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Protein

High affinity nerve growth factor receptor

Gene

Ntrk1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.3 Publications

Catalytic activityi

ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.PROSITE-ProRule annotation

Enzyme regulationi

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.3 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei547ATPPROSITE-ProRule annotation1
Active sitei653Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi519 – 527ATPPROSITE-ProRule annotation9

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Developmental protein, Kinase, Receptor, Transferase, Tyrosine-protein kinase

Keywords - Biological processi

Differentiation, Neurogenesis

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

ReactomeiR-MMU-170968. Frs2-mediated activation.
R-MMU-170984. ARMS-mediated activation.
R-MMU-177504. Retrograde neurotrophin signalling.
R-MMU-187042. TRKA activation by NGF.
R-MMU-198203. PI3K/AKT activation.

Names & Taxonomyi

Protein namesi
Recommended name:
High affinity nerve growth factor receptor (EC:2.7.10.1)
Alternative name(s):
Neurotrophic tyrosine kinase receptor type 1
Gene namesi
Name:Ntrk1
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 3

Organism-specific databases

MGIiMGI:97383. Ntrk1.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini34 – 420ExtracellularSequence analysisAdd BLAST387
Transmembranei421 – 441HelicalSequence analysisAdd BLAST21
Topological domaini442 – 799CytoplasmicSequence analysisAdd BLAST358

GO - Cellular componenti

  • axon Source: MGI
  • cell surface Source: MGI
  • cytoplasm Source: MGI
  • cytoplasmic vesicle Source: Ensembl
  • dendrite Source: Ensembl
  • early endosome Source: UniProtKB
  • early endosome membrane Source: UniProtKB-SubCell
  • integral component of plasma membrane Source: UniProtKB
  • late endosome Source: UniProtKB
  • late endosome membrane Source: UniProtKB-SubCell
  • neuronal cell body Source: Ensembl
  • plasma membrane Source: UniProtKB
  • protein complex Source: UniProtKB
  • receptor complex Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Endosome, Membrane

Pathology & Biotechi

Disruption phenotypei

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 E17.5 in the superior cervical ganglion, a major component of the sympathetic system.1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 33Sequence analysisAdd BLAST33
ChainiPRO_000027853734 – 799High affinity nerve growth factor receptorAdd BLAST766

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi67N-linked (GlcNAc...)Sequence analysis1
Glycosylationi121N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi154 ↔ 193PROSITE-ProRule annotation
Glycosylationi190N-linked (GlcNAc...)Sequence analysis1
Glycosylationi204N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi217 ↔ 267PROSITE-ProRule annotation
Glycosylationi255N-linked (GlcNAc...)Sequence analysis1
Glycosylationi264N-linked (GlcNAc...)Sequence analysis1
Glycosylationi320N-linked (GlcNAc...)Sequence analysis1
Glycosylationi325N-linked (GlcNAc...)Sequence analysis1
Glycosylationi341N-linked (GlcNAc...)Sequence analysis1
Glycosylationi361N-linked (GlcNAc...)Sequence analysis1
Glycosylationi404N-linked (GlcNAc...)Sequence analysis1
Modified residuei499Phosphotyrosine; by autocatalysisBy similarity1
Modified residuei679Phosphotyrosine; by autocatalysisBy similarity1
Modified residuei683Phosphotyrosine; by autocatalysisBy similarity1
Modified residuei684Phosphotyrosine; by autocatalysisBy similarity1
Modified residuei794Phosphotyrosine; by autocatalysisBy similarity1

Post-translational modificationi

Ligand-mediated autophosphorylation. Interaction with SQSTM1 is phosphotyrosine-dependent. Autophosphorylation at Tyr-499 mediates interaction and phosphorylation of SHC1.
N-glycosylated.By similarity
Ubiquitinated. Undergoes polyubiquitination upon activation; regulated by NGFR. Ubiquitination regulates the internalization of the receptor.1 Publication

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiQ3UFB7.
PeptideAtlasiQ3UFB7.
PRIDEiQ3UFB7.

PTM databases

iPTMnetiQ3UFB7.
PhosphoSitePlusiQ3UFB7.

Expressioni

Developmental stagei

First detected at E13.5, a time coinciding with the requirement of sympathetic neurons for NGF.1 Publication

Inductioni

Expression oscillates in a circadian manner in the suprachiasmatic nucleus (SCN) of the brain.1 Publication

Gene expression databases

BgeeiENSMUSG00000028072.
CleanExiMM_NTRK1.
GenevisibleiQ3UFB7. MM.

