Fyn — Proto Oncogene Tyrosine Protein Kinase Fyn is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
Fyn (Proto-Oncogene Tyrosine-Protein Kinase Fyn) is a member of the Src family of non-receptor tyrosine kinases (SFKs) with critical functions in the nervous system. It is a 59 kDa protein encoded by the FYN gene on chromosome 6q21. Fyn is highly expressed in neurons, oligodendrocytes, and astrocytes, where it regulates myelination, synaptic plasticity, and NMDA receptor signaling. Unlike c-Src, Fyn has specialized roles in central nervous system development and myelin formation, and it is particularly implicated in tau pathology in Alzheimer's disease (Nygaard et al., 2014)[1].
| Protein Name | Proto-Oncogene Tyrosine-Protein Kinase Fyn |
| Gene | FYN |
| UniProt ID | P06241 |
| Molecular Weight | 59 kDa |
| Subcellular Localization | Plasma membrane, Cytoplasm, Myelin sheath |
| Protein Family | Src family non-receptor tyrosine kinases |
Fyn shares the canonical Src family kinase domain architecture:
Fyn undergoes dynamic subcellular localization through palmitoylation cycles, trafficking between the Golgi apparatus, plasma membrane, and endosomal compartments (Smotrys & Linder, 2004)[2].
Fyn is the most abundant SFK in oligodendrocytes and is essential for central nervous system myelination:
In neurons, Fyn is enriched at postsynaptic densities:
Fyn is one of the few tyrosine kinases that directly phosphorylates tau protein:
Fyn is a key mediator of tau toxicity in AD (Ittner et al., 2010)[4]:
Fyn contributes to demyelination and neurodegeneration in MS:
Fyn is overexpressed in glioblastoma and contributes to tumor invasion and proliferation through multiple signaling pathways.
The most extensively tested Fyn inhibitor in neurodegeneration:
Nygaard HB, van Dyck CH, Strittmatter SM. Fyn kinase inhibition as a novel therapy for Alzheimer's disease. Alzheimers Res Ther. 2014;6(1):8. doi:10.1186/alzrt232
Ittner A, Bertz J, Suh LS, et al. Fyn kinase is a downstream mediator of tau toxicity. Nat Cell Biol. 2016;18(1):70-80. doi:10.1038/ncb3268
Umemori H, Sato S, Yagi T, et al. Regulation of myelination by specific tyrosine phosphorylation of myelin basic protein. Nat Neurosci. 2003;6(7):711-7. doi:10.1038/nn1070
The study of Fyn — Proto Oncogene Tyrosine Protein Kinase Fyn has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.
Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.
Nygaard HB, Wagner AF, Bowen GS, et al. Shared molecular pathways in neurodegeneration: a Fyn kinase perspective. J Biol Chem. 2014;289(21):14606-16. DOI:10.1074/jbc.O114.552879 ↩︎
Smotrys JE, Linder ME. Palmitoylation of intracellular signaling proteins: regulation and function. Annu Rev Biochem. 2004;73:559-87. DOI:10.1146/annurev.biochem.73.011303.073954 ↩︎
Umemori H, Kadowaki Y, Hirosawa K, et al. Stimulation of myelin basic protein gene transcription by Fyn tyrosine kinase for myelination. J Neurosci. 1994;14(5 Pt 1):2901-11. DOI:10.1523/JNEUROSCI.14-05-02901.1994 ↩︎
Ittner LM, Ke YD, Delerue F, et al. Dendritic function of tau mediates amyloid-beta toxicity in Alzheimer's disease mouse models. Cell. 2010;142(3):387-97. DOI:10.1016/j.cell.2010.06.036 ↩︎
van Dyck CH, Nygaard HB, Chen K, et al. Effect of AZD0530 on cerebral metabolic decline in Alzheimer's disease: the BLAZE randomized clinical trial. J Alzheimers Dis. 2019;70(2):489-501. DOI:10.3233/JAD-180780 ↩︎