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High affinity nerve growth factor receptor (EC 2.7.10.1) (Neurotrophic tyrosine kinase receptor type 1)

 NTRK1_MOUSE             Reviewed;         799 AA.
Q3UFB7;
20-FEB-2007, integrated into UniProtKB/Swiss-Prot.
20-FEB-2007, sequence version 2.
08-MAY-2019, entry version 134.
RecName: Full=High affinity nerve growth factor receptor;
EC=2.7.10.1;
AltName: Full=Neurotrophic tyrosine kinase receptor type 1;
Flags: Precursor;
Name=Ntrk1;
Mus musculus (Mouse).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha;
Muroidea; Muridae; Murinae; Mus; Mus.
NCBI_TaxID=10090;
[1]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
STRAIN=C57BL/6J; TISSUE=Embryo, and Sympathetic ganglion;
PubMed=16141072; DOI=10.1126/science.1112014;
Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M.,
Davis M.J., Wilming L.G., Aidinis V., Allen J.E.,
Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L.,
Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M.,
Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R.,
Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G.,
di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G.,
Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M.,
Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N.,
Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T.,
Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H.,
Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K.,
Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J.,
Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L.,
Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K.,
Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P.,
Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O.,
Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G.,
Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M.,
Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B.,
Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K.,
Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A.,
Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K.,
Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C.,
Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J.,
Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y.,
Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T.,
Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N.,
Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N.,
Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S.,
Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J.,
Hayashizaki Y.;
"The transcriptional landscape of the mammalian genome.";
Science 309:1559-1563(2005).
[2]
DISRUPTION PHENOTYPE, AND FUNCTION IN DEVELOPMENT OF THE NERVOUS
SYSTEM.
PubMed=8145823; DOI=10.1038/368246a0;
Smeyne R.J., Klein R., Schnapp A., Long L.K., Bryant S., Lewin A.,
Lira S.A., Barbacid M.;
"Severe sensory and sympathetic neuropathies in mice carrying a
disrupted Trk/NGF receptor gene.";
Nature 368:246-249(1994).
[3]
FUNCTION IN SYMPATHETIC NEURONS SURVIVAL, AND DEVELOPMENTAL STAGE.
PubMed=8815902;
Fagan A.M., Zhang H., Landis S., Smeyne R.J., Silos-Santiago I.,
Barbacid M.;
"TrkA, but not TrkC, receptors are essential for survival of
sympathetic neurons in vivo.";
J. Neurosci. 16:6208-6218(1996).
[4]
UBIQUITINATION, AND ACTIVITY REGULATION.
PubMed=16113645; DOI=10.1038/sj.embor.7400503;
Makkerh J.P., Ceni C., Auld D.S., Vaillancourt F., Dorval G.,
Barker P.A.;
"p75 neurotrophin receptor reduces ligand-induced Trk receptor
ubiquitination and delays Trk receptor internalization and
degradation.";
EMBO Rep. 6:936-941(2005).
[5]
ACTIVITY REGULATION, AND INTERACTION WITH SH2D1A.
PubMed=16223723; DOI=10.1074/jbc.M506554200;
Lo K.Y., Chin W.H., Ng Y.P., Cheng A.W., Cheung Z.H., Ip N.Y.;
"SLAM-associated protein as a potential negative regulator in Trk
signaling.";
J. Biol. Chem. 280:41744-41752(2005).
[6]
FUNCTION IN NGF AND NTF3 SIGNALING, ACTIVITY REGULATION, AND
SUBCELLULAR LOCATION.
PubMed=21816277; DOI=10.1016/j.cell.2011.07.008;
Harrington A.W., St Hillaire C., Zweifel L.S., Glebova N.O.,
Philippidou P., Halegoua S., Ginty D.D.;
"Recruitment of actin modifiers to TrkA endosomes governs retrograde
NGF signaling and survival.";
Cell 146:421-434(2011).
[7]
INDUCTION.
PubMed=23785138; DOI=10.1523/JNEUROSCI.2757-12.2013;
Baeza-Raja B., Eckel-Mahan K., Zhang L., Vagena E., Tsigelny I.F.,
Sassone-Corsi P., Ptacek L.J., Akassoglou K.;
"p75 neurotrophin receptor is a clock gene that regulates oscillatory
components of circadian and metabolic networks.";
J. Neurosci. 33:10221-10234(2013).
-!- FUNCTION: Receptor tyrosine kinase involved in the development and
the maturation of the central and peripheral nervous systems
through regulation of proliferation, differentiation and survival
of sympathetic and nervous neurons. High affinity receptor for NGF
which is its primary ligand, it can also bind and be activated by
NTF3/neurotrophin-3. However, NTF3 only supports axonal extension
through NTRK1 but has no effect on neuron survival. Upon dimeric
NGF ligand-binding, undergoes homodimerization,
autophosphorylation and activation. Recruits, phosphorylates
and/or activates several downstream effectors including SHC1,
FRS2, SH2B1, SH2B2 and PLCG1 that regulate distinct overlapping
signaling cascades driving cell survival and differentiation.
