Docking protein 6 (DOK6)

Docking protein 6 is an intracellular adaptor protein predominantly expressed in the nervous system, functioning as a key mediator of signal transduction downstream of receptor tyrosine kinases such as TrkC and RET[1][2][3][4][5]. It is characterized by N-terminal pleckstrin-homology (PH) and phosphotyrosine-binding (PTB) domains, and multiple C-terminal tyrosine phosphorylation sites[2][4]. DOK6 selectively interacts with the NPQY motif of the TrkC receptor in a kinase activity-dependent manner, facilitating ERK/MAPK activation and promoting neurite outgrowth and axonal survival[1][2]. Genetic variants in DOK6 are linked to increased susceptibility to Hirschsprung’s disease and experimental models implicate its deficiency in peripheral neuropathy symptoms due to disrupted axonal transport[2]. DOK6 functions as a scaffold for protein complexes involved in neural development and is essential for appropriate neurotrophic signaling and maintenance of neural circuits throughout development and into adulthood[1][2][4][5].\nIf additional, highly structured, or clinical data are needed downstream (e.g., drug targeting or biomarker panels), further investigation in translational neuroscience and neurodevelopmental disorders literature is recommended.

Other names

DOK6DOK5LMGC20785HsT3226docking protein 6downstream of tyrosine kinase 6

For upstream receptor activation (e.g., TrkC, RET), neurotrophic growth factors bind receptors, inducing autophosphorylation. DOK6 is recruited via its PTB domain, interacting with phosphorylated motifs (e.g., NPQY motif of TrkC), triggering downstream signaling cascades (particularly ERK/MAPK pathway for axonal maintenance and neurite outgrowth)