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Chang EJ, et al.  (2007) Prediction of cyclin-dependent kinase phosphorylation substrates. PLoS One 2(7):e656

Abstract: Protein phosphorylation, mediated by a family of enzymes called cyclin-dependent kinases (Cdks), plays a central role in the cell-division cycle of eukaryotes. Phosphorylation by Cdks directs the cell cycle by modifying the function of regulators of key processes such as DNA replication and mitotic progression. Here, we present a novel computational procedure to predict substrates of the cyclin-dependent kinase Cdc28 (Cdk1) in the Saccharomyces cerevisiae. Currently, most computational phosphorylation site prediction procedures focus solely on local sequence characteristics. In the present procedure, we model Cdk substrates based on both local and global characteristics of the substrates. Thus, we define the local sequence motifs that represent the Cdc28 phosphorylation sites and subsequently model clustering of these motifs within the protein sequences. This restraint reflects the observation that many known Cdk substrates contain multiple clustered phosphorylation sites. The present strategy defines a subset of the proteome that is highly enriched for Cdk substrates, as validated by comparing it to a set of bona fide, published, experimentally characterized Cdk substrates which was to our knowledge, comprehensive at the time of writing. To corroborate our model, we compared its predictions with three experimentally independent Cdk proteomic datasets and found significant overlap. Finally, we directly detected in vivo phosphorylation at Cdk motifs for selected putative substrates using mass spectrometry.

Status: Published Type: Journal Article PubMed ID: 17668044

Topics addressed in this paper

Number of different genes curated to this paper: 91

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ACC1 ACE2 ACM1 ADY3 AFI1 ALY2 ASE1 ASH1 BCK1 BEM3
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BNI1 BNI4 BOI1 BUD3 BUD4 CAF120 CDC15 CDC28 CDC6 CDH1
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CHD1 DAL81 DNA2 EXO84 FAR1 FIN1 FIR1 FPK1 FUN30 GAC1
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Topics Genes linked to topics (#31 - 40 )
HCM1 HOS4 HPC2 INP52 IQG1 IRC8 KEL1 LEU1 LRE1 LTE1
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MCM3 MDS3 MLP1 MPC54 MPS2 MSA1 MSB1 MSE1 MYO3 NDD1
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Topics Genes linked to topics (#51 - 60 )
NET1 NUP60 ORC2 ORC6 PDS1 PKC1 PKH2 PLM2 PMS1 PSK1
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Topics Genes linked to topics (#61 - 70 )
RAD9 RGA2 RIM15 RPO21 SAC3 SAK1 SFI1 SIR4 SLD2 SLH1
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SMC4 SNT1 SPA2 SRS2 SSN2 STB1 STE20 SWI4 SWI5 TAF4
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Topics Genes linked to topics (#81 - 90 )
TFG1 TRA1 TUS1 UBP2 ULP2 YEN1 YHR080C YMR124W YOX1 ZIP1
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Topics Genes linked to topics (#91 )
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