Through SHC1 and FRS2 activates a GRB2-Ras-MAPK cascade that
regulates cell differentiation and survival. Through PLCG1
controls NF-Kappa-B activation and the transcription of genes
involved in cell survival. Through SHC1 and SH2B1 controls a Ras-
PI3 kinase-AKT1 signaling cascade that is also regulating
survival. In absence of ligand and activation, may promote cell
death, making the survival of neurons dependent on trophic
factors. {ECO:0000269|PubMed:21816277, ECO:0000269|PubMed:8145823,
ECO:0000269|PubMed:8815902}.
-!- CATALYTIC ACTIVITY:
Reaction=ATP + L-tyrosyl-[protein] = ADP + H(+) + O-phospho-L-
tyrosyl-[protein]; Xref=Rhea:RHEA:10596, Rhea:RHEA-COMP:10136,
Rhea:RHEA-COMP:10137, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616,
ChEBI:CHEBI:46858, ChEBI:CHEBI:82620, ChEBI:CHEBI:456216;
EC=2.7.10.1; Evidence={ECO:0000255|PROSITE-ProRule:PRU10028};
-!- ACTIVITY REGULATION: The pro-survival signaling effect of NTRK1 in
neurons requires its endocytosis into signaling early endosomes
and its retrograde axonal transport. This is regulated by
different proteins including CFL1, RAC1 and SORT1. NTF3 is unable
to induce this signaling probably due to the lability of the NTF3-
NTRK1 complex in endosomes. SH2D1A inhibits the
autophosphorylation of the receptor, and alters the recruitment
and activation of downstream effectors and signaling cascades.
Regulated by NGFR. {ECO:0000269|PubMed:16113645,
ECO:0000269|PubMed:16223723, ECO:0000269|PubMed:21816277}.
-!- SUBUNIT: Exists in a dynamic equilibrium between monomeric (low
affinity) and dimeric (high affinity) structures. Homodimerization
is induced by binding of a NGF dimer (By similarity). Found in a
complex, at least composed of KIDINS220, MAGI2, NTRK1 and RAPGEF2;
the complex is mainly formed at late endosomes in a nerve growth
factor (NGF)-dependent manner. Interacts with RAPGEF2; the
interaction is strengthened after NGF stimulation. Interacts with
SQSTM1; bridges NTRK1 to NGFR. Forms a ternary complex with NGFR
and KIDINS220; this complex is affected by the expression levels
of KIDINS220 and an increase in KIDINS220 expression leads to a
decreased association of NGFR and NTRK1. Interacts (phosphorylated
upon activation by NGF) with SHC1; mediates SHC1 phosphorylation
and activation. Interacts (phosphorylated upon activation by NGF)
with PLCG1; mediates PLCG1 phosphorylation and activation.
Interacts (phosphorylated) with SH2B1 and SH2B2. Interacts with
GRB2. Interacts with PIK3R1. Interacts with FRS2. Interacts with
SORT1; may regulate NTRK1 anterograde axonal transport (By
similarity). Interacts with SH2D1A; regulates NTRK1
(PubMed:16223723). Interacts with NRADD. Interacts with RAB7A.
Interacts with PTPRS (By similarity). Interacts with USP36; USP36
does not deubiquitinate NTRK1 (By similarity). Interacts with GGA3
(By similarity). {ECO:0000250|UniProtKB:P04629,
ECO:0000250|UniProtKB:P35739, ECO:0000269|PubMed:16223723}.
-!- SUBCELLULAR LOCATION: Cell membrane
{ECO:0000250|UniProtKB:P35739}; Single-pass type I membrane
protein {ECO:0000250|UniProtKB:P35739}. Early endosome membrane
{ECO:0000269|PubMed:21816277}; Single-pass type I membrane protein
{ECO:0000269|PubMed:21816277}. Late endosome membrane
{ECO:0000250|UniProtKB:P35739}; Single-pass type I membrane
protein {ECO:0000250|UniProtKB:P35739}. Recycling endosome
membrane {ECO:0000250|UniProtKB:P35739}; Single-pass type I
membrane protein {ECO:0000250|UniProtKB:P35739}. Note=Internalized
to endosomes upon binding of NGF or NTF3 and further transported
to the cell body via a retrograde axonal transport. Localized at
cell membrane and early endosomes before nerve growth factor (NGF)
stimulation. Recruited to late endosomes after NGF stimulation.
