protein
RAC-gamma serine/threonine-protein kinase
Gene
AKT3
Organism
Homo sapiens(9606)
Length
479 aa
Mass
55,775 Da
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.
Generated from the curated entity record below. May contain errors — verify against source links.
Proteomics Evidence · AD
↓ Down in ADP3
not detected
P2
not detected
S2
-0.326
S3
not detected
Mean log₂FC across detected fractions: -0.3255 (1 of 4 fractions detected)
Human post-mortem AD brain vs age-matched controls, TMT-labeled, 4 subcellular fractions (P2, P3, S2, S3), DDA proteomics.
Related Publications
Browse all →Tau molecular diversity contributes to clinical heterogeneity in Alzheimer's disease.
Dujardin Simon et al.Nature medicine2020PMID 32572268Deep Multilayer Brain Proteomics Identifies Molecular Networks in Alzheimer's Disease Progression.
Bai Bing et al.Neuron2020PMID 31926610A Multi-network Approach Identifies Protein-Specific Co-expression in Asymptomatic and Symptomatic Alzheimer's Disease.
Seyfried Nicholas T et al.Cell systems2017PMID 27989508Large-scale deep multi-layer analysis of Alzheimer's disease brain reveals strong proteomic disease-related changes not observed at the RNA level.
Johnson Erik C B et al.Nature neuroscience2022PMID 35115731Organization and regulation of gene transcription.
Cramer PatrickNature2019PMID 31462772
Function
AKT3 is one of 3 closely related serine/threonine-protein kinases (AKT1, AKT2 and AKT3) called the AKT kinase, and which regulate many processes including metabolism, proliferation, cell survival, growth and angiogenesis. This is mediated through serine and/or threonine phosphorylation of a range of downstream substrates. Over 100 substrate candidates have been reported so far, but for most of them, no isoform specificity has been reported. AKT3 is the least studied AKT isoform. It plays an important role in brain development and is crucial for the viability of malignant glioma cells. AKT3 isoform may also be the key molecule in up-regulation and down-regulation of MMP13 via IL13. Required for the coordination of mitochondrial biogenesis with growth factor-induced increases in cellular energy demands. Down-regulation by RNA interference reduces the expression of the phosphorylated form of BAD, resulting in the induction of caspase-dependent apoptosis
Disease associations
Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 2MPPH2
A syndrome characterized by megalencephaly, hydrocephalus, and polymicrogyria; polydactyly may also be seen. There is considerable phenotypic similarity between this disorder and the megalencephaly-capillary malformation syndrome.
Sources
Last updated 5/8/2026, 6:34:43 AM