Protein

High affinity nerve growth factor receptor

Gene

NTRK1

Organism

Homo sapiens (Human)

Status

Reviewed-Annotation score: -Experimental evidence at protein levelⁱ

Functionⁱ

Receptor tyrosine kinase involved in the development and the maturation of the central and peripheral nervous systems through regulation of proliferation, differentiation and survival of sympathetic and nervous neurons. High affinity receptor for NGF which is its primary ligand (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

Isoform TrkA-III:

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.

Catalytic activityⁱ

ATP
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See the description of this molecule in ChEBI.
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L-tyrosyl-[protein]
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=
ADP
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See the description of this molecule in ChEBI.
+
H⁺
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See the description of this molecule in ChEBI.
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O-phospho-L-tyrosyl-[protein]
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PROSITE-ProRule annotation
Manual assertion according to rulesⁱ
- PROSITE-ProRule:PRU10028
2 Publications
Manual assertion based on experiment inⁱ
- Ref.1
  "Molecular and biochemical characterization of the human trk proto-oncogene."
  Martin-Zanca D., Oskam R., Mitra G., Copeland T.D., Barbacid M.
  Mol. Cell. Biol. 9:24-33(1989) [PubMed] [Europe PMC] [Abstract]
  Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM TRKA-I), CATALYTIC ACTIVITY, PHOSPHORYLATION, GLYCOSYLATION, SUBCELLULAR LOCATION.
- Ref.14
  "Nerve growth factor mediates signal transduction through trk homodimer receptors."
  Jing S., Tapley P., Barbacid M.
  Neuron 9:1067-1079(1992) [PubMed] [Europe PMC] [Abstract]
  Cited for: FUNCTION, SUBUNIT, CATALYTIC ACTIVITY, PHOSPHORYLATION, SUBCELLULAR LOCATION, MUTAGENESIS OF LYS-544.
EC:
2.7.10.1
- Search proteins in UniProtKB for this EC number.
- See the description of this EC number in ENZYME.
PROSITE-ProRule annotation
Manual assertion according to rulesⁱ
- PROSITE-ProRule:PRU10028
2 Publications
Manual assertion based on experiment inⁱ
- Ref.1
  "Molecular and biochemical characterization of the human trk proto-oncogene."
  Martin-Zanca D., Oskam R., Mitra G., Copeland T.D., Barbacid M.
  Mol. Cell. Biol. 9:24-33(1989) [PubMed] [Europe PMC] [Abstract]
  Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM TRKA-I), CATALYTIC ACTIVITY, PHOSPHORYLATION, GLYCOSYLATION, SUBCELLULAR LOCATION.
- Ref.14
  "Nerve growth factor mediates signal transduction through trk homodimer receptors."
  Jing S., Tapley P., Barbacid M.
  Neuron 9:1067-1079(1992) [PubMed] [Europe PMC] [Abstract]
  Cited for: FUNCTION, SUBUNIT, CATALYTIC ACTIVITY, PHOSPHORYLATION, SUBCELLULAR LOCATION, MUTAGENESIS OF LYS-544.
Source:
Rhea
Search for this reaction in UniProtKB.
See the description of this reaction in Rhea.
. Show »« Hide
ATP
+
L-tyrosyl-[protein]
L-tyrosine residue
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=
ADP
+
H⁺
+
O-phospho-L-tyrosyl-[protein]
L-tyrosine-phosphate residue
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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 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

Complete GO annotation on QuickGO ...

GO - Biological processⁱ

Complete GO annotation on QuickGO ...

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	cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Dipnotetrapodomorpha › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Boreoeutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo
Proteomesⁱ	UP000005640 Componentⁱ: Chromosome 1

Organism-specific databases

EuPathDBⁱ	HostDB:ENSG00000198400.11
Human Gene Nomenclature Database More...HGNCⁱ	HGNC:8031, NTRK1
MIMⁱ	164970, gene 191315, gene
neXtProtⁱ	NX_P04629

Topology

Feature key	Position(s)	DescriptionActions	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, Membrane

Pathology & Biotechⁱ

Involvement in diseaseⁱ

Congenital insensitivity to pain with anhidrosis (CIPA)14 Publications

The disease is caused by mutations 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 key	Position(s)	DescriptionActions	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 Publications	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:rs369353892Ensembl.	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; found in a compound heterozygote also carrying an premature stop codon at position 558. 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