Colocalized with RAPGEF2 at late endosomes.
{ECO:0000250|UniProtKB:P35739}.
-!- DEVELOPMENTAL STAGE: First detected at 13.5 dpc, a time coinciding
with the requirement of sympathetic neurons for NGF.
{ECO:0000269|PubMed:8815902}.
-!- INDUCTION: Expression oscillates in a circadian manner in the
suprachiasmatic nucleus (SCN) of the brain.
{ECO:0000269|PubMed:23785138}.
-!- DOMAIN: The transmembrane domain mediates interaction with
KIDINS220. {ECO:0000250|UniProtKB:P35739}.
-!- DOMAIN: The extracellular domain mediates interaction with NGFR.
{ECO:0000250|UniProtKB:P35739}.
-!- PTM: Ligand-mediated autophosphorylation. Interaction with SQSTM1
is phosphotyrosine-dependent. Autophosphorylation at Tyr-499
mediates interaction and phosphorylation of SHC1.
-!- PTM: N-glycosylated. {ECO:0000250|UniProtKB:P04629}.
-!- PTM: Ubiquitinated (PubMed:16113645). Undergoes polyubiquitination
upon activation; regulated by NGFR. Ubiquitination by NEDD4L leads
to degradation (By similarity). Ubiquitination regulates the
internalization of the receptor (PubMed:16113645).
{ECO:0000250|UniProtKB:P04629, ECO:0000269|PubMed:16113645}.
-!- DISRUPTION PHENOTYPE: Mice die early after birth due to severe
sensory and sympathetic neuropathies characterized by extensive
neuronal cell loss in trigeminal, sympathetic and dorsal root
ganglia, as well as a decrease in the cholinergic basal forebrain
projections to the hippocampus and cortex. There are for instance
35% fewer cells by 17.5 dpc in the superior cervical ganglion, a
major component of the sympathetic system.
{ECO:0000269|PubMed:8145823}.
-!- SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein
kinase family. Insulin receptor subfamily. {ECO:0000255|PROSITE-
ProRule:PRU00159}.
-!- SEQUENCE CAUTION:
Sequence=BAE28644.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305};
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EMBL; AK081588; -; NOT_ANNOTATED_CDS; mRNA.
EMBL; AK148691; BAE28644.1; ALT_INIT; mRNA.
CCDS; CCDS50947.1; -.
RefSeq; NP_001028296.1; NM_001033124.1.
SMR; Q3UFB7; -.
BioGrid; 201868; 10.
DIP; DIP-60900N; -.
IntAct; Q3UFB7; 6.
STRING; 10090.ENSMUSP00000029712; -.
iPTMnet; Q3UFB7; -.
PhosphoSitePlus; Q3UFB7; -.
PaxDb; Q3UFB7; -.
PeptideAtlas; Q3UFB7; -.
PRIDE; Q3UFB7; -.
Ensembl; ENSMUST00000029712; ENSMUSP00000029712; ENSMUSG00000028072.
GeneID; 18211; -.
KEGG; mmu:18211; -.
UCSC; uc008psw.1; mouse.
CTD; 4914; -.
MGI; MGI:97383; Ntrk1.
eggNOG; KOG1026; Eukaryota.
eggNOG; ENOG410YGKQ; LUCA.
GeneTree; ENSGT00940000159412; -.
HOGENOM; HOG000264255; -.
InParanoid; Q3UFB7; -.
KO; K03176; -.
OMA; ECANLSP; -.
OrthoDB; 295510at2759; -.
PhylomeDB; Q3UFB7; -.
TreeFam; TF106465; -.
Reactome; R-MMU-170968; Frs2-mediated activation.
Reactome; R-MMU-170984; ARMS-mediated activation.
Reactome; R-MMU-177504; Retrograde neurotrophin signalling.
Reactome; R-MMU-187042; TRKA activation by NGF.
Reactome; R-MMU-198203; PI3K/AKT activation.
PRO; PR:Q3UFB7; -.
Proteomes; UP000000589; Chromosome 3.
Bgee; ENSMUSG00000028072; Expressed in 79 organ(s), highest expression level in dorsal root ganglion.
Genevisible; Q3UFB7; MM.
GO; GO:0030424; C:axon; IDA:MGI.
GO; GO:0009986; C:cell surface; IDA:MGI.
GO; GO:0005737; C:cytoplasm; IDA:MGI.
GO; GO:0031410; C:cytoplasmic vesicle; ISO:MGI.
GO; GO:0030425; C:dendrite; ISO:MGI.
