ID NTRK1_MOUSE Reviewed; 799 AA. AC Q3UFB7; DT 20-FEB-2007, integrated into UniProtKB/Swiss-Prot. DT 20-FEB-2007, sequence version 2. DT 27-MAR-2024, entry version 159. 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 Flags: Precursor; GN Name=Ntrk1; 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 [LARGE SCALE MRNA]. RC STRAIN=C57BL/6J; TISSUE=Embryo, and Sympathetic ganglion; 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 [2] RP DISRUPTION PHENOTYPE, AND FUNCTION IN DEVELOPMENT OF THE NERVOUS SYSTEM. RX PubMed=8145823; DOI=10.1038/368246a0; RA Smeyne R.J., Klein R., Schnapp A., Long L.K., Bryant S., Lewin A., RA Lira S.A., Barbacid M.; RT "Severe sensory and sympathetic neuropathies in mice carrying a disrupted RT Trk/NGF receptor gene."; RL Nature 368:246-249(1994). RN [3] RP FUNCTION IN SYMPATHETIC NEURONS SURVIVAL, AND DEVELOPMENTAL STAGE. RX PubMed=8815902; DOI=10.1523/jneurosci.16-19-06208.1996; RA Fagan A.M., Zhang H., Landis S., Smeyne R.J., Silos-Santiago I., RA Barbacid M.; RT "TrkA, but not TrkC, receptors are essential for survival of sympathetic RT neurons in vivo."; RL J. Neurosci. 16:6208-6218(1996). RN [4] 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 [5] 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 [6] RP FUNCTION IN NGF AND NTF3 SIGNALING, ACTIVITY REGULATION, AND SUBCELLULAR RP LOCATION. RX PubMed=21816277; DOI=10.1016/j.cell.2011.07.008; RA Harrington A.W., St Hillaire C., Zweifel L.S., Glebova N.O., RA Philippidou P., Halegoua S., Ginty D.D.; RT "Recruitment of actin modifiers to TrkA endosomes governs retrograde NGF RT signaling and survival."; RL Cell 146:421-434(2011). RN [7] 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). 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, it can also bind and be activated by CC NTF3/neurotrophin-3. However, NTF3 only supports axonal extension CC through NTRK1 but has no effect on neuron survival. Upon dimeric NGF CC ligand-binding, undergoes homodimerization, autophosphorylation and CC activation. Recruits, phosphorylates and/or activates several CC downstream effectors including SHC1, FRS2, SH2B1, SH2B2 and PLCG1 that CC regulate distinct overlapping signaling cascades driving cell survival CC and 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:0000269|PubMed:21816277, CC ECO:0000269|PubMed:8145823, ECO:0000269|PubMed:8815902}. 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. CC SH2D1A inhibits the autophosphorylation of the receptor, and alters the CC recruitment and activation of downstream effectors and signaling CC cascades. Regulated by NGFR. {ECO:0000269|PubMed:16113645, CC ECO:0000269|PubMed:16223723, ECO:0000269|PubMed:21816277}. 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. Interacts with RAPGEF2; the interaction is CC strengthened after NGF stimulation. Interacts with SQSTM1; bridges CC NTRK1 to NGFR. Forms a ternary complex with NGFR and KIDINS220; this CC complex is affected by the expression levels of KIDINS220 and an CC increase in KIDINS220 expression leads to a decreased association of CC NGFR and NTRK1. Interacts (phosphorylated upon activation by NGF) with CC SHC1; mediates SHC1 phosphorylation and activation. Interacts CC (phosphorylated upon activation by NGF) with PLCG1; mediates PLCG1 CC phosphorylation and activation. Interacts (phosphorylated) with SH2B1 CC and SH2B2. Interacts with GRB2. Interacts with PIK3R1. Interacts with CC FRS2. Interacts with SORT1; may regulate NTRK1 anterograde axonal CC transport (By similarity). Interacts with SH2D1A; regulates NTRK1 CC (PubMed:16223723). Interacts with NRADD. Interacts with RAB7A. CC Interacts with PTPRS (By similarity). Interacts