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 key	Position(s)	DescriptionActions	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 mutation, Proto-oncogene

Organism-specific databases

DisGeNET More...DisGeNETⁱ	4914
GeneReviewsⁱ	NTRK1
MalaCards human disease database More...MalaCardsⁱ	NTRK1
MIMⁱ	256800, phenotype
Open Targets More...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

Pharosⁱ

P04629, Tclin

Chemistry databases

ChEMBLⁱ	CHEMBL2815
Drug and drug target database More...DrugBankⁱ	DB00321, Amitriptyline DB13926, Cenegermin DB11986, Entrectinib DB12010, Fostamatinib DB00619, Imatinib DB14723, Larotrectinib DB08896, Regorafenib
DrugCentral More...DrugCentralⁱ	P04629
IUPHAR/BPS Guide to PHARMACOLOGY More...GuidetoPHARMACOLOGYⁱ	1817

Polymorphism and mutation 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	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

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

Manual assertion based on experiment inⁱ

Ref.1
"Molecular and biochemical characterization of the human trk proto-oncogene."
Martin-Zanca D., Oskam R., Mitra G., Copeland T.D., Barbacid M.
Mol. Cell. Biol. 9:24-33(1989) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM TRKA-I), CATALYTIC ACTIVITY, PHOSPHORYLATION, GLYCOSYLATION, SUBCELLULAR LOCATION.
Ref.14
"Nerve growth factor mediates signal transduction through trk homodimer receptors."
Jing S., Tapley P., Barbacid M.
Neuron 9:1067-1079(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBUNIT, CATALYTIC ACTIVITY, PHOSPHORYLATION, SUBCELLULAR LOCATION, MUTAGENESIS OF LYS-544.
Ref.15
"Tissue-specific alternative splicing generates two isoforms of the trkA receptor."
Barker P.A., Lomen-Hoerth C., Gensch E.M., Meakin S.O., Glass D.J., Shooter E.M.
J. Biol. Chem. 268:15150-15157(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: ALTERNATIVE SPLICING (ISOFORMS TRKA-I AND TRKA-II), FUNCTION IN CELL SURVIVAL, NGF-BINDING, PHOSPHORYLATION, TISSUE SPECIFICITY.
Ref.16
"A Trk nerve growth factor (NGF) receptor point mutation affecting interaction with phospholipase C-gamma 1 abolishes NGF-promoted peripherin induction but not neurite outgrowth."
Loeb D.M., Stephens R.M., Copeland T.D., Kaplan D.R., Greene L.A.
J. Biol. Chem. 269:8901-8910(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT TYR-791, INTERACTION WITH PLCG1, MUTAGENESIS OF TYR-791.
Ref.17
"Trk receptors use redundant signal transduction pathways involving SHC and PLC-gamma 1 to mediate NGF responses."
Stephens R.M., Loeb D.M., Copeland T.D., Pawson T., Greene L.A., Kaplan D.R.
Neuron 12:691-705(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN NEURONAL DIFFERENTIATION, FUNCTION IN PHOSPHORYLATION OF SHC1 AND PLCG1, INTERACTION WITH SHC1, MUTAGENESIS OF TYR-496; LYS-544 AND TYR-791, PHOSPHORYLATION AT TYR-496; TYR-676; TYR-680; TYR-681 AND TYR-791.
Ref.19
"TrkA alternative splicing: a regulated tumor-promoting switch in human neuroblastoma."
Tacconelli A., Farina A.R., Cappabianca L., Desantis G., Tessitore A., Vetuschi A., Sferra R., Rucci N., Argenti B., Screpanti I., Gulino A., Mackay A.R.
Cancer Cell 6:347-360(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN NEURONAL CELL PROLIFERATION AND DIFFERENTIATION, FUNCTION IN SIGNALING CASCADE ACTIVATION, NGF-BINDING, SUBCELLULAR LOCATION, ALTERNATIVE SPLICING (ISOFORM TRKA-III), CHARACTERIZATION OF ISOFORM TRKA-III, PHOSPHORYLATION AT TYR-496; TYR-680; TYR-681 AND TYR-791, INTERACTION WITH FRS2; GRB2; PIK3R1; PLCG1; SHC1, GLYCOSYLATION, TISSUE SPECIFICITY, INDUCTION BY HYPOXIA.
Ref.24
"Novel NTRK1 mutations associated with congenital insensitivity to pain with anhidrosis verified by functional studies."
Nam T.S., Li W., Yoon S., Eom G.H., Kim M.K., Jung S.T., Choi S.Y.
J. Peripher. Nerv. Syst. 22:92-99(2017) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION, VARIANTS CIPA 235-SER--GLY-796 DEL; ASN-596 AND TYR-674, CHARACTERIZATION OF VARIANTS CIPA 235-SER--GLY-796 DEL AND ASN-596.
Ref.45
"A comprehensive functional analysis of NTRK1 missense mutations causing hereditary sensory and autonomic neuropathy type IV (HSAN IV)."
Shaikh S.S., Chen Y.C., Halsall S.A., Nahorski M.S., Omoto K., Young G.T., Phelan A., Woods C.G.
Hum. Mutat. 38:55-63(2017) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS CIPA GLU-517; GLU-522; PRO-657; THR-699; SER-752; SER-763 AND CYS-771, CHARACTERIZATION OF VARIANTS CIPA GLU-517; GLU-522; PRO-657; THR-699; SER-752; SER-763 AND CYS-771, GLYCOSYLATION, SUBCELLULAR LOCATION, AUTOPHOSPHORYLATION AFTER NGF STIMULATION, FUNCTION.

