UniProtKB - P04629 (NTRK1_HUMAN)
High affinity nerve growth factor receptor
NTRK1
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 (PubMed:1850821, PubMed:1849459, PubMed:1281417, PubMed:8325889, PubMed:15488758, PubMed:22649032, PubMed:17196528, PubMed:27445338).
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 (By similarity).
Upon dimeric NGF ligand-binding, undergoes homodimerization, autophosphorylation and activation (PubMed:1281417).
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.
By similarity11 PublicationsResistant to NGF, it constitutively activates AKT1 and NF-kappa-B and is unable to activate the Ras-MAPK signaling cascade. Antagonizes the anti-proliferative NGF-NTRK1 signaling that promotes neuronal precursors differentiation. Isoform TrkA-III promotes angiogenesis and has oncogenic activity when overexpressed.
1 PublicationMiscellaneous
Catalytic activityi
- ATP + L-tyrosyl-[protein] = ADP + H+ + O-phospho-L-tyrosyl-[protein]PROSITE-ProRule annotation2 PublicationsEC:2.7.10.1PROSITE-ProRule annotation2 Publications
Activity regulationi
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Binding sitei | 544 | ATPPROSITE-ProRule annotation | 1 | |
Active sitei | 650 | Proton acceptorPROSITE-ProRule annotation | 1 |
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Nucleotide bindingi | 516 – 524 | ATPPROSITE-ProRule annotation | 9 |
GO - Molecular functioni
- ATP binding Source: UniProtKB-KW
- GPI-linked ephrin receptor activity Source: Ensembl
- identical protein binding Source: IntAct
- kinase binding Source: Ensembl
- nerve growth factor binding Source: UniProtKB
- nerve growth factor receptor activity Source: UniProtKB
- neurotrophin binding Source: GO_Central
- neurotrophin p75 receptor binding Source: Ensembl
- neurotrophin receptor activity Source: GO_Central
- protein homodimerization activity Source: UniProtKB
- protein serine/threonine/tyrosine kinase activity Source: RHEA
- protein tyrosine kinase activity Source: UniProtKB
- transmembrane receptor protein tyrosine kinase activity Source: MGI
GO - Biological processi
- aging Source: Ensembl
- axon guidance Source: Ensembl
- axonogenesis involved in innervation Source: UniProtKB
- B cell differentiation Source: Ensembl
- behavioral response to formalin induced pain Source: Ensembl
- cellular response to nerve growth factor stimulus Source: UniProtKB
- cellular response to nicotine Source: Ensembl
- circadian rhythm Source: Ensembl
- detection of mechanical stimulus involved in sensory perception of pain Source: Ensembl
- detection of temperature stimulus involved in sensory perception of pain Source: Ensembl
- learning or memory Source: Ensembl
- mechanoreceptor differentiation Source: Ensembl
- negative regulation of apoptotic process Source: ARUK-UCL
- negative regulation of cell population proliferation Source: UniProtKB
- negative regulation of neuron apoptotic process Source: UniProtKB
- nerve growth factor signaling pathway Source: UniProtKB
- neuron development Source: MGI
- neuron projection development Source: MGI
- neurotrophin TRK receptor signaling pathway Source: UniProtKB
- olfactory nerve development Source: Ensembl
- peptidyl-tyrosine autophosphorylation Source: MGI
- peptidyl-tyrosine phosphorylation Source: UniProtKB
- positive regulation of angiogenesis Source: UniProtKB
- positive regulation of ERK1 and ERK2 cascade Source: UniProtKB
- positive regulation of GTPase activity Source: UniProtKB
- positive regulation of kinase activity Source: GO_Central
- positive regulation of neuron projection development Source: UniProtKB
- positive regulation of NF-kappaB transcription factor activity Source: UniProtKB
- positive regulation of phosphatidylinositol 3-kinase signaling Source: GO_Central
- positive regulation of programmed cell death Source: UniProtKB
- positive regulation of protein phosphorylation Source: BHF-UCL
- positive regulation of Ras protein signal transduction Source: UniProtKB
- positive regulation of synapse assembly Source: Ensembl
- positive regulation of synaptic transmission, glutamatergic Source: Ensembl
- programmed cell death involved in cell development Source: UniProtKB
- protein autophosphorylation Source: UniProtKB
- protein phosphorylation Source: UniProtKB
- regulation of protein kinase B signaling Source: GO_Central
- response to axon injury Source: Ensembl
- response to electrical stimulus Source: Ensembl
- response to hydrostatic pressure Source: Ensembl
- response to nutrient levels Source: Ensembl
- response to radiation Source: Ensembl