with USP36; USP36 does CC not deubiquitinate NTRK1 (By similarity). Interacts with GGA3 (By CC similarity). {ECO:0000250|UniProtKB:P04629, CC ECO:0000250|UniProtKB:P35739, ECO:0000269|PubMed:16223723}. CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:P35739}; CC Single-pass type I membrane protein {ECO:0000250|UniProtKB:P35739}. CC Early endosome membrane {ECO:0000269|PubMed:21816277}; Single-pass type CC I membrane protein {ECO:0000269|PubMed:21816277}. Late endosome CC membrane {ECO:0000250|UniProtKB:P35739}; Single-pass type I membrane CC protein {ECO:0000250|UniProtKB:P35739}. Recycling endosome membrane CC {ECO:0000250|UniProtKB:P35739}; Single-pass type I membrane protein CC {ECO:0000250|UniProtKB:P35739}. Note=Internalized to endosomes upon CC binding of NGF or NTF3 and further transported to the cell body via a CC retrograde axonal transport. Localized at cell membrane and early CC endosomes before nerve growth factor (NGF) stimulation. Recruited to CC late endosomes after NGF stimulation. Colocalized with RAPGEF2 at late CC endosomes. {ECO:0000250|UniProtKB:P35739}. CC -!- DEVELOPMENTAL STAGE: First detected at 13.5 dpc, a time coinciding with CC the requirement of sympathetic neurons for NGF. CC {ECO:0000269|PubMed:8815902}. CC -!- INDUCTION: Expression oscillates in a circadian manner in the CC suprachiasmatic nucleus (SCN) of the brain. CC {ECO:0000269|PubMed:23785138}. CC -!- DOMAIN: The transmembrane domain mediates interaction with KIDINS220. CC {ECO:0000250|UniProtKB:P35739}. CC -!- DOMAIN: The extracellular domain mediates interaction with NGFR. CC {ECO:0000250|UniProtKB:P35739}. 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 (PubMed:16113645). Undergoes polyubiquitination upon CC activation; regulated by NGFR. Ubiquitination by NEDD4L leads to CC degradation (By similarity). Ubiquitination regulates the CC internalization of the receptor (PubMed:16113645). CC {ECO:0000250|UniProtKB:P04629, ECO:0000269|PubMed:16113645}. CC -!- DISRUPTION PHENOTYPE: Mice die early after birth due to severe sensory CC and sympathetic neuropathies characterized by extensive neuronal cell CC loss in trigeminal, sympathetic and dorsal root ganglia, as well as a CC decrease in the cholinergic basal forebrain projections to the CC hippocampus and cortex. There are for instance 35% fewer cells by 17.5 CC dpc in the superior cervical ganglion, a major component of the CC sympathetic system. {ECO:0000269|PubMed:8145823}. CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein CC kinase family. Insulin receptor subfamily. {ECO:0000255|PROSITE- CC ProRule:PRU00159}. CC -!- SEQUENCE CAUTION: CC Sequence=BAE28644.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; 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; AK081588; -; NOT_ANNOTATED_CDS; mRNA. DR EMBL; AK148691; BAE28644.1; ALT_INIT; mRNA. DR CCDS; CCDS50947.1; -. DR RefSeq; NP_001028296.1; NM_001033124.1. DR AlphaFoldDB; Q3UFB7; -. DR SMR; Q3UFB7; -. DR BioGRID; 201868; 25. DR DIP; DIP-60900N; -. DR IntAct; Q3UFB7; 6. DR STRING; 10090.ENSMUSP00000029712; -. DR GlyCosmos; Q3UFB7; 11 sites, No reported glycans. DR GlyGen; Q3UFB7; 11 sites. DR iPTMnet; Q3UFB7; -. DR PhosphoSitePlus; Q3UFB7; -. DR PaxDb; 10090-ENSMUSP00000029712; -. DR PeptideAtlas; Q3UFB7; -. DR Antibodypedia; 3896; 1895 antibodies from 45 providers. DR DNASU; 18211; -. DR Ensembl; ENSMUST00000029712.5; ENSMUSP00000029712.5; ENSMUSG00000028072.7. DR GeneID; 18211; -. DR KEGG; mmu:18211; -. DR UCSC; uc008psw.1; mouse. DR AGR; MGI:97383; -. DR CTD; 4914; -. DR MGI; MGI:97383; Ntrk1. DR VEuPathDB; HostDB:ENSMUSG00000028072; -. DR eggNOG; KOG1026; Eukaryota. DR GeneTree; ENSGT00940000159412; -. DR