AKT3 - RAC-gamma serine/threonine-protein kinase - human protein (Function)
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AKT3 »  RAC-gamma serine/threonine-protein kinase   [ EC ]
Protein also known as:  Protein kinase B gamma (PKB gamma).
Gene name:  AKT3
Entry whose protein(s) existence is based on evidence at protein level
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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.  
  • UniProtKB
GO molecular function 
ATP bindingdefinition[GO:0005524]  
  • UniProtKB
Protein bindingdefinition[GO:0005515]  
  • IntAct
  • UniProtKB
Protein kinase activitydefinition[GO:0004672]  
  • PINC
Protein serine/threonine kinase activitydefinition[GO:0004674]  
  • UniProtKB
GO biological process 
Mitochondrial genome maintenancedefinition[GO:0000002]  
  • UniProtKB
Protein phosphorylationdefinition[GO:0006468] silver  
  • InterPro 2 GO
Signal transductiondefinition[GO:0007165]  
  • UniProtKB
Enzymatic activity 
This protein acts as an enzyme. It is known to catalyze the following reaction
EC ATP + a protein ADP + a phosphoprotein.  
  • UniProtKB
It is regulated in the following manner
Two specific sites, one in the kinase domain (Thr-305) and the other in the C-terminal regulatory region (Ser-472), need to be phosphorylated for its full activation (By similarity). IGF-1 leads to the activation of AKT3, which may play a role in regulating cell survival.  
  • UniProtKB
More information is available from:
According to KEGG, this protein belongs to the following pathways:
Acute myeloid leukemia  hsa05221+10000  
Adipocytokine signaling pathway  hsa04920+10000  
Apoptosis  hsa04210+10000  
B cell receptor signaling pathway  hsa04662+10000  
Carbohydrate digestion and absorption  hsa04973+10000  
Chagas disease (American trypanosomiasis)  hsa05142+10000  
Chemokine signaling pathway  hsa04062+10000  
Cholinergic synapse  hsa04725+10000  
Chronic myeloid leukemia  hsa05220+10000  
Colorectal cancer  hsa05210+10000  
Dopaminergic synapse  hsa04728+10000  
Endometrial cancer  hsa05213+10000  
ErbB signaling pathway  hsa04012+10000  
Fc epsilon RI signaling pathway  hsa04664+10000  
Fc gamma R-mediated phagocytosis  hsa04666+10000  
Focal adhesion  hsa04510+10000  
Glioma  hsa05214+10000  
Hepatitis C  hsa05160+10000  
HTLV-I infection  hsa05166+10000  
Influenza A  hsa05164+10000  
Insulin signaling pathway  hsa04910+10000  
Jak-STAT signaling pathway  hsa04630+10000  
MAPK signaling pathway  hsa04010+10000  
Measles  hsa05162+10000  
Melanoma  hsa05218+10000  
mTOR signaling pathway  hsa04150+10000  
Neurotrophin signaling pathway  hsa04722+10000  
Non-small cell lung cancer  hsa05223+10000  
Osteoclast differentiation  hsa04380+10000  
Pancreatic cancer  hsa05212+10000  
Pathways in cancer  hsa05200+10000  
Progesterone-mediated oocyte maturation  hsa04914+10000  
Prostate cancer  hsa05215+10000  
Renal cell carcinoma  hsa05211+10000  
Small cell lung cancer  hsa05222+10000  
T cell receptor signaling pathway  hsa04660+10000  
Tight junction  hsa04530+10000  
Toll-like receptor signaling pathway  hsa04620+10000  
Toxoplasmosis  hsa05145+10000  
Tuberculosis  hsa05152+10000  
VEGF signaling pathway  hsa04370+10000  
According to Reactome, this protein belongs to the following pathways:
Activation of BAD and translocation to mitochondria  R-HSA-111447  
AKT phosphorylates targets in the cytosol  R-HSA-198323  
AKT phosphorylates targets in the nucleus  R-HSA-198693  
AKT-mediated inactivation of FOXO1A  R-HSA-211163  
CD28 dependent PI3K/Akt signaling  R-HSA-389357  
Constitutive Signaling by AKT1 E17K in Cancer  R-HSA-5674400  
CTLA4 inhibitory signaling  R-HSA-389513  
Downregulation of ERBB2:ERBB3 signaling  R-HSA-1358803  
G beta:gamma signalling through PI3Kgamma  R-HSA-392451  
GPVI-mediated activation cascade  R-HSA-114604  
Negative regulation of the PI3K/AKT network  R-HSA-199418  
PIP3 activates AKT signaling  R-HSA-1257604  
TP53 Regulates Metabolic Genes  R-HSA-5628897  
VEGFR2 mediated vascular permeability  R-HSA-5218920  
In light of strong homologies in the primary amino acid sequence, the 3 AKT kinases were long surmised to play redundant and overlapping roles. More recent studies has brought into question the redundancy within AKT kinase isoforms and instead pointed to isoform specific functions in different cellular events and diseases. AKT1 is more specifically involved in cellular survival pathways, by inhibiting apoptotic processes; whereas AKT2 is more specific for the insulin receptor signaling pathway. Moreover, while AKT1 and AKT2 are often implicated in many aspects of cellular transformation, the 2 isoforms act in a complementary opposing manner. The role of AKT3 is less clear, though it appears to be predominantly expressed in brain.  
  • UniProtKB

Biophysicochemical properties

Kinetic parameters
KM 12.4 uM for peptide substrate (for purified and in vitro activated AKT3)
KM 118.7 uM for ATP (for recombinant myristoylated AKT3 expressed and immunoprecipitated from Rat-1 cells)
KM 2.3 uM for peptide substrate (for recombinant myristoylated AKT3 expressed and immunoprecipitated from Rat-1 cells)
KM 87.9 uM for ATP (for purified and in vitro activated AKT3)


Molecular function 
Kinase  definition   [KW-0418]
Serine/threonine-protein kinase  definition   [KW-0723]
Transferase  definition   [KW-0808]
Technical term 
Reference proteome  definition   [KW-1185]

Further external links

Enzyme and pathway databases
GeneWiki: AKT3
GenomeRNAi: 10000
PRO: PR:Q9Y243