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Science 6 December 2002:
Vol. 298. no. 5600, pp. 1912 - 1934
DOI: 10.1126/science.1075762
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Review

The Protein Kinase Complement of the Human Genome

G. Manning,1* D. B. Whyte,1 R. Martinez,1 T. Hunter,2 S. Sudarsanam13

We have catalogued the protein kinase complement of the human genome (the "kinome") using public and proprietary genomic, complementary DNA, and expressed sequence tag (EST) sequences. This provides a starting point for comprehensive analysis of protein phosphorylation in normal and disease states, as well as a detailed view of the current state of human genome analysis through a focus on one large gene family. We identify 518 putative protein kinase genes, of which 71 have not previously been reported or described as kinases, and we extend or correct the protein sequences of 56 more kinases. New genes include members of well-studied families as well as previously unidentified families, some of which are conserved in model organisms. Classification and comparison with model organism kinomes identified orthologous groups and highlighted expansions specific to human and other lineages. We also identified 106 protein kinase pseudogenes. Chromosomal mapping revealed several small clusters of kinase genes and revealed that 244 kinases map to disease loci or cancer amplicons.

1 SUGEN Inc., 230 East Grand Avenue, South San Francisco, CA 94080, USA.
2 Salk Institute, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA.
3 Genomics and Biotechnology, Pharmacia Corporation, 230 East Grand Avenue, South San Francisco, CA 94080, USA.
*   To whom correspondence should be addressed. E-mail: gerard-manning{at}sugen.com

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Pathways Leading to Phosphorylation of P450c17 and to the Posttranslational Regulation of Androgen Biosynthesis.
M. K. Tee, Q. Dong, and W. L. Miller (2008)
Endocrinology 149, 2667-2677
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Defining the Specificity Space of the Human Src Homology 2 Domain.
H. Huang, L. Li, C. Wu, D. Schibli, K. Colwill, S. Ma, C. Li, P. Roy, K. Ho, Z. Songyang, et al. (2008)
Mol. Cell. Proteomics 7, 768-784
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Ca2+/Calmodulin-Dependent Protein Kinase II{delta} and Protein Kinase D Overexpression Reinforce the Histone Deacetylase 5 Redistribution in Heart Failure.
J. Bossuyt, K. Helmstadter, X. Wu, H. Clements-Jewery, R. S. Haworth, M. Avkiran, J. L. Martin, S. M. Pogwizd, and D. M. Bers (2008)
Circ. Res. 102, 695-702
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Meta-prediction of phosphorylation sites with weighted voting and restricted grid search parameter selection.
J. Wan, S. Kang, C. Tang, J. Yan, Y. Ren, J. Liu, X. Gao, A. Banerjee, L. B. M. Ellis, and T. Li (2008)
Nucleic Acids Res. 36, e22
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Prediction of Cancer Driver Mutations in Protein Kinases.
A. Torkamani and N. J. Schork (2008)
Cancer Res. 68, 1675-1682
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An RNA molecule that specifically inhibits G-protein-coupled receptor kinase 2 in vitro.
G. Mayer, B. Wulffen, C. Huber, J. Brockmann, B. Flicke, L. Neumann, D. Hafenbradl, B. M. Klebl, M. J. Lohse, C. Krasel, et al. (2008)
RNA 14, 524-534
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