HOGENOM; CLU_000288_74_1_1; -. DR InParanoid; Q3UFB7; -. DR OMA; LTCHISA; -. DR OrthoDB; 1614410at2759; -. DR PhylomeDB; Q3UFB7; -. DR TreeFam; TF106465; -. DR Reactome; R-MMU-170968; Frs2-mediated activation. DR Reactome; R-MMU-170984; ARMS-mediated activation. DR Reactome; R-MMU-177504; Retrograde neurotrophin signalling. DR Reactome; R-MMU-187042; TRKA activation by NGF. DR Reactome; R-MMU-198203; PI3K/AKT activation. DR BioGRID-ORCS; 18211; 3 hits in 81 CRISPR screens. DR PRO; PR:Q3UFB7; -. DR Proteomes; UP000000589; Chromosome 3. DR RNAct; Q3UFB7; Protein. DR Bgee; ENSMUSG00000028072; Expressed in lumbar dorsal root ganglion and 82 other cell types or tissues. DR GO; GO:0030424; C:axon; IDA:MGI. DR GO; GO:0009986; C:cell surface; IDA:MGI. DR GO; GO:0005737; C:cytoplasm; IDA:MGI. DR GO; GO:0030425; C:dendrite; ISO:MGI. DR GO; GO:0005769; C:early endosome; IDA:MGI. DR GO; GO:0031901; C:early endosome membrane; IEA:UniProtKB-SubCell. DR GO; GO:0005770; C:late endosome; IDA:MGI. DR GO; GO:0031902; C:late endosome membrane; IEA:UniProtKB-SubCell. DR GO; GO:0043025; C:neuronal cell body; ISO:MGI. DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB. DR GO; GO:0032991; C:protein-containing complex; ISS:UniProtKB. DR GO; GO:0043235; C:receptor complex; ISO:MGI. DR GO; GO:0055037; C:recycling endosome; ISO:MGI. 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; ISO:MGI. DR GO; GO:0042802; F:identical protein binding; ISO:MGI. DR GO; GO:0019900; F:kinase binding; ISO:MGI. DR GO; GO:0048406; F:nerve growth factor binding; ISS:UniProtKB. 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; ISO:MGI. 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; ISO:MGI. DR GO; GO:0004714; F:transmembrane receptor protein tyrosine kinase activity; ISS:UniProtKB. DR GO; GO:0007411; P:axon guidance; ISO:MGI. DR GO; GO:0060385; P:axonogenesis involved in innervation; IMP:UniProtKB. DR GO; GO:0030183; P:B cell differentiation; IMP:MGI. DR GO; GO:0061368; P:behavioral response to formalin induced pain; IMP:MGI. DR GO; GO:0071363; P:cellular response to growth factor stimulus; ISO:MGI. DR GO; GO:1990090; P:cellular response to nerve growth factor stimulus; IDA:MGI. DR GO; GO:0071316; P:cellular response to nicotine; ISO:MGI. DR GO; GO:0007623; P:circadian rhythm; IEP:UniProtKB. DR GO; GO:0050966; P:detection of mechanical stimulus involved in sensory perception of pain; ISO:MGI. DR GO; GO:0050965; P:detection of temperature stimulus involved in sensory perception of pain; ISO:MGI. DR GO; GO:0060384; P:innervation; IMP:MGI. DR GO; GO:0007611; P:learning or memory; ISO:MGI. DR GO; GO:0042490; P:mechanoreceptor differentiation; IMP:MGI. 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:MGI. DR GO; GO:0007399; P:nervous system development; IDA:MGI. DR GO; GO:0051402; P:neuron apoptotic process; IGI:MGI. DR GO; GO:0048666; P:neuron development; ISO:MGI. DR GO; GO:0031175; P:neuron projection development; ISO:MGI. DR GO; GO:0048011; P:neurotrophin TRK receptor signaling pathway; ISS:UniProtKB. DR GO; GO:0021553; P:olfactory nerve development; IEA:Ensembl. DR GO; GO:0038083; P:peptidyl-tyrosine autophosphorylation; ISS:UniProtKB. DR GO; GO:0018108; P:peptidyl-tyrosine phosphorylation; ISS:UniProtKB. DR GO; GO:0045766; P:positive regulation of angiogenesis; ISO:MGI. 