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UniProtKB - P04629 (NTRK1_HUMAN)

Entry version 262 (25 May 2022)
Sequence version 4 (02 May 2006)
Previous versions | rss
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Protein

High affinity nerve growth factor receptor

Gene

NTRK1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score:

Annotation score:5 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>-Experimental evidence at protein leveli <p>This indicates the type of evidence that supports the existence of the protein. Note that the 'protein existence' evidence does not give information on the accuracy or correctness of the sequence(s) displayed.<p><a href='/help/protein_existence' target='_top'>More...</a></p>

<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>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 Publications

Resistant 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 Publication

Miscellaneous

Trk also stands for tropomyosin-related kinase since it was first isolated as an oncogenic protein which was the result of a fusion between the tropomyosin gene TPM3 and NTRK1.

<p>This subsection of the <a href="http://www.uniprot.org/help/function%5Fsection">Function</a> section describes the catalytic activity of an enzyme, i.e. a chemical reaction that the enzyme catalyzes.<p><a href='/help/catalytic_activity' target='_top'>More...</a></p>Catalytic activityi

<p>This subsection of the <a href="http://www.uniprot.org/help/function%5Fsection">Function</a> section describes regulatory mechanisms for enzymes, transporters or microbial transcription factors, and reports the components which regulate (by activation or inhibition) the reaction.<p><a href='/help/activity_regulation' target='_top'>More...</a></p>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 (By similarity). Regulated by NGFR (By similarity).By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/function%5Fsection">Function</a> section describes the interaction between a single amino acid and another chemical entity. Priority is given to the annotation of physiological ligands.<p><a href='/help/binding' target='_top'>More...</a></p>Binding sitei544ATPPROSITE-ProRule annotation1
<p>This subsection of the <a href="http://www.uniprot.org/help/function%5Fsection">Function</a> section is used for enzymes and indicates the residues directly involved in catalysis.<p><a href='/help/act_site' target='_top'>More...</a></p>Active sitei650Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/function%5Fsection">Function</a> section describes a region in the protein which binds nucleotide phosphates. It always involves more than one amino acid and includes all residues involved in nucleotide-binding.<p><a href='/help/np_bind' target='_top'>More...</a></p>Nucleotide bindingi516 – 524ATPPROSITE-ProRule annotation9

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

Complete GO annotation on QuickGO ...

GO - Biological processi

Complete GO annotation on QuickGO ...

<p>UniProtKB Keywords constitute a <a href="http://www.uniprot.org/keywords">controlled vocabulary</a> with a hierarchical structure. Keywords summarise the content of a UniProtKB entry and facilitate the search for proteins of interest.<p><a href='/help/keywords' target='_top'>More...</a></p>Keywordsi

Molecular functionDevelopmental protein, Kinase, Receptor, Transferase, Tyrosine-protein kinase
Biological processDifferentiation, Neurogenesis
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDA Comprehensive Enzyme Information System

More...BRENDAi		2.7.10.1, 2681

Pathway Commons web resource for biological pathway data

More...PathwayCommonsi		P04629

Reactome - a knowledgebase of biological pathways and processes

More...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

SignaLink: a signaling pathway resource with multi-layered regulatory networks

More...SignaLinki		P04629

SIGNOR Signaling Network Open Resource

More...SIGNORi		P04629

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section provides an exhaustive list of all names of the protein, from commonly used to obsolete, to allow unambiguous identification of a protein.<p><a href='/help/protein_names' target='_top'>More...</a></p>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
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section indicates the name(s) of the gene(s) that code for the protein sequence(s) described in the entry. Four distinct tokens exist: 'Name', 'Synonyms', 'Ordered locus names' and 'ORF names'.<p><a href='/help/gene_name' target='_top'>More...</a></p>Gene namesi
Name:NTRK1
Synonyms:MTC, TRK1 Publication, TRKA1 Publication
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section provides information on the name(s) of the organism that is the source of the protein sequence.<p><a href='/help/organism-name' target='_top'>More...</a></p>OrganismiHomo sapiens (Human)
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section shows the unique identifier assigned by the NCBI to the source organism of the protein. This is known as the 'taxonomic identifier' or 'taxid'.<p><a href='/help/taxonomic_identifier' target='_top'>More...</a></p>Taxonomic identifieri9606 [NCBI]
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section contains the taxonomic hierarchical classification lineage of the source organism. It lists the nodes as they appear top-down in the taxonomic tree, with the more general grouping listed first.<p><a href='/help/taxonomic_lineage' target='_top'>More...</a></p>Taxonomic lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section is present for entries that are part of a <a href="http://www.uniprot.org/proteomes">proteome</a>, i.e. of a set of proteins thought to be expressed by organisms whose genomes have been completely sequenced.<p><a href='/help/proteomes_manual' target='_top'>More...</a></p>Proteomesi
  • UP000005640 <p>A UniProt <a href="http://www.uniprot.org/manual/proteomes%5Fmanual">proteome</a> can consist of several components.<br></br>The component name refers to the genomic component encoding a set of proteins.<p><a href='/help/proteome_component' target='_top'>More...</a></p> Componenti: Chromosome 1

