NTRK1_RAT
ID NTRK1_RAT Reviewed; 799 AA.
AC P35739;
DT 01-JUN-1994, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-1994, sequence version 1.
DT 03-AUG-2022, entry version 208.
DE RecName: Full=High affinity nerve growth factor receptor;
DE EC=2.7.10.1;
DE AltName: Full=Neurotrophic tyrosine kinase receptor type 1;
DE AltName: Full=Slow nerve growth factor receptor;
DE AltName: Full=p140-TrkA;
DE Short=Trk-A;
DE Flags: Precursor;
GN Name=Ntrk1; Synonyms=Trk, Trka;
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] (ISOFORM TRKA-II), FUNCTION AS RECEPTOR FOR NGF,
RP AND SUBCELLULAR LOCATION.
RX PubMed=1312719; DOI=10.1073/pnas.89.6.2374;
RA Meakin S.O., Suter U., Drinkwater C.C., Welcher A.A., Shooter E.M.;
RT "The rat trk protooncogene product exhibits properties characteristic of
RT the slow nerve growth factor receptor.";
RL Proc. Natl. Acad. Sci. U.S.A. 89:2374-2378(1992).
RN [2]
RP ALTERNATIVE SPLICING (ISOFORMS TRKA-I AND TRKA-II).
RX PubMed=8325889; DOI=10.1016/s0021-9258(18)82449-8;
RA Barker P.A., Lomen-Hoerth C., Gensch E.M., Meakin S.O., Glass D.J.,
RA Shooter E.M.;
RT "Tissue-specific alternative splicing generates two isoforms of the trkA
RT receptor.";
RL J. Biol. Chem. 268:15150-15157(1993).
RN [3]
RP FUNCTION AS RECEPTOR FOR NGF, AND SUBCELLULAR LOCATION.
RX PubMed=1850821; DOI=10.1038/350678a0;
RA Hempstead B.L., Martin-Zanca D., Kaplan D.R., Parada L.F., Chao M.V.;
RT "High-affinity NGF binding requires coexpression of the trk proto-oncogene
RT and the low-affinity NGF receptor.";
RL Nature 350:678-683(1991).
RN [4]
RP INTERACTION WITH SHC1.
RX PubMed=8155326; DOI=10.1016/0896-6273(94)90223-2;
RA Stephens R.M., Loeb D.M., Copeland T.D., Pawson T., Greene L.A.,
RA Kaplan D.R.;
RT "Trk receptors use redundant signal transduction pathways involving SHC and
RT PLC-gamma 1 to mediate NGF responses.";
RL Neuron 12:691-705(1994).
RN [5]
RP INTERACTION WITH PLCG1; SHC1; SH2B1 AND SH2B2, AND MUTAGENESIS OF VAL-527.
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 INTERACTION WITH SQSTM1.
RX PubMed=11244088; DOI=10.1074/jbc.c000869200;
RA Wooten M.W., Seibenhener M.L., Mamidipudi V., Diaz-Meco M.T., Barker P.A.,
RA Moscat J.;
RT "The atypical protein kinase C-interacting protein p62 is a scaffold for
RT NF-kappaB activation by nerve growth factor.";
RL J. Biol. Chem. 276:7709-7712(2001).
RN [7]
RP INTERACTION WITH KIDINS220.
RX PubMed=11150334; DOI=10.1523/jneurosci.21-01-00176.2001;
RA Kong H., Boulter J., Weber J.L., Lai C., Chao M.V.;
RT "An evolutionarily conserved transmembrane protein that is a novel
RT downstream target of neurotrophin and ephrin receptors.";
RL J. Neurosci. 21:176-185(2001).
RN [8]
RP INTERACTION WITH SQSTM1, SUBCELLULAR LOCATION, AND DOMAIN.
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 [9]
RP INTERACTION WITH KIDINS220, AND DOMAIN.
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 [10]
RP INTERACTION WITH NGFR AND KIDINS220, AND DOMAIN.
