Target name

Q15759: Mitogen-activated protein kinase 11


  Protein function

Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. MAPK11 is one of the four p38 MAPKs which play an important role in the cascades of cellular responses evoked by extracellular stimuli such as proinflammatory cytokines or physical stress leading to direct activation of transcription factors. Accordingly, p38 MAPKs phosphorylate a broad range of proteins and it has been estimated that they may have approximately 200 to 300 substrates each. MAPK11 functions are mostly redundant with those of MAPK14. Some of the targets are downstream kinases which are activated through phosphorylation and further phosphorylate additional targets. RPS6KA5/MSK1 and RPS6KA4/MSK2 can directly phosphorylate and activate transcription factors such as CREB1, ATF1, the NF-kappa-B isoform RELA/NFKB3, STAT1 and STAT3, but can also phosphorylate histone H3 and the nucleosomal protein HMGN1. RPS6KA5/MSK1 and RPS6KA4/MSK2 play important roles in the rapid induction of immediate-early genes in response to stress or mitogenic stimuli, either by inducing chromatin remodeling or by recruiting the transcription machinery. On the other hand, two other kinase targets, MAPKAPK2/MK2 and MAPKAPK3/MK3, participate in the control of gene expression mostly at the post-transcriptional level, by phosphorylating ZFP36 (tristetraprolin) and ELAVL1, and by regulating EEF2K, which is important for the elongation of mRNA during translation. MKNK1/MNK1 and MKNK2/MNK2, two other kinases activated by p38 MAPKs, regulate protein synthesis by phosphorylating the initiation factor EIF4E2. In the cytoplasm, the p38 MAPK pathway is an important regulator of protein turnover. For example, CFLAR is an inhibitor of TNF-induced apoptosis whose proteasome-mediated degradation is regulated by p38 MAPK phosphorylation. Ectodomain shedding of transmembrane proteins is regulated by p38 MAPKs as well. In response to inflammatory stimuli, p38 MAPKs phosphorylate the membrane-associated metalloprotease ADAM17. Such phosphorylation is required for ADAM17-mediated ectodomain shedding of TGF-alpha family ligands, which results in the activation of EGFR signaling and cell proliferation. Additional examples of p38 MAPK substrates are the FGFR1. FGFR1 can be translocated from the extracellular space into the cytosol and nucleus of target cells, and regulates processes such as rRNA synthesis and cell growth. FGFR1 translocation requires p38 MAPK activation. In the nucleus, many transcription factors are phosphorylated and activated by p38 MAPKs in response to different stimuli. Classical examples include ATF1, ATF2, ATF6, ELK1, PTPRH, DDIT3, TP53/p53 and MEF2C and MEF2A. The p38 MAPKs are emerging as important modulators of gene expression by regulating chromatin modifiers and remodelers. The promoters of several genes involved in the inflammatory response, such as IL6, IL8 and IL12B, display a p38 MAPK-dependent enrichment of histone H3 phosphorylation on 'Ser-10' (H3S10ph) in LPS-stimulated myeloid cells. This phosphorylation enhances the accessibility of the cryptic NF-kappa-B-binding sites marking promoters for increased NF-kappa-B recruitment.

  Database links

Uniprot primary ID Q15759
PDB ID 3GP0 3GC9 3GC8
DrugBank ID DB08896
BioGrid ID 111586
GuidetoPHARMACOLOGY ID 1500
PharmGKB ID PA30618
KEGG ID hsa:5600
DIP ID
STRING ID 9606.ENSP00000333685
IntAct ID Q15759
DMDM 134047835
BRENDA 2.7.11.24
Reactome R-HSA-376172 R-HSA-4420097 R-HSA-171007 R-HSA-2559580 R-HSA-198753 R-HSA-2151209 R-HSA-168638 R-HSA-450302 R-HSA-450341 R-HSA-375170 R-HSA-450604
SignaLink Q15759
BioCyc
Entrez Gene (Gene ID) 5600
BindingDB Q15759

  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 0.731 0.010 0.959 0.008 0.845 0.005 0.823 0.008 0.935 0.005 0.704 0.010 Download
Estate fingerprints 0.744 0.015 0.802 0.007 0.773 0.007 0.765 0.007 0.866 0.005 0.539 0.013 Download
MACCS fingerprints 0.781 0.006 0.761 0.012 0.771 0.007 0.771 0.007 0.876 0.005 0.536 0.015 Download
Daylight fingerprints 0.583 0.007 0.969 0.005 0.776 0.005 0.721 0.006 0.885 0.007 0.596 0.008 Download
ECFP2 fingerprints 0.810 0.020 0.884 0.013 0.847 0.013 0.840 0.016 0.936 0.005 0.690 0.027 Download
ECFP4 fingerprints 0.812 0.016 0.948 0.005 0.880 0.009 0.872 0.010 0.952 0.004 0.764 0.017 Download
ECFP6 fingerprints 0.778 0.010 0.954 0.007 0.866 0.007 0.855 0.008 0.952 0.004 0.747 0.012 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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