NUAK2

Neurotrophic tyrosine kinase receptor type 3
Identifiers
Symbol	?
NCBI gene	4916
HGNC	8032
OMIM	191316
RefSeq	NM_002530
UniProt	Q16288
Search for Structures Swiss-model Domains InterPro

Neurotrophic tyrosine kinase receptor type 3 (NTRK3) is a protein that in humans is encoded by the NTRK3 gene. This receptor is part of the neurotrophin receptor family and plays a crucial role in the development and function of the nervous system.

Structure

NTRK3 is a transmembrane protein that belongs to the tyrosine kinase receptor family. It consists of an extracellular domain, a single transmembrane helix, and an intracellular tyrosine kinase domain. The extracellular domain is responsible for binding to its ligand, neurotrophin-3 (NT-3), which triggers receptor dimerization and activation of the kinase domain.

Function

NTRK3 is primarily expressed in the central nervous system and is involved in the development and maintenance of neurons. Upon binding to NT-3, NTRK3 undergoes autophosphorylation on specific tyrosine residues, which initiates a cascade of downstream signaling pathways. These pathways include the MAPK/ERK pathway, the PI3K/AKT pathway, and the PLCγ pathway, all of which contribute to neuronal survival, differentiation, and synaptic plasticity.

Clinical Significance

Mutations or alterations in the NTRK3 gene have been implicated in various neurological disorders and cancers. For instance, NTRK3 gene fusions have been identified in certain types of pediatric tumors, such as congenital fibrosarcoma and secretory breast carcinoma. These fusions result in constitutive activation of the kinase domain, leading to uncontrolled cell proliferation.

In addition, NTRK3 has been studied in the context of psychiatric disorders, including depression and anxiety, due to its role in neurodevelopment and synaptic function.

Research and Therapeutic Targeting

NTRK3, along with other members of the TRK family (NTRK1 and NTRK2), has become a target for cancer therapy. Small molecule inhibitors, such as larotrectinib and entrectinib, have been developed to target TRK fusion proteins and have shown efficacy in treating tumors with NTRK gene fusions.

Also see

• Neurotrophin receptor
• Neurotrophin-3
• Tyrosine kinase
• TRK family
• MAPK/ERK pathway