N-glycosylated (PubMed:2927393). Isoform TrkA-I and isoform TrkA-II are N-glycosylated.4 Publications

Manual assertion based on experiment inⁱ

Ref.1
"Molecular and biochemical characterization of the human trk proto-oncogene."
Martin-Zanca D., Oskam R., Mitra G., Copeland T.D., Barbacid M.
Mol. Cell. Biol. 9:24-33(1989) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM TRKA-I), CATALYTIC ACTIVITY, PHOSPHORYLATION, GLYCOSYLATION, SUBCELLULAR LOCATION.
Ref.19
"TrkA alternative splicing: a regulated tumor-promoting switch in human neuroblastoma."
Tacconelli A., Farina A.R., Cappabianca L., Desantis G., Tessitore A., Vetuschi A., Sferra R., Rucci N., Argenti B., Screpanti I., Gulino A., Mackay A.R.
Cancer Cell 6:347-360(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN NEURONAL CELL PROLIFERATION AND DIFFERENTIATION, FUNCTION IN SIGNALING CASCADE ACTIVATION, NGF-BINDING, SUBCELLULAR LOCATION, ALTERNATIVE SPLICING (ISOFORM TRKA-III), CHARACTERIZATION OF ISOFORM TRKA-III, PHOSPHORYLATION AT TYR-496; TYR-680; TYR-681 AND TYR-791, INTERACTION WITH FRS2; GRB2; PIK3R1; PLCG1; SHC1, GLYCOSYLATION, TISSUE SPECIFICITY, INDUCTION BY HYPOXIA.
Ref.28
"Structural and mechanistic insights into nerve growth factor interactions with the TrkA and p75 receptors."
Wehrman T., He X., Raab B., Dukipatti A., Blau H., Garcia K.C.
Neuron 53:25-38(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (3.4 ANGSTROMS) OF 36-382 IN COMPLEX WITH NGF, HOMODIMERIZATION, SUBUNIT, SUBCELLULAR LOCATION, DISULFIDE BONDS, GLYCOSYLATION AT ASN-95; ASN-121; ASN-188; ASN-262; ASN-281 AND ASN-358.
Ref.45
"A comprehensive functional analysis of NTRK1 missense mutations causing hereditary sensory and autonomic neuropathy type IV (HSAN IV)."
Shaikh S.S., Chen Y.C., Halsall S.A., Nahorski M.S., Omoto K., Young G.T., Phelan A., Woods C.G.
Hum. Mutat. 38:55-63(2017) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS CIPA GLU-517; GLU-522; PRO-657; THR-699; SER-752; SER-763 AND CYS-771, CHARACTERIZATION OF VARIANTS CIPA GLU-517; GLU-522; PRO-657; THR-699; SER-752; SER-763 AND CYS-771, GLYCOSYLATION, SUBCELLULAR LOCATION, AUTOPHOSPHORYLATION AFTER NGF STIMULATION, FUNCTION.