Organism-specific databases

Human Gene Nomenclature Database

More...HGNCi		HGNC:8031, NTRK1

Online Mendelian Inheritance in Man (OMIM)

More...MIMi		164970, gene
191315, gene

neXtProt; the human protein knowledge platform

More...neXtProti		NX_P04629

Eukaryotic Pathogen, Vector and Host Database Resources

More...VEuPathDBi		HostDB:ENSG00000198400

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/subcellular%5Flocation%5Fsection">'Subcellular location'</a> section describes the subcellular compartment where each non-membrane region of a membrane-spanning protein is found.<p><a href='/help/topo_dom' target='_top'>More...</a></p>Topological domaini33 – 423ExtracellularSequence analysisAdd BLAST391
<p>This subsection of the <a href="http://www.uniprot.org/help/subcellular%5Flocation%5Fsection">'Subcellular location'</a> section describes the extent of a membrane-spanning region of the protein. It denotes the presence of both alpha-helical transmembrane regions and the membrane spanning regions of beta-barrel transmembrane proteins.<p><a href='/help/transmem' target='_top'>More...</a></p>Transmembranei424 – 439HelicalSequence analysisAdd BLAST16
Topological domaini440 – 796CytoplasmicSequence analysisAdd BLAST357

Keywords - Cellular componenti

Cell membrane, Endosome, Membrane

<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi

<p>This subsection of the 'Pathology and Biotech' section provides information on the disease(s) associated with genetic variations in a given protein. The information is extracted from the scientific literature and diseases that are also described in the <a href="http://www.ncbi.nlm.nih.gov/sites/entrez?db=omim">OMIM</a> database are represented with a <a href="http://www.uniprot.org/diseases">controlled vocabulary</a> in the following way:<p><a href='/help/involvement_in_disease' target='_top'>More...</a></p>Involvement in diseasei

Congenital insensitivity to pain with anhidrosis (CIPA)14 Publications
The disease is caused by variants affecting the gene represented in this entry.
Disease descriptionCharacterized by a congenital insensitivity to pain, anhidrosis (absence of sweating), absence of reaction to noxious stimuli, self-mutilating behavior, and mental retardation. This rare autosomal recessive disorder is also known as congenital sensory neuropathy with anhidrosis or hereditary sensory and autonomic neuropathy type IV or familial dysautonomia type II.
Related information in OMIM
Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'Sequence' section describes natural variant(s) of the protein sequence.<p><a href='/help/variant' target='_top'>More...</a></p>Natural variantiVAR_00962493L → P in CIPA; aberrantly processed; shows diminished autophosphorylation in neuronal cells. 2 Publications1
Natural variantiVAR_079399110A → D in CIPA. 1 Publication1
Natural variantiVAR_079400146 – 796Missing in CIPA. 1 PublicationAdd BLAST651
Natural variantiVAR_079401176 – 796Missing in CIPA. 1 PublicationAdd BLAST621
Natural variantiVAR_009625213L → P in CIPA; aberrantly processed; shows diminished autophosphorylation in neuronal cells. 2 PublicationsCorresponds to variant dbSNP:rs747711259EnsemblClinVar.1
Natural variantiVAR_079402235 – 796Missing in CIPA; loss of protein. 1 PublicationAdd BLAST562
Natural variantiVAR_068481359Y → C in CIPA. 1 PublicationCorresponds to variant dbSNP:rs121964869EnsemblClinVar.1
Natural variantiVAR_079403476 – 796Missing in CIPA. 1 PublicationAdd BLAST321
Natural variantiVAR_068482492E → K in CIPA. 1 PublicationCorresponds to variant dbSNP:rs144901788EnsemblClinVar.1
Natural variantiVAR_077472517G → 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_077473522G → 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 Publication1
Natural variantiVAR_009626522G → 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_077474572I → S in CIPA. 1 Publication1
Natural variantiVAR_004103577G → 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_009627587M → V in CIPA. 1 PublicationCorresponds to variant dbSNP:rs121964870EnsemblClinVar.1
Natural variantiVAR_079404596D → N in CIPA; abolishes autophosphorylation. 1 Publication1
Natural variantiVAR_079405649R → Q in CIPA. 1 PublicationCorresponds to variant dbSNP:rs786205449EnsemblClinVar.1
Natural variantiVAR_009630649R → 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_009631654R → 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_077475657L → 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 Publication1
Natural variantiVAR_009632674D → Y in CIPA; might impair the function of the enzyme without compromising autophosphorylation. 3 PublicationsCorresponds to variant dbSNP:rs80356677EnsemblClinVar.1
Natural variantiVAR_009633695P → L in CIPA. 1 PublicationCorresponds to variant dbSNP:rs121964868EnsemblClinVar.1
Natural variantiVAR_077476699I → 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 Publication1
Natural variantiVAR_079406700L → P in CIPA. 1 Publication1
Natural variantiVAR_009634714G → 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_077477717L → R in CIPA. 1 Publication1
Natural variantiVAR_077478752C → 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 Publication1
Natural variantiVAR_077479763C → 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 Publication1
Natural variantiVAR_077480771R → 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_009635780R → P in CIPA; loss of function. 1 PublicationCorresponds to variant dbSNP:rs35669708EnsemblClinVar.1
Chromosomal aberrations involving NTRK1 are found in papillary thyroid carcinomas (PTCs) (PubMed:2869410, PubMed:7565764, PubMed:1532241). Translocation t(1;3)(q21;q11) with TFG generates the TRKT3 (TRK-T3) transcript by fusing TFG to the 3'-end of NTRK1 (PubMed:7565764). A rearrangement with TPM3 generates the TRK transcript by fusing TPM3 to the 3'-end of NTRK1 (PubMed:2869410). An intrachromosomal rearrangement that links the protein kinase domain of NTRK1 to the 5'-end of the TPR gene forms the fusion protein TRK-T1. TRK-T1 is a 55 kDa protein reacting with antibodies against the C-terminus of the NTRK1 protein (PubMed:1532241).3 Publications