RX PubMed=15378608; DOI=10.1002/jnr.20262;
RA Chang M.-S., Arevalo J.C., Chao M.V.;
RT "Ternary complex with Trk, p75, and an ankyrin-rich membrane spanning
RT protein.";
RL J. Neurosci. Res. 78:186-192(2004).
RN [11]
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 [12]
RP INTERACTION WITH RAB7A, AND SUBCELLULAR LOCATION.
RX PubMed=16306406; DOI=10.1523/jneurosci.2029-05.2005;
RA Saxena S., Bucci C., Weis J., Kruttgen A.;
RT "The small GTPase Rab7 controls the endosomal trafficking and neuritogenic
RT signaling of the nerve growth factor receptor TrkA.";
RL J. Neurosci. 25:10930-10940(2005).
RN [13]
RP INTERACTION WITH PTPRS.
RX PubMed=17967490; DOI=10.1016/j.bbamcr.2007.06.008;
RA Faux C., Hawadle M., Nixon J., Wallace A., Lee S., Murray S., Stoker A.;
RT "PTPsigma binds and dephosphorylates neurotrophin receptors and can
RT suppress NGF-dependent neurite outgrowth from sensory neurons.";
RL Biochim. Biophys. Acta 1773:1689-1700(2007).
RN [14]
RP IDENTIFICATION IN A COMPLEX WITH KIDINS220; MAGI2 AND RAPGEF2, INTERACTION
RP WITH RAPGEF2, AND SUBCELLULAR LOCATION.
RX PubMed=17724123; DOI=10.1083/jcb.200610073;
RA Hisata S., Sakisaka T., Baba T., Yamada T., Aoki K., Matsuda M., Takai Y.;
RT "Rap1-PDZ-GEF1 interacts with a neurotrophin receptor at late endosomes,
RT leading to sustained activation of Rap1 and ERK and neurite outgrowth.";
RL J. Cell Biol. 178:843-860(2007).
RN [15]
RP INTERACTION WITH NRADD.
RX PubMed=18624909; DOI=10.1111/j.1471-4159.2008.05539.x;
RA Wong A.W., Willingham M., Xiao J., Kilpatrick T.J., Murray S.S.;
RT "Neurotrophin receptor homolog-2 regulates nerve growth factor signaling.";
RL J. Neurochem. 106:1964-1976(2008).
RN [16]
RP FUNCTION IN CELL DEATH.
RX PubMed=20811452; DOI=10.1038/nature09336;
RA Nikoletopoulou V., Lickert H., Frade J.M., Rencurel C., Giallonardo P.,
RA Zhang L., Bibel M., Barde Y.A.;
RT "Neurotrophin receptors TrkA and TrkC cause neuronal death whereas TrkB
RT does not.";
RL Nature 467:59-63(2010).
RN [17]
RP INTERACTION WITH GGA3, AND SUBCELLULAR LOCATION.
RX PubMed=26446845; DOI=10.1091/mbc.e15-02-0087;
RA Li X., Lavigne P., Lavoie C.;
RT "GGA3 mediates TrkA endocytic recycling to promote sustained Akt
RT phosphorylation and cell survival.";
RL Mol. Biol. Cell 26:4412-4426(2015).
CC -!- FUNCTION: Receptor tyrosine kinase involved in the development and the
CC maturation of the central and peripheral nervous systems through
CC regulation of proliferation, differentiation and survival of
CC sympathetic and nervous neurons. High affinity receptor for NGF which
CC is its primary ligand (PubMed:1312719, PubMed:1850821). Can also bind
CC and be activated by NTF3/neurotrophin-3. However, NTF3 only supports
CC axonal extension through NTRK1 but has no effect on neuron survival.
