A-kinase anchor protein 6 (AKAP6) (AKAP6)

A-kinase anchor protein 6 (AKAP6), also known as mAKAP, is a large scaffolding protein primarily expressed in cardiac and skeletal muscle and the brain [1, 6, 10]. It serves as a critical signaling hub at the nuclear envelope and sarcoplasmic reticulum, where it coordinates the spatiotemporal activity of Protein Kinase A (PKA), phosphodiesterases (such as PDE4D3), and phosphatases (such as calcineurin) [1, 5, 10]. By anchoring these enzymes in proximity to their substrates, such as the ryanodine receptor 2 (RyR2), AKAP6 regulates essential processes including calcium homeostasis, myocyte differentiation, and hypertrophic gene expression [2, 6, 11, 13]. In the context of disease, AKAP6 is a key mediator of pathological cardiac hypertrophy and heart failure, where its upregulation leads to aberrant calcium leakage and maladaptive remodeling [2, 3, 9]. Recent research also highlights its role in neuroprotection, specifically in the survival of retinal ganglion cells through BDNF-mediated signaling [15]. While no clinical drugs currently target AKAP6, it is an active area of research for the development of small-molecule disruptors and peptidomimetics aimed at treating cardiovascular and neurodegenerative disorders [12, 17]. Genetic variants in the AKAP6 gene have also been associated with cognitive function, neuropsychiatric traits, and susceptibility to certain cancers [8, 11].

Other names

mAKAPMuscle-selective A-kinase anchoring proteinAKAP100ADAP100ADAP6PRKA6KIAA0311

Disruption of protein-protein interactions within the AKAP6 signaling complex, specifically the anchoring of Protein Kinase A (PKA), Phosphodiesterase 4D3 (PDE4D3), and Calcineurin to the nuclear envelope and sarcoplasmic reticulum.