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/manual/pathology%5Fand%5Fbiotech%5Fsection">'Pathology and Biotech'</a> section describes the effect of the experimental mutation of one or more amino acid(s) on the biological properties of the protein.<p><a href='/help/mutagen' target='_top'>More...</a></p>Mutagenesisi496Y → 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 Publication1
Mutagenesisi540 – 541LV → AA: Abolishes interaction with GGA3. 1 Publication2
Mutagenesisi544K → A: No effect on interaction with GGA3. 1 Publication1
Mutagenesisi544K → N: Loss of kinase activity. 2 Publications1
Mutagenesisi610 – 611LL → AA: No effect on interaction with GGA3. 1 Publication2
Mutagenesisi791Y → 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 Publications1

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection describes interesting single amino acid sites on the sequence that are not defined in any other subsection. This subsection can be displayed in different sections ('Function', 'PTM / Processing', 'Pathology and Biotech') according to its content.<p><a href='/help/site' target='_top'>More...</a></p>Sitei398 – 399Breakpoint for translocation to form TRK and TRK-T32
Sitei486Breakpoint for translocation to form TRK-T11

Keywords - Diseasei

Disease variant, Proto-oncogene

Organism-specific databases

DisGeNET

More...DisGeNETi		4914

GeneReviews a resource of expert-authored, peer-reviewed disease descriptions.

More...GeneReviewsi		NTRK1

MalaCards human disease database

More...MalaCardsi		NTRK1
MIMi256800, phenotype

Open Targets

More...OpenTargetsi		ENSG00000198400

Orphanet; a database dedicated to information on rare diseases and orphan drugs

More...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

The Pharmacogenetics and Pharmacogenomics Knowledge Base

More...PharmGKBi		PA31817

Miscellaneous databases

Pharos NIH Druggable Genome Knowledgebase

More...Pharosi		P04629, Tclin

Chemistry databases

ChEMBL database of bioactive drug-like small molecules

More...ChEMBLi		CHEMBL2815

Drug and drug target database

More...DrugBanki		DB00321, Amitriptyline
DB13926, Cenegermin
DB11986, Entrectinib
DB12010, Fostamatinib
DB00619, Imatinib
DB14723, Larotrectinib
DB15822, Pralsetinib
DB08896, Regorafenib

DrugCentral

More...DrugCentrali		P04629

IUPHAR/BPS Guide to PHARMACOLOGY

More...GuidetoPHARMACOLOGYi		1817

Genetic variation databases

BioMuta curated single-nucleotide variation and disease association database

More...BioMutai		NTRK1

Domain mapping of disease mutations (DMDM)

More...DMDMi		94730402

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'PTM / Processing' section denotes the presence of an N-terminal signal peptide.<p><a href='/help/signal' target='_top'>More...</a></p>Signal peptidei1 – 32Sequence analysisAdd BLAST32
<p>This subsection of the 'PTM / Processing' section describes the extent of a polypeptide chain in the mature protein following processing or proteolytic cleavage.<p><a href='/help/chain' target='_top'>More...</a></p>ChainiPRO_000001672433 – 796High affinity nerve growth factor receptorAdd BLAST764

