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P04629

- NTRK1_HUMAN

UniProt

P04629 - NTRK1_HUMAN

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Protein

High affinity nerve growth factor receptor

Gene

NTRK1

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli

Functioni

Receptor tyrosine kinase involved in the development and the maturation of the central and peripheral nervous systems through regulation of proliferation, differentiation and survival of sympathetic and nervous neurons. High affinity receptor for NGF which is its primary ligand, it can also bind and be activated by NTF3/neurotrophin-3. However, NTF3 only supports axonal extension through NTRK1 but has no effect on neuron survival. Upon dimeric NGF ligand-binding, undergoes homodimerization, autophosphorylation and activation. Recruits, phosphorylates and/or activates several downstream effectors including SHC1, FRS2, SH2B1, SH2B2 and PLCG1 that regulate distinct overlapping signaling cascades driving cell survival and differentiation. Through SHC1 and FRS2 activates a GRB2-Ras-MAPK cascade that regulates cell differentiation and survival. Through PLCG1 controls NF-Kappa-B activation and the transcription of genes involved in cell survival. Through SHC1 and SH2B1 controls a Ras-PI3 kinase-AKT1 signaling cascade that is also regulating survival. In absence of ligand and activation, may promote cell death, making the survival of neurons dependent on trophic factors.
Isoform TrkA-III is resistant to NGF, 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.

Catalytic activityi

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

Enzyme regulationi

The pro-survival signaling effect of NTRK1 in neurons requires its endocytosis into signaling early endosomes and its retrograde axonal transport. This is regulated by different proteins including CFL1, RAC1 and SORT1. NTF3 is unable to induce this signaling probably due to the lability of the NTF3-NTRK1 complex in endosomes. SH2D1A inhibits the autophosphorylation of the receptor, and alters the recruitment and activation of downstream effectors and signaling cascades (By similarity). Regulated by NGFR (By similarity).By similarity

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei398 – 3992Breakpoint for translocation to form TRK and TRK-T3
Sitei486 – 4861Breakpoint for translocation to form TRK-T1
Sitei496 – 4961Interaction with SHC1
Binding sitei544 – 5441ATPPROSITE-ProRule annotation
Active sitei650 – 6501Proton acceptorPROSITE-ProRule annotation
Sitei791 – 7911Interaction with PLCG1

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi516 – 5249ATPPROSITE-ProRule annotation

GO - Molecular functioni

  1. ATP binding Source: UniProtKB-KW
  2. nerve growth factor binding Source: UniProtKB
  3. nerve growth factor receptor activity Source: UniProtKB
  4. neurotrophin binding Source: ProtInc
  5. protein homodimerization activity Source: UniProtKB
  6. transmembrane receptor protein tyrosine kinase activity Source: UniProtKB

GO - Biological processi

  1. activation of adenylate cyclase activity Source: Reactome
  2. activation of MAPKK activity Source: Reactome
  3. activation of phospholipase C activity Source: Reactome
  4. aging Source: Ensembl
  5. axon guidance Source: Ensembl
  6. axonogenesis involved in innervation Source: UniProtKB
  7. B cell differentiation Source: Ensembl
  8. cellular response to nerve growth factor stimulus Source: UniProtKB
  9. cellular response to nicotine Source: Ensembl
  10. circadian rhythm Source: Ensembl
  11. detection of mechanical stimulus involved in sensory perception of pain Source: Ensembl
  12. detection of temperature stimulus involved in sensory perception of pain Source: Ensembl
  13. developmental programmed cell death Source: UniProtKB
  14. learning or memory Source: Ensembl
  15. mechanoreceptor differentiation Source: Ensembl
  16. negative regulation of cell proliferation Source: UniProtKB
  17. negative regulation of neuron apoptotic process Source: UniProtKB
  18. neurotrophin TRK receptor signaling pathway Source: UniProtKB
  19. olfactory nerve development Source: Ensembl
  20. peptidyl-tyrosine phosphorylation Source: GOC
  21. phosphatidylinositol-mediated signaling Source: Reactome
  22. positive regulation of angiogenesis Source: UniProtKB
  23. positive regulation of ERK1 and ERK2 cascade Source: UniProtKB
  24. positive regulation of neuron projection development Source: UniProtKB
  25. positive regulation of NF-kappaB transcription factor activity Source: UniProtKB
  26. positive regulation of programmed cell death Source: UniProtKB
  27. positive regulation of Ras GTPase activity Source: UniProtKB
  28. positive regulation of Ras protein signal transduction Source: UniProtKB
  29. positive regulation of synaptic transmission, glutamatergic Source: Ensembl
  30. protein autophosphorylation Source: UniProtKB
  31. protein phosphorylation Source: UniProtKB
  32. Ras protein signal transduction Source: Reactome
  33. response to activity Source: Ensembl
  34. response to axon injury Source: Ensembl
  35. response to drug Source: Ensembl
  36. response to electrical stimulus Source: Ensembl
  37. response to ethanol Source: Ensembl
  38. response to hydrostatic pressure Source: Ensembl
  39. response to nutrient levels Source: Ensembl
  40. response to radiation Source: Ensembl
  41. Sertoli cell development Source: Ensembl
  42. small GTPase mediated signal transduction Source: Reactome
  43. sympathetic nervous system development Source: UniProtKB
  44. transmembrane receptor protein tyrosine kinase signaling pathway Source: Reactome
Complete GO annotation...