CC Upon dimeric NGF ligand-binding, undergoes homodimerization,
CC autophosphorylation and activation. Recruits, phosphorylates and/or
CC activates several downstream effectors including SHC1, FRS2, SH2B1,
CC SH2B2 and PLCG1 that regulate distinct overlapping signaling cascades
CC driving cell survival and differentiation. Through SHC1 and FRS2
CC activates a GRB2-Ras-MAPK cascade that regulates cell differentiation
CC and survival. Through PLCG1 controls NF-Kappa-B activation and the
CC transcription of genes involved in cell survival. Through SHC1 and
CC SH2B1 controls a Ras-PI3 kinase-AKT1 signaling cascade that is also
CC regulating survival. In absence of ligand and activation, may promote
CC cell death, making the survival of neurons dependent on trophic
CC factors. {ECO:0000250|UniProtKB:P04629, ECO:0000250|UniProtKB:Q3UFB7,
CC ECO:0000269|PubMed:1312719, ECO:0000269|PubMed:1850821,
CC ECO:0000269|PubMed:20811452}.
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 -!- ACTIVITY REGULATION: The pro-survival signaling effect of NTRK1 in
CC neurons requires its endocytosis into signaling early endosomes and its
CC retrograde axonal transport. This is regulated by different proteins
CC including CFL1, RAC1 and SORT1. NTF3 is unable to induce this signaling
CC probably due to the lability of the NTF3-NTRK1 complex in endosomes (By
CC similarity). SH2D1A inhibits the autophosphorylation of the receptor,
CC and alters the recruitment and activation of downstream effectors and
CC signaling cascades. Regulated by NGFR (By similarity).
CC {ECO:0000250|UniProtKB:Q3UFB7}.
CC -!- SUBUNIT: Exists in a dynamic equilibrium between monomeric (low
CC affinity) and dimeric (high affinity) structures. Homodimerization is
CC induced by binding of a NGF dimer (By similarity). Found in a complex,
CC at least composed of KIDINS220, MAGI2, NTRK1 and RAPGEF2; the complex
CC is mainly formed at late endosomes in a nerve growth factor (NGF)-
CC dependent manner (PubMed:17724123). Interacts with RAPGEF2; the
CC interaction is strengthened after NGF stimulation (PubMed:17724123).
CC Interacts with SQSTM1; bridges NTRK1 to NGFR. Forms a ternary complex
CC with NGFR and KIDINS220; this complex is affected by the expression
CC levels of KIDINS220 and an increase in KIDINS220 expression leads to a
CC decreased association of NGFR and NTRK1. Interacts (phosphorylated upon
CC activation by NGF) with SHC1; mediates SHC1 phosphorylation and
CC activation. Interacts (phosphorylated upon activation by NGF) with
CC PLCG1; mediates PLCG1 phosphorylation and activation. Interacts
CC (phosphorylated) with SH2B1 and SH2B2. Interacts with GRB2. Interacts
CC with PIK3R1. Interacts with FRS2. Interacts with SORT1; may regulate
CC NTRK1 anterograde axonal transport. Interacts with SH2D1A; regulates
CC NTRK1. Interacts with NRADD (PubMed:18624909). Interacts with RAB7A
CC (PubMed:16306406). Interacts with PTPRS (PubMed:17967490). Interacts
CC with USP36; USP36 does not deubiquitinate NTRK1 (By similarity).
CC Interacts with GGA3 (PubMed:26446845). {ECO:0000250|UniProtKB:P04629,
CC ECO:0000269|PubMed:11150334, ECO:0000269|PubMed:11244088,
CC ECO:0000269|PubMed:12471037, ECO:0000269|PubMed:15167895,
CC ECO:0000269|PubMed:15378608, ECO:0000269|PubMed:16223723,
CC ECO:0000269|PubMed:16306406, ECO:0000269|PubMed:17724123,
CC ECO:0000269|PubMed:17967490, ECO:0000269|PubMed:18624909,
CC ECO:0000269|PubMed:26446845, ECO:0000269|PubMed:8155326,
CC ECO:0000269|PubMed:9856458}.