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the PTM / Processing":/help/ptm_processing_section section describes the positions of cysteine residues participating in disulfide bonds.<p><a href='/help/disulfid' target='_top'>More...</a></p>Disulfide bondi36 ↔ 41Combined sources
Disulfide bondi40 ↔ 50Combined sources
<p>This subsection of the <a href="http://www.uniprot.org/help/ptm%5Fprocessing%5Fsection">PTM / Processing</a> section specifies the position and type of each covalently attached glycan group (mono-, di-, or polysaccharide).<p><a href='/help/carbohyd' target='_top'>More...</a></p>Glycosylationi67N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi95N-linked (GlcNAc...) asparagine1 Publication1
Glycosylationi121N-linked (GlcNAc...) asparagine1 Publication1
Disulfide bondi154 ↔ 191PROSITE-ProRule annotationCombined sources1 Publication
Glycosylationi188N-linked (GlcNAc...) asparagineCombined sources1 Publication1
Glycosylationi202N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi215 ↔ 265PROSITE-ProRule annotationCombined sources1 Publication
Glycosylationi253N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi262N-linked (GlcNAc...) asparagineCombined sources1 Publication1
Glycosylationi281N-linked (GlcNAc...) asparagineCombined sources1 Publication1
Disulfide bondi300 ↔ 345Combined sources
Glycosylationi318N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi323N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi338N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi358N-linked (GlcNAc...) asparagineCombined sources1 Publication1
Glycosylationi401N-linked (GlcNAc...) asparagineSequence analysis1
<p>This subsection of the 'PTM / Processing' section specifies the position and type of each modified residue excluding <a href="http://www.uniprot.org/manual/lipid">lipids</a>, <a href="http://www.uniprot.org/manual/carbohyd">glycans</a> and <a href="http://www.uniprot.org/manual/crosslnk">protein cross-links</a>.<p><a href='/help/mod_res' target='_top'>More...</a></p>Modified residuei496Phosphotyrosine; by autocatalysis3 Publications1
Modified residuei676Phosphotyrosine; by autocatalysis1 Publication1
Modified residuei680Phosphotyrosine; by autocatalysis2 Publications1
Modified residuei681Phosphotyrosine; by autocatalysis2 Publications1
Modified residuei791Phosphotyrosine; by autocatalysis3 Publications1

<p>This subsection of the <a href="http://www.uniprot.org/help/ptm%5Fprocessing%5Fsection">PTM/processing</a> section describes post-translational modifications (PTMs). This subsection <strong>complements</strong> the information provided at the sequence level or describes modifications for which <strong>position-specific data is not yet available</strong>.<p><a href='/help/post-translational_modification' target='_top'>More...</a></p>Post-translational modificationi

Ligand-mediated autophosphorylation (PubMed:2927393, PubMed:1281417, PubMed:15488758, PubMed:7510697, PubMed:8155326, PubMed:8325889, PubMed:27676246, PubMed:28177573). Interaction with SQSTM1 is phosphotyrosine-dependent. Autophosphorylation at Tyr-496 mediates interaction and phosphorylation of SHC1 (PubMed:15488758, PubMed:7510697, PubMed:8155326, PubMed:8325889).8 Publications
N-glycosylated (PubMed:2927393). Isoform TrkA-I and isoform TrkA-II are N-glycosylated.4 Publications
Ubiquitinated (PubMed:27445338). Undergoes polyubiquitination upon activation; regulated by NGFR (PubMed:27445338). Ubiquitination by NEDD4L leads to degradation (PubMed:27445338). Ubiquitination regulates the internalization of the receptor (By similarity).By similarity1 Publication

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein, Ubl conjugation

Proteomic databases

MassIVE - Mass Spectrometry Interactive Virtual Environment

More...MassIVEi		P04629

PaxDb, a database of protein abundance averages across all three domains of life

More...PaxDbi		P04629

PeptideAtlas

More...PeptideAtlasi		P04629

PRoteomics IDEntifications database

More...PRIDEi		P04629

ProteomicsDB: a multi-organism proteome resource

More...ProteomicsDBi		51723 [P04629-1]
51724 [P04629-2]
51725 [P04629-3]
51726 [P04629-4]

PTM databases

GlyGen: Computational and Informatics Resources for Glycoscience

More...GlyGeni		P04629, 13 sites

iPTMnet integrated resource for PTMs in systems biology context

More...iPTMneti		P04629

Comprehensive resource for the study of protein post-translational modifications (PTMs) in human, mouse and rat.

