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G. Manning,1*D. B. Whyte,1R. Martinez,1T. Hunter,2S. 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 proteinphosphorylation in normal and disease states, as well as a
detailedview of the current state of human genome analysis through a
focuson one large gene family. We identify 518 putative protein kinasegenes, of which 71 have not previously been reported or describedas
kinases, and we extend or correct the protein sequences of56 more
kinases. New genes include members of well-studied familiesas well as
previously unidentified families, some of which areconserved in model
organisms. Classification and comparison withmodel organism kinomes
identified orthologous groups and highlightedexpansions specific to
human and other lineages. We also identified106 protein kinase
pseudogenes. Chromosomal mapping revealed severalsmall clusters of
kinase genes and revealed that 244 kinases mapto 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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Herpes Simplex Virus 1 Protein Kinase Us3 Phosphorylates Viral Envelope Glycoprotein B and Regulates Its Expression on the Cell Surface.
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Spatial Learning Impairment, Enhanced CDK5/p35 Activity, and Downregulation of NMDA Receptor Expression in Transgenic Mice Expressing Tau-Tubulin Kinase 1.
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Nordihydroguaiaretic Acid Inhibits an Activated Fibroblast Growth Factor Receptor 3 Mutant and Blocks Downstream Signaling in Multiple Myeloma Cells.
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Science Signaling
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Reproductive Sciences
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GPS 2.0, a Tool to Predict Kinase-specific Phosphorylation Sites in Hierarchy.
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Mol. Cell. Proteomics
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Palmitoylation-dependent endosomal localization of AATYK1A and its interaction with Src.
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Rho5p Is Involved in Mediating the Osmotic Stress Response in Saccharomyces cerevisiae, and Its Activity Is Regulated via Msi1p and Npr1p by Phosphorylation and Ubiquitination.
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Eukaryot. Cell
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PhosphoPOINT: a comprehensive human kinase interactome and phospho-protein database.
The Annotation of Both Human and Mouse Kinomes in UniProtKB/Swiss-Prot: One Small Step in Manual Annotation, One Giant Leap for Full Comprehension of Genomes.
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From the Cover: The protist, Monosiga brevicollis, has a tyrosine kinase signaling network more elaborate and diverse than found in any known metazoan.
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PNAS
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Glycogen Synthase Kinase (GSK) 3{beta} Directly Phosphorylates Serine 212 in the Regulatory Loop and Inhibits Microtubule Affinity-regulating Kinase (MARK) 2.
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294, E1169-E1177
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Chemicals that modulate stem cell differentiation.
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PNAS
105, 7467-7471
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Protein Kinase D3 (PKD3) Contributes to Prostate Cancer Cell Growth and Survival Through a PKC{varepsilon}/PKD3 Pathway Downstream of Akt and ERK 1/2.
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Fibronectin Type I Repeat Is a Nonactivating Ligand for EphA1 and Inhibits ATF3-dependent Angiogenesis.
Defining the Specificity Space of the Human Src Homology 2 Domain.
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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)
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102, 695-702
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Meta-prediction of phosphorylation sites with weighted voting and restricted grid search parameter selection.
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Nucleic Acids Res.
36, e22
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Prediction of Cancer Driver Mutations in Protein Kinases.
An RNA molecule that specifically inhibits G-protein-coupled receptor kinase 2 in vitro.
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Epigenetic inactivation of protein kinase D1 in gastric cancer and its role in gastric cancer cell migration and invasion.
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Combination of Clk family kinase and SRp75 modulates alternative splicing of Adenovirus E1A..
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Genes Cells
13, 233-244
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Protein-tyrosine Phosphatase {epsilon} Regulates Shc Signaling in a Kinase-specific Manner: INCREASING COHERENCE IN TYROSINE PHOSPHATASE SIGNALING.
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Characterization of Some Molecular Mechanisms Governing Autoactivation of the Catalytic Domain of the Anaplastic Lymphoma Kinase.
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283, 3743-3750
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Potassium Channel Phosphorylation in Excitable Cells: Providing Dynamic Functional Variability to a Diverse Family of Ion Channels.
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Sixteen-Kinase Gene Expression Identifies Luminal Breast Cancers with Poor Prognosis.
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Protein Kinase D in the Cardiovascular System: Emerging Roles in Health and Disease.
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Cyclic Nucleotide-dependent Protein Kinases Inhibit Binding of 14-3-3 to the GTPase-activating Protein Rap1GAP2 in Platelets.
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Physiol Genomics
32, 229-253
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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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28, 551-563
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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
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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)
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283, 1084-1093
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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)
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36, D679-D683
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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)
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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
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PhosphoBlast, a Computational Tool for Comparing Phosphoprotein Signatures among Large Datasets.
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)
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143, 31-38
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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)
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282, 37232-37243
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