CC -!- INTERACTION:
CC P35739; P62994: Grb2; NbExp=6; IntAct=EBI-976667, EBI-401775;
CC P35739; P07174: Ngfr; NbExp=2; IntAct=EBI-976667, EBI-1038810;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:1312719,
CC ECO:0000269|PubMed:16306406, ECO:0000269|PubMed:1850821,
CC ECO:0000269|PubMed:26446845}; Single-pass type I membrane protein
CC {ECO:0000305|PubMed:1850821}. Early endosome membrane
CC {ECO:0000269|PubMed:17724123, ECO:0000269|PubMed:26446845}; Single-pass
CC type I membrane protein {ECO:0000305}. Late endosome membrane
CC {ECO:0000269|PubMed:17724123, ECO:0000269|PubMed:26446845}; Single-pass
CC type I membrane protein {ECO:0000305}. Recycling endosome membrane
CC {ECO:0000269|PubMed:26446845}; Single-pass type I membrane protein
CC {ECO:0000305}. Note=Internalized to endosomes upon binding of NGF or
CC NTF3 and further transported to the cell body via a retrograde axonal
CC transport. Localized at cell membrane and early endosomes before nerve
CC growth factor (NGF) stimulation (PubMed:17724123, PubMed:26446845).
CC Recruited to late endosomes after NGF stimulation (PubMed:17724123,
CC PubMed:26446845). Colocalized with RAPGEF2 at late endosomes
CC (PubMed:17724123). {ECO:0000269|PubMed:17724123,
CC ECO:0000269|PubMed:26446845}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Comment=Both isoforms have similar biological properties.;
CC Name=TrkA-II;
CC IsoId=P35739-1; Sequence=Displayed;
CC Name=TrkA-I;
CC IsoId=P35739-2; Sequence=VSP_002900;
CC -!- TISSUE SPECIFICITY: Isoform Trka-II is primarily expressed in neuronal
CC cells; isoform Trka-I is found in non-neuronal tissues.
CC -!- DOMAIN: The transmembrane domain mediates interaction with KIDINS220.
CC {ECO:0000269|PubMed:12471037, ECO:0000269|PubMed:15167895,
CC ECO:0000269|PubMed:15378608}.
CC -!- DOMAIN: The extracellular domain mediates interaction with NGFR.
CC {ECO:0000269|PubMed:15378608}.
CC -!- PTM: Ligand-mediated autophosphorylation. Interaction with SQSTM1 is
CC phosphotyrosine-dependent. Autophosphorylation at Tyr-499 mediates
CC interaction and phosphorylation of SHC1.
CC -!- PTM: N-glycosylated. {ECO:0000250|UniProtKB:P04629}.
CC -!- PTM: Ubiquitinated. Undergoes polyubiquitination upon activation;
CC regulated by NGFR. Ubiquitination by NEDD4L leads to degradation (By
CC similarity). Ubiquitination regulates the internalization of the
CC receptor (By similarity). {ECO:0000250|UniProtKB:P04629,
CC ECO:0000250|UniProtKB:Q3UFB7}.
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; M85214; AAA42286.1; -; mRNA.
DR EMBL; L12225; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR PIR; A41981; TVRTTB.
DR RefSeq; NP_067600.1; NM_021589.1. [P35739-1]
DR AlphaFoldDB; P35739; -.
DR SMR; P35739; -.
DR BioGRID; 248731; 24.
DR CORUM; P35739; -.
DR DIP; DIP-5716N; -.
DR IntAct; P35739; 7.
DR MINT; P35739; -.
DR STRING; 10116.ENSRNOP00000018961; -.
DR BindingDB; P35739; -.
DR ChEMBL; CHEMBL4220; -.
DR GlyGen; P35739; 11 sites.
DR iPTMnet; P35739; -.
DR PhosphoSitePlus; P35739; -.
DR PaxDb; P35739; -.
DR Ensembl; ENSRNOT00000018961; ENSRNOP00000018961; ENSRNOG00000013953. [P35739-2]
DR Ensembl; ENSRNOT00000115670; ENSRNOP00000079821; ENSRNOG00000013953. [P35739-1]
DR GeneID; 59109; -.
DR KEGG; rno:59109; -.
DR UCSC; RGD:620144; rat. [P35739-1]
DR CTD; 4914; -.
DR RGD; 620144; Ntrk1.
DR eggNOG; KOG1026; Eukaryota.
DR GeneTree; ENSGT00940000159412; -.
DR HOGENOM; CLU_000288_74_1_1; -.
DR InParanoid; P35739; -.