More...PhosphoSitePlusi		P04629

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressioni

<p>This subsection of the 'Expression' section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms. By default, the information is derived from experiments at the mRNA level, unless specified 'at protein level'.<br></br>Examples: <a href="http://www.uniprot.org/uniprot/P92958#expression">P92958</a>, <a href="http://www.uniprot.org/uniprot/Q8TDN4#expression">Q8TDN4</a>, <a href="http://www.uniprot.org/uniprot/O14734#expression">O14734</a><p><a href='/help/tissue_specificity' target='_top'>More...</a></p>Tissue specificityi

Isoform TrkA-I is found in most non-neuronal tissues. Isoform TrkA-II is primarily expressed in neuronal cells. TrkA-III is specifically expressed by pluripotent neural stem and neural crest progenitors.2 Publications

<p>This subsection of the 'Expression' section reports the experimentally proven effects of inducers and repressors (usually chemical compounds or environmental factors) on the level of protein (or mRNA) expression (up-regulation, down-regulation, constitutive expression).<p><a href='/help/induction' target='_top'>More...</a></p>Inductioni

Isoform TrkA-III is up-regulated upon hypoxia in cells normally expressing it.1 Publication

Gene expression databases

Bgee dataBase for Gene Expression Evolution

More...Bgeei		ENSG00000198400, Expressed in adenohypophysis and 112 other tissues

ExpressionAtlas, Differential and Baseline Expression

More...ExpressionAtlasi		P04629, baseline and differential

Genevisible search portal to normalized and curated expression data from Genevestigator

More...Genevisiblei		P04629, HS

Organism-specific databases

Human Protein Atlas

More...HPAi		ENSG00000198400, Group enriched (adrenal gland, brain)

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni

<p>This subsection of the <a href="http://www.uniprot.org/help/interaction%5Fsection">'Interaction'</a> section provides information about the protein quaternary structure and interaction(s) with other proteins or protein complexes (with the exception of physiological receptor-ligand interactions which are annotated in the <a href="http://www.uniprot.org/help/function%5Fsection">'Function'</a> section).<p><a href='/help/subunit_structure' target='_top'>More...</a></p>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 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei496Interaction with SHC11
Sitei791Interaction with PLCG11

<p>This subsection of the '<a href="http://www.uniprot.org/help/interaction%5Fsection">Interaction</a>' section provides information about binary protein-protein interactions. The data presented in this section are a quality-filtered subset of binary interactions automatically derived from the <a href="https://www.ebi.ac.uk/intact/">IntAct database</a>. It is updated at every <a href="http://www.uniprot.org/help/synchronization">UniProt release</a>.<p><a href='/help/binary_interactions' target='_top'>More...</a></p>Binary interactionsi

Hide details

GO - Molecular functioni

Complete GO annotation on QuickGO ...

Protein-protein interaction databases

The Biological General Repository for Interaction Datasets (BioGRID)

More...BioGRIDi		110969, 1963 interactors

CORUM comprehensive resource of mammalian protein complexes

More...CORUMi		P04629

Database of interacting proteins

More...DIPi		DIP-5714N

The Eukaryotic Linear Motif resource for Functional Sites in Proteins

More...ELMi		P04629

Protein interaction database and analysis system

More...IntActi		P04629, 30 interactors

Molecular INTeraction database

More...MINTi		P04629

STRING: functional protein association networks

More...STRINGi		9606.ENSP00000431418

Chemistry databases

BindingDB database of measured binding affinities

More...BindingDBi		P04629

Miscellaneous databases

RNAct, Protein-RNA interaction predictions for model organisms.

More...RNActi		P04629, protein

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

Secondary structure

1796
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

AlphaFold Protein Structure Database

More...AlphaFoldDBi		P04629

Biological Magnetic Resonance Data Bank

More...BMRBi		P04629

SWISS-MODEL Repository - a database of annotated 3D protein structure models

More...SMRi		P04629

Database of comparative protein structure models

More...ModBasei		Search...

Protein Data Bank in Europe - Knowledge Base

More...PDBe-KBi		Search...

Miscellaneous databases

Relative evolutionary importance of amino acids within a protein sequence

More...EvolutionaryTracei		P04629

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'Family and Domains' section indicates the positions and types of repeated sequence motifs or repeated domains within the protein.<p><a href='/help/repeat' target='_top'>More...</a></p>Repeati90 – 113LRR 1Add BLAST24
Repeati116 – 137LRR 2Add BLAST22
<p>This subsection of the <a href="http://www.uniprot.org/help/family%5Fand%5Fdomains%5Fsection">Family and Domains</a> section describes the position and type of a domain, which is defined as a specific combination of secondary structures organized into a characteristic three-dimensional structure or fold.<p><a href='/help/domain' target='_top'>More...</a></p>Domaini148 – 193LRRCTAdd BLAST46
Domaini194 – 283Ig-like C2-type 1PROSITE-ProRule annotationAdd BLAST90
Domaini299 – 365Ig-like C2-type 2PROSITE-ProRule annotationAdd BLAST67
Domaini510 – 781Protein kinasePROSITE-ProRule annotationAdd BLAST272

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'Family and Domains' section describes a region of interest that cannot be described in other subsections.<p><a href='/help/region' target='_top'>More...</a></p>Regioni469 – 490Interaction with SQSTM1By similarityAdd BLAST22