Keywords - Molecular functioni

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

Keywords - Biological processi

Differentiation, Neurogenesis

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.10.1. 2681.
ReactomeiREACT_11046. NGF-independant TRKA activation.
REACT_11060. TRKA activation by NGF.
REACT_12002. ARMS-mediated activation.
REACT_12033. Signalling to RAS.
REACT_12049. Signalling to STAT3.
REACT_12076. Frs2-mediated activation.
REACT_12077. Signalling to p38 via RIT and RIN.
REACT_12079. PLC-gamma1 signalling.
REACT_12435. Retrograde neurotrophin signalling.
REACT_12464. PI3K/AKT activation.
SignaLinkiP04629.

Names & Taxonomyi

Protein namesi
Recommended name:
High affinity nerve growth factor receptor (EC:2.7.10.1)
Alternative name(s):
Neurotrophic tyrosine kinase receptor type 1
TRK1-transforming tyrosine kinase protein
Tropomyosin-related kinase A
Tyrosine kinase receptor
Tyrosine kinase receptor A
Short name:
Trk-A
gp140trk
p140-TrkA
Gene namesi
Name:NTRK1
Synonyms:MTC, TRK, TRKA
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 1

Organism-specific databases

HGNCiHGNC:8031. NTRK1.

Subcellular locationi

Cell membrane 1 Publication; Single-pass type I membrane protein 1 Publication. Early endosome membrane By similarity; Single-pass type I membrane protein By similarity. Late endosome membrane By similarity; Single-pass type I membrane protein By similarity
Note: Internalized to endosomes upon binding of NGF or NTF3 and further transported to the cell body via a retrograde axonal transport. Localized at cell membrane and early endosomes before nerve growth factor (NGF) stimulation. Recruited to late endosomes after NGF stimulation. Colocalized with RAPGEF2 at late endosomes (By similarity).By similarity

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini33 – 423391ExtracellularSequence AnalysisAdd
BLAST
Transmembranei424 – 43916HelicalSequence AnalysisAdd
BLAST
Topological domaini440 – 796357CytoplasmicSequence AnalysisAdd
BLAST

GO - Cellular componenti

  1. axon Source: Ensembl
  2. cell surface Source: Ensembl
  3. cytoplasmic vesicle Source: Ensembl
  4. dendrite Source: Ensembl
  5. early endosome Source: UniProtKB
  6. endosome Source: Reactome
  7. integral component of plasma membrane Source: UniProtKB
  8. late endosome Source: UniProtKB
  9. neuronal cell body Source: Ensembl
  10. plasma membrane Source: UniProtKB
  11. protein complex Source: UniProtKB
  12. receptor complex Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Endosome, Membrane

Pathology & Biotechi

Involvement in diseasei

Congenital insensitivity to pain with anhidrosis (CIPA) [MIM:256800]: Characterized 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.9 Publications
Note: The disease is caused by mutations affecting the gene represented in this entry.
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti93 – 931L → P in CIPA; aberrantly processed; shows diminished autophosphorylation in neuronal cells. 1 Publication
VAR_009624
Natural varianti213 – 2131L → P in CIPA; aberrantly processed; shows diminished autophosphorylation in neuronal cells. 1 Publication
VAR_009625
Natural varianti359 – 3591Y → C in CIPA. 1 Publication
VAR_068481
Natural varianti492 – 4921E → K in CIPA. 1 Publication
VAR_068482
Natural varianti522 – 5221G → R in CIPA; processed as wild-type but shows significantly diminished autophosphorylation in both neuronal and non-neuronal cells. 1 Publication
VAR_009626
Natural varianti577 – 5771G → R in CIPA; loss of function; processed as wild-type but shows significantly diminished autophosphorylation in both neuronal and non-neuronal cells. 3 Publications
VAR_004103
Natural varianti587 – 5871M → V in CIPA. 1 Publication
VAR_009627
Natural varianti649 – 6491R → W in CIPA; processed as wild-type but shows significantly diminished autophosphorylation in both neuronal and non-neuronal cells. 1 Publication
VAR_009630
Natural varianti654 – 6541R → C in CIPA; processed as wild-type but shows significantly diminished autophosphorylation in both neuronal and non-neuronal cells. 2 Publications
VAR_009631
Natural varianti674 – 6741D → Y in CIPA; unknown pathological significance; might impair the function of the enzyme without compromising autophosphorylation. 1 Publication
VAR_009632
Natural varianti695 – 6951P → L in CIPA. 1 Publication
VAR_009633
Natural varianti714 – 7141G → S in CIPA; processed as wild-type but shows significantly diminished autophosphorylation in both neuronal and non-neuronal cells. 1 Publication
VAR_009634
Natural varianti780 – 7801R → P in CIPA; loss of function. 1 Publication
Corresponds to variant rs35669708 [ dbSNP | Ensembl ].
VAR_009635
Thyroid papillary carcinoma (TPC) [MIM:188550]: A common tumor of the thyroid that typically arises as an irregular, solid or cystic mass from otherwise normal thyroid tissue. Papillary carcinomas are malignant neoplasm characterized by the formation of numerous, irregular, finger-like projections of fibrous stroma that is covered with a surface layer of neoplastic epithelial cells.
Note: The gene represented in this entry is involved in disease pathogenesis. Chromosomal aberrations involving NTRK1 are found in thyroid papillary carcinomas. Translocation t(1;3)(q21;q11) with TFG generates the TRKT3 (TRK-T3) transcript by fusing TFG to the 3'-end of NTRK1; a rearrangement with TPM3 generates the TRK transcript by fusing TPM3 to the 3'-end of NTRK1; 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.