- response to xenobiotic stimulus Source: Ensembl
- Sertoli cell development Source: Ensembl
- sympathetic nervous system development Source: UniProtKB
- transmembrane receptor protein tyrosine kinase signaling pathway Source: GO_Central
Keywordsi
Molecular function | Developmental protein, Kinase, Receptor, Transferase, Tyrosine-protein kinase |
Biological process | Differentiation, Neurogenesis |
Ligand | ATP-binding, Nucleotide-binding |
Enzyme and pathway databases
BRENDAi | 2.7.10.1, 2681 |
PathwayCommonsi | P04629 |
Reactomei | R-HSA-167021, PLC-gamma1 signalling R-HSA-167044, Signalling to RAS R-HSA-170968, Frs2-mediated activation [P04629-1] R-HSA-170984, ARMS-mediated activation R-HSA-177504, Retrograde neurotrophin signalling R-HSA-187024, NGF-independant TRKA activation R-HSA-187042, TRKA activation by NGF R-HSA-187706, Signalling to p38 via RIT and RIN R-HSA-198203, PI3K/AKT activation R-HSA-198745, Signalling to STAT3 |
SignaLinki | P04629 |
SIGNORi | P04629 |
Names & Taxonomyi
Protein namesi | Recommended name: High affinity nerve growth factor receptor (EC:2.7.10.12 Publications)Alternative name(s): Neurotrophic tyrosine kinase receptor type 1 TRK1-transforming tyrosine kinase protein Tropomyosin-related kinase A Tyrosine kinase receptor Tyrosine kinase receptor A Short name: Trk-A gp140trk1 Publication p140-TrkA |
Gene namesi | Name:NTRK1 Synonyms:MTC, TRK1 Publication, TRKA1 Publication |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:8031, NTRK1 |
MIMi | 164970, gene 191315, gene |
neXtProti | NX_P04629 |
VEuPathDBi | HostDB:ENSG00000198400 |
Subcellular locationi
Endosome
- Early endosome membrane By similarity; Single-pass type I membrane protein By similarity
- Late endosome membrane By similarity; Single-pass type I membrane protein By similarity
- Recycling endosome membrane By similarity; Single-pass type I membrane protein By similarity
Plasma membrane
- Cell membrane 5 Publications; Single-pass type I membrane protein 2 Publications
Note: Rapidly internalized after NGF binding (PubMed:1281417). 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.By similarity1 Publication
Endosome
- early endosome Source: UniProtKB
- early endosome membrane Source: UniProtKB-SubCell
- endosome membrane Source: Reactome
- late endosome Source: UniProtKB
- late endosome membrane Source: UniProtKB-SubCell
- recycling endosome membrane Source: UniProtKB-SubCell
Plasma Membrane
- integral component of plasma membrane Source: UniProtKB
- plasma membrane Source: MGI
Other locations
- axon Source: GO_Central
- cell surface Source: Ensembl
- dendrite Source: Ensembl
- neuronal cell body Source: Ensembl
- protein-containing complex Source: UniProtKB
- receptor complex Source: MGI
Topology
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Topological domaini | 33 – 423 | ExtracellularSequence analysisAdd BLAST | 391 | |
Transmembranei | 424 – 439 | HelicalSequence analysisAdd BLAST | 16 | |
Topological domaini | 440 – 796 | CytoplasmicSequence analysisAdd BLAST | 357 |
Keywords - Cellular componenti
Cell membrane, Endosome, MembranePathology & Biotechi
Involvement in diseasei
Congenital insensitivity to pain with anhidrosis (CIPA)14 Publications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_009624 | 93 | L → P in CIPA; aberrantly processed; shows diminished autophosphorylation in neuronal cells. 2 Publications | 1 | |
Natural variantiVAR_079399 | 110 | A → D in CIPA. 1 Publication | 1 | |
Natural variantiVAR_079400 | 146 – 796 | Missing in CIPA. 1 PublicationAdd BLAST | 651 | |
Natural variantiVAR_079401 | 176 – 796 | Missing in CIPA. 1 PublicationAdd BLAST | 621 | |
Natural variantiVAR_009625 | 213 | L → P in CIPA; aberrantly processed; shows diminished autophosphorylation in neuronal cells. 2 PublicationsCorresponds to variant dbSNP:rs747711259EnsemblClinVar. | 1 | |
Natural variantiVAR_079402 | 235 – 796 | Missing in CIPA; loss of protein. 1 PublicationAdd BLAST | 562 | |
Natural variantiVAR_068481 | 359 | Y → C in CIPA. 1 PublicationCorresponds to variant dbSNP:rs121964869EnsemblClinVar. | 1 | |
Natural variantiVAR_079403 | 476 – 796 | Missing in CIPA. 1 PublicationAdd BLAST | 321 | |
Natural variantiVAR_068482 | 492 | E → K in CIPA. 1 PublicationCorresponds to variant dbSNP:rs144901788EnsemblClinVar. | 1 | |
Natural variantiVAR_077472 | 517 | G → E in CIPA; following transfection in neuroblastoma cells and NGF treatment, small decrease in the percentage of cells differentiated into neuronal phenotype, but in differentiated cells, the average neurite length is comparable to wild-type; no effect on N-glycosylation, subcellular location, nor on basal and NGF-induced autophosphorylation; loss of NGF-stimulated calcium flux. 1 PublicationCorresponds to variant dbSNP:rs606231467EnsemblClinVar. | 1 | |