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'Family and Domains' section describes a short (usually not more than 20 amino acids) conserved sequence motif of biological significance.<p><a href='/help/motif' target='_top'>More...</a></p>Motifi537 – 541DXXLL1 Publication5
Motifi607 – 611DXXLL1 Publication5

<p>This subsection of the 'Family and domains' section provides general information on the biological role of a domain. The term 'domain' is intended here in its wide acceptation, it may be a structural domain, a transmembrane region or a functional domain. Several domains are described in this subsection.<p><a href='/help/domain_cc' target='_top'>More...</a></p>Domaini

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

<p>This subsection of the 'Family and domains' section provides information about the sequence similarity with other proteins.<p><a href='/help/sequence_similarities' target='_top'>More...</a></p>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

evolutionary genealogy of genes: Non-supervised Orthologous Groups

More...eggNOGi		KOG1026, Eukaryota

Ensembl GeneTree

More...GeneTreei		ENSGT00940000159412

The HOGENOM Database of Homologous Genes from Fully Sequenced Organisms

More...HOGENOMi		CLU_000288_74_1_1

InParanoid: Eukaryotic Ortholog Groups

More...InParanoidi		P04629

Identification of Orthologs from Complete Genome Data

More...OMAi		IMLKWEL

Database of Orthologous Groups

More...OrthoDBi		295510at2759

Database for complete collections of gene phylogenies

More...PhylomeDBi		P04629

TreeFam database of animal gene trees

More...TreeFami		TF106465

Family and domain databases

Gene3D Structural and Functional Annotation of Protein Families

More...Gene3Di		2.60.40.10, 2 hits
3.80.10.10, 1 hit

Intrinsically Disordered proteins with Extensive Annotations and Literature

More...IDEALi		IID00535

Integrated resource of protein families, domains and functional sites

More...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

Pfam protein domain database

More...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

Protein Motif fingerprint database; a protein domain database

More...PRINTSi		PR01939, NTKRECEPTOR
PR01940, NTKRECEPTOR1
PR00109, TYRKINASE

Simple Modular Architecture Research Tool; a protein domain database

More...SMARTi		View protein in SMART
SM00082, LRRCT, 1 hit
SM00219, TyrKc, 1 hit

Superfamily database of structural and functional annotation

More...SUPFAMi		SSF48726, SSF48726, 2 hits
SSF56112, SSF56112, 1 hit

PROSITE; a protein domain and family database

More...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

<p>This section displays by default the canonical protein sequence and upon request all isoforms described in the entry. It also includes information pertinent to the sequence(s), including <a href="http://www.uniprot.org/help/sequence%5Flength">length</a> and <a href="http://www.uniprot.org/help/sequences">molecular weight</a>. The information is filed in different subsections. The current subsections and their content are listed below:<p><a href='/help/sequences_section' target='_top'>More...</a></p>Sequences (4+)i

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences%5Fsection">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical%5Fand%5Fisoforms">canonical sequence</a> displayed by default in the entry is complete or not.<p><a href='/help/sequence_status' target='_top'>More...</a></p>Sequence statusi: Complete.

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences%5Fsection">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical%5Fand%5Fisoforms">canonical sequence</a> displayed by default in the entry is in its mature form or if it represents the precursor.<p><a href='/help/sequence_processing' target='_top'>More...</a></p>Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 4 <p>This subsection of the 'Sequence' section lists the alternative protein sequences (isoforms) that can be generated from the same gene by a single or by the combination of up to four biological events (alternative promoter usage, alternative splicing, alternative initiation and ribosomal frameshifting). Additionally, this section gives relevant information on each alternative protein isoform.<p><a href='/help/alternative_products' target='_top'>More...</a></p> isoformsi produced by alternative splicing. AlignAdd to basket
Note: TrkA-I and TrkA-II isoforms have similar biological properties but are differentially expressed.

This entry has 4 described isoforms and 5 potential isoforms that are computationally mapped.Show allAlign All

Isoform TrkA-II (identifier: P04629-1) [UniParc]FASTAAdd to basket
Also known as: TrkAII

This isoform has been chosen as the <p><strong>What is the canonical sequence?</strong><p><a href='/help/canonical_and_isoforms' target='_top'>More...</a></p>canonicali sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide
        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
Note: Major isoform.
Length:796
Mass (Da):87,497
Last modified:May 2, 2006 - v4
<p>The checksum is a form of redundancy check that is calculated from the sequence. It is useful for tracking sequence updates.</p> <p>It should be noted that while, in theory, two different sequences could have the same checksum value, the likelihood that this would happen is extremely low.</p> <p>However UniProtKB may contain entries with identical sequences in case of multiple genes (paralogs).</p> <p>The checksum is computed as the sequence 64-bit Cyclic Redundancy Check value (CRC64) using the generator polynomial: x<sup>64</sup> + x<sup>4</sup> + x<sup>3</sup> + x + 1. The algorithm is described in the ISO 3309 standard. </p> <p class="publication">Press W.H., Flannery B.P., Teukolsky S.A. and Vetterling W.T.<br /> <strong>Cyclic redundancy and other checksums</strong><br /> <a href="http://www.nrbook.com/b/bookcpdf.php">Numerical recipes in C 2nd ed., pp896-902, Cambridge University Press (1993)</a>)</p> Checksum:i6C15C721E336B601
GO
Isoform TrkA-I (identifier: P04629-2) [UniParc]FASTAAdd to basket
Also known as: TrkAI

The sequence of this isoform differs from the canonical sequence as follows:
     393-398: Missing.

