trk A protein; high affinity nerve growth factor receptor; neurotrophic tyrosine kinase receptor type 1; TRK1-transforming tyrosine kinase protein; p140-TrkA; Trk-A (NTRK1, TRK)
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Function
- required for high-affinity binding to nerve growth factor (NGF), neurotrophin-3 & neurotrophin-4/5 but not brain-derived neurotrophic factor (BDNF)
- with p75NGFR forms high affinity NGF receptor
- tyrosine kinase activity
- substrates for the Trk receptors include: SHC1, PI 3-kinase, & PLC-gamma-1
- role in the development & function of the nociceptive reception system & establishment of thermal regulation via sweating
- activates ERK1 by either SHC1- or PLC-gamma-1-dependent signaling pathway
- exists in a dynamic equilibrium between monomeric (low affinity) & dimeric (high affinity) structures
- binds SH2B2
- interacts with SQSTM1 which bridges NTRK1 to NGFR
- interacts with ARMS & NGFR
- can form a ternary complex with NGFR & ARMS; complex is affected by the expression of ARMS; an increase in ARMS expression leads to a decreased association of NGFR & NTRK1 (putative)
- ligand-mediated auto-phosphorylation
- interaction with SQSTM1 is phosphotyrosine-dependent
- trk-A is transported via fast axonal transport in the same compartment with the amyloid precursor protein APP
Structure
- transmembrane domain mediates interaction with ARMS
- extracellular domain mediates interaction with NGFR
- belongs to the protein kinase superfamily, Tyr protein kinase family, insulin receptor subfamily
- contains 2 Ig-like C2-type domaind (immunoglobulin-like)
- contains 3 LRR repeats (leucine-rich repeats)
- contains 1 protein kinase domain
Compartment
- cell membrane
- endocytosis upon treatment of cells with NGF (putative)
Alternative splicing
named isoforms=2
Expression
Pathology
- defects in NTRK1 are a cause of congenital insensitivity to pain with anhidrosis
- chromosomal aberrations involving NTRK1 are a cause of thyroid papillary carcinoma (PACT) [MIM:188550]
- t(1;3)(q21;q11) involving NTRK1 with TFG generates the TRKT3 (TRK-T3) transcript by fusing TFG to the 3'-end of NTRK1
- rearrangement with TPM3 generates the TRK transcript by fusing TPM3 to the 3'-end of NTRK1
- intrachromosomal rearrangement that links the protein kinase domain of NTRK1 to the 5'-end of the TPR gene forms the fusion protein TRK-T1 (55 kD, reacts with antibodies against the C-terminus of NTRK1)
More general terms
- tropomyosin receptor kinase (trk) proto-oncogene protein
- leucine-rich repeat-containing protein (LRRC)
- glycoprotein
- phosphoprotein
References
- ↑ UniProt http://www.uniprot.org/uniprot/P04629.html
- ↑ GeneReviews https://www.genecards.org/cgi-bin/carddisp.pl?gene=NTRK1
- ↑ Kaplan DR, Martin-Zanca D, Parada LF. Tyrosine phosphorylation and tyrosine kinase activity of the trk proto-oncogene product induced by NGF. Nature. 1991 Mar 14;350(6314):158-60. PMID: https://www.ncbi.nlm.nih.gov/pubmed/1706478
- ↑ Kaplan DR, Hempstead BL, Martin-Zanca D, Chao MV, Parada LF. The trk proto-oncogene product: a signal transducing receptor for nerve growth factor. Science. 1991 Apr 26;252(5005):554-8. PMID: https://www.ncbi.nlm.nih.gov/pubmed/1850549
- ↑ Kamal A, Almenar-Queralt A, LeBlanc JF, Roberts EA, Goldstein LS. Kinesin-mediated axonal transport of a membrane compartment containing beta-secretase and presenilin-1 requires APP. Nature. 2001 Dec 6;414(6864):643-8. PMID: https://www.ncbi.nlm.nih.gov/pubmed/11740561
Database
- Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:4914
- Kegg: http://www.genome.jp/dbget-bin/www_bget?son:SO_2
- OMIM: https://mirror.omim.org/entry/164970
- OMIM: https://mirror.omim.org/entry/188550
- OMIM: https://mirror.omim.org/entry/191315
- OMIM: https://mirror.omim.org/entry/256800
- UniProt: http://www.uniprot.org/uniprot/P04629.html