NT-3 growth factor receptor

Function

Receptor tyrosine kinase involved in nervous system and probably heart development. Upon binding of its ligand NTF3/neurotrophin-3, NTRK3 autophosphorylates and activates different signaling pathways, including the phosphatidylinositol 3-kinase/AKT and the MAPK pathways, that control cell survival and differentiation.

Classification

Family (Pfam)

PF07679 I-set, PF00047 ig, PF13855 LRR_8, PF16920 LRRCT_2, PF01462 LRRNT, PF07714 PK_Tyr_Ser-Thr

InterPro

Cys-rich_flank_reg_C, Ig-like_dom, Ig-like_dom_sf, Ig-like_fold, Ig_I-set, Ig_sub, Immunoglobulin_dom, Kinase-like_dom_sf, Leu-rich_rpt, LRR_dom_sf, LRRNT, NTRK, NTRK3, NTRK_LRRCT, Prot_kinase_dom, Protein_kinase_ATP_BS, RTK, Ser-Thr/Tyr_kinase_cat_dom, Tyr_kinase_AS, Tyr_kinase_cat_dom, Tyr_kinase_rcpt_2_CS

Functional cluster

S-Adenosylmethionine Synthases & related

Experimental structures · PDB · 5

• 1WWC X-ray 1.90A
• 3V5Q X-ray 2.20A
• 4YMJ X-ray 2.00A
• 6KZC X-ray 2.00A
• 6KZD X-ray 1.71A

A predicted model is available from AlphaFold.

Gene Ontology · 35

• GO:0030424 axon
• GO:0005737 cytoplasm
• GO:0098978 glutamatergic synapse
• GO:0005730 nucleolus
• GO:0005886 plasma membrane
• GO:0045211 postsynaptic membrane
• GO:0043235 receptor complex
• GO:0005524 ATP binding
• GO:0005004 GPI-linked ephrin receptor activity
• GO:0043121 neurotrophin binding
• GO:0005030 neurotrophin receptor activity
• GO:0002039 p53 binding
• GO:0004714 transmembrane receptor protein tyrosine kinase activity
• GO:0007169 cell surface receptor protein tyrosine kinase signaling pathway
• GO:1990090 cellular response to nerve growth factor stimulus
• GO:0071300 cellular response to retinoic acid
• GO:0007623 circadian rhythm
• GO:0090102 cochlea development
• GO:0007507 heart development
• GO:0048712 negative regulation of astrocyte differentiation
• GO:0048665 neuron fate specification
• GO:0001764 neuron migration
• GO:0030335 positive regulation of cell migration
• GO:0008284 positive regulation of cell population proliferation
• GO:0010628 positive regulation of gene expression
• GO:0043410 positive regulation of MAPK cascade
• GO:0010976 positive regulation of neuron projection development
• GO:0051897 positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction
• GO:0050927 positive regulation of positive chemotaxis
• GO:0097107 postsynaptic density assembly
• GO:2000177 regulation of neural precursor cell proliferation
• GO:1905606 regulation of presynapse assembly
• GO:0048678 response to axon injury
• GO:0051412 response to corticosterone
• GO:0045471 response to ethanol

Drugs targeting this protein · 10

• ENTRECTINIB inhibitor
• ALTIRATINIB inhibitor
• AZD-7451 inhibitor
• LAROTRECTINIB inhibitor
• LAROTRECTINIB SULFATE inhibitor
• SELITRECTINIB inhibitor
• REPOTRECTINIB inhibitor
• TALETRECTINIB inhibitor
• LESTAURTINIB inhibitor
• CEP-2563 DIHYDROCHLORIDE inhibitor

Related proteins · sequence + function similarity

• NT-3 growth factor receptor 0.99
• NT-3 growth factor receptor 0.99
• NT-3 growth factor receptor 0.99
• NT-3 growth factor receptor 0.99
• NT-3 growth factor receptor 0.99
• NT-3 growth factor receptor 0.98
• NT-3 growth factor receptor 0.98
• BDNF/NT-3 growth factors receptor 0.94
• BDNF/NT-3 growth factors receptor 0.93
• BDNF/NT-3 growth factors receptor 0.93
• BDNF/NT-3 growth factors receptor 0.93
• Inactive tyrosine-protein kinase RYK 0.78

Co-cited proteins · studied together in the literature

• BDNF/NT-3 growth factors receptor 3 shared papers
• High affinity nerve growth factor receptor 2 shared papers
• NT-3 growth factor receptor 1 shared papers
• NT-3 growth factor receptor 1 shared papers
• Receptor-type tyrosine-protein phosphatase S 1 shared papers
• Receptor-type tyrosine-protein phosphatase S 1 shared papers
• Receptor-type tyrosine-protein phosphatase S 1 shared papers

Literature · 10 cited papers

• Structural basis for extracellular cis and trans RPTPsigma signal competition in synaptogenesis. Nat. Commun. · 2014
• Mutations in NTRK3 suggest a novel signaling pathway in human congenital heart disease. Hum. Mutat. · 2014
• Frequent mutations in the neurotrophic tyrosine receptor kinase gene family in large cell neuroendocrine carcinoma of the lung. Hum. Mutat. · 2008
• Patterns of somatic mutation in human cancer genomes. Nature · 2007
• Analysis of the DNA sequence and duplication history of human chromosome 15. Nature · 2006
• Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat. Genet. · 2004
• Crystal structures of the neurotrophin-binding domain of TrkA, TrkB and TrkC. J. Mol. Biol. · 1999
• Genomic characterization of the human trkC gene. Oncogene · 1998
• Human trks: molecular cloning, tissue distribution, and expression of extracellular domain immunoadhesins. J. Neurosci. · 1995
• Molecular cloning of the cDNA for human TrkC (NTRK3), chromosomal assignment, and evidence for a splice variant. Genomics · 1994