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 02-SEP-2026, entry version 226. 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). RN [18] RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH NTRK1/TRKA. RX PubMed=31440771; DOI=10.1007/s00018-019-03282-3; RA Ferrero Restelli F., Fontanet P.A., De Vincenti A.P., Falzone T.L., RA Ledda F., Paratcha G.; RT "Tetraspanin1 promotes NGF signaling by controlling TrkA receptor RT proteostasis."; RL Cell. Mol. Life Sci. 77:2217-2233(2020). 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, CC PubMed:31440771). Can also bind and be activated by NTF3/neurotrophin- CC 3. However, NTF3 only supports axonal extension through NTRK1 but has CC no effect on neuron survival. Upon dimeric NGF ligand-binding, CC undergoes homodimerization, autophosphorylation and activation. CC Recruits, phosphorylates and/or activates several downstream effectors CC including SHC1, FRS2, SH2B1, SH2B2 and PLCG1 that regulate distinct CC overlapping signaling cascades driving cell survival and CC differentiation. Through SHC1 and FRS2 activates a GRB2-Ras-MAPK CC cascade that regulates cell differentiation and survival. Through PLCG1 CC controls NF-Kappa-B activation and the transcription of genes involved CC in cell survival. Through SHC1 and SH2B1 controls a Ras-PI3 kinase-AKT1 CC signaling cascade that is also regulating survival. In absence of CC ligand and activation, may promote cell death, making the survival of CC neurons dependent on trophic factors. {ECO:0000250|UniProtKB:P04629, CC ECO:0000250|UniProtKB:Q3UFB7, ECO:0000269|PubMed:1312719, CC ECO:0000269|PubMed:1850821, ECO:0000269|PubMed:20811452}. CC -!- CATALYTIC ACTIVITY: CC Reaction=L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + CC ADP + H(+); Xref=Rhea:RHEA:10596, Rhea:RHEA-COMP:10136, Rhea:RHEA- CC COMP:20101, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:46858, CC ChEBI:CHEBI:61978, 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). Interacts with TSPAN1; this CC interaction promotes NTRK1 stability (PubMed:31440771). CC {ECO:0000250|UniProtKB:P04629, ECO:0000269|PubMed:11150334, CC ECO:0000269|PubMed:11244088, ECO:0000269|PubMed:12471037, CC ECO:0000269|PubMed:15167895, ECO:0000269|PubMed:15378608, CC ECO:0000269|PubMed:16223723, ECO:0000269|PubMed:16306406, CC ECO:0000269|PubMed:17724123, ECO:0000269|PubMed:17967490, CC ECO:0000269|PubMed:18624909, ECO:0000269|PubMed:26446845, CC ECO:0000269|PubMed:31440771, 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, ECO:0000269|PubMed:31440771}; Single-pass CC type I membrane protein {ECO:0000305|PubMed:1850821}. Early endosome CC membrane {ECO:0000269|PubMed:17724123, ECO:0000269|PubMed:26446845}; CC Single-pass type I membrane protein {ECO:0000305}. Late endosome CC membrane {ECO:0000269|PubMed:17724123, ECO:0000269|PubMed:26446845}; CC Single-pass type I membrane protein {ECO:0000305}. Recycling endosome CC membrane {ECO:0000269|PubMed:26446845}; Single-pass type I membrane CC protein {ECO:0000305}. Note=Internalized to endosomes upon binding of CC NGF or NTF3 and further transported to the cell body via a retrograde CC axonal transport. Localized at cell membrane and early endosomes before CC nerve growth factor (NGF) stimulation (PubMed:17724123, CC PubMed:26446845). Recruited to late endosomes after NGF stimulation CC (PubMed:17724123, PubMed:26446845). Colocalized with RAPGEF2 at late CC endosomes (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}. 