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi496 – 4961Y → 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
Mutagenesisi544 – 5441K → N: Loss of kinase activity. 1 Publication
Mutagenesisi791 – 7911Y → 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

Keywords - Diseasei

Disease mutation, Proto-oncogene

Organism-specific databases

MIMi188550. phenotype.
256800. phenotype.
Orphaneti99361. Familial medullary thyroid carcinoma.
642. Hereditary sensory and autonomic neuropathy type 4.
64752. Hereditary sensory and autonomic neuropathy type 5.
146. Papillary or follicular thyroid carcinoma.
PharmGKBiPA31817.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 3232Sequence AnalysisAdd
BLAST
Chaini33 – 796764High affinity nerve growth factor receptorPRO_0000016724Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi67 – 671N-linked (GlcNAc...)Sequence Analysis
Glycosylationi95 – 951N-linked (GlcNAc...)1 Publication
Glycosylationi121 – 1211N-linked (GlcNAc...)1 Publication
Disulfide bondi154 ↔ 1911 PublicationPROSITE-ProRule annotation
Glycosylationi188 – 1881N-linked (GlcNAc...)1 Publication
Glycosylationi202 – 2021N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi215 ↔ 2651 PublicationPROSITE-ProRule annotation
Glycosylationi253 – 2531N-linked (GlcNAc...)Sequence Analysis
Glycosylationi262 – 2621N-linked (GlcNAc...)1 Publication
Glycosylationi281 – 2811N-linked (GlcNAc...)1 Publication
Glycosylationi318 – 3181N-linked (GlcNAc...)Sequence Analysis
Glycosylationi323 – 3231N-linked (GlcNAc...)Sequence Analysis
Glycosylationi338 – 3381N-linked (GlcNAc...)Sequence Analysis
Glycosylationi358 – 3581N-linked (GlcNAc...)1 Publication
Glycosylationi401 – 4011N-linked (GlcNAc...)Sequence Analysis
Modified residuei496 – 4961Phosphotyrosine; by autocatalysis2 Publications
Modified residuei676 – 6761Phosphotyrosine; by autocatalysis1 Publication
Modified residuei680 – 6801Phosphotyrosine; by autocatalysis1 Publication
Modified residuei681 – 6811Phosphotyrosine; by autocatalysis1 Publication
Modified residuei791 – 7911Phosphotyrosine; by autocatalysis3 Publications

Post-translational modificationi

Ligand-mediated autophosphorylation. Interaction with SQSTM1 is phosphotyrosine-dependent. Autophosphorylation at Tyr-496 mediates interaction and phosphorylation of SHC1.4 Publications
N-glycosylated (Probable). Isoform TrkA-I is N-glycosylated.2 PublicationsCurated
Ubiquitinated. Undergoes polyubiquitination upon activation; regulated by NGFR. Ubiquitination regulates the internalization of the receptor (By similarity).By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiP04629.
PRIDEiP04629.

PTM databases

PhosphoSiteiP04629.

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

BgeeiP04629.
ExpressionAtlasiP04629. baseline and differential.
GenevestigatoriP04629.

Organism-specific databases

HPAiCAB004606.

Interactioni

Subunit structurei

Exists in a dynamic equilibrium between monomeric (low affinity) and dimeric (high affinity) structures. Homodimerization is induced by binding of a NGF dimer. Interacts with SQSTM1; bridges NTRK1 to NGFR. Forms a ternary complex with NGFR and KIDINS220; this complex is affected by the expression levels of KIDINS220 and an increase in KIDINS220 expression leads to a decreased association of NGFR and NTRK1 (By similarity). Interacts with SH2D1A; regulates NTRK1 (By similarity). Interacts (phosphorylated upon activation by NGF) with SHC1; mediates SHC1 phosphorylation and activation. Interacts (phosphorylated upon activation by NGF) with PLCG1; mediates PLCG1 phosphorylation and activation. Interacts (phosphorylated) with SH2B1 and SH2B2. Interacts with GRB2. Interacts with PIK3R1. Interacts with FRS2. Interacts with SORT1; may regulate NTRK1 anterograde axonal transport. Interacts with RAB7A (By similarity). Found in a complex, at least composed of KIDINS220, MAGI2, NTRK1 and RAPGEF2; the complex is mainly formed at late endosomes in a nerve growth factor (NGF)-dependent manner (By similarity). Interacts with RAPGEF2; the interaction is strengthened after NGF stimulation (By similarity).By similarity

Binary interactionsi

WithEntry#Exp.IntActNotes
CBLP226812EBI-1028226,EBI-518228
NGFP011382EBI-1028226,EBI-1028250
PirbQ8K4V62EBI-1028226,EBI-8602514From a different organism.
PTPN1P180312EBI-1028226,EBI-968788

Protein-protein interaction databases

BioGridi110969. 34 interactions.
DIPiDIP-5714N.
IntActiP04629. 16 interactions.
MINTiMINT-124106.

