The Protein Kinase Complement of the Human Genome

American Association for the Advancement of Science (AAAS) - Tập 298 Số 5600 - Trang 1912-1934 - 2002
Gerard Manning1, David B. Whyte1, Robert A. Martinez1, Tony Hunter2, Sucha Sudarsanam3,1
1SUGEN Inc., 230 East Grand Avenue, South San Francisco, CA 94080, USA.
2Salk Institute, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA
3Genomics and Biotechnology, Pharmacia Corporation, 230 East Grand Avenue, South San Francisco, CA 94080, USA.

Tóm tắt

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.

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We wish to thank the dozens of kinase researchers at SUGEN for their contributions to understanding the kinome at many levels. We particularly thank G. Plowman who guided the initial stages of the project S. Caenepeel for extensive sequence analysis of kinases and G. Charydczak for the computational support that made the genome mining possible. The SUGEN sequencing group provided cDNA confirmation of most predicted sequences. T.H. is a Frank and Else Schilling American Cancer Society Research Professor and serves on the Scientific Advisory Board of SUGEN.

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American Association for the Advancement of Science (AAAS)

Tập 298 Số 5600

1912-1934

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