATION: The formation of active receptors dimers able to
CC fully transduce the ligand-mediated signal, may be negatively regulated
CC by the formation of inactive heterodimers with the non-catalytic
CC isoforms (By similarity). The neuronal activity and the influx of
CC calcium positively regulate the kinase activity and the internalization
CC of the receptor which are both important for active signaling.
CC Regulated by NGFR that may control the internalization of the receptor.
CC NGFR may also stimulate the activation by BDNF compared to NTF3 and
CC NTF4. SH2D1A inhibits the autophosphorylation of the receptor, and
CC alters the recruitment and activation of downstream effectors and
CC signaling cascades. {ECO:0000250|UniProtKB:Q63604,
CC ECO:0000269|PubMed:14581459, ECO:0000269|PubMed:16113645,
CC ECO:0000269|PubMed:16223723}.
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 (PubMed:27457814). 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 (By similarity). Interacts with APPL1
CC (PubMed:21849472). Interacts with MAPK8IP3/JIP3 and KLC1; interaction
CC with 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 (PubMed:23977241).
CC {ECO:0000250|UniProtKB:P04629, ECO:0000250|UniProtKB:Q63604,
CC ECO:0000269|PubMed:21849472, ECO:0000269|PubMed:23977241,
CC ECO:0000269|PubMed:27457814}.
CC -!- INTERACTION:
CC P15209; Q62108: Dlg4; NbExp=4; IntAct=EBI-309647, EBI-300895;
CC P15209; Q99LI8: Hgs; NbExp=2; IntAct=EBI-309647, EBI-2119135;
CC P15209; Q8K4V6: Pirb; NbExp=4; IntAct=EBI-309647, EBI-8602514;
CC P15209; P35235: Ptpn11; NbExp=2; IntAct=EBI-309647, EBI-397236;
CC P15209; Q6PHU5: Sort1; NbExp=3; IntAct=EBI-309647, EBI-6985663;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:14581459};
CC Single-pass type I membrane protein {ECO:0000269|PubMed:14581459}.
CC Endosome membrane {ECO:0000269|PubMed:14581459}; Single-pass type I
CC membrane protein {ECO:0000269|PubMed:14581459}. Early endosome membrane
CC {ECO:0000269|PubMed:21849472}. 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:0000269|PubMed:27457814}. Note=Internalized to endosomes upon
CC ligand-binding. {ECO:0000269|PubMed:21849472}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Comment=Additional isoforms seem to exist.;
CC Name=GP145-TRKB; Synonyms=L3, TrkBTK+, TRKB-FL;
CC IsoId=P15209-1; Sequence=Displayed;
CC Name=GP95-TRKB; Synonyms=TRKB-T1, TrkBTK-;
CC IsoId=P15209-2; Sequence=VSP_002908, VSP_002909;
CC Name=L1;
CC IsoId=P15209-3; Sequence=VSP_002907;
CC Name=L10;
CC IsoId=P15209-4; Sequence=VSP_002905, VSP_002906;
CC -!- TISSUE SPECIFICITY: Expressed in the brain, in neurons (at protein
CC level) (PubMed:23977241). Detected in hippocampus (at protein level)
CC (PubMed:27457814). Widely expressed in the central and peripheral
CC nervous system. The different forms are differentially expressed in
CC various cell types. Isoform GP95-TRKB is specifically expressed in
CC glial cells. {ECO:0000269|PubMed:23977241,
CC ECO:0000269|PubMed:27457814}.
CC -!- INDUCTION: Expression oscillates in a circadian manner in the liver.
CC {ECO:0000269|PubMed:23785138}.
CC -!- PTM: Phosphorylated. Undergoes ligand-mediated autophosphorylation that
CC is required for interaction with SHC1 and PLCG1 and other downstream
CC effectors (PubMed:27457814). Some isoforms are not phosphorylated (By
CC similarity). {ECO:0000250, ECO:0000269|PubMed:27457814}.
CC -!- PTM: Ubiquitinated. Undergoes polyubiquitination upon activation;
CC regulated by NGFR. Ubiquitination regulates the internalization of the
CC receptor. {ECO:0000269|PubMed:16113645}.
CC -!- DISRUPTION PHENOTYPE: Mice lacking isoform GP145-TRKB, the catalytic
CC isoform, do not display feeding activity and die at P1. This is
CC associated neuronal deficiencies in the central and the peripheral
CC nervous systems. {ECO:0000269|PubMed:8402890}.
