The DOI matches its Crossref record; 38 of the 38 references it cites were found in a registry or an index.
The Protein Kinase Complement of the Human Genome
Open accessAbstract
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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“The human protein kinase super family consists of 514 protein kinases (Manning et al., 2002), which makes up 2.5% of the total human genome.”
From Mapping the Degradable Kinome Provides a Resource for Expedited Degrader Development (2020) · cites this paper as Manning et al., 2002
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Cites
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The sequence of the human genome
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Self-citationThe eukaryotic protein kinase superfamily: kinase (catalytic) domain structure and classification 1
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Self-citationProtein kinases — the major drug targets of the twenty-first century?
Cohen, P. (2002) · Nature Reviews Drug Discovery · doi:10.1038/nrd773 · Cited by 2,232
Comparative Genomics of the Eukaryotes
Rubin, G. M., Yandell, M. D., Wortman, J. R., Gabor, G. L., Miklos, Nelson, C. R., Hariharan, I. K., Fortini, M. E., Li, P. W., Apweiler, R., et al. (2000) · Science · doi:10.1126/science.287.5461.2204 · Cited by 1,698
A thousand and one protein kinases
Hunter, T. R. (1987) · Cell · doi:10.1016/0092-8674(87)90509-5 · Cited by 1,057
Self-citationEvolution of protein kinase signaling from yeast to man
Manning, G., Plowman, G. D., Hunter, T. R., & Sudarsanam, S. (2002) · Trends in Biochemical Sciences · doi:10.1016/s0968-0004(02)02179-5 · Cited by 1,004
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Presence and utility of intrinsically disordered regions in kinases
Kathiriya, J. J., Pathak, R. R., Clayman, E., Xue, B., Uversky, V. N., & Davé, V. (2014) · Molecular BioSystems · doi:10.1039/c4mb00224e · Cited by 30
Discovery and Design of Novel Small Molecule GSK-3 Inhibitors Targeting the Substrate Binding Site
Rippin, I., Khazanov, N., Ben Joseph, S., Kudinov, T., Berent, E., Arciniegas Ruiz, S. M., Marciano, D., Levy, L., Gruzman, A., Senderowitz, H., et al. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21228709 · Cited by 25
Jiang, J., Chen, S., Tsou, T., McGinnis, C. S., Khazaei, T., Zhu, Q., Park, J. H., Strazhnik, I.-M., Vielmetter, J., Gong, Y., et al. (2023) · doi:10.1101/2023.04.19.537364 · Cited by 21
Dynamic Protein Allosteric Regulation and Disease
Nussinov, R., Tsai, C.-J., & Jang, H. (2019) · Advances in Experimental Medicine and Biology · doi:10.1007/978-981-13-8719-7_2 · Cited by 18
Parallel reverse genetic screening in mutant human cells using transcriptomics
Gapp, B. V., Konopka, T., Penz, T., Dalal, V., Bürckstümmer, T., Bock, C., & Nijman, S. M. (2016) · Molecular Systems Biology · doi:10.15252/msb.20166890 · Cited by 12
MacKay, K. B., Tu, Y., Young, S. G., & Clarke, S. G. (2013) · PLoS ONE · doi:10.1371/journal.pone.0065967 · Cited by 14
Mingione, V. R., Foda, Z. H., Paung, Y., Philipose, H., Rangwala, A. M., Shan, Y., & Seeliger, M. A. (2022) · Journal of Molecular Biology · doi:10.1016/j.jmb.2022.167628 · Cited by 13
Therapeutic Targeting the Allosteric Cysteinome of RAS and Kinase Families
Li, L., Meyer, C., Zhou, Z.-W., Elmezayen, A., & Westover, K. (2022) · Journal of Molecular Biology · doi:10.1016/j.jmb.2022.167626 · Cited by 14
Balmer, D., Bapst-Wicht, L., Pyakurel, A., Emery, M., Nanchen, N., Bochet, C. G., & Roduit, R. (2017) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2017.00043 · Cited by 6
Integrated multi-omics analysis for lung adenocarcinoma in Xuanwei, China
Jiang, B., Yang, J., He, R., Wang, D., Huang, Y., Zhao, G., Ning, M., Zeng, T., & Li, G. (2023) · Aging · doi:10.18632/aging.205300 · Cited by 5
Metadata
- Authors
- Manning, G., Whyte, D. B., Martinez, R., Hunter, T., & Sudarsanam, S.
- Affiliations
- SUGEN Inc., 230 East Grand Avenue, South San Francisco, CA 94080, USA.
- Salk Institute for Biological Studies (US)
- Corresponding author
- Manning, G.
- Venue
- Science
- Published
- 2002-12-06
- Volume
- 298
- Issue
- 5600
- Pages
- 1912-1934
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2030205108
- Cited by
- 8,145
- References
- 38
- Citations by year
- 2026: 230 · 2025: 298 · 2024: 332 · 2023: 344 · 2022: 325 · 2021: 387 · 2020: 398 · 2019: 370 · 2018: 345 · 2017: 376 · 2016: 361 · 2015: 418 · 2014: 425 · 2013: 385 · 2012: 449
- FWCI
- 13.95
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by
- Locations
- Science (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Phylogenetic Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bioinformatics and Genomic Networks
- Keywords
- protein kinases, kinome, human genome, protein phosphorylation, kinase gene family, orthogroups, disease loci
- MeSH terms
- Animals, Catalysis, Chromosome Mapping, Genes, Humans, Neoplasms, Phylogeny, Protein Kinases, Pseudogenes, Signal Transduction, Genome, Human, Sequence Analysis, DNA, Protein Structure, Tertiary, Computational Biology, Databases, Genetic
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