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Classification and functional annotation of eukaryotic protein kinases
Author(s) -
MirandaSaavedra Diego,
Barton Geoffrey J.
Publication year - 2007
Publication title -
proteins: structure, function, and bioinformatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.699
H-Index - 191
eISSN - 1097-0134
pISSN - 0887-3585
DOI - 10.1002/prot.21444
Subject(s) - biology , kinase , sh3 domain , protein serine threonine kinases , kinome , genetics , receptor tyrosine kinase , protein kinase a , computational biology , microbiology and biotechnology
Reversible protein phosphorylation by protein kinases and phosphatases is a ubiquitous signaling mechanism in all eukaryotic cells. A multilevel hidden Markov model library is presented which is able to classify protein kinases into one of 12 families, with a misclassification rate of zero on the characterized kinomes of H. sapiens, M. musculus, D. melanogaster, C. elegans, S. cerevisiae, D. discoideum, and P. falciparum. The Library is shown to outperform BLASTP and a general Pfam hidden Markov model of the kinase catalytic domain in the retrieval and family‐level classification of protein kinases. The application of the Library to the 38 unclassified kinases of yeast enriches the yeast kinome in protein kinases of the families AGC (5), CAMK (17), CMGC (4), and STE (1), thereby raising the family‐level classification of yeast conventional protein kinases from 66.96 to 90.43%. The application of the Library to 21 eukaryotic genomes shows seven families (AGC, CAMK, CK1, CMGC, STE, PIKK, and RIO) to be present in all genomes analyzed, and so is likely to be essential to eukaryotes. Putative tyrosine kinases (TKs) are found in the plants A. thaliana (2), O. sativa ssp. Indica (6), and O. sativa ssp. Japonica (7), and in the amoeba E. histolytica (7). To our knowledge, TKs have not been predicted in plants before. This also suggests that a primitive set of TKs might have predated the radiation of eukaryotes. Putative tyrosine kinase‐like kinases (TKLs) are found in the fungi C. neoformans (2), P. chrysosporium (4), in the Apicomplexans C. hominis (4), P. yoelii (4), and P. falciparum (6), the amoeba E. histolytica (109), and the alga T. pseudonana (6). TKLs are found to be abundant in plants (776 in A. thaliana , 1010 in O. sativa ssp. Indica , and 969 in O. sativa ssp. Japonica ). TKLs might have predated the radiation of eukaryotes too and have been lost secondarily from some fungi. The application of the Library facilitates the annotation of kinomes and has provided novel insights on the early evolution and subsequent adaptations of the various protein kinase families in eukaryotes. Proteins 2007. © 2007 Wiley‐Liss, Inc.