AKT1 - RAC-alpha serine/threonine-protein kinase - human protein (Function)
 
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AKT1 »  RAC-alpha serine/threonine-protein kinase   [ EC 2.7.11.1 ]
 
Protein also known as:  Protein kinase B alpha (PKB alpha).
Gene name:  AKT1
Entry whose protein(s) existence is based on evidence at protein level
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1 1513 1
GENE REF ISO

Function

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Overview 
AKT1-specific substrates have been recently identified, including palladin (PALLD), which phosphorylation modulates cytoskeletal organization and cell motility; prohibitin (PHB), playing an important role in cell metabolism and proliferation; and CDKN1A, for which phosphorylation at 'Thr-145' induces its release from CDK2 and cytoplasmic relocalization. These recent findings indicate that the AKT1 isoform has a more specific role in cell motility and proliferation. Phosphorylates CLK2 thereby controlling cell survival to ionizing radiation.  
26
  • CuratedUniProtKB
AKT1 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. AKT is responsible of the regulation of glucose uptake by mediating insulin-induced translocation of the SLC2A4/GLUT4 glucose transporter to the cell surface. Phosphorylation of PTPN1 at 'Ser-50' negatively modulates its phosphatase activity preventing dephosphorylation of the insulin receptor and the attenuation of insulin signaling. Phosphorylation of TBC1D4 triggers the binding of this effector to inhibitory 14-3-3 proteins, which is required for insulin-stimulated glucose transport. AKT regulates also the storage of glucose in the form of glycogen by phosphorylating GSK3A at 'Ser-21' and GSK3B at 'Ser-9', resulting in inhibition of its kinase activity. Phosphorylation of GSK3 isoforms by AKT is also thought to be one mechanism by which cell proliferation is driven. AKT regulates also cell survival via the phosphorylation of MAP3K5 (apoptosis signal-related kinase). Phosphorylation of 'Ser-83' decreases MAP3K5 kinase activity stimulated by oxidative stress and thereby prevents apoptosis. AKT mediates insulin-stimulated protein synthesis by phosphorylating TSC2 at 'Ser-939' and 'Thr-1462', thereby activating mTORC1 signaling and leading to both phosphorylation of 4E-BP1 and in activation of RPS6KB1. AKT is involved in the phosphorylation of members of the FOXO factors (Forkhead family of transcription factors), leading to binding of 14-3-3 proteins and cytoplasmic localization. In particular, FOXO1 is phosphorylated at 'Thr-24', 'Ser-256' and 'Ser-319'. FOXO3 and FOXO4 are phosphorylated on equivalent sites. AKT has an important role in the regulation of NF-kappa-B-dependent gene transcription and positively regulates the activity of CREB1 (cyclic AMP (cAMP)-response element binding protein). The phosphorylation of CREB1 induces the binding of accessory proteins that are necessary for the transcription of pro-survival genes such as BCL2 and MCL1. AKT phosphorylates 'Ser-454' on ATP citrate lyase (ACLY), thereby potentially regulating ACLY activity and fatty acid synthesis. Activates the 3B isoform of cyclic nucleotide phosphodiesterase (PDE3B) via phosphorylation of 'Ser-273', resulting in reduced cyclic AMP levels and inhibition of lipolysis. Phosphorylates PIKFYVE on 'Ser-318', which results in increased PI(3)P-5 activity. The Rho GTPase-activating protein DLC1 is another substrate and its phosphorylation is implicated in the regulation cell proliferation and cell growth. AKT plays a role as key modulator of the AKT-mTOR signaling pathway controlling the tempo of the process of newborn neurons integration during adult neurogenesis, including correct neuron positioning, dendritic development and synapse formation. Signals downstream of phosphatidylinositol 3-kinase (PI(3)K) to mediate the effects of various growth factors such as platelet-derived growth factor (PDGF), epidermal growth factor (EGF), insulin and insulin-like growth factor I (IGF-I). AKT mediates the antiapoptotic effects of IGF-I. Essential for the SPATA13-mediated regulation of cell migration and adhesion assembly and disassembly. May be involved in the regulation of the placental development. Phosphorylates STK4/MST1 at 'Thr-120' and 'Thr-387' leading to inhibition of its: kinase activity, nuclear translocation, autophosphorylation and ability to phosphorylate FOXO3. Phosphorylates STK3/MST2 at 'Thr-117' and 'Thr-384' leading to inhibition of its: cleavage, kinase activity, autophosphorylation at Thr-180, binding to RASSF1 and nuclear translocation. Phosphorylates SRPK2 and enhances its kinase activity towards SRSF2 and ACIN1 and promotes its nuclear translocation. Phosphorylates RAF1 at 'Ser-259' and negatively regulates its activity. Phosphorylation of BAD stimulates its pro-apoptotic activity. Phosphorylates KAT6A at 'Thr-369' and this phosphorylation inhibits the interaction of KAT6A with PML and negatively regulates its acetylation activity towards p53/TP53.  
