Target name

P42345: Serine/threonine-protein kinase mTOR


  Protein function

Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals. MTOR directly or indirectly regulates the phosphorylation of at least 800 proteins. Functions as part of 2 structurally and functionally distinct signaling complexes mTORC1 and mTORC2 (mTOR complex 1 and 2). Activated mTORC1 up-regulates protein synthesis by phosphorylating key regulators of mRNA translation and ribosome synthesis. This includes phosphorylation of EIF4EBP1 and release of its inhibition toward the elongation initiation factor 4E (eiF4E). Moreover, phosphorylates and activates RPS6KB1 and RPS6KB2 that promote protein synthesis by modulating the activity of their downstream targets including ribosomal protein S6, eukaryotic translation initiation factor EIF4B, and the inhibitor of translation initiation PDCD4. Stimulates the pyrimidine biosynthesis pathway, both by acute regulation through RPS6KB1-mediated phosphorylation of the biosynthetic enzyme CAD, and delayed regulation, through transcriptional enhancement of the pentose phosphate pathway which produces 5-phosphoribosyl-1-pyrophosphate (PRPP), an allosteric activator of CAD at a later step in synthesis, this function is dependent on the mTORC1 complex. Regulates ribosome synthesis by activating RNA polymerase III-dependent transcription through phosphorylation and inhibition of MAF1 an RNA polymerase III-repressor. In parallel to protein synthesis, also regulates lipid synthesis through SREBF1/SREBP1 and LPIN1. To maintain energy homeostasis mTORC1 may also regulate mitochondrial biogenesis through regulation of PPARGC1A. mTORC1 also negatively regulates autophagy through phosphorylation of ULK1. Under nutrient sufficiency, phosphorylates ULK1 at 'Ser-758', disrupting the interaction with AMPK and preventing activation of ULK1. Also prevents autophagy through phosphorylation of the autophagy inhibitor DAP. mTORC1 exerts a feedback control on upstream growth factor signaling that includes phosphorylation and activation of GRB10 a INSR-dependent signaling suppressor. Among other potential targets mTORC1 may phosphorylate CLIP1 and regulate microtubules. As part of the mTORC2 complex MTOR may regulate other cellular processes including survival and organization of the cytoskeleton. Plays a critical role in the phosphorylation at 'Ser-473' of AKT1, a pro-survival effector of phosphoinositide 3-kinase, facilitating its activation by PDK1. mTORC2 may regulate the actin cytoskeleton, through phosphorylation of PRKCA, PXN and activation of the Rho-type guanine nucleotide exchange factors RHOA and RAC1A or RAC1B. mTORC2 also regulates the phosphorylation of SGK1 at 'Ser-422'. Regulates osteoclastogensis by adjusting the expression of CEBPB isoforms (By similarity).

  Database links

Uniprot primary ID P42345
PDB ID 3FAP 4DRJ 4DRH 2GAQ 2NPU 2FAP 1AUE 4DRI 4JSP 1FAP 1NSG 4JT6 4JT5 4JSV 4JSN 4FAP 2RSE 4JSX
DrugBank ID DB00337 DB06287 DB00877 DB01590
BioGrid ID 108757
GuidetoPHARMACOLOGY ID 2109
PharmGKB ID PA28360
KEGG ID hsa:2475
DIP ID DIP-790N
STRING ID 9606.ENSP00000354558
IntAct ID P42345
DMDM 1169735
BRENDA
Reactome R-HSA-1632852 R-HSA-380972 R-HSA-1257604 R-HSA-165159 R-HSA-5674400 R-HSA-389357 R-HSA-3371571 R-HSA-5218920 R-HSA-5628897 R-HSA-166208
SignaLink P42345
BioCyc
Entrez Gene (Gene ID) 2475
BindingDB P42345

  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 0.880 0.000 0.924 0.000 0.902 0.004 0.900 0.000 0.960 0.000 0.810 0.000 Download
Estate fingerprints 0.835 0.005 0.761 0.004 0.798 0.004 0.803 0.005 0.870 0.000 0.595 0.005 Download
MACCS fingerprints 0.790 0.000 0.850 0.005 0.820 0.000 0.815 0.005 0.900 0.000 0.640 0.000 Download
Daylight fingerprints 0.850 0.000 0.850 0.000 0.850 0.000 0.850 0.000 0.900 0.000 0.697 0.005 Download
ECFP2 fingerprints 0.949 0.003 0.951 0.003 0.950 0.000 0.950 0.000 0.990 0.000 0.896 0.005 Download
ECFP4 fingerprints 0.947 0.005 0.993 0.000 0.970 0.000 0.970 0.000 0.990 0.000 0.940 0.000 Download
ECFP6 fingerprints 0.892 0.004 0.988 0.000 0.940 0.000 0.940 0.000 0.990 0.000 0.890 0.000 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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