Target name

P45983: Mitogen-activated protein kinase 8


  Protein function

Serine/threonine-protein kinase involved in various processes such as cell proliferation, differentiation, migration, transformation and programmed cell death. Extracellular stimuli such as proinflammatory cytokines or physical stress stimulate the stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) signaling pathway. In this cascade, two dual specificity kinases MAP2K4/MKK4 and MAP2K7/MKK7 phosphorylate and activate MAPK8/JNK1. In turn, MAPK8/JNK1 phosphorylates a number of transcription factors, primarily components of AP-1 such as JUN, JDP2 and ATF2 and thus regulates AP-1 transcriptional activity. Phosphorylates the replication licensing factor CDT1, inhibiting the interaction between CDT1 and the histone H4 acetylase HBO1 to replication origins. Loss of this interaction abrogates the acetylation required for replication initiation. Promotes stressed cell apoptosis by phosphorylating key regulatory factors including p53/TP53 and Yes-associates protein YAP1. In T-cells, MAPK8 and MAPK9 are required for polarized differentiation of T-helper cells into Th1 cells. Contributes to the survival of erythroid cells by phosphorylating the antagonist of cell death BAD upon EPO stimulation. Mediates starvation-induced BCL2 phosphorylation, BCL2 dissociation from BECN1, and thus activation of autophagy. Phosphorylates STMN2 and hence regulates microtubule dynamics, controlling neurite elongation in cortical neurons. In the developing brain, through its cytoplasmic activity on STMN2, negatively regulates the rate of exit from multipolar stage and of radial migration from the ventricular zone. Phosphorylates several other substrates including heat shock factor protein 4 (HSF4), the deacetylase SIRT1, ELK1, or the E3 ligase ITCH. Phosphorylates the CLOCK-ARNTL/BMAL1 heterodimer and plays a role in the regulation of the circadian clock (PubMed:22441692).

  Database links

Uniprot primary ID P45983
PDB ID 3PZE 3ELJ 1UKH 3O2M 2H96 2NO3 1UKI 2GMX 3O17 4IZY 4UX9 4E73 3V3V 4AWI 4L7F 4QTD 2XS0 3VUL 3VUM 3VUH 3VUI 3VUK 3VUD 3VUG 4G1W 4HYS 2XRW 2G01 4HYU
DrugBank ID
BioGrid ID 111585
GuidetoPHARMACOLOGY ID 1496
PharmGKB ID PA283
KEGG ID hsa:5599
DIP ID DIP-249N
STRING ID 9606.ENSP00000353483
IntAct ID P45983
DMDM 2507195
BRENDA 2.7.11.24
Reactome R-HSA-376172 R-HSA-139910 R-HSA-2559580 R-HSA-2871796 R-HSA-450341 R-HSA-111446 R-HSA-205043 R-HSA-193648 R-HSA-450321
SignaLink P45983
BioCyc
Entrez Gene (Gene ID) 5599
BindingDB P45983

  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 0.879 0.003 0.857 0.005 0.868 0.004 0.870 0.000 0.950 0.000 0.732 0.004 Download
Estate fingerprints 0.827 0.005 0.747 0.005 0.787 0.005 0.794 0.005 0.860 0.000 0.576 0.005 Download
MACCS fingerprints 0.824 0.005 0.754 0.003 0.789 0.003 0.795 0.005 0.874 0.005 0.578 0.006 Download
Daylight fingerprints 0.714 0.005 0.746 0.000 0.730 0.000 0.728 0.004 0.811 0.003 0.464 0.005 Download
ECFP2 fingerprints 0.931 0.003 0.869 0.004 0.900 0.000 0.902 0.004 0.970 0.000 0.803 0.005 Download
ECFP4 fingerprints 0.925 0.005 0.955 0.000 0.940 0.000 0.940 0.000 0.980 0.000 0.886 0.005 Download
ECFP6 fingerprints 0.906 0.005 0.982 0.004 0.944 0.005 0.940 0.000 0.980 0.000 0.891 0.003 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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