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

MassIVEⁱ	P04629
PaxDbⁱ	P04629
PeptideAtlas More...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

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

Inductionⁱ

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

Gene expression databases

Bgeeⁱ	ENSG00000198400, Expressed in adenohypophysis and 111 other tissues
ExpressionAtlasⁱ	P04629, baseline and differential
Genevisibleⁱ	P04629, HS

Organism-specific databases

Human Protein Atlas More...HPAⁱ	ENSG00000198400, Group enriched (adrenal gland, blood, brain)

HPAⁱ

ENSG00000198400, Group enriched (adrenal gland, blood, 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 Publications

Sites

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Siteⁱ	496	Interaction with SHC1		1
Siteⁱ	791	Interaction with PLCG1		1

Binary interactionsⁱ

Hide details

P04629

With	#Exp.	IntAct
APP - isoform APP695 [P05067-4]	7	EBI-1028226,EBI-302641
CBL [P22681]	2	EBI-1028226,EBI-518228
NGF [P01138]	3	EBI-1028226,EBI-1028250
Beta-nerve growth factor (PRO_0000019600)	2	EBI-1028226,EBI-9249861
itself	3	EBI-1028226,EBI-1028226
PTPN1 [P18031]	2	EBI-1028226,EBI-968788
SORT1 [Q99523]	3	EBI-1028226,EBI-1057058
SQSTM1 [Q13501]	2	EBI-1028226,EBI-307104
ULK1 [O75385]	2	EBI-1028226,EBI-908831
Pirb [Q8K4V6] from Mus musculus.	2	EBI-1028226,EBI-8602514

GO - Molecular functionⁱ

Complete GO annotation on QuickGO ...

Protein-protein interaction databases

BioGRIDⁱ	110969, 1960 interactors
CORUMⁱ	P04629
Database of interacting proteins More...DIPⁱ	DIP-5714N
ELMⁱ	P04629
IntActⁱ	P04629, 30 interactors
Molecular INTeraction database More...MINTⁱ	P04629
STRINGⁱ	9606.ENSP00000431418