CC -!- MISCELLANEOUS: [Isoform GP95-TRKB]: Non-catalytic isoform.
CC {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein
CC kinase family. Insulin receptor subfamily. {ECO:0000255|PROSITE-
CC ProRule:PRU00159}.
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DR EMBL; M33385; AAA40482.1; -; mRNA.
DR EMBL; X17647; CAA35636.1; -; mRNA.
DR EMBL; AK018789; BAB31412.1; -; mRNA.
DR EMBL; AK147391; BAE27880.1; -; mRNA.
DR EMBL; AK160789; BAE36012.1; -; mRNA.
DR EMBL; BC052014; AAH52014.2; -; mRNA.
DR CCDS; CCDS26573.1; -. [P15209-1]
DR CCDS; CCDS36685.1; -. [P15209-2]
DR PIR; A35104; A35104.
DR PIR; S06943; S06943.
DR RefSeq; NP_001020245.1; NM_001025074.2. [P15209-1]
DR RefSeq; NP_001269890.1; NM_001282961.1. [P15209-1]
DR RefSeq; NP_032771.1; NM_008745.3. [P15209-2]
DR RefSeq; XP_006517212.1; XM_006517149.3. [P15209-1]
DR RefSeq; XP_006517215.1; XM_006517152.3. [P15209-2]
DR RefSeq; XP_017170908.1; XM_017315419.1.
DR RefSeq; XP_017170909.1; XM_017315420.1.
DR AlphaFoldDB; P15209; -.
DR SMR; P15209; -.
DR BioGRID; 201869; 15.
DR DIP; DIP-5722N; -.
DR IntAct; P15209; 14.
DR MINT; P15209; -.
DR STRING; 10090.ENSMUSP00000078757; -.
DR ChEMBL; CHEMBL4523190; -.
DR GlyConnect; 2148; 26 N-Linked glycans (8 sites).
DR GlyGen; P15209; 12 sites, 25 N-linked glycans (8 sites).
DR iPTMnet; P15209; -.
DR PhosphoSitePlus; P15209; -.
DR MaxQB; P15209; -.
DR PaxDb; P15209; -.
DR PeptideAtlas; P15209; -.
DR PRIDE; P15209; -.
DR ProteomicsDB; 287834; -. [P15209-1]
DR ProteomicsDB; 287835; -. [P15209-2]
DR ProteomicsDB; 287836; -. [P15209-3]
DR ProteomicsDB; 287837; -. [P15209-4]
DR Antibodypedia; 2081; 1327 antibodies from 48 providers.
DR DNASU; 18212; -.
DR Ensembl; ENSMUST00000079828; ENSMUSP00000078757; ENSMUSG00000055254. [P15209-1]
DR Ensembl; ENSMUST00000109838; ENSMUSP00000105464; ENSMUSG00000055254. [P15209-2]
DR Ensembl; ENSMUST00000224259; ENSMUSP00000153270; ENSMUSG00000055254. [P15209-2]
DR Ensembl; ENSMUST00000225488; ENSMUSP00000153553; ENSMUSG00000055254. [P15209-1]
DR GeneID; 18212; -.
DR KEGG; mmu:18212; -.
DR UCSC; uc007qui.2; mouse. [P15209-1]
DR CTD; 4915; -.
DR MGI; MGI:97384; Ntrk2.
DR VEuPathDB; HostDB:ENSMUSG00000055254; -.
DR eggNOG; KOG1026; Eukaryota.
DR GeneTree; ENSGT00940000155181; -.
DR HOGENOM; CLU_030959_1_0_1; -.
DR InParanoid; P15209; -.
DR OMA; TCSCEIM; -.
DR OrthoDB; 295510at2759; -.
DR PhylomeDB; P15209; -.
DR TreeFam; TF106465; -.
DR BRENDA; 2.7.10.1; 3474.
DR Reactome; R-MMU-9026527; Activated NTRK2 signals through PLCG1.
DR Reactome; R-MMU-9028731; Activated NTRK2 signals through FRS2 and FRS3.
DR Reactome; R-MMU-9032759; NTRK2 activates RAC1.
DR BioGRID-ORCS; 18212; 2 hits in 75 CRISPR screens.
DR ChiTaRS; Ntrk2; mouse.
DR PRO; PR:P15209; -.