Natural variantiVAR_077473 | 522 | G → E in CIPA; no effect on N-glycosylation, nor on subcellular location; reduced basal autophosphorylation and complete loss of NGF-induced autophosphorylation; loss of NGF-stimulated calcium flux. 1 Publication | 1 | |
Natural variantiVAR_009626 | 522 | G → R in CIPA; processed as wild-type but shows significantly diminished autophosphorylation in both neuronal and non-neuronal cells. 2 PublicationsCorresponds to variant dbSNP:rs1571699266EnsemblClinVar. | 1 | |
Natural variantiVAR_077474 | 572 | I → S in CIPA. 1 Publication | 1 | |
Natural variantiVAR_004103 | 577 | G → R in CIPA; loss of function; processed as wild-type but shows significantly diminished autophosphorylation in both neuronal and non-neuronal cells. 4 PublicationsCorresponds to variant dbSNP:rs121964866EnsemblClinVar. | 1 | |
Natural variantiVAR_009627 | 587 | M → V in CIPA. 1 PublicationCorresponds to variant dbSNP:rs121964870EnsemblClinVar. | 1 | |
Natural variantiVAR_079404 | 596 | D → N in CIPA; abolishes autophosphorylation. 1 Publication | 1 | |
Natural variantiVAR_079405 | 649 | R → Q in CIPA. 1 PublicationCorresponds to variant dbSNP:rs786205449EnsemblClinVar. | 1 | |
Natural variantiVAR_009630 | 649 | R → W in CIPA; processed as wild-type but shows significantly diminished autophosphorylation in both neuronal and non-neuronal cells. 2 PublicationsCorresponds to variant dbSNP:rs369353892EnsemblClinVar. | 1 | |
Natural variantiVAR_009631 | 654 | R → C in CIPA; processed as wild-type but shows significantly diminished autophosphorylation in both neuronal and non-neuronal cells. 3 PublicationsCorresponds to variant dbSNP:rs764992664EnsemblClinVar. | 1 | |
Natural variantiVAR_077475 | 657 | L → P in CIPA; following transfection in neuroblastoma cells and NGF treatment, loss of differentiation into neuronal phenotype; partially decreased N-glycosylation; reduced expression at the plasma membrane; reduced basal autophosphorylation and complete loss of NGF-induced autophosphorylation; loss of NGF-stimulated calcium flux. 1 Publication | 1 | |
Natural variantiVAR_009632 | 674 | D → Y in CIPA; might impair the function of the enzyme without compromising autophosphorylation. 3 PublicationsCorresponds to variant dbSNP:rs80356677EnsemblClinVar. | 1 | |
Natural variantiVAR_009633 | 695 | P → L in CIPA. 1 PublicationCorresponds to variant dbSNP:rs121964868EnsemblClinVar. | 1 | |
Natural variantiVAR_077476 | 699 | I → T in CIPA; partially decreased N-glycosylation; reduced expression at the plasma membrane; reduced basal autophosphorylation and complete loss of NGF-induced autophosphorylation; loss of NGF-stimulated calcium flux. 1 Publication | 1 | |
Natural variantiVAR_079406 | 700 | L → P in CIPA. 1 Publication | 1 | |
Natural variantiVAR_009634 | 714 | G → S in CIPA; processed as wild-type but shows significantly diminished autophosphorylation in both neuronal and non-neuronal cells. 2 PublicationsCorresponds to variant dbSNP:rs770727871Ensembl. | 1 | |
Natural variantiVAR_077477 | 717 | L → R in CIPA. 1 Publication | 1 | |
Natural variantiVAR_077478 | 752 | C → S in CIPA; unknown pathological significance; following transfection in neuroblastoma cells and NGF treatment, no effect on neurite outgrowth, nor neurite length; no effect on N-glycosylation, subcellular location, basal and NGF-induced autophosphorylation, nor on NGF-stimulated calcium flux. 1 Publication | 1 | |
Natural variantiVAR_077479 | 763 | C → S in CIPA; following transfection in neuroblastoma cells and NGF treatment, decreased percentage of cells differentiated into neuronal phenotype and reduced neurite length compared with wild-type; slightly decreased N-glycosylation; reduced expression at the plasma membrane; reduced basal and NGF-induced autophosphorylation; small reduction in NGF-stimulated calcium flux. 1 Publication | 1 | |
Natural variantiVAR_077480 | 771 | R → C in CIPA; partially decreased N-glycosylation; reduced expression at the plasma membrane; reduced basal autophosphorylation and complete loss of NGF-induced autophosphorylation; loss of NGF-stimulated calcium flux. 1 PublicationCorresponds to variant dbSNP:rs1324983370Ensembl. | 1 | |
Natural variantiVAR_009635 | 780 | R → P in CIPA; loss of function. 1 PublicationCorresponds to variant dbSNP:rs35669708EnsemblClinVar. | 1 |