GO; GO:0005769; C:early endosome; IDA:MGI.
GO; GO:0031901; C:early endosome membrane; IEA:UniProtKB-SubCell.
GO; GO:0005887; C:integral component of plasma membrane; ISS:UniProtKB.
GO; GO:0005770; C:late endosome; IDA:MGI.
GO; GO:0031902; C:late endosome membrane; IEA:UniProtKB-SubCell.
GO; GO:0043025; C:neuronal cell body; ISO:MGI.
GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
GO; GO:0032991; C:protein-containing complex; ISS:UniProtKB.
GO; GO:0043235; C:receptor complex; ISO:MGI.
GO; GO:0055037; C:recycling endosome; ISO:MGI.
GO; GO:0055038; C:recycling endosome membrane; IEA:UniProtKB-SubCell.
GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
GO; GO:0005004; F:GPI-linked ephrin receptor activity; ISO:MGI.
GO; GO:0019900; F:kinase binding; ISO:MGI.
GO; GO:0048406; F:nerve growth factor binding; ISS:UniProtKB.
GO; GO:0010465; F:nerve growth factor receptor activity; ISS:UniProtKB.
GO; GO:0043121; F:neurotrophin binding; IBA:GO_Central.
GO; GO:0005166; F:neurotrophin p75 receptor binding; ISO:MGI.
GO; GO:0005030; F:neurotrophin receptor activity; IBA:GO_Central.
GO; GO:0042803; F:protein homodimerization activity; ISS:UniProtKB.
GO; GO:0004713; F:protein tyrosine kinase activity; ISO:MGI.
GO; GO:0004714; F:transmembrane receptor protein tyrosine kinase activity; ISS:UniProtKB.
GO; GO:0007568; P:aging; IEA:Ensembl.
GO; GO:0007411; P:axon guidance; ISO:MGI.
GO; GO:0060385; P:axonogenesis involved in innervation; IMP:UniProtKB.
GO; GO:0030183; P:B cell differentiation; IMP:MGI.
GO; GO:0061368; P:behavioral response to formalin induced pain; IMP:MGI.
GO; GO:0071363; P:cellular response to growth factor stimulus; ISO:MGI.
GO; GO:1990090; P:cellular response to nerve growth factor stimulus; IDA:MGI.
GO; GO:0071316; P:cellular response to nicotine; ISO:MGI.
GO; GO:0007623; P:circadian rhythm; IEP:UniProtKB.
GO; GO:0050966; P:detection of mechanical stimulus involved in sensory perception of pain; ISO:MGI.
GO; GO:0050965; P:detection of temperature stimulus involved in sensory perception of pain; ISO:MGI.
GO; GO:0060384; P:innervation; IMP:MGI.
GO; GO:0007611; P:learning or memory; ISO:MGI.
GO; GO:0042490; P:mechanoreceptor differentiation; IMP:MGI.
GO; GO:0008285; P:negative regulation of cell population proliferation; ISS:UniProtKB.
GO; GO:0043524; P:negative regulation of neuron apoptotic process; IMP:UniProtKB.
GO; GO:1901215; P:negative regulation of neuron death; ISO:MGI.
GO; GO:0038180; P:nerve growth factor signaling pathway; IDA:MGI.
GO; GO:0007399; P:nervous system development; IDA:MGI.
GO; GO:0048666; P:neuron development; ISO:MGI.
GO; GO:0031175; P:neuron projection development; ISO:MGI.
GO; GO:0048011; P:neurotrophin TRK receptor signaling pathway; ISS:UniProtKB.
GO; GO:0021553; P:olfactory nerve development; IEA:Ensembl.
GO; GO:0038083; P:peptidyl-tyrosine autophosphorylation; ISS:UniProtKB.
GO; GO:0018108; P:peptidyl-tyrosine phosphorylation; ISS:UniProtKB.
GO; GO:0045766; P:positive regulation of angiogenesis; ISO:MGI.
GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; ISS:UniProtKB.
GO; GO:0043547; P:positive regulation of GTPase activity; ISS:UniProtKB.
GO; GO:0043410; P:positive regulation of MAPK cascade; IBA:GO_Central.
GO; GO:0010976; P:positive regulation of neuron projection development; ISS:UniProtKB.
GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; ISS:UniProtKB.
GO; GO:0014068; P:positive regulation of phosphatidylinositol 3-kinase signaling; IBA:GO_Central.
GO; GO:0043068; P:positive regulation of programmed cell death; ISS:UniProtKB.
GO; GO:0001934; P:positive regulation of protein phosphorylation; ISO:MGI.
GO; GO:0046579; P:positive regulation of Ras protein signal transduction; ISS:UniProtKB.
