Contents

Search

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)

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: - isoform TrkA-II is primarily expressed in neurons - isoform TrkA-I is found in non-neuronal tissues 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] a) t(1;3)(q21;q11) involving NTRK1 with TFG generates the TRKT3 (TRK-T3) transcript by fusing TFG to the 3'-end of NTRK1 b) rearrangement with TPM3 generates the TRK transcript by fusing TPM3 to the 3'-end of NTRK1 c) 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)

Interactions

molecular events

Related

c-trk proto-oncogene

General

glycoprotein leucine-rich repeat-containing protein (LRRC) phosphoprotein tropomyosin receptor kinase (trk) proto-oncogene protein (NTRK)

Properties

SIZE: entity length = 796 aa MW = 87 kD COMPARTMENT: cellular membrane STATE: active state MOTIF: signal sequence {1-32} N-glycosylation site {N67} leucine-rich repeat SITE: 90-113 MOTIF: leucine residue (SEVERAL) N-glycosylation site {N95} leucine-rich repeat SITE: 115-137 MOTIF: leucine residue (SEVERAL) N-glycosylation site {N121} leucine-rich repeat SITE: 139-161 MOTIF: leucine residue (SEVERAL) cysteine residue {C154} MODIFICATION: cysteine residue {C191} N-glycosylation site {N188} cysteine residue {C191} MODIFICATION: cysteine residue {C154} immunoglobulin superfamily domain {194-283} MOTIF: N-glycosylation site {N202} cysteine residue {C215} MODIFICATION: cysteine residue {C265} N-glycosylation site {N253} N-glycosylation site {N262} cysteine residue {C265} MODIFICATION: cysteine residue {C215} N-glycosylation site {N281} immunoglobulin superfamily domain {299-365} MOTIF: N-glycosylation site {N318} N-glycosylation site {N323} N-glycosylation site {N338} N-glycosylation site {N358} breakpoint {398-399} N-glycosylation site {N401} transmembrane domain {424-439} SQSTM1 interaction {469-490} MOTIF: breakpoint {486} tyrosine residue {496} Tyr phosphorylation site {Y496} kinase domain SITE: 510-781 MOTIF: ATP-binding site NAME: ATP-binding site SITE: 516-524 ATP-binding site NAME: ATP-binding site SITE: 544-544 aspartate residue {D650} Tyr phosphorylation site {Y676} Tyr phosphorylation site {Y680} Tyr phosphorylation site {Y681} tyrosine residue {791} Tyr phosphorylation site {Y791}

Database Correlations

OMIM correlations MORBIDMAP 191315 UniProt P04629 PFAM correlations KEGG correlations ENZYME 2.7.10.1

References

  1. UniProt :accession P04629
  2. GeneReviews https://www.genecards.org/cgi-bin/carddisp.pl?gene=NTRK1
  3. 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: 1706478
  4. 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: 1850549
  5. 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: 11740561