Structurei

Secondary structure

1
796
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi38 – 403Combined sources
Beta strandi43 – 464Combined sources
Turni57 – 615Combined sources
Beta strandi69 – 724Combined sources
Helixi84 – 863Combined sources
Beta strandi94 – 974Combined sources
Helixi110 – 1123Combined sources
Beta strandi119 – 1213Combined sources
Turni133 – 1353Combined sources
Beta strandi142 – 1443Combined sources
Helixi154 – 1563Combined sources
Helixi157 – 1648Combined sources
Helixi171 – 1733Combined sources
Beta strandi178 – 1814Combined sources
Beta strandi195 – 1995Combined sources
Beta strandi211 – 2188Combined sources
Beta strandi227 – 2304Combined sources
Beta strandi234 – 2385Combined sources
Beta strandi244 – 25310Combined sources
Turni257 – 2604Combined sources
Beta strandi263 – 2653Combined sources
Beta strandi276 – 2783Combined sources
Beta strandi284 – 2907Combined sources
Beta strandi298 – 3058Combined sources
Beta strandi312 – 3176Combined sources
Beta strandi326 – 3338Combined sources
Beta strandi342 – 3509Combined sources
Helixi353 – 3553Combined sources
Beta strandi357 – 3659Combined sources
Beta strandi368 – 3769Combined sources
Turni494 – 4963Combined sources
Helixi507 – 5093Combined sources
Beta strandi510 – 5189Combined sources
Beta strandi520 – 53112Combined sources
Beta strandi540 – 5467Combined sources
Helixi553 – 56614Combined sources
Beta strandi575 – 5795Combined sources
Beta strandi581 – 5844Combined sources
Beta strandi586 – 5905Combined sources
Helixi597 – 6037Combined sources
Beta strandi605 – 6073Combined sources
Helixi608 – 6114Combined sources
Beta strandi615 – 6173Combined sources
Beta strandi619 – 6213Combined sources
Helixi624 – 64320Combined sources
Helixi653 – 6553Combined sources
Beta strandi656 – 6594Combined sources
Turni660 – 6623Combined sources
Beta strandi663 – 6664Combined sources
Helixi672 – 6754Combined sources
Helixi677 – 6793Combined sources
Beta strandi681 – 6844Combined sources
Beta strandi687 – 6893Combined sources
Helixi691 – 6933Combined sources
Helixi696 – 7016Combined sources
Helixi706 – 72116Combined sources
Turni727 – 7304Combined sources
Helixi733 – 74210Combined sources
Helixi754 – 76310Combined sources
Helixi768 – 7703Combined sources
Helixi774 – 78714Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1HE7X-ray2.00A285-413[»]
1SHCNMR-B489-500[»]
1WWAX-ray2.50X/Y278-386[»]
1WWWX-ray2.20X/Y282-382[»]
2IFGX-ray3.40A/B36-382[»]
4AOJX-ray2.75A/B/C473-796[»]
4F0IX-ray2.30A/B498-796[»]
4GT5X-ray2.40A498-796[»]
4PMMX-ray2.00A501-787[»]
4PMPX-ray1.80A501-787[»]
4PMSX-ray2.80A501-787[»]
4PMTX-ray2.10A501-787[»]
ProteinModelPortaliP04629.
SMRiP04629. Positions 36-382, 501-794.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP04629.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Repeati90 – 11324LRR 1Add
BLAST
Repeati116 – 13722LRR 2Add
BLAST
Domaini148 – 19346LRRCTAdd
BLAST
Domaini194 – 28390Ig-like C2-type 1Add
BLAST
Domaini299 – 36567Ig-like C2-type 2Add
BLAST
Domaini510 – 781272Protein kinasePROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni469 – 49022Interaction with SQSTM1By similarityAdd
BLAST

Domaini

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

Sequence similaritiesi

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

Keywords - Domaini

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

Phylogenomic databases

eggNOGiCOG0515.
GeneTreeiENSGT00760000118818.
HOVERGENiHBG056735.
InParanoidiP04629.
KOiK03176.
OMAiKNVTCWA.
OrthoDBiEOG7GTT32.
PhylomeDBiP04629.
TreeFamiTF106465.

Family and domain databases

Gene3Di2.60.40.10. 2 hits.
InterProiIPR000483. Cys-rich_flank_reg_C.
IPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR003599. Ig_sub.
IPR011009. Kinase-like_dom.
IPR001611. Leu-rich_rpt.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
IPR008266. Tyr_kinase_AS.
IPR020635. Tyr_kinase_cat_dom.
IPR020461. Tyr_kinase_neurotrophic_rcpt_1.
IPR020777. Tyr_kinase_NGF_rcpt.
IPR002011. Tyr_kinase_rcpt_2_CS.
[Graphical view]
PfamiPF13855. LRR_8. 1 hit.
PF07714. Pkinase_Tyr. 1 hit.
[Graphical view]
PRINTSiPR01939. NTKRECEPTOR.
PR01940. NTKRECEPTOR1.
PR00109. TYRKINASE.
SMARTiSM00409. IG. 1 hit.
SM00082. LRRCT. 1 hit.
SM00219. TyrKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS50835. IG_LIKE. 1 hit.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00109. PROTEIN_KINASE_TYR. 1 hit.
PS00239. RECEPTOR_TYR_KIN_II. 1 hit.
[Graphical view]

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

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

Isoform TrkA-II (identifier: P04629-1) [UniParc]FASTAAdd to Basket

Also known as: TrkAII

This isoform has been chosen as the 'canonical' 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
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.

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.

Show »
Length:698
Mass (Da):77,145
Checksum:i580555F90386A5A7
GO

Sequence cautioni

The sequence CAA27243.1 differs from that shown. Reason: Contaminating sequence. Sequence of unknown origin in the N-terminal part.Curated
The sequence CAA27243.1 differs from that shown. Reason: Frameshift at position 769. Curated
The sequence CAA27243.1 differs from that shown. Reason: Erroneous termination at position 786. Translated as Gln.Curated
The sequence CAA29888.1 differs from that shown. Reason: Contaminating sequence. Sequence of unknown origin in the N-terminal part.Curated
The sequence CAA44719.1 differs from that shown. Reason: Contaminating sequence. Sequence of unknown origin in the N-terminal part.Curated
The sequence CAA59936.1 differs from that shown. Reason: Contaminating sequence. Sequence of unknown origin in the N-terminal part.Curated