DR OMA; IMLKWEL; -.
DR OrthoDB; 295510at2759; -.
DR PhylomeDB; P35739; -.
DR TreeFam; TF106465; -.
DR BRENDA; 2.7.10.1; 5301.
DR Reactome; R-RNO-170968; Frs2-mediated activation.
DR Reactome; R-RNO-170984; ARMS-mediated activation.
DR Reactome; R-RNO-177504; Retrograde neurotrophin signalling.
DR Reactome; R-RNO-187042; TRKA activation by NGF.
DR Reactome; R-RNO-198203; PI3K/AKT activation.
DR PRO; PR:P35739; -.
DR Proteomes; UP000002494; Chromosome 2.
DR Bgee; ENSRNOG00000013953; Expressed in kidney and 10 other tissues.
DR ExpressionAtlas; P35739; baseline and differential.
DR Genevisible; P35739; RN.
DR GO; GO:0030424; C:axon; IDA:RGD.
DR GO; GO:0009986; C:cell surface; IDA:RGD.
DR GO; GO:0005737; C:cytoplasm; ISO:RGD.
DR GO; GO:0031410; C:cytoplasmic vesicle; IDA:RGD.
DR GO; GO:0030425; C:dendrite; IDA:RGD.
DR GO; GO:0005769; C:early endosome; IDA:UniProtKB.
DR GO; GO:0031901; C:early endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0000139; C:Golgi membrane; TAS:Reactome.
DR GO; GO:0005887; C:integral component of plasma membrane; ISS:UniProtKB.
DR GO; GO:0005770; C:late endosome; IDA:UniProtKB.
DR GO; GO:0031902; C:late endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0043025; C:neuronal cell body; IDA:RGD.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0032991; C:protein-containing complex; IDA:UniProtKB.
DR GO; GO:0043235; C:receptor complex; ISO:RGD.
DR GO; GO:0055037; C:recycling endosome; IDA:UniProtKB.
DR GO; GO:0055038; C:recycling endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0005004; F:GPI-linked ephrin receptor activity; IDA:BHF-UCL.
DR GO; GO:0042802; F:identical protein binding; ISO:RGD.
DR GO; GO:0019900; F:kinase binding; IPI:RGD.
DR GO; GO:0048406; F:nerve growth factor binding; IDA:RGD.
DR GO; GO:0010465; F:nerve growth factor receptor activity; ISS:UniProtKB.
DR GO; GO:0043121; F:neurotrophin binding; IBA:GO_Central.
DR GO; GO:0005166; F:neurotrophin p75 receptor binding; IPI:RGD.
DR GO; GO:0005030; F:neurotrophin receptor activity; IBA:GO_Central.
DR GO; GO:0042803; F:protein homodimerization activity; ISS:UniProtKB.
DR GO; GO:0004713; F:protein tyrosine kinase activity; IDA:MGI.
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; ISS:UniProtKB.
DR GO; GO:0007568; P:aging; IEP:RGD.
DR GO; GO:0007411; P:axon guidance; IMP:RGD.
DR GO; GO:0060385; P:axonogenesis involved in innervation; ISS:UniProtKB.
DR GO; GO:0030183; P:B cell differentiation; ISO:RGD.
DR GO; GO:0061368; P:behavioral response to formalin induced pain; ISO:RGD.
DR GO; GO:0071363; P:cellular response to growth factor stimulus; IDA:MGI.
DR GO; GO:1990090; P:cellular response to nerve growth factor stimulus; IDA:UniProtKB.
DR GO; GO:0071316; P:cellular response to nicotine; IDA:RGD.
DR GO; GO:0007623; P:circadian rhythm; ISO:RGD.
DR GO; GO:0050966; P:detection of mechanical stimulus involved in sensory perception of pain; IMP:RGD.
DR GO; GO:0050965; P:detection of temperature stimulus involved in sensory perception of pain; IMP:RGD.
DR GO; GO:0060384; P:innervation; ISO:RGD.
DR GO; GO:0007611; P:learning or memory; IMP:RGD.
