In the late 1950s, the role of reversible phosphorylation in enzymatic regulation was recognized by Fischer et al. (1). Phosphorylation events are most commonly mediated by protein kinases, which transfer the ␥-phosphate from nucleotides, usually ATP, via a phosphoester bond (O-phosphate) to the hydroxyl side chain of serine, threonine, or tyrosine residues on their protein substrates. Phosphates are bulky, negatively charged groups, and their addition to a protein can result in a profound change in its interactions with other molecules or subcellular location and/or to a conformational change of the protein itself. Kinase-mediated protein phosphorylation can be reversed through dephosphorylation after which the protein switches back to its original charge state and conformation. As protein conformation often determines function, the phosphorylation event may be considered a type of molecular switch, turning the activity of the molecule on or off. These reversible and dynamic phosphorylation events are under tight control, being governed by the opposing activities of protein kinases and protein phosphatases.Eukaryotic protein kinases (ePKs) 1 play a key role in cell communication pathways and in the transmission of information from outside the cell or between subcellular components within the cell. The ePKs constitute one of the largest mammalian gene families comprising ϳ1.7-2.5% of genes in eukaryotic genomes. Most protein kinases belong to a single superfamily, containing a conserved ePK catalytic domain that consists of a mainly -sheet, NH 2 -terminal subdomain and a larger ␣-helical COOH-terminal subdomain with the ATP-binding pocket situated between the two subdomains. Serine/threonine protein kinases constitute the majority of kinases (67%) within the human kinome; however, tyrosine protein kinases (17%) also play a key role in signaling mechanisms, particularly in cell-cell communication in multicellular organisms (2). The remainder, the atypical protein kinases (aPKs), lack sequence similarity to the ePK catalytic domain but are known to have catalytic functional activity.From the ‡Swiss-Prot group,
UniProtKB/Swiss-Prot, a curated protein database, and dictyBase, the Model Organism Database for Dictyostelium discoideum, have established a collaboration to improve data sharing. One of the major steps in this effort was the ‘Dicty annotation marathon’, a week-long exercise with 30 annotators aimed at achieving a major increase in the number of D. discoideum proteins represented in UniProtKB/Swiss-Prot. The marathon led to the annotation of over 1000 D. discoideum proteins in UniProtKB/Swiss-Prot. Concomitantly, there were a large number of updates in dictyBase concerning gene symbols, protein names and gene models. This exercise demonstrates how UniProtKB/Swiss-Prot can work in very close cooperation with model organism databases and how the annotation of proteins can be accelerated through those collaborations.
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