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti263 – 2631V → L in AAA36770. (PubMed:2927393)Curated
Sequence conflicti300 – 3001C → S in AAA36770. (PubMed:2927393)Curated
Sequence conflicti529 – 5291C → S in CAA59936. (PubMed:7565764)Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti6 – 61R → W.1 Publication
VAR_068480
Natural varianti18 – 181G → E.
Corresponds to variant rs1007211 [ dbSNP | Ensembl ].
VAR_049714
Natural varianti80 – 801Q → R.1 Publication
Corresponds to variant rs55891455 [ dbSNP | Ensembl ].
VAR_041461
Natural varianti85 – 851R → S.1 Publication
VAR_009623
Natural varianti93 – 931L → P in CIPA; aberrantly processed; shows diminished autophosphorylation in neuronal cells. 1 Publication
VAR_009624
Natural varianti107 – 1071A → V in an ovarian serous carcinoma sample; somatic mutation. 1 Publication
VAR_041462
Natural varianti213 – 2131L → P in CIPA; aberrantly processed; shows diminished autophosphorylation in neuronal cells. 1 Publication
VAR_009625
Natural varianti237 – 2371T → M.1 Publication
Corresponds to variant rs55909005 [ dbSNP | Ensembl ].
VAR_041463
Natural varianti238 – 2381V → G.1 Publication
Corresponds to variant rs56000394 [ dbSNP | Ensembl ].
VAR_041464
Natural varianti260 – 2601R → G.1 Publication
Corresponds to variant rs35116695 [ dbSNP | Ensembl ].
VAR_041465
Natural varianti359 – 3591Y → C in CIPA. 1 Publication
VAR_068481
Natural varianti444 – 4441R → Q.1 Publication
Corresponds to variant rs56320207 [ dbSNP | Ensembl ].
VAR_041466
Natural varianti452 – 4521R → C.1 Publication
Corresponds to variant rs34900547 [ dbSNP | Ensembl ].
VAR_041467
Natural varianti492 – 4921E → K in CIPA. 1 Publication
VAR_068482
Natural varianti522 – 5221G → R in CIPA; processed as wild-type but shows significantly diminished autophosphorylation in both neuronal and non-neuronal cells. 1 Publication
VAR_009626
Natural varianti566 – 5661M → T.1 Publication
Corresponds to variant rs55892037 [ dbSNP | Ensembl ].
VAR_041468
Natural varianti577 – 5771G → R in CIPA; loss of function; processed as wild-type but shows significantly diminished autophosphorylation in both neuronal and non-neuronal cells. 3 Publications
VAR_004103
Natural varianti587 – 5871M → V in CIPA. 1 Publication
VAR_009627
Natural varianti604 – 6041H → Y.5 Publications
Corresponds to variant rs6336 [ dbSNP | Ensembl ].
VAR_009628
Natural varianti613 – 6131G → V.6 Publications
Corresponds to variant rs6339 [ dbSNP | Ensembl ].
VAR_009629
Natural varianti649 – 6491R → W in CIPA; processed as wild-type but shows significantly diminished autophosphorylation in both neuronal and non-neuronal cells. 1 Publication
VAR_009630
Natural varianti654 – 6541R → C in CIPA; processed as wild-type but shows significantly diminished autophosphorylation in both neuronal and non-neuronal cells. 2 Publications
VAR_009631
Natural varianti674 – 6741D → Y in CIPA; unknown pathological significance; might impair the function of the enzyme without compromising autophosphorylation. 1 Publication
VAR_009632
Natural varianti695 – 6951P → L in CIPA. 1 Publication
VAR_009633
Natural varianti714 – 7141G → S in CIPA; processed as wild-type but shows significantly diminished autophosphorylation in both neuronal and non-neuronal cells. 1 Publication
VAR_009634
Natural varianti780 – 7801R → P in CIPA; loss of function. 1 Publication
Corresponds to variant rs35669708 [ dbSNP | Ensembl ].
VAR_009635
Natural varianti780 – 7801R → Q.2 Publications
Corresponds to variant rs35669708 [ dbSNP | Ensembl ].
VAR_009636
Natural varianti790 – 7901V → I.1 Publication
Corresponds to variant rs55948542 [ dbSNP | Ensembl ].
VAR_041469

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 7171MLRGG…NLTEL → MKEAALICLAPSVPPILTVK SWDTMQLRAARSRCTNLLAA S in isoform 3. 1 PublicationVSP_041905Add
BLAST
Alternative sequencei192 – 28493GVPTL…VNVSF → V in isoform TrkA-III. CuratedVSP_042152Add
BLAST
Alternative sequencei393 – 3986Missing in isoform TrkA-I, isoform 3 and isoform TrkA-III. 3 PublicationsVSP_002899

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M23102 mRNA. Translation: AAA36770.1.
AB019488 Genomic DNA. Translation: BAA34355.1.
AK312704 mRNA. Translation: BAG35582.1.
DB265639 mRNA. No translation available.
AL158169 Genomic DNA. Translation: CAH70010.1.
BC062580 mRNA. Translation: AAH62580.1.
BC136554 mRNA. Translation: AAI36555.1.
BC144239 mRNA. Translation: AAI44240.1.
AY321513 Genomic DNA. Translation: AAP88292.1.
X03541 mRNA. Translation: CAA27243.1. Sequence problems.
X06704 mRNA. Translation: CAA29888.1. Sequence problems.
X85960 mRNA. Translation: CAA59936.1. Sequence problems.
X62947 mRNA. Translation: CAA44719.1. Sequence problems.
CCDSiCCDS1161.1. [P04629-1]
CCDS30890.1. [P04629-3]
CCDS30891.1. [P04629-2]
PIRiA30124. TVHUTT.
S23741.
RefSeqiNP_001007793.1. NM_001007792.1. [P04629-3]
NP_001012331.1. NM_001012331.1. [P04629-2]
NP_002520.2. NM_002529.3. [P04629-1]
UniGeneiHs.406293.