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:0051092; P:positive regulation of NF-kappaB transcription factor activity; ISS:UniProtKB. DR GO; GO:0051897; P:positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction; IBA:GO_Central. DR GO; GO:0043068; P:positive regulation of programmed cell death; ISS:UniProtKB. DR GO; GO:0001934; P:positive regulation of protein phosphorylation; ISO:MGI. DR GO; GO:0046579; P:positive regulation of Ras protein signal transduction; 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:0010623; P:programmed cell death involved in cell development; ISS:UniProtKB. DR GO; GO:0046777; P:protein autophosphorylation; ISS:UniProtKB. DR GO; GO:0051896; P:regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction; IBA:GO_Central. DR GO; GO:0014823; P:response to activity; ISO:MGI. DR GO; GO:0048678; P:response to axon injury; IEA:Ensembl. DR GO; GO:0051602; P:response to electrical stimulus; ISO:MGI. DR GO; GO:0051599; P:response to hydrostatic pressure; IEA:Ensembl. DR GO; GO:0035094; P:response to nicotine; ISO:MGI. DR GO; GO:0031667; P:response to nutrient levels; ISO:MGI. DR GO; GO:0009410; P:response to xenobiotic stimulus; ISO:MGI. DR GO; GO:0060009; P:Sertoli cell development; ISO:MGI. DR GO; GO:0048485; P:sympathetic nervous system development; IMP:UniProtKB. DR GO; GO:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; IBA:GO_Central. DR CDD; cd04971; IgI_TrKABC_d5; 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; IPR007110; Ig-like_dom. DR InterPro; IPR036179; Ig-like_dom_sf. DR InterPro; IPR013783; Ig-like_fold. 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 PANTHER; PTHR24416:SF370; HIGH AFFINITY NERVE GROWTH FACTOR RECEPTOR; 1. DR PANTHER; PTHR24416; TYROSINE-PROTEIN KINASE RECEPTOR; 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; SM00219; TyrKc; 1. DR SUPFAM; SSF48726; Immunoglobulin; 2. DR SUPFAM; SSF52058; L domain-like; 1. DR SUPFAM; SSF56112; Protein kinase-like (PK-like); 1. DR PROSITE; PS50835; IG_LIKE; 1. DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1. DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1. DR PROSITE; PS00109; PROTEIN_KINASE_TYR; 1. DR PROSITE; PS00239; RECEPTOR_TYR_KIN_II; 1. DR Genevisible; Q3UFB7; MM. PE 1: Evidence at protein level; KW ATP-binding; Cell membrane; Developmental protein; Differentiation; KW Disulfide bond; Endosome; Glycoprotein; Immunoglobulin domain; Kinase; KW Leucine-rich repeat; Membrane; Neurogenesis; Nucleotide-binding; KW Phosphoprotein; Receptor; Reference proteome; Repeat; Signal; Transferase; KW Transmembrane; Transmembrane helix; Tyrosine-protein kinase; KW Ubl conjugation. FT SIGNAL 1..33 FT /evidence="ECO:0000255" FT CHAIN 34..799 FT /note="High affinity nerve growth factor receptor" FT /id="PRO_0000278537" FT TOPO_DOM 34..420 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 421..441 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 442..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 205..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 /evidence="ECO:0000250" 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" SQ SEQUENCE 799 AA; 87738 MW; 1A37F76A63564603 CRC64; MLRGQRLGQL GWHRPAAGLG SLMTSLMLAC ASAASCREVC CPVGPSGLRC TRAGSLDTLR GLRGAGNLTE LYVENQQHLQ RLEFEDLQGL GELRSLTIVK SGLRFVAPDA FRFTPRLSHL NLSSNALESL SWKTVQGLSL QDLTLSGNPL HCSCALFWLQ RWEQEGLCGV HTQTLHDSGP GDQFLPLGHN TSCGVPTVKI QMPNDSVEVG DDVFLQCQVE GLALQQADWI LTELEGAATV KKFGDLPSLG LILVNVTSDL NKKNVTCWAE NDVGRAEVSV QVSVSFPASV HLGLAVEQHH WCIPFSVDGQ PAPSLRWLFN GSVLNETSFI FTQFLESALT NETMRHGCLR LNQPTHVNNG NYTLLAANPY GQAAASVMAA FMDNPFEFNP EDPIPVSFSP VDGNSTSRDP VEKKDETPFG VSVAVGLAVS AALFLSALLL VLNKCGQRSK FGINRPAVLA PEDGLAMSLH FMTLGGSSLS PTEGKGSGLQ GHIMENPQYF SDTCVHHIKR QDIILKWELG EGAFGKVFLA ECYNLLNDQD KMLVAVKALK EASENARQDF QREAELLTML QHQHIVRFFG VCTEGGPLLM VFEYMRHGDL NRFLRSHGPD AKLLAGGEDV APGPLGLGQL LAVASQVAAG MVYLASLHFV HRDLATRNCL VGQGLVVKIG DFGMSRDIYS TDYYRVGGRT MLPIRWMPPE SILYRKFSTE SDVWSFGVVL WEIFTYGKQP WYQLSNTEAI ECITQGRELE RPRACPPDVY AIMRGCWQRE PQQRLSMKDV HARLQALAQA PPSYLDVLG //