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Protein

High affinity nerve growth factor receptor

Gene

Ntrk1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -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

Activity 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

Keywordsi

Molecular functionDevelopmental protein, Kinase, Receptor, Transferase, Tyrosine-protein kinase
Biological processDifferentiation, Neurogenesis
LigandATP-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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 3

Organism-specific databases

MGIiMGI:97383 Ntrk1

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

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

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
Disulfide bondi36 ↔ 41By similarity
Disulfide bondi40 ↔ 50By similarity
Glycosylationi67N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi121N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi154 ↔ 193PROSITE-ProRule annotation
Glycosylationi190N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi204N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi217 ↔ 267PROSITE-ProRule annotation
Glycosylationi255N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi264N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi302 ↔ 348By similarity
Glycosylationi320N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi325N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi341N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi361N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi404N-linked (GlcNAc...) asparagineSequence 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 (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).By similarity1 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 Expressed in 79 organ(s), highest expression level in dorsal root ganglion
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 (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).By similarity1 Publication

Sites

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

GO - Molecular functioni

Protein-protein interaction databases

BioGridi201868, 8 interactors
DIPiDIP-60900N
IntActiQ3UFB7, 6 interactors
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

Keywords - Domaini

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

Phylogenomic databases

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

Family and domain databases

Gene3Di2.60.40.10, 2 hits
3.80.10.10, 1 hit
InterProiView protein in InterPro
IPR007110 Ig-like_dom
IPR036179 Ig-like_dom_sf
IPR013783 Ig-like_fold
IPR011009 Kinase-like_dom_sf
IPR001611 Leu-rich_rpt
IPR032675 LRR_dom_sf
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
PfamiView protein in Pfam
PF13855 LRR_8, 1 hit
PF07714 Pkinase_Tyr, 1 hit
PF16920 TPKR_C2, 1 hit
PRINTSiPR01939 NTKRECEPTOR
PR01940 NTKRECEPTOR1
PR00109 TYRKINASE
SMARTiView protein in SMART
SM00219 TyrKc, 1 hit
SUPFAMiSSF48726 SSF48726, 2 hits
SSF56112 SSF56112, 1 hit
PROSITEiView protein in PROSITE
PS50835 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

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. Translation N-terminally extended.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

Similar proteinsi

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, 8 interactors
DIPiDIP-60900N
IntActiQ3UFB7, 6 interactors
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
OMAiANETMRH
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

PROiPR:Q3UFB7
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000028072 Expressed in 79 organ(s), highest expression level in dorsal root ganglion
CleanExiMM_NTRK1
GenevisibleiQ3UFB7 MM

Family and domain databases

Gene3Di2.60.40.10, 2 hits
3.80.10.10, 1 hit
InterProiView protein in InterPro
IPR007110 Ig-like_dom
IPR036179 Ig-like_dom_sf
IPR013783 Ig-like_fold
IPR011009 Kinase-like_dom_sf
IPR001611 Leu-rich_rpt
IPR032675 LRR_dom_sf
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
PfamiView protein in Pfam
PF13855 LRR_8, 1 hit
PF07714 Pkinase_Tyr, 1 hit
PF16920 TPKR_C2, 1 hit
PRINTSiPR01939 NTKRECEPTOR
PR01940 NTKRECEPTOR1
PR00109 TYRKINASE
SMARTiView protein in SMART
SM00219 TyrKc, 1 hit
SUPFAMiSSF48726 SSF48726, 2 hits
SSF56112 SSF56112, 1 hit
PROSITEiView protein in PROSITE
PS50835 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
ProtoNetiSearch...

Entry informationi

Entry nameiNTRK1_MOUSE
AccessioniPrimary (citable) accession number: Q3UFB7
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 20, 2007
Last sequence update: February 20, 2007
Last modified: November 7, 2018
This is version 130 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

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

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