Target name

P51812: Ribosomal protein S6 kinase alpha-3


  Protein function

Serine/threonine-protein kinase that acts downstream of ERK (MAPK1/ERK2 and MAPK3/ERK1) signaling and mediates mitogenic and stress-induced activation of the transcription factors CREB1, ETV1/ER81 and NR4A1/NUR77, regulates translation through RPS6 and EIF4B phosphorylation, and mediates cellular proliferation, survival, and differentiation by modulating mTOR signaling and repressing pro-apoptotic function of BAD and DAPK1. In fibroblast, is required for EGF-stimulated phosphorylation of CREB1 and histone H3 at 'Ser-10', which results in the subsequent transcriptional activation of several immediate-early genes. In response to mitogenic stimulation (EGF and PMA), phosphorylates and activates NR4A1/NUR77 and ETV1/ER81 transcription factors and the cofactor CREBBP. Upon insulin-derived signal, acts indirectly on the transcription regulation of several genes by phosphorylating GSK3B at 'Ser-9' and inhibiting its activity. Phosphorylates RPS6 in response to serum or EGF via an mTOR-independent mechanism and promotes translation initiation by facilitating assembly of the preinitiation complex. In response to insulin, phosphorylates EIF4B, enhancing EIF4B affinity for the EIF3 complex and stimulating cap-dependent translation. Is involved in the mTOR nutrient-sensing pathway by directly phosphorylating TSC2 at 'Ser-1798', which potently inhibits TSC2 ability to suppress mTOR signaling, and mediates phosphorylation of RPTOR, which regulates mTORC1 activity and may promote rapamycin-sensitive signaling independently of the PI3K/AKT pathway. Mediates cell survival by phosphorylating the pro-apoptotic proteins BAD and DAPK1 and suppressing their pro-apoptotic function. Promotes the survival of hepatic stellate cells by phosphorylating CEBPB in response to the hepatotoxin carbon tetrachloride (CCl4). Is involved in cell cycle regulation by phosphorylating the CDK inhibitor CDKN1B, which promotes CDKN1B association with 14-3-3 proteins and prevents its translocation to the nucleus and inhibition of G1 progression. In LPS-stimulated dendritic cells, is involved in TLR4-induced macropinocytosis, and in myeloma cells, acts as effector of FGFR3-mediated transformation signaling, after direct phosphorylation at Tyr-529 by FGFR3. Phosphorylates DAPK1.

  Database links

Uniprot primary ID P51812
PDB ID 4D9U 4D9T 5D9L 4NW6 4NW5 4JG8 5D9K 4JG7 4JG6 4NUS
DrugBank ID DB00945
BioGrid ID 112111
GuidetoPHARMACOLOGY ID 1528
PharmGKB ID PA34847
KEGG ID hsa:6197
DIP ID DIP-38247N
STRING ID 9606.ENSP00000368884
IntAct ID P51812
DMDM 1730070
BRENDA 2.7.11.1
Reactome R-HSA-2559582 R-HSA-198753 R-HSA-881907 R-HSA-437239 R-HSA-199920 R-HSA-444257 R-HSA-442742
SignaLink P51812
BioCyc
Entrez Gene (Gene ID) 6197
BindingDB P51812

  Model Performance Metrics

Fingerprint type Sensitivity SEN_std Specificity SPE_std Accuracy ACC_std F1-score F1-score_std AUC AUC_std MCC MCC_std Download model
FP2 fingerprints 0.720 0.007 0.946 0.005 0.833 0.008 0.812 0.008 0.909 0.003 0.684 0.015 Download
Estate fingerprints 0.736 0.007 0.762 0.011 0.749 0.006 0.748 0.004 0.820 0.000 0.501 0.013 Download
MACCS fingerprints 0.750 0.007 0.812 0.014 0.781 0.007 0.779 0.007 0.849 0.003 0.570 0.014 Download
Daylight fingerprints 0.723 0.005 0.857 0.012 0.790 0.009 0.776 0.007 0.822 0.004 0.584 0.018 Download
ECFP2 fingerprints 0.796 0.012 0.880 0.010 0.838 0.008 0.833 0.009 0.921 0.003 0.681 0.014 Download
ECFP4 fingerprints 0.758 0.011 0.952 0.010 0.855 0.010 0.843 0.012 0.933 0.005 0.729 0.020 Download
ECFP6 fingerprints 0.726 0.016 0.986 0.004 0.856 0.007 0.834 0.010 0.940 0.000 0.742 0.013 Download

  Download datasets

Positive dataset Negative dataset


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School of Pharmaceutical Sciences, Central South University. All rights reserved.

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