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P04629

- NTRK1_HUMAN

UniProt

P04629 - NTRK1_HUMAN

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
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    • History
      Entry version 197 (01 Oct 2014)
      Sequence version 4 (02 May 2006)
      Previous versions | rss
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    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 binding Source: UniProtKB
    6. protein homodimerization activity Source: UniProtKB
    7. 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. detection of mechanical stimulus involved in sensory perception of pain Source: Ensembl
    11. detection of temperature stimulus involved in sensory perception of pain Source: Ensembl
    12. developmental programmed cell death Source: UniProtKB
    13. learning or memory Source: Ensembl
    14. mechanoreceptor differentiation Source: Ensembl
    15. negative regulation of cell proliferation Source: UniProtKB
    16. negative regulation of neuron apoptotic process Source: UniProtKB
    17. neurotrophin TRK receptor signaling pathway Source: UniProtKB
    18. olfactory nerve development Source: Ensembl
    19. peptidyl-tyrosine phosphorylation Source: GOC
    20. phosphatidylinositol-mediated signaling Source: Reactome
    21. positive regulation of angiogenesis Source: UniProtKB
    22. positive regulation of ERK1 and ERK2 cascade Source: UniProtKB
    23. positive regulation of neuron projection development Source: UniProtKB
    24. positive regulation of NF-kappaB transcription factor activity Source: UniProtKB
    25. positive regulation of programmed cell death Source: UniProtKB
    26. positive regulation of Ras GTPase activity Source: UniProtKB
    27. positive regulation of Ras protein signal transduction Source: UniProtKB
    28. positive regulation of synaptic transmission, glutamatergic Source: Ensembl
    29. protein autophosphorylation Source: UniProtKB
    30. protein phosphorylation Source: UniProtKB
    31. Ras protein signal transduction Source: Reactome
    32. response to activity Source: Ensembl
    33. response to axon injury Source: Ensembl
    34. response to drug Source: Ensembl
    35. response to electrical stimulus Source: Ensembl
    36. response to ethanol Source: Ensembl
    37. response to hydrostatic pressure Source: Ensembl
    38. response to nutrient levels Source: Ensembl
    39. response to radiation Source: Ensembl
    40. Sertoli cell development Source: Ensembl
    41. small GTPase mediated signal transduction Source: Reactome
    42. sympathetic nervous system development Source: UniProtKB
    43. transmembrane receptor protein tyrosine kinase signaling pathway Source: Reactome

    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

    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. early endosome membrane Source: UniProtKB-SubCell
    7. endosome Source: Reactome
    8. integral component of plasma membrane Source: UniProtKB
    9. late endosome Source: UniProtKB
    10. late endosome membrane Source: UniProtKB-SubCell
    11. neuronal cell body Source: Ensembl
    12. plasma membrane Source: UniProtKB
    13. protein complex Source: UniProtKB
    14. receptor complex Source: MGI

    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...)2 Publications
    Glycosylationi121 – 1211N-linked (GlcNAc...)2 Publications
    Disulfide bondi154 ↔ 1911 PublicationPROSITE-ProRule annotation
    Glycosylationi188 – 1881N-linked (GlcNAc...)2 Publications
    Glycosylationi202 – 2021N-linked (GlcNAc...)Sequence Analysis
    Disulfide bondi215 ↔ 2651 PublicationPROSITE-ProRule annotation
    Glycosylationi253 – 2531N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi262 – 2621N-linked (GlcNAc...)2 Publications
    Glycosylationi281 – 2811N-linked (GlcNAc...)2 Publications
    Glycosylationi318 – 3181N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi323 – 3231N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi338 – 3381N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi358 – 3581N-linked (GlcNAc...)2 Publications
    Glycosylationi401 – 4011N-linked (GlcNAc...)Sequence Analysis
    Modified residuei496 – 4961Phosphotyrosine; by autocatalysis3 Publications
    Modified residuei676 – 6761Phosphotyrosine; by autocatalysis1 Publication
    Modified residuei680 – 6801Phosphotyrosine; by autocatalysis2 Publications
    Modified residuei681 – 6811Phosphotyrosine; by autocatalysis2 Publications
    Modified residuei791 – 7911Phosphotyrosine; by autocatalysis4 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

    ArrayExpressiP04629.
    BgeeiP04629.
    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
    PirbQ8K4V62EBI-1028226,EBI-8602514From a different organism.
    PTPN1P180312EBI-1028226,EBI-968788

