RAC-gamma serine/threonine-protein kinase

AKT3 (RAC-gamma serine/threonine-protein kinase) is one of three closely related AKT isoforms that regulate cellular metabolism, proliferation, survival, growth, and angiogenesis through phosphorylation of downstream substrates (UniProt: Q9Y243). AKT3 is particularly important in brain development and mitochondrial biogenesis, with over 100 reported substrate candidates identified to date.

AKT3 is predominantly expressed in the brain and plays a crucial role in neuronal development and glioma cell viability. Mutations in AKT3 are associated with megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 2 (MPPH2), a developmental disorder affecting brain and limb morphogenesis (UniProt: Q9Y243).

In Alzheimer's disease, AKT3 is down-regulated in post-mortem AD brain tissue compared to age-matched controls (mean log2 fold-change: −0.33; Chaparral AD proteomics). This reduction was detected in TMT-labeled proteomics analysis of four subcellular fractions from human brain tissue, suggesting altered kinase signaling capacity in AD pathology that may impact cell survival and metabolic regulation.