Interactioni

Subunit structurei

Exists in a dynamic equilibrium between monomeric (low affinity) and dimeric (high affinity) structures. Homodimerization is induced by binding of a NGF dimer. 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. Interacts with NRADD (By similarity). Interacts with SH2D1A; regulates NTRK1. Interacts with RAB7A (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 (By similarity). Interacts with RAPGEF2; the interaction is strengthened after NGF stimulation (By similarity).By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei499Interaction with SHC1By similarity1
Sitei794Interaction with PLCG1By similarity1

GO - Molecular functioni

Protein-protein interaction databases

BioGridi201868. 9 interactors.
DIPiDIP-60900N.
IntActiQ3UFB7. 1 interactor.
STRINGi10090.ENSMUSP00000029712.

Structurei

3D structure databases

ProteinModelPortaliQ3UFB7.
SMRiQ3UFB7.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati90 – 113LRR 1Add BLAST24
Repeati116 – 137LRR 2Add BLAST22
Domaini148 – 219LRRCTAdd BLAST72
Domaini196 – 285Ig-like C2-type 1Add BLAST90
Domaini205 – 368Ig-like C2-type 2Add BLAST164
Domaini513 – 784Protein kinasePROSITE-ProRule annotationAdd BLAST272

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni472 – 493Interaction with SQSTM1By similarityAdd BLAST22

Domaini

The transmembrane domain mediates interaction with KIDINS220.By similarity
The extracellular domain mediates interaction with NGFR.By similarity

Sequence similaritiesi

Belongs to the protein kinase superfamily. Tyr protein kinase family. Insulin receptor subfamily.PROSITE-ProRule annotation
Contains 2 LRR (leucine-rich) repeats.Curated
Contains 1 LRRCT domain.Curated
Contains 1 protein kinase domain.PROSITE-ProRule annotation

Keywords - Domaini

Immunoglobulin domain, Leucine-rich repeat, Repeat, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG1026. Eukaryota.
ENOG410YGKQ. LUCA.
GeneTreeiENSGT00760000118818.
HOGENOMiHOG000264255.
HOVERGENiHBG056735.
InParanoidiQ3UFB7.
KOiK03176.
OMAiKNVTCWA.
OrthoDBiEOG091G01JY.
PhylomeDBiQ3UFB7.
TreeFamiTF106465.

Family and domain databases

Gene3Di2.60.40.10. 2 hits.
3.80.10.10. 1 hit.
InterProiIPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR011009. Kinase-like_dom.
IPR032675. L_dom-like.
IPR001611. Leu-rich_rpt.
IPR031635. NTRK_C2.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
IPR008266. Tyr_kinase_AS.
IPR020635. Tyr_kinase_cat_dom.
IPR020461. Tyr_kinase_neurotrophic_rcpt_1.
IPR020777. Tyr_kinase_NGF_rcpt.
IPR002011. Tyr_kinase_rcpt_2_CS.
[Graphical view]
PfamiPF13855. LRR_8. 1 hit.
PF07714. Pkinase_Tyr. 1 hit.
PF16920. TPKR_C2. 1 hit.
[Graphical view]
PRINTSiPR01939. NTKRECEPTOR.
PR01940. NTKRECEPTOR1.
PR00109. TYRKINASE.
SMARTiSM00219. TyrKc. 1 hit.
[Graphical view]
SUPFAMiSSF48726. SSF48726. 2 hits.
SSF52058. SSF52058. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEiPS50835. IG_LIKE. 1 hit.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00109. PROTEIN_KINASE_TYR. 1 hit.
PS00239. RECEPTOR_TYR_KIN_II. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q3UFB7-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MLRGQRLGQL GWHRPAAGLG SLMTSLMLAC ASAASCREVC CPVGPSGLRC
60 70 80 90 100
TRAGSLDTLR GLRGAGNLTE LYVENQQHLQ RLEFEDLQGL GELRSLTIVK
110 120 130 140 150
SGLRFVAPDA FRFTPRLSHL NLSSNALESL SWKTVQGLSL QDLTLSGNPL
160 170 180 190 200
HCSCALFWLQ RWEQEGLCGV HTQTLHDSGP GDQFLPLGHN TSCGVPTVKI
210 220 230 240 250
QMPNDSVEVG DDVFLQCQVE GLALQQADWI LTELEGAATV KKFGDLPSLG
260 270 280 290 300
LILVNVTSDL NKKNVTCWAE NDVGRAEVSV QVSVSFPASV HLGLAVEQHH
310 320 330 340 350
WCIPFSVDGQ PAPSLRWLFN GSVLNETSFI FTQFLESALT NETMRHGCLR
360 370 380 390 400
LNQPTHVNNG NYTLLAANPY GQAAASVMAA FMDNPFEFNP EDPIPVSFSP
410 420 430 440 450
VDGNSTSRDP VEKKDETPFG VSVAVGLAVS AALFLSALLL VLNKCGQRSK
460 470 480 490 500
FGINRPAVLA PEDGLAMSLH FMTLGGSSLS PTEGKGSGLQ GHIMENPQYF
510 520 530 540 550
SDTCVHHIKR QDIILKWELG EGAFGKVFLA ECYNLLNDQD KMLVAVKALK
560 570 580 590 600
EASENARQDF QREAELLTML QHQHIVRFFG VCTEGGPLLM VFEYMRHGDL
610 620 630 640 650
NRFLRSHGPD AKLLAGGEDV APGPLGLGQL LAVASQVAAG MVYLASLHFV
660 670 680 690 700
HRDLATRNCL VGQGLVVKIG DFGMSRDIYS TDYYRVGGRT MLPIRWMPPE
710 720 730 740 750
SILYRKFSTE SDVWSFGVVL WEIFTYGKQP WYQLSNTEAI ECITQGRELE
760 770 780 790
RPRACPPDVY AIMRGCWQRE PQQRLSMKDV HARLQALAQA PPSYLDVLG
Length:799
Mass (Da):87,738
Last modified:February 20, 2007 - v2
Checksum:i1A37F76A63564603
GO