Note: Has enhanced responsiveness to NTF3 neurotrophin.Curated
Show »
Length:790
Mass (Da):86,880
Checksum:i25F05BADA8A2A50C
GO
Isoform 3 (identifier: P04629-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-71: MLRGGRRGQL...LPGAENLTEL → MKEAALICLA...SRCTNLLAAS
     393-398: Missing.

Show »
Length:760
Mass (Da):83,993
Checksum:i2452CA9C211243C9
GO
Isoform TrkA-III (identifier: P04629-4) [UniParc]FASTAAdd to basket
Also known as: TrkAIII

The sequence of this isoform differs from the canonical sequence as follows:
     192-284: GVPTLKVQVP...EVSVQVNVSF → V
     393-398: Missing.

Note: Constitutively active. Does not bind NGF and does not interact with GRB2 and FRS2.Curated
Show »
Length:698
Mass (Da):77,145
Checksum:i580555F90386A5A7
GO

<p>In eukaryotic reference proteomes, unreviewed entries that are likely to belong to the same gene are computationally mapped, based on gene identifiers from Ensembl, EnsemblGenomes and model organism databases.<p><a href='/help/gene_centric_isoform_mapping' target='_top'>More...</a></p>Computationally mapped potential isoform sequencesi

There are 5 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
J3KP20J3KP20_HUMAN
Tyrosine-protein kinase receptor
NTRK1
793Annotation score:

Annotation score:3 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
A0A6Q8PHG5A0A6Q8PHG5_HUMAN
Tyrosine-protein kinase receptor
NTRK1
736Annotation score:

Annotation score:3 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
A0A6Q8PGU5A0A6Q8PGU5_HUMAN
High affinity nerve growth factor r...
NTRK1
59Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
A0A6Q8PF65A0A6Q8PF65_HUMAN
High affinity nerve growth factor r...
NTRK1
149Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
E9PQG0E9PQG0_HUMAN
High affinity nerve growth factor r...
NTRK1
364Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>

<p>This subsection of the 'Sequence' section reports difference(s) between the protein sequence shown in the UniProtKB entry and other available protein sequences derived from the same gene.<p><a href='/help/sequence_caution' target='_top'>More...</a></p>Sequence cautioni