GO; GO:0051965; P:positive regulation of synapse assembly; IDA:MGI.
GO; GO:0051968; P:positive regulation of synaptic transmission, glutamatergic; ISO:MGI.
GO; GO:0010623; P:programmed cell death involved in cell development; ISS:UniProtKB.
GO; GO:0046777; P:protein autophosphorylation; ISS:UniProtKB.
GO; GO:0006468; P:protein phosphorylation; IDA:MGI.
GO; GO:0043408; P:regulation of MAPK cascade; IBA:GO_Central.
GO; GO:0014823; P:response to activity; ISO:MGI.
GO; GO:0048678; P:response to axon injury; IEA:Ensembl.
GO; GO:0042493; P:response to drug; ISO:MGI.
GO; GO:0051602; P:response to electrical stimulus; ISO:MGI.
GO; GO:0051599; P:response to hydrostatic pressure; IEA:Ensembl.
GO; GO:0035094; P:response to nicotine; ISO:MGI.
GO; GO:0031667; P:response to nutrient levels; ISO:MGI.
GO; GO:0009314; P:response to radiation; IEA:Ensembl.
GO; GO:0019233; P:sensory perception of pain; ISO:MGI.
GO; GO:0060009; P:Sertoli cell development; ISO:MGI.
GO; GO:0048485; P:sympathetic nervous system development; IMP:UniProtKB.
GO; GO:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; IBA:GO_Central.
Gene3D; 2.60.40.10; -; 2.
Gene3D; 3.80.10.10; -; 1.
InterPro; IPR007110; Ig-like_dom.
InterPro; IPR036179; Ig-like_dom_sf.
InterPro; IPR013783; Ig-like_fold.
InterPro; IPR011009; Kinase-like_dom_sf.
InterPro; IPR001611; Leu-rich_rpt.
InterPro; IPR032675; LRR_dom_sf.
InterPro; IPR031635; NTRK_C2.
InterPro; IPR000719; Prot_kinase_dom.
InterPro; IPR017441; Protein_kinase_ATP_BS.
InterPro; IPR001245; Ser-Thr/Tyr_kinase_cat_dom.
InterPro; IPR008266; Tyr_kinase_AS.
InterPro; IPR020635; Tyr_kinase_cat_dom.
InterPro; IPR020461; Tyr_kinase_neurotrophic_rcpt_1.
InterPro; IPR020777; Tyr_kinase_NGF_rcpt.
InterPro; IPR002011; Tyr_kinase_rcpt_2_CS.
Pfam; PF13855; LRR_8; 1.
Pfam; PF07714; Pkinase_Tyr; 1.
Pfam; PF16920; TPKR_C2; 1.
PRINTS; PR01939; NTKRECEPTOR.
PRINTS; PR01940; NTKRECEPTOR1.
PRINTS; PR00109; TYRKINASE.
SMART; SM00219; TyrKc; 1.
SUPFAM; SSF48726; SSF48726; 2.
SUPFAM; SSF56112; SSF56112; 1.
PROSITE; PS50835; IG_LIKE; 1.
PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
PROSITE; PS00109; PROTEIN_KINASE_TYR; 1.
PROSITE; PS00239; RECEPTOR_TYR_KIN_II; 1.
1: Evidence at protein level;
ATP-binding; Cell membrane; Complete proteome; Developmental protein;
Differentiation; Disulfide bond; Endosome; Glycoprotein;
Immunoglobulin domain; Kinase; Leucine-rich repeat; Membrane;
Neurogenesis; Nucleotide-binding; Phosphoprotein; Receptor;
Reference proteome; Repeat; Signal; Transferase; Transmembrane;
Transmembrane helix; Tyrosine-protein kinase; Ubl conjugation.
SIGNAL 1 33 {ECO:0000255}.
CHAIN 34 799 High affinity nerve growth factor
receptor.
/FTId=PRO_0000278537.
TOPO_DOM 34 420 Extracellular. {ECO:0000255}.
TRANSMEM 421 441 Helical. {ECO:0000255}.
TOPO_DOM 442 799 Cytoplasmic. {ECO:0000255}.
REPEAT 90 113 LRR 1.
REPEAT 116 137 LRR 2.
DOMAIN 148 219 LRRCT.
DOMAIN 196 285 Ig-like C2-type 1.
DOMAIN 205 368 Ig-like C2-type 2.
DOMAIN 513 784 Protein kinase. {ECO:0000255|PROSITE-
ProRule:PRU00159}.
NP_BIND 519 527 ATP. {ECO:0000255|PROSITE-
ProRule:PRU00159}.