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; 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 RefSeq; XP_038958932.1; XM_039103004.2. [P35739-2] DR AlphaFoldDB; P35739; -. DR SMR; P35739; -. DR BioGRID; 248731; 24. DR CORUM; P35739; -. DR DIP; DIP-5716N; -. DR FunCoup; P35739; 992. DR IntAct; P35739; 7. DR MINT; P35739; -. DR STRING; 10116.ENSRNOP00000018961; -. DR BindingDB; P35739; -. DR ChEMBL; CHEMBL4220; -. DR GlyCosmos; P35739; 11 sites, No reported glycans. DR GlyGen; P35739; 11 sites. DR iPTMnet; P35739; -. DR PhosphoSitePlus; P35739; -. DR PaxDb; 10116-ENSRNOP00000018961; -. DR Ensembl; ENSRNOT00000018961.5; ENSRNOP00000018961.3; ENSRNOG00000013953.10. [P35739-1] DR Ensembl; ENSRNOT00055039763; ENSRNOP00055032286; ENSRNOG00055023126. [P35739-1] DR Ensembl; ENSRNOT00060054994; ENSRNOP00060045463; ENSRNOG00060031729. [P35739-1] DR Ensembl; ENSRNOT00065051271; ENSRNOP00065042210; ENSRNOG00065029663. [P35739-1] DR GeneID; 59109; -. DR KEGG; rno:59109; -. DR UCSC; RGD:620144; rat. [P35739-1] DR AGR; RGD:620144; -. 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; LTCHISA; -. DR OrthoDB; 10005095at2759; -. DR PhylomeDB; P35739; -. 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 cell types or tissues. DR ExpressionAtlas; P35739; baseline and differential. DR GO; GO:0030424; C:axon; IDA:RGD. DR GO; GO:0009986; C:cell surface; IDA:MGI. DR GO; GO:0005737; C:cytoplasm; ISO: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; EXP:UniProtKB. DR GO; GO:0000139; C:Golgi membrane; TAS:Reactome. DR GO; GO:0005770; C:late endosome; IDA:UniProtKB. DR GO; GO:0031902; C:late endosome membrane; EXP:UniProtKB. DR GO; GO:0005739; C:mitochondrion; IDA:RGD. 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:0055037; C:recycling endosome; IDA:UniProtKB. DR GO; GO:0055038; C:recycling endosome membrane; EXP:UniProtKB. DR GO; GO:0043235; C:signaling receptor complex; ISO:RGD. DR GO; GO:0005524; F:ATP binding; IEA:InterPro. 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: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:0007169; P:cell surface receptor protein tyrosine kinase signaling pathway; IBA:GO_Central. 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:0038180; P:nerve growth factor signaling pathway; IDA:UniProtKB. DR GO; GO:0007399; P:nervous system development; ISO:RGD. DR GO; GO:0048666; P:neuron development; ISO:RGD. DR GO; GO:0031175; P:neuron projection development; ISO:RGD. 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:0045766; P:positive regulation of angiogenesis; 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:0010976; P:positive regulation of neuron projection development; ISS:UniProtKB. DR GO; GO:0051897; P:positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction; IDA:BHF-UCL. DR GO; GO:0043068; P:positive regulation of programmed cell death; IDA:UniProtKB. DR GO; GO:0046579; P:positive regulation of Ras protein signal transduction; ISS:UniProtKB. 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: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:0009410; P:response to xenobiotic stimulus; IDA:RGD. DR GO; GO:0060009; P:Sertoli cell development; IMP:RGD. DR GO; GO:0007283; P:spermatogenesis; IEP:RGD. DR GO; GO:0048485; P:sympathetic nervous system development; ISS:UniProtKB. DR CDD; cd04971; IgI_TrKABC_d5; 1. DR FunFam; 1.10.510.10:FF:000034; Tyrosine-protein kinase receptor; 1. DR FunFam; 2.60.40.10:FF:000522; Tyrosine-protein kinase receptor; 1. DR FunFam; 2.60.40.10:FF:000664; Tyrosine-protein kinase receptor; 1. DR FunFam; 3.30.200.20:FF:000033; Tyrosine-protein kinase receptor; 1. DR FunFam; 3.80.10.10:FF:000163; Tyrosine-protein kinase receptor; 1. DR Gene3D; 2.60.40.10; Immunoglobulins; 2. DR Gene3D; 3.30.200.20; Phosphorylase Kinase, domain 1; 1. DR Gene3D; 3.80.10.10; Ribonuclease Inhibitor; 1. DR Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 1. 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; 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; IPR050122; RTK. 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:SF370; HIGH AFFINITY NERVE GROWTH FACTOR RECEPTOR; 1. DR PANTHER; PTHR24416; TYROSINE-PROTEIN KINASE RECEPTOR; 1. DR Pfam; PF07679; I-set; 1. 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; 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; 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 //