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 496 | Y → F: Loss of interaction with SHC1 and altered phosphorylation of SHC1. Altered neurite outgrowth and altered activation of the MAPK pathway; when associated with F-791. 1 Publication | 1 | |
Mutagenesisi | 540 – 541 | LV → AA: Abolishes interaction with GGA3. 1 Publication | 2 | |
Mutagenesisi | 544 | K → A: No effect on interaction with GGA3. 1 Publication | 1 | |
Mutagenesisi | 544 | K → N: Loss of kinase activity. 2 Publications | 1 | |
Mutagenesisi | 610 – 611 | LL → AA: No effect on interaction with GGA3. 1 Publication | 2 | |
Mutagenesisi | 791 | Y → F: Loss of interaction with PLCG1 and altered phosphorylation of PLCG1. Altered neurite outgrowth and altered activation of the MAPK pathway; when associated with F-496. 2 Publications | 1 |
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sitei | 398 – 399 | Breakpoint for translocation to form TRK and TRK-T3 | 2 | |
Sitei | 486 | Breakpoint for translocation to form TRK-T1 | 1 |
Keywords - Diseasei
Disease variant, Proto-oncogeneOrganism-specific databases
DisGeNETi | 4914 |
GeneReviewsi | NTRK1 |
MalaCardsi | NTRK1 |
MIMi | 256800, phenotype |
OpenTargetsi | ENSG00000198400 |
Orphaneti | 146, Differentiated thyroid carcinoma 99361, Familial medullary thyroid carcinoma 642, Hereditary sensory and autonomic neuropathy type 4 64752, Hereditary sensory and autonomic neuropathy type 5 |
PharmGKBi | PA31817 |
Miscellaneous databases
Pharosi | P04629, Tclin |
Chemistry databases
ChEMBLi | CHEMBL2815 |
DrugBanki | DB00321, Amitriptyline DB13926, Cenegermin DB11986, Entrectinib DB12010, Fostamatinib DB00619, Imatinib DB14723, Larotrectinib DB15822, Pralsetinib DB08896, Regorafenib |
DrugCentrali | P04629 |
GuidetoPHARMACOLOGYi | 1817 |
Genetic variation databases
BioMutai | NTRK1 |
DMDMi | 94730402 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Signal peptidei | 1 – 32 | Sequence analysisAdd BLAST | 32 | |
ChainiPRO_0000016724 | 33 – 796 | High affinity nerve growth factor receptorAdd BLAST | 764 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Disulfide bondi | 36 ↔ 41 | Combined sources | ||
Disulfide bondi | 40 ↔ 50 | Combined sources | ||
Glycosylationi | 67 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 95 | N-linked (GlcNAc...) asparagine1 Publication | 1 | |
Glycosylationi | 121 | N-linked (GlcNAc...) asparagine1 Publication | 1 | |
Disulfide bondi | 154 ↔ 191 | PROSITE-ProRule annotationCombined sources1 Publication | ||
Glycosylationi | 188 | N-linked (GlcNAc...) asparagineCombined sources1 Publication | 1 | |
Glycosylationi | 202 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Disulfide bondi | 215 ↔ 265 | PROSITE-ProRule annotationCombined sources1 Publication | ||
Glycosylationi | 253 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 262 | N-linked (GlcNAc...) asparagineCombined sources1 Publication | 1 | |
Glycosylationi | 281 | N-linked (GlcNAc...) asparagineCombined sources1 Publication | 1 | |
Disulfide bondi | 300 ↔ 345 | Combined sources | ||
Glycosylationi | 318 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 323 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 338 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 358 | N-linked (GlcNAc...) asparagineCombined sources1 Publication | 1 | |
Glycosylationi | 401 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Modified residuei | 496 | Phosphotyrosine; by autocatalysis3 Publications | 1 | |
Modified residuei | 676 | Phosphotyrosine; by autocatalysis1 Publication | 1 | |
Modified residuei | 680 | Phosphotyrosine; by autocatalysis2 Publications | 1 | |
Modified residuei | 681 | Phosphotyrosine; by autocatalysis2 Publications | 1 | |
Modified residuei | 791 | Phosphotyrosine; by autocatalysis3 Publications | 1 |
Post-translational modificationi
Keywords - PTMi
Disulfide bond, Glycoprotein, Phosphoprotein, Ubl conjugationProteomic databases
MassIVEi | P04629 |
PaxDbi | P04629 |
PeptideAtlasi | P04629 |
PRIDEi | P04629 |
ProteomicsDBi | 51723 [P04629-1] 51724 [P04629-2] 51725 [P04629-3] 51726 [P04629-4] |
PTM databases
GlyGeni | P04629, 13 sites |
iPTMneti | P04629 |
PhosphoSitePlusi | P04629 |
Expressioni
Tissue specificityi
Inductioni
Gene expression databases
Bgeei | ENSG00000198400, Expressed in adenohypophysis and 112 other tissues |
ExpressionAtlasi | P04629, baseline and differential |
Genevisiblei | P04629, HS |
Organism-specific databases
HPAi | ENSG00000198400, Group enriched (adrenal gland, brain) |
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 (PubMed:1281417, PubMed:10490030, PubMed:17196528).