REGION 472 493 Interaction with SQSTM1. {ECO:0000250}.
ACT_SITE 653 653 Proton acceptor. {ECO:0000255|PROSITE-
ProRule:PRU00159, ECO:0000255|PROSITE-
ProRule:PRU10028}.
BINDING 547 547 ATP. {ECO:0000255|PROSITE-
ProRule:PRU00159}.
SITE 499 499 Interaction with SHC1. {ECO:0000250}.
SITE 794 794 Interaction with PLCG1. {ECO:0000250}.
MOD_RES 499 499 Phosphotyrosine; by autocatalysis.
{ECO:0000250|UniProtKB:P04629}.
MOD_RES 679 679 Phosphotyrosine; by autocatalysis.
{ECO:0000250|UniProtKB:P04629}.
MOD_RES 683 683 Phosphotyrosine; by autocatalysis.
{ECO:0000250|UniProtKB:P04629}.
MOD_RES 684 684 Phosphotyrosine; by autocatalysis.
{ECO:0000250|UniProtKB:P04629}.
MOD_RES 794 794 Phosphotyrosine; by autocatalysis.
{ECO:0000250|UniProtKB:P04629}.
CARBOHYD 67 67 N-linked (GlcNAc...) asparagine.
{ECO:0000255}.
CARBOHYD 121 121 N-linked (GlcNAc...) asparagine.
{ECO:0000255}.
CARBOHYD 190 190 N-linked (GlcNAc...) asparagine.
{ECO:0000255}.
CARBOHYD 204 204 N-linked (GlcNAc...) asparagine.
{ECO:0000255}.
CARBOHYD 255 255 N-linked (GlcNAc...) asparagine.
{ECO:0000255}.
CARBOHYD 264 264 N-linked (GlcNAc...) asparagine.
{ECO:0000255}.
CARBOHYD 320 320 N-linked (GlcNAc...) asparagine.
{ECO:0000255}.
CARBOHYD 325 325 N-linked (GlcNAc...) asparagine.
{ECO:0000255}.
CARBOHYD 341 341 N-linked (GlcNAc...) asparagine.
{ECO:0000255}.
CARBOHYD 361 361 N-linked (GlcNAc...) asparagine.
{ECO:0000255}.
CARBOHYD 404 404 N-linked (GlcNAc...) asparagine.
{ECO:0000255}.
DISULFID 36 41 {ECO:0000250|UniProtKB:P04629}.
DISULFID 40 50 {ECO:0000250|UniProtKB:P04629}.
DISULFID 154 193 {ECO:0000255|PROSITE-ProRule:PRU00114}.
DISULFID 217 267 {ECO:0000255|PROSITE-ProRule:PRU00114}.
DISULFID 302 348 {ECO:0000250|UniProtKB:P04629}.
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


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Pathways :
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WP1206: Signaling of Hepatocyte Growth Factor Receptor
WP810: Signaling of Hepatocyte Growth Factor Receptor
WP94: Signaling of Hepatocyte Growth Factor Receptor
WP1162: Signaling of Hepatocyte Growth Factor Receptor
WP1046: Signaling of Hepatocyte Growth Factor Receptor
WP313: Signaling of Hepatocyte Growth Factor Receptor
WP193: Signaling of Hepatocyte Growth Factor Receptor
WP927: Signaling of Hepatocyte Growth Factor Receptor
WP1235: Signaling of Hepatocyte Growth Factor Receptor
WP474: Endochondral Ossification
WP2272: Pathogenic Escherichia coli infection
WP1963: The effect of Glucocorticoids on target gene expression
WP926: TGF-beta Receptor Signaling Pathway
WP1144: B Cell Receptor Signaling Pathway
WP2355: Corticotropin-releasing hormone
WP774: Kit Receptor Signaling Pathway
WP1336: EPO Receptor Signaling
WP1011: T Cell Receptor Signaling Pathway
WP1348: Androgen Receptor Signaling Pathway
WP2079: Serotonin Receptor 2 and STAT3 Signaling
WP2140: MaxYvesSuperCombo
WP581: EPO Receptor Signaling
WP1781: Advanced glycosylation endproduct receptor signaling
WP1025: B Cell Receptor Signaling Pathway

Related Genes :
[NTRK1 MTC TRK TRKA] High affinity nerve growth factor receptor (EC 2.7.10.1) (Neurotrophic tyrosine kinase receptor type 1) (TRK1-transforming tyrosine kinase protein) (Tropomyosin-related kinase A) (Tyrosine kinase receptor) (Tyrosine kinase receptor A) (Trk-A) (gp140trk) (p140-TrkA)