Chemistry databases

BindingDBⁱ	P04629

BindingDBⁱ

P04629

Miscellaneous databases

RNActⁱ	P04629, protein

RNActⁱ

P04629, protein

Structureⁱ

Secondary structure

Legend: HelixTurnBeta strandPDB Structure known for this area

Feature key	Position(s)	DescriptionActions	Length
Beta strandⁱ	38 – 40	Combined sources	3
Beta strandⁱ	43 – 46	Combined sources	4
Turnⁱ	57 – 61	Combined sources	5
Beta strandⁱ	69 – 72	Combined sources	4
Helixⁱ	84 – 86	Combined sources	3
Beta strandⁱ	94 – 97	Combined sources	4
Helixⁱ	110 – 112	Combined sources	3
Beta strandⁱ	119 – 121	Combined sources	3
Turnⁱ	133 – 135	Combined sources	3
Beta strandⁱ	142 – 144	Combined sources	3
Helixⁱ	154 – 156	Combined sources	3
Helixⁱ	157 – 164	Combined sources	8
Helixⁱ	171 – 173	Combined sources	3
Beta strandⁱ	178 – 181	Combined sources	4
Beta strandⁱ	195 – 199	Combined sources	5
Beta strandⁱ	211 – 218	Combined sources	8
Beta strandⁱ	227 – 230	Combined sources	4
Beta strandⁱ	234 – 238	Combined sources	5
Beta strandⁱ	244 – 253	Combined sources	10
Turnⁱ	257 – 260	Combined sources	4
Beta strandⁱ	263 – 265	Combined sources	3
Beta strandⁱ	276 – 278	Combined sources	3
Beta strandⁱ	284 – 290	Combined sources	7
Beta strandⁱ	298 – 305	Combined sources	8
Beta strandⁱ	312 – 317	Combined sources	6
Beta strandⁱ	326 – 333	Combined sources	8
Beta strandⁱ	342 – 350	Combined sources	9
Helixⁱ	353 – 355	Combined sources	3
Beta strandⁱ	357 – 365	Combined sources	9
Beta strandⁱ	368 – 376	Combined sources	9
Helixⁱ	418 – 441	Combined sources	24
Beta strandⁱ	476 – 478	Combined sources	3
Helixⁱ	490 – 492	Combined sources	3
Turnⁱ	494 – 496	Combined sources	3
Helixⁱ	507 – 509	Combined sources	3
Beta strandⁱ	510 – 517	Combined sources	8
Beta strandⁱ	520 – 522	Combined sources	3
Beta strandⁱ	524 – 533	Combined sources	10
Turnⁱ	534 – 536	Combined sources	3
Beta strandⁱ	537 – 545	Combined sources	9
Helixⁱ	552 – 566	Combined sources	15
Beta strandⁱ	575 – 579	Combined sources	5
Beta strandⁱ	581 – 584	Combined sources	4
Beta strandⁱ	586 – 590	Combined sources	5
Helixⁱ	597 – 603	Combined sources	7
Beta strandⁱ	605 – 607	Combined sources	3
Helixⁱ	608 – 611	Combined sources	4
Beta strandⁱ	615 – 617	Combined sources	3
Beta strandⁱ	619 – 621	Combined sources	3
Helixⁱ	624 – 643	Combined sources	20
Beta strandⁱ	646 – 648	Combined sources	3
Helixⁱ	653 – 655	Combined sources	3
Beta strandⁱ	656 – 659	Combined sources	4
Helixⁱ	660 – 662	Combined sources	3
Beta strandⁱ	663 – 666	Combined sources	4
Helixⁱ	672 – 675	Combined sources	4
Helixⁱ	677 – 679	Combined sources	3
Beta strandⁱ	680 – 683	Combined sources	4
Turnⁱ	684 – 686	Combined sources	3
Beta strandⁱ	687 – 689	Combined sources	3
Helixⁱ	691 – 693	Combined sources	3
Helixⁱ	696 – 701	Combined sources	6
Helixⁱ	706 – 721	Combined sources	16
Turnⁱ	722 – 724	Combined sources	3
Turnⁱ	727 – 730	Combined sources	4
Helixⁱ	733 – 742	Combined sources	10
Helixⁱ	754 – 763	Combined sources	10
Helixⁱ	768 – 770	Combined sources	3
Helixⁱ	774 – 786	Combined sources	13
Helixⁱ	789 – 793	Combined sources	5

Show more details

3D structure databases

BMRBⁱ	P04629
SMRⁱ	P04629
ModBaseⁱ	Search...
PDBe-KBⁱ	Search...

Miscellaneous databases

EvolutionaryTraceⁱ	P04629

EvolutionaryTraceⁱ

P04629

Family & Domainsⁱ

Domains and Repeats

Feature key	Position(s)	DescriptionActions	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

The transmembrane domain mediates interaction with KIDINS220.By similarity

The extracellular domain mediates interaction with NGFR.By similarity

Sequence similaritiesⁱ

Belongs to the protein kinase superfamily. Tyr protein kinase family. Insulin receptor subfamily.PROSITE-ProRule annotation

Keywords - Domainⁱ

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

Phylogenomic databases

eggNOGⁱ	KOG1026, Eukaryota
Ensembl GeneTree More...GeneTreeⁱ	ENSGT00940000159412
HOGENOMⁱ	CLU_000288_74_1_1
InParanoidⁱ	P04629
KEGG Orthology (KO) More...KOⁱ	K03176
OMAⁱ	FLQCQVE
Database of Orthologous Groups More...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 IPR031635, NTRK_C2 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 IPR020461, Tyr_kinase_neurotrophic_rcpt_1 IPR020777, Tyr_kinase_NGF_rcpt IPR002011, Tyr_kinase_rcpt_2_CS
Pfam protein domain database More...Pfamⁱ	View protein in Pfam PF13855, LRR_8, 1 hit PF07714, PK_Tyr_Ser-Thr, 1 hit PF16920, TPKR_C2, 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

Sequences (4+)ⁱ

Sequence statusⁱ: Complete.

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

This entry describes 4 isoformsⁱ produced by alternative splicing. Align Add to basket

Note: TrkA-I and TrkA-II isoforms have similar biological properties but are differentially expressed.