Genome annotation databases

EnsembliENST00000368196; ENSP00000357179; ENSG00000198400. [P04629-2]
ENST00000392302; ENSP00000376120; ENSG00000198400. [P04629-3]
ENST00000524377; ENSP00000431418; ENSG00000198400. [P04629-1]
GeneIDi4914.
KEGGihsa:4914.
UCSCiuc001fqf.1. human. [P04629-3]
uc001fqh.1. human. [P04629-1]
uc001fqi.1. human. [P04629-2]
uc009wsi.1. human. [P04629-4]

Polymorphism databases

DMDMi94730402.

Keywords - Coding sequence diversityi

Alternative splicing, Chromosomal rearrangement, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M23102 mRNA. Translation: AAA36770.1 .
AB019488 Genomic DNA. Translation: BAA34355.1 .
AK312704 mRNA. Translation: BAG35582.1 .
DB265639 mRNA. No translation available.
AL158169 Genomic DNA. Translation: CAH70010.1 .
BC062580 mRNA. Translation: AAH62580.1 .
BC136554 mRNA. Translation: AAI36555.1 .
BC144239 mRNA. Translation: AAI44240.1 .
AY321513 Genomic DNA. Translation: AAP88292.1 .
X03541 mRNA. Translation: CAA27243.1 . Sequence problems.
X06704 mRNA. Translation: CAA29888.1 . Sequence problems.
X85960 mRNA. Translation: CAA59936.1 . Sequence problems.
X62947 mRNA. Translation: CAA44719.1 . Sequence problems.
CCDSi CCDS1161.1. [P04629-1 ]
CCDS30890.1. [P04629-3 ]
CCDS30891.1. [P04629-2 ]
PIRi A30124. TVHUTT.
S23741.
RefSeqi NP_001007793.1. NM_001007792.1. [P04629-3 ]
NP_001012331.1. NM_001012331.1. [P04629-2 ]
NP_002520.2. NM_002529.3. [P04629-1 ]
UniGenei Hs.406293.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
1HE7 X-ray 2.00 A 285-413 [» ]
1SHC NMR - B 489-500 [» ]
1WWA X-ray 2.50 X/Y 278-386 [» ]
1WWW X-ray 2.20 X/Y 282-382 [» ]
2IFG X-ray 3.40 A/B 36-382 [» ]
4AOJ X-ray 2.75 A/B/C 473-796 [» ]
4F0I X-ray 2.30 A/B 498-796 [» ]
4GT5 X-ray 2.40 A 498-796 [» ]
4PMM X-ray 2.00 A 501-787 [» ]
4PMP X-ray 1.80 A 501-787 [» ]
4PMS X-ray 2.80 A 501-787 [» ]
4PMT X-ray 2.10 A 501-787 [» ]
ProteinModelPortali P04629.
SMRi P04629. Positions 36-382, 501-794.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 110969. 34 interactions.
DIPi DIP-5714N.
IntActi P04629. 16 interactions.
MINTi MINT-124106.

Chemistry

BindingDBi P04629.
ChEMBLi CHEMBL2815.
DrugBanki DB00321. Amitriptyline.
DB00619. Imatinib.
DB08896. Regorafenib.
GuidetoPHARMACOLOGYi 1817.

PTM databases

PhosphoSitei P04629.

Polymorphism databases

DMDMi 94730402.

Proteomic databases

PaxDbi P04629.
PRIDEi P04629.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000368196 ; ENSP00000357179 ; ENSG00000198400 . [P04629-2 ]
ENST00000392302 ; ENSP00000376120 ; ENSG00000198400 . [P04629-3 ]
ENST00000524377 ; ENSP00000431418 ; ENSG00000198400 . [P04629-1 ]
GeneIDi 4914.
KEGGi hsa:4914.
UCSCi uc001fqf.1. human. [P04629-3 ]
uc001fqh.1. human. [P04629-1 ]
uc001fqi.1. human. [P04629-2 ]
uc009wsi.1. human. [P04629-4 ]

Organism-specific databases

CTDi 4914.
GeneCardsi GC01P156786.
GeneReviewsi NTRK1.
HGNCi HGNC:8031. NTRK1.
HPAi CAB004606.
MIMi 164970. gene.
188550. phenotype.
191315. gene.
256800. phenotype.
neXtProti NX_P04629.
Orphaneti 99361. Familial medullary thyroid carcinoma.
642. Hereditary sensory and autonomic neuropathy type 4.
64752. Hereditary sensory and autonomic neuropathy type 5.
146. Papillary or follicular thyroid carcinoma.
PharmGKBi PA31817.
GenAtlasi Search...

Phylogenomic databases

eggNOGi COG0515.
GeneTreei ENSGT00760000118818.
HOVERGENi HBG056735.
InParanoidi P04629.
KOi K03176.
OMAi KNVTCWA.
OrthoDBi EOG7GTT32.
PhylomeDBi P04629.
TreeFami TF106465.

Enzyme and pathway databases

BRENDAi 2.7.10.1. 2681.
Reactomei REACT_11046. NGF-independant TRKA activation.
REACT_11060. TRKA activation by NGF.
REACT_12002. ARMS-mediated activation.
REACT_12033. Signalling to RAS.
REACT_12049. Signalling to STAT3.
REACT_12076. Frs2-mediated activation.
REACT_12077. Signalling to p38 via RIT and RIN.
REACT_12079. PLC-gamma1 signalling.
REACT_12435. Retrograde neurotrophin signalling.
REACT_12464. PI3K/AKT activation.
SignaLinki P04629.

Miscellaneous databases

ChiTaRSi NTRK1. human.
EvolutionaryTracei P04629.
GenomeRNAii 4914.
NextBioi 18907.
PROi P04629.
SOURCEi Search...

Gene expression databases

Bgeei P04629.
ExpressionAtlasi P04629. baseline and differential.
Genevestigatori P04629.