Interacts with SQSTM1; bridges NTRK1 to NGFR (PubMed:11244088).
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 (By similarity).
Interacts with SH2D1A; regulates NTRK1 (By similarity).
Interacts (phosphorylated upon activation by NGF) with SHC1; mediates SHC1 phosphorylation and activation (PubMed:8155326, PubMed:15488758).
Interacts (phosphorylated upon activation by NGF) with PLCG1; mediates PLCG1 phosphorylation and activation (PubMed:7510697, PubMed:15488758).
Interacts (phosphorylated) with SH2B1 and SH2B2 (By similarity).
Interacts with GRB2 (PubMed:15488758).
Interacts with PIK3R1 (PubMed:15488758).
Interacts with FRS2 (PubMed:15488758).
Interacts with SORT1; may regulate NTRK1 anterograde axonal transport (PubMed:21102451).
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).
Interacts with PTPRS (By similarity).
Interacts with USP36; USP36 does not deubiquitinate NTRK1 (PubMed:27445338).
Interacts with GGA3 (PubMed:26446845).
By similarity12 PublicationsSites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sitei | 496 | Interaction with SHC1 | 1 | |
Sitei | 791 | Interaction with PLCG1 | 1 |
Binary interactionsi
P04629
GO - Molecular functioni
- identical protein binding Source: IntAct
- kinase binding Source: Ensembl
- nerve growth factor binding Source: UniProtKB
- neurotrophin binding Source: GO_Central
- neurotrophin p75 receptor binding Source: Ensembl
- protein homodimerization activity Source: UniProtKB
Protein-protein interaction databases
BioGRIDi | 110969, 1963 interactors |
CORUMi | P04629 |
DIPi | DIP-5714N |
ELMi | P04629 |
IntActi | P04629, 30 interactors |
MINTi | P04629 |
STRINGi | 9606.ENSP00000431418 |
Chemistry databases
BindingDBi | P04629 |
Miscellaneous databases
RNActi | P04629, protein |
Structurei
Secondary structure
3D structure databases
AlphaFoldDBi | P04629 |
BMRBi | P04629 |
SMRi | P04629 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | P04629 |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Repeati | 90 – 113 | LRR 1Add BLAST | 24 | |
Repeati | 116 – 137 | LRR 2Add BLAST | 22 | |
Domaini | 148 – 193 | LRRCTAdd BLAST | 46 | |
Domaini | 194 – 283 | Ig-like C2-type 1PROSITE-ProRule annotationAdd BLAST | 90 | |
Domaini | 299 – 365 | Ig-like C2-type 2PROSITE-ProRule annotationAdd BLAST | 67 | |
Domaini | 510 – 781 | Protein kinasePROSITE-ProRule annotationAdd BLAST | 272 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 469 – 490 | Interaction with SQSTM1By similarityAdd BLAST | 22 |
Motif
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Motifi | 537 – 541 | DXXLL1 Publication | 5 | |
Motifi | 607 – 611 | DXXLL1 Publication | 5 |
Domaini
Sequence similaritiesi
Keywords - Domaini
Immunoglobulin domain, Leucine-rich repeat, Repeat, Signal, Transmembrane, Transmembrane helixPhylogenomic databases