DR GO; GO:0042490; P:mechanoreceptor differentiation; ISO:RGD.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; ISS:UniProtKB.
DR GO; GO:0043524; P:negative regulation of neuron apoptotic process; IMP:UniProtKB.
DR GO; GO:1901215; P:negative regulation of neuron death; IDA:RGD.
DR GO; GO:0038180; P:nerve growth factor signaling pathway; IDA:UniProtKB.
DR GO; GO:0007399; P:nervous system development; ISO:RGD.
DR GO; GO:0051402; P:neuron apoptotic process; IEA:Ensembl.
DR GO; GO:0048011; P:neurotrophin TRK receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0021553; P:olfactory nerve development; IEP:RGD.
DR GO; GO:0038083; P:peptidyl-tyrosine autophosphorylation; ISS:UniProtKB.
DR GO; GO:0018108; P:peptidyl-tyrosine phosphorylation; ISO:RGD.
DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; ISS:UniProtKB.
DR GO; GO:0043547; P:positive regulation of GTPase activity; ISS:UniProtKB.
DR GO; GO:0033674; P:positive regulation of kinase activity; IBA:GO_Central.
DR GO; GO:0010976; P:positive regulation of neuron projection development; ISS:UniProtKB.
DR GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; ISS:UniProtKB.
DR GO; GO:0014068; P:positive regulation of phosphatidylinositol 3-kinase signaling; IBA:GO_Central.
DR GO; GO:0043068; P:positive regulation of programmed cell death; IDA:UniProtKB.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; IDA:BHF-UCL.
DR GO; GO:0046579; P:positive regulation of Ras protein signal transduction; ISS: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:0010623; P:programmed cell death involved in cell development; IDA:UniProtKB.
DR GO; GO:0046777; P:protein autophosphorylation; IDA:MGI.
DR GO; GO:0006468; P:protein phosphorylation; ISS:UniProtKB.
DR GO; GO:0051896; P:regulation of protein kinase B signaling; IBA:GO_Central.
DR GO; GO:0048678; P:response to axon injury; IEP:RGD.
DR GO; GO:0051602; P:response to electrical stimulus; IDA:RGD.
DR GO; GO:0051599; P:response to hydrostatic pressure; IEP:RGD.
DR GO; GO:0035094; P:response to nicotine; IDA:RGD.
DR GO; GO:0031667; P:response to nutrient levels; IDA:RGD.
DR GO; GO:0009314; P:response to radiation; IEP:RGD.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IDA:RGD.
DR GO; GO:0019233; P:sensory perception of pain; IMP:RGD.
DR GO; GO:0060009; P:Sertoli cell development; IMP:RGD.
DR GO; GO:0048485; P:sympathetic nervous system development; ISS:UniProtKB.
DR GO; GO:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; IBA:GO_Central.
DR Gene3D; 2.60.40.10; -; 2.
DR Gene3D; 3.80.10.10; -; 1.
DR InterPro; IPR007110; Ig-like_dom.
DR InterPro; IPR036179; Ig-like_dom_sf.
DR InterPro; IPR013783; Ig-like_fold.
DR InterPro; IPR003599; Ig_sub.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR001611; Leu-rich_rpt.
DR InterPro; IPR032675; LRR_dom_sf.
DR InterPro; IPR020777; NTRK.
DR InterPro; IPR020461; NTRK1.
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; PF13855; LRR_8; 1.
DR Pfam; PF16920; LRRCT_2; 1.
DR Pfam; PF07714; PK_Tyr_Ser-Thr; 1.
DR PRINTS; PR01939; NTKRECEPTOR.
DR PRINTS; PR01940; NTKRECEPTOR1.
DR PRINTS; PR00109; TYRKINASE.
DR SMART; SM00409; IG; 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; Developmental protein;
KW Differentiation; Disulfide bond; Endosome; Glycoprotein;
KW Immunoglobulin domain; Kinase; Leucine-rich repeat; Membrane; Neurogenesis;
KW Nucleotide-binding; Phosphoprotein; Receptor; Reference proteome; Repeat;
KW Signal; Transferase; Transmembrane; Transmembrane helix;
KW Tyrosine-protein kinase; Ubl conjugation.
