Target name

P23443: Ribosomal protein S6 kinase beta-1

  Protein function

Serine/threonine-protein kinase that acts downstream of mTOR signaling in response to growth factors and nutrients to promote cell proliferation, cell growth and cell cycle progression. Regulates protein synthesis through phosphorylation of EIF4B, RPS6 and EEF2K, and contributes to cell survival by repressing the pro-apoptotic function of BAD. Under conditions of nutrient depletion, the inactive form associates with the EIF3 translation initiation complex. Upon mitogenic stimulation, phosphorylation by the mammalian target of rapamycin complex 1 (mTORC1) leads to dissociation from the EIF3 complex and activation. The active form then phosphorylates and activates several substrates in the pre-initiation complex, including the EIF2B complex and the cap-binding complex component EIF4B. Also controls translation initiation by phosphorylating a negative regulator of EIF4A, PDCD4, targeting it for ubiquitination and subsequent proteolysis. Promotes initiation of the pioneer round of protein synthesis by phosphorylating POLDIP3/SKAR. In response to IGF1, activates translation elongation by phosphorylating EEF2 kinase (EEF2K), which leads to its inhibition and thus activation of EEF2. Also plays a role in feedback regulation of mTORC2 by mTORC1 by phosphorylating RICTOR, resulting in the inhibition of mTORC2 and AKT1 signaling. Mediates cell survival by phosphorylating the pro-apoptotic protein BAD and suppressing its pro-apoptotic function. Phosphorylates mitochondrial URI1 leading to dissociation of a URI1-PPP1CC complex. The free mitochondrial PPP1CC can then dephosphorylate RPS6KB1 at Thr-412, which is proposed to be a negative feedback mechanism for the RPS6KB1 anti-apoptotic function. Mediates TNF-alpha-induced insulin resistance by phosphorylating IRS1 at multiple serine residues, resulting in accelerated degradation of IRS1. In cells lacking functional TSC1-2 complex, constitutively phosphorylates and inhibits GSK3B. May be involved in cytoskeletal rearrangement through binding to neurabin. Phosphorylates and activates the pyrimidine biosynthesis enzyme CAD, downstream of MTOR.

  Database links

Uniprot primary ID P23443
PDB ID 3WE4 4L3L 4RLP 4L3J 3A62 3WF9 3A60 3A61 3WF5 3WF6 3WF7 3WF8 4RLO 4L42 4L43 4L44 4L45 4L46
DrugBank ID
BioGrid ID 112112
PharmGKB ID PA34851
KEGG ID hsa:6198
Entrez Gene (Gene ID) 6198
DIP DIP-29986N
STRING 9606ENSP00000225577
MINT MINT-203709
IntAct P23443
DMDM 54041234
BREDNA 27111
Rectome R-HSA-166208
SignaLink P23443 B4DTG1 F6UYM1 B2R779
BindingDB P23443

  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 0.901 0.917 0.908 0.839 0.976 0.913 0.928 0.914 0.864 0.969 Download
MACCS fingerprints 0.894 0.956 0.896 0.876 0.916 0.898 0.965 0.896 0.875 0.919 Download
Daylight fingerprints 0.890 0.900 0.899 0.813 0.987 0.911 0.917 0.914 0.847 0.988 Download
ECFP2 fingerprints 0.901 0.936 0.908 0.844 0.972 0.907 0.950 0.908 0.864 0.956 Download
ECFP4 fingerprints 0.902 0.930 0.909 0.839 0.979 0.919 0.953 0.920 0.875 0.969 Download
ECFP6 fingerprints 0.904 0.915 0.911 0.836 0.987 0.918 0.944 0.920 0.858 0.988 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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