Target name

P24941: Cyclin-dependent kinase 2

  Protein function

Serine/threonine-protein kinase involved in the control of the cell cycle; essential for meiosis, but dispensable for mitosis. Phosphorylates CTNNB1, USP37, p53/TP53, NPM1, CDK7, RB1, BRCA2, MYC, NPAT, EZH2. Interacts with cyclins A, B1, B3, D, or E. Triggers duplication of centrosomes and DNA. Acts at the G1-S transition to promote the E2F transcriptional program and the initiation of DNA synthesis, and modulates G2 progression; controls the timing of entry into mitosis/meiosis by controlling the subsequent activation of cyclin B/CDK1 by phosphorylation, and coordinates the activation of cyclin B/CDK1 at the centrosome and in the nucleus. Crucial role in orchestrating a fine balance between cellular proliferation, cell death, and DNA repair in human embryonic stem cells (hESCs). Activity of CDK2 is maximal during S phase and G2; activated by interaction with cyclin E during the early stages of DNA synthesis to permit G1-S transition, and subsequently activated by cyclin A2 (cyclin A1 in germ cells) during the late stages of DNA replication to drive the transition from S phase to mitosis, the G2 phase. EZH2 phosphorylation promotes H3K27me3 maintenance and epigenetic gene silencing. Phosphorylates CABLES1 (By similarity). Cyclin E/CDK2 prevents oxidative stress-mediated Ras-induced senescence by phosphorylating MYC. Involved in G1-S phase DNA damage checkpoint that prevents cells with damaged DNA from initiating mitosis; regulates homologous recombination-dependent repair by phosphorylating BRCA2, this phosphorylation is low in S phase when recombination is active, but increases as cells progress towards mitosis. In response to DNA damage, double-strand break repair by homologous recombination a reduction of CDK2-mediated BRCA2 phosphorylation. Phosphorylation of RB1 disturbs its interaction with E2F1. NPM1 phosphorylation by cyclin E/CDK2 promotes its dissociates from unduplicated centrosomes, thus initiating centrosome duplication. Cyclin E/CDK2-mediated phosphorylation of NPAT at G1-S transition and until prophase stimulates the NPAT-mediated activation of histone gene transcription during S phase. Required for vitamin D-mediated growth inhibition by being itself inactivated. Involved in the nitric oxide- (NO) mediated signaling in a nitrosylation/activation-dependent manner. USP37 is activated by phosphorylation and thus triggers G1-S transition. CTNNB1 phosphorylation regulates insulin internalization. Phosphorylates FOXP3 and negatively regulates its transcriptional activity and protein stability (By similarity).

  Database links

Uniprot primary ID P24941
PDB ID 3RNI 2WEV 2WXV 1GZ8 2V0D 3QU0 1H28 1H25 1H24 2DS1 1H26 1H27 3F5X 2VTI 5CYI 1V1K 3R71 3S00 1FQ1 3QL8 3S0O 2C5X 2C5Y 4D1Z 3DOG 2C5V 3R7I 2BHH 1PF8 3R7U 2C5N 2C5O 2A0C 2BHE 4FKU 3R7Y 3R7V 4D1X 3TNW 2VTQ 1WCC 2VTS 2VTT 2VTH 2VTP 2VTJ 2VTL 3ULI 2VTN 2VTO 2VTA
DrugBank ID DB06616
BioGrid ID 107452
PharmGKB ID PA101
KEGG ID hsa:1017
STRING ID 9606.ENSP00000266970
IntAct ID P24941
DMDM 116051
Reactome R-HSA-68911 R-HSA-68962 R-HSA-2559586 R-HSA-176408 R-HSA-2559582 R-HSA-69202 R-HSA-69656 R-HSA-912446 R-HSA-69200 R-HSA-69563 R-HSA-69017 R-HSA-68949 R-HSA-69273 R-HSA-983231 R-HSA-1538133 R-HSA-176187 R-HSA-187577
SignaLink P24941
Entrez Gene (Gene ID) 1017
BindingDB P24941

  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 0.820 0.000 0.838 0.000 0.829 0.003 0.829 0.003 0.900 0.000 0.653 0.005 Download
Estate fingerprints 0.801 0.003 0.699 0.000 0.750 0.000 0.762 0.004 0.823 0.005 0.505 0.005 Download
MACCS fingerprints 0.810 0.000 0.750 0.000 0.780 0.000 0.790 0.000 0.850 0.000 0.566 0.005 Download
Daylight fingerprints 0.776 0.005 0.684 0.000 0.730 0.000 0.740 0.000 0.780 0.000 0.458 0.004 Download
ECFP2 fingerprints 0.930 0.000 0.850 0.000 0.890 0.000 0.890 0.000 0.950 0.000 0.780 0.000 Download
ECFP4 fingerprints 0.910 0.000 0.930 0.000 0.920 0.000 0.920 0.000 0.970 0.000 0.841 0.003 Download
ECFP6 fingerprints 0.888 0.004 0.952 0.000 0.920 0.000 0.916 0.005 0.960 0.000 0.840 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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