The sequence CAA27243 differs from that shown. Contaminating sequence. Sequence of unknown origin in the N-terminal part.Curated
The sequence CAA27243 differs from that shown. Reason: Frameshift.Curated
The sequence CAA27243 differs from that shown. Reason: Erroneous termination. Truncated C-terminus.Curated
The sequence CAA29888 differs from that shown. Contaminating sequence. Sequence of unknown origin in the N-terminal part.Curated
The sequence CAA44719 differs from that shown. Contaminating sequence. Sequence of unknown origin in the N-terminal part.Curated
The sequence CAA59936 differs from that shown. Contaminating sequence. Sequence of unknown origin in the N-terminal part.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'Sequence' section reports difference(s) between the canonical sequence (displayed by default in the entry) and the different sequence submissions merged in the entry. These various submissions may originate from different sequencing projects, different types of experiments, or different biological samples. Sequence conflicts are usually of unknown origin.<p><a href='/help/conflict' target='_top'>More...</a></p>Sequence conflicti263V → L in AAA36770 (PubMed:2927393).Curated1
Sequence conflicti300C → S in AAA36770 (PubMed:2927393).Curated1
Sequence conflicti529C → S in CAA59936 (PubMed:7565764).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_0684806R → W1 PublicationCorresponds to variant dbSNP:rs201472270EnsemblClinVar.1
Natural variantiVAR_04971418G → E. Corresponds to variant dbSNP:rs1007211EnsemblClinVar.1
Natural variantiVAR_04146180Q → R1 PublicationCorresponds to variant dbSNP:rs55891455EnsemblClinVar.1
Natural variantiVAR_00962385R → S2 PublicationsCorresponds to variant dbSNP:rs543320028EnsemblClinVar.1
Natural variantiVAR_00962493L → P in CIPA; aberrantly processed; shows diminished autophosphorylation in neuronal cells. 2 Publications1
Natural variantiVAR_041462107A → V in an ovarian serous carcinoma sample; somatic mutation. 1 PublicationCorresponds to variant dbSNP:rs540521894EnsemblClinVar.1
Natural variantiVAR_079399110A → D in CIPA. 1 Publication1
Natural variantiVAR_079400146 – 796Missing in CIPA. 1 PublicationAdd BLAST651
Natural variantiVAR_079401176 – 796Missing in CIPA. 1 PublicationAdd BLAST621
Natural variantiVAR_009625213L → P in CIPA; aberrantly processed; shows diminished autophosphorylation in neuronal cells. 2 PublicationsCorresponds to variant dbSNP:rs747711259EnsemblClinVar.1
Natural variantiVAR_079402235 – 796Missing in CIPA; loss of protein. 1 PublicationAdd BLAST562
Natural variantiVAR_041463237T → M1 PublicationCorresponds to variant dbSNP:rs55909005EnsemblClinVar.1
Natural variantiVAR_041464238V → G1 PublicationCorresponds to variant dbSNP:rs56000394Ensembl.1
Natural variantiVAR_041465260R → G1 PublicationCorresponds to variant dbSNP:rs35116695Ensembl.1
Natural variantiVAR_068481359Y → C in CIPA. 1 PublicationCorresponds to variant dbSNP:rs121964869EnsemblClinVar.1
Natural variantiVAR_041466444R → Q1 PublicationCorresponds to variant dbSNP:rs56320207EnsemblClinVar.1
Natural variantiVAR_041467452R → C1 PublicationCorresponds to variant dbSNP:rs34900547EnsemblClinVar.1
Natural variantiVAR_079403476 – 796Missing in CIPA. 1 PublicationAdd BLAST321
Natural variantiVAR_068482492E → K in CIPA. 1 PublicationCorresponds to variant dbSNP:rs144901788EnsemblClinVar.1
Natural variantiVAR_077472517G → 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_077473522G → 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 Publication1
Natural variantiVAR_009626522G → 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_041468566M → T1 PublicationCorresponds to variant dbSNP:rs55892037EnsemblClinVar.1
Natural variantiVAR_077474572I → S in CIPA. 1 Publication1
Natural variantiVAR_004103577G → 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_009627587M → V in CIPA. 1 PublicationCorresponds to variant dbSNP:rs121964870EnsemblClinVar.1
Natural variantiVAR_079404596D → N in CIPA; abolishes autophosphorylation. 1 Publication1
Natural variantiVAR_009628604H → Y6 PublicationsCorresponds to variant dbSNP:rs6336EnsemblClinVar.1
Natural variantiVAR_009629613G → V7 PublicationsCorresponds to variant dbSNP:rs6339EnsemblClinVar.1
Natural variantiVAR_079405649R → Q in CIPA. 1 PublicationCorresponds to variant dbSNP:rs786205449EnsemblClinVar.1
Natural variantiVAR_009630649R → 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_009631654R → 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_077475657L → 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 Publication1
Natural variantiVAR_009632674D → Y in CIPA; might impair the function of the enzyme without compromising autophosphorylation. 3 PublicationsCorresponds to variant dbSNP:rs80356677EnsemblClinVar.1
Natural variantiVAR_009633695P → L in CIPA. 1 PublicationCorresponds to variant dbSNP:rs121964868EnsemblClinVar.1
Natural variantiVAR_077476699I → 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 Publication1
Natural variantiVAR_079406700L → P in CIPA. 1 Publication1
Natural variantiVAR_009634714G → 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_077477717L → R in CIPA. 1 Publication1
Natural variantiVAR_077478752C → 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 Publication1
Natural variantiVAR_077479763C → 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 Publication1
Natural variantiVAR_077480771R → 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_009635780R → P in CIPA; loss of function. 1 PublicationCorresponds to variant dbSNP:rs35669708EnsemblClinVar.1
Natural variantiVAR_009636780R → Q2 PublicationsCorresponds to variant dbSNP:rs35669708EnsemblClinVar.1
Natural variantiVAR_041469790V → I1 PublicationCorresponds to variant dbSNP:rs55948542EnsemblClinVar.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'Sequence' section describes the sequence of naturally occurring alternative protein isoform(s). The changes in the amino acid sequence may be due to alternative splicing, alternative promoter usage, alternative initiation, or ribosomal frameshifting.<p><a href='/help/var_seq' target='_top'>More...</a></p>Alternative sequenceiVSP_0419051 – 71MLRGG…NLTEL → MKEAALICLAPSVPPILTVK SWDTMQLRAARSRCTNLLAA S in isoform 3. 1 PublicationAdd BLAST71
Alternative sequenceiVSP_042152192 – 284GVPTL…VNVSF → V in isoform TrkA-III. CuratedAdd BLAST93
Alternative sequenceiVSP_002899393 – 398Missing in isoform TrkA-I, isoform 3 and isoform TrkA-III. 3 Publications6

Sequence databases

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