DR Proteomes; UP000000589; Chromosome 13.
DR RNAct; P15209; protein.
DR Bgee; ENSMUSG00000055254; Expressed in median eminence of neurohypophysis and 251 other tissues.
DR ExpressionAtlas; P15209; baseline and differential.
DR Genevisible; P15209; MM.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0030424; C:axon; ISO:MGI.
DR GO; GO:0043679; C:axon terminus; ISO:MGI.
DR GO; GO:0009986; C:cell surface; ISO:MGI.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0005829; C:cytosol; IDA:MGI.
DR GO; GO:0030425; C:dendrite; ISS:UniProtKB.
DR GO; GO:0043197; C:dendritic spine; ISO:MGI.
DR GO; GO:0005769; C:early endosome; IDA:UniProtKB.
DR GO; GO:0031901; C:early endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005768; C:endosome; IDA:MGI.
DR GO; GO:0060076; C:excitatory synapse; ISO:MGI.
DR GO; GO:0098978; C:glutamatergic synapse; ISO:MGI.
DR GO; GO:0030426; C:growth cone; ISO:MGI.
DR GO; GO:0005887; C:integral component of plasma membrane; ISS:UniProtKB.
DR GO; GO:0043025; C:neuronal cell body; ISO:MGI.
DR GO; GO:0043204; C:perikaryon; ISO:MGI.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:MGI.
DR GO; GO:0098794; C:postsynapse; ISO:MGI.
DR GO; GO:0014069; C:postsynaptic density; IDA:ARUK-UCL.
DR GO; GO:0048786; C:presynaptic active zone; ISO:MGI.
DR GO; GO:0043235; C:receptor complex; ISO:MGI.
DR GO; GO:0005791; C:rough endoplasmic reticulum; ISO:MGI.
DR GO; GO:0043195; C:terminal bouton; IDA:MGI.
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; ISO:MGI.
DR GO; GO:0002020; F:protease binding; ISO:MGI.
DR GO; GO:0042803; F:protein homodimerization activity; ISS:UniProtKB.
DR GO; GO:0030971; F:receptor tyrosine kinase binding; ISO:MGI.
DR GO; GO:0004714; F:transmembrane receptor protein tyrosine kinase activity; ISO:MGI.
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; IMP:UniProtKB.
DR GO; GO:0071230; P:cellular response to amino acid stimulus; IDA:MGI.
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; IMP:UniProtKB.
DR GO; GO:0021987; P:cerebral cortex development; IMP:UniProtKB.
DR GO; GO:0007623; P:circadian rhythm; IEP:UniProtKB.
DR GO; GO:0007631; P:feeding behavior; IMP:MGI.
DR GO; GO:0014047; P:glutamate secretion; IPI:MGI.
DR GO; GO:0007612; P:learning; IMP:UniProtKB.
DR GO; GO:0007616; P:long-term memory; ISO:MGI.
DR GO; GO:0060291; P:long-term synaptic potentiation; IMP:UniProtKB.
DR GO; GO:0042490; P:mechanoreceptor differentiation; IMP:MGI.
DR GO; GO:0022011; P:myelination in peripheral nervous system; IGI:MGI.
DR GO; GO:1902430; P:negative regulation of amyloid-beta formation; ISO:MGI.
DR GO; GO:2000811; P:negative regulation of anoikis; IDA:UniProtKB.
DR GO; GO:0043524; P:negative regulation of neuron apoptotic process; ISS:UniProtKB.
DR GO; GO:0030182; P:neuron differentiation; IMP:UniProtKB.
DR GO; GO:0001764; P:neuron migration; IMP:UniProtKB.
DR GO; GO:0019227; P:neuronal action potential propagation; IGI:MGI.
DR GO; GO:0048709; P:oligodendrocyte differentiation; IMP:UniProtKB.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; IMP:MGI.
DR GO; GO:0048935; P:peripheral nervous system neuron development; IMP:UniProtKB.
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; IMP:UniProtKB.
DR GO; GO:2000324; P:positive regulation of glucocorticoid receptor signaling pathway; ISO:MGI.
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; IDA:UniProtKB.
DR GO; GO:0033138; P:positive regulation of peptidyl-serine phosphorylation; IMP:MGI.
DR GO; GO:0014068; P:positive regulation of phosphatidylinositol 3-kinase signaling; ISS:UniProtKB.