Sequence cautioni

The sequence BAE28644 differs from that shown. Reason: Erroneous initiation.Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK081588 mRNA. No translation available.
AK148691 mRNA. Translation: BAE28644.1. Different initiation.
CCDSiCCDS50947.1.
RefSeqiNP_001028296.1. NM_001033124.1.
UniGeneiMm.80682.

Genome annotation databases

EnsembliENSMUST00000029712; ENSMUSP00000029712; ENSMUSG00000028072.
GeneIDi18211.
KEGGimmu:18211.
UCSCiuc008psw.1. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK081588 mRNA. No translation available.
AK148691 mRNA. Translation: BAE28644.1. Different initiation.
CCDSiCCDS50947.1.
RefSeqiNP_001028296.1. NM_001033124.1.
UniGeneiMm.80682.

3D structure databases

ProteinModelPortaliQ3UFB7.
SMRiQ3UFB7.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi201868. 9 interactors.
DIPiDIP-60900N.
IntActiQ3UFB7. 1 interactor.
STRINGi10090.ENSMUSP00000029712.

PTM databases

iPTMnetiQ3UFB7.
PhosphoSitePlusiQ3UFB7.

Proteomic databases

PaxDbiQ3UFB7.
PeptideAtlasiQ3UFB7.
PRIDEiQ3UFB7.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000029712; ENSMUSP00000029712; ENSMUSG00000028072.
GeneIDi18211.
KEGGimmu:18211.
UCSCiuc008psw.1. mouse.

Organism-specific databases

CTDi4914.
MGIiMGI:97383. Ntrk1.

Phylogenomic databases

eggNOGiKOG1026. Eukaryota.
ENOG410YGKQ. LUCA.
GeneTreeiENSGT00760000118818.
HOGENOMiHOG000264255.
HOVERGENiHBG056735.
InParanoidiQ3UFB7.
KOiK03176.
OMAiKNVTCWA.
OrthoDBiEOG091G01JY.
PhylomeDBiQ3UFB7.
TreeFamiTF106465.

Enzyme and pathway databases

ReactomeiR-MMU-170968. Frs2-mediated activation.
R-MMU-170984. ARMS-mediated activation.
R-MMU-177504. Retrograde neurotrophin signalling.
R-MMU-187042. TRKA activation by NGF.
R-MMU-198203. PI3K/AKT activation.

Miscellaneous databases

PROiQ3UFB7.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000028072.
CleanExiMM_NTRK1.
GenevisibleiQ3UFB7. MM.

Family and domain databases

Gene3Di2.60.40.10. 2 hits.
3.80.10.10. 1 hit.
InterProiIPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR011009. Kinase-like_dom.
IPR032675. L_dom-like.
IPR001611. Leu-rich_rpt.
IPR031635. NTRK_C2.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
IPR008266. Tyr_kinase_AS.
IPR020635. Tyr_kinase_cat_dom.
IPR020461. Tyr_kinase_neurotrophic_rcpt_1.
IPR020777. Tyr_kinase_NGF_rcpt.
IPR002011. Tyr_kinase_rcpt_2_CS.
[Graphical view]
PfamiPF13855. LRR_8. 1 hit.
PF07714. Pkinase_Tyr. 1 hit.
PF16920. TPKR_C2. 1 hit.
[Graphical view]
PRINTSiPR01939. NTKRECEPTOR.
PR01940. NTKRECEPTOR1.
PR00109. TYRKINASE.
SMARTiSM00219. TyrKc. 1 hit.
[Graphical view]
SUPFAMiSSF48726. SSF48726. 2 hits.
SSF52058. SSF52058. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEiPS50835. IG_LIKE. 1 hit.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00109. PROTEIN_KINASE_TYR. 1 hit.
PS00239. RECEPTOR_TYR_KIN_II. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiNTRK1_MOUSE
AccessioniPrimary (citable) accession number: Q3UFB7
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 20, 2007
Last sequence update: February 20, 2007
Last modified: November 2, 2016
This is version 113 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  3. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.