General Information of Target

Target ID LDTP02046
Target Name High affinity nerve growth factor receptor (NTRK1)
Gene Name NTRK1
Gene ID 4914
Synonyms
MTC; TRK; TRKA; High affinity nerve growth factor receptor; EC 2.7.10.1; Neurotrophic tyrosine kinase receptor type 1; TRK1-transforming tyrosine kinase protein; Tropomyosin-related kinase A; Tyrosine kinase receptor; Tyrosine kinase receptor A; Trk-A; gp140trk; p140-TrkA
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Sequence
MLRGGRRGQLGWHSWAAGPGSLLAWLILASAGAAPCPDACCPHGSSGLRCTRDGALDSLH
HLPGAENLTELYIENQQHLQHLELRDLRGLGELRNLTIVKSGLRFVAPDAFHFTPRLSRL
NLSFNALESLSWKTVQGLSLQELVLSGNPLHCSCALRWLQRWEEEGLGGVPEQKLQCHGQ
GPLAHMPNASCGVPTLKVQVPNASVDVGDDVLLRCQVEGRGLEQAGWILTELEQSATVMK
SGGLPSLGLTLANVTSDLNRKNVTCWAENDVGRAEVSVQVNVSFPASVQLHTAVEMHHWC
IPFSVDGQPAPSLRWLFNGSVLNETSFIFTEFLEPAANETVRHGCLRLNQPTHVNNGNYT
LLAANPFGQASASIMAAFMDNPFEFNPEDPIPVSFSPVDTNSTSGDPVEKKDETPFGVSV
AVGLAVFACLFLSTLLLVLNKCGRRNKFGINRPAVLAPEDGLAMSLHFMTLGGSSLSPTE
GKGSGLQGHIIENPQYFSDACVHHIKRRDIVLKWELGEGAFGKVFLAECHNLLPEQDKML
VAVKALKEASESARQDFQREAELLTMLQHQHIVRFFGVCTEGRPLLMVFEYMRHGDLNRF
LRSHGPDAKLLAGGEDVAPGPLGLGQLLAVASQVAAGMVYLAGLHFVHRDLATRNCLVGQ
GLVVKIGDFGMSRDIYSTDYYRVGGRTMLPIRWMPPESILYRKFTTESDVWSFGVVLWEI
FTYGKQPWYQLSNTEAIDCITQGRELERPRACPPEVYAIMRGCWQREPQQRHSIKDVHAR
LQALAQAPPVYLDVLG
Target Type
Successful
Target Bioclass
Enzyme
Family
Protein kinase superfamily, Tyr protein kinase family, Insulin receptor subfamily
Subcellular location
Cell membrane
Function
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. 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]: Resistant to NGF, it constitutively activates AKT1 and NF-kappa-B and is unable to activate the Ras-MAPK signaling cascade. Antagonizes the anti-proliferative NGF-NTRK1 signaling that promotes neuronal precursors differentiation. Isoform TrkA-III promotes angiogenesis and has oncogenic activity when overexpressed.
TTD ID
T07173
Uniprot ID
P04629
DrugMap ID
TTTDVOJ
Ensemble ID
ENST00000368196.7
HGNC ID
HGNC:8031
ChEMBL ID
CHEMBL2815

Target Site Mutations in Different Cell Lines

Cell line Mutation details Probe for labeling this protein in this cell
AN3CA SNV: p.T678I .
CAMA1 SNV: p.S475C .
CORL23 SNV: p.S304C .
DOTC24510 Deletion: p.G423_V426del .
FTC133 SNV: p.M671T .
HCT15 SNV: p.A421V .
HEC1 SNV: p.E388K .
HEC1B SNV: p.E388K .
HT115 SNV: p.D412N .
IGR1 SNV: p.W514Ter .
LOXIMVI SNV: p.V420M .
MCC13 SNV: p.V393I .
MELJUSO SNV: p.G595E .
NCIH1944 SNV: p.A454V .
RL952 Insertion: p.L622PfsTer11 .
SNGM SNV: p.E518D .
SNU449 SNV: p.D793A .
UACC257 SNV: p.P387L .

Probe(s) Labeling This Target

ABPP Probe
Click To Hide/Show 1 Probe Related to This Target
Probe name Structure Binding Site(Ratio) Interaction ID Ref
DBIA
 Probe Info 
C501(1.58); C656(2.37)  LDD2412  [1]

Competitor(s) Related to This Target

Competitor ID Name Cell line Binding Site(Ratio) Interaction ID Ref
 LDCM0022  KB02 Karpas-299 C501(1.58); C656(2.37)  LDD2412  [1]
 LDCM0023  KB03 Karpas-299 C501(1.94); C656(4.46)  LDD2829  [1]
 LDCM0024  KB05 Karpas-299 C501(2.07); C656(2.96)  LDD3246  [1]

References

1 DrugMap: A quantitative pan-cancer analysis of cysteine ligandability. Cell. 2024 May 9;187(10):2536-2556.e30. doi: 10.1016/j.cell.2024.03.027. Epub 2024 Apr 22.
Mass spectrometry data entry: PXD047840