Target name

P31749: RAC-alpha serine/threonine-protein kinase

  Protein function

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

  Database links

Uniprot primary ID P31749
DrugBank ID DB01169 DB00171
BioGrid ID 106710
PharmGKB ID PA24684
KEGG ID hsa:207
Entrez Gene (Gene ID) 207
DIP DIP-24269N
STRING 9606ENSP00000270202
MINT MINT-203775
IntAct P31749
DMDM 60391226
BREDNA 27111
Rectome R-HSA-199418 R-HSA-198693 R-HSA-1257604 R-HSA-114604 R-HSA-389357 R-HSA-198323 R-HSA-203615 R-HSA-354192 R-HSA-389513 R-HSA-111447 R R-HSA-392451 R-HSA-5674400 R-HSA-1445148 R-HSA-450385 R-HSA-3769402 R-HSA-211163 R-HSA-5628897 R-HSA-5218920 R-HSA-1358803
SignaLink P31749
BindingDB P31749

  Model Performance Metrics

Fingerprint type F1_CV AUC_CV Accuracy_CV Sensitivity_CV Specificity_CV F1_test AUC_test Accuracy_test Sensitivity_test Specificity_test Download model
FP2 fingerprints 0.806 0.871 0.817 0.765 0.868 0.837 0.891 0.845 0.817 0.871 Download
MACCS fingerprints 0.810 0.874 0.800 0.858 0.743 0.801 0.869 0.793 0.841 0.746 Download
Daylight fingerprints 0.772 0.782 0.769 0.787 0.751 0.797 0.810 0.795 0.828 0.763 Download
ECFP2 fingerprints 0.887 0.933 0.888 0.885 0.891 0.913 0.962 0.915 0.913 0.917 Download
ECFP4 fingerprints 0.906 0.936 0.910 0.869 0.951 0.924 0.963 0.928 0.899 0.955 Download
ECFP6 fingerprints 0.870 0.932 0.881 0.802 0.960 0.920 0.953 0.925 0.881 0.967 Download

  Download datasets

Positive dataset Negative dataset

Copyright @ 2012-2014 Computational Biology & Drug Design Group,
School of Pharmaceutical Sciences, Central South University. All rights reserved.

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