eggNOGi | KOG1026, Eukaryota |
GeneTreei | ENSGT00940000159412 |
HOGENOMi | CLU_000288_74_1_1 |
InParanoidi | P04629 |
OMAi | IMLKWEL |
OrthoDBi | 295510at2759 |
PhylomeDBi | P04629 |
TreeFami | TF106465 |
Family and domain databases
Gene3Di | 2.60.40.10, 2 hits 3.80.10.10, 1 hit |
IDEALi | IID00535 |
InterProi | View protein in InterPro IPR000483, Cys-rich_flank_reg_C 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 IPR020777, NTRK IPR020461, NTRK1 IPR031635, NTRK_LRRCT IPR000719, Prot_kinase_dom IPR017441, Protein_kinase_ATP_BS IPR001245, Ser-Thr/Tyr_kinase_cat_dom IPR040665, TrkA_TMD IPR008266, Tyr_kinase_AS IPR020635, Tyr_kinase_cat_dom IPR002011, Tyr_kinase_rcpt_2_CS |
Pfami | View protein in Pfam PF13855, LRR_8, 1 hit PF16920, LRRCT_2, 1 hit PF07714, PK_Tyr_Ser-Thr, 1 hit PF18613, TrkA_TMD, 1 hit |
PRINTSi | PR01939, NTKRECEPTOR PR01940, NTKRECEPTOR1 PR00109, TYRKINASE |
SMARTi | View protein in SMART SM00082, LRRCT, 1 hit SM00219, TyrKc, 1 hit |
SUPFAMi | SSF48726, SSF48726, 2 hits SSF56112, SSF56112, 1 hit |
PROSITEi | View 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 |
s (4+)i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
This entry describes 4 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 4 described isoforms and 5 potential isoforms that are computationally mapped.Show allAlign All
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
10 20 30 40 50
MLRGGRRGQL GWHSWAAGPG SLLAWLILAS AGAAPCPDAC CPHGSSGLRC
60 70 80 90 100
TRDGALDSLH HLPGAENLTE LYIENQQHLQ HLELRDLRGL GELRNLTIVK
110 120 130 140 150
SGLRFVAPDA FHFTPRLSRL NLSFNALESL SWKTVQGLSL QELVLSGNPL
160 170 180 190 200
HCSCALRWLQ RWEEEGLGGV PEQKLQCHGQ GPLAHMPNAS CGVPTLKVQV
210 220 230 240 250
PNASVDVGDD VLLRCQVEGR GLEQAGWILT ELEQSATVMK SGGLPSLGLT
260 270 280 290 300
LANVTSDLNR KNVTCWAEND VGRAEVSVQV NVSFPASVQL HTAVEMHHWC
310 320 330 340 350
IPFSVDGQPA PSLRWLFNGS VLNETSFIFT EFLEPAANET VRHGCLRLNQ
360 370 380 390 400
PTHVNNGNYT LLAANPFGQA SASIMAAFMD NPFEFNPEDP IPVSFSPVDT
410 420 430 440 450
NSTSGDPVEK KDETPFGVSV AVGLAVFACL FLSTLLLVLN KCGRRNKFGI
460 470 480 490 500
NRPAVLAPED GLAMSLHFMT LGGSSLSPTE GKGSGLQGHI IENPQYFSDA
510 520 530 540 550
CVHHIKRRDI VLKWELGEGA FGKVFLAECH NLLPEQDKML VAVKALKEAS
560 570 580 590 600
ESARQDFQRE AELLTMLQHQ HIVRFFGVCT EGRPLLMVFE YMRHGDLNRF
610 620 630 640 650
LRSHGPDAKL LAGGEDVAPG PLGLGQLLAV ASQVAAGMVY LAGLHFVHRD
660 670 680 690 700
LATRNCLVGQ GLVVKIGDFG MSRDIYSTDY YRVGGRTMLP IRWMPPESIL
710 720 730 740 750
YRKFTTESDV WSFGVVLWEI FTYGKQPWYQ LSNTEAIDCI TQGRELERPR
760 770 780 790
ACPPEVYAIM RGCWQREPQQ RHSIKDVHAR LQALAQAPPV YLDVLG
The sequence of this isoform differs from the canonical sequence as follows:
393-398: Missing.
The sequence of this isoform differs from the canonical sequence as follows:
192-284: GVPTLKVQVP...EVSVQVNVSF → V
393-398: Missing.
