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Science 6 December 2002:
Vol. 298. no. 5600, pp. 1912 - 1934
DOI: 10.1126/science.1075762
Prev | Table of Contents | Next

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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Activation of the SPS Amino Acid-Sensing Pathway in Saccharomyces cerevisiae Correlates with the Phosphorylation State of a Sensor Component, Ptr3.
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Mol. Cell. Biol. 28, 551-563
   Abstract »    Full Text »    PDF »
Allosteric cooperativity in protein kinase A.
L. R. Masterson, A. Mascioni, N. J. Traaseth, S. S. Taylor, and G. Veglia (2008)
PNAS 105, 506-511
   Abstract »    Full Text »    PDF »
Identification of Functionally Distinct Regions That Mediate Biological Activity of the Protein Kinase A Homolog Tpk2.
E. J. Kennedy, G. Ghosh, and L. Pillus (2008)
J. Biol. Chem. 283, 1084-1093
   Abstract »    Full Text »    PDF »
PepCyber:P~PEP: a database of human protein protein interactions mediated by phosphoprotein-binding domains.
W. Gong, D. Zhou, Y. Ren, Y. Wang, Z. Zuo, Y. Shen, F. Xiao, Q. Zhu, A. Hong, X. Zhou, et al. (2008)
Nucleic Acids Res. 36, D679-D683
   Abstract »    Full Text »    PDF »
Comparison of Miniaturized Time-Resolved Fluorescence Resonance Energy Transfer and Enzyme-Coupled Luciferase High-Throughput Screening Assays to Discover Inhibitors of Rho-Kinase II (ROCK-II).
T. Schroter, D. Minond, A. Weiser, C. Dao, J. Habel, T. Spicer, P. Chase, P. Baillargeon, L. Scampavia, S. Schurer, et al. (2008)
J Biomol Screen 13, 17-28
   Abstract »    PDF »
Gas6 and the Tyro 3 receptor tyrosine kinase subfamily regulate the phagocytic function of Sertoli cells.
W. Xiong, Y. Chen, H. Wang, H. Wang, H. Wu, Q. Lu, and D. Han (2008)
Reproduction 135, 77-87
   Abstract »    Full Text »    PDF »
PhosphoBlast, a Computational Tool for Comparing Phosphoprotein Signatures among Large Datasets.
Y. Wang and R. L. Klemke (2008)
Mol. Cell. Proteomics 7, 145-162
   Abstract »    Full Text »    PDF »
Epidermal Growth Factor Receptor Phosphorylates Protein Kinase C {delta} at Tyr332 to form a Trimeric Complex with p66Shc in the H2O2-stimulated Cells.
M. Morita, H. Matsuzaki, T. Yamamoto, Y. Fukami, and U. Kikkawa (2008)
J. Biochem. 143, 31-38
   Abstract »    Full Text »    PDF »
Modulation of F-actin Rearrangement by the Cyclic AMP/cAMP-dependent Protein Kinase (PKA) Pathway Is Mediated by MAPK-activated Protein Kinase 5 and Requires PKA-induced Nuclear Export of MK5.
N. Gerits, T. Mikalsen, S. Kostenko, A. Shiryaev, M. Johannessen, and U. Moens (2007)
J. Biol. Chem. 282, 37232-37243
   Abstract »    Full Text »    PDF »


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