This entry has 4 described isoforms and 2 potential isoforms that are computationally mapped.Show all Align All

Isoform TrkA-II (identifier: P04629-1) [UniParc]FASTA Add to basket

Also known as: TrkAII

This isoform has been chosen as the 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

Checksum:ⁱ6C15C721E336B601

Isoform TrkA-I (identifier: P04629-2) [UniParc]FASTA Add to basket

Also known as: TrkAI

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

« 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 IPDTNSTSGD 
       410        420        430        440        450
PVEKKDETPF GVSVAVGLAV FACLFLSTLL LVLNKCGRRN KFGINRPAVL 
       460        470        480        490        500
APEDGLAMSL HFMTLGGSSL SPTEGKGSGL QGHIIENPQY FSDACVHHIK 
       510        520        530        540        550
RRDIVLKWEL GEGAFGKVFL AECHNLLPEQ DKMLVAVKAL KEASESARQD 
       560        570        580        590        600
FQREAELLTM LQHQHIVRFF GVCTEGRPLL MVFEYMRHGD LNRFLRSHGP 
       610        620        630        640        650
DAKLLAGGED VAPGPLGLGQ LLAVASQVAA GMVYLAGLHF VHRDLATRNC 
       660        670        680        690        700
LVGQGLVVKI GDFGMSRDIY STDYYRVGGR TMLPIRWMPP ESILYRKFTT 
       710        720        730        740        750
ESDVWSFGVV LWEIFTYGKQ PWYQLSNTEA IDCITQGREL ERPRACPPEV 
       760        770        780        790
YAIMRGCWQR EPQQRHSIKD VHARLQALAQ APPVYLDVLG

Note: Has enhanced responsiveness to NTF3 neurotrophin.Curated

Show »

Length:790

Mass (Da):86,880

Checksum:ⁱ25F05BADA8A2A50C

Isoform 3 (identifier: P04629-3) [UniParc]FASTA Add to basket

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

« Hide

        10         20         30         40         50
MKEAALICLA PSVPPILTVK SWDTMQLRAA RSRCTNLLAA SYIENQQHLQ 
        60         70         80         90        100
HLELRDLRGL GELRNLTIVK SGLRFVAPDA FHFTPRLSRL NLSFNALESL 
       110        120        130        140        150
SWKTVQGLSL QELVLSGNPL HCSCALRWLQ RWEEEGLGGV PEQKLQCHGQ 
       160        170        180        190        200
GPLAHMPNAS CGVPTLKVQV PNASVDVGDD VLLRCQVEGR GLEQAGWILT 
       210        220        230        240        250
ELEQSATVMK SGGLPSLGLT LANVTSDLNR KNVTCWAEND VGRAEVSVQV 
       260        270        280        290        300
NVSFPASVQL HTAVEMHHWC IPFSVDGQPA PSLRWLFNGS VLNETSFIFT 
       310        320        330        340        350
EFLEPAANET VRHGCLRLNQ PTHVNNGNYT LLAANPFGQA SASIMAAFMD 
       360        370        380        390        400
NPFEFNPEDP IPDTNSTSGD PVEKKDETPF GVSVAVGLAV FACLFLSTLL 
       410        420        430        440        450
LVLNKCGRRN KFGINRPAVL APEDGLAMSL HFMTLGGSSL SPTEGKGSGL 
       460        470        480        490        500
QGHIIENPQY FSDACVHHIK RRDIVLKWEL GEGAFGKVFL AECHNLLPEQ 
       510        520        530        540        550
DKMLVAVKAL KEASESARQD FQREAELLTM LQHQHIVRFF GVCTEGRPLL 
       560        570        580        590        600
MVFEYMRHGD LNRFLRSHGP DAKLLAGGED VAPGPLGLGQ LLAVASQVAA 
       610        620        630        640        650
GMVYLAGLHF VHRDLATRNC LVGQGLVVKI GDFGMSRDIY STDYYRVGGR 
       660        670        680        690        700
TMLPIRWMPP ESILYRKFTT ESDVWSFGVV LWEIFTYGKQ PWYQLSNTEA 
       710        720        730        740        750
IDCITQGREL ERPRACPPEV YAIMRGCWQR EPQQRHSIKD VHARLQALAQ 
       760
APPVYLDVLG

Show »

Length:760

Mass (Da):83,993

Checksum:ⁱ2452CA9C211243C9

Isoform TrkA-III (identifier: P04629-4) [UniParc]FASTA Add 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.