Computationally mapped potential isoform sequencesi
There are 5 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketJ3KP20 | J3KP20_HUMAN | Tyrosine-protein kinase receptor | NTRK1 | 793 | Annotation score: | ||
A0A6Q8PHG5 | A0A6Q8PHG5_HUMAN | Tyrosine-protein kinase receptor | NTRK1 | 736 | Annotation score: | ||
A0A6Q8PGU5 | A0A6Q8PGU5_HUMAN | High affinity nerve growth factor r... | NTRK1 | 59 | Annotation score: | ||
A0A6Q8PF65 | A0A6Q8PF65_HUMAN | High affinity nerve growth factor r... | NTRK1 | 149 | Annotation score: | ||
E9PQG0 | E9PQG0_HUMAN | High affinity nerve growth factor r... | NTRK1 | 364 | Annotation score: |
Sequence cautioni
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 263 | V → L in AAA36770 (PubMed:2927393).Curated | 1 | |
Sequence conflicti | 300 | C → S in AAA36770 (PubMed:2927393).Curated | 1 | |
Sequence conflicti | 529 | C → S in CAA59936 (PubMed:7565764).Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_068480 | 6 | R → W1 PublicationCorresponds to variant dbSNP:rs201472270EnsemblClinVar. | 1 | |
Natural variantiVAR_049714 | 18 | G → E. Corresponds to variant dbSNP:rs1007211EnsemblClinVar. | 1 | |
Natural variantiVAR_041461 | 80 | Q → R1 PublicationCorresponds to variant dbSNP:rs55891455EnsemblClinVar. | 1 | |
Natural variantiVAR_009623 | 85 | R → S2 PublicationsCorresponds to variant dbSNP:rs543320028EnsemblClinVar. | 1 | |
Natural variantiVAR_009624 | 93 | L → P in CIPA; aberrantly processed; shows diminished autophosphorylation in neuronal cells. 2 Publications | 1 | |
Natural variantiVAR_041462 | 107 | A → V in an ovarian serous carcinoma sample; somatic mutation. 1 PublicationCorresponds to variant dbSNP:rs540521894EnsemblClinVar. | 1 | |
Natural variantiVAR_079399 | 110 | A → D in CIPA. 1 Publication | 1 | |
Natural variantiVAR_079400 | 146 – 796 | Missing in CIPA. 1 PublicationAdd BLAST | 651 | |
Natural variantiVAR_079401 | 176 – 796 | Missing in CIPA. 1 PublicationAdd BLAST | 621 | |
Natural variantiVAR_009625 | 213 | L → P in CIPA; aberrantly processed; shows diminished autophosphorylation in neuronal cells. 2 PublicationsCorresponds to variant dbSNP:rs747711259EnsemblClinVar. | 1 | |
Natural variantiVAR_079402 | 235 – 796 | Missing in CIPA; loss of protein. 1 PublicationAdd BLAST | 562 | |
Natural variantiVAR_041463 | 237 | T → M1 PublicationCorresponds to variant dbSNP:rs55909005EnsemblClinVar. | 1 | |
Natural variantiVAR_041464 | 238 | V → G1 PublicationCorresponds to variant dbSNP:rs56000394Ensembl. | 1 | |
Natural variantiVAR_041465 | 260 | R → G1 PublicationCorresponds to variant dbSNP:rs35116695Ensembl. | 1 | |
Natural variantiVAR_068481 | 359 | Y → C in CIPA. 1 PublicationCorresponds to variant dbSNP:rs121964869EnsemblClinVar. | 1 | |
Natural variantiVAR_041466 | 444 | R → Q1 PublicationCorresponds to variant dbSNP:rs56320207EnsemblClinVar. | 1 | |
Natural variantiVAR_041467 | 452 | R → C1 PublicationCorresponds to variant dbSNP:rs34900547EnsemblClinVar. | 1 | |
Natural variantiVAR_079403 | 476 – 796 | Missing in CIPA. 1 PublicationAdd BLAST | 321 | |
Natural variantiVAR_068482 | 492 | E → K in CIPA. 1 PublicationCorresponds to variant dbSNP:rs144901788EnsemblClinVar. | 1 | |
Natural variantiVAR_077472 | 517 | G → E in CIPA; following transfection in neuroblastoma cells and NGF treatment, small decrease in the percentage of cells differentiated into neuronal phenotype, but in differentiated cells, the average neurite length is comparable to wild-type; no effect on N-glycosylation, subcellular location, nor on basal and NGF-induced autophosphorylation; loss of NGF-stimulated calcium flux. 1 PublicationCorresponds to variant dbSNP:rs606231467EnsemblClinVar. | 1 | |
Natural variantiVAR_077473 | 522 | G → E in CIPA; no effect on N-glycosylation, nor on subcellular location; reduced basal autophosphorylation and complete loss of NGF-induced autophosphorylation; loss of NGF-stimulated calcium flux. 1 Publication | 1 | |
Natural variantiVAR_009626 | 522 | G → R in CIPA; processed as wild-type but shows significantly diminished autophosphorylation in both neuronal and non-neuronal cells. 2 PublicationsCorresponds to variant dbSNP:rs1571699266EnsemblClinVar. | 1 | |
Natural variantiVAR_041468 | 566 | M → T1 PublicationCorresponds to variant dbSNP:rs55892037EnsemblClinVar. | 1 | |
Natural variantiVAR_077474 | 572 | I → S in CIPA. 1 Publication | 1 | |
Natural variantiVAR_004103 | 577 | G → R in CIPA; loss of function; processed as wild-type but shows significantly diminished autophosphorylation in both neuronal and non-neuronal cells. 4 PublicationsCorresponds to variant dbSNP:rs121964866EnsemblClinVar. | 1 | |