Family and domain databases

Gene3Di 2.60.40.10. 2 hits.
InterProi IPR000483. Cys-rich_flank_reg_C.
IPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR003599. Ig_sub.
IPR011009. Kinase-like_dom.
IPR001611. Leu-rich_rpt.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
IPR008266. Tyr_kinase_AS.
IPR020635. Tyr_kinase_cat_dom.
IPR020461. Tyr_kinase_neurotrophic_rcpt_1.
IPR020777. Tyr_kinase_NGF_rcpt.
IPR002011. Tyr_kinase_rcpt_2_CS.
[Graphical view ]
Pfami PF13855. LRR_8. 1 hit.
PF07714. Pkinase_Tyr. 1 hit.
[Graphical view ]
PRINTSi PR01939. NTKRECEPTOR.
PR01940. NTKRECEPTOR1.
PR00109. TYRKINASE.
SMARTi SM00409. IG. 1 hit.
SM00082. LRRCT. 1 hit.
SM00219. TyrKc. 1 hit.
[Graphical view ]
SUPFAMi SSF56112. SSF56112. 1 hit.
PROSITEi 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.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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).
    Tissue: Colon.
  2. "Human trks: molecular cloning, tissue distribution, and expression of extracellular domain immunoadhesins."
    Shelton D.L., Sutherland J., Gripp J., Camerato T., Armanini M.P., Phillips H.S., Carroll K., Spencer S.D., Levinson A.D.
    J. Neurosci. 15:477-491(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Tissue: Brain.
  3. "Structure and organization of the human TRKA gene encoding a high affinity receptor for nerve growth factor."
    Indo Y., Mardy S., Tsuruta M., Karim M.A., Matsuda I.
    Jpn. J. Hum. Genet. 42:343-351(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
  4. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
    Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
    , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
    Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM TRKA-II), NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-175 (ISOFORM 3).
    Tissue: Uterus.
  5. "The DNA sequence and biological annotation of human chromosome 1."
    Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.
    , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.
    Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  6. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS TRKA-I AND TRKA-II).
    Tissue: Brain.
  7. "Methylation adjacent to negatively regulating AP-1 site reactivates TrkA gene expression during cancer progression."
    Fujimoto M., Kitazawa R., Maeda S., Kitazawa S.
    Oncogene 24:5108-5118(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-71.
  8. "A human oncogene formed by the fusion of truncated tropomyosin and protein tyrosine kinase sequences."
    Martin-Zanca D., Hughes S.H., Barbacid M.
    Nature 319:743-748(1986) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 399-796, CHROMOSOMAL TRANSLOCATION WITH TPM3.
  9. "Activation of the receptor kinase domain of the trk oncogene by recombination with two different cellular sequences."
    Kozma S.C., Redmond S.M.S., Saurer S.M., Groner B., Hynes N.E.
    EMBO J. 7:147-154(1988) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 399-796.
  10. "The DNA rearrangement that generates the TRK-T3 oncogene involves a novel gene on chromosome 3 whose product has a potential coiled-coil domain."
    Greco A., Mariani C., Miranda C., Lupas A., Pagliardini S., Pomati M., Pierotti M.A.
    Mol. Cell. Biol. 15:6118-6127(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 399-796, CHROMOSOMAL TRANSLOCATION WITH TFG.
  11. "TRK-T1 is a novel oncogene formed by the fusion of TPR and TRK genes in human papillary thyroid carcinomas."
    Greco A., Pierotti M.A., Bongarzone I., Pagliardini S., Lanzi C., Della Porta G.
    Oncogene 7:237-242(1992) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 486-796, CHROMOSOMAL REARRANGEMENT WITH TPR.
  12. "High-affinity NGF binding requires coexpression of the trk proto-oncogene and the low-affinity NGF receptor."
    Hempstead B.L., Martin-Zanca D., Kaplan D.R., Parada L.F., Chao M.V.
    Nature 350:678-683(1991) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION AS RECEPTOR FOR NGF.
  13. "The trk proto-oncogene encodes a receptor for nerve growth factor."
    Klein R., Jing S., Nanduri V., O'Rourke E., Barbacid M.
    Cell 65:189-197(1991) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN NGF SIGNALING, IDENTIFICATION AS THE HIGH AFFINITY NGF RECEPTOR.
  14. "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.
  15. "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.
  16. "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 AND TYR-791.
  17. "The atypical protein kinase C-interacting protein p62 is a scaffold for NF-kappaB activation by nerve growth factor."
    Wooten M.W., Seibenhener M.L., Mamidipudi V., Diaz-Meco M.T., Barker P.A., Moscat J.
    J. Biol. Chem. 276:7709-7712(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN NF-KAPPA-B ACTIVATION, INTERACTION WITH SQSTM1.
  18. 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.
  19. "Sortilin associates with Trk receptors to enhance anterograde transport and neurotrophin signaling."
    Vaegter C.B., Jansen P., Fjorback A.W., Glerup S., Skeldal S., Kjolby M., Richner M., Erdmann B., Nyengaard J.R., Tessarollo L., Lewin G.R., Willnow T.E., Chao M.V., Nykjaer A.
    Nat. Neurosci. 14:54-61(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH SORT1, ENZYME REGULATION.
  20. Cited for: STRUCTURE BY NMR OF 489-500.
  21. "Crystal structures of the neurotrophin-binding domain of TrkA, TrkB and TrkC."
