NTRK1_MOUSE
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 03-AUG-2022, entry version 150.
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};
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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 GlyGen; Q3UFB7; 11 sites.
DR iPTMnet; Q3UFB7; -.
DR PhosphoSitePlus; Q3UFB7; -.
DR PaxDb; Q3UFB7; -.
DR PeptideAtlas; Q3UFB7; -.
DR PRIDE; Q3UFB7; -.
DR Antibodypedia; 3896; 1600 antibodies from 45 providers.
DR DNASU; 18211; -.
DR Ensembl; ENSMUST00000029712; ENSMUSP00000029712; ENSMUSG00000028072.
DR GeneID; 18211; -.
DR KEGG; mmu:18211; -.
DR UCSC; uc008psw.1; mouse.
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; IMLKWEL; -.
DR OrthoDB; 295510at2759; -.
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 76 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 80 other tissues.
DR Genevisible; Q3UFB7; MM.
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:0031410; C:cytoplasmic vesicle; ISO: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:0005887; C:integral component of plasma membrane; ISS:UniProtKB.
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:0007568; P:aging; IEA:Ensembl.
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:1901215; P:negative regulation of neuron death; ISO:MGI.
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: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; 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:0006468; P:protein phosphorylation; IDA:MGI.
DR GO; GO:0051896; P:regulation of protein kinase B signaling; 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:0009314; P:response to radiation; IEA:Ensembl.
DR GO; GO:0009410; P:response to xenobiotic stimulus; ISO:MGI.
DR GO; GO:0019233; P:sensory perception of pain; 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 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; 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; 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 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