26
  • CuratedUniProtKB
GO molecular function 
14-3-3 protein bindingdefinition[GO:0071889]  
1
  • IPIUniProtKB
ATP bindingdefinition[GO:0005524]  
2
  • IDAUniProtKB
Enzyme bindingdefinition[GO:0019899]  
  • ISSOrtholog Curator
Identical protein bindingdefinition[GO:0042802]  
1
  • IPIIntAct
Kinase activitydefinition[GO:0016301]  
1
  • IDAMGI
Nitric-oxide synthase regulator activitydefinition[GO:0030235]  
1
  • IMPBHF-UCL
Phosphatidylinositol-3,4,5-trisphosphate bindingdefinition[GO:0005547]  
1
  • IDAUniProtKB
Phosphatidylinositol-3,4-bisphosphate bindingdefinition[GO:0043325]  
1
  • IDAUniProtKB
Protein bindingdefinition[GO:0005515]  
41
  • IPIIntAct
  • IPIUniProtKB
  • IPIBHF-UCL
Protein kinase activitydefinition[GO:0004672]  
1
  • TASPINC
Protein kinase C bindingdefinition[GO:0005080] silver  
  • IEAOrtholog Compara
Protein serine/threonine kinase activitydefinition[GO:0004674]  
6
  • TASUniProtKB
GO biological process 
Activation-induced cell death of T cellsdefinition[GO:0006924]  
1
  • IMPMGI
Agingdefinition[GO:0007568] silver  
  • IEAOrtholog Compara
Anagendefinition[GO:0042640] silver  
  • IEAOrtholog Compara
Apoptotic mitochondrial changesdefinition[GO:0008637] silver  
  • IEAOrtholog Compara
Cell differentiationdefinition[GO:0030154]  
1
  • TASUniProtKB
Cell projection organizationdefinition[GO:0030030] silver  
  • IEAOrtholog Compara
Cell proliferationdefinition[GO:0008283]  
1
  • TASUniProtKB
Cellular protein modification processdefinition[GO:0006464]  
1
  • TASPINC
Cellular response to epidermal growth factor stimulusdefinition[GO:0071364] silver  
  • IEAOrtholog Compara
Cellular response to hypoxiadefinition[GO:0071456] silver  
  • IEAOrtholog Compara
Cellular response to insulin stimulusdefinition[GO:0032869]  
1
  • IMPBHF-UCL
  • ISSOrtholog Curator
Cellular response to mechanical stimulusdefinition[GO:0071260] silver  
  • IEAOrtholog Compara
Execution phase of apoptosisdefinition[GO:0097194] silver  
  • IEAOrtholog Compara
G-protein coupled receptor signaling pathwaydefinition[GO:0007186]  
1
  • TASPINC
Germ cell developmentdefinition[GO:0007281] silver  
  • IEAOrtholog Compara
Glucose homeostasisdefinition[GO:0042593] silver  
  • IEAOrtholog Compara
Glucose metabolic processdefinition[GO:0006006] silver  
  • IEAOrtholog Compara
Glucose transportdefinition[GO:0015758] silver  
  • IEAOrtholog Compara
Glycogen biosynthetic processdefinition[GO:0005978] silver  
  • IEAOrtholog Compara
Glycogen cell differentiation involved in embryonic placenta developmentdefinition[GO:0060709] silver  
  • IEAOrtholog Compara
Hyaluronan metabolic processdefinition[GO:0030212] silver  
  • IEAOrtholog Compara
Inflammatory responsedefinition[GO:0006954] silver  
  • IEAOrtholog Compara
Insulin receptor signaling pathwaydefinition[GO:0008286]  
1
  • IMPUniProtKB
Insulin-like growth factor receptor signaling pathwaydefinition[GO:0048009]  
1
  • IMPUniProtKB
Intracellular signal transductiondefinition[GO:0035556]  
1
  • IDAMGI
Labyrinthine layer blood vessel developmentdefinition[GO:0060716] silver  
  • IEAOrtholog Compara
Mammary gland epithelial cell differentiationdefinition[GO:0060644]  
1
  • TASUniProtKB
Maternal placenta developmentdefinition[GO:0001893] silver  
  • IEAOrtholog Compara
Negative regulation of apoptotic processdefinition[GO:0043066]  
1
  • IDAUniProtKB
Negative regulation of autophagydefinition[GO:0010507]  
1
  • IMPBHF-UCL
Negative regulation of cell sizedefinition[GO:0045792] silver  
  • IEAOrtholog Compara
Negative regulation of cysteine-type endopeptidase activity involved in apoptotic processdefinition[GO:0043154]  
  • ISSOrtholog Curator
Negative regulation of endopeptidase activitydefinition[GO:0010951]  
1
  • IMPBHF-UCL
Negative regulation of extrinsic apoptotic signaling pathway in absence of liganddefinition[GO:2001240]  