    Ultsch M.H., Wiesmann C., Simmons L.C., Henrich J., Yang M., Reilly D., Bass S.H., de Vos A.M.
    J. Mol. Biol. 290:149-159(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 278-386.
  22. "Crystal structure of nerve growth factor in complex with the ligand-binding domain of the TrkA receptor."
    Wiesmann C., Ultsch M.H., Bass S.H., de Vos A.M.
    Nature 401:184-188(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 282-382.
  23. "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, DISULFIDE BONDS, GLYCOSYLATION AT ASN-95; ASN-121; ASN-188; ASN-262; ASN-281 AND ASN-358.
  24. "Mutations in the TRKA/NGF receptor gene in patients with congenital insensitivity to pain with anhidrosis."
    Indo Y., Tsuruta M., Hayashida Y., Karim M.A., Ohta K., Kawano T., Mitsubuchi H., Tonoki H., Awaya Y., Matsuda I.
    Nat. Genet. 13:485-488(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANT CIPA ARG-577.
  25. "A novel NTRK1 mutation associated with congenital insensitivity to pain with anhidrosis."
    Greco A., Villa R., Tubino B., Romano L., Penso D., Pierotti M.A.
    Am. J. Hum. Genet. 64:1207-1210(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANT CIPA PRO-780.
  26. "Congenital insensitivity to pain with anhidrosis: novel mutations in the TRKA (NTRK1) gene encoding a high-affinity receptor for nerve growth factor."
    Mardy S., Miura Y., Endo F., Matsuda I., Sztriha L., Frossard P., Moosa A., Ismail E.A.R., Macaya A., Andria G., Toscano E., Gibson W., Graham G.E., Indo Y.
    Am. J. Hum. Genet. 64:1570-1579(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANTS CIPA PRO-213; TRP-649 AND SER-714, VARIANTS SER-85; TYR-604 AND VAL-613.
  27. "Mutation analysis reveals novel sequence variants in NTRK1 in sporadic human medullary thyroid carcinoma."
    Gimm O., Greco A., Hoang-Vu C., Dralle H., Pierotti M.A., Eng C.
    J. Clin. Endocrinol. Metab. 84:2784-2787(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANTS TYR-604; VAL-613 AND GLN-780.
  28. "A novel point mutation affecting the tyrosine kinase domain of the TRKA gene in a family with congenital insensitivity to pain with anhidrosis."
    Yotsumoto S., Setoyama M., Hozumi H., Mizoguchi S., Fukumaru S., Kobayashi K., Saheki T., Kanzaki T.
    J. Invest. Dermatol. 112:810-814(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANT CIPA VAL-587.
  29. Cited for: VARIANTS TYR-604 AND VAL-613.
  30. "Congenital insensitivity to pain with anhidrosis (CIPA) in Israeli-Bedouins: genetic heterogeneity, novel mutations in the TRKA/NGF receptor gene, clinical findings, and results of nerve conduction studies."
    Shatzky S., Moses S., Levy J., Pinsk V., Hershkovitz E., Herzog L., Shorer Z., Luder A., Parvari R.
    Am. J. Med. Genet. 92:353-360(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANT CIPA LEU-695, VARIANT VAL-613.
    Tissue: Peripheral blood.
  31. "Mutation and polymorphism analysis of the TRKA (NTRK1) gene encoding a high-affinity receptor for nerve growth factor in congenital insensitivity to pain with anhidrosis (CIPA) families."
    Miura Y., Mardy S., Awaya Y., Nihei K., Endo F., Matsuda I., Indo Y.
    Hum. Genet. 106:116-124(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANTS CIPA PRO-93; ARG-522; ARG-577; CYS-654 AND TYR-674.
  32. "The Gly571Arg mutation, associated with the autonomic and sensory disorder congenital insensitivity to pain with anhidrosis, causes the inactivation of the NTRK1/nerve growth factor receptor."
    Greco A., Villa R., Fusetti L., Orlandi R., Pierotti M.A.
    J. Cell. Physiol. 182:127-133(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANT CIPA ARG-577.
  33. "A novel TRK A (NTRK1) mutation associated with hereditary sensory and autonomic neuropathy type V."
    Houlden H., King R.H., Hashemi-Nejad A., Wood N.W., Mathias C.J., Reilly M., Thomas P.K.
    Ann. Neurol. 49:521-525(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANT CIPA CYS-359, VARIANTS TYR-604 AND VAL-613.
  34. "Congenital insensitivity to pain with anhidrosis (CIPA): effect of TRKA (NTRK1) missense mutations on autophosphorylation of the receptor tyrosine kinase for nerve growth factor."
    Mardy S., Miura Y., Endo F., Matsuda I., Indo Y.
    Hum. Mol. Genet. 10:179-188(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: CHARACTERIZATION OF VARIANTS CIPA PRO-93; PRO-213; ARG-522; ARG-577; TRP-649; CYS-654 AND SER-714, CHARACTERIZATION OF VARIANTS SER-85; TYR-604; VAL-613 AND TYR-674.
  35. "Patterns of somatic mutation in human cancer genomes."
    Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G.
    , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R.
    Nature 446:153-158(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANTS [LARGE SCALE ANALYSIS] ARG-80; VAL-107; MET-237; GLY-238; GLY-260; GLN-444; CYS-452; THR-566; TYR-604; VAL-613; GLN-780 AND ILE-790.
  36. Cited for: VARIANTS CIPA LYS-492 AND CYS-654, VARIANT TRP-6.

Entry informationi

Entry nameiNTRK1_HUMAN
AccessioniPrimary (citable) accession number: P04629
Secondary accession number(s): B2R6T5
, B7ZM34, P08119, Q15655, Q15656, Q5D056, Q5VZS2, Q7Z5C3, Q9UIU7
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 13, 1987
Last sequence update: May 2, 2006
Last modified: November 26, 2014
This is version 199 of the entry and version 4 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

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.

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  7. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3