« 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 CVPASVQLHT 
       210        220        230        240        250
AVEMHHWCIP FSVDGQPAPS LRWLFNGSVL NETSFIFTEF LEPAANETVR 
       260        270        280        290        300
HGCLRLNQPT HVNNGNYTLL AANPFGQASA SIMAAFMDNP FEFNPEDPIP 
       310        320        330        340        350
DTNSTSGDPV EKKDETPFGV SVAVGLAVFA CLFLSTLLLV LNKCGRRNKF 
       360        370        380        390        400
GINRPAVLAP EDGLAMSLHF MTLGGSSLSP TEGKGSGLQG HIIENPQYFS 
       410        420        430        440        450
DACVHHIKRR DIVLKWELGE GAFGKVFLAE CHNLLPEQDK MLVAVKALKE 
       460        470        480        490        500
ASESARQDFQ REAELLTMLQ HQHIVRFFGV CTEGRPLLMV FEYMRHGDLN 
       510        520        530        540        550
RFLRSHGPDA KLLAGGEDVA PGPLGLGQLL AVASQVAAGM VYLAGLHFVH 
       560        570        580        590        600
RDLATRNCLV GQGLVVKIGD FGMSRDIYST DYYRVGGRTM LPIRWMPPES 
       610        620        630        640        650
ILYRKFTTES DVWSFGVVLW EIFTYGKQPW YQLSNTEAID CITQGRELER 
       660        670        680        690 
PRACPPEVYA IMRGCWQREP QQRHSIKDVH ARLQALAQAP PVYLDVLG

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

Computationally mapped potential isoform sequencesⁱ

There are 2 potential isoforms mapped to this entry.BLAST Align Show all Add to basket

Entry	Entry name	Protein names	Gene names	Length	Annotation

J3KP20	J3KP20_HUMAN	Tyrosine-protein kinase receptor Tyrosine-protein kinase receptor, EC 2.7.10.1	NTRK1	793	Annotation score:
E9PQG0	E9PQG0_HUMAN	High affinity nerve growth factor r... High affinity nerve growth factor receptor	NTRK1	388	Annotation score:

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 key	Position(s)	DescriptionActions	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	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 Publications	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:rs369353892Ensembl.	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; found in a compound heterozygote also carrying an premature stop codon at position 558. 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

UniProtKB

UniParc

Help

UniRef

Proteomes

Annotation systems

Supporting data

UniProtKB - P04629 (NTRK1_HUMAN)

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High affinity nerve growth factor receptor

NTRK1

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<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

Miscellaneous

<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

Sites

Regions

<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

GO - Biological processi

Enzyme and pathway databases

<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

Organism-specific databases

<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

Endosome

Plasma membrane

Endosome

Golgi apparatus

Plasma Membrane

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Topology

Keywords - Cellular componenti

<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

Mutagenesis

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Organism-specific databases

Miscellaneous databases

Chemistry databases

Polymorphism and mutation databases

<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

Amino acid modifications

Keywords - PTMi

Proteomic databases

PTM databases

<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

Gene expression databases

Organism-specific databases

<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

Sites

P04629

GO - Molecular functioni

Protein-protein interaction databases

Chemistry databases

Miscellaneous databases

<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

3D structure databases

Miscellaneous databases

<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

Region

Motif

<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

Keywords - Domaini

Phylogenomic databases

Family and domain databases

<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

Experimental Info

Natural variant

Alternative sequence

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Functionⁱ

Catalytic activityⁱ

GO - Molecular functionⁱ

GO - Biological processⁱ

Names & Taxonomyⁱ

Subcellular locationⁱ

Keywords - Cellular componentⁱ

Pathology & Biotechⁱ

Keywords - Diseaseⁱ

PTM / Processingⁱ

Keywords - PTMⁱ

Expressionⁱ

Interactionⁱ

GO - Molecular functionⁱ

Structureⁱ

Family & Domainsⁱ

Sequence similaritiesⁱ

Keywords - Domainⁱ

Sequence cautionⁱ