    Protein-protein interaction databases

    BioGridi110969. 33 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 – 403
    Beta strandi43 – 464
    Turni57 – 615
    Beta strandi69 – 724
    Helixi84 – 863
    Beta strandi94 – 974
    Helixi110 – 1123
    Beta strandi119 – 1213
    Turni133 – 1353
    Beta strandi142 – 1443
    Helixi154 – 1563
    Helixi157 – 1648
    Helixi171 – 1733
    Beta strandi178 – 1814
    Beta strandi195 – 1995
    Beta strandi211 – 2188
    Beta strandi227 – 2304
    Beta strandi234 – 2385
    Beta strandi244 – 25310
    Turni257 – 2604
    Beta strandi263 – 2653
    Beta strandi276 – 2783
    Beta strandi284 – 2907
    Beta strandi298 – 3058
    Beta strandi312 – 3176
    Beta strandi326 – 3338
    Beta strandi342 – 3509
    Helixi353 – 3553
    Beta strandi357 – 3659
    Beta strandi368 – 3769
    Turni494 – 4963
    Helixi507 – 5093
    Beta strandi510 – 51910
    Beta strandi522 – 5298
    Beta strandi540 – 5467
    Helixi553 – 56614
    Beta strandi575 – 5795
    Beta strandi581 – 5844
    Beta strandi586 – 5905
    Helixi597 – 6037
    Beta strandi605 – 6073
    Beta strandi615 – 6173
    Beta strandi619 – 6213
    Helixi624 – 64320
    Helixi653 – 6553
    Beta strandi656 – 6583
    Turni660 – 6623
    Beta strandi664 – 6663
    Helixi672 – 6754
    Helixi677 – 6793
    Beta strandi680 – 6823
    Helixi683 – 6853
    Beta strandi686 – 6894
    Helixi691 – 6933
    Helixi696 – 7016
    Helixi706 – 72015
    Turni721 – 7244
    Turni727 – 7304
    Helixi733 – 74210
    Helixi754 – 76310
    Helixi768 – 7703
    Helixi774 – 78613

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    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.

    Topological domain

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

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei424 – 43916HelicalSequence AnalysisAdd
    BLAST

    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.
    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

    MLRGGRRGQL GWHSWAAGPG SLLAWLILAS AGAAPCPDAC CPHGSSGLRC    50
    TRDGALDSLH HLPGAENLTE LYIENQQHLQ HLELRDLRGL GELRNLTIVK 100
    SGLRFVAPDA FHFTPRLSRL NLSFNALESL SWKTVQGLSL QELVLSGNPL 150
    HCSCALRWLQ RWEEEGLGGV PEQKLQCHGQ GPLAHMPNAS CGVPTLKVQV 200
    PNASVDVGDD VLLRCQVEGR GLEQAGWILT ELEQSATVMK SGGLPSLGLT 250
    LANVTSDLNR KNVTCWAEND VGRAEVSVQV NVSFPASVQL HTAVEMHHWC 300
    IPFSVDGQPA PSLRWLFNGS VLNETSFIFT EFLEPAANET VRHGCLRLNQ 350
    PTHVNNGNYT LLAANPFGQA SASIMAAFMD NPFEFNPEDP IPVSFSPVDT 400
    NSTSGDPVEK KDETPFGVSV AVGLAVFACL FLSTLLLVLN KCGRRNKFGI 450
    NRPAVLAPED GLAMSLHFMT LGGSSLSPTE GKGSGLQGHI IENPQYFSDA 500
    CVHHIKRRDI VLKWELGEGA FGKVFLAECH NLLPEQDKML VAVKALKEAS 550
    ESARQDFQRE AELLTMLQHQ HIVRFFGVCT EGRPLLMVFE YMRHGDLNRF 600
    LRSHGPDAKL LAGGEDVAPG PLGLGQLLAV ASQVAAGMVY LAGLHFVHRD 650
    LATRNCLVGQ GLVVKIGDFG MSRDIYSTDY YRVGGRTMLP IRWMPPESIL 700
    YRKFTTESDV WSFGVVLWEI FTYGKQPWYQ LSNTEAIDCI TQGRELERPR 750
    ACPPEVYAIM RGCWQREPQQ RHSIKDVHAR LQALAQAPPV YLDVLG 796

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

    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:
    EMBL
    GenBank
    DDBJ
    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:
    EMBL
    GenBank
    DDBJ
    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:
    PDBe
    RCSB PDB
    PDBj
    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. 33 interactions.
    DIPi DIP-5714N.
    IntActi P04629. 16 interactions.
    MINTi MINT-124106.

    Chemistry

    BindingDBi P04629.
    ChEMBLi CHEMBL2815.
    DrugBanki DB00619. Imatinib.
    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.
    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

    ArrayExpressi P04629.
    Bgeei P04629.
    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

    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: October 1, 2014
    This is version 197 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