FT SIGNAL 1..32
FT /evidence="ECO:0000255"
FT CHAIN 33..799
FT /note="High affinity nerve growth factor receptor"
FT /id="PRO_0000016725"
FT TOPO_DOM 33..418
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 419..442
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 443..799
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REPEAT 90..113
FT /note="LRR 1"
FT REPEAT 116..137
FT /note="LRR 2"
FT DOMAIN 148..219
FT /note="LRRCT"
FT DOMAIN 196..285
FT /note="Ig-like C2-type 1"
FT DOMAIN 295..368
FT /note="Ig-like C2-type 2"
FT DOMAIN 513..784
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 472..493
FT /note="Interaction with SQSTM1"
FT ACT_SITE 653
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10028"
FT BINDING 519..527
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 547
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT SITE 499
FT /note="Interaction with SHC1"
FT /evidence="ECO:0000250"
FT SITE 794
FT /note="Interaction with PLCG1"
FT /evidence="ECO:0000250"
FT MOD_RES 499
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:P04629"
FT MOD_RES 679
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:P04629"
FT MOD_RES 683
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:P04629"
FT MOD_RES 684
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:P04629"
FT MOD_RES 794
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:P04629"
FT CARBOHYD 67
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 190
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 204
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 255
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 264
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 320
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 341
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 361
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 404
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 36..41
FT /evidence="ECO:0000250|UniProtKB:P04629"
FT DISULFID 40..50
FT /evidence="ECO:0000250|UniProtKB:P04629"
FT DISULFID 154..193
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 217..267
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 302..348
FT /evidence="ECO:0000250|UniProtKB:P04629"
FT VAR_SEQ 396..401
FT /note="Missing (in isoform TrkA-I)"
FT /evidence="ECO:0000305"
FT /id="VSP_002900"
FT MUTAGEN 527
FT /note="V->D: Loss of kinase activity."
FT /evidence="ECO:0000269|PubMed:9856458"
SQ SEQUENCE 799 AA; 87868 MW; D564E8801E8978F8 CRC64;
MLRGQRHGQL GWHRPAAGLG GLVTSLMLAC ACAASCRETC CPVGPSGLRC TRAGTLNTLR
GLRGAGNLTE LYVENQRDLQ RLEFEDLQGL GELRSLTIVK SGLRFVAPDA FHFTPRLSHL
NLSSNALESL SWKTVQGLSL QDLTLSGNPL HCSCALLWLQ RWEQEDLCGV YTQKLQGSGS
GDQFLPLGHN NSCGVPSVKI QMPNDSVEVG DDVFLQCQVE GQALQQADWI LTELEGTATM
KKSGDLPSLG LTLVNVTSDL NKKNVTCWAE NDVGRAEVSV QVSVSFPASV HLGKAVEQHH
WCIPFSVDGQ PAPSLRWFFN GSVLNETSFI FTQFLESALT NETMRHGCLR LNQPTHVNNG
NYTLLAANPY GQAAASIMAA FMDNPFEFNP EDPIPVSFSP VDTNSTSRDP VEKKDETPFG
VSVAVGLAVS AALFLSALLL VLNKCGQRSK FGINRPAVLA PEDGLAMSLH FMTLGGSSLS
PTEGKGSGLQ GHIMENPQYF SDTCVHHIKR QDIILKWELG EGAFGKVFLA ECYNLLNDQD
KMLVAVKALK ETSENARQDF HREAELLTML QHQHIVRFFG VCTEGGPLLM VFEYMRHGDL
NRFLRSHGPD AKLLAGGEDV APGPLGLGQL LAVASQVAAG MVYLASLHFV HRDLATRNCL
VGQGLVVKIG DFGMSRDIYS TDYYRVGGRT MLPIRWMPPE SILYRKFSTE SDVWSFGVVL
WEIFTYGKQP WYQLSNTEAI ECITQGRELE RPRACPPDVY AIMRGCWQRE PQQRLSMKDV
HARLQALAQA PPSYLDVLG