Natural variantiVAR_009627 | 587 | M → V in CIPA. 1 PublicationCorresponds to variant dbSNP:rs121964870EnsemblClinVar. | 1 | |
Natural variantiVAR_079404 | 596 | D → N in CIPA; abolishes autophosphorylation. 1 Publication | 1 | |
Natural variantiVAR_009628 | 604 | H → Y6 PublicationsCorresponds to variant dbSNP:rs6336EnsemblClinVar. | 1 | |
Natural variantiVAR_009629 | 613 | G → V7 PublicationsCorresponds to variant dbSNP:rs6339EnsemblClinVar. | 1 | |
Natural variantiVAR_079405 | 649 | R → Q in CIPA. 1 PublicationCorresponds to variant dbSNP:rs786205449EnsemblClinVar. | 1 | |
Natural variantiVAR_009630 | 649 | R → W in CIPA; processed as wild-type but shows significantly diminished autophosphorylation in both neuronal and non-neuronal cells. 2 PublicationsCorresponds to variant dbSNP:rs369353892EnsemblClinVar. | 1 | |
Natural variantiVAR_009631 | 654 | R → C in CIPA; processed as wild-type but shows significantly diminished autophosphorylation in both neuronal and non-neuronal cells. 3 PublicationsCorresponds to variant dbSNP:rs764992664EnsemblClinVar. | 1 | |
Natural variantiVAR_077475 | 657 | L → P in CIPA; following transfection in neuroblastoma cells and NGF treatment, loss of differentiation into neuronal phenotype; partially decreased N-glycosylation; reduced expression at the plasma membrane; reduced basal autophosphorylation and complete loss of NGF-induced autophosphorylation; loss of NGF-stimulated calcium flux. 1 Publication | 1 | |
Natural variantiVAR_009632 | 674 | D → Y in CIPA; might impair the function of the enzyme without compromising autophosphorylation. 3 PublicationsCorresponds to variant dbSNP:rs80356677EnsemblClinVar. | 1 | |
Natural variantiVAR_009633 | 695 | P → L in CIPA. 1 PublicationCorresponds to variant dbSNP:rs121964868EnsemblClinVar. | 1 | |
Natural variantiVAR_077476 | 699 | I → T in CIPA; partially decreased N-glycosylation; reduced expression at the plasma membrane; reduced basal autophosphorylation and complete loss of NGF-induced autophosphorylation; loss of NGF-stimulated calcium flux. 1 Publication | 1 | |
Natural variantiVAR_079406 | 700 | L → P in CIPA. 1 Publication | 1 | |
Natural variantiVAR_009634 | 714 | G → S in CIPA; processed as wild-type but shows significantly diminished autophosphorylation in both neuronal and non-neuronal cells. 2 PublicationsCorresponds to variant dbSNP:rs770727871Ensembl. | 1 | |
Natural variantiVAR_077477 | 717 | L → R in CIPA. 1 Publication | 1 | |
Natural variantiVAR_077478 | 752 | C → S in CIPA; unknown pathological significance; following transfection in neuroblastoma cells and NGF treatment, no effect on neurite outgrowth, nor neurite length; no effect on N-glycosylation, subcellular location, basal and NGF-induced autophosphorylation, nor on NGF-stimulated calcium flux. 1 Publication | 1 | |
Natural variantiVAR_077479 | 763 | C → S in CIPA; following transfection in neuroblastoma cells and NGF treatment, decreased percentage of cells differentiated into neuronal phenotype and reduced neurite length compared with wild-type; slightly decreased N-glycosylation; reduced expression at the plasma membrane; reduced basal and NGF-induced autophosphorylation; small reduction in NGF-stimulated calcium flux. 1 Publication | 1 | |
Natural variantiVAR_077480 | 771 | R → C in CIPA; partially decreased N-glycosylation; reduced expression at the plasma membrane; reduced basal autophosphorylation and complete loss of NGF-induced autophosphorylation; loss of NGF-stimulated calcium flux. 1 PublicationCorresponds to variant dbSNP:rs1324983370Ensembl. | 1 | |
Natural variantiVAR_009635 | 780 | R → P in CIPA; loss of function. 1 PublicationCorresponds to variant dbSNP:rs35669708EnsemblClinVar. | 1 | |
Natural variantiVAR_009636 | 780 | R → Q2 PublicationsCorresponds to variant dbSNP:rs35669708EnsemblClinVar. | 1 | |
Natural variantiVAR_041469 | 790 | V → I1 PublicationCorresponds to variant dbSNP:rs55948542EnsemblClinVar. | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_041905 | 1 – 71 | MLRGG…NLTEL → MKEAALICLAPSVPPILTVK SWDTMQLRAARSRCTNLLAA S in isoform 3. 1 PublicationAdd BLAST | 71 | |
Alternative sequenceiVSP_042152 | 192 – 284 | GVPTL…VNVSF → V in isoform TrkA-III. CuratedAdd BLAST | 93 | |
Alternative sequenceiVSP_002899 | 393 – 398 | Missing in isoform TrkA-I, isoform 3 and isoform TrkA-III. 3 Publications | 6 |
Sequence databases
Select the link destinations: |