DR GO; GO:0051965; P:positive regulation of synapse assembly; IDA:MGI.
DR GO; GO:0051968; P:positive regulation of synaptic transmission, glutamatergic; ISO:MGI.
DR GO; GO:0046777; P:protein autophosphorylation; ISS:UniProtKB.
DR GO; GO:0050773; P:regulation of dendrite development; ISO:MGI.
DR GO; GO:0043087; P:regulation of GTPase activity; IDA:UniProtKB.
DR GO; GO:0043408; P:regulation of MAPK cascade; ISO:MGI.
DR GO; GO:0019222; P:regulation of metabolic process; IMP:MGI.
DR GO; GO:0046928; P:regulation of neurotransmitter secretion; ISO:MGI.
DR GO; GO:0051896; P:regulation of protein kinase B signaling; IMP:UniProtKB.
DR GO; GO:0060041; P:retina development in camera-type eye; IMP:MGI.
DR GO; GO:0046548; P:retinal rod cell development; IMP:MGI.
DR GO; GO:0099183; P:trans-synaptic signaling by BDNF, modulating synaptic transmission; IDA:SynGO.
DR GO; GO:0099551; P:trans-synaptic signaling by neuropeptide, modulating synaptic transmission; IMP:SynGO.
DR GO; GO:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; IBA:GO_Central.
DR GO; GO:0001570; P:vasculogenesis; IMP:MGI.
DR Gene3D; 2.60.40.10; -; 2.
DR Gene3D; 3.80.10.10; -; 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 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; 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 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 CHAIN 32..821
FT /note="BDNF/NT-3 growth factors receptor"
FT /id="PRO_0000016728"
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 301..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:0000250|UniProtKB:Q63604"
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 /evidence="ECO:0000250"
FT SITE 816
FT /note="Interaction with PLCG1"
FT MOD_RES 515
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:18034455"
FT MOD_RES 701
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:Q63604"
FT MOD_RES 705
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 816
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:Q63604"
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:0000255"
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:0000255"
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 71
FT /note="I -> M (in isoform L10)"
FT /evidence="ECO:0000305"
FT /id="VSP_002905"
FT VAR_SEQ 72..143
FT /note="Missing (in isoform L10)"
FT /evidence="ECO:0000305"
FT /id="VSP_002906"
FT VAR_SEQ 72..120
FT /note="Missing (in isoform L1)"
FT /evidence="ECO:0000305"
FT /id="VSP_002907"
FT VAR_SEQ 466..476
FT /note="PASVISNDDDS -> FVLFHKIPLDG (in isoform GP95-TRKB)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:16141072, ECO:0000303|PubMed:2160854"
FT /id="VSP_002908"
FT VAR_SEQ 477..821
FT /note="Missing (in isoform GP95-TRKB)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:16141072, ECO:0000303|PubMed:2160854"
FT /id="VSP_002909"
FT MUTAGEN 515
FT /note="Y->F: Loss of interaction with SHC1."
FT /evidence="ECO:0000269|PubMed:12367511"
FT MUTAGEN 816
FT /note="Y->F: Loss of interaction with PLCG1."
FT /evidence="ECO:0000269|PubMed:12367511"
SQ SEQUENCE 821 AA; 92133 MW; 50E08D5FF86D8F30 CRC64;
MSPWLKWHGP AMARLWGLCL LVLGFWRASL ACPTSCKCSS ARIWCTEPSP GIVAFPRLEP
NSVDPENITE ILIANQKRLE IINEDDVEAY VGLRNLTIVD SGLKFVAYKA FLKNSNLRHI
NFTRNKLTSL SRRHFRHLDL SDLILTGNPF TCSCDIMWLK TLQETKSSPD TQDLYCLNES
SKNMPLANLQ IPNCGLPSAR LAAPNLTVEE GKSVTLSCSV GGDPLPTLYW DVGNLVSKHM
NETSHTQGSL RITNISSDDS GKQISCVAEN LVGEDQDSVN LTVHFAPTIT FLESPTSDHH
WCIPFTVRGN PKPALQWFYN GAILNESKYI CTKIHVTNHT EYHGCLQLDN PTHMNNGDYT
LMAKNEYGKD ERQISAHFMG RPGVDYETNP NYPEVLYEDW TTPTDIGDTT NKSNEIPSTD
VADQSNREHL 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 SIHTLLQNLA KASPVYLDIL G
