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AKT3 phospho S473

OverviewProducts

Domain

Binding of the PH domain to the phosphatidylinositol 3-kinase alpha (PI(3)K) results in its targeting to the plasma membrane.

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.

Involvement in disease

AKT3 is a key modulator of several tumors like melanoma, glioma and ovarian cancer. Active AKT3 increases progressively during melanoma tumor progression with highest levels present in advanced-stage metastatic melanomas. Promotes melanoma tumorigenesis by decreasing apoptosis. Plays a key role in the genesis of ovarian cancers through modulation of G2/M phase transition. With AKT2, plays a pivotal role in the biology of glioblastoma.

Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 2

MPPH2

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.

None

The disease is caused by variants affecting the gene represented in this entry.

Post-translational modifications

Phosphorylation on Thr-305 and Ser-472 is required for full activity.

Ubiquitinated. When fully phosphorylated and translocated into the nucleus, undergoes 'Lys-48'-polyubiquitination catalyzed by TTC3, leading to its degradation by the proteasome.

O-GlcNAcylation at Thr-302 and Thr-309 inhibits activating phosphorylation at Thr-305 via disrupting the interaction between AKT and PDK1.

Sequence similarities

Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. RAC subfamily.

Tissue specificity

In adult tissues, it is highly expressed in brain, lung and kidney, but weakly in heart, testis and liver. In fetal tissues, it is highly expressed in heart, liver and brain and not at all in kidney.

Cellular localization

  • Nucleus
  • Cytoplasm
  • Membrane
  • Peripheral membrane protein
  • Membrane-associated after cell stimulation leading to its translocation.

Alternative names

  • RAC-gamma serine/threonine-protein kinase
  • Protein kinase Akt-3
  • Protein kinase B gamma
  • RAC-PK-gamma
  • STK-2
  • PKB gamma
  • AKT3
  • PKBG

Database links

Target type

Proteins

Molecular weight

55775Da