The entire gene is about 54.4 Kb and contains 14 exons. The open reading frame of the coding region is 1,445 bp.

Transcript length: 4,623 bp

No human pseudogene known. A mouse Akt2 pseudogene was cloned and mapped to proximal mouse chromosome 11 by fluorescence in situ hybridization.

AKT2 protein consists of 481 amino acids, with a molecular weight of 55,769 Da.

Found in all human cell types so far analyzed; insulin responsive tissues such as normal brown fat, skeletal muscle and liver exhibit the highest expression levels of AKT2/Akt2.

Predominantly cytoplasmic; also found at the plasma membrane and in the nucleus following its activation.

AKT proteins mediate a variety of cellular functions, ranging from control of cell proliferation and survival to modulation of intermediary metabolism and angiogenesis. Such pleiotropic effects are the consequence of phosphorylation of numerous substrates, some of which are listed below. Most substrates share the consensus sequence for AKT phosphorylation, RXRXXS/T. For example, activated AKT exerts anti-apoptotic activity in part by preventing the release of cytochrome c from mitochondria, and phosphorylating and inactivating the pro-apoptotic factors BAD and pro-caspase-9. AKT also activates IkappaB kinase (IKK), a positive regulator of NF-kappaB, which results in the transcription of anti-apoptotic genes. AKT phosphorylates and inactivates FOXO transcription factors, which mediate the expression of genes critical for apoptosis, such as the Fas ligand gene.
AKT activation mediates cell cycle progression by phosphorylation and inhibition of glycogen synthase kinase 3 beta to inhibit cyclin D1 degradation. AKT phosphorylates the cell cycle inhibitors p21WAF1 and p27Kip1 near the nuclear localization signal to induce cytoplasmic retention of these cell cycle inhibitors. Moreover, phosphorylation of AKT kinases also results in increased translation of cyclin D1, D3 and E transcripts.
AKT activates the downstream mTOR kinase by inhibiting a complex formed by the tumor suppressor proteins TSC1 and TSC2, also known as hamartin and tuberin, respectively. mTOR broadly mediates cell growth and proliferation by regulating ribosomal biogenesis and protein translation and can regulate response to nutrients by restricting cell cycle progression in the presence of suboptimal growth conditions.
AKT signaling also contributes to other cellular processes considered to be cancer hallmarks. AKT promotes the phosphorylation and translocation of Mdm2 into the nucleus, where it downregulates p53 and thereby antagonizes p53-mediated cell cycle checkpoints. AKT signaling is linked to tumor cell migration, and it contributes to tumor invasion and metastasis by promoting the secretion of matrix metalloproteinases. Moreover, vascular endothelial growth factor (VEGF) effects on cell survival have been shown to be mediated by the Flk1/VEGFR2-PI3K-AKT pathway. In other cellular processes, AKT has been shown to phosphorylate human telomerase reverse transcriptase (hTERT), thereby stimulating telomerase activity and replication. Collectively, these findings implicate up-regulation of the AKT pathway in many aspects of tumorigenesis.

All three AKT kinases belong to the more general class of AGC kinases (related to AMP/GMP kinase and protein kinase C). The kinase domain of AKT shares high similarity with other members of the AGC family of kinases such as PKA, PKC, p70 S6K, and p90 RSK. The sequence identities among the three AKTs in the kinase domain exceed 87%. The three AKT kinases are identical in the ATP binding region, except for one residue: Ala 230 of AKT1 is conserved in AKT2 (Ala 232), but switches to Val 228 in AKT3. In addition, each of the three AKT kinases has a carboxy terminal extension of about 40 amino acids.
Human AKT2 is 98.1% similar to M. musculus Akt2; 97.7% similar to the R. norvegicus homolog; 61.3% similar to D. melanogaster protein kinase RAC; 52.4% similar to C. elegans Akt/PKB serine/threonine kinase; 47.7% similar to S. cerevisiae protein kinase (see UniGene Hs.631535)

Insulin resistance and a diabetes mellitus-like syndrome have been described in knockout mice lacking Akt2.

Individuals carrying a G-to-A transition in the AKT2 gene resulting in an Arg-to-His substitution at codon 274 (R274H) were found to be markedly hyperinsulinemic. However, a large case-control study showed that variation in and around the AKT2 locus is unlikely to contribute significantly to increased risk of type 2 diabetes.
Mutations in AKT2 are uncommon in human tumors. For example, AKT2 mutations have been reported in 1 of 51 gastric carcinomas and 2 of 79 lung carcinomas. The mutations consisted of one missense mutation and 2 splice site mutations in an intron.