FUNCTION: SwissProt: P04629 # Required for high-affinity binding to nerve growth factor (NGF), neurotrophin-3 and neurotrophin-4/5 but not brain- derived neurotrophic factor (BDNF). Known substrates for the Trk receptors are SHC1, PI 3-kinase, and PLC-gamma-1. Has a crucial role in the development and function of the nociceptive reception system as well as establishment of thermal regulation via sweating. Activates ERK1 by either SHC1- or PLC-gamma-1-dependent signaling pathway.
SIZE: 796 amino acids; 87497 Da
SUBUNIT: Exists in a dynamic equilibrium between monomeric (low affinity) and dimeric (high affinity) structures. Binds SH2B2. Interacts with SQSTM1 which bridges NTRK1 to NGFR (By similarity).
SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein (By similarity). Note=Endocytosed to the endosomes upon treatment of cells with NGF (By similarity).
TISSUE SPECIFICITY: Isoform TrkA-II is primarily expressed in neuronal cells; isoform TrkA-I is found in non-neuronal tissues.
PTM: Ligand-mediated auto-phosphorylation. Interaction with SQSTM1 is phosphotyrosine-dependent.
DISEASE: SwissProt: P04629 # Defects in NTRK1 are a cause of congenital insensitivity to pain with anhidrosis (CIPA) [MIM:256800]. CIPA is 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. & Chromosomal aberrations involving NTRK1 are a cause of thyroid papillary carcinoma (PACT) [MIM:188550]. 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. & Chromosomal aberrations involving NTRK1 are a cause of thyroid papillary carcinoma (PACT) [MIM:188550]. 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.
SIMILARITY: SwissProt: P04629 ## Belongs to the protein kinase superfamily. Tyr protein kinase family. Insulin receptor subfamily. & Contains 2 Ig-like C2-type (immunoglobulin-like) domains. & Contains 3 LRR (leucine-rich) repeats. & Contains 1 protein kinase domain.