Repertoire of protein kinases encoded in the genome of zebrafish shows remarkably large population of PIM kinases.
In recent times, zebrafish has garnered lot of popularity as model organism to study human cancers. Despite high evolutionary divergence from humans, zebrafish develops almost all types of human tumors when induced. However, mechanistic details of tumor formation have remained largely unknown. Present study is aimed at analysis of repertoire of kinases in zebrafish proteome to provide insights into various cellular components. Annotation using highly sensitive remote homology detection methods revealed "substantial expansion" of Ser/Thr/Tyr kinase family in zebrafish compared to humans, constituting over 3% of proteome. Subsequent classification of kinases into subfamilies revealed presence of large number of CAMK group of kinases, with massive representation of PIM kinases, important for cell cycle regulation and growth. Extensive sequence comparison between human and zebrafish PIM kinases revealed high conservation of functionally important residues with a few organism specific variations. There are about 300 PIM kinases in zebrafish kinome, while human genome codes for only about 500 kinases altogether. PIM kinases have been implicated in various human cancers and are currently being targeted to explore their therapeutic potentials. Hence, in depth analysis of PIM kinases in zebrafish has opened up new avenues of research to verify the model organism status of zebrafish.
Molecular Biophysics Unit, Indian Institute of Science, Bangalore 560012, India.
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R
Rakshambikai
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N
Srinivasan
Rupali A
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Gadkari
D020413:3' Untranslated Regions; D020816:Amino Acid Motifs; D000818:Animals; D016678:Genome; D006801:Humans; D011494:Protein Kinases / Q000235:genetics* / Q000378:metabolism; D051573:Proto-Oncogene Proteins c-pim-1 / Q000235:genetics* / Q000378:metabolism*; D015203:Reproducibility of Results; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000235:genetics* / Q000378:metabolism*
D020413:3' Untranslated Regions; D029961:Zebrafish Proteins; D011494:Protein Kinases; D051573:Proto-Oncogene Proteins c-pim-1; C406031:proto-oncogene proteins pim