1
  • TASBHF-UCL
Negative regulation of fatty acid beta-oxidationdefinition[GO:0031999]  
1
  • IMPBHF-UCL
Negative regulation of intrinsic apoptotic signaling pathway in response to oxidative stressdefinition[GO:1902176]  
1
  • NASBHF-UCL
Negative regulation of JNK cascadedefinition[GO:0046329] silver  
  • IEAOrtholog Compara
Negative regulation of plasma membrane long-chain fatty acid transportdefinition[GO:0010748]  
1
  • IMPBHF-UCL
Negative regulation of protein kinase activitydefinition[GO:0006469]  
1
  • IMPBHF-UCL
  • ISSOrtholog Curator
Negative regulation of proteolysisdefinition[GO:0045861]  
1
  • IMPBHF-UCL
Negative regulation of release of cytochrome c from mitochondriadefinition[GO:0090201]  
  • ISSOrtholog Curator
Nitric oxide biosynthetic processdefinition[GO:0006809]  
1
  • TASPINC
Osteoblast differentiationdefinition[GO:0001649] silver  
  • IEAOrtholog Compara
Peptidyl-serine phosphorylationdefinition[GO:0018105]  
1
  • IDAUniProtKB
Peripheral nervous system myelin maintenancedefinition[GO:0032287] silver  
  • IEAOrtholog Compara
Phosphorylationdefinition[GO:0016310]  
1
  • IDAUniProtKB
Positive regulation of apoptotic processdefinition[GO:0043065] silver  
  • IEAOrtholog Compara
Positive regulation of blood vessel endothelial cell migrationdefinition[GO:0043536]  
1
  • IDADFLAT
Positive regulation of cell growthdefinition[GO:0030307]  
1
  • IDAUniProtKB
Positive regulation of cellular protein metabolic processdefinition[GO:0032270]  
  • ISSOrtholog Curator
Positive regulation of cyclin-dependent protein serine/threonine kinase activity involved in G1/S transition of mitotic cell cycledefinition[GO:0031659]  
1
  • IDABHF-UCL
Positive regulation of endothelial cell proliferationdefinition[GO:0001938]  
1
  • IMPUniProtKB
Positive regulation of establishment of protein localization to plasma membranedefinition[GO:0090004]  
1
  • IMPBHF-UCL
Positive regulation of fat cell differentiationdefinition[GO:0045600]  
1
  • IMPBHF-UCL
Positive regulation of glucose importdefinition[GO:0046326]  
2
  • IMPBHF-UCL
Positive regulation of glucose metabolic processdefinition[GO:0010907]  
1
  • IMPBHF-UCL
Positive regulation of glycogen biosynthetic processdefinition[GO:0045725]  
2
  • NASBHF-UCL
Positive regulation of lipid biosynthetic processdefinition[GO:0046889]  
1
  • IMPBHF-UCL
Positive regulation of nitric oxide biosynthetic processdefinition[GO:0045429]  
1
  • IMPBHF-UCL
Positive regulation of nitric-oxide synthase activitydefinition[GO:0051000]  
1
  • IMPBHF-UCL
Positive regulation of peptidyl-serine phosphorylationdefinition[GO:0033138]  
1
  • IDAUniProtKB
Positive regulation of proteasomal ubiquitin-dependent protein catabolic processdefinition[GO:0032436] silver  
  • IEAOrtholog Compara
Positive regulation of protein phosphorylationdefinition[GO:0001934]  
1
  • IDABHF-UCL
Positive regulation of sequence-specific DNA binding transcription factor activitydefinition[GO:0051091]  
1
  • IDABHF-UCL
Positive regulation of sodium ion transportdefinition[GO:0010765] silver  
  • IEAOrtholog Compara
Positive regulation of transcription from RNA polymerase II promoterdefinition[GO:0045944] silver  
  • IEAOrtholog Compara
Positive regulation of vasoconstrictiondefinition[GO:0045907] silver  
  • IEAOrtholog Compara
Protein autophosphorylationdefinition[GO:0046777]  
1
  • TASUniProtKB
Protein catabolic processdefinition[GO:0030163] silver  
  • IEAOrtholog Compara
Protein import into nucleus, translocationdefinition[GO:0000060]  
1
  • IMPUniProtKB
Protein kinase B signalingdefinition[GO:0043491] silver  
  • IEAOrtholog Compara
Protein phosphorylationdefinition[GO:0006468]  
3
  • IDAUniProtKB
  • IDAMGI
Protein ubiquitinationdefinition[GO:0016567] silver  
  • IEAOrtholog Compara
Regulation of cell cycle checkpointdefinition[GO:1901976]