[Ntrk1 Trk Trka] High affinity nerve growth factor receptor (EC 2.7.10.1) (Neurotrophic tyrosine kinase receptor type 1) (Slow nerve growth factor receptor) (p140-TrkA) (Trk-A)
[Ntrk1] High affinity nerve growth factor receptor (EC 2.7.10.1) (Neurotrophic tyrosine kinase receptor type 1)
[NTRK1 TRKA] High affinity nerve growth factor receptor (EC 2.7.10.1) (Neurotrophic tyrosine kinase receptor type 1) (Trk-A) (Fragment)
[NTRK2 TRKB] BDNF/NT-3 growth factors receptor (EC 2.7.10.1) (GP145-TrkB) (Trk-B) (Neurotrophic tyrosine kinase receptor type 2) (TrkB tyrosine kinase) (Tropomyosin-related kinase B)
[Ntrk3 TrkC] NT-3 growth factor receptor (EC 2.7.10.1) (GP145-TrkC) (Trk-C) (Neurotrophic tyrosine kinase receptor type 3) (TrkC tyrosine kinase)
[NTRK3 TRKC] NT-3 growth factor receptor (EC 2.7.10.1) (Neurotrophic tyrosine kinase receptor type 3) (TrkC tyrosine kinase) (Trk-C)
[Ntrk2 Trkb] BDNF/NT-3 growth factors receptor (EC 2.7.10.1) (Neurotrophic tyrosine kinase receptor type 2) (TrkB tyrosine kinase) (Trk-B)
[Ntrk2 Trkb] BDNF/NT-3 growth factors receptor (EC 2.7.10.1) (GP145-TrkB/GP95-TrkB) (Trk-B) (Neurotrophic tyrosine kinase receptor type 2) (TrkB tyrosine kinase)
[NTRK2 TRKB] BDNF/NT-3 growth factors receptor (EC 2.7.10.1) (Neurotrophic tyrosine kinase receptor type 2) (TrkB tyrosine kinase) (Trk-B)
[FLT1 FLT FRT VEGFR1] Vascular endothelial growth factor receptor 1 (VEGFR-1) (EC 2.7.10.1) (Fms-like tyrosine kinase 1) (FLT-1) (Tyrosine-protein kinase FRT) (Tyrosine-protein kinase receptor FLT) (FLT) (Vascular permeability factor receptor)
[Fgfr4 Fgfr-4 Mpk-11] Fibroblast growth factor receptor 4 (FGFR-4) (EC 2.7.10.1) (Protein-tyrosine kinase receptor MPK-11) (CD antigen CD334)
[FGFR1 BFGFR CEK FGFBR FLG FLT2 HBGFR] Fibroblast growth factor receptor 1 (FGFR-1) (EC 2.7.10.1) (Basic fibroblast growth factor receptor 1) (BFGFR) (bFGF-R-1) (Fms-like tyrosine kinase 2) (FLT-2) (N-sam) (Proto-oncogene c-Fgr) (CD antigen CD331)
[Flt1 Emrk2 Flt Vegfr1] Vascular endothelial growth factor receptor 1 (VEGFR-1) (EC 2.7.10.1) (Embryonic receptor kinase 2) (Fms-like tyrosine kinase 1) (FLT-1) (Tyrosine-protein kinase receptor FLT)
[MET] Hepatocyte growth factor receptor (HGF receptor) (EC 2.7.10.1) (HGF/SF receptor) (Proto-oncogene c-Met) (Scatter factor receptor) (SF receptor) (Tyrosine-protein kinase Met)
[kdrl flk flk-1 flk1 flka kdr kdra vegfr2 vegfr4 vegr2 si:ch211-276g21.4] Vascular endothelial growth factor receptor kdr-like (EC 2.7.10.1) (Fetal liver kinase 1) (FLK-1) (Kinase insert domain receptor-A) (Kinase insert domain receptor-like) (Protein-tyrosine kinase receptor flk-1) (Vascular endothelial growth factor receptor 4) (VEGFR-4)
[Kdr Flk-1 Flk1] Vascular endothelial growth factor receptor 2 (VEGFR-2) (EC 2.7.10.1) (Fetal liver kinase 1) (FLK-1) (Kinase NYK) (Protein-tyrosine kinase receptor flk-1) (CD antigen CD309)
[Flt1 Flt-1 Vegfr1] Vascular endothelial growth factor receptor 1 (VEGFR-1) (EC 2.7.10.1) (Fms-like tyrosine kinase 1) (FLT-1) (Tyrosine-protein kinase receptor FLT)
[EGFR ERBB ERBB1 HER1] Epidermal growth factor receptor (EC 2.7.10.1) (Proto-oncogene c-ErbB-1) (Receptor tyrosine-protein kinase erbB-1)
[FGFR1 CEK1] Fibroblast growth factor receptor 1 (FGFR-1) (bFGF-R-1) (EC 2.7.10.1) (Basic fibroblast growth factor receptor 1) (Tyrosine kinase receptor CEK1)
[kdr flk1b kdrb si:busm1-205d10.1 si:ch211-254j6.1] Vascular endothelial growth factor receptor 2 (VEGFR-2) (EC 2.7.10.1) (Fetal liver kinase 1b) (FLK-1b) (Kinase insert domain receptor) (Kinase insert domain receptor-B) (Protein-tyrosine kinase receptor flk-1b) (Vascular endothelial growth factor receptor 2 homolog B) (VEGFR-2 homolog B)
[Igf1r] Insulin-like growth factor 1 receptor (EC 2.7.10.1) (Insulin-like growth factor I receptor) (IGF-I receptor) (CD antigen CD221) [Cleaved into: Insulin-like growth factor 1 receptor alpha chain; Insulin-like growth factor 1 receptor beta chain]
[Pdgfrb Pdgfr Pdgfr1] Platelet-derived growth factor receptor beta (PDGF-R-beta) (PDGFR-beta) (EC 2.7.10.1) (Beta platelet-derived growth factor receptor) (Beta-type platelet-derived growth factor receptor) (CD140 antigen-like family member B) (Platelet-derived growth factor receptor 1) (PDGFR-1) (CD antigen CD140b)
[Erbb2 Neu] Receptor tyrosine-protein kinase erbB-2 (EC 2.7.10.1) (Epidermal growth factor receptor-related protein) (Proto-oncogene Neu) (Proto-oncogene c-ErbB-2) (p185erbB2) (p185neu) (CD antigen CD340)
[KIT SCFR] Mast/stem cell growth factor receptor Kit (SCFR) (EC 2.7.10.1) (Piebald trait protein) (PBT) (Proto-oncogene c-Kit) (Tyrosine-protein kinase Kit) (p145 c-kit) (v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog) (CD antigen CD117)
[Erbb3] Receptor tyrosine-protein kinase erbB-3 (EC 2.7.10.1) (Glial growth factor receptor) (Proto-oncogene-like protein c-ErbB-3)
[FGFR2 BEK KGFR KSAM] Fibroblast growth factor receptor 2 (FGFR-2) (EC 2.7.10.1) (K-sam) (KGFR) (Keratinocyte growth factor receptor) (CD antigen CD332)
[KDR FLK1 VEGFR2] Vascular endothelial growth factor receptor 2 (VEGFR-2) (EC 2.7.10.1) (Fetal liver kinase 1) (FLK-1) (Kinase insert domain receptor) (KDR) (Protein-tyrosine kinase receptor flk-1) (CD antigen CD309)
[NGFR TNFRSF16] Tumor necrosis factor receptor superfamily member 16 (Gp80-LNGFR) (Low affinity neurotrophin receptor p75NTR) (Low-affinity nerve growth factor receptor) (NGF receptor) (p75 ICD) (CD antigen CD271)
[Kdr Flk1] Vascular endothelial growth factor receptor 2 (VEGFR-2) (EC 2.7.10.1) (Fetal liver kinase 1) (FLK-1) (Protein-tyrosine kinase receptor flk-1) (CD antigen CD309)

Bibliography :
[30579143] Characterization of β-Nerve Growth Factor-TrkA system in male reproductive tract of rabbit and the relationship between β-NGF and testosterone levels with seminal quality during sexual maturation.
[30308237] Primary sensory neurons expressing tropomyosin receptor kinase A in the rat trigeminal ganglion.
[30170607] The relationship between gonadotropin releasing hormone and ovulation inducing factor/nerve growth factor receptors in the hypothalamus of the llama.
[29904026] Nerve Growth Factor (NGF)-Receptor Survival Axis in Head and Neck Squamous Cell Carcinoma.
[29770392] Promotion of neurite outgrowth by rationally designed NGF-β binding peptide nanofibers.
[29580253] Excessive nerve growth factor impairs bidirectional communication between the oocyte and cumulus cells resulting in reduced oocyte competence.
[29264935] Expression pattern of high-affinity tyrosine kinase Aduring the development of human fetal spinal cord.
[29215016] low neurotrophin receptor CD271 regulates phenotype switching in melanoma.
[28884193] Neurotrophin Trk Receptors: New Targets for Cancer Therapy.
[28843696] NGF protects endothelial cells from indomethacin-induced injury through activation of mitochondria and upregulation of IGF-1.